Clinicopathologic and Prognostic Significance of Cytotoxic Molecule Expression in Nodal Peripheral T-Cell Lymphoma, Unspecified

Cytotoxic molecules (CMs) are apoptosis-inducing molecules that are present in azurophilic cytoplasmic granules of T lymphocytes. Expression of TIA-1 and granzyme B was examined for 100 cases of nodal peripheral T-cell lymphoma, unspecified (PTCL-U) to assess clinicopathologic significance of CM. Forty-one were positive for at least one CM. Patients with CM-positive PTCL-U showed younger onset (median, 55 years vs. 64 years, P = 0.01) and less male predominance (male:female ratio, 21:20 vs. 44:15, P = 0.02). CM-positive PTCL-U was significantly associated with several clinical factors to indicate poor prognosis, in comparison with CM-negative PTCL-U, such as poorer performance status (P = 0.006), more frequent B-symptoms (68% vs. 35%, P = 0.002), higher serum lactate dehydrogenase levels (P = 0.003), and more frequent extranodal involvement, particularly bone marrow involvement (33% vs. 9%, P = 0.004). Epstein-Barr virus was mostly found in CM-positive PTCL-U (51% vs. 2%, P < 0.0001). The CM-positive group showed higher distribution of the International Prognostic Index (P = 0.009) and the Prognostic Index for T-cell lymphoma (P = 0.004) scores than CM-negative group. Complete remission rate was 30% for the former but 63% for the latter. Overall survival of CM-positive PTCL-U was significantly lower than that of CM-negative patients (P = 0.004). Multivariate analyses confirmed that CM expression is a significant prognostic factor, independent from other clinical factors or prognostic index scores. These findings suggest that nodal CM-positive PTCL-U show distinct clinicopathologic characteristics among the current category of PTCL-U.