Pemeriksaan

3/17/2019
laboratorium pada

Ukrida
dr Iskandar H., Bag PK FK
keganasan darah
Blok 24

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Topik
• Klasifikasi keganasan darah
• Pemeriksaan laboratorium

3/17/2019
• Mieloproliferatif
• Limfoproliferatif

Ukrida
dr Iskandar H., Bag PK FK
• Leukemia akut, kronik
• Penyakit keganasan darah
• Transformasi
• MDS (myelodysplastic syndrome)

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Klasifikasi keganasan darah

• kelainan mieloproliferatif

3/17/2019
• Akut

Ukrida
dr Iskandar H., Bag PK FK
• Kronik
• kelainan limfoproliferatif

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 dr Iskandar H., Bag PK FK
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 dr Iskandar H., Bag PK FK
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Ukrida
Kelainan mieloproliferatif
Sekelompok keadaan yang ditandai dgn proliferasi
abnormal satu atau lebih sel-sel hemopoetik dalam
sumsum tulang dan pada banyak kasus juga di

3/17/2019
hepar, limpa.

Ukrida
dr Iskandar H., Bag PK FK
Kelainan2 ini saling berhubungan erat, ada bentuk2 transisi & bisa
terjadi evolusi dari satu bentuk ke bentuk yang lain, selama
perjalanan penyakitnya.
Sel-sel hemopoetik :
• Eritroid
• Granulosit dan monosit
• Megakariosit
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Mieloproliferatif akut
• Leukemia mielositik akut / leukemia mieloblastik akut /
leukemia granulositik akut (LGA / AML)

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• Leukemia promielositik akut
• Leukemia mielomonositik akut

Ukrida
dr Iskandar H., Bag PK FK
• Leukemia monositik akut
• Eritroleukemia

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Mieloproliferatif kronik
• Polisitemia vera
• Mielofibrosis

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• Trombositemia esensial
• Leukemia granulositik kronik (LGK, CML, CGL)

Ukrida
dr Iskandar H., Bag PK FK
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Limfoproliferatif
Selompok keadaan yang ditandai oleh proliferasi abnormal
sistem limforetikuler (limfosit, plasmosit, histiosit).
Sel neoplastik dominan di darah dan sumsum tulang 

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leukemia
• Leukemia limfositik akut (LLA, ALL)

Ukrida
dr Iskandar H., Bag PK FK
• Leukemia limfositik kronik (LLK, CLL)

Sel neoplastik dominan di kelenjar limfe dan organ tubuh

 limfoma
• Limfoma non Hodgkin
• Hodgkin’s disease
Bila disertai sintesis Ig abnormal : disebut: plasma cell
dyscrasias:
• Mieloma 9
• Waldenstrom makroglobulinemia
Klasifikasi

berdasarkan

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1. Maturitas sel : akut, kronik
2. Tipe sel : mieloid, limfoid

Ukrida
dr Iskandar H., Bag PK FK
3. Maturitas & tipe sel :AML, CML,
ALL, CLL

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Klasifikasi lain (FAB) (1976)
Morfologi & pewarnaan sitokimia
ANLL (acute non lymphocytic leukemia) dibagi menjadi

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:
M0 : undifferentiated AML

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dr Iskandar H., Bag PK FK
M1 : AML tanpa maturasi
M2 : AML dgn maturasi
M3 : APL (acute promyelocytic leukemia)
M4 : AMMoL (acute myelomonocytic leukemia)
M5a : AMoL (acute monoblastic leukemia) poor differentiation
M5b : AMoL good differentiation
M6 : Erythroleukemia
M7 : AMgL (acute megakaryoblastic leukemia) 11
M0 : MPO (-) sulit dibedakan dari ALL. Pastikan dengan myeloid marker.
M1 : dominasi blas, blas tanpa granula (tipe 1), sejumlah kecil granula azurofil, Auer
bodies. Tipe ini paling sering.
M2 : diferensiasi  promielosit / lebih lanjut

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M3 : leuk promielositik : gran azurofil besar, Auer rods bundle (faggot). Sering disertai
DIC
M4 :leuk mielomonositik : pewarnaan esterase utk monosit

Ukrida
dr Iskandar H., Bag PK FK
M5 : M5a, M5b. Pewarnaan esterase utk monosit.
M6 : Eritroleukemia. Eritroblas sering PAS (+)
M7 : leuk megakarioblastik. MPO (-),sulit dibedakan dari ALL. Perlu pemeriksaan
khusus.

