Difference between revisions of "Leukemia"

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The article addresses '''leukemia''', which is uncommonly seen by anatomical pathologists.  It is a subset of [[hematopathology]].
[[Image:Acute leukemia-ALL.jpg | thumb|right|A bone marrow of an individual with precursor B-cell lymphoblastic leukemia. [[Wright stain]]. (WC)]]
The term '''leukemia''' is broadly used to refer to any haematological malignancy where the neoplastic cells in the circulation are the prominent feature. It is generally only seen by anatomical pathologists only in countries where hematopathology reporting is done by anatomical pathologists rather than hematologists.


Lymphoma is discussed in the ''[[lymphoma]]'' article, and overlaps somewhat with leukemia as the clear distinction between the two is historical (see below).
Lymphoma is discussed in the ''[[lymphoma]]'' article, and overlaps somewhat with leukemia as the clear distinction between the two is somewhat arbitrary and historical:<ref>{{Ref PCPBoD8|314}}</ref>
 
Historical classification:<ref>{{Ref PCPBoD8|314}}</ref>
*Leukemia = involves bone marrow +/- peripheral blood.
*Leukemia = involves bone marrow +/- peripheral blood.
**Classic presentation: infection, bleeding, anemia.
**Classic presentation: infection, bleeding, anemia.
*Lymphoma = discrete mass(es), usu. [[lymph node]].
*Lymphoma = discrete mass(es), usu. [[lymph node]].
**Classic presentation: non-tender lymph nodes
**Classic presentation: non-tender lymph nodes
Leukemias may present as discrete massess, e.g. in the skin ([[leukemia cutis]]) or at other sites, where it is known by various names ([[myeloid sarcoma]], chloroma, etc.).
Most leukemias are typically classified into acute or chronic. As a general rule, the designation of '''acute''' signifies a more immature and aggressive phenotype, whilst '''[[chronic]]''' leukemias generally show a more differentiated phenotype and run a more indolent course. There are exceptions, of course, and some chronic leukemias may transform into acute lymphomas.


=Definition=
=Definition=
All of the following:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
This varies with the type.
 
For acute myeloid leukemia, all of the following:<ref name=dg21mar20011>D. Good. 21 March 2011.</ref>
#Morphologic abnormalities.
#Morphologic abnormalities.
#>20% blasts ''or'' recurrent cytogenetic abnormality.
#>20% blasts ''or'' recurrent cytogenetic abnormality.


Some recurrent cytogenetic abnormalities:
=Leukemia classification=
*t(8;21).
*[[Acute myeloid leukemia]] (AML). In this context, myeloid is used broadly to refer to non-lymphoid precursors rather than the more limited meaning granulopoietic:
*inv(16).
*#AML.
*t(15;17).
*#AML with recurrent cytogenetic abnormalities, e.g. t(8;21), inv(16) and t(15;17).
*#AML arising from [[MDS]].
*#AML in the setting of [[Down syndrome]].
 
*[[Acute lymphoblastic leukemia]] (ALL):
*#B cell.
*#B cell with recurrent cytogenetic abnormalities.
*#T cell (sometimes abbreviated to T-ALL)
 
*T-ALL should not to be confused with [[adult T-cell leukemia/lymphoma]] (ATLL) - this is associated with HTLV-1 infection
 
*[[Chronic lymphocytic leukemia]] (CLL) - usually classified with lymphomas
 
A few fall under the umbrella of '''[[myeloproliferative neoplasm]]s''':
*[[Chronic myeloid leukemia]] (CML)
*[[Chronic neutrophilic leukemia]] (rare)
*[[Chronic eosinophilic leukemia]] (rare)
 
And others under the myeloproliferative/myelodysplastic overlap syndromes:
*[[Chronic myelomonocytic leukemia]]
 
Other less common leukemias:
*Hairy cell leukemia
*T-cell prolymphocytic leukemia
*T-cell large granular lymphocyte leukaemia (T-LGL)
*Plasma cell leukaemia
*Mast cell leukemia


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


=Algorithms=
=Algorithms=
Line 48: Line 78:
*[[Down syndrome]]?
*[[Down syndrome]]?


