T- cell lymphoproliferative disorders

Question 1

What immunophenotype do cortical T thymocytes have?

Answer 1

• cytoCD3+, CD5+, CD7+, CD4+, CD8+, TdT+, CD1a+

Question 2

What immunophenotypic features are associated with gamma delta T cell lymphoma?

Answer 2

• Lack of expression of CD4, CD8 and CD5

Question 3

What immunophenotypic features are associated with the follicular helper T cell subset?

Answer 3

• CD4+, CD10+, BCL-6+, CD57+ , CXCR5+, PD-1+

- Secrete CXCL13 (receptor= CXCR5), IL4 and IL21

Question 4

What T cell disorders can be CD4+ and CD8+

Answer 4

• Cortical thymocyte T-ALL

- T-PLL

Question 5

What T cell disorders can be CD4- and CD8-

Answer 5

• Hepatosplenic T cell lymphoma
• EATL
• Some anaplastic T cell lymphomas
• (NK lymphoma/ leukaemia)

Question 6

Expression of what two genes has been proposed as being important in the delineation of different subtypes of peripheral T cell lymphoma NOS

Answer 6

1) GATA3 (Th2 cells, worse prognosis, more monotonous/ sheet-like)
2) TBX21/ T-BET (Th1, better prognosis, more heterogenous with an inflammatory background)

Question 7

What is the “null-cell phenotype” in anaplastic T cell lymphoma and how can it be distinguished from HL?

Answer 7

• Refers to the loss of the pan T cell antigens
• Can be difficult to distinguish from HL as both are CD30+
• In anaplastic T cell lymphoma: CD15 usually -ve, PAX5-, EBV-. May be ALK+. Granzyme and TIA positive.
• In Hodgkin’s: LMP1 positive

Question 8

What are the four histological subtypes of anaplastic T cell lymphoma?

Answer 8

1) Common pattern
2) Lymphohistiocytic
3) Small cell pattern
4) Hodgkin-like

Question 9

What are the four subtypes of anaplastic T cell lymphoma

Answer 9

1) ALK+ (good prognosis)
2) DUSP22+ (good prognosis)
3) TP63+ (bad prognosis)
4) Triple negative (prognosis in between DUSP22 and TP63+)

Question 10

What are the morphological features of angioimmunoblastic T cell lymphoma?

Answer 10

• Polymorphous infiltrate with atypical T cells, plasma cells, histiocytes, eosinophils.
• T cells have T helper follicular phenotype with 2 or more of: CD10, CXCR5, CXCL13, ICOS, PD1
• Expanded FDC network
• Large B cells in the background that are CD20 and EBV +
• Arborising venules.

Question 11

What mutations/ gene fusions are seen in angioimmunoblastic T cell lymphoma?

Answer 11

• Mutations in TET2, DNMT3A, IDH2, RHOA, CD28

- Gene fusions in ITK-SYK, CTLA4- CD28

Question 12

What is the immunophenotype of T-LGL?

Answer 12

CD3+, CD8+, C16+, CD57+
Diminished expression of CD5 and/or CD7
TIA, granzyme B positive

Question 13

What genetic aberrations are typically seen in T-PLL?

Answer 13

• Overexpression of TCL1, caused by genetic rearrangements that bring the TCL1 gene under the control of the TRA
  
  • inv(14) in 80%, t(14;14) in 10%
• MTCP1 (a homologue of TCL1) is located on the X chromosme
  
  • t(X;14) in <10%

TCL1 and MTCP1 alterations enhance cell proliferation and survival through activation of a tyrosine kinase.

Question 14

What is the definition of blood involvement in sezary syndrome?

Answer 14

• Presence of an absolute Sézary cell count of greater than 1000/µL,
• CD4:CD8 ratio greater than or equal to 10 due to CD4 cell expansion
• Loss of one or more T-cell antigens (>30% of T-cells with CD4+/CD7– phenotype or >40% of T cells with a CD4+/CD26–phenotype)

Question 15

What are the immunophenotypic features of sezary cells?

Answer 15

• CD3+, CD5+ and CD4+, typically without expression of CD7 or CD26.
• PD1+
• Loss of CD2 in ~25% of cases.