PATOLOGI

INDRA KHUSUS
DAN HEMATOLIMFOID

dr. Aswiyanti Asri,

M.Si.Med,SpPA
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 palpabre

cornea
Lacrimal
caruncle
sclera
Medial lateral
commisure commisure

tear iris
drainage pupil
palpabre
canal
Olfactory
epithelium

Olfactory tract
Olfactory bulb

Nasal
conchae

Route of
inhaled air
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 Melanoma Malignum
Conjunctival, intraocular
Intraocular melanoma : tumor intraocular tersering
pada dewasa
Jarang
2%
Usia pertengahan atau lebih tua
Unilateral
Massa berpigment-non pigmented di conjunctiva

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10
 Retinoblastoma
Tumor ganas
intraocular pada anak-
anak yang terbanyak
Gen pRb
Leucocoria dan
strabismus

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 Usia tua Lesi awal : eosinofil
Terlokalisir atau intraepidermal
generalisata
Lesi matur : celah
Membran mukosa, kulit
kepala,wajah, dada, ketiak, suprabasilar dan
bokong vesikel berisi netrofil
Bullae yang tegang, bila dan eosinofil
pecah cepat terjadi erosi Acantholysis
Antibodi yang beredar dan Papila dermal
menyerang protein normal
prominent dengan sel
dalam struktur desmosom
sehingga antar sel jadi basal yang akantolitik
terpisah
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 Penyakit dermatosis
kronik, inflamasi non-
infeksius
laki-laki = perempuan
Koebner phenomen
(trauma epidermis dan
dermis), stress psikis,
obat (lithium, beta-
bloker), sunlight,
infeksi streptococcus

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ECCRINE SPIRADENOMA
29
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LYMPHOID SYSTEM
Network yang berperan
dalam menyaring antigen dari
cairan interstitial
Lokasi utama respon imun
dari antigen di jaringan
Saluran limfatik terdapat di
seluruh tubuh kecuali otak,
mata, sumsum tulang dan
tulang rawan
600 KGB
Aliran lambat

Secondary
lymphoid tissue
 Abnormalitas KGB baik dalam
jumlah, ukuran, atau
konsistensi
Digolongkan normal apabila :
1) KGB submandibular lunak,
tipis (<1cm) pada anak dan
dewasa; 2) KGB inguinal yang
teraba dengan diameter
sampai 2 cm pada dewasa.
"generalisata" bila KGB yang
membesar pada 2 atau lebih
KGB di area berbeda dan
lokalisata bila hanya pada 1
area
 Limfadenopati
Reactive
lymphadenopathy

Limfoma Malignum

Metastasis
Reactive lymphadenopathy

Autoimmune
B

Infection A C Hypersensitivity
Major
causes

E D
Idiopathic Iatrogenic
Limfadenopati e.c Neoplasma

Dendritic,
Histiocytic,
Granulocytic
Vascular
Classic, NLP

LMH LMNH
Karsinoma, B-cell, T-cell
Sarkoma
Metastasis
 Jarang dilakukan biopsi karena FNAB banyak
digunakan sebagai metode skrining (perlu
operasi/tidak).
Penyebab spesifik tidak mudah dipastikan ok
kemiripan morfologi KGB walaupun penyebab
berbeda.
Diagnosis spesifik hanya dapat ditegakkan pada 20
40% kasus.
Tetapi diagnosis non-specific ini bermanfaat
dalam mengeliminasi :
Proses keganasan
Penyebab bisa diobati (seperti infeksi)
 Reactive Follicular A
Hyperplasia
Diagnostic
Reactive Paracortical B labels
Hyperplasia

