Myelodisplastic syndrome,

Reaksi Leukemoid, Multipel

Mieloma
Haerani Harun
Departemen Ilmu Patologi Klinik
FK UNTAD
Myelodysplastic
Syndrome
 Myelodysplastic Syndromes
 MDS Definition:
 A group of disorders presenting with some
evidence of bone marrow failure and
dysplasia of one or more of the myeloid
lineages, with <20% blasts in the blood or
marrow.
 MDS comprises a group of malignant stem
cell disorders characterized by ineffective
blood cell production and variable risk of
transformation to acute leukemia.
 Prevalence
 4.1 MDS / 2.1 AML per 100,000
 Risk of Development increases w/ Age
 Unusual <50yrs, unless tx induced
 Median age 65 or greater, w/ male
predominance
 MDS Etiology
 Two etiologic categories of MDS:
1.) De Novo:
Associated with:
-benzene exposure (gasoline)
-cigarettesmoking
-viruses -Fanconi’s anemia

2.) Therapy related:

Associated with:
-alkylating agent chemotherapy
-radiation
 MDS subtypes
 Refractory Anemia 21% (RA)
 RARS (refractory anemia w/ ringed sideroblasts
17%)
 RA w/ excess blasts 37% (RAEB)
 RA w/ excess blasts in transformation 12% (RAEB-T)
 CMML (chronic myelomonoctic leukemia) 13%
 5q- syndrome (myelodysplastic syndrome associated
with isolated del (5q) chromosome abnormality)
TYPE BM Blasts% Peripheral Auer Rods Monocytes > Ringed
blood blasts 1000 /uL Sideroblasts
% >15%

RA <5 <1 No No No

RAS <5 <1 No No Yes

RAEB 5-20 <5 No No +-

CMML <20 <5 No Yes +-

RAEB-T 21-30 >5 +- +- +-

 MDS – Clinical Symptoms

 Ecchymoses
 Fatigue
 Pallor
 Ecchymoses/petechiae
 Abnormal bleeding
 Infection
 Physical Findings
 60% Pale
 26% Petechaie and/or Purpura
 Cutaenous Manifestations uncommon…but 2
recognized syndromes can occur in MDS
--> Sweet’s – acute febrile neutrophilic dermatosis
--> Myeloid Sarcoma – “chloroma”
 Laboratory
 Bone Marrow and Blood changes variable,
divided into FAB MDS subtypes.
 Chromosomal Abnormalities are associated
as well.
 Anemia almost always present w/ low retic
response
 Pancytopenia in up to 50% of cases
 <5% have isolated neutropenia or
thrombocytopenia w/o anemia
 Differential Dx
 Megaloblastic Anemia
 Aplastic Anemia
 Myelofibrosis
 Atypical CML
 HIV
 Medications (VPA, Cellcept, Ganciclovir)
 Prognostic Groups
 Two groups based on survival and evolution to acute
leukemia

 1.) “Good” group

– Refractory anemia (RA)
– Refractory anemia with ringed sideroblasts (RARS)
– 5q - syndrome
 2.) “Bad” group
– Refractory anemia with excess blasts (RAEB)
– Refractory cytopenia with multilineage dysplasia (RCMD)
 MDS unclassified can be either
Ringed Sideroblasts
Binukleasi
Pelgeroid (pseudo Pelger-Huet)
Neutrophil
Dyserythropoiesis on Bone Marrow
Aspirate
Hypersegmented Neutrophil
Internuclear bridging
Mikromegakariosit dan
hipolobulasi
Hypercellular Bone Marrow
Blasts and Hypogranulation
Myeloblast with Auer Rod
Hypolobated megakaryocytes
Reaksi Leukemoid
 Leukemoid reaction
 A leukemoid reaction is an increase in the
white blood cell count, which can mimic 
leukemia
 The reaction is actually due to an infection
or another disease and is not a sign of
cancer.
 Blood counts often return to normal when
the underlying condition is treated.
 Penyebab
 Severe infection like Clostridium, Tuberculosis, Pertussis and Infectious
mononucleosis.
 Visceral larva migration leads to eosinophilia.
 Tuberculosis gives rise monocytosis.
 Leukemoid lymphocytosis is seen in Tuberculosis, Whooping cough and
infectious mononucleosis.
 Intoxication.
 malignancies.
 Severe hemorrhage.
 Acute hemolysis.
 Drugs like Sulfa, Dapsone, Glucocorticoids, and use of G-CSF factor.
 Diabetic ketoacidosis.
 Ischemic colitis.
 Hepatic necrosis.
 Diagnosis Banding
 Chronic myeloblastic leukemia
 Chronic neutropilic leukemia
Test                                 Leukemoid Chronic myeloid
       reaction                        leukemia 
WBC count usually <50,000/cmm usually >50,000/cmm
Basophils absent usually increased count
platelets normal Increased
Eosinophil normal Increased
Hemoglobin usually normal usually low
Band form these are prominent all stages (myelocytes)
Toxic granules and Dohle these are present toxic granules ± to 0
bodies             
Spleen usually not present usually enlarged
Philadelphia chromosome absent present in 90% of the
cases
Leucocytes Alk.phosphatas > 100 < 10
e (LAP)
History  short long
 Granulasi toksik
 Sel-sel muda
Leukemoid reaction
Multiple Myeloma
Multiple myeloma is a
cancer that begins in
plasma cells, a type of
white blood cell.

