EndometriumKarsinoma

Karsinoma, endometrium
the fourth most common cancer in women and the most common gynaecological malignancy.
kanker keempat yang paling umum pada wanita dan keganasan ginekologi yang paling umum.
The overall mortality of this disease has decreased by 28% over the last two decades. Mortalitas
keseluruhan dari penyakit ini mengalami penurunan sebesar 28% selama dua dekade terakhir.
This decrease has largely been attributed to earlier detection and advances in treatment.
Penurunan ini sebagian besar telah dikaitkan dengan deteksi dini dan kemajuan pengobatan.
Additional improvement in the mortality rate of endometrial carcinoma may come from
improved staging and therapy optimization. Tambahan perbaikan dalam angka kematian
endometrium karsinoma dapat berasal dari pementasan peningkatan dan optimalisasi terapi. The
peak incidence of endometrial carcinoma is between the ages of 55 and 65 years. Kejadian
puncak endometrium karsinoma adalah antara usia 55 dan 65 tahun. The disease is uncommon
before the age of 40, with only 2 5% of patients presenting prior to this age. Carcinoma of the
endometrium is more common in whites than in blacks. Penyakit ini jarang terjadi sebelum usia
40, dengan hanya 2 5% dari pasien yang sebelum usia ini. Karsinoma endometrium lebih sering
terjadi pada kulit putih daripada kulit hitam. Other epidemiological risk factors include
nulliparity, infertility, obesity, diabetes, hypertension and Stein Leventhal syndrome . Faktor-
faktor risiko epidemiologi termasuk nulliparity, infertilitas, obesitas, diabetes, hipertensi dan
sindrom Stein Leventhal . One important and potentially confounding variable is prolonged or
unopposed stimulation of the endometrium by oestrogen. Satu variabel penting dan berpotensi
perancu yang berkepanjangan atau terlindung stimulasi endometrium oleh estrogen. An increased
incidence of endometrial carcinoma is seen in women taking unopposed oestrogen for
postmenopausal prevention of osteoporosis or oral contraception. Peningkatan insiden
endometrium karsinoma terlihat pada wanita yang menggunakan estrogen untuk pencegahan
menopause terlindung dari osteoporosis atau oral kontrasepsi. An increased incidence is also
seen in women with oestrogen-secreting neoplasms. Peningkatan insiden juga terlihat pada
wanita dengan neoplasma-mensekresi estrogen. In addition, endometrial carcinoma is rare in
individuals with ovarian agenesis or who undergo bilateral oophorectomy at an early age. Selain
itu, endometrium karsinoma jarang terjadi pada individu dengan agenesis ovarium atau yang
menjalani ooforektomi bilateral pada usia dini.
Postmenopausal bleeding is the most important presenting symptom of endometrial carcinoma .

perdarahan postmenopause adalah menyajikan gejala yang paling penting dari endometrium
karsinoma . There are multiple benign causes of postmenopausal bleeding including oestrogen
therapy, endometrial hypertrophy, atrophic vaginitis, endometrial or cervical polyps. Ada
beberapa jinak penyebab pendarahan pascamenopause termasuk terapi estrogen, endometrium
hipertrofi, atrofi vaginitis, endometrium atau serviks polip. Only 10 20% of patients presenting
with this symptom actually have a malignancy. Hanya 10 20% dari pasien dengan gejala ini
sebenarnya sudah keganasan. A purulent or serous discharge is a less common presenting
complaint. A discharge purulen atau serosa adalah keluhan menyajikan kurang umum. Less than
5% of patients with carcinoma of the endometrium are asymptomatic at the time of presentation.
Kurang dari 5% pasien dengan karsinoma endometrium tidak menunjukkan gejala pada saat
presentasi. These cases are usually detected by abnormal cervical cytology or histological
examination of a uterus removed for a benign cause. Kasus-kasus ini biasanya terdeteksi oleh
abnormal serviks sitologi atau pemeriksaan histologi uterus yang dihapus demi jinak penyebab.
Endometrial carcinoma in premenopausal women usually presents as abnormal uterine bleeding,
ranging from oligomenorrhoea to menometrorrhagia. Endometrial carcinoma pada wanita
premenopause biasanya muncul sebagai perdarahan uterus abnormal, mulai dari
oligomenorrhoea ke menometrorrhagia.
The diagnosis of endometrial carcinoma is made by histological examination of endometrial

tissue. Diagnosis endometrium karsinoma dibuat dengan pemeriksaan histologi jaringan
endometrium. Endometrial biopsy with endocervical curettage is a safe and effective procedure
in the evaluation of patients with postmenopausal bleeding. Endometrial biopsi dengan kuretase
endoserviks merupakan prosedur yang aman dan efektif dalam evaluasi pasien dengan
perdarahan postmenopause. This procedure can be performed in the outpatient setting and has
largely replaced fractional curettage under anaesthesia as the first step in diagnosing endometrial
carcinoma . Prosedur ini dapat dilakukan di luar pasien dan sebagian besar telah digantikan
kuretase pecahan di bawah anestesi sebagai langkah pertama dalam mendiagnosis endometrium
karsinoma . Curettage under anaesthesia or hysteroscopy can be performed in appropriate
instances. Kuret bawah anestesi atau histeroskopi dapat dilakukan dalam kasus yang sesuai.
Atypical or malignant endometrial cells are usually seen on cervical cytology. Atypical atau
ganas sel endometrium biasanya dilihat pada serviks sitologi. The pap smear, however, is
inadequate as the sole test to exclude endometrial cancer. Pap smear, bagaimanapun, adalah tidak
memadai sebagai uji tunggal untuk mengecualikan kanker endometrium. Up to 13% of
postmenopausal patients with cancer of the endometrium may present with normal cervical
cytology. Sampai dengan 13% dari pasien pascamenopause dengan kanker endometrium dapat
hadir dengan normal serviks sitologi. An elevated serum (carcinoembryonic antigen) CA-125
usually indicates extrauterine disease. Sebuah serum (antigen Carcinoembryonic) CA-125
biasanya menunjukkan penyakit extrauterine.
Approximately 90% of uterine malignancies are true epithelial carcinomas. Sekitar 90% dari
keganasan rahim adalah karsinoma epitel benar. The remaining 10% of nonepithelial uterine
cancers are comprised of sarcomas, mixed tumours and secondary malignancies. 10% sisa
kanker rahim nonepithelial terdiri dari sarkoma, tumor campuran dan keganasan sekunder.
Nearly 90% of the epithelial cancers are typical adenocarcinomas. Hampir 90% dari kanker
epitel adalah adenocarcinoma khas. Somewhere between 10 and 20% of adenocarcinomas
demonstrate some degree of squamous differentiation (adenosquamous variety). Di suatu tempat
antara 10 dan 20% dari adenocarcinoma menunjukkan beberapa derajat diferensiasi skuamosa
(varietas adenosquamous). Other less common epithelial varieties include clear cell, mucinous,
secretory and papillary serous carcinoma . kurang umum epitel varietas lainnya termasuk sel
jernih, mucinous, sekresi dan serosa papiler karsinoma . The clear cell and papillary serous types
demonstrate highly malignant behaviour, and thus, have a much worse prognosis. Sel jelas dan
jenis serous papiler menunjukkan sangat ganas perilaku, dan dengan demikian, memiliki
prognosis buruk banyak. Typical endometrial carcinomas are assigned one of three grades based
on the cellular architecture. karsinoma endometrium khas ditugaskan salah satu dari tiga kelas
berdasarkan arsitektur selular. Grade 1 cancers are predominately glandular and are well
differentiated. Kelas 1 kanker adalah predominately kelenjar dan dibedakan dengan baik. Grade
3 lesions are poorly differentiated adenocarcinomas, with predominantly solid elements. Grade 3
lesi yang buruk dibedakan adenocarcinoma, dengan unsur-unsur dominan yang solid. A high
degree of nuclear atypia can also increase tumour grade. Tingkat tinggi nuklir atypia juga dapat
meningkatkan tumor kelas.
Endometrial carcinoma typically arises from the endometrial muc the lymphatic drainage system
results in marked variability in the pattern of nodal metastases. Endometrial carcinoma biasanya
timbul dari MUC endometrium hasil sistem drainase limfatik di variabilitas ditandai dengan pola
nodal metastasis. Haematogenous dissemination tends to occur late in the disease. diseminasi
Hematogen cenderung terjadi di akhir penyakit. The most common sites of distant metastases are
lung, liver, brain and bone. Situs yang paling umum dari metastasis jauh adalah paru-paru, hati,
otak dan tulang. Depth of myometrial invasion appears to be a very important independent and
confounding prognostic variable. Kedalaman invasi miometrium tampaknya menjadi variabel
yang sangat penting prognostik independen dan perancu.
Staging Pementasan
In 1988, the International Federation of Gynecology and Obstetrics (FIGO) recommended a

surgical staging system for endometrial cancer. Pada tahun 1988, Federasi Internasional
Ginekologi dan Obstetri (FIGO) yang direkomendasikan sistem pementasan bedah untuk kanker
endometrium. Stage I disease is confined to the uterine corpus. Tahap I penyakit ini terbatas pada
korpus uterus. Stage II denotes spread into the uterine cervix. Tahap II menunjukkan menyebar
ke dalam serviks uterus. A number of factors define stage III disease, including vaginal
extension, spread into the adnexa or parametrium, positive peritoneal cytology, or nodal
metastases to the iliac or para-aortic chains. Sejumlah faktor menentukan stadium penyakit III,
termasuk perpanjangan vagina, menyebar ke adneksa atau parametrium, sitologi peritoneum
positif, atau metastasis nodal ke rantai iliaka atau para-aorta. Bowel or bladder mucosal
involvement, as well as distant metastases define stage IV disease. Keterlibatan mukosa usus
atau kandung kemih, serta metastasis jauh menentukan stadium IV penyakit. In recognition that
tumour grade is a major determinant of prognosis, each surgical stage is additionally stratified by
assigning a grading system. Dalam pengakuan bahwa tumor kelas merupakan penentu utama
prognosis, setiap tahap bedah tambahan bertingkat dengan memberikan sistem grading. Tumours
are graded from one to three, with lower scores representing greater tumour differentiation.
Tumor yang dinilai dari satu sampai tiga, dengan skor rendah yang mewakili lebih besar tumor
diferensiasi.
Approximately 70% of patients present with stage I disease. Sekitar 70% dari pasien datang
dengan stadium I penyakit. The five-year survival is seen in 76% of these patients. Kelangsungan
hidup lima tahun terlihat di 76% dari pasien tersebut. The five-year survival rate decreases to
59% for stage II and 29% for stage III. Tumour grade also has an effect on five year survival.
Tahun kesintasan-lima berkurang menjadi 59% untuk tahap II dan 29% untuk tahap III. Tumor
grade juga memiliki efek pada kelangsungan hidup lima tahun. Retrospective analysis of patients
with stage Ia and Ib disease showed a consistent drop in the five-year survival rate with
increasing tumour grade. Analisis retrospektif dari pasien dengan stadium Ia dan penyakit Ib
menunjukkan penurunan konsisten dalam tahun sintasan-lima dengan meningkatnya tumor
grade.
Imaging Imaging
A chest radiograph is obtained in almost every patient diagnosed with endometrial carcinoma .
Sebuah rontgen dada diperoleh di hampir setiap pasien didiagnosis dengan endometrium
karsinoma . In addition to detecting lung metastases, chest radiography is useful in identifying
comorbid pulmonary conditions. Selain mendeteksi metastase paru, radiografi dada berguna
dalam mengidentifikasi komorbid paru kondisi. Other conventional radiographic studies are not
routinely performed. Lain konvensional radiografi studi tidak secara rutin dilakukan. Skeletal
scintigraphy and bone radiography can be performed when skeletal metastases are suspected.
Intravenous pyelography and lymphangiography have largely been replaced by cross-sectional
modalities . Endoscopy is the preferred method for detection of suspected rectal or colonic
involvement over barium enema . Kerangka skintigrafi dan radiografi tulang dapat dilakukan
ketika metastasis kerangka yang diduga. intravena pyelography dan lymphangiography sebagian
besar telah digantikan oleh cross-sectional modalitas . Endoskopi adalah metode yang disukai
untuk mendeteksi keterlibatan rektum atau kolon dicurigai atas barium enema .
On ultrasound , stage I endometrial carcinoma typically appears as widening of the echogenic

endometrial stripe. Pada USG , tahap I endometrium karsinoma biasanya muncul sebagai
pelebaran dari garis endometrium Echogenic. The postmenopausal endometrium atrophies,
generally measuring less than 3 mm. The atrophies endometrium pascamenopause, umumnya
berukuran kurang dari 3 mm. A double layer thickness measurement of greater than 5 mm is
almost always considered abnormal ( Fig.1 ). Sebuah pengukuran ketebalan lapisan ganda lebih
besar dari 5 mm hampir selalu dianggap abnormal ( Gambar 1 ). The exception is in women on
estrogen therapy. Pengecualian adalah pada wanita pada terapi estrogen. In these individuals, an
endometrial stripe thickness of 7 mm or less is considered to be within normal limits. Dalam
individu, dengan ketebalan garis endometrium 7 mm atau kurang dianggap dalam batas normal.
Endovaginal ultrasound may be a useful tool for screening women with postmenopausal
bleeding. Endovaginal USG mungkin merupakan alat yang berguna untuk wanita skrining
dengan perdarahan postmenopause. Several studies have shown that demonstration of a normal
endometrium virtually excludes the presence of endometrial carcinoma . Beberapa studi telah
menunjukkan bahwa demonstrasi dari endometrium normal hampir tidak termasuk keberadaan
endometrium karsinoma . This is important because 80 90% of patients with postmenopausal
bleeding do not have endometrial carcinoma . Ultrasound has been utilized to evaluate the depth
of myometrial invasion. Hal ini penting karena 80 90% dari pasien dengan perdarahan
postmenopause tidak memiliki endometrium karsinoma . USG telah digunakan untuk
mengevaluasi kedalaman invasi miometrium. The inner myometrium is hypoechoic relative to
the outer myometrium. Focal thinning of this hypoechoic ring is suggestive of superficial
invasion. The miometrium batin adalah relatif hypoechoic ke luar miometrium. Focal penipisan
cincin ini hypoechoic adalah sugestif invasi dangkal. Obliteration of the hypoechoic inner layer
suggests deep (> 50%) myometrial invasion. Penghapusan dari lapisan dalam hypoechoic
menyarankan dalam (> 50%) invasi miometrium. The accuracy of ultrasound in the evaluation of
myometrial invasion is 68 69%. Ultrasound has been advocated in the staging of known
endometrial carcinoma . Akurasi USG dalam evaluasi invasi miometrium adalah 68 69%. USG
ini telah diadvokasi dalam pementasan endometrium dikenal karsinoma . Relatively poor
contrast resolution , however, may hamper the ability of ultrasound to differentiate between
tumour , normal myometrium and benign uterine diseases. Sebaliknya miskin relatif resolusi ,
bagaimanapun, dapat menghambat kemampuan ultrasound untuk membedakan antara tumor ,
miometrium normal dan jinak penyakit rahim. In addition, large body habitus or extreme uterine
flexion can hinder study quality. Polypoid lesions, pyometria, adenomyosis, leiomyomas and
myometrial atrophy all have the potential to mimic myometrial invasion, resulting in false
positives. Selain itu, habitus tubuh besar atau fleksi rahim ekstrim dapat menghambat kualitas
belajar. Polypoid lesi, pyometria, adenomiosis, leiomyomas dan atrofi miometrium semua
memiliki potensi untuk meniru invasi miometrium, menghasilkan positif palsu. False negatives
can occur with superficial tumour spread or microinvasion. negatif palsu dapat terjadi dengan
dangkal tumor menyebar atau microinvasion. The value of ultrasound in the detection of lymph
node metastases or cervical invasion has not been established. Nilai USG dalam deteksi getah
bening atau node metastasis serviks invasi belum ditetapkan.
Carcinoma of the endometrium appears as diffuse or foc demonstrate small volume or

microscopic spread to the cervix, parametrium, lymph nodes, bladder or rectum . Karsinoma
endometrium muncul sebagai difus atau kecil volume menunjukkan Foc atau menyebar
mikroskopis ke parametrium, leher rahim, kelenjar getah bening, kandung kemih atau rektum .
False positive errors generally occur with reactive adenopathy or parametritis. Salah kesalahan
positif umumnya terjadi dengan adenopati reaktif atau parametritis. There is insufficient data on
the value of spiral CT in staging endometrial carcinoma . Ada data tidak memadai pada nilai
spiral CT dalam pementasan endometrium karsinoma .
Endometrial carcinoma can have a variable appearance on MRI . Endometrial carcinoma dapat
memiliki penampilan variabel pada MRI . Typically, the signal characteristics are similar to the
normal endometrium on nonenhanced MR studies. Biasanya, karakteristik sinyal yang mirip
dengan endometrium normal pada studi MR nonenhanced. Tumours are generally hyperintense
with respect to myometrium on T2-weighted images and isointense on T1-weighted images.
Tumor umumnya hyperintense sehubungan dengan miometrium pada gambar T2-rata dan
isointense pada gambar T1-tertimbang. The presence of blood products within these lesions can
make them heterogeneous. Kehadiran produk darah dalam lesi ini dapat membuat mereka
heterogen. Larger tumours are often seen as a polypoid mass expanding the endometrial cavity.
tumor yang lebih besar sering dipandang sebagai polypoid massa memperluas rongga
endometrium. Secondary signs of small tumours include increased thickness or lobulation of the
endometrium. tanda-tanda sekunder tumor kecil meliputi peningkatan ketebalan atau lobulation
dari endometrium. Endometrial carcinoma enhances to a variable degree on dynamic post-
gadolinium images. Endometrial karsinoma meningkatkan sampai tingkat variabel dinamis
-gadolinium gambar pos. This enhancement is typically greater than or less than that of the
myometrium and normal endometrium. Perangkat tambahan ini biasanya lebih besar dari atau
kurang dari itu dari miometrium dan endometrium normal. Contrast enhancement improves the
detection of small tumours and differentiation between lesions and fluid or necrosis. Peningkatan
Kontras meningkatkan deteksi tumor kecil dan diferensiasi antara lesi dan cairan atau nekrosis.
Myometrial invasion is best determined on post-gadolinium and T2-weighted images ( Fig.4 ).
invasi miometrium yang terbaik ditentukan pada posting-gadolinium dan berbobot gambar T2 (
Gbr.4 ). An intact junctional zone on T2-weighted images implies that there is no myometrial
invasion (stage Ia ) ( Fig.5 ). Sebuah zona junctional utuh di berbobot gambar T2 menyiratkan
bahwa tidak ada invasi miometrium (stadium Ia ) ( Gbr.5 ). Stage Ib lesions are present when
there is disruption of the junctional zone and an intact outer two thirds of the myometrium. Tahap
Ib lesi yang hadir ketika ada gangguan dari zona junctional dan luar utuh dua pertiga dari
miometrium. Invasion of more than 50% of the myometrium on dynamic gadolinium images
indicates stage Ic disease. Invasi lebih dari 50% dari miometrium pada dinamika gambar
gadolinium menunjukkan stadium penyakit Ic. False positive and negative results can occur in
patients with coexisting benign pathology, elderly patients without normal zonal anatomy, or
patients with bulky tumours that thin, rather than invade, the myometrium. hasil positif dan
negatif palsu dapat terjadi pada pasien dengan hidup berdampingan jinak patologi, pasien usia
lanjut tanpa anatomi zona normal, atau pasien dengan tumor besar yang tipis, daripada
menyerang, miometrium. The reported accuracy of contrast-enhanced MR in estimating the
depth of myometrial invasion varies from 85 94%. Cervical involvement (stage II) is best
demonstrated on sagittal contrast-enhanced and T2-weighted images ( Fig.6 ). Keakuratan
dilaporkan disempurnakan MR kontras dalam mengestimasi kedalaman invasi miometrium
bervariasi dari 85 94%. Cervical keterlibatan (tahap II) yang terbaik adalah menunjukkan pada
sagital -ditingkatkan dan T2 berbobot gambar kontras ( Gbr.6 ). Enhancing or high signal tumour
is readily identified against the background of normal cervical tissue ( Fig.7 ). Meningkatkan
atau sinyal tinggi tumor ini mudah diidentifikasi dengan latar belakang normal serviks jaringan (
Gbr.7 ). Postcurrettage haemorrhage can simulate cervical involvement if only unenhanced
sequences are utilized. Postcurrettage perdarahan dapat mensimulasikan serviks keterlibatan jika
hanya urutan unenhanced dimanfaatkan. The accuracy of contrast-enhanced MR in the
evaluation of cervical extension ranges between 91% and 95%. Keakuratan disempurnakan MR
kontras dalam evaluasi serviks ekstensi berkisar antara 91% dan 95%.
Extrauterine disease Extrauterine penyakit
Local extrauterine disease (stage III) is seen as transmyometrial extension of tumour , adnexal
masses, vaginal metastases or pelvic lymphadenopathy . penyakit extrauterine Lokal (tahap III)
dipandang sebagai perpanjangan transmyometrial dari tumor , massa adnexal, metastasis vagina
atau panggul limfadenopati . Disruption or irregularity of the uterine serosal surface adjacent to
tumour is indicative of transmyometrial spread. Gangguan atau ketidakteraturan permukaan
rahim serosal berdekatan dengan tumor merupakan indikasi penyebaran transmyometrial. T1-
weighted images are helpful in this regard. gambar T1-tertimbang sangat membantu dalam hal
ini. Increased nodal size (greater than 1 cm) is required for the detection of metastatic
lymphadenopathy . Peningkatan ukuran nodal (lebih besar dari 1 cm) diperlukan untuk
mendeteksi metastasis limfadenopati . Detection rates of nodal metastases are similar to those of
CT . Deteksi tingkat nodal metastasis mirip dengan CT . Interruption of normal tissue planes and
focal increased T2 signal intensity within the rectal or bladder wall is indicative of tumour
invasion (stage IVa). MRI has been shown to be useful as an adjunct to clinical staging in biopsy-
proven cases. Gangguan dari pesawat jaringan normal dan fokus meningkat T2 intensitas sinyal
dalam dinding rektum atau kandung kemih merupakan indikasi tumor invasi (stadium IVa). MRI
telah terbukti bermanfaat sebagai untuk klinis dalam pementasan biopsi-terbukti kasus tambahan.
The overall accuracy of gadolinium-enhanced MRI in the staging of endometrial carcinoma is
between 84% and 94%. Keakuratan keseluruhan gadolinium-ditingkatkan MRI dalam
pementasan endometrium karsinoma adalah antara 84% dan 94%. The staging accuracy drops to
as low as 75% for unenhanced MRI . Keakuratan pementasan turun ke level 75% untuk
unenhanced MRI .
Recurrence Kambuh
The pattern of tumour recurrence usually depends on the type of therapy. Pola tumor
kekambuhan biasanya tergantung pada jenis terapi. Patients treated with radiation and surgery
typically present with distant metastases without local pelvic recurrence. Pasien yang diobati
dengan radiasi dan pembedahan biasanya hadir dengan metastasis jauh tanpa kekambuhan
panggul lokal. Patients treated with surgery alone, on the other hand, usually present with
parametrial, pelvic side wall, or vaginal apex treatment failures. Pasien yang dirawat dengan
pembedahan saja, di sisi lain, biasanya hadir dengan parametrium, dinding samping panggul,
atau kegagalan puncak vagina pengobatan. The vast majority of recurrences occur within 3 years
of treatment initiation. Para luas mayoritas kambuh terjadi dalam 3 tahun inisiasi pengobatan. It
is not uncommon, however, for early stage, low-grade tumours to recur late, often more than 5
years after the initiation of treatment therapy. Hal ini tidak jarang, namun untuk tahap awal,
tumor grade rendah kambuh akhir, seringkali lebih dari 5 tahun setelah mulai terapi pengobatan.
When pelvic failures do occur, factors improving 5-year survival include late recurrence, size
less than 2 cm, and vaginal location. Ketika kegagalan panggul memang terjadi, faktor
meningkatkan ketahanan hidup 5 tahun termasuk kambuh akhir, ukuran kurang dari 2 cm, dan
lokasi vagina. Post treatment surveillance should be performed with greatest frequency during
the first 3 years, as between 75 and 95% of recurrences occur during this time. Post surveilans
pengobatan harus dilakukan dengan frekuensi terbesar selama 3 tahun pertama, seperti antara 75
dan 95% dari rekuren terjadi selama ini. Ultrasonography, CT , or MRI can be performed to
confirm suspected pelvic recurrences. Ultrasonography, CT , atau MRI dapat dilakukan untuk
mengkonfirmasi kambuh panggul dicurigai. Contrast-enhanced abdominal and pelvic CT should
be obtained periodically in patients with advanced disease or known nodal metastases. Contrast-
enhanced perut dan panggul CT harus diperoleh secara berkala pada pasien dengan penyakit
lanjut atau metastasis nodal diketahui.
HH HH
Tujuan dari kajian ini adalah untuk mengusulkan suatu model dualistik karsinogenesis
endometrium yang menggabungkan dua jalur yang berbeda dalam kaitannya dengan faktor risiko
epidemiologi, lesi histopatologi, dan acara molekul ( 1 ). The classic pathway is proposed as a
mechanism by which indolent tumors develop from hyperplastic precursors in an estrogen-rich
milieu. Jalur klasik diusulkan sebagai mekanisme dimana tumor lamban berkembang dari
prekursor hiperplastik dalam lingkungan yang kaya estrogen. In contrast, the alternative pathway
is thought to account for the development of many aggressive tumors that are not associated with
hyperplasia or estrogen excess. Sebaliknya, jalur alternatif diperkirakan untuk menjelaskan
perkembangan tumor agresif banyak yang tidak berhubungan dengan hiperplasia atau kelebihan
estrogen. This dualistic model represents an extension of clinicopathologic observations
published nearly 2 decades ago. Model dualistik merupakan perpanjangan dari pengamatan
klinikopatologi diterbitkan hampir 2 dekade lalu.
Based on clinicopathologic observations in 366 endometrial cancers, Bokhman ( 2 ) proposed

that there are two main types of endometrial carcinomas: type 1 tumors related to hormonal
imbalances and type 2 tumors that seem largely unrelated to estrogen. Berdasarkan pengamatan
di 366 klinikopatologi kanker endometrium, Bokhman ( 2 ) mengusulkan bahwa ada dua jenis
utama karsinoma endometrium: tipe 1 tumor berkaitan dengan ketidakseimbangan hormon dan
tipe 2 sebagian besar tumor yang tampaknya tidak berhubungan dengan estrogen. According to
this model, type 1 tumors are indolent neoplasms that are associated with hyperlipidemia,
obesity, and signs of hyperestrogenism, such as anovulatory bleeding, infertility, late menopause,
and endometrial and ovarian stromal hyperplasia. Menurut model ini, tipe 1 tumor neoplasma
indolen yang berhubungan dengan hiperlipidemia, obesitas, dan tanda-tanda hyperestrogenism,
seperti pendarahan anovulasi, infertilitas, menopause terlambat, dan hiperplasia stroma
endometrium dan ovarium. Type 2 tumors are unrelated to these features, behave aggressively,
and lack the progesterone responsiveness of type 1 tumors. Tipe 2 tumor tidak ada hubungannya
dengan fitur ini, berperilaku agresif, dan kurang respon progesteron tipe 1 tumor. Building on
these clinical observations, it has been suggested that the majority of type 1 tumors correspond to
the endometrioid type of endometrial carcinoma, whereas type 2 tumors probably include most
serous carcinomas and some other aggressive types ( 1 ). Membangun pengamatan ini klinis,
telah disarankan bahwa mayoritas tipe 1 tumor sesuai dengan jenis endometrioid karsinoma
endometrium, sedangkan tipe 2 tumor mungkin termasuk yang paling karsinoma serosa agresif
dan beberapa jenis lain ( 1 ). Although the correspondence between specific histopathologic
tumor types and risk factors is imperfect, this generalization has been used to propose a dualistic
model of endometrial carcinogenesis that may prove useful in planning future etiologic studies
and, ultimately, in clinical practice. Meskipun korespondensi antara tipe histopatologis tumor
tertentu dan faktor risiko tidak sempurna, generalisasi ini telah digunakan untuk mendapatkan
model dualistik karsinogenesis endometrium yang mungkin berguna dalam perencanaan
penelitian etiologi masa mendatang dan, pada akhirnya, dalam praktek klinis. Accordingly, the
terms type 1 and endometrioid and the terms type 2 and serous are used interchangeably in this
article. Dengan demikian, jenis syarat 1 dan endometrioid dan tipe 2 dan serosa istilah digunakan
secara bergantian dalam artikel ini.
Top of page Ke ujung atas halaman
EPIDEMIOLOGIC OBSERVATIONS Epidemiologi PENGAMATAN

