short lecture about T-cell and NK-cell neoplsms

1. T-cell and NK-cell
neoplasms
Dr
Abdullah A.Hashish

2. Pre-test.
• What is the role of stem cell differentiation stage in
the lymphoid classification? Give examples?
• True or False:
– Hodgkin lymphomas are derived from neoplastic T-cell.
– B-cell leukemias/lymphomas are more aggressive than T-
cell leukemias/ lymphomas.
– NK-cell lymphomas are more aggressive than B-cell
lymphomas.
• Short account about Sezary syndrome.

3. Post-natal lymphopoiesis in human

6. NK cells
• NK cells are defined as:
1. cytotoxic cells.
2. with the predominant morphology of large granular
lymphocytes (LGLs).
3. neither productively rearrange any of the genes
encoding the T-cell receptor (TCR) chains
4. nor express on their surface the CD3-TCR complex
5. express the CD56 (N-CAM), CD335 (NKp46), and CD16
(FcγRIIIA), antigens in humans.
6. can kill cells not expressing major histocompatibility
complex (MHC) class I or class II antigens.

7. Morphology of NK cells
• Size of LGLs: medium- to large.
• Nucleus: round or indented.
• Chromatin: condensed.
• Nucleoli: usually prominent.
• Cytoplasm: abundant and contains a variety of
organelles and granules.
• many NK cells have the morphology typical of LGL, a
significant proportion of NK cells are agranular and
indistinguishable from other lymphocytes.6

8. T-cell neoplsms
1.Immature.
1.Lymphoblastic
leukemia/lymphoma.
2.Mature.
– Different subtypes.

9. T-cell lymphoblastic
leukemia/lymphoma
•Morphology:
–Size: Medium to large cells.
–Chromatin: finely stippled.
–Cytoplasm: scanty.

10. T-cell lymphoblastic
leukemia/lymphoma
• Immunophenotyping:
– TdT+,
– cytoplasmic CD3+,
– CD7+,
– CD34+/-, CD2+/-CD1a+/-, CD5+/-,
– CD4+/CD8+ or CD4-/CD8-
– CD10-/+.

11. T-cell lymphoblastic
leukemia/lymphoma
• Genotyping:
–Abnormalities in:
1. TCR loci at:
1. 14q11 (TCR-α),
2. 7q34 (TCR-β), or
3. 7p15 (TCR-γ),
2. t(1;14)(p32-34; q11) involving TAL1

12. Mature T and NK cell neoplasms
1. Leukemias:
1. T-cell prolymphocytic leukemia.
2. T-cell large granular lymphocytic leukemia.
2. Lymphomas/Lymphoproliferative
Disorders:
– Many subtypes.

13. T-cell prolymphocytic leukemia
• Morphology:
– Size: Small to medium.
– Cytoplams: cytoplasmic protrusions or blebs.
• Immunophenotyping:
– TdT-,
– CD2+, CD3+, CD5+, CD7+,
– CD4+ and CD8- is more common than CD4- and
CD8+, but can be CD4+ and CD8+

14. T-cell large granular lymphocytic
leukemia
• Morphology:
– Cytoplasm:
• Abundant.
• Sparse azurophilic granules
• Immunophenotyping:
– CD2+, CD3+, CD5+, CD7+,
– CD8+/-, CD16+/-, CD57+/-,
– CD4 -/+,
– CD56-.

15. Lymphomas/Lymphoproliferative
Disorders
• Extranodal T/NK-cell lymphoma, nasal
type “angiocentric lymphoma”
–Immunophenotyping:
• CD2+, cytoplasmic CD3+, CD7, CD56,CD4-,
CD8- & EBV+.
–Genotyping:
• TCR rearrangements usually NEGATIVE
• EBV present by in situ hybridization.

16. Lymphomas/Lymphoproliferative
Disorders
• Cutaneous T-cell lymphoma (mycosis fungoides):
– Morphology:
• Size: Small to large cells.
• cerebriform nuclei.
– Immunophenotyping:
• CD2+, CD3+, CD4+, CD5+, CD26+
• CD7+/-, CD8-, CD25-.

17. Lymphomas/Lymphoproliferative
Disorders
• Sezary syndrome:
–mostly typical as Cutaneous T-
cell lymphoma (mycosis
fungoides)

18. Lymphomas/Lymphoproliferative
Disorders
• Adult T-cell leukemia/lymphoma:
–Morphology:
•Highly pleomorphic with multilobed
nuclei.
–Immunophenotyping:
•CD2+, CD3+, CD5+, CD25+, CD7-,
•CD4+CD8- more often than CD4-CD8+

19. Lymphomas/Lymphoproliferative
Disorders
• Hepatosplenic T-cell lymphoma:
–Morphology:
• Size: Small to medium cells.
• Chromatin: condensed.
• round nuclei.
–Immunophenotyping:
• CD2+, CD3+, CD5+, CD7+/-
• CD4-, CD8+/-.

20. Lymphomas/Lymphoproliferative
Disorders
• Enteropathy associated T cell lymphoma:
–Morphology:
• Size: Medium to large cells.
• prominent nucleoli.
• Cytoplasm: abundant pale, invading mucosal
membranes of the small intestine.
–Immunophenotyping:
• CD3+, CD7+, CD 103+, CD30+ (most cases),
• CD8+/-, CD4-, CD5-, TCRβ+/-.

21. NATURAL KILLER (NK) CELL
NEOPLASMS
• Large granular lymphocytic leukemia.
• Aggressive NK-cell leukemia.
• Extranodal NK-cell lymphoma, nasal type “angiocentric
lymphoma”.
• Immunodeficiency-associated lymphoproliferative
disorders.
– Lymphoproliferative disorders associated with primary
immune disorders.
– Lymphomas associated with HIV infection.
• Post-transplant lymphoproliferative disorders (PTLDs).

22. NATURAL KILLER (NK) CELL
NEOPLASMS
• Large granular lymphocytic leukemia:
– Morphology:
• Cytoplasm: Abundant cytoplasm and sparse azurophilic
granules.
– immunophenotyping:
• TdT-, CD2+, CD 7+, CD11b+, CD16+, CD56+,
• CD3-, CD4-, CD5-/+, CD8-/+, CD57+/-.
– Genotyping: No TCR rearrangement
• Aggressive NK-cell leukemia (show the same but
EBV present).

23. NATURAL KILLER (NK) CELL
NEOPLASMS
• Extranodal NK-cell lymphoma, nasal
type “angiocentric lymphoma”
–Immunophenotyping:
•CD2+, cytoplasmic CD3ε +, CD 56, CD 7+
•CD4-, CD5-/+, CD8-.
–Genotyping:
•No TCR rearrangement, EBV present.

24. NATURAL KILLER (NK) CELL
NEOPLASMS
• Post-transplant lymphoproliferative
disorders (PTLDs):
–Early lesions: plasmacytic hyperplasia
(PH) and infectious mononucleosis
(IM)-like.
–Polymorphic PTLD.
–Monomorphic PTLD.

25. NATURAL KILLER (NK) CELL
NEOPLASMS

26. NATURAL KILLER (NK) CELL
NEOPLASMS

27. THANK
YOU