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We report a 75-year-old man with a previously unreported cystic and papillary ACC metastatic to the liver. Histologically, the tumor exhibited cystic and papillary proliferations of epithelial cells with eosinophilic cytoplasm, prominent nucleoli, and frequent mitoses. Immunohistochemical analysis showed positivity for trypsin and BCL-10, confirming ACC. The cyst lining displayed both acinar and ductal features, suggesting origin from acinar cystic transformation with acinar-to-ductal metaplasia rather than a true intraductal neoplasm. Molecular studies identified NRAS, CTNNB1, and SMAD4 mutations. Despite reports of indolent behavior in similar variants, our patient developed peritoneal metastasis and died 2 years after surgery and chemotherapy, highlighting the potential for aggressive clinical behavior and the importance of distinguishing these tumors from benign cystic pancreatic neoplasms.<\/jats:p>","DOI":"10.1007\/s00428-025-04315-y","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:21:15Z","timestamp":1761092475000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A rare cystic and papillary variant of acinar cell carcinoma with liver metastasis and molecular analysis"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6164-5836","authenticated-orcid":false,"given":"Meredith K.","family":"Herman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1202-1858","authenticated-orcid":false,"given":"Eric","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4893-1587","authenticated-orcid":false,"given":"Jiaqi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"4315_CR1","doi-asserted-by":"publisher","first-page":"808","DOI":"10.5858\/arpa.2019-0472-RA","volume":"144","author":"ED Thompson","year":"2020","unstructured":"Thompson ED, Wood LD (2020) Pancreatic neoplasms with acinar differentiation: a review of pathologic and molecular features. 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All clinical pathological investigations were conducted according to the recommendations from the committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}