Endometrial carcinoma ranks first in incidence and second in mortality among female genital
tract tumors, with projections of 37,400 new cases and 6,400 related deaths among women in the
United States in 1999 ( 3 ). karsinoma endometrium menempati urutan pertama dalam kejadian
dan kedua kematian di antara perempuan tumor saluran kelamin, dengan proyeksi dari 37.400
kasus baru dan 6.400 kematian terkait di kalangan wanita di Amerika Serikat pada tahun 1999 ( 3
). Incidence rates for endometrial carcinoma have remained stable at 20/100,000 women-years
since the 1970s, when rates climbed to more than 30/100,000 in conjunction with widespread use
of unopposed estrogen among postmenopausal women. Tingkat insiden karsinoma endometrium
tetap stabil pada 20/100, 000-tahun perempuan sejak tahun 1970-an, ketika tingkat naik ke lebih
dari 30 / 100, 000 bersama dengan meluasnya penggunaan estrogen terlindung di antara wanita
postmenopause. Decline in the use of these hormone preparations was paralleled by a decrease in
endometrial cancer incidence, supporting the role of excess estrogen exposure in endometrial
carcinogenesis. Penurunan dalam penggunaan preparat hormon ini disejajarkan dengan
penurunan kejadian kanker endometrium, mendukung peran paparan estrogen berlebihan dalam
karsinogenesis endometrium. Data from the population-based Surveillance and Epidemiology
End Results Program indicate that incidence rates are 60% higher among whites, whereas
mortality is 30% higher among African Americans ( 4 ). Data dari berbasis penduduk dan
Surveilans Epidemiologi Program Akhir Hasil penelitian menunjukkan bahwa tingkat insiden
adalah 60% lebih tinggi dibandingkan orang kulit putih, sedangkan kematian adalah 30% lebih
tinggi di antara Amerika Afrika ( 4 ). It is unclear whether these mortality data reflect interracial
differences in diagnosis and treatment or an unexplained tendency for African Americans to
develop aggressive tumors that are disproportionately high grade, often contain p53
abnormalities, and frequently are serous or clear cell in type ( 5 , 6 , 7 , 8 ). Tidak jelas apakah
data kematian mencerminkan perbedaan antar-ras dalam diagnosis dan pengobatan atau
kecenderungan dijelaskan bagi orang Amerika Afrika untuk mengembangkan tumor agresif yang
tidak proporsional kelas tinggi, sering mengandung kelainan p53, dan seringkali serosa atau sel
yang jelas dalam tipe ( 5 , 6 , 7 , 8 ). Because population-based screening programs for
endometrial carcinoma have not been developed in the United States, our knowledge of the
frequency and natural history of endometrial cancer precursors is limited. Karena program
skrining berbasis populasi untuk karsinoma endometrium belum dikembangkan di Amerika
Serikat, pengetahuan kita tentang frekuensi dan sejarah alam prekursor kanker endometrium
terbatas. Many endometrial hyperplasias could be asymptomatic and regress spontaneously
without ever being detected. hyperplasias Banyak endometrium bisa asimptomatik dan regresi
spontan tanpa pernah terdeteksi. Etiologic and mechanistic studies have been largely limited to
the biased fraction of cases that are persistent and produce clinical symptoms and those
associated with invasive carcinoma. Etiologi dan studi mekanistik telah banyak terbatas pada
fraksi bias kasus yang gigih dan menghasilkan gejala-gejala klinis dan yang berhubungan dengan
karsinoma invasif.
Most epidemiologic studies have analyzed all types of endometrial carcinoma as a single entity,
rather than consider different histopathologic types separately. Sebagian besar penelitian
epidemiologi menganalisa semua jenis karsinoma endometrium sebagai entitas tunggal, daripada
mempertimbangkan jenis histopatologi yang berbeda secara terpisah. Because endometrioid
carcinomas comprise over 80% of endometrial carcinomas and most endometrioid tumors are
type 1 tumors, epidemiologic studies have promoted the view that nearly all endometrial cancer
risk factors are mediated through estrogen and that protective factors act by opposing estrogen.
Karena karsinoma endometrioid terdiri dari lebih dari 80% dari karsinoma endometrium dan
paling tumor endometrioid adalah tipe 1 tumor, studi epidemiologi telah mempromosikan
pandangan bahwa hampir semua faktor risiko kanker endometrium dimediasi melalui estrogen
dan yang bertindak faktor pelindung dengan melawan estrogen. Published data regarding
endometrial cancer risk factors have been recently summarized in detail ( 4 ). Diterbitkan data
tentang faktor risiko kanker endometrium baru-baru ini diringkas secara rinci ( 4 ). Selected
exposures related to endometrial carcinoma are presented in Table 1 . Dipilih eksposur yang
terkait dengan karsinoma endometrium disajikan pada Tabel 1 .
TABLE 1 - Selected Epidemiologic Exposures Related to Endometrial Carcinoma.

TABEL 1 - Eksposur Epidemiologi Dipilih Terkait dengan Carcinoma endometrium.
Full table Meja penuh
Risk associated with exogenous estrogen use among postmenopausal women is related to
duration of exposure, with approximately 10-fold increases associated with a decade of use.
Risiko yang terkait dengan penggunaan estrogen eksogen pada wanita postmenopause
berhubungan dengan lama pemaparan, dengan kenaikan kira-kira 10 kali lipat terkait dengan satu
dekade digunakan. Menstrual factors, such as early menarche and late menopause, and
nulliparity are thought to increase cumulative estrogen exposure by increasing a woman's total
lifetime number of menstrual cycles. faktor menstruasi, seperti menarche awal dan menopause
terlambat, dan nulliparity diperkirakan untuk meningkatkan pemaparan estrogen kumulatif
dengan meningkatnya total seumur hidup wanita jumlah siklus haid. Even in polycystic ovary
disease, which is characterized by virilization, it is postulated that chronically elevated
luteinizing hormone levels promote increased androstenedione production by the ovary, which in
turn is converted to estrone in peripheral tissue stores. Bahkan dalam penyakit ovarium
polikistik, yang dicirikan oleh virilisasi, adalah mendalilkan bahwa kronis peningkatan kadar
hormon luteinizing mempromosikan meningkatkan produksi androstenedione oleh ovarium,
yang pada gilirannya diubah menjadi estrone di toko-toko jaringan perifer. Because adipose
tissue and other peripheral stores are a major source of aromatase, an enzyme that converts
androgens to estrogens, obesity is believed to confer risk in postmenopausal women by
promoting increased production of estrogen from adrenal and ovarian androgens. Karena
jaringan lemak dan toko perangkat lainnya adalah sumber utama dari aromatase, enzim yang
mengubah androgen ke estrogen, obesitas diyakini memberikan risiko pada wanita menopause
dengan mendorong peningkatan produksi estrogen dari androgen adrenal dan ovarium. However,
it is unclear whether the risk associated with obesity is entirely attributable to elevations in serum
estrogen, and the possibility that non-hormonal mechanisms may be involved has been
considered. Namun, tidak jelas apakah risiko yang terkait dengan obesitas sepenuhnya
disebabkan oleh peningkatan dalam serum estrogen, dan kemungkinan bahwa mekanisme non-
hormonal mungkin terlibat telah dipertimbangkan. Tamoxifen is a nonsteroidal estrogen agonist
and antagonist that may have nonhormonal effects, including the formation of DNA adducts.
Tamoxifen adalah agonis estrogen nonsteroid dan antagonis yang mungkin memiliki efek
nonhormonal, termasuk pembentukan adduct DNA. Although tamoxifen use increases
endometrial cancer risk, data are conflicting as to whether type 1 or type 2 tumors predominate,
perhaps reflecting the dualistic action of this drug. Meskipun menggunakan tamoxifen
meningkatkan risiko kanker endometrium, data bertentangan mengenai apakah tipe 1 atau tipe 2
tumor mendominasi, mungkin mencerminkan tindakan dualistik obat ini. Protective factors are
believed to operate by opposing the actions of estrogen. faktor pelindung diyakini untuk
beroperasi dengan menentang tindakan estrogen. For example, oral contraceptives contain
progesterone, which may directly oppose the effects of estrogen, and smoking may reduce
estrogen levels by producing alterations in hormone metabolism. Sebagai contoh, kontrasepsi
oral mengandung progesteron, yang secara langsung dapat menentang efek estrogen, dan
merokok dapat mengurangi tingkat estrogen dengan menghasilkan perubahan dalam
metabolisme hormon.
EPIDEMIOLOGIC EVIDENCE FOR TWO PATHWAYS OF ENDOMETRIAL

CARCINOGENESIS Epidemiologi BUKTI UNTUK DUA JALUR DARI
karsinogenesis endometrium
In a past study, data from 328 endometrioid and 26 serous carcinomas and 320 population-based
controls without endometrial cancer were analyzed to evaluate whether epidemiologic data
support a dualistic model of endometrial carcinogenesis ( 9 ). Dalam studi terakhir, data dari 328
endometrioid dan 26 karsinoma serosa dan 320 berbasis kontrol penduduk tanpa kanker
endometrium dianalisa untuk mengevaluasi apakah data epidemiologi mendukung model
dualistik karsinogenesis endometrium ( 9 ). In that analysis, the average age of patients with
serous carcinomas was 6 years greater than that of patients with endometrioid carcinoma. Dalam
analisis itu, rata-rata usia pasien dengan karsinoma serosa adalah 6 tahun lebih besar dari pasien
dengan karsinoma endometrioid. Predictably, obesity and exogenous hormone use were
associated with increased risk for endometrioid carcinoma, but these exposures were not related
to risk for serous carcinoma. Bisa ditebak, obesitas dan menggunakan hormon eksogen dikaitkan
dengan peningkatan risiko karsinoma endometrioid, tetapi eksposur tersebut tidak terkait dengan
risiko karsinoma serosa. However, concurrent smoking and oral contraceptive use were
protective for both tumor types. Namun, bersamaan merokok dan penggunaan kontrasepsi oral
pelindung untuk kedua jenis tumor. Comparison of selected serum hormone levels, determined
using validated laboratory assays, demonstrated that both estrogens and androgens were elevated
in women with endometrioid carcinoma, compared with controls, whereas levels for patients
with serous carcinoma were similar to those in the controls ( Table 2 ). Perbandingan kadar
hormon serum yang dipilih, ditentukan dengan menggunakan tes laboratorium divalidasi,
menunjukkan bahwa baik estrogen dan androgen meningkat pada wanita dengan karsinoma
endometrioid, dibandingkan dengan kontrol, sedangkan tingkat untuk pasien dengan karsinoma
serosa adalah serupa dengan yang ada di kontrol ( Tabel 2 ). In contrast, levels of sex-hormone-
binding globulin, a circulating protein that reduces bioavailable estrogen, were higher among
serous carcinoma patients than controls or endometrioid carcinoma patients. Sebaliknya, tingkat
globulin seks-hormon-mengikat, sebuah protein sirkulasi yang mengurangi estrogen
bioavailable, lebih tinggi di antara pasien karsinoma serosa dari kontrol atau pasien karsinoma
endometrioid. Because serum hormone data were adjusted for age and body mass index (a
measure of obesity), the differences in levels between endometrioid and serous carcinoma
patients do not merely reflect the fact that women with serous carcinoma are older and thinner.
Karena data serum hormon yang disesuaikan dengan usia dan indeks massa tubuh (ukuran
obesitas), perbedaan tingkat antara pasien karsinoma endometrioid dan serosa tidak hanya
mencerminkan fakta bahwa perempuan dengan karsinoma serosa lebih tua dan lebih tipis. These
results suggest a fundamental difference in the hormonal milieu in which these two types of
tumors develop. Hasil ini menunjukkan perbedaan mendasar dalam lingkungan hormon di mana
kedua jenis tumor berkembang. In summary, available epidemiologic data support the proposed
dualistic model of endometrial carcinogenesis, but the analyses are limited by the small number
of serous carcinoma patients studied. Singkatnya, tersedia data epidemiologi mendukung model
dualistik diusulkan karsinogenesis endometrium, tetapi analisis yang dibatasi oleh sejumlah kecil
pasien karsinoma serosa dipelajari. Although these data suggest that exogenous estrogen use is
not a risk factor for serous carcinoma, there are no data to suggest that estrogen is protective
against the development of these tumors. Meskipun data ini menunjukkan bahwa penggunaan
estrogen eksogen bukan merupakan faktor risiko untuk kanker serosa, tidak ada data untuk
menyarankan estrogen yang melindungi terhadap perkembangan tumor ini.
TABLE 2 - Comparison of Mean Levels of Selected Hormones in Endometrioid (Type
1) and Serous (Type 2) Carcinomas. TABEL 2 - Perbandingan Tingkat Rerata Hormon
Dipilih di endometrioid (Tipe 1) dan serosa (Tipe 2) karsinoma.
Many questions regarding endometrial cancer risk factors persist ( 10 ). Banyak pertanyaan
tentang faktor risiko kanker endometrium bertahan ( 10 ). For example, what changes occur at
the cellular level to explain why exposures early in life ( eg , oral contraceptive use) reduce
cancer risk decades after the exposure has ended? Sebagai contoh, perubahan apa yang terjadi
pada tingkat sel untuk menjelaskan mengapa paparan awal dalam kehidupan (misalnya,
penggunaan kontrasepsi oral) mengurangi risiko kanker setelah terpapar dekade telah berakhir?
Why is the increased risk associated with elevated serum estrogen levels relatively modest if
endometrial carcinoma results from systemic estrogenism, and why are elevated androgens
associated with increased risk? Mengapa peningkatan risiko terkait dengan tingkat estrogen
serum yang relatif sederhana jika hasil karsinoma endometrium dari estrogenism sistemik, dan
mengapa androgen tinggi berhubungan dengan peningkatan risiko? Are these observations only
artifacts of study designs that rely on single hormone measurements in postmenopausal women,
or do these findings reflect the fundamental complexity inherent in understanding the chronic
exposures that lead to cancer? Apakah ini hanya pengamatan artefak desain studi yang
mengandalkan pengukuran hormon tunggal pada wanita menopause, atau melakukan temuan ini
mencerminkan kompleksitas mendasar yang melekat dalam memahami eksposur kronis yang
menyebabkan kanker? Finally, the recognition that some endometrioid carcinomas arise in
patients lacking classic risk factors and that endometrial hyperplasia is not always identified in
uteri containing endometrioid carcinoma raises the question as to whether some endometrioid
carcinomas represent type 2 tumors. Akhirnya, pengakuan bahwa beberapa karsinoma
endometrioid muncul pada pasien kekurangan faktor risiko klasik dan yang hiperplasia
endometrium tidak selalu diidentifikasi dalam uteri yang mengandung karsinoma endometrioid
menimbulkan pertanyaan, apakah beberapa karsinoma endometrioid merupakan jenis 2 tumor.
However, in an analysis that examined the relationship between different patterns of
endometrioid carcinoma and risk factors, differences were not identified among tumors stratified
by grade, stage, presence of squamous differentiation, or endometrial hyperplasia ( 11 ). Namun,
dalam analisis yang menguji hubungan antara pola-pola yang berbeda dari karsinoma
endometrioid dan faktor risiko, perbedaan tersebut tidak teridentifikasi antara tumor
dikelompokkan berdasarkan kelas, panggung, kehadiran skuamosa diferensiasi, atau hiperplasia
endometrium ( 11 ). Continued research on this topic is needed. Lanjutan penelitian tentang topik
ini diperlukan.
CLINICOPATHOLOGIC EVIDENCE FOR TWO PATHWAYS OF ENDOMETRIAL

CARCINOGENESIS Klinikopatologi BUKTI UNTUK DUA JALUR DARI
karsinogenesis endometrium
Histopathologic support for an alternative pathway of endometrial carcinogenesis unrelated to
hormone imbalances is derived largely from clinicopathologic studies of serous carcinoma.
Histopatologi dukungan untuk jalur alternatif karsinogenesis endometrium tidak berhubungan
dengan ketidakseimbangan hormon berasal sebagian besar dari studi klinikopatologi karsinoma
serosa. In a seminal report, Hendrickson et al. ( 12 ) reported that serous carcinomas accounted
for 50% of recurrences in a series of 256 clinical Stage I tumors, even though only 10% of these
tumors were serous. Dalam laporan mani, Hendrickson et al (. 12 ) melaporkan bahwa karsinoma
serosa menyumbang 50% dari kambuh dalam serangkaian 256 Tahap klinis saya tumor,
meskipun hanya 10% dari tumor serous. These authors emphasized that women with serous
carcinoma were considerably older than those with endometrioid carcinoma and that serous
tumors behaved more aggressively than even Grade 3 endometrioid tumors. Para penulis ini
menekankan bahwa wanita dengan kanker serosa yang jauh lebih tua dibandingkan dengan
karsinoma endometrioid dan bahwa tumor serous bersikap lebih agresif daripada tumor Grade 3
endometrioid. In addition, this report highlighted the similar morphology of uterine serous
carcinoma and its homologue in the ovary and the tendency for both tumors to produce ascites
and spread along peritoneal surfaces. Selain itu, laporan ini menyoroti morfologi serupa
karsinoma serosa uterus dan homolog pada ovarium dan kecenderungan untuk kedua tumor
untuk menghasilkan ascites dan menyebar di sepanjang permukaan peritoneal.
Another contribution of this study, and possibly the finding that received the most immediate
attention, was the development of criteria for distinguishing the two main types of uterine
papillary carcinoma: villoglandular endometrioid carcinoma and serous carcinoma. Kontribusi
lain dari penelitian ini, dan mungkin menemukan yang mendapat perhatian paling cepat, adalah
pengembangan kriteria untuk membedakan dua jenis utama kanker rahim papiler: karsinoma
endometrioid villoglandular dan karsinoma serosa. Classic examples of serous carcinoma
demonstrate coarse, edematous papillae lined by cuboidal, low columnar, or hobnail-shaped cells
displaying anaplastic nuclear cytology and mitoses, often including abnormal figures. contoh
klasik serous carcinoma menunjukkan kasar, pembengkakan papila dibatasi oleh cuboidal,
kolumnar rendah, atau sel-sel berbentuk paku sepatu menampilkan sitologi nuklir anaplastik dan
mitoses, sering termasuk angka normal. In contrast, the papillae in villoglandular carcinoma are
generally thinner and more uniform, and most important, the cells lining the papillae are
columnar in shape, monomorphic, and display minimal nuclear atypia ( Fig. 1 ). Sebaliknya,
papila pada karsinoma villoglandular umumnya lebih tipis dan lebih seragam, dan yang paling
penting, sel-sel lapisan papila adalah columnar pada bentuk, monomorfik, dan menampilkan
atypia nuklir minimal ( Gambar. 1 ). In summary, the report of Hendrickson et al. ( 12 ) clarified
the confusion regarding the two main types of papillary carcinomas that occur in the uterus and
paved the way for broadening the morphologic criteria for diagnosing serous carcinoma. Secara
ringkas, laporan Hendrickson et al. ( 12 ) mengklarifikasi kebingungan tentang dua jenis utama
karsinoma papiler yang terjadi dalam rahim dan membuka jalan untuk memperluas kriteria
morfologi untuk mendiagnosis karsinoma serosa.
FIGURE 1. GAMBAR 1.
A , endometrioid carcinoma, villoglandular type. Sebuah endometrioid karsinoma,, tipe

villoglandular. Note delicate fibrovascular core with bulbous, uniform-appearing fronds. B ,
endometrioid carcinoma, villoglandular type. Catatan inti fibrovascular halus dengan bulat,
seragam-muncul daun. B, karsinoma endometrioid, tipe villoglandular. Columnar cells lining the
papillae possess bland ovoid nuclei. C , serous carcinoma. Columnar sel lapisan papila yang
memiliki inti bulat telur hambar. C, karsinoma serosa. Papillae are well formed with broad
edematous fibrovascular cores. D , serous carcinoma. Papillae baik dibentuk dengan luas core
fibrovascular pembengkakan. D, karsinoma serosa. Cells contain round nuclei with irregularly
distributed chromatin, macronucleoli, and mitoses. Sel berisi inti bulat dengan kromatin
beraturan terdistribusi, macronucleoli, dan mitoses.
Full figure and legend (72 K ) dan Full tokoh legenda (72 K)
Recent studies have emphasized that serous carcinomas vary widely in appearance to include
tumors composed largely or exclusively of gaping glands with intraluminal papillary
proliferations, tumors associated with benign polyps, and mixed tumors in which serous
carcinoma coexists with endometrioid, clear cell, or other differentiation patterns ( 13 ).
Penelitian terbaru telah menekankan bahwa karsinoma serosa bervariasi dalam penampilan untuk
memasukkan sebagian besar terdiri tumor atau eksklusif dari kelenjar menganga dengan
proliferations papiler intraluminal, tumor yang terkait dengan polip jinak, dan tumor campuran di
mana serosa karsinoma berdampingan dengan endometrioid, sel jernih, atau pola diferensiasi
lainnya ( 13 ). The unifying feature that distinguishes serous carcinoma from endometrioid
carcinoma is that in serous carcinoma, well-differentiated architecture, defined as formation of
glands or papillae, is usually associated with high-grade nuclear atypia, whereas in endometrioid
carcinoma, architectural and nuclear grade are nearly always concordant ( Fig. 2 ). Fitur
pemersatu yang membedakan karsinoma serosa dari karsinoma endometrioid adalah bahwa pada
karsinoma serous, arsitektur baik dibedakan, yang didefinisikan sebagai pembentukan kelenjar
atau papila, biasanya dikaitkan dengan atypia nuklir bermutu tinggi, sedangkan pada karsinoma
endometrioid, arsitektur dan nuklir kelas hampir selalu sesuai ( Gambar. 2 ). Because all serous
carcinomas are high-grade by definition, grading is superfluous, and in contrast to endometrioid
carcinomas, depth of myometrial invasion does not accurately predict stage. Karena semua
karsinoma serosa yang bermutu tinggi dengan definisi, grading yang berlebihan, dan berbeda
dengan karsinoma endometrioid, kedalaman invasi miometrium tidak akurat memprediksi
panggung. Tumors with mixed differentiation, in which 25% of the neoplasm appears serous,
usually behave as aggressively as pure serous carcinoma; consequently, we regard these tumors
as serous carcinoma for clinical purposes. Tumor dengan diferensiasi campuran, di mana 25%
dari neoplasma muncul serous, biasanya berperilaku sebagai agresif sebagai kanker serosa
murni; akibatnya, kita menganggap ini sebagai karsinoma tumor serous untuk tujuan klinis.
However, we suspect that the etiology and pathogenesis of some mixed tumors may differ from
that of pure serous carcinoma (see below). Namun, kami menduga bahwa etiologi dan
patogenesis beberapa tumor campuran mungkin berbeda dari karsinoma serous murni (lihat di
bawah).
FIGURE 2. GAMBAR 2.
A , serous carcinoma, glandular pattern. Sebuah serous carcinoma,, pola kelenjar. Large glands
show open, irregularly shaped lumina with papillary infoldings. B, serous carcinoma, glandular
pattern. kelenjar besar menunjukkan terbuka, lumina berbentuk tidak teratur dengan infoldings
papiler. B, karsinoma serosa, pola kelenjar. Cells with anaplastic nuclei form glands that are
architecturally well differentiated. Sel dengan anaplastik kelenjar bentuk arsitektural inti yang
dibedakan dengan baik.
EVIDENCE FROM PRECURSOR STUDIES SUPPORTING THE EXISTENCE OF

