Category Archives: Organ Systems

Organ Systems, Bone Marrow, WHO Classification

AML with Recurrent Genetic Abnormalities

Immunohistochemistry in AML with Recurrent Cytogenetic Abnormalities
AML t(8;21)
Usually Positive
HLA_DR
Usually Positive (flow marker)
CD13
Usually Positive
Often Positive
Often Positive
CD79a  
May be Positve (Cytoplasmic)
-/+ (usually weak)
Occasional cases may be positive.  Adverse prognostic indicator.
 
AML inv(16) or t(16;16)
Usually Positive
Usually Positive
Often positive, but not specific
 
Varying expression of granulocytic and monocytic markers may be seen depending upon differentiation.
APL t(15;17) PML-RARA
Weak or negative
HLA_DR
Weak or negative (flow marker)
Often Positive (may be weak)
~20% of cases are positive, associated with a worse prognosis.
 
AML t(9;11) MLLT3-MLL
Variably Positive
Variably Positive
Often strong expression
 
AML t(6;9) DEK-NUP214
MPO
Often Positive
Usually Positive
Usually Positive
~50% are Positive
 
AML inv(3) or t(3;3) RPN1-EVI1
There is limited data available.  Some studies show CD7 may be aberrantly expressed.
AML t(1;22) RBM15-MKL1 (Megakaryoblastic AML)
CD41  
Often Positive
CD61
Often Positive
CD42
Mature platelet marker, which is less often expressed.
Usually Negative
MPO
Usually Negative
Negative
 
AML with Mutated NPM1
CD34 is usually negative.  Myeloid and/or monocytic markers may be positive.
AML with Mutated CEBPA
CD34  
Usually Positive
~50-73% of cases are positive
Usually negative
 
One or more myeloid markers are usually positive.
 
References
 
Organ Systems, Bone Marrow, WHO Classification

Myeloid Sarcoma

Myeloid sarcoma is essentially AML occurring outside the bone marrow.   It has been referred to by many names including leukemia cutis, granulocytic sarcoma, myeloid sarcoma, and chloroma.  Diagnosis may be difficult to make because many of the usual IHC characteristics in the bone marrow are not mirrored when AML presents in the skin or other locations.  Additionally, flow cytomtery is often not performed when lesions present in unusual locations (e.g. skin, etc.). 
 
The 2008 WHO Classification lists the following helpful IHC markers from most sensitive to least sensitive:  CD68/KP1 > MPO > CD117 > CD99 > CD68/PG-M1 > Lysozyme > CD34 > TdT > CD56 > CD61 > CD30 > CD4.
 
It is important to remember the individual markers characteristics and that some are less specific than others.  It is critical to evaluate the results using a panel of markers combined with the morphology.
Myeloid Leukemia Cutis
The following is the IHC performance from 33 cases studied at Stanford Medical Center:
IHC Marker
% Positive
97% (N=33)
MPO
42% (N=33)
94% (N=33)
CD163
25% (N=28)
47% (N=30)
Predominately Negative
Predominately Negative
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
 
Cronin DM, et al. Am J Clin Pathol2009, Jul;132(1):101-10.
Organ Systems, Bone Marrow, WHO Classification, MDS

Myelodysplastic Syndrome, Unclassifiable – (MDS-U)

2016 revision subdivides category into three entities

  • with 1% blood blasts
  • with single lineage dyaplasia (SLD) and pancytopenia
  • based on defining cytogenetic abnormality
Diagnostic Criteria – with 1% PB blasts
  • Multiple lineages (1-3) with dysplasia (>10% for each affected lineage)
  • 1-3 cytopenias
  • +/- ring sideroblasts
  • <5% bone marrow blasts
  • 1% peripheral blood blasts
  • No Auer Rods
  • Any cytogenetic abnormalities
Diagnostic Criteria – with SLD and pancytopenia
  • Single lineage with dysplasia (>10% for affected lineage)
  • 3 cytopenias
  • +/- ring sideroblasts
  • <5% bone marrow blasts
  • <1% peripheral blood blasts
  • No Auer Rods
  • Any cytogenetic abnormalities
Diagnostic Criteria – with defining cytogenetic abnormality
Immunohistochemistry
The use of immunohistochemistry (IHC) in many of the MDS syndromes is limited.  Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute myelogenous leukemia (AML).  Helpful IHC markers may include:
 
Stain
Comment
CD34 marks immature cells including myeloblasts.  In the setting of AML, it is ~70% sensitive.  A subset of lymphoblasts may express CD34.
CD117 is a specific myeloid marker, and marks a subset of myeloblasts.  The expression is dim, and one often must look at 20-40X to clearly see expression.  Mast cells (fried egg looking cell) will have very strong expression.
CD71 marks nucleated erythroid cells.  This may be helpful in quantitating and differentiating erythroid cells from myeloid cells.  This marker may be set-up as a double stain with CD34.
In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells.  Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT is a sensitive lymphoblast (~95%) marker.  It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).  
References
Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017
 