L1 : prolif uniform limfoblas kecil. Pd anak2, prog (+)

L2 : limfoblas besar-kecil. Heterogen. Jarang < 5thn. DD/ M1
L3 : prolif uniform sel tipe Burkitt limfoma
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Klasifikasi lain
Cell surface marker (immuno- phenotyping) :
contoh
ALL dibagi menjadi :

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- common ALL : cALL Ag(+) (c = common)
- pre B ALL : CIg (+) (cytoplasmic Ig)

Ukrida
dr Iskandar H., Bag PK FK
- B ALL : SIg (surface Ig) (+)
- T ALL : ER (E rosettes +)
- Null ALL : TdT (+) Terminal deoxy-nucleotidyl Transferase
***

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Table 1. The 2008 World Health Organization classification scheme
for myeloid neoplasms .A
1. Acute myeloid leukemia
2. Myelodysplastic syndromes (MDS)
2.1 Refractory cytopenia with unilineage dysplasia
Refractory anemia; Refractory neutropenia; Refractory thrombocytopenia

2.2 Refractory anemia with ring sideroblasts

2.3 Refractory cytopenia with multilineage dysplasia
2.4 Refractory anemia with excess blasts-1
2.5 Refractory anemia with excess blasts-2
2.6 Myelodysplastic syndrome with isolated del(5q)

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2.7 Myelodysplastic syndrome, unclassifiable
3. Myeloproliferative neoplasms (MPN)
3.1 Chronic myelogenous leukemia
3.2 Polycythemia vera
3.3 Essential thrombocythemia
3.4 Primary myelofibrosis

Ukrida
dr Iskandar H., Bag PK FK
3.5 Chronic neutrophilic leukemia
3.6 Chronic eosinophilic leukemia, not otherwise categorized
3.7 Hypereosinophilic syndrome
3.8 Mast cell disease
3.9 MPNs, unclassifiable
4. Myeloplastic/myeloproliferative neoplasms (MDS/MPN)

4.1 Chronic myelomonocytic leukemia

4.2 Juvenile myelomonocytic leukemia
4.3 Atypical chronic myeloid leukemia
4.4 MDS/MPN, unclassifiable
5. Myeloid neoplasms associated with eosinophilia and
abnormalities of PDGFR-A or -B, or FGFR1
5.1 Myeloid neoplasms associated with PDGFRA rearrangement

5.2 Myeloid neoplasms associated with PDGFRB rearrangement

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5.3 Myeloid neoplasms associated with FGFR1 rearrangement

(8p11 myeloproliferative syndrome)

 FAB (publikasi 2003)

• M0 AML minimally differentiated

• M1 AML without maturation
• M2 AML with maturation
•

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M3 APL hypergranular
• M3v APL variant, microgranular
• M4 Acute myelomonocytic leukemia

Ukrida
dr Iskandar H., Bag PK FK
• M4eo Acute myelomonocytic leukemia with eosinophilia
• M5a Acute monoblastic leukemia, poorly differentiated
• M5b Acute monoblastic leukemia, differentiated
• M6 Acute erythroleukemia
• M7 Acute megakaryoblastic leukemia

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Pemeriksaan lab (rutin)
• Darah lengkap (CBC)
– Hb
– Leuko

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– Diff
• B /E/ S/ S/ L/ M
– Eri

Ukrida
dr Iskandar H., Bag PK FK
• Ht
• Jumlah eritrosit
• MCV MCH MCHC RDW
- Trombosit
- Retikulosit
– (LED)
• Urin lengkap (urinalysis)
– Alb - Keton
– Gluk - Bil
– Darah - Ubg
– pH - Nitrit 16
– BJ - Esterase
Pendekatan diagnostik
• Informasi klinis (anamnese, riwayat sakit, riwayat keluarga,
pemeriksaan fisik)

3/17/2019
• Lab (bahan : darah tepi)
• Morfologi

Ukrida
dr Iskandar H., Bag PK FK
• Sitokimia
• Evaluasi sumsum tulang (bahan : aspirat)
• Sito genetik. Contoh t(15;17)   APL (M3)
• Immunophenotyping
• Molecular genetic

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Contoh hasil pemeriksaan lab
• Tn H 32 thn dimintakan pemeriksaan darah perifir
lengkap oleh seorang Dr, tanpa diagnosis.
• LED 4 Gamb.darah tepi :

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• Hb 9,6 Eri : normositik normokrom, anisositosis,
• Ht 24 eritrosit polikrom (+)
•

Ukrida
dr Iskandar H., Bag PK FK
Eri 2,28 Leuko : juml meningkat, hipersegmentasi,
• MCV 93 anomali Pelger Huet, hipogranulasi neu-
• MCH 36 trofil
• MCHC 39 Hitung jenis : 2/0/4/72/2/6 Blast 10 Pro –
mielosit 2 metamielosit 2
• RDW 17,5 Trombosit : juml & morfologi normal
• Leuko 290 Anemia normositik normokrom, leukosito-
• Trombo 192 sis berat, shift to the left, disgranulopoesis 18
neutrofilia absolut
 • LLA (ALL)
Leukemia akut
LMA (AML)

dr Iskandar H., Bag PK FK

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Ukrida
 • CML / LMK
Leukemia Kronik
LLK / CLL

dr Iskandar H., Bag PK FK

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Contoh Pewarnaan sitokimia
(myeloperoxidase stain)

