Category Archives: Bone Marrow

Organ Systems, Bone Marrow, WHO Classification, MDS

MDS-EB

October 10, 2017 peferguson

Myelodysplastic Syndrome with Excess Blasts (MDS-EB)

2016 revision largely remains unchanged from the 2008 designation of refractory anemia with excess blasts (RAEB). As in the 2008 classification, MDS-EB is subdivided based on blast percentage. Continue reading MDS-EB →

Organ Systems, Bone Marrow, WHO Classification

MDS-MLD

October 10, 2017 peferguson

Myelodysplastic Syndrome with Multilineage Dysplasia (MDS-MLD)

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

Diagnostic Criteria

Multiple lineages (2-3) with dysplasia (>10% for each affected lineage)
1-3 cytopenias
No increased ring sideroblasts (≤15% or ≤5% with SB3F1 mutation)
<5% bone marrow blasts
<1% peripheral blood blasts
No Auer Rods
Any abnormalities, except for isolated 5q deletion (MDS with isolated 5q-)

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	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Organ Systems, Bone Marrow, WHO Classification, MDS

MDS-RS (SLD & MLD)

October 10, 2017 peferguson

Myelodysplastic Syndrome with Ring Sideroblasts (MDS-RS)

2016 WHO revision effectively replaces the category of refractory anemia with ringed sideroblasts (RARS) as MDS-RS with single lineage dysplasia (MDS-RS-SLD), and is expanded to include cases of MDS with ring sideroblasts and multilineage dysaplasia (MDS-RS-MLD). Continue reading MDS-RS (SLD & MLD) →

Organ Systems, Bone Marrow, WHO Classification

Refractory Cytopenia with Unilineage Dysplasia (RCUD)

October 10, 2017 peferguson

Immunohistochemistry

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Organ Systems, Bone Marrow, WHO Classification, IHC Panels

Immunohistochemistry – MDS

October 10, 2017 peferguson

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Organ Systems, Bone Marrow, WHO Classification

MDS-SLD

October 10, 2017 peferguson

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

Single lineage dysplasia (>10%)
1-2 cytopenias
No increased ring sideroblasts (≤15% or ≤5% with SB3F1 mutation)
<5% bone marrow blasts
<1% peripheral blood blasts
No Auer Rods
Any abnormalities, except for isolated 5q deletion (MDS with isolated 5q-)

Immunohistochemistry

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Organ Systems, Bone Marrow, WHO Classification

Myelodysplastic/Myeloproliferative Neoplasm – Unclassifiable (MDS/MPN-U)

October 10, 2017 peferguson

Immunohistochemistry

The use of immunohistochemistry (IHC) in many of the MPN/MDS neoplasms 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	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Organ Systems, Bone Marrow, WHO Classification

Juvenile Myelomonocytic Leukemia

October 10, 2017 peferguson

Immunohistochemistry

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Organ Systems, Bone Marrow, WHO Classification

Atypical Chronic Myelogenous Leukemia (aCML)

October 10, 2017 peferguson

2016 WHO Criteria

PB leukocytosis with increased PMNs and precursors (evidence of dysgranulopoiesis)
Neutrophil precursors (less mature than a band-form) make up ≥10% of leukocytes
Absence of significant basophilia (<2% or leukocytes)
No monocytosis (<10% of leukocytes)
Hypercellular bone marrow with granulocytic dysplasia (+/- dysplasia in other lineages)
<20% blasts in PB and BM
Does not meet diagnostic criteria for BCR-ABL1+ CML, PMF, PV, or ET (if you compare to the criteria for other MPNs, this is a circular argument)
No PDGFA, PDGFB, FGFR1, or JAK2-PCM1 rearrangement

In the past has been difficult to differentiate from CNL. This category has been somewhat better clarified in the 2016 WHO revision.

<10% have CSF3R mutation (strong association with CNL, if present should closely examine to exclude CNL – mutation may have therapeutic implications irregardless of diagnosis)
Not usually associated with JAK2, CALR, or MPL mutations
Up to 1/3rd of cases have SETBP1 and/or ETNK1 mutations

Immunohistochemistry

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127: 2391–2405. doi:10.1182/blood-2016-03-643544

WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. SH Swerdlow, et al. International Agency for Research on Cancer. Lyon, 2008.

Organ Systems, Bone Marrow, WHO Classification

Chronic Myelomonocytic Leukemia (CMML)

October 10, 2017 peferguson

2016 WHO Diagnostic Criteria

Persistent peripheral blood monocytosis >1,000/μL (and accounts for ≥10% of the WBC count)
Does not meet diagnostic criteria for BCR-ABL1+ CML, PMF, PV, or ET (if you compare to the criteria for other MPNs, this is a circular argument)
No PDGFA, PDGFB, FGFR1, or JAK2-PCM1 rearrangement (specificity exclude if there is eosinophilia)
<20% blasts (blood or bone marrow); blasts defined as promonocytes, myeloblasts, or monoblasts
Myeloid dysplasia in one or more lineages, or
(If dysplasia is absent or minimal) presence of an acquired cytogenetic/molecular abnormality in the hematologic cell lineage

or, in the absence of the above criteria

At 3 months of persistent monocytosis (and)
Other causes have been excluded

CMML is unlikely if there is a previous diagnosis of a MPN, as such entities can progress to a phase with monocytosis (and this should be closely evaluated)

“Proliferative type” CMML – WBC ≥13,000/μL

“Dysplastic type” CMML – SBC <13,000/μL

CMML-0

<2% blasts in PB and
<5% blasts in BM

CMML-1

2-4% blasts in PB and/or
5-9% blasts in BM

CMML-2

5-19% blasts in PB
10-19% blasts in BM and/or
Presence of Auer rods

Immunohistochemistry

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	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	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.
E_Cadherin	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	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

WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. SH Swerdlow, et al. International Agency for Research on Cancer. Lyon, 2008.