TWO PATHWAYS OF ENDOMETRIAL CARCINOGENESIS BUKTI DARI STUDI
Prekursor MENDUKUNG KEBERADAAN DUA JALUR DARI karsinogenesis
endometrium
Atypical endometrial hyperplasia (AH) undoubtedly represents the precursor of many, but
possibly not all, endometrioid (type 1) carcinomas. Atypical hyperplasia endometrium (AH) pasti
merupakan prekursor banyak, tetapi mungkin tidak semua, endometrioid (tipe 1) karsinoma. The
similar appearance of AH and Grade 1 endometrioid carcinoma underscores the pathogenetic
relationship between the two lesions. Tampilan sama AH dan Kelas 1 karsinoma endometrioid
menggarisbawahi hubungan pathogenetic antara dua luka. In addition, AH and endometrioid
carcinoma are often present concurrently and in topographic proximity in hysterectomy
specimens. Selain itu, AH dan karsinoma endometrioid sering hadir bersamaan dan kedekatan
topografi di spesimen histerektomi. Furthermore, natural history studies have demonstrated that a
significant percentage of AHs progress to carcinoma if untreated. Selanjutnya, studi sejarah alam
telah menunjukkan bahwa persentase signifikan kemajuan AHS untuk karsinoma jika tidak
diobati. Finally, recent studies have demonstrated similar immunohistochemical and molecular
markers in the two lesions. Akhirnya, studi terbaru menunjukkan imunohistokimia serupa dan
penanda molekuler dalam dua lesi.
Natural history studies have provided us with insights into endometrial carcinogenesis, despite
the limitations imposed by the lack of population-based screening data. studi sejarah alam telah
memberikan kita wawasan ke dalam karsinogenesis endometrium, meskipun keterbatasan yang
ditetapkan oleh kurangnya data screening berbasis. Most cases of endometrial hyperplasia that
have been studied were identified because of symptoms (causal or coincidental) or surveillance
related to specific risk factors ( eg , hormone replacement), or they were discovered
serendipitously in women investigated for other pathology. Sebagian besar kasus hiperplasia
endometrium yang telah dipelajari diidentifikasi karena gejala (kausal atau kebetulan) atau
pengawasan yang terkait dengan faktor risiko spesifik (misalnya, penggantian hormon), atau
mereka ditemukan secara kebetulan pada wanita diselidiki untuk patologi lain. Furthermore,
these lesions were often treated or rebiopsied for clinical indications, which may have altered
their natural history in an unpredictable manner. Selanjutnya, lesi ini sering diobati atau
rebiopsied untuk indikasi klinis, yang mungkin telah mengubah sejarah alam mereka dengan cara
yang tidak terduga. Nonetheless, these studies are revealing. Meskipun demikian, studi ini
mengungkapkan. For example, Kurman et al. ( 14 ) reported the follow-up of 170 patients with
endometrial hyperplasia, diagnosed at the Armed Forces Institute of Pathology, who were
followed for at least 1 year without hysterectomy. Sebagai contoh, Kurman et al. ( 14 )
melaporkan tindak lanjut dari 170 pasien dengan hiperplasia endometrium, didiagnosis pada
Angkatan Bersenjata Institut Patologi, yang diikuti selama minimal 1 tahun tanpa histerektomi.
Most lesions of all types regressed, including 80% of both simple and complex hyperplasias
without atypia. lesi Kebanyakan dari semua jenis kemunduran, termasuk 80% dari kedua
hyperplasias sederhana dan kompleks tanpa atypia. Hyperplasia without atypia progressed to
carcinoma only rarely, whereas 8% of atypical simple and 29% of atypical complex hyperplasias
progressed. Hiperplasia tanpa atypia berlanjut ke karsinoma jarang, sedangkan 8% dari
sederhana atipikal dan 29% dari hyperplasias kompleks atipikal berkembang. These data suggest
that most hyperplasias without atypia probably represent early, highly reversible lesions in the
pathogenesis of endometrial carcinoma. Data ini menunjukkan bahwa kebanyakan hyperplasias
tanpa atypia mungkin merupakan awal, lesi sangat reversibel dalam patogenesis karsinoma
endometrium. Although every untreated AH may not progress to carcinoma and some
endometrioid (type 1) carcinomas may arise without hyperplasia, these data support the thesis
that AH is the immediate precursor of endometrioid carcinoma. Meskipun setiap AH tidak
diobati bisa berkembang menjadi karsinoma dan beberapa endometrioid (tipe 1) karsinoma
mungkin timbul tanpa hiperplasia, data ini mendukung pendapat bahwa AH adalah prekursor
langsung dari karsinoma endometrioid.
The recognition that AH and endometrioid carcinoma express both estrogen and progesterone
receptors is consistent with the status of AH as a precursor lesion and suggests that progesterone
therapy may permit the reversal of these lesions in young women seeking to retain fertility.
Pengakuan bahwa AH dan karsinoma endometrioid mengekspresikan reseptor estrogen dan
progesteron konsisten dengan status AH sebagai lesi prekursor dan menunjukkan bahwa terapi
progesteron dapat mengizinkan pemulihan lesi pada wanita muda mencari untuk
mempertahankan kesuburan. Randall and Kurman ( 15 ) reported that 16 (94%) of 17 women
with AH and 9 (75%) of 12 with endometrioid carcinoma were successfully treated with 3 to 18
months of progesterone, enabling 5 women to become pregnant. Randall dan Kurman ( 15 )
melaporkan bahwa 16 (94%) dari 17 wanita dengan AH dan 9 (75%) dari 12 dengan karsinoma
endometrioid telah berhasil diobati dengan 3 sampai 18 bulan dari progesteron, memungkinkan 5
perempuan untuk menjadi hamil. Residual hyperplasia was identified in three women treated for
AH and three with carcinoma. Sisa hiperplasia diidentifikasi dari tiga wanita diperlakukan untuk
AH dan tiga dengan karsinoma. Kim et al. ( 16 ) reported the results of seven young women
treated for carcinoma and reviewed the outcomes of 14 published cases. Kim et al. ( 16 )
melaporkan hasil tujuh perempuan muda dirawat karena karsinoma dan meninjau hasil-hasil dari
14 kasus dipublikasikan. They reported that an initial response was achieved in 13 (62%) of 21
patients, but 3 patients recurred, including one with metastases. Mereka melaporkan bahwa
tanggapan awal dicapai dalam 13 (62%) dari 21 pasien, namun 3 pasien terulang, termasuk satu
dengan metastasis. Ferenczy et al. ( 17 ) reported that 52 (80%) of 65 postmenopausal women
(mean age, 56 y) with hyperplasia without atypia responded to hormonal therapy; however, only
5 (25%) of 20 women with AH regressed, and an equal percentage progressed to carcinoma. et.
al Ferenczy ( 17 ) melaporkan bahwa 52 (80%) dari 65 wanita menopause (usia rata-rata, 56 y)
dengan hiperplasia tanpa atypia merespon terhadap terapi hormonal, namun hanya 5 (25%) dari
20 wanita dengan AH mundur, dan persentase yang sama berkembang menjadi karsinoma. In
aggregate, these data suggest that both AH and endometrioid carcinoma in young women are
highly reversible, at least in the short term, when treated with progesterone. Secara agregat, data
ini menunjukkan bahwa kedua AH dan karsinoma endometrioid pada wanita muda sangat
reversibel, setidaknya dalam jangka pendek, ketika diobati dengan progesteron. However, AH in
older women may differ biologically from its counterpart in younger women because it is less
responsive to hormonal therapy. Namun, AH pada wanita yang lebih tua mungkin berbeda secara
biologis dari pasangannya pada wanita muda karena kurang responsif terhadap terapi hormonal.
This finding is intriguing because it has been hypothesized that the hormonal imbalances leading
to carcinoma differ in pre- and postmenopausal women. Temuan ini menarik karena telah
dihipotesiskan bahwa ketidakseimbangan hormon menyebabkan karsinoma berbeda pada wanita
pra dan pascamenopause. Imbalances in young women may reflect a relative lack of
progesterone, whereas in older women, an absolute excess of estrogen may be involved.
Ketidakseimbangan pada wanita muda mungkin mencerminkan kurangnya relatif progesteron,
sedangkan pada wanita yang lebih tua, kelebihan mutlak estrogen mungkin terlibat.
In contrast to the findings in uteri removed for endometrioid (type 1) carcinoma, the uninvolved
endometrium in uteri containing serous carcinoma (type 2) is usually atrophic. Berbeda dengan
temuan di uteri dihapus untuk endometrioid (tipe 1) karsinoma, endometrium tidak dilibatkan
dalam uteri mengandung serous carcinoma (tipe 2) biasanya atrofi. In one study, 76% of serous
carcinomas were associated with atrophy and 5% with hyperplasia, whereas 29% of
endometrioid carcinomas were associated with atrophy and 46% with hyperplasia ( 18 ). Dalam
sebuah penelitian, 76% dari karsinoma serosa dikaitkan dengan atrofi dan 5% dengan
hiperplasia, sedangkan 29% dari karsinoma endometrioid dikaitkan dengan atrofi dan 46%
dengan hiperplasia ( 18 ). Endometrial hyperplasia is a more frequent finding in uteri removed
for mixed endometrioid/serous carcinomas than in uteri removed for pure serous carcinoma.
hiperplasia endometrium merupakan temuan lebih sering di uteri dihapus untuk campuran
endometrioid / karsinoma serosa daripada di uteri dihapus untuk karsinoma serous murni.
Carcangiu et al. ( 19 ) identified associated endometrial hyperplasia in 46% of uteri removed for
mixed tumors, as opposed to only 8% with pure serous carcinomas. Carcangiu et al. ( 19 ) yang
diidentifikasi terkait hiperplasia endometrium di 46% dari uteri dihapus untuk tumor campuran,
dibandingkan dengan hanya 8% dengan karsinoma serous murni. It has been shown that when
endometrial hyperplasia is identified in a uterus containing a carcinoma that is partly or
exclusively serous, the hyperplasia and the carcinoma are usually topographically unrelated and
appear distinct. Telah menunjukkan bahwa ketika hiperplasia endometrium diidentifikasi dalam
rahim yang mengandung karsinoma yang sebagian atau eksklusif serosa, yang hiperplasia dan
karsinoma yang biasanya topografi tidak terkait dan tampil berbeda. Therefore, we suggest that
mixed endometrioid/serous carcinomas may begin as endometrioid carcinomas that arise from
AH and that serous differentiation develops secondarily in these already established
endometrioid carcinomas through a process of clonal evolution. Oleh karena itu, kami sarankan
bahwa endometrioid dicampur / karsinoma serosa mungkin mulai sebagai karsinoma
endometrioid yang timbul dari AH dan bahwa diferensiasi serosa berkembang sekunder dalam
karsinoma endometrioid sudah ditetapkan melalui proses evolusi klonal. Consequently, we think
that the classification of mixed endometrioid/serous carcinomas as serous is appropriate for
clinical management but may be unsatisfactory from an etiologic point of view. Akibatnya, kita
berpikir bahwa klasifikasi endometrioid campuran / karsinoma serous sebagai serosa sesuai
untuk manajemen klinis tetapi mungkin tidak memuaskan dari sudut pandang etiologi. To my
knowledge, this hypothesis has not been systematically assessed in a large series using molecular
techniques. Untuk pengetahuan saya, hipotesis ini belum sistematis dinilai dalam serangkaian
besar menggunakan teknik molekuler.
Histopathologic studies suggest that the majority of serous carcinomas develop from a distinctive
lesion termed endometrial intraepithelial carcinoma (EIC), which appears to represent malignant
transformation of atrophic surface endometrium ( 13 , 18 ). penelitian histopatologi menunjukkan
bahwa mayoritas karsinoma serosa mengembangkan dari lesi yang khas disebut karsinoma
endometrium intraepithelial (EIC), yang muncul untuk mewakili transformasi ganas permukaan
endometrium atrofi ( 13 , 18 ). EIC has been identified in 89% of uteri containing serous (type 2)
carcinoma (18). EIC telah diidentifikasi di 89% dari uteri mengandung serosa (tipe 2) karsinoma
(18). Spiegel ( 20 ) and Zheng et al. ( 21 ) have described lesions resembling EIC as endometrial
carcinoma in situ and as uterine surface carcinoma, respectively. Spiegel ( 20 ) dan Zheng et al. (
21 ) telah dijelaskan lesi menyerupai EIC sebagai karsinoma endometrium in situ dan karsinoma
permukaan uterus, masing-masing. We prefer the term EIC, because endometrial carcinoma in
situ has been applied historically to an entirely different lesion and uterine surface carcinoma
may be incorrectly interpreted as suggesting that the prognosis of pure EIC and serous carcinoma
are identical (see below). Kami lebih suka EIC panjang, karena karsinoma endometrium di situ
telah diterapkan historis ke lesi sepenuhnya berbeda dan karsinoma permukaan uterus mungkin
salah ditafsirkan sebagai menyatakan bahwa prognosis EIC murni dan karsinoma serosa adalah
identik (lihat di bawah).
EIC is characterized by the replacement of benign surface endometrium and underlying glands
by cells with anaplastic nuclei resembling serous carcinoma ( Fig. 3 ). EIC should not be
diagnosed in areas in which the surface tumor appears to represent overgrowth of an adjacent
invasive carcinoma. EIC may consist of a single or multilayered epithelium with or without
micropapillary tufting. Cytologically, the cells show marked nuclear membrane irregularities,
chromatin that varies from vesicular to smudgy, mitoses including abnormal forms, and apoptotic
bodies. EIC may be found in the absence of invasive serous carcinoma, and like the latter, EIC
demonstrates strong, diffuse immunostaining for p53 protein and Ki-67 and p53 gene mutations (
1 , 21 , 22 ). Noninvasive lesions resembling EIC, termed intraepithelial carcinoma, may be
identified in approximately 25% of serous carcinoma patients in the endocervix, fallopian tube,
and peritoneum and on the surface of the ovary ( Fig. 4 ) ( 13 ). In summary, the resemblance of
EIC to invasive serous carcinoma, its association with p53 mutation, and its identification in uteri
that do not contain invasive serous carcinoma support its proposed designation as a precursor of
serous (type 2) carcinoma.
FIGURE 3. GAMBAR 3.
Endometrial intraepithelial carcinoma. A, surface endometrium is replaced by a monolayer of

pleomorphic cells containing large, atypical nuclei. Underlying endometrium is atrophic and
consists mainly of stroma. B , multilayered epithelium composed of cells with Grade 3 nuclei
containing mitotic figures. C , cells with Grade 3 nuclei form micropapillae on endometrial
surface.
Full figure and legend (68 K )
FIGURE 4. GAMBAR 4.
Intraepithelial carcinoma involving endocervix. Lining of endocervical gland shows partial

intermittent replacement by markedly atypical cells. Inset , Note nuclear irregularities and
macronucleoli.
Because we advocate immediate hysterectomy and staging for all women with EIC, even in the
absence of invasion, we know relatively little about the natural history of this lesion. However,
we have reviewed eight cases of pure EIC that were not associated with invasion in the uterus,
two of which were present in biopsies performed up to 7 and 17 months before hysterectomy.
The uteri of these two patients showed EIC only without invasion, and both are alive and well.
The benign course in these cases suggests that EIC does not merely reflect the spread of invasive
serous carcinoma on the surface of the uterus, and it indicates that EIC does not necessarily
progress to invasion within months. However, there are many reported examples of women with
lesions that we would probably classify as EIC and that have been associated with extrauterine
disease, despite the lack of identifiable endometrial stromal or myometrial invasion ( 13 , 19 ,
23 , 24 , 25 ). In these cases, extrauterine disease may reflect multifocality, transtubal expulsion
with implantation and growth or occult invasion in the uterus with lymphatic or hematogenous
dissemination.
The differential diagnosis of EIC includes both benign reparative/metaplastic changes and
surface changes associated with other tumor types. Features favoring EIC include patient age
over 60 years, a background of atrophic endometrium, and strong, diffuse p53 and Ki-67
immunostaining ( 1 , 18 , 21 ). Eosinophilic metaplasia with atypia may pose an especially
challenging differential diagnosis, but metaplastic lesions are usually more focal and the cells
show degenerative, smudgy chromatin lacking well-preserved nuclear features of malignancy. In
addition, metaplasias occur more often in perimenopausal women who are generally about 10 to
15 years younger than women with EIC. Some cases of eosinophilic metaplasia are associated
with endometrial hyperplasia or endometrioid carcinoma, whereas in many others, the remaining
endometrium is normal. The endometrium adjacent to a minor percentage of endometrioid
carcinomas shows focal surface changes resembling EIC, but these lesions usually measure less
than a low power microscopic field and are less cytologically atypical than EIC. In addition, the
base of an exophytic endometrioid carcinoma that remains after subtotal removal by biopsy or
curettage may also mimic EIC. EIC tends to spread into benign glands, often showing partial
replacement of the benign epithelium or pagetoid involvement with intercalation between the
basement membrane and the normal epithelium. Lesions associated with endometrioid
carcinoma that mimic EIC do not typically show this pattern of intramucosal spread.
Intraepithelial carcinoma in the fallopian tube and ovary may be indistinguishable from second
primary tumors and may represent synchronous carcinomas in some cases. Intraepithelial
carcinoma in the endocervix differs from adenocarcinoma in situ of the cervix, because the cells
in EIC are generally polygonal rather than columnar, show greater architectural disarray and
pleomorphism, and possess round nuclei with prominent nucleoli instead of elongate
hyperchromatic nuclei lacking visible nucleoli.

MOLECULAR EVIDENCE FOR TWO PATHWAYS OF ENDOMETRIAL
CARCINOGENESIS
Most molecular studies of endometrial carcinoma have consisted of small series reported from
single institutions. Many studies have used frozen samples, probably resulting in a bias toward
inclusion of larger, grossly identifiable lesions. Finally, some discrepancies between studies may
reflect variations in histopathologic typing of tumors, use of fixed as opposed to frozen tissue,
and technical differences in the performance and interpretation of assays. Nonetheless, studies
have produced several consistent findings that support the proposed model of carcinogenesis as
summarized in Table 3 and as described below.
TABLE 3 - Comparison of Selected Molecular Markers in Serous (Type 1) Carcinoma

and Endometrioid (Type 2) Carcinoma and Their Respective Precursors.
p53 Mutation
Mutations in the p53 tumor suppressor gene and accumulation of p53 protein have been detected
in approximately 90% of serous carcinomas and EIC ( 1 , 22 ) but comparatively rarely in
endometrioid carcinomas. Most endometrioid carcinomas that harbor p53 mutations are large
high-grade tumors, suggesting that p53 mutation in endometrioid carcinoma is more closely
related to dedifferentiation as is the case in other tumor systems.
Because wild type p53 protein has a short half-life, it is generally undetectable in normal cells,
whereas mutant p53 protein is more stable and often reaches immunohistochemically detectable
levels. Accordingly, immunohistochemistry has been used as an imperfect surrogate marker for
p53 gene mutation. However, reported results for p53 immunostaining in endometrial carcinoma
have been conflicting because of differences in histopathologic classification, preparation of
fresh or fixed tissue, use of different antibodies, differences in staining protocols, criteria for
determining positivity, and other factors ( 1 , 21 , 22 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ,
35 ). In our institution, strong diffuse immunopositivity for p53 protein has been strongly
associated with p53 mutation in endometrial carcinoma, as determined by sensitive gene
sequencing methods ( Fig. 5 ) ( 22 ). Use of less than diffuse and intense p53 staining as a cut-off
for immunopositivity or reliance on less sensitive p53 mutation assays has not always produced a
clear association between immunopositivity and gene mutation. Because p53 mutations may
uncommonly lead to a total absence of protein production, immunohistochemical staining is
expected to produce some false-negative results. Despite the possibility of both false-positive
and false-negative results, most studies have found that p53 accumulation occurs frequently in
serous carcinoma and EIC and less commonly in endometrioid carcinoma. Immunopositivity has
been reported more commonly in endometrioid carcinomas that are high grade as opposed to
those that are low grade, and nearly all of the endometrial hyperplasias tested have been
negative.
FIGURE 5. GAMBAR 5.
A , invasive serous carcinoma, p53 immunohistochemical stain. Cells display diffuse intense
nuclear staining. B, endometrial intraepithelial carcinoma, p53 stain. Intense staining for p53
highlights endometrial intraepithelial carcinoma involving surface endometrium and partially
replacing endocervical gland.
Mutations at specific loci in the p53 gene have been linked to predisposing exposures and their
respective tumor types in several organs ( 36 ). For example, aflatoxin-related hepatocellular
carcinomas, sun-related skin carcinomas, and lung carcinomas in smokers have all been
associated with mutations at certain loci within the p53 gene. Similar associations have not been
established in serous carcinoma; however, the consistent identification of p53 mutations in
serous carcinomas may suggest that an environmental exposure, hypoxia, or another factor
associated with p53 mutation may be involved. Interestingly, uterine serous carcinoma does not
seem to be characteristic of the Li-Fraumeni syndrome in which patients with germline p53
mutations show a strong predisposition to developing other types of cancer. Therefore, many
factors other than p53 mutation must be involved in the pathogenesis of these tumors.
Microsatellite Instability
Microsatellites are short, highly polymorphic tracts of simple repeating units that are widely
dispersed throughout the genome and are usually noncoding ( 37 ). It is believed that the
repetitive nature of microsatellite sequences predisposes to DNA replication errors but that the
lengths of these tracts are scrupulously maintained in normal cells by robust DNA repair
mechanisms. Microsatellite instability (MI) refers to alterations in the lengths of these repetitive
sequences in tumor DNA as compared with normal DNA obtained from the same person.
Because the microsatellite regions that are examined in assays for MI are usually noncoding, the
significance of MI in these assays is that it represents a marker for defects in mismatch repair
mechanisms rather than a mutation in a specific gene. On the basis of theoretical calculations, it
takes multiple mutations in a single cell to develop cancer, which is unlikely to occur in normal
cells with intact repair mechanisms and low spontaneous mutation rates. However, mismatch
repair defects, such as those indicated by MI, could result in increased spontaneous mutation
rates, potentially permitting a cell to acquire sufficient mutations for the development of cancer (
38 ).
MI has been identified in about 20% of endometrioid (type 1) carcinomas and associated AHs,
but is almost never found in pure serous tumors ( 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ). Because
MI does not seem to be a frequent finding in endometrial hyperplasia that has not progressed to
endometrioid carcinoma, MI may be a late event in the transition from AH to carcinoma. Given
that it is difficult to distinguish some cases of well-developed AH from the earliest examples of
Grade 1 endometrioid carcinoma, exact determination of when MI occurs in the pathogenesis of
endometrioid carcinoma may be challenging. MI has been identified in mixed endometrioid and
serous tumors ( 46 ), but we postulate that these alterations are related to the development of the
endometrioid component.
Germline mutations in mismatch repair genes have been identified in endometrial cancers
associated with hereditary nonpolyposis colorectal cancer syndrome but rarely in sporadic
endometrial cancers. Recent studies have suggested that inactivation of mismatch repair genes
may result from hypermethylation of promoter regions, resulting in loss of repair function
without mutation (epigenetic effect) ( 47 ).
Mutation in PTEN
PTEN is a tumor suppressor gene that derives its name from its preserved tyrosine phophatase
domain and its sequence homology with the matrix protein tensin. Germline PTEN mutations
have been identified in hereditary cancer syndromes, including Cowden's disease and Bannayan-
Zonona syndrome. PTEN mutations have been identified in approximately 40% of endometrioid
carcinomas and in both AHs associated with carcinoma and those that have not progressed to
invasive carcinoma ( 48 , 49 , 50 , 51 ). Mutations in PTEN have been identified in up to 86% of
endometrioid carcinomas with MI, suggesting a relationship between these lesions, although the
mutations in PTEN do not involve microsatellite sequences. The PTEN gene has also been
described under the acronym-MMAC 1, which stands for mutated in multiple advanced cancer 1.
This name refers to the association of PTEN mutations with aggressive behavior in most tumor
systems. However, in endometrioid carcinoma, PTEN mutations have been associated with
Grade 1 endometrioid carcinomas having a favorable prognosis in some series.
Mutation in ras
Mutations in the ras oncogene have been identified in approximately 20% of endometrioid
carcinomas but are not found in serous tumors ( 52 , 53 , 54 , 55 , 56 ). It has been suggested that
ras mutations may be detected more frequently in Japan, a country with a historically low
endometrial cancer incidence, and less frequently in the United States, where rates are higher.
Hormone Receptors Hormon Reseptor
Estrogen and progesterone receptors are usually identifiable in endometrial hyperplasia and in
endometrioid carcinomas, especially those that are low grade ( 57 ). Serous carcinomas and EIC
are generally negative for receptors when evaluated with reliable immunohistochemical
techniques, but early reports using biochemical methods to test tissue extracts reported positivity,
most likely reflecting contamination of the samples with normal endometrium or myometrium,
both of which are rich in receptor protein. It is interesting that EIC and serous carcinoma lack
receptors, but the atrophic endometrium in which these tumors arise is receptor positive.
Theoretically, this could explain why oral contraceptives might be protective for serous
carcinoma, even though hormonal therapy is ineffective in treating these tumors.
Clonality Clonality
Studies have demonstrated that AH is a clonal lesion and when associated with endometrioid
carcinoma, AH is derived from the same clone as the tumor ( 58 , 59 ). Benign endometrium and
other types of endometrial hyperplasia do not appear clonal with the assays that have been used.
If one views clonality as a test for neoplasia, then AH could be viewed as a form of noninvasive
neoplasm.
SUMMARY OF MOLECULAR DATA

In summary, molecular evidence, though not abundant or entirely consistent between studies,
supports the existence of a dualistic model of endometrial carcinogenesis. Endometrioid (type 1)
carcinomas are associated with mutations in ras, PTEN , and MI, whereas serous (type 2)
carcinomas are associated with p53 mutations. The coherence of the molecular findings between
the carcinomas and their respective precursors supports the view that AH is the immediate
precursor of endometrioid carcinoma and that EIC is the precursor of serous tumors.