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dr Iskandar H., Bag PK FK
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Ukrida
 Fagot cell (FAB AML M3)

dr Iskandar H., Bag PK FK

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Ukrida
M3
• Some cases of acute leukemia are composed entirely of
undifferentiated-appearing blasts. These cases are difficult (or
impossible) to diagnose morphologically (under the
microscope) – you really need special tests like
immunophenotyping in order to make a definitive

3/17/2019
diagnosis.Other cases of acute leukemia have obvious
morphologic clues. Acute promyelocytic leukemia (APL) falls

Ukrida
dr Iskandar H., Bag PK FK
into the latter category. It is composed of malignant
promyelocytes, which often have a distinctive appearance. But
the really characteristic finding in APL is the fagot cell, so
named because it contains a ton of Auer rods all piled up on
each other, resembling a bundle of sticks (or fagot). When you
see these, you can make the diagnosis of APL based on
morphology alone, without waiting for molecular or
cytogenetic studies (which will show the characteristic 25
t(15;17) of APL – but which take some time to perform).
M3
• Making an immediate, morphologic diagnosis is critical in
cases of APL, because these patients cannot be given routine
acute myeloid leukemia chemotherapeutic agents. The
malignant promyelocytes of APL contain lots of granules which
have strong procoagulant activity. If you give the patient

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typical acute leukemia treatment, the promyelocytes will
burst, the nasty granules will be released, and the patient will

Ukrida
dr Iskandar H., Bag PK FK
be at high risk for disseminated intravascular coagulation
(DIC), a very dangerous syndrome in which patients bleed and
clot all over the body. However, there is a drug called all-trans
retinoic acid (or ATRA) that works great for patients with APL
because it causes the malignant promyelocytes to mature
(into myelocytes, then metamyelocytes, then neutrophils).
Then the patient can be treated with regular chemotherapy
without risk of DIC.
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Leukemia akut - Pemeriksaan lab
• Hb,Ht, E <<  anemia
• Trombositopenia

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• Hit leukosit : > / < / N
• SHDT : E normo-normo, E berinti, Blas

Ukrida
dr Iskandar H., Bag PK FK
(gambaran monoton). Pd ANLL blas mungkin
berisi Auer rod.
• Berdasarkan hit.leukosit & adanya blas,
leukemia dibagi :
- Leukemia leukemik : leukositosis 30.000> , blas ++
- Leukemia subleukemik : leuko N, blas(+)10.000-an
- Leukemia aleukemik : leukopeni 4000-an , blas(-) 27
Leukemia akut
• Sumsum tulang :
- hiperseluler, blas >/= 30%, gambaran monoton.

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- E-poesis, trombopoesis tertekan.
- pd ALL aspirasi : mungkin dry-tap (krn serabut retikulin

Ukrida
dr Iskandar H., Bag PK FK
bertambah)
ALL

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ALL
• Anemia , biasanya berat
• WBC bervariasi, biasanya terjadi neutropenia

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• Blast basofilik, kecil, sedikit granula, “hand
mirrir cells”

Ukrida
dr Iskandar H., Bag PK FK
• Kejadian DIC pada 10% kasus
• limfadenopathi, splenomegali (10-20% kasus),
bisa disertai gejala CNS
• Mass mediastinal pada beberapa kasus ALL sel
T
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Ukrida
Pemeriksaan sumsum tulang
• Tujuan : menilai hematopoesis
• Tempat :

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• Corpus sterni
• Os ileum (crista iliaca)

Ukrida
dr Iskandar H., Bag PK FK
• Processus spinosus vertebra lumbalis
• Spina ischiadica posterior superior
• Os tibia ujung cranio-medial (anak < 2thn)

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 dr Iskandar H., Bag PK FK
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Punksi sumsum tulang
• Pemeriksaan yang dikerjakan :
• Pewarnaan Wright : morfologi

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• Pewarnaan besi : Prussian blue
• Pewarnaan sitokimia

Ukrida
dr Iskandar H., Bag PK FK
• dll……
• Antikoagulan :
• Tanpa :  spesimen 0,3 mL saja, segera dibuat
sediaan hapus
• Dengan (EDTA 10%, heparin), spesimen 4 – 5 mL
• Sterilitas, anesthesi 34
Evaluasi Sumsum tulang
• Pembesaran 10 x :
• Kepadatan sel (cellularity)

