HIV-negative, HHV-8-unrelated primary effusion lymphoma-like lymphoma with genotypic infidelity and c-MYC expression

Dear Editor, HIVor HHV-8-related primary effusion lymphoma (PEL) is a rare and poor prognostic disease which presents as serous effusion without detectable tumor masses. PEL occasionally has both immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements, so-called genotypic infidelity [1, 2]. Recently, HIV-negative HHV-8-unrelated primary effusion lymphomalike lymphoma (PEL-LL) has been reported, and some cases are associated with c-MYC amplification. Although HHV-8 virus antigen can increase c-MYC stability in PEL [3], c-MYC expression in PEL-LL has not been confirmed so far. A 76-year-old male had suffered from esophageal cancer, which responded to chemoradiotherapy. Three years after treatment, however, he had experienced cough, general fatigue, and night sweats. Physical examination revealed no breath sounds on the right hemithorax. Chest X-ray showed severe pleural effusion in the right lung (Fig. 1a). However, no tumor mass or lymphadenopathy was detected. Gastrointestinal fiberscope showed no sign of esophageal cancer recurrence. Complete blood count and serum biochemistry studies were as follows: WBC 7,170/μl, hemoglobin 10.6 g/dL, platelet 402,000/μl, AST 20 IU/L, ALT 12 IU/L, LDH 377 IU/L, total bilirubin 0.4 mg/dL, and sIL-2R 525 U/ml. Serological tests for HIV, HTLV-1, and HCV were negative. Bone marrow was intact. In analysis of pleural effusion, there were many large atypical lymphocytes which were positive for CD19, CD20, CD30, CD79a, and Ig lambda light chain but negative for CD10 and CD56 (Fig. 1b). HHV-8 and EBVencoded RNA by immunochemistry were negative. There was a small fraction of normal T cells. Eighty percent of lymphocytes were Ki-67 positive. Southern blot analysis of tumor cells demonstrated Ig heavy chain (IgH) as well as TCR rearrangement (Fig. 1c). Karyotype analysis showed complex karyotype, including add(8)(q24) and c-MYC amplification, and these cells strongly expressed c-MYC protein by immunostaining (Fig.1d). He was diagnosed with PEL-LL and was treated with six courses of R-CHOP. He remains alive and well with slight pleural effusion without additional therapy for more than 18 months. There are only two cases of PEL-LL with both IgH and TCR rearrangements. The first case is a pleural cavity-based T cell-rich B cell lymphoma [4]. Actually, it was reported for this lymphoma to show the dual gene rearrangement [5]. It could be bi-clonal lymphoma, of which the T cell clone was derived from abundant background Tcells. The second case is post-liver transplant effusion lymphoma [6]. It demonstrated incomplete TCR-β rearrangements by PCR; wherein, these rearrangements can be found in some B cell lymphomas [7]. In our case, most cells in the effusion were B cells. In addition, we confirmed both rearrangements by southern blot analysis (Fig. 1c). Therefore, we believe that this is the first definitive case of genotypic infidelity in PEL-LL. In addition, we confirmed strong c-MYC expression on tumor cells along with T. Kashiwagi :K. Minagawa :H. Kawano : T. Hirata : S. Kashiwagi :Y. Nakagawa : S. Kusaka : T. Suzuki : T. Inagaki : M.Kishi :N.Miwa : S. Kimura :M. Takechi :M. Koide :M. Iwai : T. Matsui Department of Internal Medicine, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo 677-0043, Japan