Leukemia

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The article addresses leukemia, which is uncommonly seen by anatomical pathologists. It is a subset of hematopathology.

Lymphoma is discussed in the lymphoma article, and overlaps somewhat with leukemia as the clear distinction between the two is historical (see below).

Historical classification:[1]

  • Leukemia = involves bone marrow +/- peripheral blood.
    • Classic presentation: infection, bleeding, anemia.
  • Lymphoma = discrete mass(es), usu. lymph node.
    • Classic presentation: non-tender lymph nodes

Definition

All of the following:[2]

  1. Morphologic abnormalities.
  2. >20% blasts or recurrent cytogenetic abnormality.

Some recurrent cytogenetic abnormalities:

  • t(8;21).
  • inv(16).
  • t(15;17).

Histomorphologic overview

Disease/Feature Blast size Auer rods Granulation of cytoplasm
Acute myeloid leukemia (AML) larger present present
Acute lymphoid leukemia (ALL) smaller † none absent or present

† should be easy to remember as smALL people, i.e. kids, get this type of acute leukemia.


Algorithms

There is a nice set of algorithms from D. Arber - that were presented at the 2009 USCAP.

Clinical factors in classification

Clinical are important in the classification of leukemia.

Leukemia classification

Acute myeloid leukemia (AML):

  1. AML.
  2. AML with recurrent cytogenetic abnormalities.
  3. AML from MDS.
  4. AML in the setting of Down syndrome.

Acute lymphoid leukemia (ALL):

  1. B cell.
  2. B cell with recurrent cytogenetic abnormalities.
  3. T cell.

Specific diagnoses

Acute myeloid leukemia

  • Abbreviated AML.

General

  • Adults.

Exclusions for this diagnosis:

Microscopic

Features:

  • Auer rods present
  • Cytoplasmic granularity.
  • Large cells.

Image:

Molecular

  • Must exclude all the recurrent cytogenetic abnormalities - see below.

AML with recurrent cytogenetic abnormalities

Acute myeloid leukemia with t(8;21)

  • t(8;21)(q22;q22).[3]

IHC:

  • CD34+, CD13+, MPO+ (cytoplasm), CD33+ (weak).
  • CD56+, CD117+.
    • Usu. assoc. with a bad prognosis.

Flow cytometry:

  • CD19+, PAX5+, CD79a +/-.

Acute myeloid leukemia with inv(16)

  • inv(16)(p13.1q22).[4]

Microscopic:

  • Blast count usu. ~20% (low).
  • Eosinophilic granules.
    • Used to be classified as "M4" with eosinophilia.

IHC:

  • CD2+ -- common.

Acute myeloid leukemia with t(15;17)

  • t(15;17)(q22;q12).

Comes in two flavours.

Microscopic (Hypergranular or typical APL):

  • Bean-shaped nucleus or bilobed nucleus.
  • Buddles of Auer rods - known as "Faggot cells".

Microscopic (Microgranular or hypogranular APL):

  • Bilobed nuclei with nuclear overlap. (???)
  • Absence of granules on light microscopy.

IHC:

  • CD2+, CD34+/-, CD56+/-.

Flow cytometry:

  • CD34-, HLA-DR-.
  • CD33+, CD13+/-, CD117+ (weak), CD56+/-.

Clinical:

  • Assoc. with DIC.
  • Treatment: ATRA.

Variants:

  • t(11;17) -- ATRA doesn't work.
  • t(17;17) -- ATRA doesn't work.
  • t(5;17). (???)

Acute myeloid leukemia with t(9;11)

  • t(9;11).

Microscopic:

  • Monoblastic morphology. (???)
  • Myelomonocytic morphology. (???)

Clinical:

  • +/-DIC.
  • Usu. children.

IHC:

  • CD33+, CD65+, CD4+, HLA-DR+.
  • CD34+. (???)
  • CD13+. (???)

See also

References

  1. Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 314. ISBN 978-1416054542.
  2. D. Good. 21 March 2011.
  3. Berger, R. (1994). "Translocation t(8;21)(q22;q22): cytogenetics and molecular biology.". Nouv Rev Fr Hematol 36 Suppl 1: S67-9. PMID 8177719.
  4. Lu, CM.; Murata-Collins, JL.; Wang, E.; Siddiqi, I.; Lawrence, HJ. (Dec 2006). "Concurrent acute myeloid leukemia with inv(16)(p13.1q22) and chronic lymphocytic leukemia: molecular evidence of two separate diseases.". Am J Hematol 81 (12): 963-8. doi:10.1002/ajh.20716. PMID 16917916.