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• Kesan jumlah megakariosit
• Hitung jenis 1000 sel
• Sel lemak

Ukrida
dr Iskandar H., Bag PK FK
• Megakariosit
• Sel tumor
• Perbandingan myeloid – eritroid (ME ratio)

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Spesimen sumsum tulang
Penghitungan sel
Mieloblas Rubriblas
Promielosit Prorubrisit

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Mielosit Rubrisit
Metamielosit Metarubrisit

Ukrida
dr Iskandar H., Bag PK FK
Basofil, Eosinofil (Retikulosit)
Staf
Segmen / Neutrofil
Limfosit / Plasmosit
Monosit
Reticulum cell (histiosit)
Megakariosit
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Secara morfologi
Mieloblas Limfoblas

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Ukuran besar Lebih kecil

Sitoplasma lebih banyak Lebih sedikit

Ukrida
dr Iskandar H., Bag PK FK
Kromatin halus Padat

Nukleoli jelas, > 2 Tidak jelas, 2 / <

Auer rods 10-40% kasus Tidak ada

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Pewarnaan sitokimia
Identifikasi komponen kimia sel
blas limfoblas monoblas megakarioblas

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POX + - +/- -
SBB

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dr Iskandar H., Bag PK FK
+ - +/- -
PAS - + -/+ +
NSE - - + +________
Peroxidase
Sudan black B
Periodic acid Schiff
Non specific esterase
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 dr Iskandar H., Bag PK FK
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Ukrida
AML
• Limfadenopathi +/-
• Anemia : biasanya berat
• WBC : bervariasi, neutropenia
• Auer rod : large hypergranular myeloblasts

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• DIC pada M3
• Hipokalemia pd Leukemia monositik

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dr Iskandar H., Bag PK FK
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 dr Iskandar H., Bag PK FK
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Ukrida
Membedakan blas ALL & AML
pewarnaan sitokimia, tes enzim, lain-lain
ALL AML

Mieloperoksidase - + (Auer.rods)
SBB - +

3/17/2019
NSE - + (in Monocytic type)
PAS + (kasar) + (halus)

Ukrida
dr Iskandar H., Bag PK FK
Acid phosphatase + (Thy-ALL) -
TdT + (raised) - (normal)
Terminal deoxynucleotidyl
transferase

Serum Lysozyme - ++ (in monocytic type)

Electron microscopy - + (early granule
ALL dws 75-80% Bcell formation)
20-25% Tcell
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Penanda imunologik utk dif. Leukemia
I a = stem cell antigen. Thy = thymic antigen. E-ros = rosettes with sheep red cells

c-ALL Thy- B-ALL, CLL, AML

• Penyakit  (non-T non- ALL other mature B
Reagen B ALL) cell tumors

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Anti c-ALL + - - -

Ukrida
dr Iskandar H., Bag PK FK
Anti Ia + - + +/-
Anti Tdt + + - -
E – ros - + - -
Anti Thy - + - -
S Ig - - + - 43
 Immunophenotyping (ringkasan)

Ag
C-ALL

C Ig

S Ig

E Rosett

T dT

FAB
Marker (Ag)
Penyakit

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Common ALL + - - - + L1 L2

Ukrida
dr Iskandar H., Bag PK FK
Pre B ALL + + - - + L1 L2

B – ALL - - + - - L3
T – ALL - - - + + L1 L2

Null ALL - - - - + L1 L2
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Manfaat Immunophenotyping
• Dalam satu subgroup FAB yg sama, pasien yg satu
memberi respon lebih baik/-buruk dibanding yg lain
• Petanda permukaan (surface marker): jumlahnya

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banyak sekali. Diidentifikasi dgn antibodi (CD..)cluster of
differentiation

• Walaupun sel leukemia secara sitologik sama, fenotip

Ukrida
dr Iskandar H., Bag PK FK
maupun karakteristik molekulernya dapat berbeda 
(perbedaan perangai penyakit secara klinis maupun
respons terhadap pengobatan)

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 MRD

dr Iskandar H., Bag PK FK

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Ukrida
 Dasar immunophenotyping

dr Iskandar H., Bag PK FK

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Ukrida
Contoh
• Bcells : hampir semua CD19, CD20, CD22
• Beberapa Bcell limfoma : CD5, CD43
• T cells : CD2(all Tcells),CD3 (all mature Tcells), CD5 (all Tcells & small subset
of developin Bcells), CD7

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• T helper : CD4
• T suppressor/T cytotoxic CD8
• NK cells CD16, CD56,CD57

Ukrida
dr Iskandar H., Bag PK FK
• CD10 (developing Bcells), CD19 CD20 (developing& mature Bcells)
• CD13 (granulocytes,monocytes) CD14 (monocytes) CD15 (granulocytes)
• CD33 (myeloid precursors & monocytes)
• CD41 CD61(megakaryocytes &platelets)
• CD45 (all leukocytes)

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Ukrida
 Leukemia limfositik kronik
• Keganasan sel darah ditandai : akumulasi limfosit
matur dlm darah, sumsum tulang,klj getah bening,
hepar, lien.

