RESUMO
BACKGROUND & AIMS: Cancer therapy with immune checkpoint inhibitors can cause colitis and colon perforation. We investigated whether infection with Epstein Barr virus (EBV) associates with development and severity of colitis in patients receiving immune checkpoint inhibitor therapies. METHODS: We performed a retrospective analysis of fixed colon tissues from 16 patients (12 men, 4 women, median age, 69.5 y) with colitis after immune checkpoint inhibitor therapy (9 patients treated with anti-CTLA4, 3 patients treated with anti-PD1, and 4 patients received a combination). Ten tissue samples were biopsies and 6 were collected during resection (4 surgeries for colon perforation). Patients were treated between 2010 and 2018 in the United Kingdom. The tissues were analyzed by pathology, in situ hybridization (to detect EBV-encoded small RNAs [EBERs]), and immunohistochemistry. Clinical data were also collected. RESULTS: Colon tissues from 4 of the 13 patients who received anti-CTLA4 (alone or in combination, 4 with colon perforation) had EBV-positive lymphoproliferations that manifested as florid ulcers associated with polymorphous infiltrates containing EBV-positive blasts (CD30+ or CD30-negative, CD20+, CD3-negative, and EBER+), plasma cells (CD138+, CD20-negative, and EBER+ or EBER-negative), and small B cells (CD20+, CD3-negative, and EBER+ or EBER-negative), consistent with EBV-positive mucocutaneous ulcers (EBVMCUs). In analyses of biopsies collected from 2 patients with EBVMCUs over multiple time points, we found that earlier biopsies had no or only a few EBV-positive cells, whereas 1 later biopsy had EBVMCU and co-infection with cytomegalovirus. EBVMCUs were associated with steroid-refractory colitis (100% of EBV-positive patients vs 12.5% of EBV-negative patients; P = .008) and colon perforation (100% of EBV-positive patients vs no EBV-negative patients; P = .001). CONCLUSIONS: We found that colon tissues from 4/13 patients with colitis after anti-CTLA4 therapy (4/6 patients who underwent resection and 4/4 patients with colon perforation) contained EBVMCUs. EBVMCUs seem to arise secondarily in areas of inflamed colon due to immunosuppressive treatment for colitis. EBVMCUs are associated with steroid-refractory colitis and colon perforation.
Assuntos
Colite , Infecções por Vírus Epstein-Barr , Idoso , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , RNA Viral , Estudos Retrospectivos , ÚlceraRESUMO
Plasma cell granuloma, also known as inflammatory myofibroblastic tumour or inflammatory pseudotumour, is a nonneoplastic process characterized by an unregulated growth of inflammatory cells. It most commonly occurs in the lung and upper respiratory tract, and only six other cases of gastric plasma cell granuloma exist. There are no other cases of intragastric laparoscopic resection of this type of lesion. Here, we present a case of a 60-year-old gentleman who had gradual onset epigastric discomfort and was thought to have a gastrointestinal stromal tumour on gastroscopy. Subsequent imaging and laparoscopic transgastric resection of the lesion confirmed the presence of a plasma cell granuloma. We discuss the aetiologies, presentation, investigation, and treatment of this rare disorder and make recommendations on the management.