Tumors - Reproductive System TUMORS REPRODUCTIVE SYSTEM Name

Site

Morphological features

Metastasis

Clinical features

SQUAMOUS CELL CARCINOMA VULVAL INTRAEPITHELIAL NEOPLASIA (VIN) VAGINAL INTRAEPITHELIAL NEOPLASIA (VAIN)

Vulva

mainly de novo

- local invasion - spread to inguinal LN - often coexisting HPV warts

elderly women

Vulva

younger women

Vagina

mostly in women previously treated for CIN or invasive cervical cancer - extremly rare - Squamous cell carinoma / Adenocarcinoma - more common (spread from other near-by organs) Vaginal bleeding after hysterectomy possible sign!

PRIMARY MALIGNANT Vagina TUMORS SECONDARY TUMORS Vagina

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Tumors - Reproductive System CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) Cervix - preneoplastic (dysplastic) proliferation of epithelium of transitional zone of cervix - strongly associated with HPV 16,18,31,33 - classification see below Risk of progression to invasive carcinoma CIN I. (mild dysplasia) Cervix Upper 2/3 of epithelium normal, basal third atypical cells Risk factors: - sexual intercourse - early intercourse - STDs - smoking - HPV (90%!) - HIV infection

CIN II. (moderate dysplasia)

Cervix

of epithelium normal, abnormal d only atypical cells throught the whole epithelium

CIN III. (severe Cervix dysplasia) = CARCINOMA-IN-SITU

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Tumors - Reproductive System SQUAMOUS CELL CARCINOMA Cervix transformation zone / ectocervix MACROSCOPY: - 1st) granular irregularity hard cervix - 2nd) fungating ulcers MICROSCOPY: 3 histological patterns: 1) Keratinizing, large cell squamous carcinoma 2) Nonkeratinizing, large cell squamous carcinoma 3) Nonkeratinzing, small cell squamous carcinoma - preceded by CIN! - stages I. - IV. - early stages: presents as VAGINAL BLEEDING - late stages: URINARY OBSTRUCTION (if bladder involvement) - involvement of paraaortic LN bad prognosis

ENDOMETRIAL POLYPS

Uterus

- due to inappropriate estrogen stimulus - in fundus uteri - 1-3 cm - microscopically: cystically dilated endometrial glands

- very common - perimenopausal age - Menstrual abnormalities - Dysmenorrhea

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Tumors - Reproductive System LEIOMYOMA (FIBROIDS) Uterus - estrogen- sensitive grow fastly in pregnancy shrink in menopause / GnRH agonist therapy - sites: INTERSTITIAL (most common) SUBSEROUS SUBMUCOSAL - typically multiple - 2-4 cm - smooth mm. Islands with intervening collagenous stroma - no cellular atypia ENDOMETRIAL CARCINOMA Uterus - Adenocarcinoma - 2 groups: - mainly local invasion of surrounding 1) HYPERESTROGENIC TUMORS structures good prognosis ass. with endometrial hyperplasia / estrogenic stimuli adenocarcinomas (60%) 2) NONHYPERESTROGENIC TUMORS bad prognosis postmenopausal deep myometrial invasion - most common of all tumors - affect 50% of women over 30 years - more common in nulliparous women or with low fertility - genetic factors - presents as: ABNORMAL BLEEDING DYSMENORRHEA INFERTILITY - beginning/postmenopausal age (mean age: 55 years) - risk factors:

- widespread Hyperestrogenic states metastasis via (Obesity, DM, Late Menopause, hemato-genous Estrogen-secreting tumors) route uncommon! Previous Pelvic irradiation Lower parity - presents as: POSTMENOPAUSAL BLEEDING

