EBV-positive diffuse large B-cell lymphoma of the elderly with aberrant expression of CD3 and TIA-1
A 72-year-old, HIV-negative Korean female presented with easy fatigue and epigastric discomfort, which had been gradually worsening over a period of 4 months, and weight loss of 3 kg over a period of 1 month. She had a history of stroke, hypertension, and osteoporosis with spinal fractures. Laboratory tests on admission revealed an elevated serum lactate dehydrogenase level (489 IU/L; reference range, 120-250 IU/L) with a slightly decreased serum hemoglobin level (10.2 g/dL; reference range, 12-16 g/dL). Computed tomography (CT) scans of the neck, chest, and abdomen showed multiple lymph node enlargements in the left supraclavicular area and the retroperitoneum, with a 7.5 cm cystic lesion in the left perirenal space. A 2 cm-sized gastric mass with central ulceration was noted during esophagogastroduodenoscopy (EGD). A biopsy of the left supraclavicular lymph node showed a partial effacement of the nodal architecture with diffuse infiltration by large atypical tumor cells separated by collagenous septae (). There were also multiple foci of geographic necrosis. These cells had pleomorphic nuclei, vesicular chromatin, prominent macronucleoli, and numerous mitotic figures, with many bizarre Reed-Sternberg (RS)-like multinucleated cells. Admixed with the tumor cells were small numbers of mature small lymphocytes and macrophages. A gastric biopsy also revealed similar findings. Immunohistochemistry showed that the tumor cells were positive for CD20, CD79a, CD3, MUM-1, BCL-2, TIA-1, CD43, OCT-2, and BOB-1, weakly positive for PAX-5, but negative for CD2, CD5, CD4, CD8, granzyme B, TCR-β F1, TCR-γ receptor, BCL-6, CD10, ALK-1, CD30, CD15, myeloperoxidase, and CD163. In the background, there were only a few scattered T cells, some of which were positive for TIA-1. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed positive nuclear signals in almost all tumor cells. A quantitative real-time PCR for Epstein-Barr virus (EBV) in the patient's serum showed that the EBV load was high (131,000 copies/mL). Clonality studies using multiplex PCR with BIOMED-2 primers (InVivoScribe Technologies, San Diego, CA, USA) revealed a dual rearrangement of IgH genes and TCR-γ genes (), whereas a TCR-β gene rearrangement study failed to identify a monoclonal T-cell population. Based on the expression of almost all B-cell-associated antigens and the monoclonal rearrangement of IgH genes, the patient was diagnosed with EBV-positive DLBCL of the elderly with an aberrant expression of CD3 and TIA-1. Tumor cells were also noted in bone marrow biopsy and clot sections, assigning her to the Ann Arbor stage 4B. She received 6 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), which resulted in almost complete remission. A follow-up positron emission tomography (PET) scan 8 months after the diagnosis revealed the disappearance of hypermetabolic lesions from the left supraclavicular area, retroperitoneum, and stomach. However, a cystic lesion with calcifications in the perirenal space, which seemed to be non-neoplastic (e.g., a postinflammatory calcification, a pseudocyst, or an old hematoma), was persistently observed on 3 follow-up CT scans after chemotherapy (R-CHOP) with salvage radiotherapy (3,060 cGy/20 fx, 5 weeks) for the perirenal lesion.