A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects

Abstract

Epstein-Barr virus (EBV)-positive mucocutaneous ulcers (EBVMCUs) were first described as a lymphoproliferative disorder in 2010. Clinically, EBVMCUs are shallow, sharply circumscribed, unifocal mucosal or cutaneous ulcers that occur in immunosuppressed patients, including those with advanced age-associated immunosenescence, iatrogenic immunosuppression, primary immune disorders, and HIV/AIDS-associated immune deficiencies. In general, patients exhibit indolent disease progression and spontaneous regression. Histologically, EBVMCUs are characterized by the proliferation of EBV-positive, variable-sized, atypical B-cells. According to conventional histopathologic criteria, EBVMCUs may diagnosed as lymphomas. However, EBVMCUs are recognized as pseudomalignant lesions because they spontaneously regress without anti-cancer treatment. Therefore, overtreatment must be carefully avoided and multilateral differentiation is important. In this article, we reviewed previously reported EBVMCUs focusing on their clinical and pathological aspects in comparison with other EBV-positive B-cell neoplasms.

Keywords: EBV-positive mucocutaneous ulcer; clinical features; immunosuppression; pathological features.

Fig. 1

Macroscopic findings of a gingival Epstein-Barr virus-positive mucocutaneous ulcer. The ulcer appearance while the patient was undergoing methotrexate treatment (A). After reducing the methotrexate dose, the lesion spontaneously resolved (B).

Fig. 5

A gingival Epstein-Barr virus-positive mucocutaneous ulcer (diffuse large B-cell lymphoma [DLBCL] type) in a 69-year-old male. Large, atypical lymphoid cells, with plasmacytoid differentiation are infiltrating the subepithelial lesion. This lesion is similar to a DLBCL with plasma cell differentiation. These atypical lymphoid cells are CD20-negative and positive for CD79a and Epstein-Barr virus-encoded small RNA. Immunoglobulin light chain analysis, using in situ hybridization, showed a κ chain monotype.

Fig. 2

A cutaneous Epstein-Barr virus-positive mucocutaneous ulcer (polymorphous type) on the lower leg of a 72-year-old female undergoing methotrexate treatment. Atypical lymphoid cells with a polymorphous morphology are infiltrating the epidermal, dermal, and subcutaneous tissues. After reducing the methotrexate dose, the lesion spontaneously resolved.

Fig. 4

A gingival Epstein-Barr virus-positive mucocutaneous ulcer (polymorphous type) in a 91-year-old male undergoing methotrexate treatment. The lesion showed polymorphous morphology with Hodgkin and Reed-Sternberg-like cells.

Fig. 3

An Epstein-Barr virus-positive mucocutaneous ulcer (diffuse large B-cell lymphoma [DLBCL] type) in the nasopharyngeal mucosa of an 80-year-old female undergoing methotrexate treatment. This case resembles DLBCL morphology. The lymphoid cells are positive for CD20 and Epstein-Barr virus-encoded small RNA. Following chemotherapy that included rituximab, the lesion showed complete remission.

Fig. 6

A lingual Epstein-Barr virus-positive mucocutaneous ulcer (mucosa-associated lymphoid tissue lymphoma type) in a 66-year-old female undergoing methotrexate treatment. Atypical, medium-sized lymphoid cells demonstrate plasmacytoid features and Russel bodies. In situ hybridization shows that the atypical cells are Epstein-Barr virus-encoded small RNA-positive. After reducing the methotrexate dose, the lesion spontaneously regressed.