The diagnosis of a T-cell malignancy is best made in the context of clinical information,tissue morphology,immuno-histochemical stains, and immunophenotypic analysis. In contrast to the restricted IGL protein expression in mature B-cell lymphomas, however, T cells do not have a definitive immunophenotypic marker of clonality. Therefore, TCR gene rearrangement studies can be essential to complement a diagnostic evaluation and to distinguish polyclonal from monoclonal lymphoproliferations. When clonality is assessed by TCR polymerase chain reaction (PCR), a visible band with products of exactly the same size is indicative of the presence of a clone, whereas polyclonal amplification generates a smear of nondistinct products of various sizes. A result is considered oligoclonal if more than two distinct bands are visible. The number of bands that would lead to a determination of oligoclonality varies by method, but the band size often will vary between duplicate PCR reactions in oligoclonal proliferations. In addition to the differentiation of reactive and neoplastic proliferations, molecular methods can be applied to identify disease-related findings, such as an associated virus or a specific gene fusion product, that enable subclassification of the malignancy.
Anaplastic large cell lymphoma, characterized by translocation t(2;5)(p23;q35), is the only translocation for which testing is widely available. Diagnostic testing is complicated by the variety of ALK fusion partners and inconsistency of genetic anomalies seen during tumor progression.
Adult T-cell leukemia/lymphoma (ATLL) is strongly associated with HTLV-1 infections.7 The provirus is clon-ally integrated in the host DNA in virtually all ATLL patients, but in situ hybridization studies for this virus are difficult to perform and are not routinely offered. Serologic studies or PCR analysis are better suited to detect the virus.
Vp VP Dpi Jpi
Cpi DP2 JP2
D/J rearrangement v v
DP1 JP2 I Cp2
V/D rearrangement il-
VP DP1 JP2 T Cp
VP DP1 JP2 T Cp
Figure 33-2. The TCRB locus on chromosome region 7q34 is used as an example to demonstrate the rearrangement of the variable (V), diversity (D), joining (J), and constant (C) regions. N, nucleotides added by the enzyme TdT.
Table 33-1. T-Cell and NK-Cell Neoplasms of the WHO Classification
Precursor T-lymphoblastic leukemia/lymphoma T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Aggressive NK-cell leukemia Adult T-cell leukemia/lymphoma Extranodal NK/T-cell lymphoma, nasal type Enteropathy-type T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Blastic NK-cell lymphoma Mycosis fungoides/Sezary syndrome
Primary cutaneous CD30 positive T-cell lymphoproliferative disorders
Primary cutaneous anaplastic large cell lymphoma Lymphomatoid papulosis Borderline lesions Angioimmunoblastic T-cell lymphoma Peripheral T-cell lymphoma, unspecified Anaplastic large cell lymphoma
Many NK-cell lymphomas are extranodal proliferations frequently associated with Epstein-Barr virus (EBV) infection within tumor cells.8 In situ hybridization testing for EBER-1 RNA of EBV is offered in many laboratories and often is useful in the diagnosis of this tumor type. Because of the high frequency of latent infection by EBV in normal adults, serologic and PCR tests for EBV are of little value in determining a disease association, and the in situ hybridization procedure is the preferred method of testing.
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