These cells are part of

immune system, which
helps protect the
body from germs and
other harmful
substances.

3
3
Incidence
 Increases with age
 Ages from 45 up to 68 years

 Males > Females (slightly)

 Accounts for about

 1% of all malignancies in whites
 13% of all hematologic cancers in
whites
Myeloma classification
Monoclonal Gammopathy of Undetermined Significance
Serum M-protein < 3 g/dL
Bone marrow plasma cells < 10%
Absence of anemia, renal failure, hypercalcemia, lytic bone lesions
Asymptomatic Multiple Myeloma
Smoldering Multiple Myeloma Indolent Multiple Myeloma
Serum M-protein > 3 g/dL and/or Bone marrow plasmacytosis bone
marrow plasma cells ≥ 10%
No anemia, renal failure, Mild anemia or few
small lytic bone hypercalcemia, lytic lesions
bone lesions
No symptoms
Stable serum/urine M-protein
Presence of serum/urine M-protein
Symptomatic Multiple Myeloma
Bone marrow plasmacytosis (> 10%)
Anemia, renal failure, hypercalcemia, or lytic bone lesions
Sign and symptoms:

3
7
 Clinical Manifestations of Multiple Myeloma

•Pain in the lower back, long •Symptoms of hyperviscosity

bones or ribs ●
Headaches
●
Bruising
•Generalized malaise ●
Ischemic neurologic
symptoms
•Infections
•Other neurologic symptoms
•Fever ●
Peripheral neuropathy
●
Meningitis
•Bleeding

•Symptoms of hypercalcemia
●
Nausea
●
Fatigue
●
Thirst
 Clinical Manifestations
Susceptibility to bacterial
infections
 Recurrent infections are the presenting features in 25%
of patients

 Most common infections are

 Pneumonias (Streptococcus pneumoniae,
Staphylococcus aureus, and Klebsiella pneumoniae)
 Pyelonephritis ( Escherichia coli and other gram-
negative organisms )
 Clinical Manifestations Renal
failure / pathology
 Failure occurs in nearly 25%

 Some renal pathology is noted in > 50%

 Factors contributing to renal dysfunction

 Hypercalcemia ( most common cause of renal failure)
 Glomerular deposits of amyloid
 Hyperuricemia
 Recurrent infections
 Infiltration of the kidney by myeloma cells
 Tubular damage associated with the excretion of light chains
(almost always present )
 Clinical Manifestations Anemia
 Occurs in 80% of myeloma patients

 Types
 Usually normocytic and normochromic
 Can be megaloblastic due to either folate or vitamin B12
deficiency

 Due to
 Replacement of normal marrow by expanding tumor cells
 Inhibition of hematopoiesis by factors made by the tumor
 Mild hemolysis
 Staging:
Durie-Salmon system: widely used since
1975
Stage based on M-protein levels, bone
lesions, Hb values, serum calcium—
many variables
International Staging System
Simplified staging based on serum β2-
microglobulin
International Staging System
Stage
Criteria
I β2-microglobulin < 3.5; albumin ≥ 3.5
II III Neither stage I nor stage III values
β2-microglobulin > 5.5
Test :

 Blood and urine tests for monoclonal protein

 Bone marrow examination
 Imaging
 Genetic and chromosomal tests

4
3
4
6
 Confirmation of 1 major and 1
minor criterion or 3 minor
criteria in symptomatic patients
Major Diagnostic Criteria Minor Diagnostic Criteria
Biopsy-proven Bone marrow sample = 10%
plasmacytoma to 30% plasma cells
Minor monoclonal
Bone marrow sample =
immunoglobulin levels in
30% plasma cells
blood or urine (< 3 g/dL)
Elevated monoclonal Osteopenia/lytic bone
immunoglobulin levels in lesions (confirmed through
blood or urine imaging studies)
Abnormally low antibody
levels (not associated with
malignant cells) in the blood
 Blood studies
 CBC (anemia , pancytopenia ,)
 ESR (elevated)
 Ca, BUN , Cr and uric acid (elevated)
 Serum alkaline phosphatase is usually normal
(absence of osteoblastic activity)
 Hypoalbuminemia
Rouleaux formation
Sel plasma
Bone marrow aspirate demonstrating plasma cells of multiple myeloma.
Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone
 Clinical evaluation
Protein electrophoresis
 In Monoclonal
gammopathies &
Myeloma the single clone of
plasma
cells produce a
homogeneous
monoclonal immunoglobulin (
M
protein) characterized by the
presence of a sharp, well-
defined
band with a single heavy
chain and a
similar band with a kappa or
lambda light chain

 The M protein is identified

as a narrow peak or
"spike" in the g, ß or a 2
regions
THANK YOU FOR YOUR
ATTENTION