3/17/2019
• Berasal dari transformasi tunggal sel B (99%) dan
sisanya sel T

Ukrida
dr Iskandar H., Bag PK FK
• Akumulasi karena gangguan apoptosis 
menyebabkan pemanjangan lifespan limfosit.
• No specific genetic abnormality

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Ukrida
LLK – gambaran hasil lab
• 20% kasus diketahui dari pemeriksaan rutin
• Limfadenopathi, splenomegali

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Pem laboratorium
• Leukositosis, limfositosis absolut. SHDT 70-99%

Ukrida
dr Iskandar H., Bag PK FK
leukosit = limfosit matang. Smudge cells (+)
• Anemia normo-normo pd std lanjt
• Trombositopenia pd banyak kasus
• SSTL lymphocytic replacement. Limfosit 25-95% sel
• Kadar Ig serum < pd std lanjut
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CML
Biasa asimtomatik, splenomegali (std lanjut). Anemia ringan mula2,
Leukositosis berat, Sed.apus : granulosit imatur & matang, eosinofilia,
basofilia
Sumsum tulang
• Hiperseluler, E-poesis <, trombopoesis bervariasi, sering trombositosis
• CML: granulopoesis >

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CLL: limfopoesis >
Kimia darah

Ukrida
dr Iskandar H., Bag PK FK
• As urat, LDH meningkat krn increased inefective turn-over of hemopoetic
cells.
• Vit B12 serum, vit B12 binding capacity meningkat.
Lain-lain
• Kromosom Philadelphia (translokasi sebagian lengan panjang
krom.22 ke lengan panj krom. 9). “TYPICAL” CML
• “ATYPICAL” CML: leukosit <, tromb <, pd pend anak2, respons terapi
<, survival < 55
BCR = Breakpoint Cluster Region
ABL = Abelson

• Normal

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dr Iskandar H., Bag PK FK
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Contoh-contoh Cytogenetic abnormalities in hematopoietic tumors

• CML: t(9;22)
• AML in general: Flt-3 mutation (bad prognosis)
• AML-M2: t(8;21) (relatively good prognosis)
• AML-M3: t(15;17) (relatively good prognosis)

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• AML-M4: inv(16) (relatively good prognosis)
• AML with a monocytic component (like AML-M4 or AML-M5):

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dr Iskandar H., Bag PK FK
translocations involving 11q23 (bad prognosis)
• Burkitt lymphoma: t(8;14)
• Follicular lymphoma: t(14;18)
• Mantle cell lymphoma: t(11;14)
• Polycythemia vera: Jak-2 mutation

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 Diagnosis banding
Leukositosis berat

Reaksi CML
Leukemoid
Etiologi Infeksi ?Keganasan

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Organomegali - +
Anemia - +

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dr Iskandar H., Bag PK FK
Trombositopenia - +
Kelainan neutrofil ++ -/+
Basofilia - +/-
Eosinofilia - +/-
Aktivitas NAP Meningkat Menurun
Sumsum tulang
-Selularitas Hiperseluler Hiperseluler
-Eritropoesis Normal Tertekan
-Trombopoesis Normal Tertekan 58
Reaksi Leukemoid
• Hitung leukosit >50.000/uL
• Sebagai reaksi terhadap hal-hal di luar sumsum
tulang

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• Dominasi neutrofil matang disertai pergeseran
kekiri (stab, metamielosit, mielosit)

Ukrida
dr Iskandar H., Bag PK FK
• Sel imatur -, basofilia -, monositosis -, LAP >,
kromosom Phildph -
• D/ RL dengan exklusi CML & CNL
• DD/ RL dgn CNL harus hati-hati karena morfologi,
LAP> dan krom.Phildph -
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Kausa RL
• Infeksi
• C.difficile colitis
• Disseminated tuberculosis
• Shigellosis berat

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• Keganasan
• Karsinoma (paru, oropharyngeal, gastrointestinal, genitourinary)
• Limfoma Hodgkin

Ukrida
dr Iskandar H., Bag PK FK
• Melanoma
• Sarcoma
• Obat Kortikosteroid, Minocycline, Recombinant Hematopoietic Growth Factors
• Intoksikasi Ethylene Glycol
• Perdarahan masif / hemolisis akut Retroperitoneal hemorrhage
• Aneka penyebab
• Mesenteric inflammatory Pseudotumor
• Alcoholic steatohepatitis 60
(Mieloproliferatif) Mielofibrosis – pemeriksaan lab
• DT :Hb, Ht, hit E : anemia  kggl sstl, eritropoesis inefektif,
hemolisis.
• Awalnya hit L > Tr > lambat laun L < , Tr <

