Malignant Disorders of

Leukocytes

Supachai A. Basit, RMT, PhD

Leukemia
 neoplastic disease characterized by
purposeless, malignant proliferation of
hemopoietic cellsin the BM and other
organs
 these cells can appear in PBS
 high WBC count and immature forms
Predisposing Factors
Factors related to the occurrence of
Leukemia and Lymphoma
Genetic and Immunologic
Factors
Oncogenes
Occupation Hazards
Early signs
• night sweats
• short breath
• loss of appetite and weight
• loss of strength
Late signs
 hemorrhage and ulceration of mouth
 blood spots under the skin
 enlarged spleen
 swelling of lymph glands
 severe infections
 anemia
 increased metabolic rate
 headache, disorientation
 enlarged organs
 hyperuricemia
 lymphadenopathy and bone pain
Classification
 Conventional
 FAB
 WHO
Conventional Classification of
Leukemia
According to
 duration of the disease

 number of wbc

 types of cells involved

 age
Duration of disease
 acute leukemia
 sub acute leukemia
 chronic leukemia
Acute Leukemia
 many blast cells
 life expentacy <6 mos
 rapidly developing anemia,
thrombocytopenia
Sub acute leukemia
 slightly differentiated or older cells
 6 mos-1 yr
Chronic leukemia
 high number of mature or older cells
 1 year up to several years
 gradual onset
 tender bones due to leukemic infiltration
According to number of wbc
 leukemic leukemia – high percent of
blasts, >15,000/mm3
 subleukemic leukemia – slightly
differentiated cells < 15,000/mm3
 aleukemic leukemia – high % of mature
and normal cells < 15,000/mm3
 According to the cell types
 blast cell leukemia  basophilic leukemia
 lymphocytic leukemia  monocytic leukemia
 promyelocytic leukemia  plasmacytic
 CML leukemia
 neutrophilic leukemia  mast cell leukemia
 eosinophilic leukemia  erythremic myelosis
 leukemia of uncertain  erythroleukemia
type  CNL
Blast cell leukemia
 predominance of
blast that cannot be
otherwise identified
at the time
ALL CLL
 predominance of  predominance of
lymphoblast mature lymphocytes
Promyelocytic leukemia
 preponderance of atypical
progranulocyte containing large irregular
azurophilic granulation
CML
 predominance of neutrophilic,
eosinophilic and basophilic types that are
variants and need not be classified
separately
 Philadelphia chromosomes are present
in 70-90% of patient with CML
Neutrophilic leukemia
 preponderance of neutrophilic
myelocytes
Eosinophilic leukemia
 preponderance of eosinophilic
myelocytes
Basophilic leukemia
 preponderance of basophilic myelocytes
Monocytic leukemia
 Naegeli type (myelomonocytic leukemia)
-resembles granulocytic leukemia
-myelomonocytes (nuclear features of
monocytes and cytoplasmic features of
myeloid cells
 Schilling’s (histiocytic leukemia)
-true monocytic leukemia
-true features of blood monocytes
Plasma cell leukemia
 terminal stage of multiple myeloma
 myeloma: neoplasms of proliferating
plasma cells
1. solitary (BM only)
2. multiple (BM and other organs)
Plasma cell leukemia
Mast cell leukemia
• rarest; tissue basophil leukemia
• arises from basophils by a process of
differentiation and replication
Erythremic myelosis
 Di Guglielmo’s disease
 pure erythroblastic proliferation
 may progress to a mixed erythroblastic-
myeloblastic and terminate as an acute
myeloblastic leukemia
Erythroleukemia
 Di Guglielmo’s syndrome
 erythroblastic and myeloblasitc
proliferation
CNL
 preponderance of adult segmented
neutrophils and band neutrophils
Leukemias of uncertain type
 reticulum cell leukemia
 leukemic reticuloendotheliosis
 histiocytic medullary reticulosis (Robb-
Smith)
FAB Classifications of Leukemia
 AML
M0-M7
 ALL
L1-L3
 CML
 CLL
AML FAB classification
MPO SBB NASDA PAS
M0 - - - -
