Classification of T-cell disorders

Vasantha Brito-Babapulle, Estella Matutes, Daniel Catovsky

Academic Haematology and Cytogenetics, Royal Marsden Hospital/Institute of Cancer Research London UK.

February 2001

  Summary: T-cell lymphoid disorders include a variety of disease entities which result from the clonal neoplastic expansion of an uncommitted (thymic) or a committed (post thymic) T-cell. Some of these diseases have distinct cytogenetic/molecular genetic features which allow to better define the various entities and understand their pathogenesis.

 

 

Disease entity

Immunophenotype/

Functional

activity

Cytogenetics

Molecular

genetics

Disease Features.

T-prolymphocytic leukemia(T-PLL)

Variants:small cell

and cerebriform cell

TdT-,CD1a-,

CD4+ CD8-

CD4 - CD8+

CD4+ CD8+

 

 

 

Inv(14)(q11q32)

t(14;14)(q11; q32)

Xq28 abnorm.

idic(8)(p11)

t(8; 8)(p11;q1-2)

11q22-23 abnorm.

12p abnorm

13q14.3 deletions

ATMgene (11q22-23) mutated.

TCL1 (14q32.1) or

MTCP1(Xq28)

activated

Aggressive course splenomegaly, high WBC with prolymphocytes

Large granular lymphocyte leukemia(LGL)

a.T-cell Type

 

 

 

 

 

b.NK type

 

 

 

 

TdT-,CD1a —

 

 

CD3+,CD2+,CD8+

CD4 -,CD57+, CD16+/-

Cytotoxic or suppressor activity

 

CD2+,CD56+, CD16+ ,CD7+/-

CD3-, CD5-,TCR-

Natural killer

Activity.

Clonal abnormalities.in some cases,but

no consistent specific

abnormalities

 

 

 

 

del(6)(q21-25)

Clonality established by

TCR rearrangements

 

 

 

 

 

 

TCR chain genes in germ line.

 

 

 

 

Indolent, cytopenias, splenomegaly, lymphocytosis with granular lymphocytes

.

 

 

 

Aggressive or indolent lymphocytosis

Splenomegaly

hepatomegaly

Sezary syndrome (SS)

 

 

 

 

TdT-, CD1a-, CD3+,CD4+,CD8-

Helper or no functional activity

.

Complex,clonal,oligoclonal or nonclonal with variable ploidy

Abnorm.2p,6q

i(17q),del 13q14

P53 gene deletion and protein expression in the absence of gene mutation.

Few cases express MDM2

Variable clinical course with skin involvement and cells with cerebriform nuclei

Adult T-cell leukemia lymphoma (ATLL

)

 

 

 

 

 

TdT-,CD1a-CD7-CD4+CD8-CD25+

Suppressor activity

Complex and often oligoclonal.

Numerical abnorm;3,7,X

Structural abnorm.1q,3q 6q,14q.

Oligoclonal/mono clonal integration of HTLV-1in host DNA

Abnormalities of p53, p16 and p15 genes.

Aggressive , hypercalcaemia

Lymph - adenopathy, ‘flower cells’, HTLV-1

Positive.

a/d T-NHL hepatosplenic lymphoma

 

 

TdT- CD1a-CD3+/- CD56+,

CD7+,granzymeA+,TCR g/d+

Abnorm.7q,

i (7p)

TCR genes gamma/delta

Rearranged but

alpha/beta not

rearranged

Aggressive,

Hepato splenomegaly

Peripheral/post-thymic T cell lymphoma (pleomorphic and immunoblastic subtypes

)

TdT-,CD1a-

Variable expression of CD4 or CD8

variable

  

Aggressive

Advanced stages

.

Angio immunoblastic T-cell lymphoma

 

 

 

 

TdT-,CD1a-, CD2+, CD5+,CD3+ CD4+ CD8-

Complex with multiple related or unrelated clones.+3 or i(3q),+5, del(6)(q). Progression from normal karyotype to abnormal clone observed during transition from hyperplasia to neoplasia.

Integrated EBV sequences present in both B-and T-cells and is unlikely to be the etiological

agent.

Disproteinemia

lymphadenopathy,immune abnormalities

Angiocentric (nasal) T-cell lymphoma

 

 

TdT-,CD1a-,T-cell or NK phenotype

.

i(1q), del(6)(q),i(6p)

Majority have no TCR rearrangement EBV clonally integrated and plays a role in the etiology of the disease

Prevalent in Asia and south America

Extra nodal involvement.

Anaplastic (Ki 1+) large cell lymphoma

.

 

TdT-,CD1a-,CD3+/- CD30+ (Ki 1+),CD15-,

CD25+, HLA-Dr+, CD71+.

t(2;5)(p23;q35)

Fusion gene NPM-ALK

2p23 -Nucleolar phosphoprotein-NPM

5q35 -Anaplastic

lymphoma kinase-ALK

Aggressive with skin,nodes and extranodal involvement

.

Intestinal T-cell lymphoma

 

 

TdT — CD1a -, CD3+, CD8+, CD103+

CD4-,CD8-

  

EBV genome present in

mexican population but not in the europeans.

Bone pain

Coeliac disease,

Mesenteric nodes

.

T-lymphoblastic

Lymphoma/leukaemia (T-Lbly/T-ALL

)

 

TDT+,CD1a+,

CD7+, cytCD3+or+/-

Other T-cell antigens.Thymic

uncommitted T-cell.

del(6)(q21-q22)

t

(11;14)(p13;q11)

t(1;14)(p34;q11)

1p34 : tal-1gene

14q11:TCR alpha

chain gene

TCR chain genes rearranged

.

 

Aggressive, mediastinal mass,high WBC,course similar to ALL

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Written2001-02Vasantha Brito-Babapulle, Estella Matutes, Daniel Catovsky
Department of Haematology, Cytogenetics, The Royal Marsden NHS Trust, London, UK

Citation

This paper should be referenced as such :
Brito-Babapulle V, Matutes E, Catovsky D
Classification of T-cell disorder
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Deep/TcellClassifID20022.htm

Citation

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Classification of T-cell disorders

Online version: http://atlasgeneticsoncology.org/deep-insight/20022/classification-of-t-cell-disorders