Immunosuppressed Solid Organ Transplant Recipient

Abstract

Question: A 47-year-old woman with a history of renal-pancreas transplant was admitted to the hospital for intractable nausea and vomiting in the setting of month-long dysphagia initially to solids which then progressed to liquids and intermittent odynophagia. She denied any nonsteroidal anti-inflammatory drug use, weight loss, diarrhea, or constipation. Past medical history was remarkable for a renal-pancreas transplant 5 years prior for diabetic complications with pancreas retransplantation owing to allograft arterial thrombosis. Previous Helicobacter pylori serology was positive 6 months prior, but she was unable to complete the prescribed triple therapy. Medications included mycophenolate mofetil 750 mg BID, tacrolimus 2 mg BID, and prednisone 5 mg/d. Initial examination was remarkable for oral thrush in the absence of other lesions. Abdominal examination was benign. Notable laboratory findings included creatinine of 1.6 mg/dL, tacrolimus level 3.9 ng/mL, H pylori immunoglobulin G >8 U/mL (normal, <0.89). Epstein-Barr virus viral load was 2379 log copies/mL. Computed tomography of the abdomen and pelvis showed normal-appearing renal and pancreatic allografts and atrophic native kidneys and pancreas. Because of the concern for an infectious etiology for her symptomatology given her degree of immunosuppression, the patient underwent an esophagogastroduodenoscopy which revealed LA grade D erosive esophagitis (Figure A) and distal esophageal candidiasis. Esophageal biopsies were obtained (Figure B, stain: H&E; original magnification, ×20; Figure C, stain: H&E; original magnification, ×400). What is the most likely diagnosis? How should this patient be treated? Look on page 590 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Tissue biopsy of the esophagus demonstrated large atypical lymphocytes with marked nuclear pleomorphism, multinucleation, and enlarged nucleoli associated areas of necroinflammatory debris and granulation tissue. In situ hybridization of the biopsy specimens for Epstein-Barr virus was widely positive, suggestive of posttransplant lymphoproliferative disorder (PTLD; Figure D). Lymphocytic markers for CD20+ as well as clonal immunoglobulin heavy chain gene rearrangement demonstrated a large population of clonal B cells and confirmed the diagnosis. The patient was treated with 4 cycles of rituximab with complete radiographic regression of her disease. PTLD is characterized by lymphoid proliferations that occur as a result of T-cell immunosuppression in the setting of solid organ transplantation1Hanto D.W. Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategies.Annu Rev Med. 1995; 46: 381Crossref PubMed Scopus (114) Google Scholar and is the most common malignancy found in solid organ recipients (excluding nonmelanoma skin cancer and in situ cervical cancer).2Adami J. Gäbel H. Lindelöf B. et al.Cancer risk following organ transplantation: a nationwide cohort study in Sweden.Br J Cancer. 2003; 89: 1221Crossref PubMed Scopus (556) Google Scholar PTLD accounts for roughly 20% of all cancers in this population. The majority of PTLD occurs in the presence of Epstein-Barr virus infection and is most likely to occur during the first year after transplantation. The presentation of PTLD is variable and depends on the areas involved, although the majority of patients have a combination of nonspecific constitutional symptoms such as fever, weight loss, fatigue, and flu-like symptoms. Diagnosis of PTLD requires biopsy to perform histologic, immunophenotypic, and genetic studies. Initial treatment is focused on a reduction of immunosuppression, immunotherapy with rituximab for CD20-positive patients, chemotherapy, radiation therapy, or a combination of these modalities.3Straathof K.C. Savoldo B. Heslop H.E. et al.Immunotherapy for post-transplant lymphoproliferative disease.Br J Haematol. 2002; 118: 728Crossref PubMed Scopus (58) Google Scholar Although esophageal lymphoma in general is rarely reported in the literature, having a high index of suspicion for PTLD of any organ including the gastrointestinal tract is necessary in solid organ transplant recipients, even in the case of common systemic complaints or disorders.