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
AML larger present present
ALL smaller none absent or present

Clinical factors

Clinical are important in the classification of leukemia.

Algorithms

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

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.

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.