C
Sinus Histiocytosis/Sinus Catarrh

D
Reactive Lymphoid Hyperplasia

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Reactive follicular
hyperplasia
Reactive paracortical
hyperplasia
Sinus
histiocytosis
Reactive lymphoid
hyperplasia
BENIGN VS MALIGNANT
Arsitektur normal Sinus intak,
KGB arsitektur tidak
Jenis sel normal terganggu
Jenis sel tertentu Tidak membentuk

pada kondisi massa ekspansil

reaktif Berbagai jenis sel

Imunoarsitektur limfoid
normal KGB Atipia seluler <
Two populations: small Continuous range of
and large cells cell size Pure small cells

Reactive lymphoid
Small cell lymphoma
hyperplasia Lymphoma,
Reactive lymphoid
T-cell-rich large B cell especially T-cell
hyperplasia
lymphoma lymphoma
Hodgkin lymphoma
 Limfoma malignum :
cancer of the
lymphatic system
Lymphatic vessels
Lymph nodes
(underarms, groin,
neck, spleen, tonsils
and bone marrow)
Extra nodal (GIT)
Extra lymphatic
(skin,mammae,thyroid)
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LMH LMNH
NLPHL B-cell

Classic T-cell
 LMH
Usia Rata rata 27.7 dengan 2
puncak yaitu antara 15-24
tahun dan > 55 tahun.
Gender Men 0.23%
Women 0.20%
Kejadian 15% dari seluruh LM
Lokasi >> KGB supraclavicula.
Rongga dada (mediastinum t.u
pasien usia muda
Hanya 15% - 20% kasus
dibawah dafragma
Ekstranodal 4 %
LMNH
Rata-rata 67 tahun
Men 2.12%
Women 1.79%
85% dari seluruh LM
Abdomen (KGB mesenterik)
Mediastinum < 40 % kecuali
pada lymphoblastic lymphoma,
yang banyak ditemukan pada
usia muda
Ekstranodal 23%.
LM yang tumbuh lambat sering
ditemukan di hepar dan
sumsum tulang
 LMH LMNH

Sel B-Lymphocytes B-Lymphocytes, T-

yang Reed-Sternberg Cell Lymphocytes atau Natural
terkena Killer (NK) Cells
tergantung subtype

Gejala 40% ada gejala sistemik Gejala sistemik lebih

(demam, keringat malam) sedikit (27%)
Progre 10% terdiagnosis pada 36% terdiagnosis pada
sifitas stadium IV . Menyebar ke stadium IV (bervariasi
KGB di dekatnya. Tumbuh sesuai subtipe). Behaviour
lambat t.u usia muda atau lebih sulit diperkirakan dan
sangat agresif. lebih cepat menyebar.
 Staging of lymphoma
Stage I Stage II Stage III Stage IV

A: absence of B symptoms
B: fever, night sweats, weight loss
 1. NODULAR LYMPHOCYTE-PREDOMINANT HL
(NLPHL)
2. CLASSICAL HL (CHL)
A. NODULAR-SCLEROSIS HODGKIN
LYMPHOMA/NSHL
B. MIXED-CELLULARITY HODGKIN
LYMPHOMA/MCHL
Klasifikasi C. LYMPHOCYTE-RICH HODGKIN
LIMFOMA LYMPHOMA/LRHL
D. LYMPHOCYTE-DEPLETED HODGKIN
MALIGNUM LYMPHOMA/LDHL

HODGKIN
Jenis ini harus dibuktikan dahulu sebagai
Hodgkin Lymphoma baru kemudian
ditentukan
sub jenisnya.
 Lebih sedikit dari LMNH
1 Prognosis lebih baik
Stadium lebih dini.

