Reactive lymphoid hyperplasia of the terminal ileum: a benign (lymphoma-like) condition that may harbor aberrant immunohistochemical patterns or clonal immunoglobulin heavy chain gene rearrangements.

Small endoscopic biopsies of the terminal ileum may be difficult to assess for early involvement by lymphoma. Immunophenotypic and genotypic analyses are often utilized, but the performance of these studies in this setting is not well defined. Terminal ileal biopsies from 66 patients with prominent lymphoid hyperplasia and abnormal "lymphoma-like" morphology were evaluated by immunohistochemistry (IHC) for CD3, CD5, CD43, CD20, CD21, and CD10 expression and for IGH@ gene rearrangement by polymerase chain reaction using BIOMED-2 primers. Patients ranged in age from 3 to 80 years. Indications for endoscopy included inflammatory bowel disease (29), diarrhea and/or abdominal pain (28), history of lymphoma (13), and others (4). Four biopsies with abnormal morphology had abnormal IHC and a clonal IGH@ peak; all were obtained from patients with a history of lymphoma and determined to be recurrent lymphoma. Three biopsies with abnormal morphology and abnormal IHC but no clonal IGH@ peak were obtained from patients with a history of lymphoma (2) and chronic diarrhea (1); all showed symptom resolution or remission of disease (mean follow-up, 37 mo). Eight biopsies with abnormal morphology but no abnormal IHC expression also had abnormal IGH@ results (4 clonal and 4 borderline). IGH@ evaluation of follow-up biopsies for these cases were nonclonal (7) or clonal, but with a different clone from the prior biopsy (1); follow-up of the 8 patients showed no evidence of lymphoma (mean, 37.8 mo). Abnormal IHC expression pattern or clonal IGH@ rearrangement in endoscopic biopsies of the lymphoid-rich terminal ileum do not necessarily warrant a diagnosis of lymphoma. To prevent misdiagnosis, B-cell clonality studies should only be performed when there is strong clinical suspicion for lymphoma and compelling IHC data; the absence of a reproducible clone in repeat biopsy specimens may be useful in patients that do not have other clinical evidence of lymphoma.