=Leukemia classification=
=Prognosis=
Acute myeloid leukemia (AML):
Highly dependent on health care system and treatment available<ref>{{Cite journal  | last1 = Bonaventure | first1 = A. | last2 = Harewood | first2 = R. | last3 = Stiller | first3 = CA. | last4 = Gatta | first4 = G. | last5 = Clavel | first5 = J. | last6 = Stefan | first6 = DC. | last7 = Carreira | first7 = H. | last8 = Spika | first8 = D. | last9 = Marcos-Gragera | first9 = R. | title = 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. | journal = Lancet Haematol | volume = | issue = | pages = | month = Apr | year = 2017 | doi = 10.1016/S2352-3026(17)30052-2 | PMID = 28411119 }}</ref>
#AML.
*5-year overall survival in children ranges:
#AML with recurrent cytogenetic abnormalities.
#lymphoid leukaemia: 52.4% (Colombia) to 91.6% (Germany)
#AML from [[MDS]].
#acute myleoid leukemia: 33.3% (Bulgaria) to 78.2% (Germany)
#AML in the setting of [[Down syndrome]].
 
Acute lymphoid leukemia (ALL):
#B cell.
#B cell with recurrent cytogenetic abnormalities.
#T cell.
 
Chronic myeloid leukemia (CML).
 
=Specific diagnoses=
==Acute myeloid leukemia==
*Abbreviated ''[[AML]]''.
===General===
*Adults.
 
Exclusions for this diagnosis:
*Prior [[MDS]].
*[[Down syndrome]].
 
===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:
*[http://commons.wikimedia.org/wiki/File:Auer_rods.PNG Auer rods in an AML (WC)].
*[http://path.upmc.edu/cases/case344.html AML - several images (upmc.edu)].
 
===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).<ref>{{Cite journal  | last1 = Berger | first1 = R. | title = Translocation t(8;21)(q22;q22): cytogenetics and molecular biology. | journal = Nouv Rev Fr Hematol | volume = 36 Suppl 1 | issue = | pages = S67-9 | month =  | year = 1994 | doi =  | PMID = 8177719 }}</ref>
 
IHC:
*CD34+, CD13+, MPO+ (cytoplasm), CD33+ (weak).
*[[CD56]]+, CD117+.
**Usu. assoc. with a bad prognosis.
 
Flow cytometry:
*CD19+, PAX5+, CD79a +/-.
 
Images:
*[http://path.upmc.edu/cases/case712.html AML with t(8;21) (upmc.edu)].
 
===Acute myeloid leukemia with inv(16)===
*inv(16)(p13.1q22).<ref name=pmid16917916>{{Cite journal  | last1 = Lu | first1 = CM. | last2 = Murata-Collins | first2 = JL. | last3 = Wang | first3 = E. | last4 = Siddiqi | first4 = I. | last5 = Lawrence | first5 = HJ. | title = Concurrent acute myeloid leukemia with inv(16)(p13.1q22) and chronic lymphocytic leukemia: molecular evidence of two separate diseases. | journal = Am J Hematol | volume = 81 | issue = 12 | pages = 963-8 | month = Dec | year = 2006 | doi = 10.1002/ajh.20716 | PMID = 16917916 }}
</ref>
 
*Associated with [[myeloid sarcoma]].
 
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<ref name=omim102578>{{OMIM|102578}}</ref>-RARA.<ref name=omim180240>{{OMIM|180240}}</ref>
 
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:
*[http://path.upmc.edu/cases/case457/images/fig01.jpg AML - showing Auer rods (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case457.html http://path.upmc.edu/cases/case457.html]. Accessed on: 21 January 2012.</ref>
*[http://path.upmc.edu/cases/case705.html APML - several images (upmc.edu)].
 
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.
 
Clinical:
*Associated with [[DIC]].
*Treatment: all-trans retinoic acid (ATRA).
 
Variants:
*t(11;17) -- ATRA doesn't work.<ref>{{Ref APBR|623 Q2}}</ref>
*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+. (???)
 
==Chronic myeloid leukemia==
*Abbreviated ''CML''.
*[[AKA]] ''chronic myelogenous leukemia''.
===General===
*Adults - usu. 50s or 60s.
 
Clinical - commonly:<ref>{{Ref PCPBoD8|336}}</ref>
*Leukocytosis - neutrophils, myelocytes, metamyelocytes, +/-eosinophilia, +/-basophilia.
 
Progression:
#Chronic phase - potentially curable.
#Accelerated phase.
#Blast crisis.
 
Treatment:
*[[Imatinib]].
 
