Case Report: Pancreatic amphicrine-like carcinoma with acinar differentiation harboring a KANK4-RAF1 gene fusion.

Pancreatic amphicrine-like carcinoma (ALC) is an exceptionally rare neoplasm characterized by simultaneous exocrine and endocrine differentiation within the same tumour cells. These tumours represent a diagnostic challenge because they must be distinguished from mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), which consist of morphologically distinct tumour components. We report a case of pancreatic ALC with acinar differentiation harboring a KANK4::RAF1 fusion identified by comprehensive genomic profiling. Histologically, the tumour demonstrated acinar differentiation with expression of trypsin and BCL10 together with neuroendocrine differentiation characterized by synaptophysin and INSM1 expression within the same neoplastic population. Molecular analysis revealed a RAF1 rearrangement, a potentially actionable alteration previously described in a subset of pancreatic acinar carcinomas. The patient showed rapid disease progression despite systemic chemotherapy. Treatment with the MEK inhibitor trametinib was initiated based on the presence of a RAF1 fusion but was discontinued after 1 month because of toxicity, preventing assessment of therapeutic efficacy. This case expands the molecular spectrum of pancreatic ALC with acinar differentiation and highlights the importance of comprehensive molecular profiling in rare pancreatic neoplasms to identify potentially actionable genomic alterations.