M a l i g n a n t   H e m a t o p a t h o l o g y

Types of Hematopoietic Malignancies
Leukemias
•  Acute leukemias
  •  Acute myeloid leukemia
  •  Acute lymphoblastic leukemia
•  Chronic leukemias
  •  Chronic myeloproliferative disorders
  •  Chronic lymphoproliferative disorders
•  Myelodysplastic syndromes

Lymphomas
•  Non-Hodgkin's lymphoma
•  Hodgkin's disease

Plasma cell disorders
•  Myeloma

Myeloid vs. Lymphoid
Myeloid malignancies
•  Acute myeloid leukemia
•  Chronic myeloproliferative disorders
•  Myelodysplastic syndromes

Lymphoid malignancies
•  B-cell malignancies
  •  Acute lymphoblastic leukemia, B-cell type
  •  Non-Hodgkin’s lymphoma, B-cell types
•  Myeloma
•  T-cell malignancies
  •  Acute lymphoblastic leukemia, T-cell type
  •  Non-Hodgkin’s lymphoma, T-cell types
•  Hodgkin’s disease

Acute vs. Chronic Leukemia

































How to Think About a Patient With Leukemia
Age
•  Kids - almost always acute; almost always lymphoid.
•  Adults - more often chronic; if acute, more likely to be myeloid.

Acute vs. chronic
•  Clinical setting (abrupt or insidious onset?).
•  Morphology (lots of blasts or lots of maturing cells?).

Myeloid vs. lymphoid
•  Clinical setting may be helpful.
•  Morphologic clues (eg, Auer rods).
•  Often need to do special stains or markers (see below).

How to Diagnose a Leukemia
Morphology (Wright-Giemsa stain)
•  Blood smear
•  Bone marrow biopsy

Cytochemistry (special stains)
•  Most important stains:
  •  Myeloperoxidase (MPO) - stains neutrophilic cells (and sometimes
      monocytic cells).
    Sudan black B (SBB) - same pattern as MPO.
    Non-specific esterase (NSE) - stains monocytic cells.
•  Usually negative in lymphoid leukemias.
•  Frequently positive in myeloid leukemias.
•  See reference section for a more detailed list of cytochemical stains.

Immunophenotyping (looking for antigens or “markers” on the cell surface)
•  Some useful markers:
    CD5 - Expressed on all T cells
    CD10 - Expressed on developing B cells
    CD19 - Expressed on mature B cells
    CD20 - Expressed on mature B cells
    CD33 - Expressed on myeloid precursors and monocytes
•  Immunophenotyping is most helpful in lymphoid leukemias.
•  See reference section for a more detailed list of cell markers.

Cytogenetics (examination of chromosomes under a microscope)
•  Gives a rough overall look at ALL the patient's chromosomes - but can only
   detect abnormalities that cause big chunks of the chromosomes to move
   around or disappear.
•  Sometimes confirms diagnosis; often more useful for prognosis.
•  See reference section for a list of some cytogenetic abnormalities.

Molecular studies (examination of DNA using PCR, Southern blotting, etc.)
•  Very sensitive way of looking for a specific chromosomal abnormality (but
   you have to know the exact DNA sequence of the abnormality you are
   looking for!).
•  Can often detect abnormalities that don't show up on cytogenetics; but can
   only look for specific abnormalities (no information about the rest of the
   patient's chromosomes).

Electron microscopy
•  Not routinely used for diagnosis - but on rare occasions can be very helpful.


Malignant Hematopathology
in a nutshell

•  Leukemia vs. lymphoma
•  Myeloid vs. lymphoid
•  Acute vs. chronic
Introduction
Anemia
Benign Leukocytoses
Malignant Hematopathology
Acute Leukemia
Chronic Myeloid Leukemia
Chronic Lymphocytic Leukemia
Lymphoma
Myeloma
Lymphoid
Myeloid
Acute
Chronic
Chronic lymphocytic leukemia
Hairy cell leukemia
Prolymphocytic leukemia
Large granulated lymphocyte leukemia
ALL
Chronic myeloid leukemia
Chronic myelofibrosis
Polycythemia vera
Essential thrombocythemia
AML
Age
Symptoms
AML
ALL
CML
CLL
Median survival
Morphology
Adults
Children (rarely, adults)
Older adults
Older adults
Sudden onset; symptoms of bone marrow failure
Sudden onset; symptoms of bone marrow failure
Slow onset; variable symptoms
Slow onset; variable symptoms
1 year
Many years
(in children)
2 year
Several year
Lots of
blasts
Lots of
blasts
Mature cells;
heterogeneous
Mature cells;
heterogeneous