Leukemia

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A bone marrow of an individual with precursor B-cell lymphoblastic leukemia. Wright stain. (WC)

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.

Chronic myeloid leukemia (CML).

Prognosis

Highly dependent on health care system and treatment available[3]

  • 5-year overall survival in children ranges:
  1. lymphoid leukaemia: 52.4% (Colombia) to 91.6% (Germany)
  2. acute myleoid leukemia: 33.3% (Bulgaria) to 78.2% (Germany)

Specific diagnoses

Acute myeloid leukemia

  • Abbreviated AML.

General

  • Adults.

Exclusions for this diagnosis:

Microscopic

Features:

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

Note:

  • May be classified by morphology, using the (old) French-American-British (FAB) classification (M0-M7).

Image

  • Auer rods in an AML. (WC)

www:

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).[4]

IHC:

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

Flow cytometry:

  • CD19+, PAX5+, CD79a +/-.

Images:

Acute myeloid leukemia with inv(16)

  • inv(16)(p13.1q22).[5]

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)

  • AKA acute promyelocytic leukemia
    • Abbreviated APL.
  • t(15;17)(q22;q12).
    • Fusion transcripts: PML[6]-RARA.[7]

General

Clinical:

  • Associated with DIC.
  • Treatment: all-trans retinoic acid (ATRA).

Variants:

  • t(11;17) -- ATRA doesn't work.[8]
  • t(17;17) -- ATRA doesn't work.
  • t(5;17). (???)

Microscopic

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.
Images

  • Faggot cell in AML-M3. (WC)

www:

IHC

  • CD2 +ve, CD34 +ve/-ve, CD56 +ve/-ve.

Flow cytometry

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

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+. (???)

Chronic myeloid leukemia

  • Abbreviated CML.
  • AKA chronic myelogenous leukemia.

General

  • Adults - usu. 50s or 60s.

Clinical - commonly:[10]

  • Leukocytosis - neutrophils, myelocytes, metamyelocytes, +/-eosinophilia, +/-basophilia.

Progression:

  1. Chronic phase - potentially curable.
  2. Accelerated phase.
  3. Blast crisis.

Treatment:

Notes:

  • Myeloblast (common granulocyte precursor) -> promyelocyte -> metamyelocyte -> myelocyte -> band -> mature myelocyte.[11]

Microscopic

Features:

  • Bone marrow with too many granulocytes/granulocyte precursors.
    • Granulocyte precursors:[11]
      1. Myeloblast (common granulocyte precursor) ~ 90% nucleus, multiple nucleoli.
        • Should be less than 10%.
      2. Promyelocyte (committed to a specific linage (neutrophil, basophil or eosinophil)) - dia. 2x mature, 40-50% nucleus, one nucleolus.
      3. Metamyelocyte - dia. 2x mature, 30-40% nucleus, no nucleolus.
      4. Myelocyte - dia. 1x mature, 50-60% nucleus - kidney bean shape, no nucleolus.
      5. Band - dia. 1x mature, 30-40% nucleus - C shape/irregular, no nucleolus.

IHC

Features:[12] (???)

  • Chronic:
    • CD20+ CD19+ CD10-.
  • Accelerated:
    • CD20+ CD19+ CD10+.
  • Blast:
    • CD20- CD19+ CD10+.
    • CD34+ TdT+.[13]

Molecular

  • t(9;22) BCR-ABL - required for diagnosis.
    • May be found in other leukemias.

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. ↑ Bonaventure, A.; Harewood, R.; Stiller, CA.; Gatta, G.; Clavel, J.; Stefan, DC.; Carreira, H.; Spika, D. et al. (Apr 2017). "Worldwide comparison of survival from childhood leukaemia for 1995-2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries.". Lancet Haematol. doi:10.1016/S2352-3026(17)30052-2. PMID 28411119.
  4. ↑ Berger, R. (1994). "Translocation t(8;21)(q22;q22): cytogenetics and molecular biology.". Nouv Rev Fr Hematol 36 Suppl 1: S67-9. PMID 8177719.
  5. ↑ 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.
  6. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 102578
  7. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 180240
  8. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 623 Q2. ISBN 978-1416025887.
  9. ↑ URL: http://path.upmc.edu/cases/case457.html. Accessed on: 21 January 2012.
  10. ↑ 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. 336. ISBN 978-1416054542.
  11. ↑ 11.0 11.1 URL: http://commons.wikimedia.org/wiki/File:Hematopoiesis_%28human%29_diagram.png. Accessed on: 14 January 2012.
  12. ↑ Muñoz, L.; Bellido, M.; Sierra, J.; Nomdedéu, JF. (Feb 2000). "Flow cytometric detection of B cell abnormal maturation in chronic myeloid leukemia.". Leukemia 14 (2): 339-40. PMID 10673756.
  13. ↑ URL: http://path.upmc.edu/cases/case271.html. Accessed on: 14 January 2012.
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