LMNH Proliferasi ganas limfosit (sel B atau sel T) Etiologi unknown. Insidens LMNH semakin meningkat LMNH : campuran dari limfosit yang

sudag bertransformasi ganas, sel limfoid reaktif dan stroma

85% LMNH dari sel B 20 subtipe LMNH yang sudah diketahui. Identifikasi subtipe berdasarkan

morfologik dan pewarnaan khusus (IHK)

LMNHUsia puncak 50-70 tahun (67% kasus

pada pasien berusia > 60 tahun)Dapat mengenai semua umurLimfadenopati generalisata-

painless,>> visceral lymphadenopathy, 40% extranodal

Hepatosplenomegali, BB menurun, fatigue, keringat malam, anemia, infeksi, purpura

LMNH

80-85% sel B, sisanya sel T Subtipe : ukuran dan morfologi sel >> Difus, kk Nodular (Follicular lymphoma) Makroskopik

KGB membesar Padat atau seperti daging ikan Bisa menyatu Permukaan abu-abu

Mikroskopik hilangnya arsitektur KGB Limfosit normal digantikan oleh limfosit ganas Tipe limfosit yang predominan menentukan subtipe

LMNH

KLASIFIKASI LMNH

“Nowhere in pathology has a chaos of names clouded clear concepts as inthe subject of lymphoid tumors”

RAPPAPORTKIELLUKES & COLLINSWF

B-areas and cell types

T-areas and cell types

Disease states correlate with stages in normal B-cell development

Diseases: AML Pro-B-ALL Pre-B-ALL -B-CLL-DLBCL-FLL-BL-Mantle Cell lymphoma-Marginal Zone lymphoma-MALT-GALT-Hodgkins (?)

B-ALL -MGUS-Multiple Myeloma-Plasmacytoma

Precursor lymphoblastic lymphoma/leukemia(B or T cell type)

Mature B-cell neoplasms

Mature T-cell and NK-cell lymphomas

Mature B-cell neoplasms (WHO)B-cell CLL/SLLB-cell prolymphocytic

leukemiaLymphoplasmacytic

lymphomaMantle cell lymphomaFollicular lymphomaExtranodal marginal

zone B-cell lymphoma of MALT type

Nodal marginal zone B-cell lymphoma

Splenic marginal zone B cell lymphoma

Hairy cell leukemiaDiffuse large B-cell

lymphoma (including mediastinal large B-cell lymphoma)

Burkitt lymphomaPlasmacytoma, myeloma

Mature T-cell & NK-cell neoplasms (WHO) T-cell prolymphocytic

leukemia T-cell large granular

lymphocytic leukemia Aggressive NK cell

leukemia Extranodal NK/T cell

lymphoma, nasal & nasal-type

Mycosis fungoides, Sezary syndrome

Angioimmunoblastic T cell lymphoma

Peripheral T-cell lymphoma unspecified

Adult T-cell leukemia/lymphoma

Anaplastic large cell lymphoma (T or null cell), primary systemic type

Primary cutaneous anaplastic large cell lymphoma

Subcutaneous panniculitis-like T-cell lymphoma

Enteropathy-type intestinal T-cell lymphoma

Hepatosplenic T-cell lymphoma

Leukemia Limfoblastik Akut

LMNH lymphoblastic type

Leukemia Limfositik Kronik

Small Lymphocytic Lymphoma

Anak : cut off sel blast < 25 % di sumsum tulang

Tanpa sitopenia;

<5 x 109 /L sel B di darah

tepi

BASED BY BEHAVIOURIndolent •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 fungoidesPrimary cutaneous anaplastic large cell lymphomaT-cell LGL leukemia

BASED BY BEHAVIOUR

Highly Aggressive

•Lymphoblastic lymphoma• Burkitt lymphoma

Unusual localized indolent lymphoma

•Extranodal marginal zone B-cell lymphoma of MALT type•Primary cutaneous anaplastic large cell lymphoma

Chronic lymphocytic leukemia/Small lymphocytic lymphoma

Epidemiology 6,7% dari seluruh LMNHLM/Leukemia terbanyak pada dewasa

Etiology Diduga (auto) antigen (IGHV gene) Sites of involvement

Peripheral blood, sumsum tulang dan peripheral lymph node, limpa, hepar

Clinical features Asimptomatik >>Bisa fatigue, AIHA, infeksi, hepatosplenomegali

Morphology Diffuse, monomorphicPola “pseudofollicular” yaitu “proliferation centre” yang mengandung sel besar dengan latar belakang sel kecil

Immunophenotype

CD20, CD22,CD5,CD19,CD79a,CD23,CD43,Cd11c (weak)

PlasmacytomaEpidemiology 3-5% plasma cell neoplasms, 65%

laki-lakiEtiology Infeksi/penyakit kronik, bahan

toksik dan radiasiSites of involvement

Vertebra, cranium, pelvis, costae, femur,klavikula, skapula

Clinical features Multipel = Multiple Myeloma; bone pain, fraktur patologik; M-protein dalam serum atau urine

Morphology Proliferasi sel plasma; Dutcher bodies, Mott cell

Immunophenotype

CD79a, CD38,VS38c,CD138; CD19(-)

Marginal Zone LymphomaEpidemiology 1,5-1,8 % LM. Usia 60 tahun.

