Testicular diffuse large cell lymphoma with tubule preservation--molecular genetic evidence of transformation from previous follicular lymphoma.

Testicular lymphomas usually occur in older men and are mostly diffuse large B-cell lymphomas (DLBL). They may be primary manifestation of lymphoma or represent a relapse of a previous non-Hodgkin's lymphoma. This report details a testicular large cell lymphoma, which was proven to be large cell transformation of a low-grade follicular lymphoma biopsied 8 years earlier. Initially, a 38-year old man was diagnosed with cervical lymphadenopathy, and biopsy was interpreted as reactive follicular hyperplasia; no treatment was given, and the lymphadenopathy resolved spontaneously. Eight years later, the patient underwent surgery for a left testicular mass and gastroscopy for gastric symptoms. The patient died 7 months later with evidence for intra-abdominal and central nervous system lymphoma after a brief but temporary response to M-BACOD chemotherapy. Orchiectomy specimen and gastroscopic biopsy showed diffuse large B-cell lymphoma (CD20+), which infiltrated between well-preserved tubules in the testis. Histological comparison with 20 testicular lymphomas without previous lymphoma showed tubule infiltration in all cases, suggesting that the tubule-preserving infiltration pattern could be a histological marker for secondary lymphoma involvement in testis. On re-examination, the lymph node 8 years prior was verified as follicular, predominantly small, cleaved cell lymphoma with bcl2-positive follicles. The earlier follicular lymphoma and the subsequent diffuse large cell lymphoma were analyzed using polymerase chain reaction and showed identical sequences of the t(14;18) translocation and immunoglobulin heavy chain gene rearrangement. Analysis of the VH-gene sequences from the follicular lymphoma revealed sequence heterogeneity consistent with ongoing mutation. However, the transformed diffuse large cell lymphoma had no intraclonal variation, with the sequence matching with one of the subclones from the low-grade follicular lymphoma. These results confirm that the large cell transformation of follicular lymphoma occurs in a single follicular lymphoma cell. This case also indicates that the selection of the transformed clone can be part of the natural history of disease and can occur without exposure to chemotherapy.