Diagnostic and therapeutic challenges of EBV-positive mucocutaneous ulcer: a case report and systematic review of the literature

Jay Justin Liao,Xueyan Chen,Toni K Roberts

doi:10.1186/s40164-016-0042-5

Abstract

BackgroundEpstein–Barr virus-positive mucocutaneous ulcer (EBVMCU) is a recently recognized B cell lymphoproliferative disorder that is driven by latent EBV infection and causes discrete ulcerations in the oropharynx, gastrointestinal tract, and skin. Local attenuation of immunosurveillance associated with iatrogenic immunosuppressant use, primary immunodeficiency, or age-associated immunosenescence has been implicated as a predisposing factor. This disorder is likely under reported, as it was only first defined in 2010 and shares histological features with other B-cell proliferative neoplasms. The first case series that described EBVMCU suggested that EBVMCU is generally self-limited and is likely to resolve without treatment. Since that publication, additional cases have been reported that describe a more heterogeneous clinical course, often requiring aggressive therapy. We now systematically review all published cases of EBVMCU and detail a case of aggressive and progressive EBVMCU, including diagnostic and management challenges, as well as successful treatment with radiation therapy.Case presentationA forty-nine year old woman presented with painful and debilitating multifocal oral EBVMCU that initially responded to four weekly doses of rituximab. Her disease relapsed within 3 months and continued to progress and cause significant morbidity. She was successfully treated with local external beam radiation therapy of 30 Gy in 15 fractions, with duration of response of at least 6 months.ConclusionsWe suggest that although many patients with EBVMCU experience a self-limited course, for others EBVMCU can be a debilitating, persistent disorder that requires aggressive therapy to prevent disease progression. CD20- and CD30-directed antibody therapy, local radiation therapy, local surgical excision, systemic chemotherapy, and a combination of these therapies have all been successfully used to treat EBVMCU with high rates of durable clinical remission. As EBVMCU is not currently included in the 2008 WHO classification of lymphoproliferative disorders and no evidence-based guidelines or expert opinions have been proposed to guide therapy, this case report and systematic review provides a foundation on which to guide therapeutic decisions.

Highlights

Epstein–Barr virus-positive mucocutaneous ulcer (EBVMCU) is a recently recognized B cell lymphoproliferative disorder that is driven by latent EBV infection and causes discrete ulcerations in the oropharynx, gastrointestinal tract, and skin
Extensive mucosal ulceration was noted with an underlying dense infiltration of small lymphocytes and frequent admixed large atypical lymphocytes including rare Hodgkin and Reed-Sternberg (HRS)-like forms that were positive for CD30, paired box protein 5 (PAX5), CD20, Epstein–Barr virus-encoded small ribonucleic acids (EBER), and negative for CD3, CD15, and CD79a
EBVMCU has not been included in the 2008 Word Health Organization (WHO) classification schema of B-cell neoplasms, the presence of discrete ulcer(s) with an underlying polymorphous infiltrate of small lymphocytes, immunoblasts with frequent HRS morphology, plasma cells, eosinophils, and histiocytes is characteristic of the disorder

Summary

Conclusions

EBVMCU is a rare EBV-associated lymphoproliferative disorder that is likely under reported secondary to its recent recognition and morphologic and immunophenotypic similarities to Hodgkin lymphoma and diffuse large B cell lymphoma. We suggest consideration of its inclusion in the iteration of the WHO classification of lymphoproliferative disorders. This disease is characterized by solitary or multifocal ulcers of the oropharynx, gastrointestinal tract, and skin that result from EBV-driven proliferation of B- and T-lymphocytes in the setting of local lapse in immunosurveillance secondary to iatrogenic immunosuppression, primary immunodeficiency, or age-related immunosenescence. JJL performed radiation therapy planning, prepared radiographic planning images, and edited the manuscript. Author details 1 Department of Hematology Oncology, Fred Hutchinson Cancer Research Center, University of Washington Allied Hospitals, 1100 Fairview Ave N‐D5‐100, Seattle, WA 98109‐1024, USA. 3 Department of Radiation Oncology, University of Washington, 1959 NE Pacific St, 1st floor, NN106, Seattle, WA 98195, USA.

Background

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