Phenotypic Markers Flashcards
What diagnosese can
TdT be positive in ?
- B-ALL
- T-ALL
- Thymocytes
- thymic hyperplasia
- thymoma
- AML
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
- Hematogones
What type of molecule is TdT ?
- it is a unique intranuclear DNA polymerase
- in AMLs usually seen in
- minimally differentiated
- or rarely monoblastic leukemias
What diseases is MPO positive in ?
- AML
- Mixed phenotypic acute leukemia (MPAL)
What is the threshold for MPO positivity ?
- 3% threshold has been used historically for cytochemistry
- 10% threshold has been recommended for flow cytometry
- recent proposal for 13-28% positivity
Is there MPO positivity in B-ALL ?
- yes there can be without it being classified as an MPAL
- if there is homogeneous expression of lymphoid markers on the single blast population and there is no evidence of other myeloid marker expression othere than MPO
- B-ALL has been known to show low levels of MPO expression
What populations is HLA-DR positive in?
- expressed on B cells at different stages of maturation
- except in plasma cells where it is lost
What is HLA-DR negative in ?
- hematopoietic progenitor cells
- myeloid
- erythroid
- megakaryocytic
- monocytic/macrophage
- Hypo and hypergranular APL
- Plasma cell neoplasms
- Majority of T cell lymphoma/leukemias
What malignancies are typically
HLA-DR positive ?
- HLA-DR is positive on precursors and mature B cell lymphoproliferations
- majority of AML
CD235a (glycophorin A) is positive
in which cell populations?
- expressed on RBCs and their precursors
- very early precursors are usually negative or only dimly positive
- IMP:
- this is in contrast to CD71
- CD71 is strongly expressed by even the early precursors
- IMP:
CD138 is positive in what situations ?
- majority of plasma cell neoplasms
- subsets of mature B cell lymphoproliferations
- Plasmablastic lymphoma
- DLBCL with activated B cell like phenotype
What malignancies is CD123
positive in ?
- Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
- Benign plasmacytoid dendritic cells
- AML (subsets)
- APL (subset)
- CMML
- B-ALL (subset)
- Hairy cell leukemia (bright)
- Hairy cell leukemia variant (subset)/lower intensity of expression
- NK-cell malignancies
- Dendritic cell malignancies
- MDS blasts may be CD123+
What is the normal role of CD123 ?
- CD123 binds to the alpha subunit of the interleukin-3 receptor
When CD123 is positive in AML
what should you suspect is present ?
- usually NPM1 positive
- also positive in monoblastic leukemias
- the leukemias are also positive for FLT3-ITD mutations and show low expression of CD34
- positive for CD11b and CD14
Note: CD123 is positive in a subset of APL
What is the expected expression
of CD123 in HCL?
- expression of CD123 is bright
- Other rare cases of mature B cell lymphomas with CD123 (but expression is usually partial or dim)
- HCLv (~40% of cases)
- splenic marginal zone
- CLL
- MCL
- FL
What disease processes can have
CD123+ associated plasmacytoid dendritic cells?
- seen in the bone marrows of patients with CMML
- lymph nodes with Kikuchi-fujimoto lymphadenopathy
What type of B-ALL can you
see expression of CD123 ?
- usually hypodiploid B-ALL
- IMP
- normal bone marrow hematogones are negative for CD123
What benign cells are positive for CD117?
- Myeloblasts
- Promyelocytes
- Mast cells
Which leukemias are typically
positive for CD117?
- most AMLs are CD117 positive
- even AML without maturation
- AMML
- pure erythroid leukemias
- acute megakaryoblastic leukemia
What leukemias are typically
negative for CD117 ?
- acute monoblastic leukemia
What other hematopoietic tumors are
positive for CD117 ?
- Mast cell proliferations
- plasma cell neoplasms
- subsets of T-ALL
- especially ETP-ALL
- rare cases of mature CD8+ peripheral T cell proliferations
- notably T-PLL
What non-hematopoietic things
are positive for CD117 ?
- GIST
- occasionally malignant melanomas
- poorly differentiated caricnomas/neuroendocrine tumors
What are the 3 maturational stages of dendritic cells based on the expression of CD34 and CD117?
- immature cell (CD34+)
- intermediate cell (CD117+/CD34-)
- mature cells (CD117-/CD34-)
Note: these maturational stages explain the different presentations of BPDCN
What benign cells are positive for CD103?
