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

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

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.