M1 >3% + - -
M2 + + + -
M3 + + + -
M4 + + + -
M5 + + + -
M6 - - - +
M7 - - + +
Cytochemistry of FAB-AML
M0
• minimally myeloid leukemia
• myeloblast lacking myeloid differentiation
M1
 Acute myeloblastic leukemia without
maturation
 undifferentiated cells <10%
promyelocyte/monocytes
 constitutes about 20% cases of AML
M1
M2
 acute myeloblastic leukemia with partial
differentiation
 >10% promyelocytes and myelocytes
 20% monocytic cells
M2
M3
 acute promyelocytic leukemia
 hypergranular promyelocytes 20%
 auer rods
 translocation of chro. #15 and 17
 DIC may occur
 M3v (microgranular)
 M3eo
 Variants
Classical Microgranular Hyperbasophilic
M3
M4
 acute myelomonocytic leukemia
 >20% promonocytes/monocytes
 >20% granulocyte component
 account 25% cases of AML
M4
M5
 acute monocytic leukemia
 >80% monocytic cells
 promonocytes which has less basophilic
cytoplasm with a grayish ground glass
appearance
 M5a and M5b
M5a M5b
M5
M6
 acute erythroleukemia
 Di Guglielmo’s syndrome
 megaloblastoid, erythroid and myeloid
blast
 rare only 5% of AML cases
M6
M7
 acute megakaryocytic leukemia
 systematic and rapidly progressive
proliferation of a typical and immature
megakaryocytes
 pancytopenia
 + platelet perooxidase
M7
In summary
Favorable Factors
WHO-AML
FAB - ALL
L1 L2 L3
PAS + + -
Oil red O - - +
MPO - - -
Sudan Black - - -
Blast cells Many Few Burkitt type
Adult 31% 60% 9%
Children 85% 15% 1%
 Feature of L1
Cell size Small cells
Chromatin Homogenous
Nuclear shape Regular, occ clefting
Nucleoli Not visible
Amount of cytoplasm Scanty
Basophilia of cytoplasm Slight or moderate
Cytoplasmic vacuolation variable
L1
Features of L2
Cell size Large, heterogenous
Chromatin Variable, heerogenous
Nuclear shape Irregular, clefting common
Nucleoli 1 or more, large
Amount of cytoplasm Variable, often abundant
Basophilia of cytoplasm Variable, deep in some
Cytoplasmic vacuolation Variable
L2
 Features of L3
Cell size Large, homogenous
Chromatin Homogenous, finely stippled
Nuclear shape Regular, oval to round
Nucleoli 1 or more, prominent
Amount of cytoplasm Moderately abundant
Basophilia of cytoplasm Very deep
Cytoplasmic vacuolation Often prominent
L3
In summary
Immunologic Markers in ALL
CML
 young/middle age; above 50
y.o.
 insidious onset
 anemia, weight loss,
malaise
 WBC: 50-300 x 109/L
 few myeloblast
 reduced NAP activity
 Ph1 chro – translocation of
chro 22 & 9
CML
 Leukemoid Reactions
 excessive leukocytic response
 50 x 109/L
 shift to the left
 neutrophilic (hemolysis, Hodgkin’s, hemorrhage,
myelofibrosis)
 eosinophilic (parasitic infections)
 erythroblastosis
 lymphocytic (pertussis, tuberculosis)
 Difference between CML and LR
CML LR
WBC – PBS Blasts/promyelo. Myelocytes, few young
cells
Toxic granulation Absent Present
Eo/Baso Increased Decreased
RBC nRBC, HJ Less likely
NAP Low to zero High
Ph1 Usually present Absent
Splenomegaly Usually Mild if present
prominent
Other Chronic Myeloproliferative
Disorders
Other Chronic Myeloproliferative
Disorders
Other Chronic Myeloproliferative
Disorders
CLL
 rare under age of 40
 occurs over the age of 60
 common in men
 WBC 30-200 x 109/L
 80-90% small lymphocytes
 persistent lymphocytosis 15.0 x 109/L
 neoplastic cells 95% B cell; 5% T cells
Lymphoma
 neoplastic expansion of lymphoid cells
presenting a discrete tumor mass
 generally associated with lymphoid
organs
 neoplastic lymphoid cells are mature
 Hodgkin’s and non-Hodgkin’s
Hodgkin’s
 spread by contiguity
 extranodal: rare
 systemic symptoms
 central and axial lymph nodes
 single disease
Non Hodgkin’s
 random spread via blood
 extranodal
 less systemic symptoms
 peripheral/mesenteric lymph node
 multiple diseases