CLASSIC PATHWAY OF ENDOMETRIAL CARCINOGENESIS (GENESIS OF TYPE
1 TUMORS)
Details of the proposed classic pathway of endometrial carcinogenesis are summarized in Figure
6 . Many endometrioid carcinomas (type 1 tumors) develop in the setting of excess estrogen
relative to progesterone. These imbalances may result from absolute excesses of endogenous or
exogenous estrogen or relative deficiencies of progesterone. Androgens and other growth factors
may also play a role in this pathway, but this has not been well studied. Hormone levels reflect
multiple interrelated processes including exposure (exogenous intake + endogenous production),
catabolism, and excretion, which in turn reflect the levels and functional activity of specific
metabolic enzymes in the uterus, liver, and other organs. Because hormone balance reflects
complex gene-environment interactions, every woman has her own unique hormonal physiology,
which may vary over her lifetime.
FIGURE 6. GAMBAR 6.
Dualistic model of endometrial carcinogenesis, type 1 pathway. ?MMR, possible role for
mismatch repair defects.
To further complicate the process, estrogen imbalance may be systemic or occur locally within
the endometrium. Systemic estrogenism may be assessed by evaluating risk factor data and
serum hormone levels, but interpretation of these data has been confusing, suggesting that
simultaneous assessment of local tissue levels might be informative ( 10 ). Measurement of
tissue hormone levels is a new, technically challenging area that suffers from some of the same
limitations as single serum measurements obtained in case-control studies; it reflects only a
single point in time when a tumor is already present.
Historically, estrogen has been viewed as directly promoting endometrial carcinogenesis by

stimulating rapid proliferation of epithelial cells. However, recent experimental data suggest that
estrogen may produce diverse effects and that some of the actions on epithelial cells may be
mediated by endometrial stroma. For example, aromatase activity has been identified in extracts
of tumor tissue using biochemical techniques ( 60 ), but Wantanabe et al. ( 61 ), using
immunohistochemical and in situ hybridization, have localized the source of aromatase in tumor
masses to the desmoplastic stroma surrounding the neoplastic cells rather than the tumor cells. In
this study, aromatase protein and message were not found in normal or hyperplastic
endometrium. These data suggest that invasive carcinoma may induce aromatase activity in
desmoplastic stroma, which in turn could provide paracrine stimulation to an already established
invasive carcinoma. The absence of aromatase activity in normal and hyperplastic endometrium
suggests that local estrogen production within the uterus may not precede and promote the
development of cancer, but it could play a role in its progression. This may challenge the classic
view that endometrial cancer risk is merely a matter of excess estrogen exposure, because neither
elevated serum estrogens (albeit based on single measurements) nor local production of estrogen
in benign endometrium seems to adequately account for endometrial cancer risk. Future
investigations to confirm and extend these findings are needed.
Observations produced by transplanting various combinations of stroma and epithelial cells

obtained from wild type and estrogen receptor knockout mice into nude mice have also
demonstrated the importance of epithelial-stromal interactions in endometrial carcinogenesis ( 62
). Transplants of estrogen receptornegative stroma and estrogen receptorpositive epithelial
cells do not proliferate in response to exogenous estrogen. However, if estrogen receptor
positive stroma is transplanted with estrogen receptornegative epithelium, the epithelial cells
demonstrate receptordependent proliferation. If confirmed in human tissues, this would suggest
that stroma directs the estrogen-dependent proliferative response in epithelial cells.
Finally, data suggest that the role of estrogen in carcinogenesis is not limited to stimulating
proliferation. Experimental data suggest that the p450 enzyme, CYP 1B1, which is widely
distributed in many human organs, can transform estrogens into 4-hydroxy catechols that may
produce DNA damage ( 63 ). Therefore, high tissue levels of estrogen could theoretically
promote carcinogenesis via two mechanisms: producing DNA damage and stimulating
proliferation.
The development of endometrial hyperplasia and endometrioid carcinoma (type 1 tumors) in

women with irregular or anovulatory cycles suggests that prolonged periods without endometrial
sloughing may be important in the development of fixed endometrial lesions. Although risk
factors may be operative in premenopausal women, initiating events occurring in young women
may be masked as a result of periodic endometrial shedding. However, these occult alterations
may develop into hyperplasia or neoplasia in the postmenopausal period. Because anovulatory
states are often associated with concurrent hormone imbalances, entangling the relative
importance of these two potential mechanisms would be difficult. Nevertheless, progression of
endometrial hyperplasia, including AH, to invasion is neither inevitable nor rapid.
The identification of MI in AH associated with endometrioid carcinomas, but not in AH without
associated carcinoma, suggests that mismatch repair defects may occur in the transition between
the two lesions. The factors that are related to the acquisition of atypia in endometrial
hyperplasia have not been well studied, but data suggest that AH shares features with carcinoma
that are not found in hyperplasia without atypia. Specifically, AH seems to represent a clonal
lesion associated with MI and mutations in ras and PTEN . In addition, cells of debated
histogenesis, referred to as foam cells, are a frequent finding in carcinoma and its well-developed
precursors, and they may be involved in tumor development through production of inflammatory
mediators that stimulate aromatase production and proliferation. The relationship between
endometritis and endometrial carcinoma has received little attention. The molecular changes
associated with the development of myometrial invasion require further study, because
endometrioid tumors without myometrial invasion almost never metastasize. In fact, some of the
criteria for the diagnosis of early endometrial carcinoma, such as the development of back-to-
back glands and papillae formation, are often cited as examples of stromal invasion, but
nonmorphologic support for this dogma is lacking.
Histopathologic examination suggests that Grade 3 endometrioid carcinomas develop from

Grade 1 tumors that have undergone clonal evolution and dedifferentiation. This process of
tumor progression may be associated with loss of hormone receptor expression and the
development of p53 mutations. The development of malignant mixed mullerian tumors (or
carcinosarcomas) may represent another pathway of dedifferentiation in a preexisting carcinoma,
because clinicopathologic, ultrastructural, immunohistochemical, and molecular evidence
suggests that the sarcomatous component represents divergent differentiation of the epithelial
component ( 64 , 65 , 66 , 67 ). Accordingly, many pathologists view these tumors as metaplastic
carcinomas.
ALTERNATIVE PATHWAY (GENESIS OF TYPE II TUMORS)

The proposed alternative pathway of endometrial carcinogenesis is outlined in Figure 7 . Serous
carcinoma typically develops in elderly women with atrophic endometrium. Risk factors for
serous carcinoma have not been identified, but available evidence suggests that excess estrogen
exposure is not a risk factor for the development of serous tumors. Therefore, the only definite
risk factor for serous carcinoma is age. Serous carcinomas are usually diagnosed in women over
60, and these neoplasms are exceedingly uncommon in younger women. One possible approach
to understanding the etiology of these tumors is to examine factors that seem related to the
development of p53 mutations in experimental systems. The nearly universal detection of p53
mutations in serous carcinoma and its precursor, EIC, including examples of EIC without
associated invasion, suggests that p53 mutation may represent the molecular signature of serous
carcinoma and possibly define the entity in combination with morphology. Mixed tumors
displaying serous differentiation associated with endometrioid differentiation or other histologic
patterns may not arise directly from atrophic endometrium and could therefore have an entirely
different pathogenesis.
FIGURE 7. GAMBAR 7.
Dualistic model of endometrial carcinogenesis, type 2 pathway. EIC, endometrial intraepithelial

carcinoma.
From a histopathologic perspective, serous carcinomas seem to develop rapidly from EIC in the
setting of endometrial atrophy in an estrogen-deficient hormonal milieu. However, the
observation that EIC may remain stable without treatment for up to 17 months challenges this
view. Paradoxically, the aggressive behavior of extrauterine tumor in patients with pure EIC
suggests that the cells that compose EIC possess many of the biologic features of full-blown
serous carcinoma.
The development of sarcomatous differentiation in serous tumors presumably occurs through a

process of clonal evolution akin to what has been postulated for endometrioid tumors. In one
study, malignant mixed mullerian tumors with an epithelial component showing serous
differentiation were more often associated with EIC, whereas endometrial hyperplasia was
identified more often in uteri containing malignant mixed mullerian tumors with an epithelial
component showing endometrioid differentiation ( 68 ).
FUTURE DIRECTIONS ARAH MASA DEPAN

Future studies are needed to understand the critical transitions that occur in the classic pathway
of type 1 carcinogenesis: (1) the development of atypical hyperplasia from hyperplasia without
atypia and (2) the development of invasion. Continued search for etiologic heterogeneity within
tumors diagnosed as endometrioid carcinoma may be worthwhile, because hyperplasia is not
identified in a significant proportion of uteri containing these tumors. Identifying risk factors for
serous (type 2) carcinomas and elucidating the changes in atrophic endometrium that precede the
development of EIC would also be of interest. Attempts to study the pathogenesis of unusual
types of carcinoma, such as clear cell carcinoma, may be useful because of the aggressive nature
of these neoplasms. Immunohistochemical studies suggest that these tumors may have a unique
phenotype with respect to receptor status and p53 accumulation ( 69 ). The role of endometrial
stroma in carcinogenesis and progression and the mechanisms of estrogen action in promoting
proliferation and possibly acting as a procarcinogen are provocative and deserve systematic
study in human tissues. Studies of genetic polymorphisms in key hormone metabolizing enzymes
may have application in identifying women at risk for endometrial carcinoma and in
understanding hormonal mechanisms related to carcinogenesis. Finally, determining the earliest
alterations that commit cells to tumor development may be useful in identifying neoantigens that
could be targets for early detection and treatment. It is hoped that studies successfully addressing
these and other questions will provide a clearer picture of endometrial carcinogenesis and give us
better tools to prevent, detect, and treat patients with these tumors.
References Referensi
1. Sherman ME, Bur ME, Kurman RJ. p53 in endometrial cancer and its putative
precursors: evidence for diverse pathways of tumorigenesis. Hum Pathol
1995; 26 : 126874. | PubMed | ISI | ChemPort |
2. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol

Oncol 1983; 15 : 107. | Article | PubMed | ISI | ChemPort |
3. Parker SL, Tong T, Bolden, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin
1996; 65 : 527.
4. Grady D, Ernster VL. Endometrial cancer. In: Schottenfeld D, Fraumeni JF, Jr

editors. Cancer epidemiology and prevention . 2nd ed. 2nd ed. New York:
Oxford University Press; 1996. p. p. 105889.
5. Barrett RJ II, Harlan LC, Wesley MN, Hill Ha, Chen VW, Clayton LA, et al .
Endometrial cancer: stage at diagnosis and associated factors in black and
white patients. Am J Obstet Gynecol 1995; 173 : 41423. | PubMed | ISI |
6. Hicks ML, Kim W, Abrams J, Johnson CC, Blount AC, Parham GP. Racial
differences in surgically staged patients with endometrial cancer. J Natl Med
Assoc 1997; 89 : 13440. | PubMed | ChemPort |
7. Hill HA, Eley JW, Harlan LC, Greenberg RS, Barrett RJ, Chen VW. Racial
differences in endometrial cancer survival: the black/white cancer survival
study. Obstet Gynecol 1996; 88 : 91926. | Article | PubMed | ISI | ChemPort |
8. Liu JR, Conaway M, Rodriguez GC, Soper JT, Clarke-Pearson DL, Berchuck A.
relationship between race and interval to treatment in endometrial cancer.
Obstet Gynecol 1995; 86 : 48690. | Article | PubMed | ISI | ChemPort |
9. Sherman ME, Sturgeon S, Brinton LA, Potischman N, Kurman RJ, Berman ML,
et al . Risk factors and hormone levels in patients with serous and
endometrioid uterine carcinomas. Mod Pathol 1997; 10 : 9638. | PubMed | ISI
| ChemPort |
10.Potischman N, Hoover RN, Brinton LA, Siiteri P, Dorgan JF, Swanson CA, et al .
A case-control study of endogenous steroid hormones and endometrial
cancer. J Natl Cancer Inst 1996; 88 : 112735. | PubMed | ChemPort |
11.Sturgeon SR, Sherman ME, Kurman RJ, Berman ML, Mortel R, Twiggs LB, et al .
Analysis of histopathological features of endometrioid uterine carcinomas and
epidemiologic risk factors. Cancer Epidemiol Biomarkers Prev 1998; 7 : 231
5. | PubMed | ISI | ChemPort |
12.Hendrickson M, Ross J, Eifel P, Cox RS, Martinez A, Kempson R. Uterine

papillary serous carcinoma: a highly malignant form of endometrial
adenocarcinoma. Am J Surg Pathol 1982; 6 : 93108. | PubMed | ISI |
ChemPort |
13.Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine

serous carcinoma: a morphologically diverse neoplasm with unifying
clinicopathologic features. Am J Surg Pathol 1992; 16 : 60010. | PubMed | ISI
| ChemPort |
14.Kurman RJ, Kaminski PF, Norris HJ. Kurman RJ, PF Kaminski, Norris HJ. The
behavior of endometrial hyperplasia. Perilaku hiperplasia endometrium. A
long-term study of untreated hyperplasia in 170 patients. Cancer 1985; 56 :
40312. | PubMed | ISI | ChemPort | Sebuah studi jangka panjang hiperplasia
tidak diobati di 170 pasien:. Kanker 1985; 56. 403-12 | PubMed | ISI |
ChemPort |
15.Randall TC, Kurman RJ. Randall TC, Kurman RJ. Progestin treatment of atypical
hyperplasia and well-differentiated carcinoma of the endometrium in women
under age 40. Obstet Gynecol 1997; 90 : 43440. | Article | PubMed | ISI |
ChemPort | Progestin pengobatan hiperplasia atipikal dan membedakan
karsinoma baik dari endometrium pada wanita di bawah usia 40.. Obstet
Gynecol 1997; 90: | 434-40 Artikel | PubMed | ISI | ChemPort |
16.Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Kim YB,
Holschneider CH, K Ghosh, RK Nieberg, Montz FJ. Progestin alone as primary
treatment of endometrial carcinoma in premenopausal women. Progestin saja
perlakuan sebagai primer karsinoma endometrium pada wanita
premenopause. Report of seven cases and review of the literature. Cancer
1997; 3207. Laporan tujuh kasus dan kajian literatur;. Kanker 1997 320-7.
17.Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in
progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol 1989; 160
: 12631. | PubMed | ISI | ChemPort | Ferenczy A, Gelfand M. signifikansi
biologis atypia sitologi dalam diperlakukan endometrium hiperplasia-
progestogen |. Am J Obstet Gynecol 1989; 160 126-31:. PubMed | ISI |
ChemPort |
18.Ambros RA, Sherman ME, Zahn CM, Bitterman P, Kurman RJ. Ambros RA,
Sherman ME, CM Zahn, P Bitterman, Kurman RJ. Endometrial intraepithelial
carcinoma: a distinctive lesion specifically associated with tumors displaying
serous differentiation. Hum Pathol 1995; 26 : 12607. | PubMed | ISI |
ChemPort | Endometrial carcinoma intraepithelial: lesi khas khusus yang
terkait dengan tumor menampilkan diferensiasi serosa.. Hum Pathol 1995;
26: | 1260-7 PubMed | ISI | ChemPort |
19.Carcangiu ML, Chambers JT. Carcangiu ML, Chambers JT. Uterine papillary
serous carcinoma: a study of 108 cases with emphasis on the prognostic
significance of associated endometrioid carcinoma, absence of invasion, and
concomitant ovarian carcinoma. Gynecol Oncol 1992; 47 : 298305. | Article |
PubMed | ISI | ChemPort | Karsinoma uterus serosa papiler: studi dari 108
kasus dengan penekanan pada pentingnya prognostik karsinoma
endometrioid terkait, tidak adanya invasi, dan karsinoma ovarium seiring..
Gynecol Oncol 1992; 47: | 298-305 Artikel | PubMed | ISI | ChemPort |
20.Spiegel GW. Spiegel GW. Endometrial carcinoma in situ in postmenopausal

women. Am J Surg Pathol 1995; 19 : 41732. | PubMed | ISI | ChemPort |
Endometrial karsinoma in situ pada wanita postmenopause.. Am J Surg Pathol
1995; 19: | 417-32 PubMed | ISI | ChemPort |
21.Zheng W, Khurana R, Farahmand S, Wang Y, Zhang Z, Felix JC. Zheng W, R

Khurana, S Farahmand, Wang Y, Zhang Z, JC Felix. p53 immunostaining as a
significant adjunct diagnostic method for uterine surface carcinoma. Am J
Surg Pathol 1998; 22 : 16373. | Article | PubMed | ISI | ChemPort | p53
immunostaining sebagai metode diagnostik tambahan yang signifikan untuk
karsinoma permukaan uterus:. Am J Surg Pathol 1998; 22. 163-73 | Artikel |
PubMed | ISI | ChemPort |
22.Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L. p53 gene
mutations are common in uterine serous carcinoma and occur early in their
pathogenesis. Am J Pathol 1997; 150 : 17785. | PubMed | ISI | ChemPort |
Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick mutasi gen p53 L.
yang umum pada karsinoma serosa uterus dan terjadi pada awal patogenesis
mereka:. Am J Pathol 1997; 150 177-85 |. PubMed | ISI | ChemPort |
23.Lee KR, Belinson JL. Lee KR, JL Belinson. Recurrence in noninvasive

endometrial carcinoma. Am J Surg Pathol 1991; 15 : 96573. | PubMed | ISI |
ChemPort | Kekambuhan pada karsinoma endometrium noninvasif:. Am J Surg
Pathol 1991; 15. 965-73 | PubMed | ISI | ChemPort |
24.Goff BA, Kata D, Schmidt RA. Goff BA, Kata D, RA Schmidt. Uterine papillary
serous carcinoma: patterns of metastatic spread. Gynecol Oncol 1994; 54 :
2648. | Article | PubMed | ISI | ChemPort | Karsinoma uterus serosa papiler:
pola penyebaran metastasis.. Gynecol Oncol 1994; 54: | 264-8 Artikel |
25.Silva EG, Jenkins R. Serous carcinoma in endometrial polyps. Mod Pathol

1990; 3 : 1208. | PubMed | ISI | ChemPort | Silva EG, R. Jenkins karsinoma
serosa dalam polip endometrium.. Mod Pathol 1990; 3: | 120-8 PubMed | ISI |
ChemPort |
26.Ambros RA, Ross JS, Kallakury BV, Malfetano J, Kim Y, Hwang J, et al . Ambros
RA, JS Ross, BV Kallakury, Malfetano J, Y Kim, Hwang J, et al. p53 gene status
in endometrial carcinomas showing diffuse positivity for p53 protein by
immunohistochemical analysis. Mod Pathol 1995; 8 : 4415. | PubMed | ISI |
ChemPort | gen p53 status dalam karsinoma endometrium menyebar
menunjukkan positif untuk protein p53 dengan analisis imunohistokimia:.
Mod Pathol 1995; 8. 441-5 | PubMed | ISI | ChemPort |
27.Ambros RA, Sheehan CE, Kallakury BV, Ross JS, Malfetano J, Paunovich E, et al
. Ambros RA, CE Sheehan, BV Kallakury, JS Ross, Malfetano J, E Paunovich, et
al. MDM2 and p53 protein expression in the histologic subtypes of
endometrial carcinoma. Mod Pathol 1996; 9 : 11659. | PubMed | ISI |
ChemPort | MDM2 dan ekspresi protein p53 dalam subtipe histologis
karsinoma endometrium:. Mod Pathol 1996; 9. 1165-9 | PubMed | ISI |
ChemPort |
28.Bur ME, Perlman C, Edelman L. p53 expression in neoplasms of the uterine

corpus. Am J Clin Pathol 1992; 98 : 817. | PubMed | ISI | ChemPort | Tetapi
ME, Perlman C, Edelman L. p53 ekspresi dalam neoplasma dari korpus
uterus:. Am J Clin Pathol 1992; 98. 81-7 | PubMed | ISI | ChemPort |
29.Ito K, Sasano H, Matsunaga G, Sato S, Yajima A, Nasim S, et al . K Ito, H

Sasano, G Matsunaga, Sato S, Yajima A, S Nasim, et al. Correlations between
p21 expression and clinicopathologic findings, p53 gene and protein
alterations, and survival in patients with endometrial carcinoma. J Pathol
1997; 183 : 31824. | Article | PubMed | ISI | ChemPort | Korelasi antara
ekspresi p21 dan klinikopatologi temuan, gen p53 dan perubahan protein,
dan kelangsungan hidup pada pasien dengan karsinoma endometrium.. J
Pathol 1997; 183: | 318-24 Artikel | PubMed | ISI | ChemPort |
30.Jiko K, Sasano H, Ito K, Ozawa N, Sato S, Yajima A. Immunohistochemical, and

in situ hybridization analysis of p53 in human endometrial carcinoma of the
uterus. Anticancer Res 1993; 13 : 30510. | PubMed | ISI | ChemPort | Jiko K,
Sasano H, Ito K, Ozawa N, Sato S, Yajima A. imunohistokimia, dan dalam
analisis hibridisasi in situ p53 pada karsinoma endometrium manusia rahim..
Antikanker Res 1993; 13: | 305-10 PubMed | ISI | ChemPort |
31.King SA, Adas AA, LiVolsi VA, Takahashi H, Behbakht K, McGovern P, et al . SA
Raja, Adas AA, LiVolsi VA, H Takahashi, K Behbakht, McGovern P, et al.
Expression and mutation analysis of the p53 gene in uterine papillary serous
carcinoma. Cancer 1995; 75 : 27005. | PubMed | ISI | ChemPort | Ekspresi
dan analisis mutasi gen p53 di serosa papiler karsinoma uterus.. Kanker
32.Kohler MF, Nishii H, Humphrey PA, Saski H, Marks J, Bast RC, et al . Kohler MF,
H Nishii, PA Humphrey, H Saski, Marks J, Bast RC, et al. Mutation of the p53
tumor-suppressor gene is not a feature of endometrial hyperplasia. Am J
Obstet Gynecol 1993; 169 : 6904. | PubMed | ISI | ChemPort | Mutasi gen
penekan tumor p53 bukan merupakan fitur dari hiperplasia endometrium:.
Am J Obstet Gynecol 1993; 169. 690-4 | PubMed | ISI | ChemPort |
33.Kohler MF, Berchuck A, Davidoff AM, Humphrey PA, Dodge RK, Iglehart JD, et
al . MF Kohler, Berchuck A, Davidoff AM, PA Humphrey, Dodge RK, Iglehart JD,
et al. Overexpression and mutation of p53 in endometrial carcinoma. Cancer
Res 1992; 52 : 16227. | PubMed | ISI | ChemPort | dan mutasi p53 pada
endometrium. karsinoma Ekspresi Cancer Res 1992; 52: 1622-7 |. PubMed |
ISI | ChemPort |
34.Moll UM, Chalas E, Auguste M, Meaney D, Chumas J. Uterine papillary serous

carcinoma evolves via a p53-driven pathway. Hum Pathol 1996; 27 : 1295
300. | Article | PubMed | ISI | ChemPort | Moll UM, Chalas E, Auguste M,
Meaney D, Chumas J. serous carcinoma rahim papiler berevolusi melalui jalur
p53-driven:. Hum Pathol 1996; 27. 1295-300 | Artikel | PubMed | ISI |
ChemPort |
35.Soslow RA, Shen PU, Chung MH, Isacson C. Distinctive p53 and mdm2
immunohistochemical expression profiles suggest different pathogenetic
pathways in poorly differentiated endometrial carcinoma. Int J Gynecol Pathol
1998; 17 : 12934. | PubMed | ISI | ChemPort | Soslow RA, Shen PU, Chung
MH, Isacson C. p53 Distinctive dan ekspresi imunohistokimia profil mdm2
menunjukkan jalur pathogenetic berbeda dalam endometrium karsinoma
dibedakan buruk:. Int J Gynecol Pathol 1998; 17. 129-34 | PubMed | ISI |
ChemPort |
36.Hussain SP, Harris CC. SP Hussain, Harris CC. Molecular epidemiology of

human cancer: contribution of mutation spectra studies of tumor suppressor
genes. Cancer Res 1998; 58 : 402337. | PubMed | ISI | ChemPort | Molekul
epidemiologi kanker manusia: kontribusi studi spektrum mutasi gen supresor
tumor:. Cancer Res 1998; 58. 4023-37 | PubMed | ISI | ChemPort |
37.Eschelman JR, Markowitz SD. Eschelman JR, Markowitz SD. Microsatellite

instability in inherited and sporadic neoplasms. Curr Opin Oncol 1995; 7 : 83
9. | PubMed | ChemPort | Ketidakstabilan mikrosatelit dan sporadis neoplasma
diwariskan:. Curr Opin Oncol 1995; 7. 83-9 | PubMed | ChemPort |
38.Loeb LA. Loeb LA. Microsatellite instability: marker of a mutator phenotype in
cancer. Cancer Res 1994; 54 : 505963. | PubMed | ISI | ChemPort |
Ketidakstabilan mikrosatelit: penanda dari fenotipe mutator kanker:. Cancer
Res 1994; 54. 5059-63 | PubMed | ISI | ChemPort |
39.Burks RT, Kessis TD, Cho KR, Hedrick L. Microsatellite instability in

endometrial carcinoma. Oncogene 1994; 11 : 11636. Burks RT, Kessis TD,
Cho KR, Hedrick L. ketidakstabilan mikrosatelit pada karsinoma
endometrium:. Onkogen 1994; 11 1163-6.
40.Caduff RF, Johnston CM, Svoboda-Newman SM, Poy EL, Merajver SD, Frank TS.
Caduff RF, CM Johnston, Svoboda-Newman SM, Poy EL, Merajver SD, TS Frank.
Clinical and pathological significance of microsatellite instability in sporadic
endometrial carcinoma. Am J Pathol 1996; 148 : 16718. | PubMed | ISI |
ChemPort | Signifikansi klinis dan patologis ketidakstabilan mikrosatelit pada
karsinoma endometrium sporadis |. Am J Pathol 1996; 148 1671-8:. PubMed |
ISI | ChemPort |
41.Duggan BD, Felix JC, Muderspach LI, Tourgeman D, Zheng J, Shibata D.

Microsatellite instability in sporadic endometrial carcinoma. J Natl Cancer Inst
1994; 86 : 121621. | PubMed | ChemPort | Duggan BD, Felix JC, Muderspach
LI, Tourgeman D, Zheng J, Shibata D. ketidakstabilan mikrosatelit pada
karsinoma endometrium sporadis.. J Natl Cancer Inst 1994; 86: | 1216-21
PubMed | ChemPort |
42.Mutter GL, Boynton KA, Faquin WC, Ruiz RE, Jovanovic AS. Bergumam GL, KA
Boynton, WC Faquin, RE Ruiz, Jovanovic AS. Allelotype mapping of unstable
microsatellites establishes direct lineage continuity between endometrial
precancers and cancer. Cancer Res 1996; 56 : 44836. | PubMed | ISI |
ChemPort | pemetaan Allelotype dari mikrosatelit tidak stabil menetapkan
kesinambungan garis keturunan langsung antara precancers endometrium
dan kanker.. Cancer Res 1996; 56: | 4483-6 PubMed | ISI | ChemPort |
43.Peiffer SL, Herzog TJ, Tribune DJ, Mutch DG, Gersell DJ, Goodfellow PJ. SL
Peiffer, Herzog TJ DG, Tribune DJ, Mutch, Gersell DJ, Goodfellow PJ. Allelic loss
of sequences from the long arm of chromosome 10 and replication errors in
endometrial cancers. Cancer Res 1995; 55 : 19226. | PubMed | ISI |
ChemPort | Alelik hilangnya urutan dari lengan panjang kromosom 10 dan
kesalahan replikasi pada kanker endometrium.. Kanker Res 1995; 55: | 1922-
6 PubMed | ISI | ChemPort |
44.Risinger JI, Berchuck A, Kohler MF, Watson P Lynch HT, Boyd J. Genetic
instability of microsatellites in endometrial carcinoma. Cancer Res 1993; 53 :
51003. | PubMed | ISI | ChemPort | Risinger JI, Berchuck A, Kohler MF, Watson
P Lynch HT, Boyd J. Genetik ketidakstabilan mikrosatelit pada karsinoma
endometrium.. Kanker Res 1993; 53: | 5100-3 PubMed | ISI | ChemPort |
45.Tashiro H, Lax SF, Gaudin PB, Isacson C, Cho KR, Hedrick L. Microsatellite
instability is uncommon in uterine serous carcinoma. Am J Pathol 1997; 150 :
759. | PubMed | ISI | ChemPort | Tashiro H, Lax SF, Gaudin PB, Isacson C, Cho
KR, Hedrick L. ketidakstabilan mikrosatelit jarang pada karsinoma serosa
uterus:. Am J Pathol 1997; 150. 75-9 | PubMed | ISI | ChemPort |
46.Catasus L, Machin P, Matias-Guiu X, Prat J. Microsatellite instability in

endometrial carcinomas. Catasus L, Machin P, Matias-Guiu X, Prat J.
ketidakstabilan mikrosatelit karsinoma endometrium. Clinicopathologic
correlations in a series of 42 cases. Hum Pathol 1998; 29 : 11604. | Article |
PubMed | ISI | ChemPort | Klinikopatologi korelasi dalam serangkaian 42
kasus.. Hum Pathol 1998; 29: | 1160-4 Artikel | PubMed | ISI | ChemPort |
47.Gurin CC, Federici MG, Kang L, Boyd J. Causes and consequences of

microsatellite instability in endometrial carcinoma. Cancer Res 1999; 59 :
4626. | PubMed | ISI | ChemPort | CC, Federici MG, Kang L, Boyd J. Penyebab
dan konsekuensi ketidakstabilan mikrosatelit endometrium. Karsinoma Gurin
Cancer Res 1999; 59:. 462-6 | PubMed | ISI | ChemPort |
48.Levine RL, Cargile CB, Blazes MS, van Rees B, Kurman RJ, Ellenson LH. PTEN
mutations and microsatellite instability in complex atypical hyperplasia, a
precursor lesion to uterine endometrioid carcinoma. Cancer Res 1998; 58 :
35248. Levine RL, Cargile CB, blazes MS, van Rees B, Kurman RJ, Ellenson LH
58. PTEN mutasi dan ketidakstabilan mikrosatelit atipikal kompleks dalam
hiperplasia, prekursor lesi endometrioid rahim untuk: karsinoma. Cancer Res
1998; 3524-8.
49.Maxwell GL, Risinger JI, Gumbs C, Shaw H, Bentley RC, Barrett JC, et al .
Maxwell GL, JI Risinger, Gumbs C, H Shaw, Bentley RC, JC Barrett, et al.
Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.
Cancer Res 1998; 58 : 25003. | PubMed | ISI | ChemPort | dari PTEN dalam
gen penindas tumor endometrium. hyperplasias Mutasi Cancer Res 1998; 58:.
2500-3 | PubMed | ISI | ChemPort |
50.Risinger JI, Hayes AK, Berchuck A, Barrett JC. PTEN/MMAC1 mutations in

endometrial cancers. Cancer Res 1997; 57 : 47368. | PubMed | ISI |
ChemPort | Risinger JI, Hayes AK, Berchuck A, Barrett JC. PTEN/MMAC1. Mutasi
endometrium pada 4736-8 kanker. Cancer Res 1997; 57 |: PubMed | ISI |
ChemPort |
51.Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, et al . H Tashiro, blazes
MS, R Wu, KR Cho, S Bose, Wang SI, et al. Mutations in PTEN are frequent in
endometrial carcinoma but rare in other common gynecological malignancies.
Cancer Res 1997; 57 : 393540. | PubMed | ISI | ChemPort | Mutasi di PTEN
sering terjadi pada karsinoma endometrium tetapi jarang di lain keganasan
ginekologi umum.. Kanker Res 1997; 57: | 3935-40 PubMed | ISI | ChemPort |
52.Boyd J, Risinger JI. Boyd J, Risinger JI. Analysis of oncogene alterations in

human endometrial carcinoma: prevalence of ras mutations. Mol Carcinog
1991; 4 : 18995. | PubMed | ISI | ChemPort | Analisis perubahan onkogen
pada karsinoma endometrium manusia: Prevalensi mutasi ras:. Mol Carcinog
1991; 4. 189-95 | PubMed | ISI | ChemPort |
53.Caduff RF, Johnston CM, Frank TS. Caduff RF, Johnston CM, TS Frank.
Mutations of the Ki- ras oncogene in carcinoma of the endometrium. Am J
Pathol 1995; 146 : 1828. | PubMed | ISI | ChemPort | Mutasi dari-ras onkogen
Ki dalam karsinoma endometrium.. Am J Pathol 1995; 146: | 182-8 PubMed |
ISI | ChemPort |
54.Enomoto T, Inoue M, Perantoni AO, Buzard GS, Miki H, Tanizawa O, et al .

