Download - Kelainan leukosit
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KELAINAN LEUKOSIT
Diah Puspita Rini,dr.,SpPK
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KELAINAN LEUKOSIT
1. LEUKOPENIA : LEUKOSIT < 4.000/µL
2. LEUKOSITOSIS : LEUKOSIT > 10.000/µL
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DIFFERENTIAL DIAGNOSIS
Leukopenia Infeksi : virus Obat: analgesik, antibiotik, antikonvulsan Autoimun Hipersplenisme Anemia aplastik
Leukositosis Reaksi leukemoid : respon terhadap infeksi,
terdapat peningkatan mieloid imatur = “shift to the left”
Leukemia
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SHIFT TO THE LEFT
promielosit
Pergeseran populasi netrofil ke arah neutrofil imatur (band, metamielosit, mielosit dst)
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LEUKEMIA
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LEUKEMIA Definisi: Leukemia adalah keganasan yang berasal dari SIH
yang mengakibatkan PROLIFERASI sel darah putih tidak terkontrol→ akumulasi sel lekosit dalam sutul, darah dan organ
PROLIFERASI
MATURASI
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ETIOLOGI
Mutasi DNA gen sel akibat:- Pemaparan karsinogen- Virus onkogen- Radiasi- Mutasi gen spontan / idiopatik
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SIFAT SEL LEUKEMIA
Tinggal di sirkulasi lebih lama Mengeluarkan bahan yang dapat
menghambat proliferasi sel normal Dapat berproliferasi di organ lain Proliferasi abnormal salah satu populasi
hemopoitik dapat menekan proliferasi populasi hemopoitik yang lain, mengakibatkan :
- Anemia
- Trombositopenia
- Granulositopenia
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FUNGSI SEL LEUKEMIA
Respon terhadap kemotaksin Mobilitas Metabolisme Fungsi fagosit terganggu
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KLASIFIKASI LEUKEMIA
Tergantung dari sel leukemia yang dominan
yang ditemukanSel muda (blast) banyak → LEUKEMIA AKUT
Sel matur banyak → LEUKEMIA KRONIK
MYELOID
Leukemia akut: sel primitif akan tertahan maturasinya, menumpuk di
sutul → mengganggu fungsi sumsum tulang normal lainnya
Leukemia kronis: sel cenderung meninggalkan sutul, menumpuk di
ekstra meduler ( limpa dan kel limfe)
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LEUKEMIA
AKUT
KRONIK
AML
ALL
CML
CLL
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KLASIFIKASI LEUKEMIA
Morfologi ( mikroskop ) : French – American – British (FAB)
Sitokimia (pengecatan):
myeloperoksidase (MPO), sudan black (SB), PAS, Esterase
Imunologi ( immunophenotyping )
Sitogenetika
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LEUKEMIA AKUT
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CIRI - CIRI
penderita dewasa muda / anak tampak sakit keras suhu badan naik ada tanda infeksi perdarahan nyeri tulang pucat, lesu
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AML (ACUTE MYELOGENOUS LEUKEMIA)
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MYELOID MATURATION
myeloblast
promyelocyte myelocyte metamyelocyte band neutrophil
MATURATION
Adapted and modified from U Va website
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KLASIFIKASI AML
WHO Classification- Immunophenotype- Clinical features- Cytogenetics and chromosomal abnormalities
FAB (French-American-British)- Degree of differentiation
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FAB ClassificationFAB subtype Name Adult AML
patiens (%)
M0 Undifferentiated acute myeloblastic leukemia
5 %
M1 Acute myeloblastic leukemia with minimal maturation
15 %
M2 Acute myeloblastic leukemia with maturation
25%
M3 Acute promyelocytic leukemia 10%
M4 Acute myelomonocytic leukemia
20%
M4 Eos Acute myelomonocytic leukemia with eosinophilia
5%
M5 Acute monocytic leukemia 10%
M6 Acute erythroid leukemia 5%
M7 Acute megakaryocytic leukemia
5%
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GAMBARAN KLINISClassic triad:
Anemia : pucat/lemah, dyspneu, palpitasi Functional neutropenia: infeksi → panas Trombositopenia: mudah memar, ptechiae,
purpura, epistaksis, perdarahan pada gusi, konjungtiva.
