A case of iatrogenic immunodeficiency-associated colonic lymphoma complicating ulcerative colitis

A 68-year-old man was diagnosed with left-sided UC 26 months prior and was followed up without any treatment. He was first treated with 5-aminosalicylate because of worsening of diarrhea. A dose of 30–50 mg/day of prednisolone was also administered for the control of diarrhea and bloody stools. However, his symptoms repeatedly recurred with the sequentially decreasing usage of prednisolone. He was treated with an initial dose of 25 mg/day of azathioprine and a dose of 5 mg/kg twice daily of infliximab 8 months prior, but he could not obtain a satisfactory improvement in symptoms. Ultimately, he was diagnosed with pancolitic UC by colonoscopy. Ganciclovir was administered 1 month prior due to cytomegalovirus (CMV) antigenemia. Though the serum CMV antigen disappeared, the patient was transferred to our hospital with a complaint of a persistent fever and a perianal fistula. Immediately, abdominal computed tomography showed circumferential thickening of the rectal wall and a discontinuity in contrast enhancement of the posterior rectal wall. Because of suspicion of rectal perforation, an emergency total proctocolectomy was performed. After the total proctocolectomy, the patient achieved clinical remission without any additional treatment. There was no recurrence for 40 months after the operation, as shown by computed tomography. The resected specimen was fixed in 10% buffered formalin, and paraffin-embedded tissue sections were used for histological examination.

The resected specimen exhibited irregular wall thickening and elevated multinodular lesions extending from the mid-transverse colon to the rectum, measuring up to 52 cm in length (Fig. 1). Multiple sharply circumscribed ulcers and geographic necrosis were present. A rectal perforation, approximately 2 cm in diameter, was also noted. No abnormal mesenteric lymphadenopathy was noted.

Microscopically, the resected lesion exhibited the diffuse transmural proliferation of lymphocytes and immunoblasts (Fig. 2a). Many polymorphic, large, atypical lymphocytes and scattered Hodgkin-like cells were present intermingled with scattered plasma cells, histiocytes and eosinophils in the background (Fig. 2b & c). Apoptotic bodies with plasmacytoid features were absent. Additionally, around the lymphoma, more remarkably in the distal colon than in the proximal colon remote to the lymphoma, admixed inflammatory cells composed of reactive lymphocytes with occasional lymphoid follicles, plasma cells including basal plasmacytosis, histiocytes, neutrophils often with cryptitis and crypt abscesses, and eosinophils infiltrated in the lamina propria mucosae with or without erosion or ulcers, indicating histological features compatible with UC, grade 5 in the maximal degree (Fig. 2d). Pleomorphic, large, atypical lymphocytes were immunohistochemically positive for CD20 (Fig. 3a), CD79a, MUM-1, and κ-light chain and negative for CD3, CD5, BCL-2, BCL-6, c-Myc, GCET1, Foxp1, and λ-light chain. The cells were also positive for κ-light chain but not λ-light chain according to in situ hybridization (ISH) (Fig. 3b & c). Scattered Hodgkin-like cells were immunohistochemically positive for CD20, CD30 (Fig. 3d), CD79a, PAX5, and LMP-1 (partially) but not CD10, CD15, BOB1, OCT2, BCL-6, or MUM-1. In both atypical lymphocytes and Hodgkin-like cells, Epstein-Barr encoding region (EBER)-1 positivity was detected by ISH (Fig. 3e). The base of the ulcer was rimmed by numerous medium-sized T-cells positive for CD3. Polymerase chain reaction (PCR) revealed a gene rearrangement of the immunoglobulin heavy chain but not the γ-chain of the T-cell receptor. Based on these clinical, histological and immunohistochemical findings, this lesion was diagnosed as Oii-LPD, DLBCL phenotype, polymorphous subtype. Large, atypical cells with a viral inclusion body were absent and immunohistochemically negative for CMV.

As a retrospective analysis, immunohistochemistry for CMV and ISH for EBER-1, κ-light chain, and λ-light chain were performed on paraffin-embedded tissue sections obtained from the colorectal biopsies of our patient at 9 days, 3 weeks, 6 months, 8 months, and 10 months before admission to our hospital. CMV-positive cells were present on the 3-week and 6-month tissue sections. EBER-1-positive large, atypical cells were present on the 9-day and 3-week tissue sections (Fig. 3f & g). There was no restriction of the κ-light chain or λ-light chain by ISH on any biopsied specimen.