Morfologi sel : heterogen

2
Sel ganas : Reed Sternberg

Sebagian besar berasal dari limfosit

3 B
Keterlibatan EBV

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 Relative 5 Year Stage at "b" Symptoms
Subtypes
Frequency Survival Dx at Dx

Lymphocyte 90% PS I-
5-l0% 90% 4%
predominant II

60% PS I-
Nodular sclerosis 50-70% 80% 34%
II

54% PS
Mixed cellularity 20-30% 50-60% 37%
III-IV

Lymphocyte 77% PS
<5% 20% 73%
depletion III-IV
 Mixed Cellularity
20-25%
Pasien dengan HIV dan negara sedang
berkembang
38 tahun, 70% laki-laki
Peripheral lymph node, B symptoms (+)
Arsitektur jar.limfoid digantikan oleh sel HRS
(klasik) dengan latar belakang sel limfoid non
neoplastik; bisa disertai fibrosis intersititial tetapi
tidak ada collagen bands
 55 % kasus LMNH agresif/fast growing
1 Kanker no 3 plg agresif ssd melanoma
dan kanker paru

Insiden meningkat 3-7

2
%/tahun

Terutama pada dewasa

3 Insiden puncak usia 45 60 tahun

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 WHO Classification of
non-Hodgkin lymphoma

Precursor lymphoblastic lymphoma/leukemia

(B or T cell type)

Mature B-cell neoplasms

Mature T-cell and NK-cell lymphomas

B cell 75-85 %
T cell 20 %
 Mature B-cell neoplasms (WHO)

B-cell CLL/SLL Nodal marginal zone B-

B-cell prolymphocytic cell lymphoma
leukemia Splenic marginal zone B
Lymphoplasmacytic cell lymphoma
lymphoma Hairy cell leukemia
Mantle cell lymphoma Diffuse large B-cell
Follicular lymphoma lymphoma (including
mediastinal large B-cell
Extranodal marginal
lymphoma)
zone B-cell lymphoma
of MALT type Burkitt lymphoma
Plasmacytoma, myeloma
 Mature T-cell & NK-cell neoplasms (WHO)

T-cell prolymphocytic Peripheral T-cell lymphoma

leukemia unspecified
T-cell large granular Adult T-cell
lymphocytic leukemia leukemia/lymphoma
Aggressive NK cell Anaplastic large cell
leukemia lymphoma (T or null cell),
Extranodal NK/T cell primary systemic type
lymphoma, nasal & Primary cutaneous anaplastic
nasal-type large cell lymphoma
Mycosis fungoides, Subcutaneous panniculitis-
Sezary syndrome like T-cell lymphoma
Angioimmunoblastic T Enteropathy-type intestinal
cell lymphoma T-cell lymphoma
Hepatosplenic T-cell
lymphoma
 Non-Hodgkin's Lymphomas
Type Histologic Features
Small Lymphocytic Small and well-differentiated B
Lymphoma lymphocytes, with diffuse
effacement of nodal architecture
and no follicles
Follicle Center Nodal architecture is effaced by
Lymphoma monotonous, crowded follicles
(predominantly composed of monomorphous
small cell) small cleaved B-lymphocytes
Diffuse Large B- Cells are large, with prominent
cell Lymphoma nucleoli and abundant
cytoplasm and many mitoses.
Most are B-cell, but 20% are T-
cell phenotype
Burkitt Lymphoma Intermediate sized B-
lymphocytes (small-noncleaved
cells)
Immunogenetics Clinical Features
CD19, 5; Bcl-2 and Bcl- Seen in older adults, it is essentially
6 expression the solid tissue (lymph nodal)
component of chronic lymphocytic
leukemia; disease tends to be
generalized but with indolent course
and prolonged survival; some may
transform to more aggressive
lymphomas
CD19, 20, 79a; t(14:18); Most common type, seen in adults,
Bcl-2 expression often involves multiple lymph nodes,
course is indolent, with prolonged
survival, though some may transform
to a large cell lymphoma
CD19, 20, 79a; some Though often localized, they tend to be
have t(14;18); some aggressive extranodal masses; seen in
have Bcl-2 and Bcl-6 adults and children, can be seen in HIV
expression; linked to infection
EBV infection; negative
TdT
CD10, 19, 20, 79a; Endemic in Africa with mandibular and
t(8:14) is characteristic; abdominal involvement; sporadic
African form linked to elsewhere with abdominal involvement;
EBV infection; negative affects mainly children and young
TdT adults
High-grade B-cell Intermediate CD19, 20 Sporadic; may be seen with HIV infection
Lymphoma (small sized B-
non-cleaved) lymphocytes
Burkitt-like (small non-
Lymphoma cleaved cells)

