Classification of T-Cell disorders

2001-02-01   Estella Matutes  , Daniel Catovsky  , Vasantha Brito-Babapulle  

1.Academic Department of Haematology, Cytogenetics, The Royal Marsden NHS Trust, London, UK

Clinics and Pathology

Disease

T-prolymphocytic leukemia (T-PLL)
Variants: small cell and cerebriform cell.

Phenotype stem cell origin

TdT-, CD1a-,
CD4+ CD8-
CD4- CD8+
CD4+ CD8+ , CD3+, CD2+, CD8+ CD4-, CD57+, CD16+/-Cytotoxic or suppressor activity. , CD2+, CD56+, CD16+, CD7+/-CD3-, CD5-, TCR-Natural killer Activity.

Clinics

Aggressive course
Splenomegaly, high WBC with prolymphocytes. , Cytopenias, splenomegaly, lymphocytosis with granular lymphocytes. , Lymphocytosis, splenomegaly, hepatomegaly , Hypercalcaemia, lymphadenopathy, flower cells, HTLV-1 Positive. , Hepato splenomegaly , Mediastinal mass, high WBC.

Cytogenetics

inv(14)(q11q32), t(14;14)(q11;q32)
Xq28 abnormalities
idic(8)(p11), t(8;8)(p11;q1-2)
11q22-23 abnormalities
12p abnormalities
13q14.3 deletions , Abnormal.2p,
 , Abnormal.6q,
 , i(17q),
 , del(13)(q14) , Numerical abnormalities: 3, 7, X.
 , Structural abnormalities: 1q, 3q, 6q, 14q. , +3 or i(3q), +5, del(6q).
 , Progression from normal karyotype to abnormal clone observed during transition from hyperplasia to neoplasia. , t(11;14)(p13;q11)
 , t(1;14)(p34;q11); 1p34: tal-1gene; 14q11: TCR alpha

Genes

ATM gene (11q22-23) mutated.
TCL1 (14q32.1) or
MTCP1 (Xq28) activated. , Few cases express MDM2 , Abnormalities of p53, p16 and p15 genes.

Phenotype stem cell origin

TdT-, CD1a

Clinics

Indolent

Cytogenetics

Clonal abnormalities. In some cases, but no consistent specific abnormalities.

Genes

Clonality established by TCR rearrangements.

Phenotype stem cell origin

TdT-, CD1a

Clinics

Aggressive or indolent

Cytogenetics

Genes

TCR chain genes in germ line.

Phenotype stem cell origin

TdT-, CD1a-, CD3+, CD4+, CD8-, Helper or no functional activity.

Clinics

Variable clinical course with skin involvement and cells with cerebriform nuclei.

Cytogenetics

Complex, clonal, oligoclonal or nonclonal with variable ploidy.

Genes

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

Disease

Adult T-cell leukemia lymphoma (ATLL)

Phenotype stem cell origin

TdT-, CD1a-, CD7- CD4+ CD8- CD25+, Suppressor activity.

Clinics

Aggressive,

Cytogenetics

Complex and often oligoclonal.

Genes

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

Phenotype stem cell origin

TdT-, CD1a-, CD3+/- CD56+, CD7+, granzyme A+, TCR g/d+

Clinics

Aggressive,

Cytogenetics

Abnormal.7q, i(7q)

Genes

TCR genes gamma/delta rearranged but alpha/beta not rearranged.

Disease

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

Phenotype stem cell origin

TdT-, CD1a-, Variable expression of CD4 or CD8

Clinics

Aggressive; advanced stages.

Cytogenetics

Variable

Phenotype stem cell origin

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

Clinics

Disproteinemia, lymphadenopathy, immune abnormalities.

Cytogenetics

Complex with multiple related or unrelated clones.

Genes

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

Phenotype stem cell origin

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

Clinics

Prevalent in Asia and south America; extra nodal involvement.

Cytogenetics

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

Genes

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

Phenotype stem cell origin

TdT-, CD1a-, CD3+/- CD30+ (Ki 1+), CD15-, CD25+, HLA-Dr+, CD71+

Clinics

Aggressive with skin nodes and extranodal involvement.

Cytogenetics

Genes

Fusion gene NPM-ALK; 2p23 -Nucleolar phosphoprotein- NPM; 5q35 -Anaplastic lymphoma kinase- ALK.

Phenotype stem cell origin

TdT, CD1a-, CD3+, CD8+, CD103+, CD4-, CD8-

Clinics

Bone pain, coeliac disease, mesenteric nodes.

Genes

EBV genome present in mexican population but not in the europeans.

Disease

T-lymphoblastic Lymphoma/leukaemia (T-Lbly/T-ALL)

Phenotype stem cell origin

TDT+, CD1a+, CD7+, cytCD3+ or +/-, other T-cell antigens.Thymic uncommitted T-cell.

Clinics

Aggressive; course similar to ALL.

Cytogenetics

Genes

TCR chain genes rearranged.

Article Bibliography

Pubmed IDLast YearTitleAuthors
109309962000p53 allele deletion and protein accumulation occurs in the absence of p53 gene mutation in T-prolymphocytic leukaemia and Sezary syndrome.Brito-Babapulle V et al
86082061996Classification of natural killer (NK) cell and NK-like T-cell malignancies.Jaffe ES et al
15409561992Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report.Kamada N et al
83242141993Clonal diseases of large granular lymphocytes.Loughran TP Jr et al
21565481990CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.Mason DY et al
88398581996Indication of an involvement of interleukin-1 beta converting enzyme-like protease in intramedullary apoptotic cell death in the bone marrow of patients with myelodysplastic syndromes.Mundle SD et al
79193781994Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics.Schlegelberger B et al
75364541995Consistent presence of isochromosome 7q in hepatosplenic T gamma/delta lymphoma: a new cytogenetic-clinicopathologic entity.Wang CC et al
93261901997Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma/leukaemia.Wong KF et al

Summary

Note

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.

Citation

Estella Matutes ; Daniel Catovsky ; Vasantha Brito-Babapulle

Classification of T-Cell disorders

Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

Online version: http://atlasgeneticsoncology.org/haematological/2079/classification-of-t-cell-disorders