Gene Rearrangements in Primary Testicular Lymphomas: A FISH Analysis with Split Signal Probes
Silvia Uccella, Barbara Bernasconi, Isabella Ricotti, Vittoria Martin, Luca Mazzucchelli, Graziella Pinotti, Ilaria Proserpio, Emanuele Zucca, Francesco Bertoni, Fausto Sessa, Carlo Capella, Maria Grazia Tibiletti. University of Insubria, Varese, Italy; Cantonal Institute of Pathology, Locarno, Switzerland; Ospedale di Circolo e Fondazione Macchi, Varese, Italy; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Multimedica, Milan, Italy
Background: Primary testicular lymphomas are exceedingly rare and are nearly always represented by diffuse large B-cell lymphomas (DLBCL). Clinically, these neoplasms are highly aggressive and, despite the administration of intensive chemotherapeutic regimens, they still bear a poor prognosis. This behaviour is strikingly different form that of other primary extranodal DLBCL. Cytogenetic alterations in DLBCL encompass complex abnormalities such as translocations, trisomies, amplifications and deletions of a number of chromosomal regions. Bcl2, Bcl6 and MYC seem to be the most frequently involved genes. Specific chromosomal alteration have not been described in DLBCL arising in extranodal sites, except for gastric lymphomas and, due to their rarity, primary testicular lymphomas have not been extensively studied under this aspect.
Design: FISH analysis was performed on histological sections of a series of 17 primary testicular DLBCL. Probes for split signal FISH targeting BCL2, BCL6, MYC, CCND1,MALT1, BCL10 and IgH (Dako, Copenhagen, Denmark) were used. The results were compared with those obtained in a previously studied series of 74 primary nodal DLBCL (Tibiletti et al., Hum Pathol, 2009).
Results: Gene rearrangements were identified in 10 out of 17 analysed cases (58%). All genes were involved in rearrangements. BCL6 was the most rearranged gene (6/17 cases, 35%), analogously to what observed in primary nodal cases, followed by MYC and IgH (3/17 cases, 23%), with a higher frequency than in nodal lymphomas. In 2 cases (11,7%) we found a MALT1 rearrangement, which was never observed in primary nodal DLBCL. Multiple rearrangements were detected in 4 cases (23,5%). Interestingly, we found 4 lymphomas in which gene rearrangements were detected only in small clones of neoplastic cells (less than 5% of neoplastic population). This finding may lead to speculate that major rearrangements other than those described in nodal lymphomas may take place in the pathogenesis of testicular lymphomas. Molecular cytogenetic analysis revealed also polysomies of one or more of the investigated regions in 9 of the analyzed lymphomas (53%).
Conclusions: This study highlights a peculiar pattern of gene rearrangements detected by FISH analysis in primary testicular DLBCL, compared with primary nodal DLBCL.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 187, Tuesday Afternoon