Leukemias

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Leukemias
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Etiology of Leukemias General outlines
Acute leukemias Single cell mutation with
freezing farther cells differentiation and
maturation in early stages of development (e.g.
stem cell) Chronic leukemias The abnormal
mutated (or transformed) cells will retain some
capabilities to maturate (and differentiate)
beyond the early cells (blasts) BUT they are all
abnormal and useless malignant cells.
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• A systematic approach to diagnose different
  hematologic neoplasms
• 1) CBC (Complete Blood Count), CBP (Complete
  Blood Picture)
• a) WBC total, differential count, left shift?,
• b) Peripheral blood film evaluate the cellular
  constituents and search for abnormalities
  (abnormal cells?).
• 2) Special staining (SBB, MPO, NSE, etc).
• 3) Bone marrow aspiration
• assess the cellularity
• ME ratio
• percentage of blast cells
• The maturation and differentiation of various
  cell lineage (Lymphoid, Myeloid).
• 4) Bone marrow biopsy (trephine biopsy)
• ? in solid tumors (as lymphomas with invasion to
  Bone marrow)
• ? in cases that Bone marrow aspiration not
  possible (AML-M7 due to fibrosis, Hairy cell
  Leukemias, etc)
• ? in cases with a compact bone marrow very high
  cellular proliferation and a dry tap

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• Leukemia classification
• ?1976
• French, American and British hematologists (FAB
  group) proposed
• a classification system (FAB classification)
• Morphologic assessment
• Special staining techniques (if required)
• Limited use of Monoclonal antibodies (in selected
  cases)
• ? 2001
• WHO classification of Hematopoietic and Lymphoid
  malignancies.
• i) Adopting the FAB morphologic classification.
• ii) Limited use of special staining techniques.
• iii) Wider use of immunophenotyping (cell
  markers) studies (FC, IHC)
• iv) Cytogentics and Molecular genetics studies
  used heavily to define
• v) The character and prognosis of various
  disease entities.
• ? 2008
• An Updated WHO classification has been edited.

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• Differences between FAB and WHO
• FAB-classification
• Heavily used Morphologic Findings
• Special staining (SBB, MPO, NSE, etc), if
  required
• WHO-classification
• Morphologic findings
• Special staining (decreased role)
• Immunophenotyping (in the form of FC and IHC)
  heavily used.
• Cytogentics and Molecular genetics studies
  frequently used.

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The original FAB-Classification system of Acute
Leukemias, heavily based on morphologic findings
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Types of blast cells in ALL and AML
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Special staining methods in acute leukemias
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FAB-classification of ALL L1-lymphoblasts in
the BM ALL-L1
L2-lymphobalsts in the BM ALL-L2 ALL-L3
L3-lymphoblasts in the BM SBB
(SHOULD BE ve) MPO (SHOULD BE ve)
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FAB-classification of AML M0 Undifferentiated
blast cells (Myeloid origin by immunophenotyping),
Special staining SBB-ve, MPO-ve M1
Myeloblasts ( 20 in BM) SBBve, MPOve M2
Myeloblasts (20 in BM) SBBve, MPOve M3
Abnormal Promyelocytes SBBve, MPOve M4
Myeloblasts (20-80) Monocytes (gt20), NSE ve
M5 (a) Monoblasts 80 NSE ve (b)
Monoblasts lt80, more promonocytes and monocytes
in BM,NSE ve M6 Erythroleukemia, 50 of BM
cells are of erythroid lineage M7 Blast cells
are 20 of BM cells (they are identifiable as
Megakaryoblasts).
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• 2 important Practical points
• BM aspiration results in acute leukemia, although
  may be
• i) dry tap or
• ii) difficult to aspirate (hypercellular marrow
  with excessive marrow blasts)
• BUT is never ever an empty marrow.
• Leukemoid reaction should be distinguished from
  Leukemias of particular CML
• Neutrophil Alkaline Phosphatase Score
• C-reactive protein, ESR, and other inflammatory
  indicators.
• Blood film finding (left shift).
• Bone marrow aspiration, Bone marrow biopsy,
  immunophenotyping
• and cytogentics studies may required
  accordingly.

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The Current WHO classification has widely used
the immunophenotyping to characterize leukemias
and lymphomas Frequently used Immunophenotyping
Genetics studies
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Non-lineage restricted TdT CD45 HLA-DR
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• Immunological subtypes of Acute Leukemia
• ?B-ALL (B-lineage markers are positive), 75 of
  ALL
• pro B-ALL
• common ALL (CD19/CD10/TdT/CD34/-)THE MOST
  COMMON
• B-ALL (the most mature) (CD34-ve/cytoplasmic and
  surface Ig positive)
• ?T-ALL (T-lineage markers are positive), 15 of
  ALL
• ?AML (Myeloid lineage markers (CD13/CD33, CD117,
  cyMPO) are positive
• ?Bi-lineage
• ?Bi-Phenotypic

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Cytogenetics/molecular genetics findings in ALL
(as example) ONLY FOR YOUR REVIEW
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ALL-L1 Small and homogenous blasts. These may
closely resemble lymphocytes but are
distinguished by their finer chromatin structure
and the occasional presence of nucleoli
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ALL-L2 Lymphoblasts of varying size (small and
large)
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Large blast cells with marked cytoplasmic budding
(blebing). The differential diagnosis will be
AML-M7 and ALL. Farther cytochemical and
immunophenotyping studies showed to be case of
B-lineage ALL.
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Mature B-ALL with prominent cytoplasmic vacuoles
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Auer rods in AML (pathogmonomic for myeloid
lineage origin), A case of AML-M3
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Auer rods in malignant promyelocytes
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Auer rods in an M1/M2 AML
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Thank You