Phenotypic Markers Flashcards

1
Q

What diagnosese can

TdT be positive in ?

A
  • B-ALL
  • T-ALL
  • Thymocytes
    • thymic hyperplasia
    • thymoma
  • AML
  • Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
  • Hematogones
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2
Q

What type of molecule is TdT ?

A
  • it is a unique intranuclear DNA polymerase
  • in AMLs usually seen in
    • minimally differentiated
    • or rarely monoblastic leukemias
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3
Q

What diseases is MPO positive in ?

A
  • AML
  • Mixed phenotypic acute leukemia (MPAL)
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4
Q

What is the threshold for MPO positivity ?

A
  • 3% threshold has been used historically for cytochemistry
  • 10% threshold has been recommended for flow cytometry
    • recent proposal for 13-28% positivity
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5
Q

Is there MPO positivity in B-ALL ?

A
  • 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
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6
Q

What populations is HLA-DR positive in?

A
  • expressed on B cells at different stages of maturation
    • except in plasma cells where it is lost
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7
Q

What is HLA-DR negative in ?

A
  • hematopoietic progenitor cells
    • myeloid
    • erythroid
    • megakaryocytic
    • monocytic/macrophage
  • Hypo and hypergranular APL
  • Plasma cell neoplasms
  • Majority of T cell lymphoma/leukemias
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8
Q

What malignancies are typically

HLA-DR positive ?

A
  • HLA-DR is positive on precursors and mature B cell lymphoproliferations
  • majority of AML
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9
Q

CD235a (glycophorin A) is positive

in which cell populations?

A
  • 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
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10
Q

CD138 is positive in what situations ?

A
  • majority of plasma cell neoplasms
  • subsets of mature B cell lymphoproliferations
    • Plasmablastic lymphoma
    • DLBCL with activated B cell like phenotype
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11
Q

What malignancies is CD123

positive in ?

A
  • 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+
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12
Q

What is the normal role of CD123 ?

A
  • CD123 binds to the alpha subunit of the interleukin-3 receptor
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13
Q

When CD123 is positive in AML

what should you suspect is present ?

A
  • 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

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14
Q

What is the expected expression

of CD123 in HCL?

A
  • 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
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15
Q

What disease processes can have

CD123+ associated plasmacytoid dendritic cells?

A
  • seen in the bone marrows of patients with CMML
  • lymph nodes with Kikuchi-fujimoto lymphadenopathy
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16
Q

What type of B-ALL can you

see expression of CD123 ?

A
  • usually hypodiploid B-ALL
  • IMP
    • normal bone marrow hematogones are negative for CD123
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17
Q

What benign cells are positive for CD117?

A
  • Myeloblasts
  • Promyelocytes
  • Mast cells
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18
Q

Which leukemias are typically

positive for CD117?

A
  • most AMLs are CD117 positive
    • even AML without maturation
    • AMML
    • pure erythroid leukemias
    • acute megakaryoblastic leukemia
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19
Q

What leukemias are typically

negative for CD117 ?

A
  • acute monoblastic leukemia
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20
Q

What other hematopoietic tumors are

positive for CD117 ?

A
  • 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
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21
Q

What non-hematopoietic things

are positive for CD117 ?

A
  • GIST
  • occasionally malignant melanomas
  • poorly differentiated caricnomas/neuroendocrine tumors
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22
Q

What are the 3 maturational stages of dendritic cells based on the expression of CD34 and CD117?

A
  • immature cell (CD34+)
  • intermediate cell (CD117+/CD34-)
  • mature cells (CD117-/CD34-)

Note: these maturational stages explain the different presentations of BPDCN

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23
Q

What benign cells are positive for CD103?

A
  • minor subset of T-cells in the GI tract and liver
  • dendritic cells, subset
  • rare circulating B cells
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24
Q

What neoplasms is CD103 expressed in ?