Anoreksia, BB ↓, nyeri tulang Hepatomegali, splenomegali pada 1/3 pasienHipertrofi ginggiva (AML M4, M5) Disseminated Intravascular Coagulation (AML M3), krn granula bersifat tromboplastin (prokoagulan)
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PETECHIAE
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Ecchymoses
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Purpura
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GAMBARAN LABORATORIUM
HAPUSAN DARAH TEPI ANEMIA : normokromik normositik, normoblast ±LEKOSIT : Netropenia/normal/meningkat
Myeloblast ≥ 20%, Auer Rods ± Hiatus leukemia
TROMBOSITOPENIA
HAPUSAN SUMSUM TULANGSelularitas meningkat (hiperseluler) : 75% mieloblasSistem granulopoietik: terdapat infiltrasi sel muda seri mieloidSistem eritropoiesis terdesakSistem trombopoeisis terdesak
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NORMAL MARROW
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ENTIRE MARROW REPLACED BY BLAST
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MYELOBLAST WITH AUER RODS (M3,M4,M5)
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AML M0 (differensiasi minimal) blast > 20% tanpa granul
AML M1(tanpa maturasi) blast sutul > 20% dengan/tanpa granul, maturasi
maksimal 10% AML M2 (dengan maturasi)
Blast > 20%, 10 % > sel matur (promyelosit) < 30% AML M3 (acute promyelocytic leukemia)
Blast > 20%, myeloblast+promyelosit granula sitoplasma kasar (tromboplastin like
substance) → DIC AML M4 (Acute myelomonocytic leukemia)
blast > 20 % ( monoblast ,myeloblast >>) terdapat monosit & pro monosit DD:
M-5 peroxidase tes M5 (negatif)
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AML M5 (Acute Monocytic Leukemia)Blast > 20% : monosit >>, promonosit
AML M6 (Eritroleukemia)Terdiri dari : ERITROBLAST > 50% MYELOBLAST > 30% , PROMYELOCYT , MONOSITPerjalanan penyakit AML
AML M7 (Megakaryocytic Leukemia) Jarang terdiagnosis Sulit di bedakan dengan : ALL ( L1-L2 & M1) Biasanya disertai dengan pansitopenia Retikulin di sutul meningkat (fibrosis) sulit diaspirasi / dry
tap
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ALL
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→ invasi sel blast ke jaringan /organ lain:
- SSP
- Hati
- Limpa
- KGB
Penekanan terhadap:-Eritropoiesis → anemia- Trombopoiesis → trombositopenia
PROLIFERASI LIMFOBLAST
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GEJALA KLINIS
(INFILTRASI ORGAN)
Febris
Lemah (krn anemia)
Limfadenopati superfisial
Nyeri tulang atau sendi
Hepato splenomegali
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Gambaran laboratorium
Darah tepiLekositosis, limfoblast >>Anemia, trombositopenia
Sumsum tulang → HIPERSELULERSel normal terdesak oleh limfoblast
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KLASIFIKASI ALL (FAB)
L1 L2 L3
Ukuran sel kecil,homogen besar, heterogen
Besar, homogen
sitoplasma sedikit relatif lebar Relatif lebar
Anak inti Tak tampak 1/>, besar menonjol
1/>, besar menonjol
Inti reguler unreguler reguler
Kromatin inti bergumpal halus halus
Vakuola sitoplasma
variabel variabel prominen
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Immunologic subtype
% of cases FAB subtype
Pre B ALL 75 L1,L2
T cell ALL 20 L1,L2
Mature B cell ALL (burkitt leukemia)
5 L3
Klasifikasi WHO
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T CELL ALL(L1)
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T CELL ALL (L2)IRREGULAR CLEFTS OF NUCLEUS
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BURKITT LEUKEMIA-MATURE B CELL ALL (L3)-VACUOLATIONS
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LEUKEMIA KRONIK
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Ciri – ciri :1.Sering terjadi pada usia lanjut2.Perjalanan penyakit berangsur-angsur,
progresif & sering tidak bergejala3.Dapat berubah menjadi leukemia akut4.Terdapat organomegali5.Jumlah lekosit sangat tinggi6.Hb sedikit turun, kecuali pada stadium
akhir
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KELAINAN MYELOPROLIFERATIVE
1. POLISITEMIA VERA2. ESSENTIAL TROMBOSITEMIA3. MYELOFIBROSIS4. CML
KELAINAN LIMFO PROLIFERATIVE
• HODKIN DISEASE• NON HODKIN LYMFOMA• HAIRY CELL LEUKEMIA• MYCOSIS FUNGUIDES• CLL
KLASIFIKASI LEUKEMIA
LEUKEMIAKRONIK
CML CLL
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CHRONIC MYELOCYTIC LEUKEMIA (CML)
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Kelainan pada SIH multipoten Ditandai dengan proliferasi yg tdk teratur
dari sel myeloid di sutul, hepar, limpa → leukositosis dan organomegali
