CD20-Negative Primary Intestinal Diffuse Large B-cell Lymphoma With TP53 Mutation in Poorly Controlled Celiac Disease: A Diagnostic Challenge

Celiac disease (CD) is associated with an increased risk of intestinal lymphoma, predominantly of T-cell origin. Primary intestinal large B-cell lymphoma arising in the setting of CD is exceptionally rare. We report the case of a 34-year-old woman with poorly controlled CD who presented with abdominal pain, weight loss, and diarrhea. CT revealed a large jejunal mass. The patient underwent segmental jejunal resection with lymph node dissection. Histological examination showed a diffuse proliferation of large atypical lymphoid cells with focal anaplastic features. Immunohistochemical analysis demonstrated positivity for CD19, CD79a, PAX5, CD2, and perforin, whereas CD20, CD3, CD30, CD138, MUM1, and ALK were negative. Epstein-Barr virus-encoded RNA in situ hybridization was also negative. CD103 highlighted reactive intraepithelial lymphocytosis consistent with active CD. Next-generation sequencing (NGS) identified a pathogenic TP53 mutation associated with p53 overexpression. PCR analysis confirmed B-cell clonality. The final diagnosis was CD20-negative primary intestinal large B-cell lymphoma with a TP53 mutation arising in the context of poorly controlled CD, a combination that, to the best of our knowledge, has not been previously reported in the literature. This case highlights the diagnostic challenges posed by intestinal lymphomas associated with CD and emphasizes the importance of integrating histopathological, immunophenotypic, and molecular findings to achieve an accurate diagnosis and provide prognostic assessment.