A
  • 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
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25
Q

What other tumors may express CD103?

A
  • BPDCN, subset
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26
Q

What neoplasms are negative for

CD103 ?

A
  • MCL
  • FL
  • CLL
  • MZL
    • including splenic marginal zone lymphoma
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27
Q

What normal cells express CD79a ?

A
  • benign, B cells
    • this includes plasma cells which are essentially terminally differentiated B cells
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28
Q

What can pick up CD79a staining in a

non-specific manner in the BM ?

A
  • megakaryocytes
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29
Q

What neoplaasms are often positive for CD81 ?

A
  • mature B cell proliferations
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30
Q

What normal cells and neoplasms

is CD71 positive in?

A
  • early erythroid precursors
  • pure erythroid leukemia
  • AML
  • B-ALL subset
  • T-ALL subset
  • High grade B and T cell lymphomas
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31
Q

What benign cells express CD71 (transferrin receptor)?

A
  • 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+)
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32
Q

What is the normal function of CD71 ?

A
  • it is the transferrin receptor
  • it mediates the uptake of transferrin-iron complexes
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33
Q

What normal cells express CD71 ?

A
  • strongly positive in erythroid precursors
  • myocytes
  • hepatocytes
  • endocrine pancreas cells
  • spermatocytes
  • basal keratinocytes
  • placental syncitiotropholblasts
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34
Q

How is the expression of CD71 compared to glycophorin A?-

A
  • CD71 is positive in early precursors while negative on mature red blood cells
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35
Q

What is the expression pattern of CD71

in erythroid precursors ?

A
  • 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
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36
Q

How does the intensity of CD71 vary

amongst lymphomas?

A
  • 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
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37
Q

What is the expression of CD71

in the BM and why ?

A
  • 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
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38
Q

CD71 is expressed more inT-ALL or B-ALL?

A
  • usually more common in T-ALL
  • also IMP
    • ATLL shows some expression
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39
Q

What can CD71 be a surrogate marker

for by flow cytometry ?

A
  • it can be a surrogate for Ki67
  • or a proliferation marker
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40
Q

How is CD71 expression affected in dysplasia?

A
  • The expression of CD71 is decreased in dysplastic erythroid precursors
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41
Q

In bone marrow specimens how is CD71 expressed?

A
  • CD71 expression is restricted to the erythroid lineage

Note: myeloblasts, neoplastic plasma cells and metastatic carcinoma cells are usually negative.

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42
Q

What is CD64 expressed in ?

A
  • 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
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43
Q

What is different about the expression of

CD64 in acute monocytic leukemias vs. others ?

A
  • CD64 is brighter
  • in other AMLs the expression is dim or partial
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44
Q

What is CD61 expression seen in?

A
  • megakaryocytes
  • Acute megakaryoblastic leukemia
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45
Q

What is CD57 expression seen in?

A
  • 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
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46
Q

Where are the CD57+ T cells

in NLPHL ?

A
  • they form characteristic rosettes around the large neoplastic cells
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47
Q

What non-hematopoietic tumors can express CD57?

A
  • Primitive Neuroectodermal Tumor (PNET)
  • Rhabdomyosarcoma
  • Small cell carcinoma
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48
Q

What is CD56 and what cells typically express it ?

A
  • neural cell adhesion molecule (N-CAM)
  • expressed by natural killer cells, subsets of T cells, and monocytes
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49
Q

When can CD56 expression be unregulated?

A
  • subsets of granulocytes and monocytes from patients with MDS, MPNs and mixed MDS/MPN (such as CMML)
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50
Q

What non-leukemic, hematolymphoid

neoplasms express CD56?

A
  • 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
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51
Q

What leukemia’s often express CD56 ?

A
  • 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

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52
Q

In what neoplasms is CD56 been associated

with a poor risk factor ?

A
  • AML with t(8;21) and t(15;17)
    • in t(8;21) associated with significantly shorter complete remission duration and survival
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53
Q

What non-hematopoietic neoplasms can express CD56?