Precursor T or B- Intermediate B-cells are CD19, Seen in children and adolescents; T-cell
cell Lymphoblastic sized 20, sometimes type often in mediastinum; very
Lymphoma/Leuke lymphocytes in a CD10; T-cells are aggressive and can progress to acute
mia diffuse pattern CD3 and 8; all are lymphocytic leukemia
(Lymphoblastic TdT positive
Lymphoma)

Mantle Cell Small to medium CD 19, 20, 43; Seen in adults in middle age; often
Lymphoma sized B cells t(11;14); Bcl-1 advanced at diagnosis and may be
(Cyclin D1) extranodal, including multifocal
expression submucosal nodules in bowel

Marginal Zone Small to medium CD19, 20, 79a; Seen in middle aged adults; typically
Lymphoma sized B cells negative CD5 and arises in areas of immune activation
10 (Hashimoto thyroiditis, Sjogren syndrome,
H. pylori gastritis); similar lesions
asociated with mucosal lymphoid tissue
are called MALTomas (mucosa-associated
lymphoid tissue tumors); may transform
to diffuse large B-cell lymphoma
 Prognosis

Perangai Biologik

Highly Unusual
Indolent aggressive localized
Aggressive
indolent

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 BASED BY BEHAVIOUR
Indolent Follicular lymphoma
B-cell CLL/small lymphocytic lymphoma
Lymphoplasmacytic lymphoma
Splenic marginal zone B-cell lymphoma
Mantle cell lymphoma*
*Most aggressive of the group
Aggressive Diffuse large B-cell lymphoma
All peripheral T cell lymphomas (including
ALCL)
& NK cell lymphomas except:
Mycosis fungoides
Primary cutaneous anaplastic large cell
lymphoma
T-cell LGL leukemia
 BASED BY BEHAVIOUR

Highly Aggressive Lymphoblastic lymphoma

Burkitt lymphoma

Unusual localized Extranodal marginal zone B-

indolent cell lymphoma of MALT type
lymphoma Primary cutaneous anaplastic
large cell lymphoma
B-Cell Lymphoma
Lymphomas are caused
when a mutation arises
during the B-cell life
cycle
Various different
lymphomas can occur
during several different
stages of the cycle
Follicular lymphoma,
which is a type of B-cell
lymphoma is caused by a
gene translocation which
results in an over
expressed gene called
BCL-2, which blocks
apoptosis.
 Diffuse Large B Cell Lymphoma/DLBCL
Epidemiology 25-30% LMNH. Dekade ke-7. Sedikit lebih banyak pada
pria

Etiology De novo atau transformasi dari SLL, FL, MZL, NLPHL.

Imunodefisiensi dan EBV

Sites of involvement Nodal atau extranodal. Extranodal : GIT (>>), tulang,

testis, limpa, Waldeyer ring, kelenjar liur, tiroid, hepar,
ginjal, kelenjar adrenal
Clinical features Massa tumor yang cepat membesar baik nodal maupun
extranodal

Morphology Proloferasi difus sel limfoid besar. Centroblastic,

immunoblastic dan Anaplastic variant

Immunophenotype CD19,CD20,CD22,CD79a. Ki-67 (+) tinggi

 Limfoma burkitt
Epidemiology Endemic (Afrika, 4-7 tahun), Sporadic (anak dan dewasa
muda) dan Immunodeficiency-associated BL (HIV-AIDS).

