Polymorphic EBV-positive post-transplant lymphoproliferative disorder of the colon mimicking EBV-positive mucocutaneous ulcer: a case report

Epstein-Barr virus (EBV)–driven lymphoproliferative disorders (LPDs) are important complications of post-transplant immunosuppression. EBV-positive mucocutaneous ulcer (EBV-MCU) is typically a localized, solitary, sharply circumscribed ulcer with an indolent clinical course, whereas post-transplant lymphoproliferative disorder (PTLD) may be multifocal, disseminated, and life-threatening; however, these entities can overlap histologically on limited gastrointestinal biopsies.

We report a 60-year-old woman with autoimmune hepatitis/primary sclerosing cholangitis (PSC) status-post liver transplantation (2017; re-transplant 2019 for recurrent PSC) who presented with diarrheal illness and subsequently developed gastrointestinal bleeding. Imaging showed enterocolitis with periportal/mesenteric lymphadenopathy, and endoscopy demonstrated severe colitis with multiple superficial ulcers, without a mass lesion. Biopsies revealed severe active ileocolitis with ulceration and an atypical EBV-positive B cell proliferation (CD20/PAX5+, MUM1+, variably CD30+, EBV-LMP1+; polytypic light chains). The differential diagnosis included EBV-MCU and PTLD -  although the superficial ulcerative pattern and absence of a mass initially raised consideration of EBV-MCU, the presence of multiple ulcers and lack of classic EBV-MCU histologic features favored EBV-positive polymorphic PTLD.

Later, a PET-CT demonstrated extensive FDG-avid lymphadenopathy above and below the diaphragm with splenic and adrenal involvement, supporting disseminated EBV-positive PTLD and prompting rituximab-based chemotherapy.

This case highlights the practical challenges of classifying EBV-positive ulcerative gastrointestinal lesions on small biopsies and underscores the need for radiologic and clinical correlation and close follow-up when EBV-MCU and PTLD are both plausible.