A
  • Small cell carcinoma
  • Carcinoma with NE differentiation
  • Malignant melanoma
  • Neuroblastoma
  • Wilms Tumor
  • Rhabdomyosarcoma
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54
Q

What benign cells express CD19?

A
  • Hematogones
  • B- cells
  • Plasma cells (variable, often dim or partial expression)
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55
Q

What neoplastic B cell lymphoproliferations express CD19?

A
  • Majority of mature B cell LPDs
  • PCM, rare cases
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56
Q

What neoplastic B cell lymphoproliferations are often negative for CD19?

A
  • PEL
  • ALK + Large B cell lymphoma
  • Plasmablast lymphoma
  • Subset of PTLD
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57
Q

What other tumors are positive for CD19?

A
  • 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
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58
Q

What type of molecule is CD19?

A
  • integral membrane protein
  • expression is limited to B cells and follicular dendritic cells
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59
Q

What is the possible function of CD20?

A
  • poorly understood
  • been implicated in B cell activation, regulation of B cell growth and regulation of transmembrane calcium flux
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60
Q

What cells is CD20 typically expressed on normally?

A
  • B cells
  • Germinal center cells show brighter expression than mantle zone cells
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61
Q

What B cell lymphoproliferative disorders often show CD20 expression?

A
  • CLL, dim expression
  • HCL and HCL-v
  • Majority of B cell lymphomas
  • PCM, minor subset
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62
Q

What T cell lymphoproliferations have been known to show CD20 expression?

A
  • 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
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63
Q

What other neoplastic conditions have shown aberrant CD20 expression?

A
  • B-ALL/LBL (rare cases, usually dim and or partial expression)
  • NLPHL
  • Hodgkin Lymphoma, minor subset
  • Thymoma, Type A (spindle, medullary subset)
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64
Q

What B cell lymphomas are notably negative for CD20?

A
  • PBL
  • PEL
  • DLBCL associated with chronic inflammation
  • ALK positive large B cell lymphoma
  • DLBCL, rare cases
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65
Q

What is CD22 positive in ?

A
  • CD22 is a B cell specific marker
  • Plasma cells are CD22 negative
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66
Q

What cells is CD22 positive in ?

A
  • B-cells
  • Basophils, subset
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67
Q

What B cell lymphoproliferatie disorders is CD22 positive in ?

A

-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+

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68
Q

What acute leukemia’s can express CD22 ?

A
  • B-ALL/LBL - cytoplasmic expression of CD22
  • MPAL; AML and B-ALL
  • Acute basophilic leukemia, subset
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69
Q

What other tumors can express CD22 ?

A
  • Basophils in CML and AMLs with basophilic differentiation, they may also show CD13 and CD25 expression
  • Mast cell neoplasms
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70
Q

What neoplasms are notably negative for CD22 ?

A
  • CLL
  • Plasma cell neoplasms
    • BUT clonal plasma cell components of LPL may be CD22+
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71
Q

What cells is CD23 normally positive in?

A
  • benign B cells of the blood, mantle zone and germinal centers of lymph node and tonsil
  • subset of plasma cells
  • follicular dendritic cells
  • subset of activated T cells
  • subset of activated monocytes
72
Q

What B cell lymphoproliferations are positive for CD23 ?

A
  • CLL, strong expression
  • Follicular lymphoma, minor subset but particularly seen in the diffuse variant
  • MZL, very rare cases
  • B-PLL, rare cases
  • LPL, rare cases
  • HCL, rare cases
  • DLBCL, rare cases
  • PMBL, subset of cells
  • MCL, very rare cases
  • PCM, very rare cases
73
Q

What acute leukemias may show CD23 expression ?

A
  • Acute monoblastic leukemia, subset
74
Q

What myeloid tumors may show CD23 expression ?