Enomoto T, M Inoue, Perantoni AO, GS Buzard, H Miki, Tanizawa O, et al. K-
ras activation in premalignant and malignant epithelial lesions of the human
uterus. Cancer Res 1991; 51 : 530814. | PubMed | ISI | ChemPort | K-ras
aktivasi ganas epitel lesi dan premaligna dari rahim manusia.. Kanker Res
55.Ignar-Trowbridge D, Risinger JI, Dent GA, Kohler M, Berchuck A, McLachlan JA,

et al . Ignar-Trowbridge D, Risinger JI, Dent GA, M Kohler, Berchuck A JA
McLachlan,, et al. Mutations of the Ki- ras oncogene in endometrial
carcinoma. Am J Obstet Gynecol 1992; 167 : 22732. | PubMed | ChemPort |
Mutasi dari Ki-ras onkogen pada karsinoma endometrium:. Am J Obstet
Gynecol 1992; 167. 227-32 | PubMed | ChemPort |
56.Sasaki H, Nishii H, Takahashi H, Tada A, Furusato M, Terashima Y, et al . Sasaki

H, H Nishii, Takahashi H, Tada A Furusato M, Terashima, Y et al,. Mutation of
the Ki- ras protooncogene in human endometrial hyperplasia and carcinoma.
Cancer Res 1993; 53 : 190610. | PubMed | ISI | ChemPort | dari Ki ras
protoonkogen di-manusia dan hiperplasia endometrium karsinoma. Mutasi
Cancer Res 1993; 53: 1906-10 |. PubMed | ISI | ChemPort |
57.Nyholm HCJ, Nielsen AL, Lyndrup J, Norup P, Thorpe SM. Nyholm HCJ AL,
Nielsen, Lyndrup J, P Norup, SM Thorpe. Biochemical and
immunohistochemical estrogen and progesterone receptors in adenomatous
hyperplasia and endometrial carcinoma: correlations with stage and other
clinicopathologic features. Am J Obstet Gynecol 1992; 167 : 133442. |
PubMed | ISI | ChemPort | Biokimia dan estrogen imunohistokimia dan
reseptor progesteron di adenomatosa hiperplasia dan karsinoma
endometrium: korelasi dengan panggung dan fitur klinikopatologi lainnya..
Am J Obstet Gynecol 1992; 167: | 1334-42 PubMed | ISI | ChemPort |
58.Esteller M, Garcia A, Martinez-Palones JM, Xercavins J, Reventos J. Detection of

clonality and genetic alterations in endometrial pipelle biopsy and its surgical
specimen counterpart. Lab Invest 1997; 76 : 10916. | PubMed | ISI |
ChemPort |
59.Mutter GL, Chaponot ML, Fletcher JA. A polymerase chain reaction assay for
non-random X chromosome inactivation identifies monoclonal endometrial
cancers and precancers. Am J Pathol 1995; 146 : 5018. | PubMed | ISI |
ChemPort |
60.Bulun SE, Economos K, Miller D, Simpson ER. CYP19 (aromatase cytochrome
P450) gene expression in human malignant endometrial tumors. J Clin
Endocrinol Metab 1994; 79 : 18314. | Article | PubMed | ISI | ChemPort |
61.Wantanabe K, Sasano H, Harada N, Ozaki M, Niikura H, Sato S, et al .

Aromatase in human endometrial carcinoma and hyperplasia.
Immunohistochemical, in situ hybridization, and biochemical studies. Am J
Pathol 1995; 146 : 491500. | PubMed | ISI | ChemPort |
62.Cooke PS, Buchanan DL, Young P, Setiawan T, Brody J, Korach KS, et al .

Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine
epithelium. Proc Natl Acad Sci USA 1997; 94 : 653540. | Article | PubMed |
ChemPort |
63.Yager JD, Liehr JG. Molecular mechanisms of estrogen carcinogenesis. Ann

Rev Pharmacol Toxicol 1996; 36 : 20332. | Article | ISI | ChemPort |
64.Bitterman P, Chun B, Kurman RJ. The significance of epithelial differentiation

in mixed mesodermal tumors of the uterus. A clinicopathologic and
immunohistochemical study. Am J Surg Pathol 1990; 14 : 31728. | PubMed |
ISI | ChemPort |
65.de Brito PA, Silverberg SG, Orenstein JM. Carcinosarcoma (malignant mixed
mullerian (mesodermal) tumor) of the female genital tract: immuno-
histochemical and ultrastructural analysis of 28 cases. Hum Pathol 1993; 24 :
13242. | Article | PubMed | ChemPort |
66.Emoto M, Iwasaki H, Kikuchi M, Shirakawa K. Characteristics of cloned cells of

mixed mullerian tumor of the human uterus. Carcinoma cells showing
myogenic differentiation in vitro. Cancer 1993; 71 : 306575. | Article |
67.Gorai I, Doi C, Minaguchi H. Establishment and characterization of

carcinosarcoma cell line of the human uterus. Cancer 1993; 71 : 77586. |
68.Ambros R, Sherman M, Zahn C, Bitterman P, Kurman RJ. Association of

endometrial hyperplasia and endometrial intraepithelial carcinoma and
malignant mixed mullerian tumors [abstract]. Mod Pathol 1993; 6 : 72A.
69.Lax SF, Pizer ES, Ronnett BM, Kurman RJ. Clear cell carcinoma of the
endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen,
and progesterone receptor expression. Hum Pathol 1998; 29 : 5518. | Article
| PubMed | ISI | ChemPort |
Endometrial Carcinoma
Carcinoma of the endometrium is mainly adenocarcinoma arising from the lining of the uterus
and is an oestrogen-dependent tumour. Karsinoma endometrium terutama adenokarsinoma
timbul dari lapisan rahim dan merupakan tumor estrogen-tergantung. This is distinct from
carcinoma of the cervix which is squamous cell carcinoma. Hal ini berbeda dari karsinoma leher
rahim yang karsinoma sel skuamosa. Cancer of the body of the uterus could include myometrial
sarcoma. Kanker badan rahim dapat mencakup sarkoma miometrium.
Pathogenesis Patogenesis
Although carcinoma of the endometrium is basically adenocarcinoma, the histology is not so

simple: Meskipun karsinoma endometrium pada dasarnya adenokarsinoma, histologi tidak begitu
sederhana:
Endometrioid represents 75 to 80% and includes ciliated adenocarcinoma,

secretory adenocarcinoma, papillary or villoglandular and adenocarcinoma
with squamous differentiation Endometrioid sejumlah 75 sampai 80% dan
termasuk adenokarsinoma bersilia, adenokarsinoma sekretori, papilari atau
villoglandular dan adenocarcinoma dengan diferensiasi skuamosa
Uterine papillary serous is less than 10% Papiler serosa uterus kurang dari
10%
Mucinous 1% Mucinous 1%
Clear cell 4% Hapus sel 4%
Squamous cell is less than 1% sel skuamosa kurang dari 1%
Mixed is 10% Campuran adalah 10%
It may be undifferentiated. Ini mungkin tidak dibedakan.
Epidemiology Epidemiologi
This malignancy is rare below the age of 40. keganasan Ini jarang di bawah usia 40. It affects
about 1 woman in 100, usually in the mid to late 50s but it can be into later life. Ini
mempengaruhi sekitar 1 wanita di 100, biasanya pada pertengahan hingga akhir 50-an tapi bisa
dalam kehidupan nanti.
It is most common in western societies but is becoming more common in Asia. Hal ini paling
umum dalam masyarakat Barat, tetapi menjadi lebih umum di Asia. In the UK there are about
5,100 new cases per year. Di Inggris ada sekitar 5.100 kasus baru per tahun.
Risk factors Faktor risiko
Prolonged periods of unopposed oestrogen are the main risk factor. periode
berkepanjangan estrogen terlindung merupakan faktor risiko utama. Unopposed oestrogen
means when oestrogen is not modified by the effects of progesterone . estrogen dilawan
berarti ketika estrogen tidak dimodifikasi oleh pengaruh progesteron.
This may occur as a result of medication or in anovulatory cycles where the corpus luteum does
not mature and secrete progesterone. Hal ini mungkin terjadi sebagai akibat dari pengobatan atau
dalam siklus anovulasi mana korpus luteum tidak matang dan mengeluarkan progesteron. The
histological diagnosis can be difficult in that gross endometrial hyperplasia can look like a well-
differentiated carcinoma. Diagnosis histologis bisa sulit dalam kotor hiperplasia endometrium
dapat terlihat seperti sebuah-diferensiasi karsinoma baik.
Risk factors for endometrial carcinoma include: 1 Faktor risiko karsinoma endometrium antara
lain: 1
Being nulliparous increases the risk 2- or 3-fold. Menjadi meningkatkan risiko

nulipara 2 - atau 3 kali lipat. This may be by choice or as a result of infertility
with anovulatory cycles. Ini mungkin karena pilihan atau sebagai akibat dari
infertilitas dengan siklus anovulasi.
Menopause past the age of 52. Menopause melewati usia 52.
Obesity raises oestrogen levels: Obesitas meningkatkan kadar estrogen:
o Diabetes mellitus and hypertension also increase the risk but this may
simply be linked to obesity. Diabetes mellitus dan hipertensi juga
meningkatkan risiko tapi ini hanya dapat dihubungkan dengan
obesitas.
o Polycystic ovarian syndrome and (insulin resistance) metabolic

syndrome are also associated with obesity. Sindrom polikistik ovarium
dan (resistensi insulin) sindrom metabolik juga terkait dengan obesitas.
o The greater the obesity, the greater the risk. Semakin besar obesitas,
semakin besar risikonya.
Women who have hereditary nonpolyposis colon cancer (HNPCC) 2 have a 22

to 50% chance of developing endometrial carcinoma and are likely to get it
about 15 years earlier than other women. Wanita yang memiliki kanker usus
turun temurun nonpolyposis (HNPCC) 2 memiliki hingga 50% peluang 22
mengembangkan karsinoma endometrium dan cenderung untuk
mendapatkannya sekitar 15 tahun lebih awal daripada wanita lain. There is a
lack of evidence to suggest benefit but annual endometrial biopsy after the
age of 35 is suggested. Ada kurangnya bukti yang menunjukkan manfaat tapi
tahunan biopsi endometrium setelah usia 35 disarankan.
Exogenous hormones can have markedly different effects. hormon eksogen
dapat memiliki efek yang sangat berbeda. The antioestrogenic or pro-
oestrogenic effect of a synthetic hormone varies between tissues. Efek
antioestrogenic atau pro-estrogen dari hormon sintetik bervariasi antara
jaringan. For example, tamoxifen is used to treat breast cancer because it has
an antioestrogen effect on breast tissue but it has a pro-oestrogen effect on
bone, reducing the risk of osteoporosis and a pro-oestrogen effect on the
endometrium, increasing the risk of endometrial carcinoma. Misalnya,
tamoksifen digunakan untuk mengobati kanker payudara karena memiliki
efek antioestrogen pada jaringan payudara tetapi memiliki dampak pro-
estrogen pada tulang, mengurangi resiko osteoporosis dan efek pro-estrogen
pada endometrium, meningkatkan resiko endometrium karsinoma. Tamoxifen
is associated with an increased risk of endometrial cancer that tends to be at
a more advanced stage and with a less favourable histology. 3 In the
treatment of breast cancer, benefits outweigh risks but its use in prevention
of the disease has been questioned. Tamoxifen dikaitkan dengan peningkatan
risiko kanker endometrium yang cenderung berada pada tahap yang lebih
maju dan dengan histologi yang kurang menguntungkan. 3 Dalam
pengobatan kanker payudara, manfaat lebih besar daripada risiko namun
penggunaannya dalam pencegahan penyakit telah dipertanyakan.
Tibolone doubles the risk of endometrial carcinoma compared with those not
on hormone replacement therapy (HRT). Tibolone melipatgandakan risiko
karsinoma endometrium dibandingkan dengan mereka yang tidak di terapi
penggantian hormon (HRT).
Taking combined oral contraceptives reduces the risk of developing

endometrial cancer in later life. 4 Prolonged use increases the benefit that
lasts for at least 15 years after stopping. Mengambil kontrasepsi oral
kombinasi mengurangi risiko kanker endometrium di kemudian hari. 4
penggunaan jangka panjang meningkatkan manfaat yang berlangsung
selama minimal 15 tahun setelah berhenti.
The Million Women Study The Juta Studi Perempuan

This study showed that women taking unopposed oestrogen are at increased risk of endometrial
carcinoma compared with those who have never taken HRT but, if progestogen is added, this
increased risk disappears. 5 Studi ini menunjukkan bahwa wanita yang menggunakan estrogen
terlindung berada pada peningkatan risiko karsinoma endometrium dibandingkan dengan mereka
yang tidak pernah mengambil HRT tetapi, jika progestogen ditambahkan, peningkatan risiko
menghilang. 5
The risk of breast cancer is greater in those on HRT with progestogen, than unopposed HRT or
tibolone. Risiko kanker payudara lebih besar pada mereka pada HRT dengan progestogen, dari
HRT terlindung atau Tibolone. Breast cancer is about 8 times more frequent than endometrial
cancer. Kanker payudara adalah sekitar 8 kali lebih sering dari kanker endometrium. The study
showed that for every 100 women on combined HRT for 5 years, 3 will develop either breast or
endometrial carcinoma, compared with 2.5 for those on unopposed HRT or tibolone and 1.5 for
those not on HRT. Hasil penelitian menunjukkan bahwa untuk setiap 100 wanita pada HRT
gabungan selama 5 tahun, 3 akan mengembangkan salah satu atau endometrium karsinoma
payudara, dibandingkan dengan 2,5 bagi mereka pada HRT terlindung atau Tibolone dan 1,5 bagi
mereka yang tidak pada HRT.
Since the million women were recruited in the late 1990s, around 1,300 have developed
endometrial cancer and over 10,000 have developed breast cancer. Karena juta perempuan
direkrut di akhir 1990-an, sekitar 1.300 telah mengembangkan kanker endometrium dan lebih
dari 10.000 telah mengembangkan kanker payudara.
Presentation Presentasi
History Sejarah
Classically, endometrial carcinoma presents as postmenopausal bleeding (PMB) and, although
this is not the only cause, it must be excluded. Klasik, karsinoma endometrium muncul sebagai
perdarahan postmenopause (PMB) dan, walaupun ini bukan satu-satunya penyebab, itu harus
dikecualikan. It may also present around or before the menopause in about 20 to 25% of cases
with irregularities of the menstrual cycle. Mungkin juga hadir di sekitar atau sebelum menopause
pada sekitar 20 sampai 25% dari kasus dengan penyimpangan dari siklus haid.
Examination Pemeriksaan
Unless the disease is well advanced there is unlikely to be any physical abnormality. Kecuali
penyakit ini juga sudah lanjut ada tidak akan ada kelainan fisik.
If a recent cervical smear has not been taken this should be done. Jika baru-baru ini hapusan
serviks belum diambil ini harus dilakukan. (Occasionally a smear may show clumps of
adenocarcinoma, but this is unreliable and is not a substitute for further investigation.) (Kadang-
kadang smear mungkin menunjukkan gumpalan adenokarsinoma, tapi ini tidak dapat diandalkan
dan bukan merupakan pengganti untuk penyelidikan lebih lanjut.)
Investigation Investigasi
Transvaginal ultrasound (TVUS) scan USG transvaginal (TVUS) scan

Where sufficient local skills and resources exist, TVUS scan is an appropriate first-line
procedure to identify which women with PMB are at higher risk of endometrial cancer. Mana
keterampilan yang memadai dan sumber daya lokal yang ada, TVUS scan merupakan prosedur
pertama-baris yang sesuai untuk mengidentifikasi wanita dengan PMB berada pada risiko tinggi
kanker endometrium.
The mean endometrial thickness in postmenopausal women is much thinner than in
premenopausal women. Ketebalan endometrium pada wanita menopause berarti jauh lebih tipis
dibandingkan pada wanita premenopause. Thickening of the endometrium may indicate the
presence of pathology. Penebalan endometrium dapat mengindikasikan adanya patologi. In
general, the thicker the endometrium, the higher the likelihood of important pathology - ie
endometrial cancer being present. Secara umum, tebal endometrium, semakin tinggi
kemungkinan patologi penting - yaitu kanker endometrium yang sekarang. The threshold in the
UK is 5 mm; a thickness of >5 mm gives 7.3% likelihood of endometrial cancer. 6 A thickness of
<5 mm has a negative predictive value of 98%. 1 Ambang di Inggris adalah 5 mm; Dengan
ketebalan> 5 mm memberikan 7,3% kemungkinan kanker endometrium. 6 A ketebalan <5 mm
memiliki nilai prediksi negatif 98%. 1
A recent meta-analysis found that a TVUS result of 5 mm or less reduced the risk of disease by
84%. 7 Some pathology may be missed and it is recommended that hysteroscopy and biopsy
should be performed if clinical suspicion is high. 8 , 9 The accuracy of assessing endometrial
thickness in women with diabetes and obesity has been questioned, 10 but models have been
developed to take personal characteristics into account when predicting the risk of cancer. 11
Sebuah analisis baru-meta menemukan bahwa hasil TVUS 5 mm atau kurang mengurangi risiko
penyakit dengan 84%. 7 patologi Beberapa mungkin akan terjawab dan dianjurkan bahwa
histeroskopi dan biopsi harus dilakukan jika kecurigaan klinis tinggi. 8 , 9 Keakuratan menilai
ketebalan endometrium pada wanita dengan diabetes dan obesitas telah mempertanyakan, 10
tetapi model telah dikembangkan untuk mengambil karakteristik pribadi ke account user ketika
memprediksi risiko kanker. 11
Endometrial biopsy Biopsi endometrium

A definitive diagnosis in PMB is made by histology. Diagnosis definitif di PMB dibuat oleh
histologi. Historically, endometrial samples have been obtained by dilatation and curettage.
Secara historis, sampel endometrium telah diperoleh oleh dilatasi dan kuretase. Nowadays it is
more usual to obtain a sample by endometrial biopsy, which can be undertaken using samplers.
Saat itu lebih biasa untuk mendapatkan sampel dengan biopsi endometrium, yang dapat
dilakukan dengan menggunakan sampler. Endometrial biopsy can be performed as either an
outpatient procedure, or under general anaesthetic. Biopsi endometrium dapat dilakukan sebagai
prosedur rawat jalan, atau di bawah anestesi umum. All methods of sampling the endometrium
will miss some cancers. Semua metode sampling endometrium akan kehilangan beberapa jenis
kanker.
Hysteroscopy Histeroskopi
Hysteroscopy and biopsy (curettage) is the preferred diagnostic technique to detect polyps and
other benign lesions. Histeroskopi dan biopsi (kuretase) adalah teknik diagnostik disukai untuk
mendeteksi polip dan lesi jinak lainnya. Hysteroscopy may be performed as an outpatient
procedure, although some women will require general anaesthetic. Histeroskopi dapat dilakukan
sebagai prosedur rawat jalan, meskipun beberapa wanita akan membutuhkan anestesi umum.
A significant development has been direct referral to 'one stop' specialist clinics. 12 , 13 At such
clinics several investigations are available to complement clinical evaluation, including
ultrasound, endometrial sampling techniques and hysteroscopy. Perkembangan yang signifikan
telah rujukan langsung untuk menghentikan 'spesialis klinik satu'. 12 , 13 Pada klinik tersebut
tersedia beberapa penyelidikan untuk melengkapi evaluasi klinis, termasuk USG, teknik
pengambilan sampel endometrium dan histeroskopi. Following such assessment, reassurance can
be given, or further investigations or treatment can be discussed and arranged. Setelah penilaian
tersebut, jaminan bisa diberikan, atau penyelidikan lebih lanjut atau perawatan dapat dibahas dan
diatur.
Staging Pementasan
Total abdominal hysterectomy with bilateral salpingo-oophorectomy is required both as a

primary treatment and for the purpose of staging. Total abdominal histerektomi dengan bilateral-
ooforektomi salpingo diperlukan baik sebagai pengobatan primer dan untuk tujuan pementasan.
The International Federation of Obstetrics and Gynaecology (FIGO) gives the following staging:
14
Federasi Internasional Obstetri dan Ginekologi (FIGO) memberikan pementasan berikut: 14
Stage I endometrial cancer is carcinoma confined to the corpus uteri:

Stadium I kanker endometrium adalah karsinoma terbatas pada korpus uteri:
o IA confined to endometrium IA terbatas pada endometrium
o IB invasion to less than half of myometrium IB invasi sampai kurang

dari setengah miometrium
o IC invasion beyond half of myometrium IC invasi melampaui setengah

dari miometrium
Stage II involves the corpus and the cervix, but has not extended outside the
uterus: Tahap II melibatkan korpus dan serviks, tetapi tidak diperpanjang di
luar rahim:
o Stage IIA is endocervical glandular involvement only Tahap IIA adalah

keterlibatan kelenjar endoserviks hanya
o Stage IIB is cervical stromal invasion Tahap IIB adalah invasi stroma
serviks
Stage III extends outside of the uterus but is confined to the true pelvis:
Tahap III meluas di luar rahim, tetapi hanya terbatas pada panggul benar:
o Stage IIIA is invasion of serosa or adnexa or positive peritoneal

cytology and possibly more than one of these Tahap IIIA adalah invasi
serosa atau adneksa atau sitologi peritoneum positif dan mungkin
lebih dari satu ini
o Stage IIIB is vaginal metastases Tahap IIIB adalah metastasis vagina
o Stage IIIC is metastases to pelvic or para-aortic lymph nodes, or both

Tahap IIIC adalah metastasis ke kelenjar getah bening panggul atau
para-aorta, atau keduanya
Stage IV is involvement of the bladder or bowel mucosa, or distant
metastasis: Tahap IV adalah keterlibatan mukosa kandung kemih atau usus,
atau metastasis jauh:
o Stage IVA is involvement of bowel or bladder mucosa Tahap IVA adalah

keterlibatan mukosa usus atau kandung kemih
o Stage IVB is distant metastases including nodes in the abdomen or

inguinal region Tahap IVB adalah metastasis jauh termasuk kelenjar di
perut atau wilayah inguinalis
A further grouping with prognostic significance is possible with FIGO approval, based on degree
of tumour differentiation as follows: Sebuah pengelompokan lebih lanjut dengan makna
prognostik adalah mungkin dengan persetujuan FIGO, berdasarkan tingkat diferensiasi tumor
sebagai berikut:
G1 is 5% or less of a non-squamous or non-morular solid growth pattern G1

adalah 5% atau kurang dari pola pertumbuhan non-skuamosa atau non-
morular padat
G2 is 6 to 50% of a non-squamous or non-morular solid growth pattern G2

adalah 6 sampai 50% dari pola pertumbuhan non-skuamosa atau non-
morular padat
G3 is over 50% of a non-squamous or non-morular solid growth pattern G3

adalah lebih dari 50% dari pola pertumbuhan non-skuamosa atau non-
morular padat
Management Manajemen
Treatment depends upon stage: Pengobatan tergantung pada tahap:
Stage IA and IB require total abdominal hysterectomy with bilateral salpingo-

oophorectomy. Tahap IA dan IB memerlukan histerektomi abdominal total
dengan bilateral-ooforektomi salpingo.
In stage IC and stage II, in addition there should be pelvic radiotherapy.