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• SHDT : E normo-normo, (mod) aniso, marked poikilo (tear drop
cells, eliptosit). Leukoeritroblastosis : NRBC+ immature

Ukrida
dr Iskandar H., Bag PK FK
neutrophils.
Trombosit atipik, mikromegakariosit
• SSTL : dry tap, needle biopsy. Awal : hiperseluler, panmielosis,
megakariosit ,serabut retikulin difus
• Lanjut : makin fibrotik, ‘residual islands’ of atypical
megakariocytes, eryhtroid and granulocytic cells.
• Serum : as folat <, B12 >, skor NAP >, as urat,LDH, bil ind, urobilinogen >
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 DT
Mielofibrosis – sediaan hapus

dr Iskandar H., Bag PK FK

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 Mieloma multipel - Plasmosit

dr Iskandar H., Bag PK FK

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 dr Iskandar H., Bag PK FK
3/17/2019
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Ukrida
Mieloma adalah
• Penyakit ekspansi klonal sel B dengan diferensiasi terminal
• Mensekresi Ig homogen, disebut protein M(onoklonal)/paraprotein,
juga dikenal sebagai protein gamopati monoklonal yang terdapat pada
kelompok penyakit Neoplasma Plasmosit

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dr Iskandar H., Bag PK FK
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Mieloma multipel : pemeriksaan laboratorium

• Hb, Ht, hit E < (anemia). Hit L bervariasi </N/>. Hit

trombosit N/<

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• LED >> SHDT: E normo-normo, rouleaux, NRBC +/-,
neutropenia, limfositosis relatif, plasmosit (15% kasus).
Kadang2 pansitopenia, leukoeritroblastosis.

Ukrida
dr Iskandar H., Bag PK FK
• SSTL: hiperseluller, megakariosit N, plasmosit >10%
biasanya >30% dgn bentuk abnormal, disbt sel
Mieloma (besar, inti 1/2/3, nukleoli jelas, sitopl – asma
banyak, kurang basofilik, benda inklusi : eosinophylic
intracytoplasmic material (aggr Ig)= Russell bodies.
Red staining cytoplasm (Flame cell). Vacuolized
cytoplasm (Grape cell) 68
 Myeloma cell “Grape cell”

dr Iskandar H., Bag PK FK

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69

Ukrida
 dr Iskandar H., Bag PK FK
3/17/2019
70

Ukrida
 “Flame cell”

dr Iskandar H., Bag PK FK

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71

Ukrida
 Myeloma cell “Russel bodies”

dr Iskandar H., Bag PK FK

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Ukrida
Mieloma – kimia darah
Total protein & globulin >>. Albumin <. As urat >.
Kreatinin > (50% kasus). Ca > (30% kasus)
(destruksi tulang – mobilisasi Ca)
Protein elektroforesis : M spike

3/17/2019
Urin : protein Bence Jones (50% kasus)
Imuno elektrf : protein monoklonal nya IgG (2/3

Ukrida
dr Iskandar H., Bag PK FK
kasus), IgA 1/3, jarang IgM, IgD.
Ig abn >>, Ig normal <<

* hiperkalsemia * hiperviskositas
* renal impairment * amiloidosis
* Anemia * infeksi
* Bone disease 73
 dr Iskandar H., Bag PK FK
3/17/2019
74

Ukrida
Manifestasi klinik mieloma
• Proliferasi & sekresi sel mieloma
• Destruksi tulang
• Nyeri tulang
• Hiperkalsemia

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• Protein M serum & urin
• Gagal ginjal

Ukrida
dr Iskandar H., Bag PK FK
• Perdarahan
• Neuropati
• Imun paresis
• Infeksi
• Infiltrasi sumsum tulang
• Kegagalan fungsi sumsum tulang
• Anemia 75
Mieloma – elektroforesis &
imunoelektroforesis

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Ukrida
dr Iskandar H., Bag PK FK
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 dr Iskandar H., Bag PK FK
3/17/2019
77

Ukrida
Elektroforesis serum – gama globulin poli- & mono-
klonal

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Ukrida
dr Iskandar H., Bag PK FK
78
Kriteria D/ mieloma (Durie & Salmon)
• Kriteria mayor
1. Plasmosit sumsum tulang > 30%
2. Plasmositoma pada biopsi jaringan
3. Komponen M serum : IgG > 3,5 g/dL, IgA > 2 g/dL