- minor subset of T-cells in the GI tract and liver
- dendritic cells, subset
- rare circulating B cells
What neoplasms is CD103 expressed in ?
- HCL
- may be dim and or partial
- HCL(v)
- may be dim and or partial
- Enteropathy associated T-cell lymphoma (EATL)
- MEITL
- Diffuse large B cell lymphoma (rare cases)
- Marginal zone lymphoma (occasional cases)
- rare cases of PTCL, ATLL, and T-PLL
What other tumors may express CD103?
- BPDCN, subset
What neoplasms are negative for
CD103 ?
- MCL
- FL
- CLL
- MZL
- including splenic marginal zone lymphoma
What normal cells express CD79a ?
- benign, B cells
- this includes plasma cells which are essentially terminally differentiated B cells
What can pick up CD79a staining in a
non-specific manner in the BM ?
- megakaryocytes
What neoplaasms are often positive for CD81 ?
- mature B cell proliferations
What normal cells and neoplasms
is CD71 positive in?
- early erythroid precursors
- pure erythroid leukemia
- AML
- B-ALL subset
- T-ALL subset
- High grade B and T cell lymphomas
What benign cells express CD71 (transferrin receptor)?
- B and T cell precursors
- Myeloblasts
- Activated B and T/NK cells
- Erythroblasts/Pronormoblasts
- Germinal center B-cells (centroblasts)
- Reactive follicular hyperplasia (CD10+ B cells are CD71+)
What is the normal function of CD71 ?
- it is the transferrin receptor
- it mediates the uptake of transferrin-iron complexes
What normal cells express CD71 ?
- strongly positive in erythroid precursors
- myocytes
- hepatocytes
- endocrine pancreas cells
- spermatocytes
- basal keratinocytes
- placental syncitiotropholblasts
How is the expression of CD71 compared to glycophorin A?-
- CD71 is positive in early precursors while negative on mature red blood cells
What is the expression pattern of CD71
in erythroid precursors ?
- strongly positive in early precursors
- level of expression decreases gradually through the reticulocyte stage
- this is contrast to glycophorin (CD235a), CD71 is negative in mature erythrocytes
- CD71 has a similar expression pattern to E-cadherin
How does the intensity of CD71 vary
amongst lymphomas?
- CD71 is low intensity in low-grade lymphomas
- while it is high intensity in high grade lymphomas
- Note: expression is higher in DLBCL as compared to Burkitt lymphoma
What is the expression of CD71
in the BM and why ?
- CD71 is expressed at a higher level on cells that have a high proliferation rate (due to high iron demand)
- myeloblasts, promyelocytes, and erythroblasts are CD71+
- more mature forms are negative
CD71 is expressed more inT-ALL or B-ALL?
- usually more common in T-ALL
- also IMP
- ATLL shows some expression
What can CD71 be a surrogate marker
for by flow cytometry ?
- it can be a surrogate for Ki67
- or a proliferation marker
How is CD71 expression affected in dysplasia?
- The expression of CD71 is decreased in dysplastic erythroid precursors
In bone marrow specimens how is CD71 expressed?
- CD71 expression is restricted to the erythroid lineage
Note: myeloblasts, neoplastic plasma cells and metastatic carcinoma cells are usually negative.
What is CD64 expressed in ?
- monocytes (classical, CD14 bright +/CD16 -)
- acute monoblastic leukemia
- CMML
- monocytic components of AMML
- blasts in subsets of AML
- APL, subset dim partial
- Acute megakaryoblastic leukemia
What is different about the expression of
CD64 in acute monocytic leukemias vs. others ?
- CD64 is brighter
- in other AMLs the expression is dim or partial
What is CD61 expression seen in?
- megakaryocytes
- Acute megakaryoblastic leukemia
What is CD57 expression seen in?
- NK cells and a subset of T cells
- Positive in:
- T-LGL leukemia
- subset of NK-cell neoplasms
- rare T cell lymphoblastic tumors
- T-PLL, rare (mostly dim and partial)
- Chronic LPD of NK cells
Where are the CD57+ T cells
in NLPHL ?
- they form characteristic rosettes around the large neoplastic cells
What non-hematopoietic tumors can express CD57?
- Primitive Neuroectodermal Tumor (PNET)
- Rhabdomyosarcoma
- Small cell carcinoma
What is CD56 and what cells typically express it ?
- neural cell adhesion molecule (N-CAM)
- expressed by natural killer cells, subsets of T cells, and monocytes
When can CD56 expression be unregulated?