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification, MDS

MDS with Isolated del(5q) – (5q Minus)

Myelodysplastic Syndrome with Isolated del(5q)

2016 WHO revision is largely unchanged from the 2008 classification.

Diagnostic Criteria
  • Single or multiple lineages (1-3) with dysplasia (>10% for each affected lineage)
  • 1-2 cytopenias
  • +/- ring sideroblasts
  • <5% bone marrow blasts
  • <1% peripheral blood blasts
  • No Auer Rods
  • Isolated 5q deletion (can have one additional abnormality so long as it is not loss of chromosome 7 or del(7q) 

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Organ Systems, Bone Marrow, WHO Classification

MDS-MLD

Myelodysplastic Syndrome with Multilineage Dysplasia (MDS-MLD)

2016 WHO revision that effectively replaces refractory cytopenia with multilineage dysplasia (RCMD).

Diagnostic Criteria
Immunohistochemistry
The use of immunohistochemistry (IHC) in many of the MDS syndromes is limited.  Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute myelogenous leukemia (AML).  Helpful IHC markers may include:
 
Stain
Comment
CD34 marks immature cells including myeloblasts.  In the setting of AML, it is ~70% sensitive.  A subset of lymphoblasts may express CD34.
CD117 is a specific myeloid marker, and marks a subset of myeloblasts.  The expression is dim, and one often must look at 20-40X to clearly see expression.  Mast cells (fried egg looking cell) will have very strong expression.
CD71 marks nucleated erythroid cells.  This may be helpful in quantitating and differentiating erythroid cells from myeloid cells.  This marker may be set-up as a double stain with CD34.
In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells.  Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT is a sensitive lymphoblast (~95%) marker.  It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).  
References
Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017
 
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification

Refractory Cytopenia with Unilineage Dysplasia (RCUD)

Immunohistochemistry
The use of immunohistochemistry (IHC) in many of the MDS syndromes is limited.  Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute myelogenous leukemia (AML).  Helpful IHC markers may include:
 
Stain
Comment
CD34 marks immature cells including myeloblasts.  In the setting of AML, it is ~70% sensitive.  A subset of lymphoblasts may express CD34.
CD117 is a specific myeloid marker, and marks a subset of myeloblasts.  The expression is dim, and one often must look at 20-40X to clearly see expression.  Mast cells (fried egg looking cell) will have very strong expression.
CD71 marks nucleated erythroid cells.  This may be helpful in quantitating and differentiating erythroid cells from myeloid cells.  This marker may be set-up as a double stain with CD34.
In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells.  Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT is a sensitive lymphoblast (~95%) marker.  It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).  
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification, IHC Panels

Immunohistochemistry – MDS

The use of immunohistochemistry (IHC) in many of the MDS syndromes is limited.  Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute myelogenous leukemia (AML).  Helpful IHC markers may include:
 
Stain
Comment
CD34 marks immature cells including myeloblasts.  In the setting of AML, it is ~70% sensitive.  A subset of lymphoblasts may express CD34.
CD117 is a specific myeloid marker, and marks a subset of myeloblasts.  The expression is dim, and one often must look at 20-40X to clearly see expression.  Mast cells (fried egg looking cell) will have very strong expression.
CD71 marks nucleated erythroid cells.  This may be helpful in quantitating and differentiating erythroid cells from myeloid cells.  This marker may be set-up as a double stain with CD34.
In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells.  Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT is a sensitive lymphoblast (~95%) marker.  It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).  
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification

MDS-SLD

Myelodysplastic Syndrome with Single Lineage Dysplasia (MDS-SLD)

2016 WHO revision that effectively replaces the 2008 category of refractory cytopenia with unilineage dysplasia (RCUD).

Diagnostic Criteria
Immunohistochemistry
The use of immunohistochemistry (IHC) in many of the MDS syndromes is limited.  Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute myelogenous leukemia (AML).  Helpful IHC markers may include:
 
Stain
Comment
CD34 marks immature cells including myeloblasts.  In the setting of AML, it is ~70% sensitive.  A subset of lymphoblasts may express CD34.
CD117 is a specific myeloid marker, and marks a subset of myeloblasts.  The expression is dim, and one often must look at 20-40X to clearly see expression.  Mast cells (fried egg looking cell) will have very strong expression.
CD71 marks nucleated erythroid cells.  This may be helpful in quantitating and differentiating erythroid cells from myeloid cells.  This marker may be set-up as a double stain with CD34.
In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells.  Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT is a sensitive lymphoblast (~95%) marker.  It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).  
References
Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017
 
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.