A Case Report - Posttransplantation Lymphoproliferative Disorder

Linda S. Lee, MD, David L. Carr-Locke, MD, FRCP

Disclosures

February 12, 2003

Introduction

Gastrointestinal complications are common after solid organ transplantation. Studies of heart-lung and lung transplants report incidences of gastrointestinal complications ranging from 16% to 42%.[1] Half of the complications occur early, within 30 days of transplantation.[2] Complications include ileus, gastroparesis, gastritis, peptic ulcer disease, cholelithiasis, and colonic perforation.[1] Infections and malignancies, including posttransplantation lymphoproliferative disorder (PTLD), occur later. Lymphoproliferative disorders account for a larger percentage of all malignancies in organ transplant recipients (21%) compared with the general population (5%).[3] In addition, although non-Hodgkin's lymphoma accounts for 65% of lymphomas in the general population, it accounts for 93% of lymphomas in transplant recipients, with the majority having extranodal rather than lymph node involvement.

A 53-year-old woman who had undergone a single right lung transplant in 2001 for chronic obstructive pulmonary disease was admitted 1 year later with fatigue, dyspnea on exertion, and watery diarrhea.

Prior to transplantation she was cytomegalovirus (CMV)-negative and Epstein-Barr virus (EBV)-positive, whereas the donor was CMV-positive. The initial posttransplantation course was complicated by upper gastrointestinal bleeding. Upper endoscopy revealed Barrett's esophagus, fundal erosions, and duodenitis with small pink duodenal nodules. Results of biopsy were normal and negative for CMV, herpes simplex virus, and adenovirus.

At 1 month, acute rejection was successfully treated with pulses of intravenous steroid. Chest computed tomography (CT) scan performed at 1 year revealed multiple new right lung nodules, and subsequent fine-needle aspiration was negative for tumor or infection. During the following week, the patient developed dyspnea on exertion, fever, anorexia, and watery diarrhea and was admitted to hospital. Her outpatient immunosuppressive regimen included prednisone 15 mg per day, mycophenolate mofetil 1000 mg twice daily, and tacrolimus 5 mg twice daily.

Bronchoalveolar lavage on admission revealed CMV for which the patient was started on valganciclovir. Initial abdominal CT scan without intravenous contrast demonstrated pericecal fat stranding with associated retroperitoneal lymphadenopathy. Repeat abdominal CT scan with intravenous contrast 5 days later showed a newly thickened cecum with regional lymphadenopathy, a 2-cm left para-aortic lymph node, and 3 masses in the right lobe of the liver, the largest of which was 1.8 cm. In addition, the bilateral pulmonary nodules had enlarged. Colonoscopy revealed multiple ulcers with regular borders and heaped-up edges varying in size from a few millimeters to several centimeters throughout the entire colon, but more numerous in the proximal colon (Figures 1 and 2).

Colonic ulcers.

Colonic ulcers.

Biopsies were consistent with a large, B-cell-type non-Hodgkin's lymphoma that was EBV-positive by in situ hybridization (Figures 3-5).

Low-power H&E (hematoxylin and eosin) stain; colonic mucosa with atypical lymphocytes.

Diffusely positive CD20 (B-cell marker) immunostain.

In situ hybridization of EBV-associated early mRNA (dark nuclear stain).

The patient subsequently underwent a video-assisted thoracoscopic surgery procedure with lung wedge biopsy confirming the diagnosis of lymphoma and CMV pneumonitis. Therapy was begun with rituximab, and mycophenolate mofetil was discontinued; the dose of tacrolimus was reduced by half.

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