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Tumors - Reproductive System OVARIAN CANCER Ovary 3 TYPES (according to tissue part they derive from): 1) SURFACE EPITHELIAL TUMORS 2) GERM CELL TUMORS 3) SEX CORD AND STROMAL TUMORS SURFACE EPITHELIAL Ovary TUMORS - 70% of all ovarian tumors, 90 % of malignant ones - derived from embyronal coelomic epithelium - differentiate into different types of tumors: 1) SEROUS TUMORS 2) ENDOMETRIAL & CLEAR-CELL TUMORS 3) MUCINOUS TUMORS 4) BRENNER TUMORS - adult life - classification: - Benign (mostly) - Borderline malignant (= atypical cells but no invasion) - Malignant - presents often in advanced stage - 5% hereditary (BRCA1 gene mutations)

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Tumors - Reproductive System SEROUS TUMORS Ovary tubal differentiation Types: 1) Serous cystadenoma (70%) 2) Serous cystadencarcinoma 3) Borderline serous tumor endometrial differentiation CLEAR CELL CARCINOMA variant containing cells with clear cytoplasm and glycogen MUCINOUS TUMORS Ovary endocervical differentiation Types: 1) Mucinous cystadenoma 2) Borderline mucinous tumor 3) Mucinous cystadenocarcinoma MAINLY BENIGN UNILOCAR CYST (watery) MAINLY MALIGNANT (20% of all ovarian carcinomas) MULTI-LOCULAR CYSTS (gelatinous)

ENDOMETRIAL TUMORS

Ovary

BRENNERS TUMORS (TRANSITIONAL)

Ovary

transitional differentiation tumor nests resembling transitional epithelium of UT spindle cell stroma - types: 1) TERATOMA 2) DYSGERMINOMA 3) YOLK-SAC TUMOR Seite 6

GERM CELL TUMORS

Ovary

Tumors - Reproductive System TERATOMA Ovary 2 types: a) benign cystic b) solid similar to SEMINOMA of TESTES types: - cystic - solid - hemorrhagic - types: 1) GRANULOSA CELL TUMOR 2) SERTOLI LEYDIG CELL TUMOR 3) GONADOBLASTOMA 4) STEROID CELL TUMOR SECONDARY TUMORS Ovary KRUKENBERG'S TUMOR Ovary common site of metastasis, usually from BREAST and GIT typically GASTRIC origin signet ring-cell adenocarcinoma ADENOMATOID TUMOR Fallopian tube ADENOCARCINOMA Fallopian tube typically of mesosalpyinx extremly rare - Postmenopausal women - POOR prognosis late presentation SECONDARY TUMORS Fallopian tube from endometrial carcinoma secrete Alpha-fetoprotein

DYSGERMINOMA YOLK-SAC TUMOR

Ovary Ovary

SEX CORD AND STROMAL TUMORS

Ovary

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Tumors - Reproductive System HYDRATIDIFORM MOLE Placenta / Trophoblast = abnormal development of a gestational trophoblast - benign mass of cystic vesicles derived from chorionic villi - 2 types: PARTIAL triploid (1 maternal, 2 paternal haploid sets of chromosomes); cysts only partially; fetal parts and some normal placental villi COMPLETE paternal origin; bulky, grape-like mass filling the uterine cavity; no fetal parts - 1 in 2000 births - low risk of becoming malignant - presentation: AMENORRHEA followed by continous/intermittent vaginal bleeding PREGNANY SYMPTOMS (vomiting, preeclampsia) ENLARGED SOFT UTERUS (larger than date would suggest) - diagnosis: hCG in urine (higher than in normal pregnancies) US: ABSENCE of FETUS

INVASIVE MOLE

Placenta / Trophoblast

- hydratidiform mole which invades myometrium & associated blood vessels - perforation of uterus possible parametrium invasion - malignant transformation rare

