Gingival ulcer in a patient with psoriatic arthritis

A 70-year-old woman was referred presenting a symptomatic, ulcerated intraoral lesion with a 5-month evolution. Her medical history revealed a diagnosis of psoriatic arthritis 15 years ago, treated with methotrexate (MTX), and use of risedronate sodium 3 years ago for osteoporosis treatment. On extraoral examination, there was no involvement of the skin or other mucous membranes. On intraoral examination, a symptomatic, extensive ulcerative lesion with necrotic tissue bed, slightly erythematous and hardened edges, involving palatine gingiva of tooth #27, which presented with attachment loss and grade III mobility (Figure 1). Periapical radiography was consistent with periodontal disease. The panoramic radiograph did not show any sign of bone involvement in another location. Thus, an incisional biopsy was performed. The correct diagnosis is C, Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU). The histopathological examination showed a large lymphoid infiltrate with defined edges at the base of the lesion. At high-power view, a small- to medium-sized lymphoid cell population was predominant, admixed with large atypical cells, some of them resembling Hodgkin and Reed-Sternberg (HRS) cells (Figure 2a–c). The immunohistochemical (IHC) analysis showed numerous CD3+ T-cells surrounding the large atypical cells, which were positive for PAX5, CD30, and focally for CD20. CD15 and HHV-8 were negative. The Ki-67 highlighted most large atypical cells. By in situ hybridization (ISH), numerous polymorphous cells were positive for EBER1/2 (Figure 2d–n). In the current case, intraoral ulceration in patients treated with MTX is relevant and usually guides the clinical diagnostic process. However, necrotizing ulcerative periodontitis (Delgado et al., 2009) and deep fungal infection should be taken into consideration, especially the latter as Brazil is an endemic area of paracoccidioidomycosis, with histoplasmosis may affect elderly individuals. EBVMCU is a self-limiting ulcerative lesion that develops in immunosuppressed patients, often affecting the upper aerodigestive tract (Dojcinov et al., 2010; Sawada et al., 2023; Takahama Jr et al., 2019). Immunodeficient status of the patients may be due to immunosenescence or variety of drug-induced immunosuppression, including MTX (Satou et al., 2019), azathioprine (McGinness et al., 2012), chloroquine diphosphate (Takahama Jr et al., 2019), mycophenolate mophetil, prednisone (León et al., 2011), among others. Additionally, EBVMCU cases have been reported associated with organ transplantation (Hart et al., 2014; León et al., 2011) and HIV infection (Bunn & van Heerden, 2015). To date, 52 cases of EBVMCU affecting the oral cavity have been reported. Of them, 25 cases (48%) were associated with the use of MTX (MTX-EBVMCU) (Ohata et al., 2017; Sawada et al., 2023). Eighteen were female and 7 were male, with a mean age of 71 years (range 52–84 years) (Ohata et al., 2017; Sawada et al., 2023). The most common location of MTX-EBVMCU was gingiva (16 cases), followed by tongue (4 cases), oral mucosa, NOS (4 cases) and lip (1 case). EBVMCU is a lymphoproliferative disorder showing polymorphous lymphoid infiltrate admixed with EBV+ atypical large and/or HRS-like cells of B phenotype (Dojcinov et al., 2010; WHO, 2022). Most EBVMCU cases spontaneously regress or require reduction or discontinuation of the medication, without progression to disseminated disease (Dojcinov et al., 2010; León et al., 2011; WHO, 2022). By molecular studies, monoclonal TCR or BCR rearrangements are found in about 35% of EBVMCU cases. These findings suggest an overlap of some polymorphic lymphoproliferative disorders and overt lymphomas with an EBVMCU subset (WHO, 2022). In summary, an immusupressive patient presenting an ulcer in mucosal/cutaneous site, microscopically exhibiting a polymorphous lymphoid infiltrate admixed with EBV+ atypical large B-cells, regressing spontaneously or responding to the withdrawal of immunosuppression, such as reported here, is typical for EBVMCU diagnosis. After biopsy, mainly due to increased tooth mobility, extraction of tooth # 27 was performed. After 30 days of discontinuing MTX, on medical advice, complete resolution of the lesion was observed (Figure 2o). On regular follow-up, the patient remained asymptomatic and reported no further episodes of oral ulceration, under the care of multidisciplinary medical team. Camila Oliveira Barbeiro: Investigation; writing – review and editing; writing – original draft; visualization; formal analysis. Evânio Vilela Silva: Investigation; writing – review and editing; writing – original draft; formal analysis. Elaine Maria Sgavioli Massucato: Investigation; writing – original draft; writing – review and editing; formal analysis. Andreia Bufalino: Investigation; writing – original draft; writing – review and editing; supervision; funding acquisition. Fernando Chahud: Writing – review and editing; writing – original draft; supervision; investigation; conceptualization; funding acquisition. Jorge Esquiche León: Conceptualization; investigation; writing – original draft; writing – review and editing; funding acquisition; supervision. Jorge Esquiche León has received research Grants (2016/11419-0, 2022/07479-9, and 2022/12760-9) from the State of São Paulo Research Foundation (FAPESP) and research Grant (304241/2021-0) from the National Council for Scientific and Technological Development (CNPq), Brazil. All authors have no conflicts of interest to disclose. The case reported in this manuscript provided written informed consent for the publication. The data that support the findings of this study are available from the corresponding author upon reasonable request.