T and NK cell LPD Flashcards by Imogen Caldwell

T Follicular Helper immunophenotype

CD10, BCL6, CXCL13, CXCR5, ICOS, PD1, SAP

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Clinical features of AITCL

Patients generally present with advanced disease

Generalised lymphadenopathy
Hepatosplenomegaly
Skin rash +/- pruritus
Ascites, pleural effusion, arthritis
Often associated with autoimmune conditions
Immunodeficiency

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Laboratory features of AITCL

Hypergammaglobulinaemia
RF and anti-smooth muscle antibodies
Cold agglutinins with haemolytic anaemia
Circulating immune complexes

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Immunophenotype of T-PLL

Positive T cell markers: CD2, CD5, CD3 and CD7 (CD3 can be weak)
CD52 is usually strongly expressed and can be a target of therapy
60% CD4+/CD8-
25% CD4+/CD8+ (dual positivity is not really seen in any other mature T cell neoplasm, ddx T-ALL)
15% CD4-/CD8+
Negative: CD1a, TdT

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Features of T-PLL (disease of 52)

Aggressive T-cell leukaemia
Affects older adults (52 year olds)
PB lymphocyte count > 100 (520)
CD2+, CD5+, CD52+
5 cytogenetic abnormalities, 2 are very common
Inv(14) or t(14;14)
Trisomy 8
Deletions at 12p and amplification of 5p
TP53
Median survival 5 months to 2 years

Anaemia and thrombocytopenia
Lymphadenopathy, hepatosplenomegaly
Skin infiltration in 20% (blebs = skin lumps)

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What are the cytogenetics abnormalities in T-PLL?

Inversions of chromosome 14
- Inv(14) in 80%, t(14;14) in 10%
Abnormalities of chromosome 8
- idic(8), t(8;8) and trisomy 8q are seen in 80%
Deletions at 12p13 and amplification of 5p are also common
TP53 deletions

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Clinical and laboratory features of aggressive NK cell leukaemia

Patients usually present with fevers, weight loss, fatigue
Pancytopenia with leukaemic cells
Hepatosplenomegaly
Effusions are common
High LDH
May have coagulopathy, haemophagocytic syndrome or multiorgan failure
Median survival < 2months

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Is aggressive NK cell leukaemia EBV driven?

Yes - 80-100% association with EBV. Seen in adults, median age is 40 years.
N.B. Chronic lymphoproliferative disorder of NK cells is EBV negative.

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Immunophenotype of extranodal NK/T cell lymphoma

CD2+, sCD3- (but CD3ε+), CD56+, usually CD16-, CD4- and CD8-
Cytotoxic molecules positive
(EBV positive)

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Immunophenotype of Adult T-cell leukaemia/lymphoma

T cell antigens: CD2+, CD3+, CD5+, usually CD4+
CD7-
CD25 is strongly expressed in nearly all cases
CD30 may be positive

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Clinical features of ATLL

Acute - leukaemic presentation with high WBCs, high LDH, hypercalcaemia, hepatosplenomegaly, lytic bone lesions, rash and BM infiltration.
Lymphomatous - LNs but no PB, otherwise similar to acute form.
Chronic - mildly increased lymphocytes, mildly raised LDH. May have hepatosplenomegaly. Ca2+ normal.
Smouldering - leukaemic cells >5% but WBC count normal. No systemic symptoms.

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Features of Sezary Syndrome (triad + additional)

Erythroderma
Generalised lymphadenopathy
Leukaemia - abnormal clonal cerebriform T cells circulating
Plus one of the following additional criteria:
Sezary count >1000/uL
CD4:CD8 >10:1
Loss of T cell antigens e.g. CD7 and CD26

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Immunophenotype of Sezary Syndrome

CD3+/CD4+/CD8-
CD7- and CD26-
PD1 +

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Define T-LGL

Persistent (>6 months) increase in LGLs in the peripheral blood
Usually 2-20

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What are reactive causes of increased T-LGLs?

Infection
G-CSF
Immune reconstitution following SCT and chemotherapy

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What are the clinical features of T-LGL?

Usually affects middle aged to older adults
Indolent
Symptomatic from cytopenias - neutropenia is common, then anaemia. Thrombocytopenia is rare.
Splenomegaly
Associated with RA
Hypergammaglobulinaemia and immune complexes

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Describe morphology in T-LGL

- PB and BM

Intermediate to large lymphocytes, abundant cytoplasm and fine or coarse azurophilic granules
BM hypocellular/normocellular /mildly hypercellular
Intrasinusoidal +/- interstitial infiltrates
BM fibrosis common
Granulocytic hypoplasia
Very common to find reactive lymphoid aggregates (CD4+ lymphocytes rather than CD8+)

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What is the immunophenotype of T-LGL?