A
  • CMML, minor subset
75
Q

What other tumors may show CD23 expression?

A
  • Follicular dendritic cell tumors
76
Q

Can MCL express CD23?

A
  • most are CD23 negative
  • subset of MCL may be dim for CD23
77
Q

What B cell lymphoproliferations are negative for CD23 ?

A
  • MCL
  • BL
  • HCL
  • majority of DLBCL
  • majority of nodal and splenic MZL
78
Q

What other cells may express CD23 ?

A
  • benign plasma cells
  • subset of plasma cells
79
Q

What type of protein is CD24?

A
  • it is a GPI linked protein also known as heat stable antigen (HSA)
80
Q

What cells normally express CD24?

A
  • surface of B cells (but not plasma cells)
  • granulocytes
  • follicular dendritic cells
  • epithelial cells
81
Q

What diagnosis is CD24 typically used in a flow cytometry panel for?

A
  • diagnosis of PNH
82
Q

What lymphoproliferations can express CD24?

A
  • B-ALL
  • majority of mature B cell LPDs
    • HCL, MZL
    • subset of DLBCL are usually negative or show dim expression
83
Q

What type of protein is CD25 ?

A

-interleukin 2 receptor

84
Q

What neoplasms are negative for CD25?

A
  • AITL
  • HSTL
  • T-PLL
  • T-LGLL
  • HCL-v
85
Q

The presence of CD25 expression by an AML is generally associated with what molecular findings?

A
  • FLT3-ITD
  • DNMT3A
  • NPM1
86
Q

What benign cells often express CD25 ?

A
  • T-cells, subset
  • NK cells
  • B-cells, minor subset (dim expression)
  • Basophils
87
Q

What B cell lymphoproliferations express CD25?

A
  • HCL (not HCL-v)
  • CLL, rare cases
  • B-ALL, subset
  • Follicular lymphoma, rare cases
  • Splenic marginal zone lymphoma, subset
    -B- cell lymphoma subsets (MCLs and splenic red pulp B cell lymphoma are CD25 (-))
88
Q

What T cell lymphoproliferations are positive for CD25?

A
  • ATLL, strong expression (100% of cases)
  • ALCL, subset
  • MF, subset
  • PTCL, subset
  • Follicular T cell lymphoma, subset
  • ENKTL, majority of cases
89
Q

Which acute leukemias can express CD25 ?

A
  • AML, minor subset
  • B-ALL, subset
  • T-ALL, rare cases
90
Q

What myeloid tumors can express CD25?

A
  • Chronic eosinophilic leukemia, subset
  • CML in blast crisis, subset
91
Q

What other tumors can express CD25?

A
  • systemic mastocytosis (benign mast cells should be CD25-)
  • langerhans cell histiocytosis (LCH)
92
Q

What type of protein is CD26?

A
  • type II membrane protein, which is expressed on the membrane of mature thymocytes
93
Q

What other normal cells can express CD26?

A
  • T lymphocytes (upregulated upon activation)
  • B cells
  • NK cells
  • MacrophagesI
94
Q

In what situations is the evaluation of CD26 particularly useful?

A
  • patient’s with MF
  • there is a loss of CD26 in ~92% of cases of transformed MF
95
Q

In what neoplasms is CD26 negative?

A
  • circulating neoplastic T cells from patient’s with MF (Sezary Syndrome)
  • ATLL
96
Q

What benign cells show expression of CD27?

A
  • T-cells, subset
  • NK cells
  • B-cells (memory)
  • Thymocytes
  • Plasma cells
97
Q

What B cell lymphoproliferations express CD27?

A
  • CLL
  • B-APLL
  • FL
  • LPL
  • SMZL
  • Nodal marginal zone lymphoma
  • DLBCL
  • BL
  • MGUS ( CD27 is positive only in rare PCMs)
98
Q

What T cell lymphoproliferations express CD27?