- subsets of granulocytes and monocytes from patients with MDS, MPNs and mixed MDS/MPN (such as CMML)
What non-leukemic, hematolymphoid
neoplasms express CD56?
- Extranodal NK/T cell lymphoma, nasal type
- Peripheral T cell lymphoma, NOS (subset)
- T-LGL leukemia (subset)
- NK-cell proliferations
*Chronic lymphoproliferative disorder of NK cells - ALCL (subset)
- Subcutaneous panniculitis-like T cell lymphoma (subset)
*Primary cutaneous gamma delta T cell lymphoma
*HSTL - MEITL
- EITL, subset
- Lymphomatoid papulosis (LyP)
- DLBCL (rare cases)
- Plasma cell myeloma
What leukemia’s often express CD56 ?
- acute monoblastic leukemia
- acute myeloid leukemia with t(8;21)
- usually with co-expression of CD19 by myeloblasts
- APL (rare cases)
- AML (rare cases)
Also, cutaneous gamma-delta T cell lymphoma and BPDCN
In what neoplasms is CD56 been associated
with a poor risk factor ?
- AML with t(8;21) and t(15;17)
- in t(8;21) associated with significantly shorter complete remission duration and survival
What non-hematopoietic neoplasms can express CD56?
- Small cell carcinoma
- Carcinoma with NE differentiation
- Malignant melanoma
- Neuroblastoma
- Wilms Tumor
- Rhabdomyosarcoma
What benign cells express CD19?
- Hematogones
- B- cells
- Plasma cells (variable, often dim or partial expression)
What neoplastic B cell lymphoproliferations express CD19?
- Majority of mature B cell LPDs
- PCM, rare cases
What neoplastic B cell lymphoproliferations are often negative for CD19?
- PEL
- ALK + Large B cell lymphoma
- Plasmablast lymphoma
- Subset of PTLD
What other tumors are positive for CD19?
- B-ALL/LBL
- AML, subset (AML with t(8;21)(RUNX1-RUNX1T1)
- MPAL; AML/B-ALL
- CML in lymphoid blast crisis
- Nodular lymphocyte predominant Hodgkin lymphoma
What type of molecule is CD19?
- integral membrane protein
- expression is limited to B cells and follicular dendritic cells
What is the possible function of CD20?
- poorly understood
- been implicated in B cell activation, regulation of B cell growth and regulation of transmembrane calcium flux
What cells is CD20 typically expressed on normally?
- B cells
- Germinal center cells show brighter expression than mantle zone cells
What B cell lymphoproliferative disorders often show CD20 expression?
- CLL, dim expression
- HCL and HCL-v
- Majority of B cell lymphomas
- PCM, minor subset
What T cell lymphoproliferations have been known to show CD20 expression?
- Aberrant expression has been documented in many cases
- Usually seen only in a subset of the neoplastic cells
- PTCL, NOS
- ALCL, T-PLL, follicular T cell lymphoma, and AITL
What other neoplastic conditions have shown aberrant CD20 expression?
- B-ALL/LBL (rare cases, usually dim and or partial expression)
- NLPHL
- Hodgkin Lymphoma, minor subset
- Thymoma, Type A (spindle, medullary subset)
What B cell lymphomas are notably negative for CD20?
- PBL
- PEL
- DLBCL associated with chronic inflammation
- ALK positive large B cell lymphoma
- DLBCL, rare cases
What is CD22 positive in ?
- CD22 is a B cell specific marker
- Plasma cells are CD22 negative
What cells is CD22 positive in ?
- B-cells
- Basophils, subset
What B cell lymphoproliferatie disorders is CD22 positive in ?
-Majority of mature B cell LPDs (somewhat dim)
**IMP: CLL is negative
-PCM, very rare cases
- CD22 is bright in HCL and splenic MZL
-Clonal plasma cell components of LPL may be CD22+
What acute leukemia’s can express CD22 ?
- B-ALL/LBL - cytoplasmic expression of CD22
- MPAL; AML and B-ALL
- Acute basophilic leukemia, subset
What other tumors can express CD22 ?
- Basophils in CML and AMLs with basophilic differentiation, they may also show CD13 and CD25 expression
- Mast cell neoplasms
What neoplasms are notably negative for CD22 ?
- CLL
- Plasma cell neoplasms
- BUT clonal plasma cell components of LPL may be CD22+