MOLECULAR PATHOLOGICAL ANALYSIS OF TESTICULAR DIFFUSE LARGE-CELL LYMPHOMAS

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyze d. These lymphomas occurred in men with a median age of 69 years (rang e, 37 to 87 years). Nine of the 14 patients with follow-up died of lym phoma (median survival, 12 months). All cases were diffuse large B-cel l lymphomas that were positive for CD20 and commonly showed plasmacyto id differentiation (10 of 20 cases). Three cases were Burkitt's-like l arge cell lymphomas. Infiltration by lymphoma in the seminiferous tubu les was seen in most cases. All lymphomas were negative for human herp esvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reac tion (PCR), suggesting that these viruses are not involved in the path ogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cas es. Nucleotide sequences of the V-D- and J segments of the immunoglobu lin heavy chain gene (IgH) rearrangements obtained in 12 cases after P CR amplification were analyzed and compared with known germ-lines. The frequency of VH-family use in testicular DLBCL was similar to that re ported for normal peripheral blood lymphocytes and follicular lymphoma s, This contrasts with the previously published findings of preferenti al use of the VH3- or VH4-family by nodal DLBCL. Comparison with the p ublished germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutat ion, as indicated by intraclonal variation in IgH sequence, was observ ed in all sequenced cases, suggesting direct antigen stimulation, whic h represents another difference between primary testicular and nodal D LBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respec ts. Their histological and molecular features show some similarities t o those seen in marginal zone (MALT) lymphomas. This is a US governmen t work. There are no restrictions on its use.