Etiology Epstein Barr Virus t.u endemik; EBV (+) pada 30% sporadik,
sosek rendah
Sites of involvement Extranodal (rahang atau tulang wajah lainnya, ovarium, ginjal,
breast (endemik); abdomen (ileo-caecal), ovarium, ginjal,
breast (sporadik); CNS
Clinical features Proliferasi sel sangat cepat (gejala dalam beberapa minggu)

Morphology Medium-sized cells, pola pertumbuhan monoton, inti bulat,

kromatin bergumpal, sitoplasma basofilik dan mengandung
vakuol lipid, mitosis banyak, starry sky pattern (makrofag
yang memakan sel tumor yang apoptotik)

Immunophenotype CD19,Cd20,CD22,CD10,BCL6,CD38,CD77,CD43
5-YR OVERALL SURVIVAL
(NHL CLASSIFICATION PROJECT, BLOOD 1997)
Overall survival
100% Anaplastic large cell lymphoma,
T/null cell

50% Diffuse large B cell lymphoma

Peripheral T-cell lymphoma

0%
0 4 8 Years
Pemeriksaan PA-Limfadenopati

Jinak vs
Ganas FNAB

LMH/LMNH/Me
Diagnosis tastasis

Subtipe LM Blok
IHK para
fin

Biopsi in
toto
 Primer

Ganas

Sekunder
Limfadenopati

Spesifik/non
Jinak
spesifik
 FNAB
Kurang invasif, cepat
Sebagian besar pasien dengan lesi jinak :
tidak perlu biopsi
Diameter minimal 1 cm
Lesi jinak vs Ganas
Jinak : hiperplasia reaktif, limfadenitis kronik
non spesifik, limfadenitis tuberkulosa dll
Ganas ? Konfirmasi histopatologi
 Triase limfadenopati , superfisial atau deep
a. Haematolymphoid neoplasm versus other
malignancy
b. Reactive lymphoid hyperplasia versus
lymphoma
Monitoring untuk : Residual disease,
rekurensi, tumor progression
Sebagai tambahan biopsi untuk menilai detail
sitologi lebih baik
Untuk mendapatkan sampel segar untuk
flow cytometry, sitogenetik, molecular
studies dll etc.
 Keuntungan FNAB
Kurang invasif, minimal scarring
High patient acceptance
Cost-effectiveness
Komplikasi sedikit : perdarahan, infeksi
Rapid results
Easy to perform
Avoidance of a two-stage surgical procedure
in case of malignant disease
 Kerugian FNAB
Akurasi bervariasi tergantung sampel
Sulit diagnosis pasti pada LM
Kompleksitas klasifikasi LM dan
pentingnya penilaian arsitektur KGB
membatasi diagnosis sitologik
 KESALAHAN SAMPEL JIKA
Nodus kecil dan dalam
nekrosis dan inflamasi luas
fibrosis
Lesi hanya melibatkan
sebagian limfonodus
SKEMA PROSEDUR & TEHNIK FNAB

Tumor Mass

86
Non-palp mass Palp mass

CT-Scan MRI Solid + Cyst Cyst

USG FNAB

FNAB-Guiding FNAB Aspempty

Conclusion Re asp mass

Confirm Th/.
Prosedur & Tehnik Biopsi Jarum Halus
( Aspirasi / tanpa aspirasi )

87
PULASAN

Umum digunakan
MGG Sitoplasma

Evaluasi inti
PAP Misal: untuk bedakan
dengan metastasis SCC
 Non-Hodgkins Lymphoma

H and N(1) Salivary(2)

1990-2004(3) >2005(4)

Sensitivity 75.0% 68.2% Up to 100% 81.0%

Specificity 96.0% 87.7% Up to 100% 73.0%

Accuracy 58.8% 82.3% 86.6% 64.0%

False positive 6.7% NR NR NR

False negative 13.3% NR NR 14.0%

(+) predictive value 86.0% 68.2% 100% NR

H and N= Head and Neck; NR=not reported

(-) predictive value 93.0% 87.7% 99% NR

 PERMASALAHAN

LESI NON
1 LESI LIMFOID LIMFOID

VS
2 LIMFOMA NON LIMFOMA
HODGKIN HODGKIN

3 LIMFOMA NON HIPERPLASIA

HODGKIN REAKTIF

4 SUBKLASIFIKASI LIMFOMA ???

 Key point

Fine-needle aspiration (FNA) biopsy

should not be used in the definitive
diagnosis or subtyping of lymphomas,
for which excision biopsy remains the
definitive procedure.
TOUCH IMPRINT/SMEARS