Dalam IC panggung dan tahap II, selain harus ada radioterapi pelvis. Bowel
complications occur in about 4%. komplikasi usus terjadi pada sekitar 4%. If
the patient is unfit for surgery then radiotherapy alone may be used. Jika
pasien tidak layak untuk operasi maka radioterapi saja dapat digunakan.
Stage III is best treated with surgery, external beam radiotherapy and
intracavity radiotherapy but if the tumour is adherent to the pelvic wall it may
be inoperable. Tahap III lebih baik diobati dengan operasi, radioterapi berkas
eksternal dan radioterapi intrakaviter, tetapi jika tumor melekat ke dinding
panggul mungkin bisa dioperasi.
For stage IV, if metastases are in the pelvis then combination radiotherapy is
used as in stage III but for distant, such as pulmonary metastases,
progestational agents are best. Untuk stadium IV, jika metastasis berada di
panggul maka kombinasi radioterapi digunakan sebagai dalam tahap III tapi
untuk metastasis jauh, seperti paru, agen progestational adalah yang terbaik.
Progestational agents may be used in any advanced disease and there is a

response in 15 to 30%. agen Progestational dapat digunakan dalam penyakit
lanjut dan ada respon di 15 sampai 30%. Stage IV tends to occur in the
elderly. Tahap IV cenderung terjadi pada orang tua. Treatment can produce a
useful response but outlook is poor. 15 Pengobatan dapat menghasilkan
respon yang berguna tetapi pandangan buruk. 15
Recurrence may respond to radiotherapy. Kekambuhan dapat menanggapi

radioterapi. Radical radiotherapy for local recurrence is effective in over half
the cases. 16 It may be possible to detect progestogen receptor sites on the
tumour. radioterapi radikal untuk kekambuhan lokal efektif pada lebih dari
separuh kasus. 16 Dimungkinkan untuk mendeteksi situs reseptor
progestogen pada tumor. If they are positive there is a 75% chance of
response but if negative only 7%. Jika positif ada kemungkinan 75% dari
respon tetapi jika negatif hanya 7%. Negative receptor disease may respond
better to chemotherapy. penyakit reseptor negatif dapat merespon lebih baik
terhadap kemoterapi.
Doxyrubicin gives a good but often temporary response. Doxyrubicin

memberikan respon yang baik tetapi sering sementara.
17
Paclitaxel and carboplatin are also used. Paclitaxel dan carboplatin juga
digunakan. 17
Progestogen therapy is usually given with either medroxyprogesterone or

megestrol. Progestogen terapi biasanya diberikan dengan baik
medroksiprogesteron atau megestrol. Tamoxifen may have a useful adjuvant
effect. 18 Tamoxifen mungkin memiliki efek adjuvant berguna. 18
Prognosis Prognosa
The overall 20 years survival rate for all forms of endometrial carcinoma is about 80%. 19
Staging is not the only variable and aggressiveness of the tumour is very variable. Tahun-tahun
secara keseluruhan 20 sintasan untuk semua bentuk karsinoma endometrium adalah sekitar 80%.
19
Staging bukan hanya variabel dan agresivitas tumor sangat bervariasi. Most women present at
stage I. Kebanyakan wanita hadir pada tahap I.
The overall mortality for endometrial carcinoma according to stage is roughly: 20 Angka
kematian keseluruhan untuk karsinoma endometrium menurut tahap kira-kira: 20
IIA IIB IIIA IIIB IIIC IVA IVB

Stage Tahap IA IA IB IB IC IC
IIA IIB IIIA IIIB IIIC IVA IVB
5-year Survival 5 91% 88% 81% 77% 67% 60% 41% 32% 20% 5%
tahun Survival 91% 88% 81% 77% 67% 60% 41% 32% 20% 5%
The majority of endometrial cancers are relatively benign and curable but about 20% have a
bleak outlook. 21 More virulent tumours include papillary adenocarcinoma, papillary serous
adenocarcinoma, adenosquamous carcinoma, and clear cell carcinoma. Sebagian besar kanker
endometrium relatif jinak dan dapat disembuhkan, tetapi sekitar 20% memiliki pandangan
suram. 21 tumor ganas Lebih meliputi adenokarsinoma papiler, adenokarsinoma serosa papiler,
adenosquamous karsinoma, dan karsinoma sel jernih.
Document references Dokumen Referensi
1. Sahdev A ; Imaging the endometrium in postmenopausal bleeding. Sahdev

A ; Imaging endometrium pada perdarahan postmenopause. BMJ. BMJ. 2007
Mar 24;334(7594):635-6. 2007 Maret 24, 334 (7594) :635-6.
2. OMIM ; Colorectal Cancer, Hereditary Nonpolyposis, Type 1. OMIM ; Kanker

Kolorektal, Nonpolyposis herediter, Tipe 1. Online Mendelian Inheritance in
Man. Warisan online Mendel di Man.
3. Bergman L, Beelen ML, Gallee MP, et al ; Risk and prognosis of endometrial

cancer after tamoxifen for breast cancer. Bergman L, Beelen ML, Gallee MP,
et al ; Risiko dan prognosis kanker endometrium setelah tamoxifen untuk
kanker payudara. Comprehensive Cancer Centres' ALERT Group. Pusat Kanker
Komprehensif 'ALERT Group. Assessment of Liver and Endometrial cancer
Risk following Tamoxifen. Penilaian Hati dan Risiko kanker endometrium
berikut Tamoxifen. Lancet. Lancet. 2000 Sep 9;356(9233):881-7. 2000
September 9; 356 (9233) :881-7. [abstract] [Abstrak]
4. Deligeoroglou E, Michailidis E, Creatsas G ; Oral contraceptives and

reproductive system cancer.; Ann NY Acad Sci. 2003 Nov;997:199-208.
Deligeoroglou E, Michailidis E, Creatsas G ; Kontrasepsi oral dan kanker
sistem reproduksi;. Ann NY Acad Sci;. 2003 November 997:199-208.
[abstract] [Abstrak]
5. Beral V, Bull D, Reeves G ; Endometrial cancer and hormone-replacement

therapy in the Million Women Study. Beral V, Bull D, Reeves G , kanker
endometrium dan-penggantian terapi hormon dalam Studi Perempuan Juta.
Lancet. Lancet. 2005 Apr 30-May 6;365(9470):1543-51. 2005 30-06 April Mei;
365 (9470) :1543-51. [abstract] [Abstrak]
6. Smith-Bindman R, Weiss E, Feldstein V ; How thick is too thick? Smith-

Bindman R, Weiss E, Feldstein V ; Bagaimana tebal terlalu tebal? When
endometrial thickness should prompt biopsy in postmenopausal women
without vaginal bleeding. Ketika ketebalan endometrium akan dimintakan
biopsi pada wanita postmenopause tanpa perdarahan vagina. Ultrasound
Obstet Gynecol. Ultrasound Obstet Gynecol. 2004 Oct;24(5):558-65. 2004
Oktober; 24 (5) :558-65. [abstract] [Abstrak]
7. Gupta JK, Chien PF, Voit D, et al ; Ultrasonographic endometrial thickness for

diagnosing endometrial pathology in women with postmenopausal bleeding:
a meta-analysis. Gupta JK, Chien PF, Voit D, et al ; ketebalan endometrium
ultrasonografi untuk mendiagnosis patologi endometrium pada wanita
dengan perdarahan postmenopause: meta-analisis. Acta Obstet Gynecol
Scand. Acta Obstet Gynecol Scand. 2002 Sep;81(9):799-816. 2002
September; 81 (9) :799-816. [abstract] [Abstrak]
8. Garuti G, Sambruni I, Cellani F, et al ; Hysteroscopy and transvaginal

ultrasonography in postmenopausal women with uterine bleeding. Garuti G,
Sambruni saya, Cellani F, et al , dan ultrasonografi transvaginal Histeroskopi
pada wanita pascamenopause dengan perdarahan rahim. Int J Gynaecol
Obstet. Int J Obstet Gynaecol. 1999 Apr;65(1):25-33. 1999 April; 65 (1) :25-
33. [abstract] [Abstrak]
9. Litta P, Merlin F, Saccardi C, et al ; Role of hysteroscopy with endometrial

biopsy to rule out endometrial cancer in postmenopausal women with
abnormal uterine bleeding. Litta P, Merlin F, Saccardi C, et al ; Peran
histeroskopi dengan biopsi endometrium untuk menyingkirkan kanker
endometrium pada wanita menopause dengan perdarahan uterus abnormal.
Maturitas. Maturitas. 2005 Feb 14;50(2):117-23. 2005 Februari 14, 50 (2) :
117-23. [abstract] [Abstrak]
10.van Doorn LC, Dijkhuizen FP, Kruitwagen RF, et al ; Accuracy of transvaginal

ultrasonography in diabetic or obese women with postmenopausal bleeding.
van Doorn LC, Dijkhuizen FP, Kruitwagen RF, et al ; Akurasi ultrasonografi
transvaginal atau obesitas wanita diabetes dengan perdarahan
postmenopause. Obstet Gynecol. Obstet Gynecol. 2004 Sep;104(3):571-8.
2004 September; 104 (3) :571-8. [abstract] [Abstrak]
11.Opmeer BC, van Doorn HC, Heintz AP, et al ; Improving the existing
diagnostic strategy by accounting for characteristics of the women in the
diagnostic work up for postmenopausal bleeding. Opmeer SM, van Doorn HC,
Heintz AP, et al ; Meningkatkan strategi diagnostik yang ada dengan
akuntansi untuk karakteristik perempuan dalam pekerjaan diagnostik
Facebook perdarahan postmenopause. BJOG. BJOG. 2007 Jan;114(1):51-8.
2007 Jan; 114 (1) :51-8. [abstract] [Abstrak]
12.Panda JK ; One-stop clinic for postmenopausal bleeding. Panda JK ;-stop klinik

Satu untuk pendarahan pascamenopause. J Reprod Med. J Reprod Med. 2002
Sep;47(9):761-6. 2002 September; 47 (9) :761-6. [abstract] [Abstrak]
13.Lotfallah H, Farag K, Hassan I, et al ; One-stop hysteroscopy clinic for

postmenopausal bleeding. Lotfallah H, Farag K, Hassan saya, et al ; berhenti
histeroskopi klinik-One untuk perdarahan postmenopause. J Reprod Med. J
Reprod Med. 2005 Feb;50(2):101-7. 2005 Februari; 50 (2) :101-7. [abstract]
[Abstrak]
14.Shepherd JH ; Revised FIGO staging for gynaecological cancer. Gembala JH ;

Revisi stadium FIGO untuk kanker ginekologi. Br J Obstet Gynaecol. Br J
Obstet Gynaecol. 1989 Aug;96(8):889-92. Agustus 1989; 96 (8) :889-92.
15.Cook AM, Lodge N, Blake P ; Stage IV endometrial carcinoma: a 10 year

review of patients. Cook AM, Lodge N, Blake P ; Tahap IV karsinoma
endometrium: setahun review 10 pasien. Br J Radiol. Br Radiol J. 1999
May;72(857):485-8. 1999 Mei; 72 (857) :485-8. [abstract] [Abstrak]
16.Wylie J, Irwin C, Pintilie M, et al ; Results of radical radiotherapy for recurrent

endometrial cancer. Wylie J, Irwin C, Pintilie M, et al ; Hasil radioterapi radikal
untuk kanker endometrium berulang. Gynecol Oncol. Gynecol Oncol. 2000
Apr;77(1):66-72. 2000 April; 77 (1) :66-72. [abstract] [Abstrak]
17.Sovak MA, Dupont J, Hensley ML, et al ; Paclitaxel and carboplatin in the

treatment of advanced or recurrent endometrial cancer: a large retrospective
study. Sovak MA, Dupont J, Hensley ML, et al ; Paclitaxel dan carboplatin
dalam pengobatan kanker endometrium berulang atau lanjutan: sebuah studi
retrospektif besar. Int J Gynecol Cancer. Int J Gynecol Cancer. 2007 Jan-
Feb;17(1):197-203. 2007 Jan-Feb; 17 (1) :197-203. [abstract] [Abstrak]
18.Lai CH, Huang HJ ; The role of hormones for the treatment of endometrial
hyperplasia and endometrial cancer. Lai CH, Huang HJ ; Peran hormon untuk
pengobatan hiperplasia endometrium dan kanker endometrium. Curr Opin
Obstet Gynecol. Curr Opin Obstet Gynecol. 2006 Feb;18(1):29-34. Februari
2006; 18 (1) :29-34. [abstract] [Abstrak]
19.Brenner H ; Long-term survival rates of cancer patients achieved by the end

of the 20th century: a period analysis. Brenner H ; jangka-panjang tingkat
ketahanan hidup pasien kanker dicapai pada akhir abad ke-20: analisis
periode. Lancet. Lancet. 2002 Oct 12;360(9340):1131-5. 2002 Oktober 12,
360 (9340) :1131-5. [abstract] [Abstrak]
20.Hernandez E ; Endometrial adenocarcinoma: a primer for the generalist.

Hernandez E ; adenokarsinoma endometrium: primer untuk generalis itu.
Obstet Gynecol Clin North Am. Obstet Gynecol Clin North Am. 2001
Dec;28(4):743-57. Desember 2001; 28 (4) :743-57. [abstract] [Abstrak]
21.Gusberg SB ; Virulence factors in endometrial cancer. Gusberg SB ; faktor

Virulensi pada kanker endometrium. Cancer. Kanker. 1993 Feb 15;71(4
Suppl):1464-6. 1993 Februari 15, 71 (4 Suppl) :1464-6. [abstract] [Abstrak]
Latar belakang
Carcinoma of the endometrium is among the most common female pelvic malignancies and may
develop in normal, atrophic, or hyperplastic endometrium. Karsinoma endometrium merupakan
salah satu keganasan yang paling umum panggul wanita dan bisa terjadi pada endometrium
normal, atrofi, atau hiperplastik. Most of the cancers are detected at an early stage, with the
tumor confined to the uterine corpus in 75% of patients. Sebagian besar kanker yang terdeteksi
pada tahap awal, dengan tumor terbatas pada korpus uterus dalam 75% pasien. The prognosis
generally is favorable. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 Prognosis umumnya baik. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8
Images of endometrioid carcinoma are provided below: Gambar karsinoma endometrioid

disediakan di bawah ini:
A 76-year-old woman with poorly differentiated endometrial adenocarcinoma. A-

tahun wanita 76 dengan diferensiasi buruk adenokarsinoma endometrium. Sagittal
transvaginal ultrasound image of the uterus shows a central mass replacing the
endometrial stripe, with hyperechoic and hypoechoic regions. Sagital citra
transvaginal USG rahim menunjukkan suatu massa pusat mengganti garis
endometrium, dengan dan hypoechoic daerah hyperechoic.
[ CLOSE WINDOW ] [ CLOSE WINDOW ]

tahun wanita 76 dengan diferensiasi buruk adenokarsinoma endometrium. Sagittal
transvaginal ultrasound image of the uterus shows a central mass replacing the
endometrial stripe, with hyperechoic and hypoechoic regions. Sagital citra
transvaginal USG rahim menunjukkan suatu massa pusat mengganti garis
endometrium, dengan dan hypoechoic daerah hyperechoic.

tahun wanita 76 dengan diferensiasi buruk adenokarsinoma endometrium. CT
image shows a relatively hypoattenuated mass in the region of the endometrial
cavity. Diffuse myometrial thinning is evident. gambar CT menunjukkan
hypoattenuated massa yang relatif di wilayah rongga endometrium. membaur
miometrium menipis jelas. Surgical pathology revealed approximately 4.0 cm of
pedunculated endometrial tumor associated with only superficial myometrial
invasion (limited to inner one third). Patologi bedah mengungkapkan sekitar 4,0 cm
dari tumor endometrium pedunculated terkait dengan hanya invasi miometrium
dangkal (terbatas pada satu bagian dalam ketiga).

tahun wanita 76 dengan diferensiasi buruk adenokarsinoma endometrium. CT
image shows a relatively hypoattenuated mass in the region of the endometrial
cavity. Diffuse myometrial thinning is evident. gambar CT menunjukkan
hypoattenuated massa yang relatif di wilayah rongga endometrium. membaur
miometrium menipis jelas. Surgical pathology revealed approximately 4.0 cm of
pedunculated endometrial tumor associated with only superficial myometrial
invasion (limited to inner one third). Patologi bedah mengungkapkan sekitar 4,0 cm
dari tumor endometrium pedunculated terkait dengan hanya invasi miometrium
dangkal (terbatas pada satu bagian dalam ketiga).
An 83-year-old woman with moderately differentiated endometrioid endometrial
adenocarcinoma. An-tahun wanita 83 agak berbeda dengan adenokarsinoma
endometrium endometrioid. Axial T1-weighted MR image of the uterus shows a
multilobulated, low signal intensity, polypoid tumor arising from the right side of the
endometrium and surrounded by fluid. Aksial T1-tertimbang MR gambar rahim
menunjukkan sinyal, intensitas rendah multilobulated, tumor polypoid yang timbul
dari sisi kanan endometrium dan dikelilingi oleh cairan. The fluid markedly
distending the endometrial cavity is hyperintense on T1- and T2-weighted images,
consistent with hematometra. Cairan nyata distending rongga endometrium
hyperintense on-dan T2-tertimbang gambar T1, konsisten dengan hematometra.
Examination under anesthesia revealed significant benign stenosis of the atrophic
cervix. Pemeriksaan dengan anestesi mengungkapkan stenosis jinak yang signifikan
dari serviks atrofi. Dilatation and curettage confirmed the fluid to be old blood and
established the diagnosis of endometrial malignancy. Dilatasi dan kuret dikonfirmasi
cairan yang akan darah tua dan mendirikan diagnosis keganasan endometrium.
Note that the marked myometrial thinning, due to both the elderly age and the
marked distension of the uterine cavity, limits the assessment of myometrial
invasion. Perhatikan bahwa miometrium ditandai menipis, karena kedua orang tua
usia dan distensi ditandai rongga rahim, membatasi penilaian invasi miometrium.

An 83-year-old woman with moderately differentiated endometrioid endometrial
adenocarcinoma. An-tahun wanita 83 agak berbeda dengan adenokarsinoma
endometrium endometrioid. Axial T1-weighted MR image of the uterus shows a
multilobulated, low signal intensity, polypoid tumor arising from the right side of the
endometrium and surrounded by fluid. Aksial T1-tertimbang MR gambar rahim
menunjukkan sinyal, intensitas rendah multilobulated, tumor polypoid yang timbul
dari sisi kanan endometrium dan dikelilingi oleh cairan. The fluid markedly
distending the endometrial cavity is hyperintense on T1- and T2-weighted images,
consistent with hematometra. Cairan nyata distending rongga endometrium
hyperintense on-dan T2-tertimbang gambar T1, konsisten dengan hematometra.
Examination under anesthesia revealed significant benign stenosis of the atrophic
cervix. Pemeriksaan dengan anestesi mengungkapkan stenosis jinak yang signifikan
dari serviks atrofi. Dilatation and curettage confirmed the fluid to be old blood and
established the diagnosis of endometrial malignancy. Dilatasi dan kuret dikonfirmasi
cairan yang akan darah tua dan mendirikan diagnosis keganasan endometrium.
Note that the marked myometrial thinning, due to both the elderly age and the
marked distension of the uterine cavity, limits the assessment of myometrial
invasion. Perhatikan bahwa miometrium ditandai menipis, karena kedua orang tua
usia dan distensi ditandai rongga rahim, membatasi penilaian invasi miometrium.
Multiple risk factors associated with endometrial cancer include conditions

associated with disorders of menstruation, increased perimenopausal bleeding,
menopause after age 52 years, long time period between menarche and
menopause, estrogen replacement therapy, tamoxifen therapy for breast cancer,
endometrial hyperplasia, obesity, nulliparity, diabetes mellitus, and hypertension.
Beberapa faktor risiko yang terkait dengan kanker endometrium termasuk kondisi
yang berhubungan dengan gangguan menstruasi, meningkatkan pendarahan
perimenopause, menopause setelah usia 52 tahun, jangka waktu yang lama antara
menarche dan menopause, terapi pengganti estrogen, terapi tamoxifen untuk
kanker payudara, hiperplasia endometrium, obesitas, nulliparity, diabetes mellitus,
dan hipertensi. Genetic predisposition appears to play a role, since risk factors also
include a family history of endometrial or breast cancer and a personal history of
ovarian or breast cancer. genetik predisposisi tampaknya memainkan peran, karena
faktor risiko juga termasuk riwayat keluarga kanker endometrium atau payudara
dan sejarah pribadi ovarium atau kanker payudara.
Recent studies Studi baru-baru ini
Alcazar and Galvan evaluated the role of 3-dimensional power Doppler

angiography (3D-PDA) to discriminate between benign and malignant
endometrial disease in women with postmenopausal bleeding and thickened
endometrium. Alcazar dan Galvan mengevaluasi peran 3-dimensi power
Doppler angiography (3D-PDA) untuk membedakan antara penyakit
endometrium jinak dan ganas pada wanita dengan perdarahan
postmenopause dan endometrium menebal. Histologic diagnoses were
endometrial cancer (44 cases), hyperplasia (13 cases), polyp (23 cases),
cystic atrophy (14 cases), and submucous myoma (5 cases). diagnosis
histologis adalah kanker endometrium (44 kasus), hiperplasia (13 kasus),
polip (23 kasus), atrofi kistik (14 kasus), dan myoma submukosa (5 kasus).
Endometrial volume, VI, and vascularity-flow index were significantly higher
in malignant conditions. volume Endometrial, VI, dan indeks vaskularisasi-
aliran secara signifikan lebih tinggi dalam kondisi ganas. Receiver operating
characteristic analysis revealed that VI was the best parameter for the
prediction of endometrial cancer. 9 operasi analisis karakteristik Receiver
mengungkapkan bahwa VI parameter terbaik untuk prediksi kanker
endometrium. 9
Signorelli et al performed a retrospective study to determine the diagnostic
accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed
tomography (18F-FDG PET/CT) in detecting nodal metastases in patients with
high-risk endometrial cancer. Signorelli dkk melakukan penelitian retrospektif
untuk menentukan akurasi diagnostik tomografi emisi positron 18F-
fluorodeoxyglucose / computed tomography (18F-FDG PET / CT) dalam
mendeteksi metastasis sentral pada pasien dengan kanker endometrium
berisiko tinggi. Pelvic node metastases were found at histopathologic analysis
in 9 of the 37 patients (24.3%). node metastasis panggul ditemukan pada
analisis histopatologi di 9 dari 37 pasien (24,3%). Patient-based sensitivity,
specificity, positive predictive value, negative predictive value, and accuracy
were 77.8%, 100.0%, 100.0%, 93.1% and 94.4%, respectively. Pasien
berbasis sensitivitas, spesifisitas, nilai prediksi positif, nilai prediksi negatif,
dan akurasi adalah 77,8%, 100.0%, 100.0%, 93,1% dan 94,4%, masing-
masing. Nodal lesion site-based sensitivity, specificity, positive predictive
value, negative predictive value, and accuracy were 66.7%, 99.4%, 90.9%,
97.2% and 96.8%, respectively. 10 Nodal lesi berbasis situs sensitivitas,
spesifisitas, nilai prediksi positif, nilai prediksi negatif, dan akurasi adalah
66,7%, 99,4%, 90,9%, 97,2% dan 96,8%, masing-masing. 10
Khoury-Collado et al described sentinel lymph node (SLN) detection rates in

endometrial cancer and estimated how many cases are needed to achieve
greater than 90% SLN detection. Khoury-Collado et al dijelaskan kelenjar
getah bening sentinel (SLN) tingkat deteksi pada kanker endometrium dan
diperkirakan berapa banyak kasus yang diperlukan untuk mencapai lebih dari
90% SLN deteksi. Lymph node mapping was performed using blue-dye
injection into the cervix; blue-dye injection in the uterine fundus; and cervical
injection of technetium-99m. pemetaan simpul getah bening dilakukan
menggunakan suntikan biru-dye ke leher rahim; injeksi biru-dye di fundus
uterus, dan injeksi leher rahim dari teknesium-99m. The study included 115
patients with endometrial cancer. Penelitian ini melibatkan 115 pasien
dengan kanker endometrium. The cervix was the only site of injection in 82
cases (71%); a combined cervical and fundal injection was performed in 33
cases (29%). Leher rahim adalah satu-satunya situs injeksi dalam 82 kasus
(71%), sebuah injeksi serviks dan fundal gabungan dilakukan pada 33 kasus
(29%). Overall, SLN detection was achieved in 98 (85%) cases. Secara
keseluruhan, SLN deteksi dicapai dalam 98 (85%) kasus. In the initial 27
months of the study, an SLN was identified in 50 of 64 cases (78%), with 2
false negatives. Dalam 27 bulan awal penelitian, SLN sebuah diidentifikasi di
50 dari 64 kasus (78%), dengan 2 negatif palsu. In the subsequent 15
months, successful mapping was achieved in 48 of 51 cases (94%), with no
false negatives. Dalam 15 bulan berikutnya, pemetaan berhasil dicapai dalam
48 dari 51 kasus (94%), tanpa negatif palsu. When examining an individual
provider's performance, after the first 30 cases, the rate of successful
mapping significantly increased from 77% to 94%. 11 Ketika memeriksa
penyedia kinerja individu, setelah kasus pertama 30, tingkat keberhasilan
pemetaan secara signifikan meningkat dari 77% menjadi 94%. 11
Hoekstra et al performed a retrospective review of 85 patients who

underwent surgical staging with lymph node dissection to determine the
clinicopathologic characteristics, nodal distribution, and postoperative
treatment of patients with FIGO stage IIIC endometrial carcinoma and to
determine patterns of recurrence and survival. Hoekstra dkk melakukan
peninjauan retrospektif terhadap 85 pasien yang menjalani bedah
pementasan dengan diseksi kelenjar getah bening untuk menentukan
karakteristik klinikopatologi, distribusi nodal, dan perawatan pasca operasi
pasien dengan karsinoma stadium FIGO IIIC endometrium dan untuk
menentukan pola kekambuhan dan kelangsungan hidup. At median follow-up
of 50 months, 5-year overall survival (OS) was 61.3%; recurrence-free
survival (RFS), 58.0%; and disease-specific survival (DSS), 71.9%. Pada
median follow up 50 bulan, kelangsungan hidup secara keseluruhan 5 tahun
(OS) adalah 61,3%; kelangsungan hidup kambuh-bebas (RFS), 58,0%, dan
kelangsungan hidup penyakit-spesifik (DSS), 71,9%. Age, non-endometrioid
histology, and more than 50% invasion were significantly associated with OS;
and age and non-endometrioid histology were associated with RFS. Umur,
histologi non-endometrioid, dan lebih dari 50 invasi% nyata terkait dengan
OS; dan usia dan histologi non-endometrioid dikaitkan dengan RFS. Disease
recurred in 21 patients (24.7%): 15 distant, 4 abdominal, 1 para-aortic, and 1
pelvic. Penyakit terulang pada 21 pasien (24,7%): 15 jauh, 4 perut, 1 para-
aorta, dan 1 panggul. Disease recurred outside the field of radiation in all
patients. 12 Penyakit terulang luar bidang radiasi pada semua pasien. 12
For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and
Women's Health Center . Untuk sumber daya pendidikan yang sangat baik pasien, kunjungi
eMedicine's Kanker dan Tumor Pusat dan Women's Health Center . Also, see eMedicine's patient
education articles Cervical Cancer and Menopause . Juga, lihat pasien pendidikan's eMedicine
artikel Leher Rahim Kanker dan Menopause .
Pathophysiology Patofisiologi
The most frequent risk factor contributing to the development of endometrial cancer is protracted
exposure to endogenous or exogenous estrogen that is unopposed by progesterone. Faktor risiko
yang paling sering berkontribusi terhadap perkembangan kanker endometrium adalah paparan
yang berlarut-larut dengan estrogen endogen atau eksogen yang terlindung oleh progesteron.
Overexposure to endogenous estrogen has been reported in patients with chronic anovulation
(eg, secondary to Stein-Leventhal syndrome). Overexposure dengan estrogen endogen telah
dilaporkan pada pasien dengan anovulasi kronis (misalnya, sekunder untuk sindrom Stein-
Leventhal). Overexposure to estrogen may be the result of an estrogen-producing neoplasm (eg,
granulosa or theca cell tumor of the ovary). Overexposure untuk estrogen mungkin hasil dari
neoplasma estrogen-memproduksi (misalnya, granulosa atau tumor sel teka ovarium). There may
be an association with increased peripheral conversion of androstenedione to estrone in the
adipose tissue of obese women. Mungkin ada hubungan dengan perangkat konversi meningkat
androstenedion untuk estrone dalam jaringan adiposa perempuan obesitas.
Tamoxifen is a nonsteroidal drug that has a therapeutic antiestrogen effect on the breast and an
estrogenic effect on the endometrium of postmenopausal women. Tamoxifen adalah obat non
steroid yang memiliki efek antiestrogen terapeutik pada payudara dan efek estrogenik pada
endometrium wanita postmenopause. Patients with breast cancer on prolonged tamoxifen therapy
are reported to have increased risk of developing endometrial polyps, hyperplasia, and cancer.
Pasien dengan kanker payudara pada terapi tamoxifen berkepanjangan dilaporkan peningkatan
risiko polip endometrium, hiperplasia, dan kanker.
In estrogen-related conditions, endometrial cancer most likely progresses from endometrial

