Category Archives: Bone Marrow

Organ Systems, Bone Marrow, Lymph Node, WHO Classification

B-ALL

B-Cell Acute Lymphoblastic Leukemia/Lymphoma (B-ALL) accounts for ~80-85% of ALL cases.  75% occur in children < 6 years of age.  The remainder of ALL cases are of T-cell origin.  T-ALL more commonly presents as extra nodal disease.
Immunohistochemical Profile
Stain
Comment
Positive
Positive.  Up to 10% of T-ALL cases may be positive.
Positive in most cases.  CD10 negative cases may be associated with MLL gene rearrangements.
Variably positive.
CD22
Positive (cytoplasmic)
Variably positive.  t(12;21) and hyperploidy cases are often CD34+.
+/-
Positive.  Approximately 95% sensitive.
CD13
+/-  Myeloid markers do not exclude the possibility of an ALL.
+/-  Myeloid markers do not exclude the possibility of an ALL.
MPO
Negative.  Positivity would support either an AML or a B/myeloid leukemia.
Typically Negative
Expression is associated with t(9;22) in adults.
Positive (nuclear expression).  Sensitive and specific marker of B-cell lineage, but a subset of AMLs may express PAX-5 [t(8;21)].
MPO – myeloperoxidase
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, Lymph Node, WHO Classification

Blastic Plasmacytoid Dendritic Cell Neoplasm

IHC Expression Pattern
Positive
Positive
CD45RA
Positive
Positive.  Rare cases may be negative, but should express CD4, CD123, and TCL1.
Expressed in ~50% of cases (small cytoplasmic dots)
Often Positive
Negative
MPO
Negative
Negative in tissue sections (may be + by flow)
Negative
Negative
EBV-EBER
Negative
TCL-1
Positive
References
Hematopathology. [edited by] Jaffe, ES. 1st. ed. Elsevier, Inc. © 2011.
Organ Systems, Bone Marrow, WHO Classification

Acute Myeloid Leukemia, NOS (AML-NOS)

Immunohistochemistry in AML-NOS
AML with Minimal Differentiation (M0)
MPO
While negative by cytochemistry (by definition) a subset may have expression by flow cytometry or IHC.
CD34  
Most cases are Positive.
~50% Positive (not a specific marker of lymphoblasts)
~40% are Positive

 

AML without maturation (M1)
MPO
Usually positive
CD34
~70% of cases are positive
Often Positive
CD7
~30% of cases are positive
10-20% of cases may show expression of CD2, CD4, CD19, and CD56.
AML with maturation (M2)
CD34
Usually Positive, but may only be expressed on a subset of the blasts.
CD117
Usually Positive, but may only be expressed on a subset of the blasts.
CD7
~20-30% of cases are positive.

Expression of CD4, CD2, CD19, or CD56 is not common (~10% of cases).

Acute Myelomonocytic Leukemia (M4)
CD34
Usually Positive, but may only be expressed on a subset of the blasts (not in the monocytic derived cells).
CD117
Usually Positive, but may only be expressed on a subset of the blasts.
CD7
~30% of cases are positive.
Acute Monoblastic and Monocytic Leukemia (M5)
CD34
~30% of cases are positive (flow data)
Usually Positive, more often than CD34. (flow data)
CD7
~25-40% of cases are positive. (flow data)
~25-40% of cases are positive. (flow data)
 
Acute Erythroid Leukemia (M6)
 
ERYTHROLEUKEMIA (erythroid/myeloid)
CD71  
May show abnormal dim expression in the erythroblasts.
 
The myeloid population may excess myeloid markers similar to that of AMO with minimal maturation.
 
PURE ERYTHROID LEUKEMIA
CD34
Usually negative
CD117
+/-
Acute Megakaryoblastic Leukemia (M7)
CD41  
Often Positive
CD61
Often Positive
CD42
Less often positive (more mature platelet marker)
Usually Negative
Usually Negative
MPO
Negative
TdT
Negative
CD7
+/-
 
Acute Panmyelosis with Myelofibrosis
CD34
Usually Positive
CD117
Often Positive
MPO
Usually Negative
Organ Systems, Bone Marrow, WHO Classification

AML with Myelodysplasia-Related Changes

Immunohistochemistry in AML with Myelodysplasia-Related Changes
Often positive with abnormalities of chromosomes 5 and 7.  CD34 may only be expressed in a subpopulation of the blasts.
Variably positive, but may be seen more commonly in 
cases with abnormalities of chromosomes 5 and 7.
Variably positive
Variably positive
 
Other myeloid antigens may be positive.
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
 
WHO Classification, Organ Systems, Bone Marrow

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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