A
  • Sezary syndrome (SS), subset (MF is negative!)
  • PTCL, minor subset
  • Follicular T cell lymphoma, subset
  • AITL, subset
99
Q

What benign cells express CD30?

A
  • activated B and T cells with immunoblast morphology
  • Atypical cells (immunoblasts) in EBV lymphadenitis or Kikuchi lymphadenopathy
100
Q

What B cell lymphoproliferations can express CD30 ?

A
  • DLBCL, subset
  • PEL - most cases
  • FL, rare cases
  • Primary mediastinal large B cell lymphoma (PMBL)
  • Lymphomatoid granulomatosis (LyG)
  • PCM, rare cases
101
Q

What neoplasms generally have 100% expression of CD30?

A

-CHL
- ALCL
- PEL
- Pagetoid reticulosis (variant of MF)
- MF with large cell transformation

102
Q

CD30 expression can help classify T cell lymphomas. What T cell lymphomas in general have strong and uniform expression of CD30?

A
  • ALCL (ALK + and - )
  • ATLL (large cells, subset of cells in acute form of ATLL)
  • Primary cutaneous ALCL
  • Breast-implant associated ALCL
  • MF with large cell transformation
  • rare cases of PTCL, NOS
  • ENKTL
103
Q

What T cell lymphomas have focal, variable and weak expression of CD30?

A
  • AITL
  • subset of PTCL, EATL, ENKTL, and MEITL
104
Q

What other tumors can express CD30?

A
  • subset of AML
    *often associated with FLT3-ITD, high leukocytosis and high risk disease
  • CHL
  • Aggressive systemic mastocytosis (benign mast cells are CD30 negative)
105
Q

Approximately what percentage of DLBCL express CD30?

A
  • 14-21% express CD30
  • often associated with a unique gene expression profile
  • generally non-GC subtype
  • have a favorable prognosis
106
Q

What is the recommendation for reporting of CD30 ?

A
  • intensity of staining(1-3+)
  • percentage of tumor cells with membranous or Golgi staining (>1% or <1%)
  • this is due to the availability of anti-CD30 medications
107
Q

What normal cells are positive for CD34?

A
  • it is a marker of immaturity (myeloid and lymphoid)
  • hematogones
  • myeloblasts
  • immature megakaryocytes
  • mast cell progenitors
108
Q

What types of AML’s are typically negative for CD34?

A
  • classic hyper granular APL
  • monocytic leukemias
  • AML’s with NPM1 mutation

Note: hypo granular APL is often CD34 positive

109
Q

What other leukemias are CD34 positive ?

A
  • B-ALL
  • T-ALL
  • MPAL

Note: BPDCN’s are negative for CD34

110
Q

What other marker is positive in leukemias that are NPM1 negative but FLT3-ITD positive?

A
  • CD34+
  • also TdT+
111
Q

What is the normal number and distribution of CD34+ blasts in the bone marrow?

A
  • normal bone marrow has < 2% blasts
  • they are typically scattered individually without forming significant clusters
112
Q

In myeloid neoplasms, what abnormal marker expression of CD34+ blasts can be helpful in diagnosing an abnormality by flow cytometry?

A
  • CD117 (-)
  • CD123 +
  • down regulation of CD13, CD33, or CD45
  • aberrant expression of CD7 or CD56
113
Q

What markers may be helpful in fibrotic marrows to differentiate myeloblasts, hematogones, mast cells, immature basophils, immature erythroid cells and plasma cells?

A
  • CD34, CD117, Pax5, MUM1, CD71, and tryptase
  • Myeloblasts: CD34 +, CD117 +
  • Hematogones: CD34+, Pax5+
  • Mast cells: CD117+, Tryptase +
  • Immature basophils: Tryptase +, CD34 (-), CD117 (-)
  • Immature erythroid precursors: CD117+, CD71+, CD34(-)
  • Plasma cells: CD117+, MUM1+
114
Q

What are some non-hematopoietic tumors that are CD34 positive?