hyperplasia, tends to be well differentiated, and is associated with a generally favorable
prognosis. Dalam kondisi yang berhubungan dengan estrogen, kanker endometrium
kemungkinan besar berlangsung dari hiperplasia endometrium, cenderung dibedakan dengan
baik, dan berhubungan dengan prognosis umumnya baik. In other conditions with unknown
cause, the cancer typically develops de novo in the setting of an atrophic or inert endometrium,
tends to have more aggressive or undifferentiated cell types, and usually has a poorer prognosis
than do the estrogen-related endometrial cancers. Dalam kondisi lain dengan penyebab yang
tidak diketahui, kanker biasanya berkembang de novo dalam pengaturan sebuah endometrium
atrofi atau inert, cenderung memiliki jenis sel yang lebih agresif atau dibedakan, dan biasanya
memiliki prognosis yang lebih buruk dari pada kanker endometrium estrogen-terkait.
Endometrial cancer usually arises from the glandular component of the endometrium in the
upper uterus. kanker endometrium biasanya timbul dari komponen kelenjar endometrium di
rahim bagian atas. It may grow in a focal circumscribed pattern presenting as a friable mass
protruding into the endometrial cavity. Ini dapat tumbuh dalam pola terbatas focal menyajikan
sebagai massa meremah menonjol ke dalam rongga endometrium. The cancer may be diffuse,
involving multiple regions of the endometrium or the whole endometrial surface. Kanker bisa
menyebar, melibatkan beberapa daerah endometrium atau permukaan endometrium keseluruhan.
It can occasionally arise within an endometrial polyp. Hal ini terkadang bisa timbul dalam
sebuah polip endometrium.
Spread of the disease occurs initially within the endometrium and/or myometrium, as well as
from the fundus toward the isthmic portion of the uterus and the cervix. Penyebaran penyakit ini
terjadi awalnya di dalam endometrium dan / atau miometrium, serta dari fundus ke arah bagian
isthmic dari rahim dan leher rahim. Progression beyond the uterus occurs through lymphatic
pathways into pelvic and abdominal lymph nodes. Perkembangan di luar rahim terjadi melalui
jalur limfatik ke kelenjar getah bening panggul dan perut. The cancer eventually may metastasize
hematogenously to the lungs and, in decreasing frequency, to the liver, brain, or bones. Kanker
mungkin akhirnya hematogenously bermetastasis ke paru-paru dan, dalam menurunkan
frekuensi, ke otak, hati, atau tulang. Transmural or transtubal tumor spread into the peritoneal
cavity occurs with more aggressive cancers. Transtubal Transmural atau tumor menyebar ke
rongga peritoneal terjadi dengan kanker yang lebih agresif.
The rate of extrauterine tumor spread and lymph node metastasis increases with the depth of
myometrial invasion, the degree of endocervical extension, and the presence of poor prognostic
histologic factors. Tingkat penyebaran tumor extrauterine dan meningkatkan metastasis kelenjar
getah bening dengan kedalaman invasi miometrium, derajat ekstensi endoservikal, dan adanya
faktor histologis prognosis miskin. Approximately one half of patients with metastatic
lymphadenopathy in the pelvis also have metastasis to the para-aortic lymph nodes. Sekitar satu
setengah pasien dengan limfadenopati metastasis di panggul juga memiliki metastasis ke kelenjar
getah bening para-aorta. Solitary para-aortic lymph node metastasis rarely occurs. Solitary getah
bening para-aorta node metastasis jarang terjadi.
Histopathologic types Jenis histopatologik
Endometrioid adenocarcinoma is the histologic prototype and the most common form of
endometrial carcinoma, occurring in as many as 75-80% of affected patients. adenocarcinoma
endometrioid adalah prototipe histologis dan bentuk yang paling umum dari karsinoma
endometrium, terjadi pada sebanyak 75-80% dari pasien yang terkena. Tumors vary from well
differentiated to undifferentiated and are graded from 1-3 based on architectural and cytologic
features. Tumor bervariasi dari sumur dibedakan dibedakan dan dinilai dari 1-3 berdasarkan fitur
arsitektur dan sitologi. The most aggressive and least differentiated cell types are categorized as
grade 3. Jenis sel yang paling agresif dan paling sedikit dibedakan dikategorikan sebagai kelas 3.
Well-differentiated tumors occur most commonly and include a low-grade endometrioid cell
type, which is usually associated with estrogen-related endometrial hyperplasia. tumor Yah-
dibedakan terjadi paling sering dan termasuk tipe sel yang rendah kelas endometrioid, yang
biasanya dikaitkan dengan hiperplasia endometrium estrogen-terkait. It tends to occur in younger
perimenopausal patients. Hal ini cenderung terjadi pada pasien perimenopause lebih muda.
Variants of endometrioid adenocarcinoma, including villoglandular or papillary carcinoma,
secretory carcinoma, ciliated carcinoma, and adenocarcinoma with squamous differentiation,
also occur. Varian dari adenokarsinoma endometrioid, termasuk karsinoma villoglandular atau
papiler, karsinoma sekretori, karsinoma bersilia, dan adenokarsinoma dengan diferensiasi
skuamosa, juga terjadi.
Uterine serous papillary carcinoma constitutes 5-10% of endometrial carcinomas, occurs in

women older than those seen with the endometrioid prototype, and commonly arises in atrophic
endometrium. karsinoma uterus papiler serosa merupakan 5-10% dari karsinoma endometrium,
terjadi pada wanita yang lebih tua daripada yang dilihat dengan prototipe endometrioid, dan
umumnya muncul di atrofi endometrium. This type of carcinoma is aggressive, with a
predilection for early deep myometrial and vascular invasion that frequently is associated with
early extrauterine spread and, in some patients, with transtubal peritoneal dissemination. Jenis
karsinoma yang agresif, dengan kecenderungan untuk invasi miometrium dan vaskular awal
mendalam yang sering dikaitkan dengan menyebar extrauterine awal dan, pada beberapa pasien,
dengan penyebaran peritoneal transtubal.
Additional aggressive tumors include clear cell carcinoma, constituting 3-5% of endometrial
carcinomas, and the less common undifferentiated carcinomas. tumor agresif tambahan termasuk
karsinoma sel jernih, merupakan 3-5% dari karsinoma endometrium, dan karsinoma dibeda-
bedakan kurang umum. Similar to the serous papillary variety, clear cell carcinoma and
undifferentiated carcinoma tend to occur in older women, have dismal prognoses, and are usually
unrelated to protracted unopposed exposure to estrogen. Serupa dengan berbagai papiler serous,
karsinoma sel jelas dan karsinoma dibedakan cenderung terjadi pada wanita yang lebih tua,
memiliki prognosis suram, dan biasanya tidak terkait dengan eksposur terlindung
berkepanjangan terhadap estrogen.
Miscellaneous rare endometrial carcinomas include mucinous adenocarcinoma , squamous cell

carcinoma , mixed cell type carcinoma, postmenopausal-occurring choriocarcinoma ,
endodermal sinus tumor, small cell carcinoma , and metastatic carcinoma Miscellaneous
Karsinoma endometrium jarang termasuk mucinous adenokarsinoma , karsinoma sel skuamosa ,
karsinoma sel jenis campuran, postmenopause-terjadi koriokarsinoma , endodermal sinus tumor,
karsinoma sel kecil , dan karsinoma metastasis
Frequency Frekuensi
United States Amerika Serikat
Cancer of the endometrium is the most common genital malignancy in the United States and
ranks as the fourth most common malignancy in women after breast, bronchopulmonary, and
colorectal cancers. Kanker endometrium merupakan keganasan genital yang paling umum di
Amerika Serikat dan peringkat sebagai kanker yang paling umum keempat pada wanita setelah
payudara, bronkopulmonalis, dan kanker kolorektal. Approximately 1 in 100 women may
develop the disease in the United States. 13 Sekitar 1 dari 100 wanita mungkin mengembangkan
penyakit di Amerika Serikat. 13
International Internasional
Worldwide, cancer of the endometrium ranks as the third most common genital malignancy after
cancers of the cervix and ovary. Di seluruh dunia, kanker endometrium peringkat sebagai
keganasan genital yang paling umum ketiga setelah kanker leher rahim dan ovarium. The
estimated total number of new cases of cancer of the corpus uteri is 142,000 per year worldwide
or 3.7% of cancers in women. Jumlah perkiraan kasus baru dari kanker korpus uteri adalah
142.000 per tahun di seluruh dunia atau 3,7% dari kanker pada wanita.
Reported global cancer statistics show the incidence to be highest in North America, followed by
Europe and temperate South America. Dilaporkan statistik menunjukkan kejadian kanker global
yang akan tertinggi di Amerika Utara, diikuti oleh Eropa dan subtropis Amerika Selatan. The
increased prevalence of the disease in the United States relative to other gynecologic cancers is
influenced by the earlier diagnosis and decreasing incidence of cervical cancer, prolonged life
expectancy, and dietary factors (perhaps related to increased obesity). Peningkatan prevalensi
penyakit di Amerika Serikat relatif terhadap kanker ginekologi lainnya dipengaruhi oleh
diagnosis dini dan insiden penurunan kanker serviks, harapan hidup berkepanjangan, dan faktor
makanan (mungkin terkait dengan obesitas meningkat). The incidence of endometrial carcinoma
is low in southern and eastern Asia, as well as in most of Africa. Insiden karsinoma endometrium
rendah di Asia selatan dan timur, serta di sebagian besar Afrika.
Mortality/Morbidity Mortalitas / Morbiditas

Endometrial carcinoma usually has a favorable prognosis. karsinoma endometrium biasanya
memiliki prognosis yang baik. Good survival rates, 84% in the United States and 72% in Europe,
have been reported. tingkat kelangsungan hidup yang baik, 84% di Amerika Serikat dan 72% di
Eropa, telah dilaporkan. However, worldwide, approximately 42,000 deaths occur annually from
cancer of the corpus uteri, which represents 1.9% of cancer deaths in women. Namun, di seluruh
dunia, sekitar 42.000 kematian terjadi setiap tahun dari kanker korpus uteri, yang merupakan
1,9% dari kematian akibat kanker pada wanita.
Race Ras
The prevalence and survival rates of endometrial carcinoma appear to be higher in whites than in
blacks. Tingkat prevalensi dan kelangsungan hidup karsinoma endometrium tampaknya lebih
tinggi dalam putih dibandingkan kulit hitam. A review of the Gynecologic Oncology Group
database showed a relatively higher number of African American patients were older than 70
years at the time of diagnosis and had more aggressive histologic cell types and more advanced
local and metastatic disease. 14 Sebuah tinjauan dari Gynecologic Oncology Group database
menunjukkan jumlah yang relatif lebih tinggi pasien African American lebih tua dari 70 tahun
pada saat diagnosis dan memiliki jenis histologis sel yang lebih agresif dan metastasis penyakit
lanjut lokal dan banyak lagi. 14
Age Umur
Endometrial carcinoma is primarily a disease of menopausal and postmenopausal women, with
the peak incidence in women aged 55-65 years. Karsinoma endometrium terutama penyakit yang
menopause dan wanita menopause, dengan kejadian puncak pada wanita berusia 55-65 tahun.
Approximately 75% of patients are aged 50 years and older, and 5% are younger than 40 years.
Sekitar 75% dari pasien berusia 50 tahun dan lebih tua, dan 5% lebih muda dari 40 tahun.
Endometrial carcinoma is rare in patients younger than age 30 years. Karsinoma endometrium
jarang terjadi pada pasien yang lebih muda dari usia 30 tahun.
Anatomy Anatomi
The endometrium is the mucosal lining of the uterine cavity. Endometrium adalah lapisan
mukosa rongga rahim. It consists of a columnar surface epithelium overlying a stroma of round
to ovoid cells intermixed with glands and a characteristic vascular system. Ini terdiri dari epitel
permukaan kolumnar atasnya suatu stroma putaran ke sel bulat telur bercampur dengan kelenjar
dan sistem vaskular karakteristik. The glands open into the surface epithelium and are
surrounded by a network of fibrillar elements. Kelenjar terbuka ke dalam epitel permukaan dan
dikelilingi oleh jaringan elemen berhubung dgn urat saraf.
The thickness and sonographic appearance of the normal endometrium vary with the menstrual
cycle. Tampilan ketebalan dan sonografi dari endometrium normal bervariasi dengan siklus haid.
Endometrial thickness, as reported in the ultrasound (US) literature, is measured on a midline
sagittal image of the uterus and is a summation of the anteroposterior (AP) width of both the
anterior and posterior endometrial layers, exclusive of possible intracavitary content. ketebalan
endometrium, sebagaimana dilaporkan dalam USG literatur (AS), diukur pada gambar sagital
garis tengah uterus dan merupakan penjumlahan dari anteroposterior yang (AP) lebar kedua
lapisan endometrium anterior dan posterior, eksklusif konten intracavitary mungkin.
During menses, the endometrium is thin, patchy, and not clearly delineated. Selama mens,
endometrium tipis, merata, dan tidak jelas digambarkan. In the proliferative phase, the
endometrial stripe develops a multilayered sonographic appearance; the wider inner portion of
the proliferative endometrium is hypoechoic, and the outer portion is relatively hyperechoic.
Pada fase proliferatif, yang garis endometrium mengembangkan penampilan sonografi berlapis-
lapis, bagian dalam lebih luas endometrium proliferatif adalah hypoechoic, dan bagian luar
relatif hyperechoic. In the secretory phase, the endometrial stripe thickens to a mean of 14-16
mm in AP width and becomes diffusely hyperechoic secondary to accumulation of mucus and
glycogen in the increasingly tortuous glands. Dalam fase sekresi, mengental garis endometrium
menjadi rata-rata 14-16 mm lebar AP dan menjadi difus hyperechoic sekunder untuk akumulasi
lendir dan glikogen dalam kelenjar semakin berliku-liku.
The endometrium progressively atrophies following menopause. Endometrium semakin

atrophies berikut menopause. The rate at which this process occurs is influenced by the variable
presence of adrenal sources of genital hormones and by the degree of ovarian activity. Tingkat di
mana proses ini terjadi dipengaruhi oleh keberadaan variabel sumber adrenal hormon kelamin
dan tingkat aktivitas ovarium. Many authorities will report as abnormal measurements of 5 mm
or greater in postmenopausal patients not on hormone replacement therapy (HRT). Banyak pihak
berwenang akan melaporkan sebagai pengukuran abnormal 5 mm atau lebih besar pada pasien
pascamenopause bukan pada terapi hormon pengganti (HRT). Some will allow as great as 8-mm
thickness if the patient is on HRT. Beberapa akan memungkinkan begitu besar seperti 8-mm
ketebalan jika pasien pada HRT. Others will limit the AP measurement, even in that group, to up
to 5 mm. Orang lain akan membatasi pengukuran AP, bahkan dalam kelompok itu, untuk sampai
dengan 5 mm.
CT does not depict the endometrium consistently and is not reliable for accurate evaluation of its
thickness. CT tidak menggambarkan endometrium konsisten dan tidak dapat diandalkan untuk
evaluasi akurat ketebalannya. Immediate postcontrast dynamic CT scans of the uterus often show
central hypoattenuation that may be related to secretions in the cavity or a lag in contrast
enhancement of the endometrium compared to myometrium; however, the endometrium is not
visualized distinctly as separate from the myometrium, and accurate measurement of its
thickness is not feasible. Segera postcontrast dinamis CT scan dari rahim sering menunjukkan
hypoattenuation pusat yang mungkin berhubungan dengan sekresi dalam rongga atau lag dalam
meningkatkan kontras pada endometrium dibandingkan dengan miometrium, namun,
endometrium tidak divisualisasikan jelas sebagai terpisah dari miometrium, dan akurat
pengukuran ketebalan tidak layak. This is because the endometrium and myometrium have
similar attenuation and cannot be distinguished either on CT scans obtained without intravenous
contrast or on routine or delayed postcontrast CT scans. Hal ini karena endometrium dan
miometrium memiliki redaman yang sama dan tidak dapat dibedakan baik pada CT scan
diperoleh tanpa kontras intravena atau di scan postcontrast rutin atau tertunda CT.
MRI depicts the endometrium as a central zone of high signal intensity on T2-weighted images,
while the myometrium is depicted at its inner aspect as a zone of low signal intensity (junctional
zone) and at its outer aspect as a wider zone of intermediate signal intensity. MRI
menggambarkan endometrium sebagai zona sentral intensitas sinyal tinggi pada gambar T2-
tertimbang, sedangkan miometrium digambarkan pada aspek batin sebagai zona intensitas sinyal
rendah (zona junctional) dan pada aspek luar sebagai zona yang lebih luas dari sinyal
intermediate intensitas. On T1-weighted images, the endometrium has intermediate signal
intensity similar to the myometrium; therefore, the endometrium is not visualized distinctly as
separate from the myometrium. Pada gambar T1-tertimbang, endometrium memiliki intensitas
sinyal menengah mirip dengan miometrium, sehingga endometrium tidak divisualisasikan jelas
sebagai terpisah dari miometrium.
As measured on MRI, endometrial thickness reportedly is almost always less than that measured
on US. Yang diukur pada MRI, ketebalan endometrium dilaporkan hampir selalu kurang dari
yang diukur pada AS. Endometrial thickness varies in menstruating women from 4 mm in the
early proliferative phase to 13 mm in the late secretory phase. Endometrial ketebalan bervariasi
pada wanita menstruasi dari 4 mm dalam fase proliferasi awal untuk 13 mm pada fase sekretori
terlambat. The upper limit of normal thickness in asymptomatic postmenopausal women has
been suggested at 8 mm, regardless of hormonal therapy. Batas atas ketebalan normal pada
wanita postmenopause asimtomatik telah diusulkan pada 8 mm, terlepas dari terapi hormonal.
Presentation Presentasi
Early endometrial cancer is usually asymptomatic. Dini kanker endometrium biasanya tanpa
gejala. Eventually, 80% of patients present with vaginal bleeding, mostly postmenopausal.
Akhirnya, 80% dari pasien datang dengan pendarahan vagina, kebanyakan postmenopause. Ten
percent of patients present with purulent vaginal discharge, which sometimes is tinged with
blood. Sepuluh persen dari pasien datang dengan vagina purulen, yang terkadang diwarnai
dengan darah.
In patients with endometrial cancer, 5% or fewer cases are diagnosed while the patient still is
asymptomatic, with the cancer being discovered after a hysterectomy is performed for benign
indications or during a diagnostic workup for abnormal Papanicolaou smear results. Pada pasien
dengan kanker endometrium, kasus 5% atau kurang didiagnosis saat pasien masih asimtomatik,
dengan kanker yang ditemukan setelah histerektomi dilakukan untuk indikasi jinak atau selama
hasil pemeriksaan diagnostik untuk hasil BTA Papanicolaou abnormal. Pain and pelvic pressure
are usually manifestations of advanced disease. Nyeri dan tekanan panggul biasanya manifestasi
dari penyakit lanjut.
Although only 10-20% of postmenopausal vaginal bleeding is the result of gynecologic

malignancy, the probability that it is caused by endometrial carcinoma progressively increases
with age. Meskipun hanya 10-20% dari perdarahan vagina pascamenopause adalah hasil dari
keganasan ginekologi, probabilitas bahwa hal itu disebabkan oleh karsinoma endometrium
semakin meningkat dengan usia.
Preferred Examination Preferred Pemeriksaan

Medical procedures Prosedur Medis
Endometrial biopsy, usually using an aspiration-type curet or other device, is generally accepted
as the first-step office procedure for the diagnosis of endometrial cancer and should be coupled
with endocervical curettage. biopsi endometrium, biasanya menggunakan curet aspirasi-jenis
atau perangkat lain, secara umum diterima sebagai prosedur kantor pertama-langkah untuk
diagnosis kanker endometrium dan harus dibarengi dengan kuretase endoserviks. The procedure
is definitive if results are positive for malignancy. Prosedur ini definitif jika hasil positif untuk
keganasan. The reported accuracy of the procedure is approximately 90%. Keakuratan
dilaporkan prosedur adalah sekitar 90%.
When endometrial sampling does not yield a conclusive histologic diagnosis and when adequate
evaluation is precluded by cervical stenosis or by limited patient tolerance, traditional fractional
curettage may be necessary because it provides the largest amount of endometrial tissue. Saat
pengambilan sampel endometrium tidak menghasilkan diagnosis histologis konklusif dan ketika
evaluasi yang memadai dihindari dengan stenosis serviks atau dengan toleransi pasien terbatas,
kuretase pecahan tradisional mungkin diperlukan karena menyediakan jumlah terbesar jaringan
endometrium. This procedure is performed under anesthesia in the operating room. Prosedur ini
dilakukan di bawah anestesi di ruang operasi. The procedure includes initial circumferential
scraping of the endocervical canal and subsequent systemic curettage of the entire endometrial
surface. Prosedur ini mencakup Scraping keliling awal dari kanal endoserviks dan kuretase
sistemik selanjutnya seluruh permukaan endometrium. Cervical and endometrial specimens are
evaluated separately to determine if endometrial cancer invaded the cervix and to allow detection
of occult endocervical cancer. Serviks dan spesimen endometrium dievaluasi secara terpisah
untuk menentukan apakah kanker endometrium menyerang leher rahim dan memungkinkan
deteksi kanker okultisme endoservikal.
Endometrial curettage may be falsely negative in 2-6% of cases because the endometrium is
sampled randomly and incompletely. Endometrial kuret mungkin palsu negatif dalam 2-6%
kasus karena endometrium adalah sampel secara acak dan tidak lengkap. Some clinicians
advocate hysteroscopy with biopsy as the preferred procedure following negative biopsy results,
because this allows the surgeon to perform the biopsy directly on focal abnormalities that may be
missed during curettage. Beberapa dokter menganjurkan histeroskopi dengan biopsi sebagai
prosedur pilihan berikut hasil biopsi negatif, karena ini memungkinkan ahli bedah untuk
melakukan biopsi langsung pada kelainan fokal yang mungkin terlewatkan selama kuretase.
Other clinicians caution against the use of hysteroscopy unless absolutely necessary, since cancer
cells may be pushed through the fallopian tubes into the peritoneal cavity. dokter lain hati-hati
terhadap penggunaan histeroskopi kecuali benar-benar diperlukan, karena sel-sel kanker dapat
didorong melalui saluran tuba ke dalam rongga peritoneal.
The thickness of the endometrial stripe, as measured by US, has been advocated as a factor in
determining the need for dilatation and curettage. Ketebalan dari garis endometrium, yang diukur
dengan AS, telah menganjurkan sebagai faktor dalam menentukan kebutuhan dilatasi dan
kuretase. Although considerable overlap exists in the endometrial thickness and appearance
between the various benign and malignant histologic types, several reports suggest that the
presence of a thin stripe is usually associated with atrophic endometrium and may indicate that a
histologic diagnosis is not necessary. Meskipun ada tumpang tindih dalam ketebalan
endometrium dan penampilan antara berbagai jenis histologis jinak dan ganas, beberapa laporan
menunjukkan bahwa kehadiran garis tipis biasanya berhubungan dengan atrofi endometrium dan
dapat menunjukkan bahwa diagnosis histologis tidak diperlukan.
Granberg et al reported that if a cutoff of 5-mm was used to define the thickness of the normal
endometrial stripe in symptomatic postmenopausal patients, approximately 70% of patients with
vaginal bleeding could have avoided curettage. 15 A multicenter study reported by Karlsson et al
revealed that dilatation and curettage found cancer in 2 of 88 patients with a 5-mm stripe, while
cancer was detected in none of 518 women with a stripe of 4-mm or less; therefore, the authors
concluded that a 4-mm cutoff may be more appropriate. Granberg dkk melaporkan bahwa jika
cutoff dari 5-mm digunakan untuk menentukan ketebalan endometrium normal pascamenopause
strip pasien bergejala pada, sekitar 70% dari pasien dengan perdarahan vagina bisa menghindari
kuretase. 15 Sebuah studi multicenter dilaporkan oleh Karlsson et al mengungkapkan bahwa
dilatasi dan kuretase ditemukan kanker di 2 dari 88 pasien dengan 5-mm garis, sedangkan kanker
terdeteksi pada satu pun dari 518 perempuan dengan garis 4-mm atau kurang, karena itu, para
penulis menyimpulkan bahwa cutoff 4-mm mungkin lebih tepat. Women on estrogen
replacement therapy typically may have endometrial stripe thickness measuring up to 8-10 mm.
16
Wanita di terapi penggantian estrogen mungkin biasanya memiliki ketebalan garis
endometrium berukuran sampai 8-10 mm. 16
No consensus has been reached regarding the cutoff for the US measurement of endometrial
thickness that definitively eliminates the need for histologic evaluation of patients with abnormal
uterine bleeding. Tidak ada konsensus telah dicapai mengenai cutoff untuk pengukuran AS
ketebalan endometrium yang definitif menghilangkan kebutuhan untuk evaluasi histologi dari
pasien dengan perdarahan uterus abnormal. In addition, many clinicians still prefer endometrial
sampling as the initial diagnostic procedure used in evaluating symptomatic postmenopausal
patients. Selain itu, banyak dokter masih lebih suka pengambilan sampel endometrium sebagai
prosedur diagnostik awal yang digunakan dalam mengevaluasi pasien pascamenopause gejala.
Radiologic procedures Prosedur radiologis
US is the modality of choice for the initial imaging evaluation of female pelvic organs. AS
adalah modalitas pilihan untuk evaluasi awal pencitraan organ panggul perempuan. US is widely
available in many regions of the world, is relatively inexpensive, is noninvasive, and does not
use ionizing radiation. AS banyak tersedia di banyak daerah di dunia, relatif murah, adalah
noninvasif, dan tidak menggunakan radiasi pengion. Typical examinations include
transabdominal sonography (TAS) and transvaginal sonography (TVS), which are supplemented
by color Doppler imaging as needed. 17 pemeriksaan umum termasuk sonografi transabdominal
(TAS) dan transvaginal sonografi (TVS), yang dilengkapi dengan pencitraan Doppler warna
yang diperlukan. 17
TAS is performed through subcutaneous fat and abdominal wall muscles and uses the full urinary
bladder as an acoustic window. TAS dilakukan melalui subkutan lemak dan otot-otot dinding
perut dan menggunakan kandung kemih penuh sebagai jendela akustik. TAS transducers, needed
in most patients to penetrate the abdominal wall and adequately visualize pelvic organs, have
lower frequency and resolution than TVS probes. transduser TAS, diperlukan pada kebanyakan
pasien untuk menembus dinding perut dan memadai memvisualisasikan organ-organ panggul,
memiliki frekuensi dan resolusi yang lebih rendah daripada probe TVS.
TVS has the advantage of using high-frequency transducers that are placed close to the regions
of interest and produce high-resolution images of significantly better quality than transabdominal
images. TVS memiliki keuntungan menggunakan transduser frekuensi tinggi yang ditempatkan
dekat ke daerah kepentingan dan menghasilkan gambar beresolusi tinggi kualitas gambar secara
signifikan lebih baik daripada transabdominal. While both TAS and TVS allow visualization of
the endometrium, exquisitely finer endometrial details are possible to depict transvaginally rather
than transabdominally. Sementara kedua TAS dan TVS memungkinkan visualisasi dari
endometrium, indah halus rincian endometrium yang mungkin untuk menggambarkan
transvaginally daripada transabdominally.
TVS is clinically established as the preferred technique for evaluation of endometrial disorders
and is especially useful in the workup of abnormal uterine bleeding. TVS secara klinis didirikan
sebagai teknik pilihan untuk evaluasi gangguan endometrium dan ini sangat berguna dalam hasil
pemeriksaan perdarahan uterus abnormal. Hysterosonography can be used to identify the cause
of endometrial stripe thickening in some patients. Hysterosonography dapat digunakan untuk
mengidentifikasi penyebab penebalan garis endometrium pada beberapa pasien. The procedure
consists of TVS performed with sterile fluid placed within the endometrial cavity and may help
show a thick endometrial stripe as secondary to diffuse or focal endometrial thickening,
endometrial polyp, submucosal leiomyoma, or synechiae. Prosedur ini terdiri dari TVS dilakukan
dengan cairan steril ditempatkan dalam rongga endometrium dan dapat membantu menunjukkan
garis tebal endometrium sebagai sekunder untuk meredakan atau penebalan endometrium fokal,
polip endometrium, leiomyoma submukosa, atau synechiae. This may help further diagnostic
planning. Hal ini dapat membantu perencanaan lebih lanjut diagnostik.
TVS is superior to CT and approaches MRI in its ability to depict endometrial carcinoma and to
provide information regarding myometrial, cervical, and, perhaps, parametrial tumor invasion.
TVS lebih unggul CT dan MRI pendekatan dalam kemampuannya untuk menggambarkan
karsinoma endometrium dan memberikan informasi mengenai invasi tumor miometrium, leher
rahim, dan, mungkin, parametrium. However, US is unable to depict the entire intrapelvic or
intra-abdominal anatomic regions adequately; therefore, US is not suitable for the comprehensive
staging of endometrial carcinoma. Namun, AS tidak dapat menggambarkan seluruh daerah
anatomis intrapelvic atau intra-abdomen memadai, sehingga AS tidak cocok untuk pementasan
komprehensif karsinoma endometrium. US has significantly lower sensitivity than CT in
detecting enlarged abdominal or pelvic lymph nodes and in depicting intraperitoneal, omental, or
mesenteric metastases. AS telah sensitivitas secara signifikan lebih rendah daripada CT dalam
mendeteksi pembesaran kelenjar getah bening perut atau panggul dan dalam menggambarkan
metastasis intraperitoneal, omentum, atau mesenterika. In addition, US is inferior to CT in
assessing pelvic sidewall extension and adjacent organ invasion. Selain itu, AS lebih rendah
daripada CT dalam menilai perpanjangan dinding samping panggul dan invasi organ yang
berdekatan.
CT and MRI are more accurate staging modalities than US. CT dan MRI modalitas pementasan
lebih akurat dari US. Both techniques allow survey of the entire pelvis, abdomen, thorax, and
brain. Kedua teknik memungkinkan survei seluruh panggul, perut, dada, dan otak. CT is
available more widely, is less costly than MRI, provides rapid image acquisition, and has high
spatial resolution. CT tersedia lebih luas, lebih murah dari MRI, menyediakan akuisisi gambar
yang cepat, dan memiliki resolusi spasial tinggi. The advantages of CT also include the
availability of GI and intravenous (IV) contrast materials. Kelebihan CT juga termasuk
ketersediaan GI dan intravena (IV) bahan kontras. Opacification of the GI tract with oral and
rectal contrast facilitates optimal evaluation of the bowel and helps distinguish intraperitoneal
and retroperitoneal masses from bowel. Kekeruhan pada saluran GI dengan kontras oral dan
dubur memfasilitasi evaluasi optimal usus dan membantu membedakan massa intraperitoneal
dan retroperitoneal dari usus. IV contrast injection improves evaluation of vascular structures and
detection of mass lesions in parenchymatous organs. suntikan kontras IV meningkatkan evaluasi
struktur vaskular dan deteksi lesi massa di organ parenchymatous. The recent advent of
spiral/helical and multidetector technology has improved the multiplanar capability of CT.
Munculnya baru-baru ini spiral / teknologi heliks dan multidetektor telah meningkatkan
kemampuan multiplanar CT.
The advantages of MRI include superior spatial and tissue contrast resolution, multiplanar
capabilities, lack of exposure to ionizing radiation, and availability of noniodinated,
nonnephrotoxic IV contrast material. Kelebihan MRI termasuk unggul dan resolusi spasial
jaringan kontras, kemampuan multiplanar, kurangnya paparan radiasi pengion, dan ketersediaan
noniodinated, bahan kontras IV nonnephrotoxic.
Preferred staging modality Preferred pementasan modalitas
Histopathologic features of the tumor and clinical findings at presentation influence the choice of
imaging modality for preoperative staging of endometrial cancer. Histopatologis fitur dari tumor
dan temuan klinis pada pengaruh presentasi pilihan modalitas pencitraan untuk pementasan
preoperatif kanker endometrium. Kinkel et al 18 provided clinical practice guidelines for staging
based on a meta-analysis of the usefulness of MRI, CT, and US in imaging patients with
endometrial cancer. Kinkel et al 18 memberikan pedoman praktek klinis untuk pementasan
berdasarkan analisis-meta kegunaan MRI, CT, dan AS pada pasien imaging dengan kanker
endometrium.
Patients with grade 1 tumor, a clinically normal-sized uterus, and no clinical

