Testicular Diffuse Large B-Cell Lymphoma of Activated B-Cel Subtype Is Frequently Associated with Clonally Related Non-Follicular Small B-Cell Lymphoma in the Bone Marrow.

Abstract

Diffuse large B-cell lymphoma (DLBCL) of the testis is an uncommon non-Hodgkin' s lymphoma. It accounts for 1 % of all lymphomas but represents the most frequent testicular tumor in men over the age of 60. Most patients have localized disease but involvement of other extranodal sites is not uncommon. Of interest, an activated B-cell like (ACT) phenotype has been reported in the majority of testicular DLBCL and even those cases with a germinal center B-cell (GC) phenotype seem by micro-array analysis to display an mRNA profile of activated B-cells (1). This contrasts with the incidence of this phenotype of DLBCL at most other locations. Whether the activated B-cell phenotype may explain the dismal outcome of DLBCL of the testis is an interesting hypothesis.As part of a retrospective study of all cases of testicular DLBCL in the lymphoma registry of the Norwegian Radium Hospital, diagnosed in the period between 1995 and 2005, we have carefully reviewed all pathology data. Nineteen patients with a diagnosis of testicular lymphoma were retrieved from the registry. The diagnoses were reviewed and immunohistochemical staining on tissue sections of testis tumors was performed in order to determine the prognostically different subgroups according to Hans et al (2). In addition, tissue sections of bone marrow biopsies or flowcytometric analyses of bone marrow aspirates, performed for staging purposes, were reviewed.Seven (36%) and 13 (65%) of the 19 testicular DLBCL were of the GC and ACT subtype, respectively. Quite unexpectedly, bone marrow involvement by a small B-cell proliferation was detected in 9/19 cases (47 %). None of the cases showed bone marrow involvement by DLBCL. Further typing of the small B-cell proliferations in the bone marrow, revealed 3 cases of lymphoplasmacytic lymphoma (LPL), 5 cases with the morphology and immunophenotype compatible with marginal zone B-cell lymphoma (MZL), and 1 case of chronic lymphocytic leukemia (CLL). None, but one of those cases of small B-cell lymphomas were diagnosed before diagnosis of the testicular DLBCL. Interestingly, 7/9 patients with a concurrent small B-cell proliferation in the bone marrow had the ACT subtype of testicular DLBCL, whereas 2 had a GC subtype DLBCL. In six cases appropriate diagnostic biopsies were available to investigate whether the testicular DLBCL and the bone marrow lymphoma were derived from the same B-cell clone by size-fractionation and/or sequencing of the respective rearranged immunoglobulin genes. Interestingly, in only one case of LPL in the bone marrow with GC testicular DLBCL, two different clones were detected, whereas in the other five cases the small B-cell proliferation in the bone marrow and the testicular DLBCL were derived from the same clone.In conclusion, testicular DLBCL of ACT subtype is often associated with clonally-related small B-cell proliferation in the bone marrow. It is of interest that none of the lymphomas in the bone marrow were follicular lymphomas. It seems therefore likely that many testicular DLBCL of ACT subtype may represent transformed non-follicular small B-cell lymphoma. This hypothesis needs corroboration by genetic data.