Epstein-Barr Virus–Positive Primary Gastrointestinal Hodgkin's Disease

Abstract

Inflammatory bowel disease (IBD) is associated with an increased risk of lymphoma, which is usually extraintestinal but sometimes may involve the diseased bowel itself. Most lymphomas described in this setting are of non-Hodgkin's type, but rare cases of Hodgkin's disease (HD) have been reported. We describe the clinicopathologic and molecular features of four patients with primary gastrointestinal HD. Three patients had preexistent Crohn's disease (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. Multifocal 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, and the fourth patient died in the postoperative period before further workup. Two patients received chemotherapy, one of whom was dead at 9 months, whereas the other has no evidence of disease at 25 months' follow-up. The patient with IE disease did not receive any therapy because only a few microscopic foci of disease were present and is also without any evidence of disease at 17 months. The Reed-Sternberg (RS) cells in all four cases expressed CD30, CD15, EBER-1, and LMP-1; two of four were focally CD20-positive. VJ-polymerase chain reaction for immunoglobulin heavy chain (IgH) rearrangement showed a polyclonal pattern in all four cases. In two cases, laser capture microdissection was used to isolate individual RS and Hodgkin's cells, which contained rearranged immunoglobulin genes, confirming a B-cell genotype. Whereas one case showed a dominant clonal band present in all isolates, cells from the patient with stage IE disease clearly showed a polyclonal population of RS cells. Our findings indicate that HD arising in the setting of IBD or chronic inflammation is the result of an Epstein-Barr virus-driven lymphoproliferation, analogous to that found in other immunodeficient states. Disordered immunoregulation inherent to CD and immunosuppressive therapy for the latter may contribute to its development. The finding of polyclonal RS cells in a patient with early stage disease and apparent cure by surgical resection versus monoclonal RS cells in the patient with disseminated disease suggests that HD in the setting of immunodeficiency also may show molecular progression, in a manner similar to that occurring in conventional B-cell lymphoproliferative disorders arising in the same setting.

Plasmablastic lymphoma in the ano-rectal junction presenting in an immunocompetent man: a case report

“…In a case series reported by Teruya-Feldstein et al . [26], two out of six cases of PBL in HIV-negative individuals occurred in the setting of iatrogenic immunosuppression; one was a recipient of a renal allograft with localization of PBL to the skin of the leg [27] and the other a patient with ulcerative colitis receiving azathioprine [28]. Both cases were EBV positive.…”

Gastrointestinal lymphoproliferative disorders

“…When, instead, this special type of malignant lymphoma presents in the gut there is usually some underlying immunodeficiency. Such cases occur predominantly in elderly patients and in those with immunodeficiency, or who are immunosuppressed and are almost always positive for EBV 45 . Because Hodgkin's lymphoma often takes on a slightly different microscopic appearance in extranodal sites, and because of its rarity in the gut, suspected cases require paraffin section immunophenotypic confirmation, e.g.…”

“…Such cases occur predominantly in elderly patients and in those with immunodeficiency, or who are immunosuppressed and are almost always positive for EBV. 45 Because Hodgkin's lymphoma often takes on a slightly different microscopic appearance in extranodal sites, and because of its rarity in the gut, suspected cases require paraffin section immunophenotypic confirmation, e.g. tumour cell reactivity for CD30 (and for CD15 in some cases) and lack of reactivity for CD45 (leucocyte common antigen) and CD43 (a marker often positive in anaplastic large-cell lymphoma).…”

Laser capture microscopy

“…It is possible that clonality in Hodgkin's disease will prove to be of prognostic importance. 14 LCM has been used to extract individual tumour cells from a basal cell carcinoma of the skin with subsequent analysis of p53 mutations by sequencing of PCR products. Identical mutations were identified in cells from diVerent parts of the tumour.…”