A
  • vascular tumors
  • Kaposi’s sarcoma
  • DFSP
  • GIST
  • other soft tissue tumors
115
Q

What type of marker is CD36?

A
  • glycoprotein IV
  • monocytic marker similar to CD14
  • expressed in mature monocytes
116
Q

What disease processes can CD36 be positive in?

A
  • BPDCN
  • Monocytic leukemias

Note: in acute monoblastic leukemia, CD36 is more often positive than CD14

  • only a minor subset of AMLs with/or without maturation may show aberrant CD36 expression
117
Q

What is the expression of CD36 in APL and Acute megakaryoblastic leukemia ?

A
  • APL: negative
  • Megakaryoblastic: usually positive and seen in cases associated with Trisomy 21
118
Q

What benign cells express CD38?

A
  • plasma cells
  • activated (stimulated ) B and T cells
  • Thymocytes
  • Hematogones
  • Neutrophils and maturing myeloid precursors
  • Eosinophils
  • Basophils
  • NK cells
  • classic monocytes (CD14 bright/ CD16 -)
119
Q

What normal cells show bright/strong CD38 expression?

A
  • high in B cell precursors and terminally differentiated plasma cells

Note: expression is low to absent in mature B cells

120
Q

What is the typical expression of CD38 in AML’s?

A
  • often positive (dim to moderate)
121
Q

What mature neoplasms have bright CD38 expression?

A
  • T cell neoplasms, esp ALCL or PTCL
  • High grade B cell lymphomas
    *Double hit, NOS, etc
    -Burkitt Lymphoma
  • subset of Hairy cell leukemia

Note: generally MYC translocated B cell lymphomas have bright CD38

122
Q

Why is CD38 evaluated in CLL and what is it’s significance?

A
  • based on the number of clonal cells expressing CD38 CLL can be divided into two categories
  • CLL >30% positive CD38
  • CLL <30% positive CD38
  • > 30% CD38 positive = unmutated IGHV
  • <30% CD38 positive = mutated IGHV
123
Q

The level of expression of CD38 in CLL correlates with clinical stage, response to treatment and overall survival. What does higher CD38 expression typically indicate/morphologically show?

A
  • > 30% = unmutated IGHV
  • more advanced stage
  • diffuse bone marrow involvement
  • atypical morphology
  • deletion 11q
  • trisomy 12
  • poorer chemosensitivity
  • significantly shorter overall survival
124
Q

What is important to remember about CD38 expression in patient’s with CLL?

A
  • in ~30% of patients the levels of CD38 expression and IGHV mutational status are discordant.
125
Q

What is important to remember regarding CD38 treatment in plasma cell myeloma?

A
  • anti-CD38 (Daratumumab) may cause a loss of CD38 expression plasma cells
  • other markers should be used to evaluate neoplastic plasma cells
126
Q

What B cell lymphoproliferations express CD38?

A
  • PCM, bright expression
  • CLL, subset
  • MCL, major subset
  • DLBCL, subset
  • FL, subset
  • HCL, minor subset
  • PEL
  • DLBCL, associated with chronic inflammation
  • PBL
  • ALK+ Large B cell lymphoma
  • BL
  • LPL
  • HGBCL
  • MZL, subset
127
Q

What T cell lymphoproliferations are positive for CD38?

A
  • ALCL, subset [ALK+ is ofte negative]
  • PTCL
  • ATLL, acute variant [chronic variant is negative]
  • T-PLL, subset
    -HTSL, subset
    -T-LGLL, majority
  • AITL, majority
  • ENKTL, majority
128
Q

What acute leukemias can express CD38?

A
  • AML, majority
  • B-ALL, majority
  • T-ALL, all cases
129
Q

What other myeloid tumors may express CD38?

