T cell LeukemiaLymphoma

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T cell Leukemia/Lymphoma

• T cell Lymphoblastic Lymphoma/Leukemia
• Post Thymic Leukemias/Lymphomas
• Prolvmphocytic leukemia/ T cell CLL
• Adult T cell leukemia/lymphoma
• Cutaneous T-cell leukemia/lymphoma
• Sezary Syndrome
• Mycosis Fungoides
• Peripheral T cell lymphoma
• Large granular lymphocytic (LGL)

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T cell Lymphoblastic Lymphoma/Leukemia

• Characteristics
• Patients tend to be young adults/adolescents
• 50-80 present with mediastinal mass (pre B
  -rarely)
• Peripheral blood involvement gt30 at presentation
• Rapidly progressive w/ dissemination to BM CSF.
  Poor prognosis
• Flow cytometry - excellent - since immature T
  cell phenotype (while a normal cellular
  phenotype) is not expected in the sample most
  commonly submitted (LN, PBL, CSF, pleural fluid).
  Difficult if thymus is specimen.

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Antigenic characteristics of T cell
lymphoblastic lymphoma/leukemia
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Case 1

• 11 year old male acute renal failure and
  mediastinal mass and lymphandenopathy
• Histology Diagnosis a) left cervical lymph
  node, biopsy T-cell lymphoblastic lymphoma (see
  note). b) mediastinal mass, biopsyT-cell
  lymphoblastic lymphoma (see note). Note Both
  specimens show sheets, clusters and strands of
  small, atypical cells infiltrating fibrofatty
  tissue. A touch prep shows morphology consistent
  with lymphoblasts.

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Case 1- Flow Cytometry
Marker Description Data CD3 Total T Cells (Pan
T) 95 CD5 Pan T Most IgCLL 99 CD20 B
Cells 0 CD19 B Cells 0 Kappa Surface
Kappa light chain 0 Lambda Surface Lambda light
chain 0 CD33 Monocyte, Myeloid progenitor,
Granulocytes 0 CD38 Thymocytes, NK, Activated T,
B Cell Subsets 99 HLA-DR HLA-DR 3 CD10 Calla-C
ommon Acute Lymphoblastic Leukemia
Ag 95 CD34 Human Progenitor Cell
Antigen 42 CD14 Monocytes/promonocytes 40
AML 0 CD45 Leukocytes 100 TDT Terminal
Deoxynucleotidyl transferase 94 CD4 Helper/Induce
r T Cells 25 CD8 Cytotoxic/Suppressor T
Cells 96 CD2 Total T Cells 97 CD1a Thymocytes
43 CD38CD34 Dual Marker 42 TDTCD10 Dual
Marker 91 CD4CD8 Dual Marker 25 CD2CD1a Du
al Marker 43
The patients tissue mass specimen demonstrates
the presence of small sized cells by light
scattering properties. These cells phenotype as T
cells which phenotype as CD3, CD2, some CD1a,
some CD34, CD38, CD5, CD10, TdT, and CD8. There
was no significant expression of DR, myeloid and
B cell markers. These results are consistant with
the diagnosis of a T cell lymphoblastic lymphoma,
however, these results must be viewed in light of
clinical presentation, history, and histology.
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Case 2

• History - 33 year old male with pleural effusion
• Cytology-Diagnosis Pleural fluid Lymphocytic
  effusion composed of small lymphocytes, some
  macrophages and mesothelial cells. Comment
  Patient has lymphoma on a recent biopsy. A
  specimen was sent to immunology for flow studies.
  Supplemental report Pleural fluid - flow
  analysis of the specimen shows cells consistent
  with lymphoblastic lymphoma.
  

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Case 2
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Case 2
The patients pleural fluid demonstrates the
presence of small to large cells by light
scattering properties. These cells phenotype as T
cells expressing CD2, CD1a, CD38, CD7, CD5,
CD10, dual express CD4 CD8, and TdT. Some CD3
was expressed. There was no significant
expression of DR, CD34, myeloid and B cell
markers. These results are consistant with the
diagnosis of a lymphoblastic lymphoma of T cell
common thymocyte origin.
Marker Description Data CD3 Total T Cells (Pan
T) 33 CD5 Pan T Most IgCLL 99 CD20 B
Cells 0 CD19 B Cells 0 Kappa Surface Kappa
light chain 0 Lambda Surface Lambda light
chain 0 CD38 Thymocytes, NK, Activated T, B
Subsets 100 HLA-DR HLA-DR 3 CD10 Calla 96 CD
34 Human Progenitor Cell Antigen 4 Glycophorin
A Erythroid 3 CD14 Monocytes/promonocytes 40
AML 1 CD45 Leukocytes 100 TDT Terminal
Deoxynucleotidyl transferase 96 CD4 Helper/Inducer
T Cells 98 CD8 Cytotoxic/Suppressor T
Cells 99 CD2 Total T Cells 100 CD7 Pan T,
T-ALL, NK cells 99 CD25 Anti-IL2 receptor
1 CD1a Thymocytes 99 CD4CD8 Dual
Marker 97 CD3CD1a Dual Marker 32 TDTCD10 Dua
l Marker 94 CD7CD38 Dual Marker 99
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Chronic T lineage Leukemias

• Characteristics
• Also referred to as post thymic leukemias
• Group of disorders with marked heterogeneity in
  clinical, morphologic, immunologic
  characteristics
• Most are clinically aggressive with a few
  exceptions
• Flow cytometry - Important, but not by itself
  diagnostic
• Eliminate B cell malignancy
• Highly suggestive with antigenic droupout or CD8
  phenotype
• Differentiate T cell LGL leukemia from NK LGL
  leukemia - great prognostic significance

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IMMUNOPHENOTYPIC CHARACTERISTICS OF CHRONIC
T-CELL LEUKEMIAS LGL Leukemias T-PLL
T-CLL ATLL CTLL T-LGL (CD3)
NK-LGL (CD3-) TdT - - -
- - - CD1 - - -
- - - CD2

CD3

- TcR-??