Bisa pada anak-anakSites of involvement

Peripheral lymph nodes

Clinical features Asimptomatik, localized or generalized lymphadenopathy

Morphology Diffuse, monomorphic; Sel tumor terdiri atas sel B marginal zone, sel plasma dan kk sel B yang bertransformasi. Follicular growth pattern yang mengelilingi centrum germinal yang reaktif

Immunophenotype

CD20 dan CD79a, CD43 (50%), BCl2

Follicular LymphomaEpidemiology 20% LM. Dekade 6Sites of involvement

Lymph nodes, juga limpa, sumsum tulang, darah perifer dan Waldeyer ring. Bisa ekstranodal (kulit, GIT, ocular adnexa, breast, testis

Clinical features Saat diagnosis sudah menyebar jauh. 40-70% mengenai sumsum tulang.

Morphology Follicle center B-cells (centrocytes atau centroblast); Mixed small and large cell, nodular or diffuse. >> Follicular pattern dengan folikel yang padat, tidak sama besar; Grade 1-3

Immunophenotype CD19, Cd20, CD22, CD79a. Marker B cells (+) di folikel dan interfollicular

Mantle Cell LymphomaEpidemiology 3-10% LMNH. Usia pertengahan,

>> laki-lakiSites of involvement

Lymph nodes, kk sumsum tulang, limpa. Ekstranodal : GIT (multiple lymphomatous polyposis) dan Waldeyer ring

Clinical features

Stadium III atau IV, limfadenopati, hepatosplenomegali, mengenai sumsum tulang

Morphology Diffuse, monomorphic, small to medium cells, kontur inti iregular, mirip centrocytes

Immunophenotype

CD5, FMC-7, CD43, BCl2, Cyclin D1

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 burkittEpidemiology 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

Precursor B-Lymphoblastic Lymphoma/Leukemia

Epidemiology 75% < 6 tahun

Sites of involvement

Sumsum tulang >>, CNS, kgb, limpa, hepar, testis.

Clinical features Manifestasi kegagalan sumsum tulang, limfadenopati, hepatosplenomegali

Morphology Medium cells, inti bulat, ireguler atau berlekuk

Immunophenotype

CD19,CD79a,CD22,CD10,Cd24,PAX5, TdT

Precursor T-Lymphoblastic Lymphoma/Leukemia

Epidemiology Remaja, laki-laki>perempuan

Sites of involvement

Sumsum tulang, kk mediastinum (thymic)

Clinical features Leukositosis, massa mediastinum, limfadenopati, hepatosplenomegali, efusi pleura (massa mediastinum)

Morphology Medium, sulit dibedakan dari Precursor B-lymphoblastic lymphoma/leukemia

Immunophenotype

TdT, CD2, CD3, CD4, CD5, CD7, CD8

Anaplastic Large Cell Lymphoma

Epidemiology 3 dekade pertama, laki-laki predominan

Sites of involvement

KGB dan extranodal (kulit, tulang, soft tissue, paru, hepar)

Clinical features

Stage III atau IV disertai limfadenopati perifer dan/atau abdominal, B symptoms

Morphology ALK (+) dan ALK (-). Large cells, Horseshoe or kidney shaped nuclei cells (hallmark)

Immunophenotype

CD30ALCL - ALK (+) mempunyai prognosis lebih baik dibanding ALCL - ALK (-)

ALCL, ALK +ALK (+) Mum 1 (+)

NK/T-Cell LymphomaEpidemiology Asia, Indian, dewasa (laki-laki

lebih >)Etiology Epstein Barr VirusSites of involvement

Extranodal : saluran napas atas ( kavum nasi, nasofaring, sinus paranasal, palatum); extranasal (kulit, soft tissue, GIT, testis)

Clinical features

Obstruksi nasal, epistaksis, destruksi midfacial (lethal midline granuloma)

Morphology Infiltrat limfomatosa difus dan permeatif. Angiocentric dan angiodestructive growth pattern

Immunophenotype

CD2,CD56,CD3Survival rates buruk (30-40%)

Intestinal NK/T-cell Lymphoma

CD 56 (+)

Mycosis FungoidesEpidemiology 50% dari primary cutaneous

lymphoma, dewasa, laki-laki lebih banyak

Sites of involvement

Kulit. Stadium lanjut bisa ke kgb, hepar, limpa, paru

Clinical features Indolent, tumbuh lambat. patches-plaques-tumours; Stage I-IV; erythtoderma stage- Sezary syndrome

Morphology Tergantung stage. Atypical cells dengan inti cerebriform, Pautrier microabscess

Immunophenotype

Cd2, Cd3, Cd5, CD4, TCRß

Metastasis Tumor Ganas

Sesuai drain sistem limfoid Bentuk = atau menyerupai tumor

primer IHK atau penanda tumor Karsinoma !!!! Jaringan limfoid diinfiltrasi sebagian

atau seluruhnya oleh sel tumor ganas

Metastasis Karsinoma Mammae

Thank You !!!