A
  • Blasts and myeloid cells in MDS, MPN and mixed MDS/MPN
130
Q

What other tumors can express CD38?

A
  • BPDCN, subset
131
Q

In what setting is the expression of CD43 useful?

A
  • CD43 is NOT a lineage specific marker
  • it is present on a wide range of both benign and neoplastic hematopoietic cells
  • BUT it can be useful in cases of poorly differentiated or anaplastic neoplasms in demonstrating whether they are hematopoietic or non-hematopoietic in origin
    *rarely expressed by non-heme tumors
132
Q

Most benign B cells are NEGATIVE for CD43 except in what location in the body?

A
  • Benign B cells in the terminal ileum may show expression of CD43
133
Q

In what subset of ALCL can CD43 be helpful?

A
  • ALCL (null cell type)
  • CD43 may be the only expressed marker aside from CD30 and ALK
134
Q

What benign cells may express CD43?

A
  • T cells
  • NK cells
  • Neutrophils
  • Eosinophils
  • Basophils
  • Mast cells
  • Monocytes
  • Hematogones
  • Erythroblasts/Pronormoblasts
  • B cells, minor subset (<10%)
135
Q

What B cell lymphoproliferations are POSITIVE for CD43?

A
  • BL
  • MCL
  • CLL
  • MZL, subset
  • DLBCL, minor subset
  • Primary cutaneous DLBCL, leg type
  • ALK+ large B cell lymphoma, rare cases
  • PCM
  • LPL, rare cases
  • HCL, subset BUT HCL-v is CD43 negative
136
Q

What T/NK cell lymphoproliferations are positive for CD43?

A
  • Mature (peripheral) T-cell and NK-cell lymphomas
137
Q

What acute leukemias may be positive for CD43?

A
  • AML
  • B-ALL
  • T-ALL
138
Q

What myeloid tumors may be positive for CD43?

A
  • Blasts and myeloid cells in MDS, MPN and mixed MDS/MPN
139
Q

What other hematopoietic tumors may be positive for CD43?

A
  • BPDCN, subset
  • Langerhans cell sarcoma
140
Q

CD45 is known as the leukocyte common antigen and is expressed on the majority of hematopoietic cells with the exception of which two?

A
  • maturing megakaryocytes
  • erythroid cells
141
Q

Which cells have the lowest expression of CD45?

A
  • lower on blasts and immature forms
142
Q

Which cells have the highest expression of CD45?

A
  • maturę myelomonocytic cells and lymphocytes
143
Q

What neoplasms are notably NEGATIVE for CD45?

A
  • PCM
  • Classic HL (R-S and H-S cells)
  • Acute erythroid leukemia
  • B-ALL/LBL, subset
  • PBL
  • Rare cases of ALCL and other mature T cell neoplasms
  • AML, rare cases
  • DLBCL, rare cases
  • T-PLL, subset
  • Dendritic cell sarcoma
144
Q

What normal cells express CD49d?

A
  • B and T cells
  • thymocytes
  • langerhan cells
  • eosinophils
  • monocytes
145
Q

In what neoplasm is CD49d emerging as a prognostic marker?

A
  • one of the most valuable markers in CLL/SLL for prognostics
  • Considered positive if >30% of cells express it
  • ~40-60% of CLL cases express this marker
  • Detection of CD49d is superior to CD38 and ZAP-70 in predicting overall and treatment-free survival
146
Q

What are high levels of expression of CD49d associated with in CLL?

A
  • shorter time from diagnosis to treatment and overall survival
  • prognostic value of CD49d is independent of other prognostic parameters including FISH and IGVH, positive CD38, and ZAP70 expression
147
Q

In what setting would you see lower expression of CD49d in CLL?

A
  • patients with a deletion of 11q
148
Q

In what setting would you see higher expression of CD49d in CLL?

A
  • patients with trisomy 12
149
Q

What is the medication name for Alemtuzumab and what antibody does it target?