Insiden: 20% dari semua leukemia Dewasa usia 25-60 th, dengan puncak 40-59 th
90 % terdapat Philadelphia kromosom
CML(CHRONIC MYELOCYTIC LEUKEMIA)
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PHILADELPHIA CHROMOSOME IN CML
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CML-Chronic phase
CML- Blastic phase
Hematopoietic Stem Cells
Common Myeloid Progenitor
Common Lymphoid Progenitor
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Karakteristik CML: Anemia Lekosit >>> (terdapat seluruh tipe sel granulosit, shift to
the left) Splenomegali Basofilia, eosinofilia Trombositosis (sering) Ph kromosom +
Differential diagnosis: LEUKEMOID REACTION
Splenomegali (-) Eosinofilia, basofilia (-) Leukosit alkali phosphatase meningkat Ph kromosom (-) Toxic granule (+)
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GEJALA KLINISClinical Features %
Fatigue
Bleeding
Weight Loss
Abdominal discomfort(left upper quadrant)
Sweats
Bone pain
Splenomegaly
Hepatomegaly
33,5
21,3
20,0
18,6
14,6
7,4
75,8
2,2
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PERJALANAN PENYAKIT
Chronic Myeloid Leukemia
Stable / chronic Advance
Accelerated Blastic
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Lekosit ↑: terdapat semua seri granulosit, dominasi oleh MYELOSIT dan NEUTROFIL SEGMEN, MYELOBLAST < 10%
Basofilia, trombositosis
Sutul: hiperseluler Splenomegali
CML FASE KRONIK
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Timbul pada ± tahun ke-3 dari diagnosis pada Px yg tidak diterapi
Sulit diterapi Fase ini akan berakhir sebagai BLAST
CRISIS
CML FASE AKSELERASI
CML FASE BLAST CRISIS Sel gagal untuk maturasi → sel BLAST ↑, > 20%
Trombositopenia, Hb Resisten terhadap kemoterapi Klinis seperti AML penderita tampak sakit keras, limpa membesar, suhu ↑ 2/3 kasus → AML, 1/3 kasus → ALL
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CHRONIC LYMPHOCYTIC LEUKEMIA
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Perubahan genetik, mutasi/delesi onkogen pada clone sel B
kegagalan apoptosis → limfosit terakumulasi di
perifer, sutul, KGB dan terkadang di limpa Sel sangat rapuh, mudah pecah, merupakan ciri
penting pada hapusan darah → Smudge cell/ basket cell
morfologi normal, fungsi ABNormal umumnya pada usia tua, jarang pada usia <40
tahun Laki-laki : Perempuan = 2:1
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GEJALA KLINIS Sering asimptomatis, sering ditemukan
secara tidak sengaja pada waktu cek DL Pada 50% Px: pembesaran KGB simetris
terutama regio cervical, axilar/inguinal
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Kegagalan sutul: anemia, trombositopenia
> 90% sel B → imunoglobulin abnormal → rentan mengalami infeksi bakteri atau jamur yang berulang
Splenomegali, hepatomegali pada stadium lanjut
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Complete Blood Count (CBC) WBC ↑ Diff. count: Limfositosis, hitung limfosit absolut
>5x109/l sampai 300x109/l atau lebih Anemia: normokromik normositik anemia Trombositopenia ( sering dijumpai )
Hapusan darah tepi70-99% terdiri dari limfosit maturSmudge atau basket cells +
ImunologyHipogamaglobulinemia: Ig A pertama turun, kmdn
IgM dan IgG
LABORATORIUM
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CLL WITH SMUDGE CELLS
Smudge cell
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KOMPLIKASI
Failure of humoral and cellular immunityOpportunistic infection common
eg shingles, pneumocystis, bacteria, fungi
Autoimmune diseasewarm autoimmune hemolytic anemiaautoimmune thrombocytopeniapure red cell aplasia
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STAGING untuk menentukan prognosis dan terapi ada 2 sistem: RAI dan BINET
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PERJALANAN PENYAKIT
Beberapa penderita tidak memerlukan terapi bertahun-tahun
tujuan terapi untuk mengatasi gejala Indikasi terapi:
Organomegali mengganggu Hemolitik Bone marrow supression
pada fase agresif, transformasi menjadi diffuse large B cell lymphoma (DLBCL) atau immunoblastic lymphoma (non Hodgkin lymphoma), disebut sindroma Richter
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Terima Kasih
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REFERENSI Williams manual of hematology, 8th
edition, Mc Graw Hill, 2011 Chronic Myeloproloferative disorders,
Tariq Mughal, Informa UK Ltd, 2008 Clinical malignant hematology, Sekeres
M, Mc Graw Hill, 2007 Leukemia and related disorders,
Whittaker, JA, Blackwell science, 1998