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







Disease Features.

T-prolymphocytic leukemia(T-PLL)

Variants:small cell

and cerebriform cell


CD4+ CD8-

CD4 - CD8+

CD4+ CD8+





t(14;14)(q11; q32)

Xq28 abnorm.


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

11q22-23 abnorm.

12p abnorm

13q14.3 deletions

ATMgene (11q22-23) mutated.

TCL1 (14q32.1) or



Aggressive course splenomegaly, high WBC with prolymphocytes

Large granular lymphocyte leukemia(LGL)

a.T-cell Type






b.NK type





TdT-,CD1a —




CD4 -,CD57+, CD16+/-

Cytotoxic or suppressor activity


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

CD3-, CD5-,TCR-

Natural killer


Clonal some cases,but

no consistent specific







Clonality established by

TCR rearrangements







TCR chain genes in germ line.





Indolent, cytopenias, splenomegaly, lymphocytosis with granular lymphocytes





Aggressive or indolent lymphocytosis



Sezary syndrome (SS)





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

Helper or no functional activity


Complex,clonal,oligoclonal or nonclonal with variable ploidy


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








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


a/d T-NHL hepatosplenic lymphoma



TdT- CD1a-CD3+/- CD56+,

CD7+,granzymeA+,TCR g/d+


i (7p)

TCR genes gamma/delta

Rearranged but

alpha/beta not



Hepato splenomegaly

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



Variable expression of CD4 or CD8




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



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+.


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+



EBV genome present in

mexican population but not in the europeans.

Bone pain

Coeliac disease,

Mesenteric nodes



Lymphoma/leukaemia (T-Lbly/T-ALL




CD7+, cytCD3+or+/-

Other T-cell antigens.Thymic

uncommitted T-cell.





1p34 : tal-1gene

14q11:TCR alpha

chain gene

TCR chain genes rearranged



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


Relationship of T leukaemias with cerebriform nuclei to T-prolymphocytic leukaemia: a cytogenetic analysis with in situ hybridization.
Brito-Babapulle V, Maljaie SH, Matutes E, Hedges M, Yuille M, Catovsky D
British journal of haematology. 1997 ; 96 (4) : 724-732.
PMID 9074412
p53 allele deletion and protein accumulation occurs in the absence of p53 gene mutation in T-prolymphocytic leukaemia and Sezary syndrome.
Brito-Babapulle V, Hamoudi R, Matutes E, Watson S, Kaczmarek P, Maljaie H, Catovsky D
British journal of haematology. 2000 ; 110 (1) : 180-187.
PMID 10930996
The D13S25 locus mapping to 13q14.3 locus is deleted in T-Prolymphocytic leukemia
Brito-Babapulle V, Baou M, Atkinson S, Catovsky D
Int.Natl.J of Hematology. 2000 ; 72 (supplement 1) : page 167.
Response to : presence of t(2;5) in primary CD30+ cutaneous lymphoproliferative disorders'
DeCocteau JF, Lowsky R, Kinney MC, Kadin ME
Blood. 1996 ; 88 : page 3251.
Classification of natural killer (NK) cell and NK-like T-cell malignancies.
Jaffe ES
Blood. 1996 ; 87 (4) : 1207-1210.
PMID 8608206
Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report.
Kamada N, Sakurai M, Miyamoto K, Sanada I, Sadamori N, Fukuhara S, Abe S, Shiraishi Y, Abe T, Kaneko Y
Cancer research. 1992 ; 52 (6) : 1481-1493.
PMID 1540956
Clonal diseases of large granular lymphocytes.
Loughran TP Jr
Blood. 1993 ; 82 (1) : 1-14.
PMID 8324214
CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.
Mason DY, Bastard C, Rimokh R, Dastugue N, Huret JL, Kristoffersson U, Magaud JP, Nezelof C, Tilly H, Vannier JP
British journal of haematology. 1990 ; 74 (2) : 161-168.
PMID 2156548
T-Cell Lymphoproliferative Disorders. Classification, Clinical and Laboratory Aspects
Matutes E
Advances in Blood Disorders. 2000.
Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas.
Schlegelberger B, Himmler A, Gödde E, Grote W, Feller AC, Lennert K
Blood. 1994 ; 83 (2) : 505-511.
PMID 8286748
Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics.
Schlegelberger B, Zhang Y, Weber-Matthiesen K, Grote W
Blood. 1994 ; 84 (8) : 2640-2648.
PMID 7919378
Consistent presence of isochromosome 7q in hepatosplenic T gamma/delta lymphoma: a new cytogenetic-clinicopathologic entity.
Wang CC, Tien HF, Lin MT, Su IJ, Wang CH, Chuang SM, Shen MC, Liu CH
Genes, chromosomes & cancer. 1995 ; 12 (3) : 161-164.
PMID 7536454
Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma/leukaemia.
Wong KF, Chan JK, Kwong YL
British journal of haematology. 1997 ; 98 (4) : 922-926.
PMID 9326190
Written2001-02Vasantha Brito-Babapulle, Estella Matutes, Daniel Catovsky
Department of Haematology, Cytogenetics, The Royal Marsden NHS Trust, London, UK


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
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