Jaringan segar
Sitologi

Papanicoloau, HE, Giemsa, Diff-Kwik

Unstained air-dried imprint : imunositokimia,

molecular studies
Menekankan jaringan segar pada objek glass

Rapid intraoperative diagnosis

BIOPSI

Blok parafin : histopatologi

Diagnosis definitif dari biopsi, terutama
keganasan, sebelum diberikan terapi
Jaringan tidak boleh terlalu sedikit agar dapat
dinilai sel dan arsitektur KGB
Biopsi in toto
BIOPSI
Core biopsy, biopsi in toto
Fresh tissue : frozen section dan imprint
Frozen section : kesulitan dalam diagnosis
Jaringan difiksasi
NBF 10%, slices
Reagen yang digunakan, metode harus
sedemikian rupa sehingga tidak merusak
protein/antigen jaringan ok dipersiapkan untuk
IHK
HE
BIOPSI

Makroskopik
Mikroskopik
Reactive vs malignant
Arsitektur KGB normal

LMH vs LMNH : sel RS

Populasi sel monoton, difus vs folikuler : LMNH

Ukuran/diameter sel dibandingkan dengan limfosit

Jenis sel kecil, sedang, besar

 IMUNOHISTOKIMIA

Terutama bermanfaat dalam :

Reactive lymphadenopathy vs
limfoma
LM vs keganasan lainnya
Klasifikasi LM
Prognosis dan stadium LM
Assay target terapi
 Imunohistokimia

Paraffin section IHC

Paling banyak digunakan
Lebih mudah dikerjakan dan diinterpretasikan..

Frozen section IHC

Mulai ditinggalkan
Kendala ketersediaan jaringan, lebih sulit dalam
pewarnaan dan interpretasi
IMUNOHISTOKIMIA

Antigen retrieval
inadekuat
B

Antigen rusak A C Metode <

sensitif
Negative
results

Reagen salah E D Antibodi

atau urutan www.themegallery.com expired
kerja salah
Lymphoma or other malignancies?

LCA Cytokeratin S100

protein
Lymphoma +* - -

Carcinoma - + -/+

Melanoma - - +

Sarcoma - - -/+
 SUBTYPING
CYCLIN
CD20 CD43 CD5 CD23
D1

SLL +/- + + + -

MZL + -/+ - - -
MALT0MA
LP + + - - -

MCL + + + - +

KPLST, 24-25/03/07, IAP KOL

 Workup lineage of lymphoma
CD20 and CD3 panel

CD20+ CD3+ CD20- CD3-

B-cell lymphoma; T-cell or NK cell Non-hematolymphoid?

add other markers lymphoma; Plasmacytoma?
for typing Add other markers Plasmablastic lymphoma?
if necessary (CD56, CD30) T cell lymphoma?
as required Lymphoblastic lymphoma?
 SLL , FL gr1 : WATCHFULL
WAITING
LB : LEUKEMIC REGIMEN
BL : AGGRESSIVE
REGIMEN
MCL : BM
TRANSPLANTATION
CD 20 + : IMUNOTERAPI ANTI
CD 20
KPLST, 24-25/03/07, IAP KOL
 Jaringan adekuat, tidak pecah-
pecah
Pengelolaan jaringan baik, fiksasi
adekuat
Prosesing jaringan dengan alkohol
bertingkat
Parafin titik lebur rendah
Slide tipis
Tidak terlipat

KPLST, 24-25/03/07, IAP KOL

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