A
  • Campath
  • targets CD52
150
Q

What is the mechanism of action of Campath?

A
  • antibody-dependent cell mediated cellular toxicity leading to complement activation and apoptosis
151
Q

What cells express CD52?

A
  • normal and malignant T cells
  • majority of B lymphoproliferations
152
Q

In what setting has Campath been used for treatment?

A
  • CLL
  • T-PLL
  • low-grade Non- Hodgkin Lymphomas
153
Q

What normal cells typically express CD65?

A
  • Neutrophils
  • Eosinophils
  • Basophils
  • Monocytes, subset
  • NK cells, minor subset
154
Q

What acute leukemias are known to express CD65?

A
  • AML, subset
  • Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), subset
155
Q

What type of marker is CD79?

A
  • it is a B cell marker which can be detected on the B cell surface or intracytoplasmic
156
Q

What benign cells express CD79?

A
  • B cells
  • Hematogones
157
Q

What B cell proliferations are positive for CD79?

A
  • Majority of mature B cell lymphoproliferative disorders (CLL, PEL, and PBL)
    *for both CD79a and CD79b
158
Q

B-ALL typically expresses which isoform of CD79?

A
  • CD79a
  • CD79b is variably expressed with a subset of cases being negative
159
Q

What is the difference in CD79 expression in CLL and MCL?

A
  • CLL: CD79b negative
  • MCL: CD79b positive
160
Q

What benign cells express CD81 ?

A
  • Hematogones (bright expression)
  • Plasma cells
  • Myeloblasts
  • B-cells
  • T-cells
  • NK cells
  • Mast cells
  • Dendritic cells
161
Q

What role does CD81 play ?

A
  • CD81 is critical for B cell development and the humoral response
  • interacts with CD19 in B cell development
162
Q

How is CD81 helpful in the evaluation of B-ALL?

A
  • CD81 is usually dimly expressed in B-ALL, which helps with the differential diagnosis with hematogones (brightly positive for CD81)
163
Q

How is CD81 helpful in the evaluation of plasma cell myeloma?

A
  • benign plasma cells show bright expression of CD81
  • most malignant plasma cells show either dim or negative CD81

IMP: expression of CD81 by PCM is a poor prognostic indicator

164
Q

What is CD81 expression in BL?

A
  • BL shows bright positive expression of CD81
165
Q

What is CD81 expression in FL and DLBCL?

A
  • dimmer expression of CD81 as compared to BL
166
Q

What is the expression of CD81 in CLL and MCL?

A
  • CLL is negative to partially dim
  • MCL is positive
167
Q

What is the expression of CD81 in HCL and HCL-v?

A
  • Both HCL and HCL-v are CD81 positive
  • BUT
    *HCL-v has brighter CD81 expression
168
Q

What is unique about CD133?

A
  • it is a primitive cell antigen that has been shown to be a more specific marker of hematopoietic stem cells as compared to CD34
169
Q

What benign cells express CD133?

A
  • Myeloblasts
170
Q

What malignancies express CD133?

A
  • AML, subset
  • Blasts in MDS and CMML may be CD133+
171
Q

In AML the expression of CD133 has been also shown to be correlated with the expression of what other markers?

A
  • HLA-DR
  • CD3
  • CD7
  • TDT
  • CD13
  • CD34
172
Q

What is the expression of CD138 in plasma cell neoplasms compared to normal plasma cells?

A
  • the expression of CD138 in plasma cell neoplasms is often dimmer than in benign plasma cells when analyzed by FC
173
Q

What B cell lymphoproliferations can express CD138?

A
  • PCM
  • ALK+ large B cell lymphoma
  • PBL
  • DLBCL, subset
  • PEL
174
Q

What is CD157 a marker of and what disease process can it be seen in?

A
  • GPI-linked protein expressed on neutrophils and monocytes
  • used in panels to evaluate for PNH
175
Q
A