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Clinicopathologic Spectrum of Gastrointestinal T-cell Lymphoma: Reappraisal Based on T-cell Receptor Immunophenotypes.

The differential diagnosis of primary gastrointestinal EBV T-cell lymphoma (GITCL) includes enteropathy-associated T-cell lymphoma (EATL), peripheral T-cell lymphoma, not otherwise specified, adult T-cell leukemia/lymphoma, and anaplastic large cell lymphoma. Type II EATL is considered to be a tumor of intraepithelial lymphocytes. However, the evaluation of intraepithelial lymphocytosis by biopsy specimens is challenging, which poses a diagnostic problem between the EATL and peripheral T-cell lymphoma, not otherwise specified. This situation requested us to establish a pragmatic diagnostic approach for the classification of GITCL. We identified 42 cases of GITCL and analyzed clinicopathologic features, especially addressing their T-cell receptor (TCR) phenotype. Nine (21%) of 42 GITCL cases were positive for TCRγ protein expression. Among these TCRγ cases, TCRβ expression or not was detected in 5 and 4, respectively, but resulted in no further clinicopathologic differences. TCRβ positivity without TCRγ expression (βγ) was seen in 9 GITCL patients (21%). Twenty-four patients (57%) were negative for TCRβ and γ expression (βγ). Compared with TCRβγ or βγ type, TCRγ cases were characterized by exclusive involvement of intestinal sites (100% vs. 11%, P<0.001; 100% vs. 58%, P=0.032, respectively), but not of stomach (0% vs. 78%, P=0.002; 0% vs. 38%, P=0.039, respectively). Notably, TCRγ positivity was an independent unfavorable prognostic factor among our GITCL patients (P<0.001). Considering our results, TCRγ GITCL, that is, intestinal γδ T-cell lymphoma, appears to constitute a distinct disease entity.

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