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Tumors - Reproductive System CHORIO-CARCINOMA Placenta / Trophoblast - propensity to invade vessel walls blood borne - rare in Western countries metastases occur early - 50% develop from HYDRATIDIFORM MOLE! mainly to LUNG and BRAIN - 20% arise after normal pregnancy - prognosis excellent responds well to chemotherapy FIBROADENOMA Breast - common - BENIGN tumor with proliferation of stroma and epithelium PHYLLODES TUMOR Breast - BENIGN (90%) - cellular stroma + epithelium - rubbery white lesions with a whorled pattern of slit-like spaces and solid areas INTRADUCTAL PAPILLOMA Breast - microscopically big variety - BENIGN - epithelial proliferation - usually solitary - low risk of carcinoma (multiple higher risk, but rare) Seite 9 - older women - presentation: BLOOD-STAINED NIPPLE DISCHARGE - young women (25-35 years) - discrete, but movable breast lumps (1-4 cm size) - peak incidence: 45 years - presents as breast lump

Tumors - Reproductive System CARCINOMA Breast - ADENOCARCINOMA derived from terminal ductal lobular epithelium Types: - direct: - 20% of all cancers in women skin + muscles of the chest wall - risk factors:

- lymphatic: atypical epithelial proliferation Axillary LN, BRCA 1 mutation internal mammary long interval between 1) NON-INVASIVE LN, menarche & menopause Supraclavicular LN late first pregnancy a) ductal carcinoma in situ can obesity and wrong diet become invasive - blood: ionizing radiation Liver, lung, b) lobular carcinoma in situ opposite breast, - presentation: marker for devloping breast cancer! bone, brain DISCRETE LUMP with 2) INVASIVE -transcoelomic: TETHERING to SKIN or to Pleural cavity, surrounding C.T Types: Pericardium - invasive ductal (85%) - Prognosis: - invasive lobular (10%) - mucinous Depends on tumor grade and - tubular type (TUBULAR best - medullary prognosis), LN status and - papillary Estrogen sensitivity - < 1% in men ductal type associated with Klinefelter's syndrome

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Tumors - Reproductive System CONDYLOMA ACUMINATUM ERYTHROPLASIA OF QUEYRAT ( = carcinoma in-situ) SQUAMOUS CELL CARCINOMA Penis Penis = genital warts - HPV 6 and 11 - Glans - resembles balanitis - often associated with HPV infection - well- differentiated, keratinizing, invasive tumor - associated with previous HPV infection untreated will lead to invasive cancer - Elderly, uncircumcised men - presents as slow- growing wart which bleeds easily

Penis

TESTICULAR TUMORS Testis

- 2 main groups: 1) GERM CELL TUMORS (97%) from multipotent germ cells of testis Teratoma Seminoma Combined 2) NON-GERM CELL TUMORS from support cells of testis Leydig cell tumor Sertoli cell tumor

- Lung (hemoptysis) - Liver (hepatomegaly) - Paraaortic LN (retroperitoneal mass)

- uncommon - young men (20-45 years) risk factors: - Maldescent of testis presentation: - Painless, unilateral enlargement - secondary hydrocele - symptoms of metastases - endocrine side effects (gynecomastia, precocious puberty)

GERM CELL TUMORS

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Tumors - Reproductive System SEMINOMA Testis - most common malignant testicular tumor! - histological subtypes: CLASSICAL SPERMATOCYTIC ANAPLASTIC with TROPHOBLASTIC GIANT CELLS composed of several types of tissues (endo, ecto and mesoderm) more aggressive than seminoma types: Mature/Immature Embyronal carcinoma Yolk sac tumor (worst prognosis) Choriocarcinoma

TERATOMA

Testis

- alpha- FETOPROTEIN detectable

NON-GERM CELL TUMORS

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Tumors - Reproductive System LEYDIG (INTERSTITIAL) Testis CELL TUMOR - mainly benign - may produce ANDROGENS, ESTROGENS or both presentation: PRECOCIOUS PUBERTY LOSS of LIBIDO GYNECOMASTIA SERTOLI CELL TUMOR Testis (ANDRO- BLASTOMA) MALIGNANT LYMPHOMA Testis - mostly benign

- B cell lymphoma with diffuse pattern - ACUTE LEUKEMIA

- peak: 60 - 80 years - 7% of testicular tumors

SECONDARY TUMORS Testis

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