3/17/2019
4. Protein Bence Jones urin : > 1g/24 jam
• Kriteria minor

Ukrida
dr Iskandar H., Bag PK FK
a. Plasmosit sumsum tulang 10-30%
b. Terdapat komponen M < kriteria mayor
c. Lesi litik tulang
d. Penurunan kadar Ig normal (M<50mg/dL, G< 600 A<100)
D/ Mieloma bila 2 kriteria may
1 mayor + 1minor
3 minor (abc / abd) 79
International staging system (ISS) myeloma
• I ) B2 mikroglobulin serum < 3,5 mg/L
Albumin serum > 3,5 g/dL
II) Bukan stadium I / III
III) B2 mikroglobulin serum > 5,5 mg/L

3/17/2019
• Untuk std II ada 2 kemungkinan :

Ukrida
dr Iskandar H., Bag PK FK
B2 mikroglob serum < 3,5mg/L & albumin serum < 3,5 g/dL
atau
B2 mikroglob serum 3,5-5,5 mg/dL, tanpa melihat kadar
albumin serum

80
 Waldenstrom
macroglobulinemia

dr Iskandar H., Bag PK FK

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81

Ukrida
 dr Iskandar H., Bag PK FK
3/17/2019
82

Ukrida
Diagnosis banding
Mieloma Waldenst
Lesi tulang + -
Infeksi berulang + -
Perdarahan + ++
Organomegali + ++

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Hiperviskositas + ++
Gagal ginjal + -

Ukrida
dr Iskandar H., Bag PK FK
Pem laboratorium
Anemia ++ +
Leukopenia +/- +/-
Trombositopenia +/- +/-
Hiperkalsemia + --
Hipervisk serum + ++

MGUS
83
MGUS
Adalah singkatan dari monoclonal gamopathy of undetermined
significance.
Monoclonal gamopathy adalah gambaran yang diperoleh dari
elektroforesis protein serum, yaitu suatu keadaan

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hipergamaglobulinemia, dengan hasil gambaran kurva yang runcing.
Gambaran ini disebut monoclonal gamopathy, karena
hipergamaglobulinemia nya diakibatkan proliferasi plasmosit secara

Ukrida
dr Iskandar H., Bag PK FK
monoklonal. Suatu keadaan yang terjadi pada multiple myeloma (MM).
Namun, pada MGUS, meski terdapat gambaran monoklonal gamopathi
pada sampel serum pasien, ternyata pada pasien tidak terdapat tanda
/ gejala mieloma sedikitpun.

Dikatakan bahwa 90% pasien MM diawali MGUS.

Dari MGUS menjadi MM, mungkin sebentar (2,2 tahun), atau lama
(15,3 tahun).
Dapat juga MGUS dalam keadaan stabil, tanpa menjadi MM.
Keadaan MGUS ini lazim dijumpai pada usia lanjut. 84
Apakah akan menjadi MM, ditentukan dengan observasi.
• Polisitemia vera, trombositemia esensial dan mielofibrosis =
kelompok kelainan mieloproliferatif kronik non-leukemik
Polisitemia vera
• PV=kelainan mieloproliferatif kronik

3/17/2019
• Autonomous proliferation of the pluripotent stem cells 
pancytosis
• Pem laboratorium :

Ukrida
dr Iskandar H., Bag PK FK
- Hb > (> 18 g/dL) # Low serum EPO
- hit E > (6-10 x 106 /uL) # JAK2 mutation in 95%
- Ht > 52% / > 48 %  55%-60%
- E normo-normo ~~ mikro-hipo. Rt N/>. Tr > ggg fungsi.
LED 2-3 mm. L 12-20x103. NAP>100

85
Klasifikasi polisitemia
Polisitemia Absolut
 Primer
- Polisitemia vera
- Polisitemia familial (congenital)
 Sekunder

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- Kompensasi peningkatan EPO (fisiologik)
- di tempat tinggi
- peny kardiovaskuler
- peny paru/hipoventilasi alveolar /COPD

Ukrida
dr Iskandar H., Bag PK FK
- perokok berat
- afinitas oksigen kuat terhadap Hb
- Peningkatan EPO ‘inappropriate’ (non fisiol.)
- peny ginjal (hidronefrosis, gangguan pb darah, kista, karsinoma)
- ‘massive uterine fibromyomata’
- ca hepatoseluler
- ‘cerebellar hemangioblastoma’
 Polisitemia Relatif
- ‘stress’/’spurious’
- dehidrasi
- ‘plasma loss’ : burns, enteropathy
86
Perbedaan PV PS PR

PV PS PR

Lien > N N

RCV red cell volume 32 > N

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>36

L > N N

Ukrida
dr Iskandar H., Bag PK FK
Tr > N N

S Cob > N N

Sat Ox art N < N

Sstul Pan hiperpl E hiperpl N

Cad besi < N N

Sitogenetik Ab N N N
87
Trombositemia esensial
• Proliferasi megakariosit & over-produksi trombosit
• Hit trombosit mencapai > 1000.000/uL
• Terkait polisitemia vera

