{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:55:17Z","timestamp":1781758517441,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer of unknown primary (CUP) remains a diagnostic and therapeutic challenge, particularly when involving rare histological and molecular subtypes. Mucinous adenocarcinoma (MAC) with neuroendocrine differentiation is exceptionally rare, and its molecular characteristics are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We report a case of CUP initially presenting with multiple liver and bone metastases. Histopathological and immunohistochemical analyses of a liver biopsy confirmed MAC with neuroendocrine differentiation. Comprehensive molecular profiling was performed to identify potential actionable mutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genomic analysis revealed a rare HER2 (ERBB2) R678Q mutation. The patient received FOLFOX chemotherapy with the addition of trastuzumab, based on HER2 status. However, the tumor demonstrated early resistance and continued progression despite subsequent treatment modification. The patient succumbed to disease progression within one year of diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first reported case of MAC with neuroendocrine features harboring a HER2 R678Q mutation in the context of CUP. The case underscores the importance of integrating broad molecular testing into CUP diagnosis to uncover rare mutations with potential therapeutic implications. It also highlights the limited efficacy of current HER2-targeted therapies in rare mutations and the urgent need for more tailored treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1814733","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:34:29Z","timestamp":1781757269000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatic metastasis of mucinous adenocarcinoma with neuroendocrine differentiation harboring a rare HER2 R678Q mutation: a case report and literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhitao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College","place":["Hangzhou, 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