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& Multiple myeloma (MM)

Sulistyo M. Agustini
Department of Clinical Pathology
Medicine Faculty of Muhammadiyah Malang University
• McCance Huether, PATHOPHYSIOLOGY “The
Biologic Basic for Disease in Adults and Children,
Fifth edition, Mosby-Elsevier, 2006
• Hoffbrand AV, Pettit JE and Moss PAH, Essential
HAEMATOLOGY, fourth edition, 2003
• Howard MR, Hamilton PJ, HAEMATOLOGY An
Illustrated Colour Text, tjird edition, 2008
• Kumar Hagler Schneider, Robin and Cotran
• Abeloff D et al, CLINICAL ONCOLOGY, 3 rd
edition, 2004
• Group of clonal disorder of multipotent
haematopoiesis stem cell (neoplastic disorder)
• MDS is heterogenous group of clonal disorders of
bone marrow, differentiates ineffectivelly
• Their common feature is bone marrow failure
ineffective haematopoiesis (reduced
haematopoiesis activity)
• Hypercellular marrow & peripheral blood cytopenia
• Predominantly a disease of the elderly
• Prognosis is highly variable dependent on the
• Increasing bone marrow failure
quantitative & qualitative abnormal all
three myeloid cell line
• Ineffective haematopoiesis (reduced
haematopoiesis activity)
• Dysplastic morphological abnormalities
form the basic for diagnosis
• Increased apoptosis within the marrow is
comman feature
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Slide 3 of 50
Myelodysplastic Syndromes
• Clonal disorders involving bone marrow
stem cells that lead to ineffective and
disorderly hematopoiesis
• Manifest as irreversible quantitative and
qualitative defects of hematopoietic cells
cause by abnormal division, maturation
and production of erythrocytes,
granulocytes/monocytes and platelet that
result in blood cytopenias.
The French American British (FAB) & WHO
type Pheripheral blood Bone marrow Approximated
survival (months)

Refractory anaemia Blast < 1% Blast < 5 % 50


RA with ring Blast <1 % Blast <5 % ring 50

sideroblasts (RARS) sideroblast > 15 %
of total erytroblast

RA with excess blasts Blast < 5 % Blast 5 – 20 % 11


RAEB in transformation Blast > 5 % Blast 20-30 % or 5

(RAEB-t) Auer rods present

Chronic As any of the above As any of the above 11

myelomonocytic 10 x 106/l promonocytes
leukemia (CMML) monocytes
Approach to Diagnosis
Laboratory diagnosis of MDS
• CBC + blood smear exam for dysplastic
• BM aspiration (Romanowsky& Iron) and
• BM Cytogenetic
• Flowcytometry (clinically indicated)
• Molecular (clinically indicated)
• Vit B12, Folate , SI-IBC,Feritin (clinically
Clinical Aspects
• Most common in elderly ( 60 – 75 ) years
• Few patients < 50 years
• May Affect any age including children
• Men are slightly more than women
Related to blood cytopenias
Clinical Aspects
• Most frequent
– Fatique, weakness and malaise due to
• Less frequent
– Infection due to the netropenia
– Hemorrhage due to thrombocytopenia.
• Some individual are asymptomatic
– Cytopeniasidentified in routine blood count
• Small percentage (rare)
– Hepato- splenomegaly
Hematologic Finding
• Highly Variable
• Various combination of Cytopenias
– Pancytopenia
– Anemia in combination with neutropenia or
• Ineffective hematopoiesis, dyserythropoiesis,
dysgranulopoiesis and dysmegakaryopoiesis
• Increased myeloblasts
• Normocellular or hypercellular BM
Hematologic Finding
• Most common example
normo or hypercellular BM with
ineffective erythropoiesis , erythroid
anemia with reticulocytopenia
Hematologic Finding
Blood cell Measurements
• Normocytic or macrocytic anemia
low or normal reticulocyte
RDW elevated (anisocytosis)
• Leukocyte normal to markedly reduced
Elevated In minority of cases
• Platelet count reduced or normal
Elevated in special type MDS isolated del (5q)
Hematologic Finding
Bone Marrow Examination
• Hypercellular or Normocellular
Hypocellular (very rare)
• Dysplastic changes
• Increased Myeloblast (< 20%)
• Iron stores often increased (RARS)
Prognostic Factors in MDS
• Clinical
– Therapy related MDS
• Blood
– Severe cytopenias
– Raised LDH & Beta 2 microglobulin
• Marrow
– Increased Blast
– Trilineage Dysplasia
• Chromosome abnormalities
– Loss of chromosome 5 or 7
– Deletion of chromosome 3q,5q (excluding 5q
syndrome),7q,17 p
– Structural abnormality of chromosome 11q 23
Prognostic Factor in MDS
• Chromosome abnormalities
– Complex chromosome abnormalities
– Karyotypic evolution
• Genetic/epigenetic abnormalities
– p53, RAS mutation
– Overexpression of WT1
– P15 hypermethylation
– Telomere shortening
– Gene expression profile
• Immunophenotyping
– CD7 positive Blast
Diagnosis MDS
• At least cytopenia of one line
• Morphologic evidence of dysplasia
• Peripheral blood smear, bone marrow
aspirate and biopsy required
• BM differential count performing 500 cells,
eliminating lymphocyte and plasma cells
for the count
• If erythroid precursors > 50 %  NEC
International Prognostic Scoring
International Prognostic Scoring
• Patients with 20-30 % blasts may be considered
as MDS or AML.
• Cytogenetics:
– Good = normal, -Y alone, del(5q) alone, del(20q)
– Poor = complex ( 3 abnormalities) or chromosome 7
– Intermediate = other abnormalities. [This excludes
karyotypes t(8;21), inv16, and t(15;17), which are
considered to be AML not MDS.] ³
• Cytopenias:
– neutrophil count <1,800/mcL, platelets <
100,000/mcL, Hb< 10g/dL.
• MDS is a heterogeneous group of clonal disorder bone
marrow (stem cell neoplasm) marked by cytopenia
and dysplasia of minimal one lineage.
• Diagnosis of MDS is mainly based on CBC, peripheral
blood smear, bone marrow aspirate and
biopsy (depends on the presence of characteristic
morfological change in the blood and marrow)
• Cytogenetic analysis and molecular biology is
important to determine prognosis, and highly variable
denpent on the subtype
• Supportive care remains but growth factor and other
specific therapeutic agent are increasing used.
Chemotherapy and stem cell transplantation may be
considered in younger patients with high-risk disease.
• Ciri khas dari penyakit multiple myeloma
(MM) adalah adanya protein M (komponen
M, protein myeloma, atau M spike)
• kadar total protein 12,3 g/dl (N=6-8,5 g/dl),
albumin 3,64 g/dl (N=3,5-5,5), dan globulin
8,66 g/dl (2,5-4,5 g/dl).
• elektroforesis protein protein
monoclonal (fraksi gamma globulin)
Sumber: Wintrobe’s Clinical Hematology 12th edition
gambaran khas suatu lesi
myeloma tunggal berupa
gambaran lusen berbatas
tegas pada regio
interocanter. Lesi-lesi lebih
kecil tampak pada