evidence of coexisting pelvic disease generally require no preoperative
imaging because the risk for myometrial, cervical, or lymph node disease is
low. Pasien dengan tumor grade 1, rahim klinis ukuran normal, dan tidak ada
bukti klinis hidup bersama penyakit panggul umumnya tidak memerlukan
pencitraan pra operasi karena risiko penyakit node miometrium, leher rahim,
atau getah bening rendah. If the clinical evaluation is inconclusive or
coexisting pelvic disease is suggested, then US, CT, or MRI may be used for
the initial imaging evaluation. Jika evaluasi klinis adalah penyakit panggul
meyakinkan atau hidup bersama disarankan, kemudian US, CT, atau MRI
dapat digunakan untuk evaluasi awal pencitraan.
In patients at risk for disease dissemination and lymph node involvement at

presentation (because of tumor grade, histologic cell type, or clinical
findings), CT or MRI of the abdomen and pelvis should be performed to
determine the extent of tumor spread. Pada pasien berisiko untuk
penyebaran penyakit dan keterlibatan kelenjar getah bening di presentasi
(karena grade tumor, tipe histologis sel, atau temuan klinis), CT atau MRI dari
perut dan panggul harus dilakukan untuk menentukan tingkat penyebaran
tumor.
Patients in whom cervical invasion is suggested clinically or in whom
endocervical curettage was inconclusive benefit in particular from MRI,
because MRI can depict cervical and myometrial invasion most accurately
and is approximately equivalent to CT in detecting enlarged lymph nodes.
Pasien yang invasi serviks disarankan klinis atau siapa kuretase endoserviks
adalah meyakinkan manfaat khususnya dari MRI, karena MRI dapat
menggambarkan invasi serviks dan miometrium yang paling akurat dan
kurang lebih setara dengan CT dalam mendeteksi pembesaran kelenjar getah
bening.
MRI, with its exquisite soft tissue contrast and multiplanar capability, is superior to US and CT
in helping assess the depth of myometrial invasion, cervical invasion, and early parametrial
invasion. MRI, dengan kontras jaringan indah yang lembut dan kemampuan multiplanar, lebih
unggul dari AS dan CT dalam membantu menilai kedalaman invasi miometrium, invasi serviks,
dan invasi parametrium awal. MRI is approximately equivalent to CT in detecting enlarged
lymph nodes, but CT is considerably superior to MRI in detecting and distinguishing
intraperitoneal, omental, and mesenteric metastases from bowel. MRI kurang lebih setara dengan
CT dalam mendeteksi pembesaran kelenjar getah bening, tetapi CT adalah sangat unggul untuk
MRI dalam mendeteksi dan membedakan metastasis intraperitoneal, omentum, dan mesenterika
dari usus.
Although MRI is superior to CT in evaluating myometrial and cervical invasion and is the best
alternative for patients with significant contrast allergies or renal malfunction, CT is more
sensitive than MRI in the overall detection of tumor spread outside the uterus. Meskipun MRI
lebih unggul dalam mengevaluasi CT invasi miometrium dan serviks dan merupakan alternatif
terbaik untuk pasien dengan alergi kontras signifikan atau kerusakan ginjal, CT lebih sensitif
dibandingkan MRI dalam deteksi keseluruhan tumor menyebar di luar rahim. In addition, CT
remains the imaging modality used most frequently in clinical practice for comprehensive
preoperative evaluation of the extent of disease. Selain itu, CT tetap merupakan modalitas
pencitraan paling sering digunakan dalam praktek klinis untuk evaluasi preoperatif komprehensif
tingkat penyakit.
CT is clinically advocated in the evaluation of patients with poorly differentiated or high-grade

tumor, serous papillary carcinoma, or clear cell carcinoma because of the high risk for advanced
disease and metastatic lymphadenopathy at the time of presentation. CT secara klinis dianjurkan
dalam evaluasi pasien dengan tumor diferensiasi buruk atau bermutu tinggi, karsinoma papiler
serosa, atau karsinoma sel jernih karena risiko tinggi untuk penyakit lanjut dan limfadenopati
metastatis pada saat presentasi. CT also is advised for patients who have abnormal liver function
test results, elevated serum cancer antigen 125 levels, clinical suggestion of advanced disease, or
inconclusive clinical evaluation. CT juga disarankan untuk pasien yang memiliki hasil tes fungsi
hati abnormal, serum antigen kanker peningkatan 125 tingkat, saran klinis penyakit lanjut, atau
evaluasi klinis tidak meyakinkan.
Limitations of Techniques Keterbatasan Teknik
US is operator-dependent; it has relatively poor spatial and tissue contrast resolution compared
with MRI and CT; its image quality is degraded by large body habitus; and visualization of
portions of the pelvis and abdomen is precluded by bowel gas and bony structures. AS
bergantung pada operator, tetapi memiliki spasial yang relatif miskin dan resolusi jaringan
kontras dibandingkan dengan MRI dan CT; kualitas gambar adalah terdegradasi oleh habitus
tubuh besar, dan visualisasi dari bagian dari panggul dan perut dihindari oleh gas usus dan
struktur tulang. The transabdominal approach also is influenced by the degree of bladder filling
and is impeded by the presence of surgical incision, dressings, drains, or skin lesions. Pendekatan
transabdominal juga dipengaruhi oleh tingkat pengisian kandung kemih dan terhambat dengan
adanya sayatan bedah, perban, saluran, atau lesi kulit. Transvaginal probes have inherent
limitations, including small field of view, short range of penetration of high-frequency
transducers, and occasional patient intolerance or lack of acceptance of the transvaginal
approach. transvaginal probe memiliki keterbatasan yang melekat, termasuk lapangan kecil
pandang, jarak dekat penetrasi transduser frekuensi tinggi, dan intoleransi pasien sesekali atau
kurangnya penerimaan dari pendekatan transvaginal.
CT uses ionizing radiation and has inferior soft tissue contrast resolution, making it less capable
than MRI of distinguishing between tumor and normal soft tissues in the uterine corpus and
cervix. CT menggunakan radiasi pengion dan memiliki resolusi kontras rendah jaringan lunak,
sehingga kurang mampu dari MRI membedakan antara tumor dan jaringan lunak normal pada
korpus uterus dan serviks. CT image quality is degraded by metallic prostheses, an extremely
large body habitus, and patient or respiratory motion. kualitas gambar CT adalah terdegradasi
oleh prostesis metalik, sebuah habitus tubuh yang sangat besar, dan gerak pasien atau
pernapasan. The iodinated IV contrast available for CT is associated with a risk of significant
allergic reactions (including fatal anaphylaxis), nephrotoxicity, and complications of contrast
extravasation. Kontras IV iodinasi tersedia untuk CT dikaitkan dengan risiko reaksi alergi yang
signifikan (termasuk anafilaksis fatal), nefrotoksisitas, dan komplikasi ekstravasasi kontras.
MRI is contraindicated in patients who have vital metallic biomedical devices or metallic objects
in strategic anatomic regions. MRI merupakan kontraindikasi pada pasien yang memiliki
perangkat penting biomedis logam atau benda-benda logam di daerah anatomis strategis. It is
more costly and less readily available than CT and requires long image acquisition times. Hal ini
lebih mahal dan kurang tersedia dari CT dan membutuhkan waktu akuisisi citra lama. MRI
image quality is degraded by artifacts related to respiratory motion and bowel peristalsis, which
are likely to occur during the long image acquisition time. MRI adalah kualitas gambar
terdegradasi oleh artefak yang berkaitan dengan gerak pernapasan dan peristaltik usus, yang
mungkin terjadi selama waktu akuisisi gambar lama. No effective GI contrast material is
currently available for MRI. Tidak ada materi GI kontras yang efektif saat ini tersedia untuk
MRI. Claustrophobia deters some patients from undergoing MRI. Claustrophobia menghalangi
beberapa pasien dari menjalani MRI.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate
dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK],
gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis
(NSF) or nephrogenic fibrosing dermopathy (NFD). agen kontras Gadolinium berbasis
(gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide
[Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) telah dikaitkan dengan
pengembangan fibrosis sistemik nephrogenic (NSF) atau dermopathy fibrosing nephrogenic
(NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The
disease has occurred in patients with moderate to end-stage renal disease after being given a
gadolinium-based contrast agent to enhance MRI or MRA scans. Untuk informasi lebih lanjut,
lihat topik eMedicine Nephrogenic Fibrosing Dermopathy. Penyakit ini terjadi pada pasien
dengan sedang sampai stadium akhir penyakit ginjal setelah diberi kontras berbasis agen-
gadolinium untuk meningkatkan MRI scan atau MRA.
NSF/NFD is a debilitating and sometimes fatal disease. NSF / NFD adalah penyakit fatal
melemahkan dan kadang-kadang. Characteristics include red or dark patches on the skin;
burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of
the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain
deep in the hip bones or ribs; and muscle weakness. Karakteristik termasuk bercak merah atau
gelap pada kulit, terbakar, gatal, bengkak, pengerasan, dan mengencangkan kulit, bintik-bintik
kuning pada bagian putih mata; kekakuan sendi dengan kesulitan bergerak atau pelurus lengan,
tangan, kaki, atau kaki; jauh di dalam tulang pinggul atau tulang rusuk sakit, dan kelemahan otot.
For more information, see the FDA Public Health Advisory or Medscape . Untuk informasi lebih
lanjut, lihat FDA Kesehatan Masyarakat Penasehat atau Medscape .
Differential Diagnoses Diferensial Diagnosa
Cervix, Cancer Leher rahim, Kanker

Leiomyoma, Uterus (Fibroid) Leiomyoma, Rahim (Fibroid)
Other Problems to Be Considered Masalah lain untuk Be Dianggap

Endometrial hyperplasia Endometrial hyperplasia
Endometrial polyp Polip endometrium
Tamoxifen-related endometrial changes Tamoxifen-terkait perubahan endometrium
Hematometra or pyometra Hematometra atau pyometra
Endometrial sarcoma Endometrial sarkoma
Myometrial malignancy Miometrium keganasan
Kanker endometrium merupakan penyakit ganas yang terjadi ketika ada pertumbuhan tidak
terkontrol sel-sel kanker pada lapisan (endometrium) rahim. The uterus is the pear shaped organ
in a female's pelvis where pregnancy occurs and a fetus grows. Rahim adalah organ berbentuk
buah pir di panggul wanita di mana terjadi kehamilan dan janin tumbuh.
Endometrial cancer is the most common form of uterine cancer , one of the most common
cancers . kanker endometrium adalah bentuk paling umum dari kanker rahim , salah satu yang
paling umum kanker . Most cases of endometrial cancer are a type of cancer called
adenocarcinoma . Sebagian besar kasus kanker endometrium adalah jenis kanker yang disebut
adenokarsinoma . Normally, cells in the endometrium of the uterus that are old or damaged will
stop dividing and die before they can become cancerous. Biasanya, sel-sel di endometrium uterus
yang sudah tua atau rusak akan berhenti membelah dan mati sebelum mereka dapat menjadi
kanker. These cells are normally replaced by healthy young cells. Sel-sel ini biasanya digantikan
oleh sel-sel muda yang sehat. Endometrial cancer occurs when old or damaged cells to continue
to divide and multiply uncontrollably. kanker endometrium terjadi ketika sel-sel tua atau rusak
dapat terus membelah dan berkembang biak tak terkendali.
The exact cause of the process of endometrial cancer is unknown, but it may be related to
excessive exposure to the hormone estrogen. Penyebab pasti dari proses kanker endometrium
tidak diketahui, tetapi mungkin terkait dengan eksposur yang berlebihan terhadap hormon
estrogen. Risk factors for the development of endometrial cancer include taking estrogen
replacement therapy without the use of progesterone. Faktor risiko perkembangan kanker
endometrium termasuk mengambil terapi penggantian estrogen tanpa menggunakan progesteron.
Other risk factors for endometrial cancer include never being pregnant, infertility , and obesity,
which increases the amount of estrogen in a woman's body. Faktor risiko lain untuk kanker
endometrium termasuk tidak sedang hamil, infertilitas , dan obesitas, yang meningkatkan jumlah
estrogen dalam tubuh wanita. Risk factors for endometrial cancer also include hypertension ,
diabetes , and starting menstruation before age 12 or menopause after age 50. Faktor risiko untuk
kanker endometrium juga termasuk hipertensi , diabetes , dan menstruasi dimulai sebelum usia
12 tahun atau menopause setelah usia 50. Having a history of endometrial polyps or taking the
drug tamoxifen for breast cancer treatment also increase the risk. Memiliki riwayat polip
endometrium atau mengambil tamoxifen obat untuk kanker payudara perawatan juga
meningkatkan resiko. Endometrial cancer occurs most often to women who are between the ages
of 50 and 70. Kanker endometrium paling sering terjadi kepada perempuan yang berusia antara
50 dan 70.
Left untreated, endometrial cancer cells can continue to multiply and spread through the wall of
the uterus. Waktu tidak diobati, sel-sel kanker endometrium dapat terus berkembang biak dan
menyebar melalui dinding rahim. Endometrial cancer can also spread to nearby lymph nodes and
abdominal organs and to the ovaries and fallopian tubes. kanker endometrium juga dapat
menyebar ke kelenjar getah bening di dekatnya dan organ-organ perut dan pada ovarium dan
saluran tuba. If left untreated, endometrial cancer can be fatal. Jika tidak diobati, kanker
endometrium bisa berakibat fatal.
Symptoms of endometrial cancer include abnormal vaginal bleeding and unusual vaginal
discharge . Gejala kanker endometrium termasuk abnormal pendarahan vagina dan tidak biasa
vagina . For additional symptoms and complications, refer to symptoms of endometrial cancer .
Untuk gejala tambahan dan komplikasi, lihat gejala kanker endometrium .
Diagnosing endometrial cancer begins with taking a medical history, including a history of
pregnancies, estrogen use, and symptoms, and completing a physical and pelvic examination.
Diagnosa kanker endometrium dimulai dengan mengambil riwayat medis, termasuk riwayat
kehamilan, penggunaan estrogen, dan gejala, dan menyelesaikan pemeriksaan fisik dan panggul.
During the pelvic examination, the health care practitioner will assess the reproductive organs
including the uterus, and the type and amount of vaginal bleeding and vaginal discharge . Selama
pemeriksaan panggul, praktisi kesehatan akan menilai organ reproduksi, termasuk rahim, dan
tipe dan jumlah perdarahan vagina dan cairan vagina .
A diagnosis of endometrial cancer is made by taking a biopsy, a sample of the endometrial tissue
in the uterus, and examining the sample under a microscope for the presence of cancer cells.
Diagnosis kanker endometrium dibuat dengan mengambil biopsi, sampel dari jaringan
endometrium di dalam rahim, dan memeriksa sampel di bawah mikroskop untuk kehadiran
kanker sel. An endometrial biopsy can be taken during a procedure called a hysteroscopy.
Sebuah biopsi endometrium dapat diambil selama prosedur yang disebut histeroskopi sebuah. In
a hysteroscopy, a special flexible lighted instrument is inserted into the uterus to view the
endometrium and to allow for taking of a sample of endometrial tissue. Dalam histeroskopi,
sebuah alat dinyalakan khusus fleksibel dimasukkan ke dalam rahim untuk melihat endometrium
dan untuk memungkinkan pengambilan contoh jaringan endometrium.
A diagnosis of endometrial cancer may be missed or delayed because symptoms can resemble
symptoms of other diseases and conditions. Diagnosis kanker endometrium mungkin akan
terjawab atau ditunda karena gejala dapat menyerupai gejala penyakit lain dan kondisi. For
information on diseases and conditions that can mimic endometrial cancer, refer to misdiagnosis
of endometrial cancer . Untuk informasi tentang penyakit dan kondisi yang dapat meniru kanker
endometrium, lihat misdiagnosis kanker endometrium .
Endometrial cancer is highly treatable and the prognosis for a complete cure is very good if it is
diagnosed and treated at an early stage. kanker endometrium sangat diobati dan prognosis untuk
sembuh total sangat baik jika didiagnosis dan diobati pada tahap awal. Treatment of endometrial
cancer varies, depending on the individual case and the stage of the cancer. Pengobatan kanker
endometrium bervariasi, tergantung pada kasus individu dan stadium kanker. Treatment may
include surgery, radiation therapy, and possibly chemotherapy. Pengobatan mungkin termasuk
pembedahan, terapi radiasi, dan mungkin kemoterapi. For more information on treatment, refer
to treatment of endometrial cancer . Untuk informasi lebih lanjut tentang pengobatan, lihat
pengobatan kanker endometrium . ... more ... lainnya

EndometriumKarsinoma

Diunggah oleh

Informasi Dokumen

Deskripsi Asli:

Judul Asli

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

EndometriumKarsinoma

Diunggah oleh

Hak Cipta:

Format Tersedia

Karsinoma, endometrium

Postmenopausal bleeding is the most important presenting symptom of endometrial carcinoma .

The diagnosis of endometrial carcinoma is made by histological examination of endometrial

In 1988, the International Federation of Gynecology and Obstetrics (FIGO) recommended a

On ultrasound , stage I endometrial carcinoma typically appears as widening of the echogenic

Carcinoma of the endometrium appears as diffuse or foc demonstrate small volume or

Extrauterine disease Extrauterine penyakit

Based on clinicopathologic observations in 366 endometrial cancers, Bokhman ( 2 ) proposed

Top of page Ke ujung atas halaman

EPIDEMIOLOGIC OBSERVATIONS Epidemiologi PENGAMATAN

TABLE 1 - Selected Epidemiologic Exposures Related to Endometrial Carcinoma.

Full table Meja penuh

Top of page Ke ujung atas halaman

EPIDEMIOLOGIC EVIDENCE FOR TWO PATHWAYS OF ENDOMETRIAL

Full table Meja penuh

Top of page Ke ujung atas halaman

CLINICOPATHOLOGIC EVIDENCE FOR TWO PATHWAYS OF ENDOMETRIAL

A , endometrioid carcinoma, villoglandular type. Sebuah endometrioid karsinoma,, tipe

EVIDENCE FROM PRECURSOR STUDIES SUPPORTING THE EXISTENCE OF

Endometrial intraepithelial carcinoma. A, surface endometrium is replaced by a monolayer of

Full figure and legend (68 K )

Intraepithelial carcinoma involving endocervix. Lining of endocervical gland shows partial

Top of page Ke ujung atas halaman

TABLE 3 - Comparison of Selected Molecular Markers in Serous (Type 1) Carcinoma

Full table Meja penuh

Full figure and legend (78 K )

Hormone Receptors Hormon Reseptor

Top of page Ke ujung atas halaman

SUMMARY OF MOLECULAR DATA

Top of page Ke ujung atas halaman

Full figure and legend (64 K )

Historically, estrogen has been viewed as directly promoting endometrial carcinogenesis by

Observations produced by transplanting various combinations of stroma and epithelial cells

The development of endometrial hyperplasia and endometrioid carcinoma (type 1 tumors) in

Histopathologic examination suggests that Grade 3 endometrioid carcinomas develop from

Top of page Ke ujung atas halaman

ALTERNATIVE PATHWAY (GENESIS OF TYPE II TUMORS)

Dualistic model of endometrial carcinogenesis, type 2 pathway. EIC, endometrial intraepithelial

The development of sarcomatous differentiation in serous tumors presumably occurs through a

Top of page Ke ujung atas halaman

FUTURE DIRECTIONS ARAH MASA DEPAN

Top of page Ke ujung atas halaman

2. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol

4. Grady D, Ernster VL. Endometrial cancer. In: Schottenfeld D, Fraumeni JF, Jr

12.Hendrickson M, Ross J, Eifel P, Cox RS, Martinez A, Kempson R. Uterine

13.Sherman ME, Bitterman P, Rosenshein NB, Delgado G, Kurman RJ. Uterine

20.Spiegel GW. Spiegel GW. Endometrial carcinoma in situ in postmenopausal

21.Zheng W, Khurana R, Farahmand S, Wang Y, Zhang Z, Felix JC. Zheng W, R

23.Lee KR, Belinson JL. Lee KR, JL Belinson. Recurrence in noninvasive

25.Silva EG, Jenkins R. Serous carcinoma in endometrial polyps. Mod Pathol

28.Bur ME, Perlman C, Edelman L. p53 expression in neoplasms of the uterine

29.Ito K, Sasano H, Matsunaga G, Sato S, Yajima A, Nasim S, et al . K Ito, H

30.Jiko K, Sasano H, Ito K, Ozawa N, Sato S, Yajima A. Immunohistochemical, and

34.Moll UM, Chalas E, Auguste M, Meaney D, Chumas J. Uterine papillary serous

36.Hussain SP, Harris CC. SP Hussain, Harris CC. Molecular epidemiology of

37.Eschelman JR, Markowitz SD. Eschelman JR, Markowitz SD. Microsatellite

39.Burks RT, Kessis TD, Cho KR, Hedrick L. Microsatellite instability in

41.Duggan BD, Felix JC, Muderspach LI, Tourgeman D, Zheng J, Shibata D.

46.Catasus L, Machin P, Matias-Guiu X, Prat J. Microsatellite instability in

47.Gurin CC, Federici MG, Kang L, Boyd J. Causes and consequences of

50.Risinger JI, Hayes AK, Berchuck A, Barrett JC. PTEN/MMAC1 mutations in

52.Boyd J, Risinger JI. Boyd J, Risinger JI. Analysis of oncogene alterations in