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Classification of T-Cell disorders

Identity

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.

Clinics and Pathology

Disease
  • T-prolymphocytic leukemia (T-PLL)
  • Variants:small cell and cerebriform cell
    • Phenotype / cell stem origin
  • TdT-, CD1a-,
  • CD4+ CD8-
  • CD4 - CD8+
  • CD4+ CD8+
    • Clinics
  • Aggressive course
  • splenomegaly, high WBC with prolymphocytes
    • 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
    • Genes
  • ATM gene (11q22-23) mutated.
  • TCL1 (14q32.1) or
  • MTCP1 (Xq28) activated

    • Disease Large granular lymphocyte leukemia (LGL) - T-cell Type
    Phenotype / cell stem origin
  • TdT-,CD1a
  • ­CD3+,CD2+,CD8+ CD4 -,CD57+, CD16+/-Cytotoxic or suppressor activity
    • Clinics
  • Indolent
  • cytopenias, splenomegaly, lymphocytosis with granular lymphocytes.
    • Cytogenetics Clonal abnormalities.in some cases, but no consistent specific abnormalities
    Genes Clonality established by TCR rearrangements

    Disease Large granular lymphocyte leukemia (LGL) - NK type
    Phenotype / cell stem origin
  • TdT-,CD1a ­
  • CD2+,CD56+, CD16+ ,CD7+/-CD3-, CD5-,TCR-Natural killer Activity.
    • Clinics
  • Aggressive or indolent
  • lymphocytosis, splenomegaly, hepatomegaly
    • Cytogenetics del(6)(q21-25)
    Genes TCR chain genes in germ line.

    Disease Sezary syndrome (SS)
    Phenotype / cell stem 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
  • Abnormal.2p,
  • Abnormal.6q
  • i(17q),
  • del (13)(q14)
    • Genes
  • P53 gene deletion and protein expression in the absence of gene mutation.
  • Few cases express MDM2

    • Disease Adult T-cell leukemia lymphoma (ATLL)
    Phenotype / cell stem origin TdT-, CD1a- CD7- CD4+ CD8- CD25+, Suppressor activity
    Clinics
  • Aggressive ,
  • hypercalcaemia, lymphadenopathy, Œflower cells', HTLV-1 Positive.
    • Cytogenetics
  • Complex and often oligoclonal.
  • Numerical abnormalities: 3, 7, X
  • Structural abnormalities: 1q, 3q, 6q, 14q.
    • Genes
  • Oligoclonal/mono clonal integration of HTLV-1in host DNA
  • Abnormalities of p53, p16 and p15 genes.

    • Disease a/d T-NHL hepatosplenic lymphoma
    Phenotype / cell stem origin TdT- CD1a- CD3+/- CD56+, CD7+, granzymeA+, TCR g/d+
    Clinics
  • Aggressive,
  • Hepato splenomegaly
    • Cytogenetics Abnormal.7q, i (7p)
    Genes TCR genes gamma/delta rearranged but alpha/beta not rearranged

    Disease Peripheral/post-thymic T cell lymphoma (pleomorphic and immunoblastic subtypes)
    Phenotype / cell stem origin TdT-, CD1a-, Variable expression of CD4 or CD8
    Clinics Aggressive; advanced stages.
    Cytogenetics variable

    Disease Angio immunoblastic T-cell lymphoma
    Phenotype / cell stem origin TdT-, CD1a-, CD2+, CD5+, CD3+ CD4+ CD8-
    Clinics Disproteinemia, lymphadenopathy,immune abnormalities
    Cytogenetics
  • Complex with multiple related or unrelated clones.
  • +3 or i(3q), +5, del(6q).
  • Progression from normal karyotype to abnormal clone observed during transition from hyperplasia to neoplasia.
    • Genes Integrated EBV sequences present in both B-and T-cells and is unlikely to be the etiological agent.

    Disease Angiocentric (nasal) T-cell lymphoma
    Phenotype / cell stem 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

    Disease Anaplastic (Ki 1+) large cell lymphoma
    Phenotype / cell stem origin TdT-, CD1a-, CD3+/- CD30+ (Ki 1+), CD15-, CD25+, HLA-Dr+, CD71+.
    Clinics Aggressive with skin nodes and extranodal involvement.
    Cytogenetics t(2;5)(p23;q35)
    Genes Fusion gene NPM-ALK; 2p23 -Nucleolar phosphoprotein- NPM; 5q35 -Anaplastic lymphoma kinase- ALK

    Disease Intestinal T-cell lymphoma
    Phenotype / cell stem 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 / cell stem origin TDT+, CD1a+, CD7+, cytCD3+ or +/-, other T-cell antigens.Thymic uncommitted T-cell.
    Clinics
  • Aggressive; course similar to ALL
  • mediastinal mass, high WBC
    • Cytogenetics
  • del(6)(q21-q22)
  • t(11;14)(p13;q11)
  • t(1;14)(p34;q11); 1p34: tal-1gene; 14q11: TCR alpha
    • Genes TCR chain genes rearranged.

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    Contributor(s)

    Written02-2001Vasantha Brito-Babapulle, Estella Matutes, Daniel Catovsky
    Academic Department of Haematology and 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 disorders. Atlas Genet Cytogenet Oncol Haematol. February 2001 .
    URL : http://AtlasGeneticsOncology.org/Genes/TcellClassifID2079.html

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    indexed on : Mon Aug 11 21:19:12 2008

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