ARID1A-Deficient and 11q13-Amplified Metastatic Pancreatic Cancer Initially Presenting as Retroperitoneal Fibrosis in a Patient with Familial CHEK2 Variant.

Background and Clinical Significance: Retroperitoneal fibrosis (RPF), a rare fibroinflammatory disorder, is classified into idiopathic (iRPF) and secondary (sRPF) forms, with the latter posing significant diagnostic challenges in routine clinical pathway due to atypical presentations, especially in malignancy-associated (maRPF) cases. Case Presentation: Here, we report a 38-year-old female with congenital pancreatic hypoplasia presenting with elusive hypometabolic retroperitoneal masses, initially suggestive of iRPF. Persistent CA19-9 elevation prompted histopathological evaluation, revealing poorly differentiated adenocarcinoma of indeterminate origin. Timely integrated molecular profiling identified maRPF secondary to metastatic pancreatic adenocarcinoma, revealing rare genomic alterations, including a truncating ARID1A mutation NM_006015:c.4336C>T (p. R1446*) and CCND1/FGF3/FGF4/FGF19 (11q13) co-amplification, which resolved diagnostic ambiguity and delineated disease biology. Despite identifying these molecular features, poor prognosis was predicted, and no clinically actionable targets were detected, underscoring the need for future therapeutic development.

Conclusions

This paradigm highlights molecular profiling as a critical adjunct to conventional diagnostics in maRPF, bridging the gap between histopathological ambiguity and biologically grounded clinical decision-making.