Epstein-Barr virus-positive primary gastrointestinal Hodgkin's disease - Association with inflammatory bowel disease and immunosuppression

Inflammatory bowel disease (IBD) is associated with an increased risk of ly mphoma, which is usually extraintestinal but sometimes may involve the dise ased bowel itself. Most lymphomas described in this setting are of non-Hodg kin's type, but rare cases of Hodgkin's disease (HD) have been reported. We describe the clinicopathologic and molecular features of four patients wit h primary gastrointestinal HD. Three patients had preexistent Crohn's disea se (CD), for which two of them had received immunosuppressive therapy. The fourth patient had a longstanding history of diverticulitis and myasthenia gravis and was receiving immunosuppressive therapy for the latter. Multifoc al involvement of the bowel by HD was noted in all four cases. Disease was staged as IVA in one patient, IIIB in one patient, and IE in one patient, a nd the fourth patient died in the postoperative period before further worku p. Two patients received chemotherapy, one of whom was dead at 9 months, wh ereas the other has no evidence of disease at 25 months' follow-up. The pat ient with 1E disease did not receive any therapy because only a few microsc opic foci of disease were present and is also without any evidence of disea se at 17 months. The Reed-Sternberg (RS) cells in all four cases expressed CD30, CD15, EBER-1, and LMP-I; two of four were focally CD20-positive. VJ-p olymerase chain reaction for immunoglobulin heavy chain (IgH) rearrangement showed a polyclonal pattern in all four cases. Tn two cases, laser capture microdissection was used to isolate individual RS and Hodgkin's cells, whi ch contained rearranged immunoglobulin genes, confirming a B-cell genotype. Whereas one case showed a dominant clonal band present in all isolates, ce lls from the patient with stage IE disease clearly showed a polyclonal popu lation of RS cells. Our findings indicate that HD arising in the setting of UBD or chronic inflammation is the result of an Epstein-Barr virus-driven lymphoproliferation, analogous to that found in other immunodeficient state s. Disordered immunoregulation inherent to CD and immunosuppressive therapy for the latter may contribute to its development. The finding of polyclona l RS cells in a patient with early stage disease and apparent cure by surgi cal resection versus monoclonal RS cells in the patient with disseminated d isease suggests that HD in the setting of immunodeficiency also may show mo lecular progression; in a manner similar to that occurring in conventional B-cell lymphoproliferative disorders arising in the same setting.