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Mature lymphoproliferative (3): Mature T-cell Neoplasms and Hodgkin lymphoma

Dr. Douaa Mohammed Sayed

T Cell Lymphomas

Translocations often involve T cell receptor genes

- and chain genes on 14q11-14 - chain gene on 14q34-36 - chain gene on 7p15

Several other oncogenes

Ttg1, LylI, HOX 11 Transcription factor families

T-PLL

·An aggressive rare type. ·Proliferation of small to medium sized prolymphocytes. ·Involving Pb, BM, LN, liver, spleen and skin. ·Genetics: inv 14q(q11;q32), t(14;14)(q11;q32), trisomy 8q, t(8;8)(p11-12;q12).

T-PLL

Marker

CD2/CD5 mCD3 CD7 CD4 CD8 CD25

T-PLL

++ + ++ ++ + -/+

LGL-leukemia

·Synonyms -T-cell CLL

-T-lymphoproliferative disorder -Proliferation of large granular lymphocytes -LGL leukemia ·An indolent course ·No unique karyotypic abnormality

LGL-L

Marker CD2/CD5 mCD3 CD7 CD4 CD8 CD25 LGL-L

++ ++ + -/+ ++ neg

Aggressive NK-cell leukemia

Systemic proliferation of NK cells. Aggressive rare clinical course. Involved Pb, BM, liver and spleen. Might represent the leukemic counter part of extranodal NK/T-cell lymphoma Circulating leukemic cells are slightly larger than normal large granular lymphocytes(NK) BM shows massive or focal infiltration by neoplastic cells and there can be reactive histiocytes with hemophagocytosis. Immunophenotyping: CD2+,CD3-, CD56+, CD57

ATLL

·A peripheral T-cell neoplasm composed of highly pleomorphic lymphoid cells. ·Caused by human retrovirus (HTLV-1). ·Endemic in several regions, in particular Japan. ·The neoplastic cells are often polylobated (flower cells) in Pb. ·Giant cells with convoluted or cerebriform nuclear contours may be present. ·Marrow infiltrates are patchy. ·Osteocastic activity may be prominent. ·There are acute, lymphomatous, chronic and smoldering clinical variants.

ATLL

Marker

CD2/CD5 mCD3 CD7 CD4 CD8 CD25

ATLL

++ + -/+ ++ neg ++

Sezary Syndrome

Marker

CD2/CD5 mCD3 CD7 CD4 CD8 CD25

SS ++ ++ + ++ neg -/+

Sezary Syndrome

·A generalised mature T-cell lymphoma characterised by presence of erythroderma, lymphadenopathy and neoplastic T-lymphocytes in Pb. ·The neoplastic T-cellshave cerebriform nuclei. ·The disease is as a variant of mycosis fungoides. ·The association with HTLV-1 is controversial.

Angioimmunoblastic T-cell lymphoma

Systemic disease, a polymorphous infiltrate involving LN , with a prominent proliferation of HEV and FDC. BM is commonly involved upon biopsy

Anaplastic large cell lymphoma

ALCL is a T-cell lymphoma and typically associates with the t(2;5)(p23;q35), which involves the fusion of nuclephosmin (NPM) gene on 5q35 to a novel anaplastic lymphoma kinase (ALK) on 2p23.

The NPM and ALK genes are fused to form a chimeric transcript. Two distinct oncogenic effects are thought to be caused by the t(2;5): First, the ALK gene, which is not physiologically expressed in normal T lymphocytes, undergoes expression; because of its juxtaposition to the promoter sequences of NPM, which are physiologically expressed in T cells.

Second, based on the activation model of other tyrosine kinase oncogenes, one would predict that the truncated ALK constitutively phosphorylates intracellular targets to trigger malignant transformation.

ALCL

Variable proportion of cells with eccentric, horseshoe- or kidneyshaped nuclei, often with an eosinophilic region near the nucleus. Positive CD30 DD: HL

Algorithm for using special techniques in lymphoma diagnosis

Epidemiology of lymphomas

5th most frequently diagnosed cancer overall for both males and females males > females incidence

NHL increasing over time Hodgkin lymphoma stable

Risk factors for NHL

immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation

Clinical manifestations

Variable

severity: asymptomatic to extremely ill time course: evolution over weeks, months, or years

Systemic manifestations

fever, night sweats, weight loss, anorexia, pruritis

Local manifestations

lymphadenopathy, splenomegaly most common any tissue potentially can be infiltrated

Complications of lymphoma

bone marrow failure (infiltration) CNS infiltration immune hemolysis or thrombocytopenia compression of structures (eg spinal cord, ureters) by bulky disease pleural/pericardial effusions, ascites

Diagnosis requires an adequate biopsy

Diagnosis should be biopsy-proven before treatment is initiated Need enough tissue to assess cells and architecture

open

vs

core needle

vs

FNA

Immunophenotyping and genetics mainly for clonality

Staging of lymphoma

Stage I Stage II Stage III Stage IV

A: absence of B symptoms B: fever, night sweats, weight loss

Hodgkin lymphoma

Thomas Hodgkin (1798 -1866)

Hodgkin lymphoma

cell of origin: germinal centre B-cell Reed-Sternberg cells (or RS variants) in the affected tissues most cells in affected lymph node are polyclonal reactive lymphoid cells, not neoplastic cells

Reed-Sternberg cell

RS cell and variants

classic RS cell

(mixed cellularity)

lacunar cell

(nodular sclerosis)

popcorn cell

(lymphocyte predominance)

Reed-Sternberg cell

The Scream, 1893

Edvard Munch

A possible model of pathogenesis

transforming event(s) EBV? loss of apoptosis

cytokines germinal centre B cell RS cell inflammatory response

Hodgkin Lymphoma

Marker · CD20 (B-cell) · CD3 (T-cell) · CD15 (myeloid) · CD30 (lymphoid activation) · Immunoglobulin

B-NHL + +

H/RS Cell + + -

Information

Mature lymphoproliferative 3: Mature T-cell Neoplasms and Hodgkin lymphoma

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