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• ‘patchy myelosclerosis’
• Gbr klinik utama : Recurrent hemorrhage, thrombosis
• Splenomegali , splenic atrophy (platelet blocking the splenic microcirc

Ukrida
dr Iskandar H., Bag PK FK
• Anemia (defis Fe krn perdrh g.i kronik) atau trombositemia esensial
disertai polisitemia
• SHDT: giant platelet, fragmen megakariosit.
• Fungsi trombosit terganggu.
• 32P / alkylating agents utk terapi

• Perdrh terkontrol TRCV >>  level Polisitemik

Total red cell volume

88
Kausa trombositosis
• Reaktif
• perdarahan, trauma, pasca bedah
• Defisiensi besi kronik
•

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Keganasan
• Infeksi kronik

Ukrida
dr Iskandar H., Bag PK FK
• Peny jar ikat / mis. Artritis reumatoid
• Post splenectomy (+anemia)
• Endogen
• Trombositemia esensial
• Polisitemia vera, mielofibrosis, LGK

89
Skema kelainan mieloproliferatif
(transformasi)
• LGK
70%
• LGA

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• Eritroleuk

Ukrida
dr Iskandar H., Bag PK FK
15%
• PV 10%

• Ess thromb 30%

• Mielofibrosis 90
 MDS : sinonim & ringkasan
There are many synonyms for this disease. They are: Refractory anaemia,
Refractory anaemia with ring sideroblasts, Refractory anaemia with
excess blasts, Refractory anaemia with excess blasts in transformation,
and Chronic myelomonocytic leukaemia, which is a distinct sub-type.
The myelodysplastic syndromes (MDS) is a group of diseases in which the
production of blood cells by the bone marrow is disrupted. This disease

3/17/2019
may affect all types of blood cells. It may happen that some of the
patients with MDS develop acute leukaemia but most of them do not. If
it does develop, it is acute myeloid leukaemia, which is more difficult to
treat than primary acute myeloid leukaemia.

Ukrida
dr Iskandar H., Bag PK FK
The bone marrow in myelodysplastic syndrome is typically more active
than normal and yet the numbers of blood cells in the circulation are
reduced. This is because most of the cells being produced in the bone
marrow are defective and are destroyed before they leave the bone
marrow to enter the blood stream.
The hallmark of the myelodysplastic syndromes is the combination of a
hyperactive marrow with low blood cell counts. A reduction in numbers
of all types of blood cell is called pancytopaenia.
(disrupted: the orderly progression is disturbed)
91
Klasifikasi MDS

• FAB 1982

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1. Refractory anemia (RA)
2. Refractory anemia with ringed sideroblasts (RARS)

Ukrida
dr Iskandar H., Bag PK FK
3. Refractory anemias with excess blasts (RAEB)
4. Chronic myelomonocytic leukemia (CMML)
5. Refractory anemia with excess blast in
transformation (RAEB-t)

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Klasifikasi MDS

• FAB 1998
• Risiko rendah

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1. RA 10%AML Survival 4 thn
2. RARS 5%AML Survival 4 thn

Ukrida
dr Iskandar H., Bag PK FK
• Risiko tinggi
1. RAEB 45%AML Survival 1,5 thn
2. CMML 15% AML Survival 2 thn
3. RAEB-t 60% AML Survival 0,5 thn

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 Klasifikasi MDS WHO (2008)
• Refractory cytopenia with unilineage dysplasia. In this type, one blood cell type is
low in number. This type of blood cell appears abnormal under the microscope.
• Refractory anemia with ringed sideroblasts. This type involves a low number of
red blood cells. The existing red blood cells contain excess amounts of iron (ringed
sideroblasts).
• Refractory cytopenia with multilineage dysplasia. In this myelodysplastic

3/17/2019
syndrome, two of the three types of blood cells are abnormal, and less than 1
percent of the cells in the bloodstream are immature cells (blasts).
• Refractory anemia with excess blasts — types 1 and 2. In both these syndromes,
any of the three types of blood cells — red blood cells, white blood cells or

Ukrida
dr Iskandar H., Bag PK FK
platelets — may be low in number and appear abnormal under a microscope. Very
immature blood cells (blasts) are found in the blood.
• Myelodysplastic syndrome, unclassified. In this uncommon syndrome, there are
reduced numbers of one of the three types of mature blood cells, and either the
white blood cells or platelets look abnormal under a microscope.
• Myelodysplastic syndrome associated with isolated del(5q) chromosome
abnormality. People with this syndrome have low numbers of red blood cells, and
the cells have a specific defect in their DNA.
• Childhood MDS
94