A Rare Cause of Esophageal Ulcers

Abstract

Question: A 64-year-old Japanese man was referred to our hospital for further investigation of a 1-month history of heartburn and epigastric pain. At presentation, the patient’s vital signs were unexceptional and he did not look seriously ill. Medical history disclosed alcoholic hepatitis. He previously consumed alcohol regularly (50 g of alcohol per day), but stopped drinking after his initial visit to our hospital. Esophagogastroduodenoscopy showed multiple ulcers in the lower esophagus and esophagogastric junction. Biopsy examinations were performed twice, 1 month apart, but histologic evaluation revealed only granulation tissues. Immunohistochemistry for cytomegalovirus was negative. Although proton pump inhibitors and gastroprokinetic agents had been administered for the following 4 months, the esophageal ulcers were unchanged (Figure A, B). Laboratory testing revealed an exacerbating elevation of liver enzyme levels: aspartate aminotransferase, 213 U/L; alanine aminotransferase, 169 U/L; and lactate dehydrogenase, 634 U/L. The results of interferon-γ release assay for Mycobacterium tuberculosis and (1–3)-β-D glucan were negative. CT demonstrated multiple ground glass opacities and granular shadows in the bilateral lung fields (Figure C), whereas slight steatosis was a sole finding in the liver. At the time of these tests, the patient suffered a high fever, night sweats, and weight loss. What is the diagnosis? Look on page 32 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. Additional laboratory testing revealed an elevated soluble interleukin-2 receptor level (1748 U/mL; normal range, 122-496). Biopsy specimens from the esophageal ulcers revealed an infiltration of lymphoma cells (Figure D) that were positive for CD3 (Figure E), T-cell intracellular antigen-1, and granzyme B (Figure F). The result of an in situ hybridization for Epstein-Barr virus-encoded small RNA-1 was also positive (Figure G). Biopsies from the liver, lung, and bone marrow showed infiltrations of lymphoma cells as well. The patient was diagnosed with systemic involvement of extranodal NK/T-cell lymphoma (ENKTL), nasal type. Chemotherapy with dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide produced no response, and gemcitabine was administered as the second line of treatment. However, the patient’s respiratory condition deteriorated rapidly and he died 1 month after diagnosis. The multiple, linear, and relatively deep ulcers described herein can be induced by cytomegalovirus or human immunodeficiency virus infection.1Rosołowski M. Kierzkiewicz M. Etiology, diagnosis and treatment of infectious esophagitis.Prz Gastroenterol. 2013; 8: 333-337Google Scholar Patients with systemic inflammatory disorders such as Behçet’s disease, although uncommon, present with deep ulcers in the esophagus as well.2Yen H.H. Soon M.S. Electronic image of the month. Fever and upper gastrointestinal bleeding: Behçet’s disease.Clin Gastroenterol Hepatol. 2010; 8: e35-e36Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar However, esophageal involvement is rare among all lymphoma patients. ENKTL commonly affects the gastrointestinal tract in addition to the nasal areas, skin, liver, and soft tissue, although a previous report found that the esophagus is the least commonly involved gastrointestinal site, accounting for only 1% of ENKTL patients with gastrointestinal involvement.3Kim S.J. Jung H.A. Chuang S.S. et al.Extranodal natural killer/T-cell lymphoma involving the gastrointestinal tract: analysis of clinical features and outcomes from the Asia Lymphoma Study Group.J Hematol Oncol. 2013; 6: 86Crossref PubMed Scopus (55) Google Scholar Biopsies and appropriate immunostaining are mandatory for the detection of lymphoma as well as for differentiation from the other diseases mentioned; different therapies are required for the different diseases.