Oral EBV-associated diffuse large B-cell lymphomas in HIV-negative immunocompromised patients

Background: Diffuse large B-cell lymphomas (DLBCL) are non-Hodgkin's lymphomas (NHL) and with a prevalence of 30-40% they comprise the most frequent NHL in adults. Although their etiology is still unknown, a virus induction, especially by the Epstein-Barr-virus (EBV), is the subject of discussion. Patients with congenital or acquired immunodeficiency are primarily afflicted. PATIENT 1: A 39-year-old female patient developed an EBV-associated DLBCL of the plasmablastic subtype in the maxillary alveolar ridge in the region of teeth 11 and 21 after 24 years of immunosuppressive therapy with azathioprine due to myasthenia gravis. Clinically the lesion presented as a localized acute necrotizing periodontitis that was resistant to symptomatic therapy. After polychemotherapy the disease is in complete remission until today. PATIENT 2: A 56-year-old male patient developed an EBV-associated DLBCL of immunoblastic variant of the right maxillary edentulous alveolar ridge in the posterior region 7 weeks after heart transplantation and immunosuppressive therapy with azathioprine and cyclosporine A. Clinically, a soft, nonpainful, swelling measuring 1.5x0.5x0.5 cm with a central ulceration was evident. The tumor was excised followed by local radiation therapy. No recurrence was noted during a 15-year-follow-up.

Conclusions: The presented clinical cases demonstrate the increased risk of occurrence of oral malignant B-cell lymphomas as adverse effects of immunosuppressive therapy. The demonstration of EBV in the tumor cells in both cases underlines the involvement of this virus in the pathogenesis of oral DLBCL arising in the setting of an immunodeficiency as has been shown previously in patients with HIV. Conclusions: Due to the varying and often nonspecific clinical appearance of oral DLBCL, an early biopsy and work-up by an institute specialized in hematopathology is essential for diagnosis, because these tumors may disseminate in early stages.