- TcR-?? - -
- - /-
- CD4/CD8-

- - CD4/CD8 /- /-
- - /- -
CD4-/CD8 /-
/- - -
/- CD4-/CD8- - - -
- - CD5

- CD7 S
/- /- CD16
- - - -
/-
CD56 - - - -
/- CD57 - -
- -
CD25 /- /- S
/- /- /- HLA-DR
- - /- /-
- lt10 are
positive LGL large granular lymphocytic s
strong antigen expression /- 10 to 25 are
positive T-PLL/T-CLL T-cell prolvmphocytic
leukemia/ T chronic LL 25 to 75 are positive
ATLL adult T cell leukemia/lymphoma
gt75 are positive CTLL cutaneous T-cell
leukemia/lymphoma
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Cutaneous T cell Lymphoma (CTCL)Characteristics

• CTCL is term often used to refer to Mycosis
  Fungoides and related entities. Should not be
  used in place of more specific description.
• Mycosis Fungoides (1806)
• Classically presents in the skin as flat patches
  that may evolve into infiltrated raised plaques
  and tumor nodules. Advanced disease may involve
  lymph nodes (40-70) and organs.
• May have a small number of circulating tumor
  cells at some time (lt5-10 of leukocytes, lt20 of
  lymphocytes - implications for diagnosis by Flow)

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Cutaneous T cell Lymphoma (CTCL)Characteristics
- continued

• Sezary Syndrome (1938)
• Erythroderma, lymphadenopathy (40-70) draining
  cutaneous sites, leukemic involvement of
  peripheral blood
• Extracutaneous involvement other than LN during
  life - rare by routine histopathology. 70-75
  visceral involvement at autopsy (spleenlungs
  liver)
• Adult T cell leukemia/lymphoma
• Often classified as large cell, immunoblastic
• Involvement of skin, blood, and lymph nodes can
  resemble MF/SS. However, aggressive clinically,
  often HTLV-I associated and CD25. MF/SS can be
  CD25.

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Cutaneous T cell Lymphoma (CTCL)Characteristics
- continued

• Peripheral T cell lymphoma
• Most are classified as large cell (including
  immunoblastic lymphomas mixed small and large
  cell lymphomas.
• Involves the skin as nodules rather than patches
  or plaques. Clinical course variable from
  aggressive to an indolent course
• Recent studies has demonstrated that CD30 cases
  had a favorable prognosis while CD30- cases were
  agressive
• T cell lymphoblastic lymphoma (rare)

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Antigenic Characteristics of CTCL

• Majority are post thymic T cell lymphomas (rarely
  B and immature T) - therefore mature T cell
  phenotype
• Majority are CD4 positive -
• Normally 21 CD4CD8 cell ratio. Reactive
  processes may be as high as 81. Depending on
  normal to tumor cell mix, must be able to
  differentiate between reactive process. Gene
  rearrangement studies may be needed
• Phenotypic dropouts are common - highly
  suggestive of clonality helpful in r/o of
  reactive processes

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Deficient Antigen Expression in T Cell
Lymphoproliferative Disorders Affecting the Skin
Diagnosis Immunophenotype
CD2 CD3 CD5 CD7 MF (cutaneous patches or plaques)
- MF (cutaneous
tumors) /- /- /- - MF (lymph
nodes) /- /- /- - SS (skin)
/- /- - SS
(blood) - ATL (lymph node,
skin) /- - PTL (lymph node, skin,
other) /- /- /- /- T-LBL (lymph node,
skin,other) /- /- lt 10, /-
11-49, - gt50
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Case 3

• 57 year old male - bone marrow
• HistologyDiagnosis bone marrow, biopsy and
  clot section The marrow is markedly
  hypercellular for age (about 98 cellularity.
  Almost all the cells are small lymphoid cells
  with clumped chromatin and irregular nuclear
  contours. Also present are numerous
  eosinophils and occasional histiocytes. Only
  rare hematopoietic precursors are seen. In a
  patient with a peripheral T-cell lymphoma, these
  findings are consistent with marrow involvement
  by that malignancy.

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Case 3 - 57yo male -bone marrow specimen
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Case 3
Dropout of CD7 CD3
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Case 4 46yo male - lymph tissue -PTL CD7 dropout
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Case 5

• History - 53yo male - lymphadenopathy with lymph
  node biopsy Diagnosis right inguinal lymph
  node, biopsy - lymphoid hyperplasia and fatty
  involution (see note)Note a subcapsular
  monocytoid B-cell hyperplasia is present.
  Sinuses remain patent, some follicular
  hyperplasia is seen, and the main process
  affecting the node is fatty involution. Flow
  cytometry of fresh tissue submitted from Mather
  hospital shows a small population of polytypic
  B-cells and a majority population of T-cells with
  an increased CD4/CD8 ratio. Diagnostic features
  of lymphoma are not seen.

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Case 5 53yo male - lymph tissue specimen
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Case 5
Polyclonal B cells
Increased CD4/CD8 ratio. No dropouts. However,
based on histology
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Case 6

• History - 73 year old female - peripheral blood
  lymphocytosis with bone marrow involvement-

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Case 6 - no dropouts - atypical T- PLL/CLL
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Conclusions

• Flow Cytometry is an important stand alone
  technology and a secondary consultative resource
  to other standard technologies
• Flow Cytometry has proven to be a widely used
  diagnostic technology that will continue to
  expand even in todays health care environment