Notes:
*Myeloblast (common granulocyte precursor) -> promyelocyte -> metamyelocyte -> myelocyte -> band -> mature myelocyte.<ref name=hemechart>URL: [http://commons.wikimedia.org/wiki/File:Hematopoiesis_%28human%29_diagram.png http://commons.wikimedia.org/wiki/File:Hematopoiesis_%28human%29_diagram.png]. Accessed on: 14 January 2012.</ref>
 
===Microscopic===
Features:
*Bone marrow with too many granulocytes/granulocyte precursors.
**Granulocyte precursors:<ref name=hemechart>URL: [http://commons.wikimedia.org/wiki/File:Hematopoiesis_%28human%29_diagram.png http://commons.wikimedia.org/wiki/File:Hematopoiesis_%28human%29_diagram.png]. Accessed on: 14 January 2012.</ref>
**#Myeloblast (common granulocyte precursor) ~ 90% nucleus, multiple nucleoli.
**#*Should be less than 10%.
**#Promyelocyte (committed to a specific linage ([[neutrophil]], basophil or [[eosinophil]])) - dia. 2x mature, 40-50% nucleus, one [[nucleolus]].
**#Metamyelocyte - dia. 2x mature, 30-40% nucleus, no nucleolus.
**#Myelocyte - dia. 1x mature, 50-60% nucleus - kidney bean shape, no nucleolus.
**#Band - dia. 1x mature, 30-40% nucleus - C shape/irregular, no nucleolus.
 
===IHC===
Features:<ref>{{Cite journal  | last1 = Muñoz | first1 = L. | last2 = Bellido | first2 = M. | last3 = Sierra | first3 = J. | last4 = Nomdedéu | first4 = JF. | title = Flow cytometric detection of B cell abnormal maturation in chronic myeloid leukemia. | journal = Leukemia | volume = 14 | issue = 2 | pages = 339-40 | month = Feb | year = 2000 | doi =  | PMID = 10673756 |URL = http://www.nature.com/leu/journal/v14/n2/full/2401549a.html }}</ref> (???)
*Chronic:
**CD20+ CD19+ CD10-.
*Accelerated:
**CD20+ CD19+ CD10+.
*Blast:
**CD20- CD19+ CD10+.
**CD34+ TdT+.<ref>URL: [http://path.upmc.edu/cases/case271.html http://path.upmc.edu/cases/case271.html]. Accessed on: 14 January 2012.</ref>
 
===Molecular===
*t(9;22) BCR-ABL - '''required for diagnosis'''.
**May be found in other leukemias.


=See also=
=See also=

Latest revision as of 20:06, 26 May 2018

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

The term leukemia is broadly used to refer to any haematological malignancy where the neoplastic cells in the circulation are the prominent feature. It is generally only seen by anatomical pathologists only in countries where hematopathology reporting is done by anatomical pathologists rather than hematologists.

Lymphoma is discussed in the lymphoma article, and overlaps somewhat with leukemia as the clear distinction between the two is somewhat arbitrary and historical:[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

Leukemias may present as discrete massess, e.g. in the skin (leukemia cutis) or at other sites, where it is known by various names (myeloid sarcoma, chloroma, etc.).

Most leukemias are typically classified into acute or chronic. As a general rule, the designation of acute signifies a more immature and aggressive phenotype, whilst chronic leukemias generally show a more differentiated phenotype and run a more indolent course. There are exceptions, of course, and some chronic leukemias may transform into acute lymphomas.

Definition

This varies with the type.

For acute myeloid leukemia, all of the following:[2]

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

Leukemia classification

  • Acute myeloid leukemia (AML). In this context, myeloid is used broadly to refer to non-lymphoid precursors rather than the more limited meaning granulopoietic:
    1. AML.
    2. AML with recurrent cytogenetic abnormalities, e.g. t(8;21), inv(16) and t(15;17).
    3. AML arising from MDS.
    4. AML in the setting of Down syndrome.

A few fall under the umbrella of myeloproliferative neoplasms:

And others under the myeloproliferative/myelodysplastic overlap syndromes:

Other less common leukemias:

  • Hairy cell leukemia
  • T-cell prolymphocytic leukemia
  • T-cell large granular lymphocyte leukaemia (T-LGL)
  • Plasma cell leukaemia
  • Mast cell leukemia

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.

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)

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.
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