CD3+, CD8+, CD16+, CD57+ (CD56-, dim CD5 and dim CD7) with alpha/beta TCR gene rearrangement
TIA1, granzyme

Rare variants:

alpha/beta with CD4+
gamma/delta type rare and may be CD8+ or CD4-/CD8-

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Definition of chronic lymphoproliferative disorder of NK cells

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Rare and heterogenous disorder characterised by persistent (>6 months) increase in NK cells in the peripheral blood (>2)

Morphology of NK-LGL

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Intermediate to large lymphocytes, abundant cytoplasm and fine or coarse azurophilic granules
Intrasinusoidal +/- interstitial infiltrates

Immunophenotype of NK-LGL

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sCD3-, CD8+, CD16+, CD56+(dim) and cytotoxic markers

Often loss of CD2, CD5 and/or CD57

Morphology of aggressive NK cell leukaemia

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Variable - ranging from normal appearing LGLs through to cells with atypical nuclei, open chromatin and nucleoli
BM - interstitial or focal infiltrate +/- haemophagocytosis

Immunophenotype of NK cell leukaemia?

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CD2+, sCD3-, CD5-, CD16+, CD56+

Definition of ATLL

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Aggressive lymphoma/leukaemia caused by HTLV1 infection.
HTLV1 infections occur in childhood but disease has long latency and presents in adulthood
2.5% of carriers develop ATLL
Flowery lymphocytes

Prognosis and predictive factors in ATLL

Acute and lymphomatous form 2weeks - 1 year Chronic and smouldering forms progress to acute phase in 25% Death from opportunistic infections is common e.g. PJP and strongyloides

Definition of hepatosplenic T cell lymphoma

Aggressive extranodal T cell lymphoma with proliferation of cytotoxic T cells that are usually the gamma/delta TCR type

Clinical features of hepatosplenic T cell lymphoma

Young adults (median age 35 years) 20% of cases arise in the setting of chronic immunosuppression e.g. infliximab + azathioprine in IBD patients. Hepatosplenomegaly without lymphadenopathy Marked thrombocytopenia +/- anaemia BM almost always involved

Morphology of hepatosplenic T cell lymphoma

Monotonous medium sized lymphocytes with a pale rim of cytoplasm and loosely condensed chromatin Prominent intrasinusoidal pattern in liver and BM

Immunophenotype of hepatosplenic T cell lymphoma

CD3+, CD8+/-, CD56+/-, gamma/delta CD4-, CD5- DDx T-LGL (57+)

Definition of Peripheral T cell lymphoma, NOS

Heterogenous group of nodal and extranodal T cell lymphoma that don't fit in any other WHO category. Excludes those with a T follicular helper phenotype

Clinical Features of Peripheral T cell lymphoma, NOS

Aggressive Mostly seen in adults B symptoms common Usually nodal but can be extranodal, rarely leukaemic Eosinophilia, pruritus and rarely HLH can occur

Immunophenotype of PTCL

Frequent loss of T cell antigens CD3+ CD4+>CD8+ but can get double positive and double negative Can have CD56+ and cytotoxic markers positive CD15 and/or CD30

Morphology of PTCL, NOS

Diffuse infiltrate which may be monomorphic or polymorphic Medium to large cells, may have RS like cells Can have histiocyte rich form

Definition of AITLC

Neoplasm of mature T cells with a T follicular helper cell phenotype Always associated with EBV positive B cells but the neoplastic T cells are negative

Morphology of AITCL (PB, BM)

Blood film - may see rouleaux or eosinophilia BM - small to intermediate sized T cells surrounded by inflammatory cells e.g. eosinophils, plasma cells, histiocytes, reactive lymphocytes Increased bone marrow vascularity May have follicular architecture or this may be effaced

Immunophenotype of AITCL

CD10, BCL6, PD1, CXCL13, CXCR5, SAP, ICOS CD2+, CD3+, CD4+, CD5+ EBV positive cells = B cells

Anaplastic large cell lymphoma - Definition

T cell lymphoma characterised by large and pleomorphic lymphoid cells with horse shoe shaped nuclei and abundant cytoplasm.

Most common translocation involving ALK gene?

t(2;5) = ALK on chromosome 2, NPM1 on chromosome 5 | But there are many partners and the partner doesn't alter prognosis.

Clinical features of ALCL

Children and young adults ALK+ has a better prognosis Advanced stage disease and B symptoms at presentation are common LNs and extranodal Less likely to have mediastinal disease compared to cHL 30% have BM involvement - need IHC to diagnose

Name the 4 morphologic variants of ALCL

1. Common 2. Lymphohistiocytic 3. Small cell 4. Hodgkin like * *all variants have Hallmark cells in them**

IHC and immunophenotype in ALCL

CD30+ (uniform) EMA+ (100% of ALK+ but 50% of ALK-) EMA is negative in PTCL. CD4+, CD2+, CD5+ CD3- in 75% ALK+ PAX5- (differentiates it from cHL) N.B. There can be a "null phenotype" but TCR gene rearrangement is clonal

Breast lymphoma

90% B cell | 10% T cell - systemic ALCL, breast implant associated ALCL

What mutations are seen in ~1/3 of T and NK cell LGL

STAT3 mutations

Immunophenotype of ATLL

CD3+, CD4+, CD2+, CD5+, CD25+ CD7- +/- CD30

Differential diagnosis of T cell leukaemias

T-PLL (CD4+/CD8+, CD7 strong, CD52+) T-LGL (CD8+, CD16+, CD57+) Sezary (CD7-, CD26-, PD1+) ATLL (CD7-, CD25+)

T and NK cell LPD Flashcards

(45 cards)