{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:25:35Z","timestamp":1787030735348,"version":"build-2736575974"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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>Pancreatic hepatoid carcinoma (PHC) is an extremely rare pancreatic malignancy characterized pathologically by hepatocellular-like differentiation. Some patients may present with elevated serum alpha-fetoprotein (AFP). Owing to the limited number of reported cases, the clinical features, molecular characteristics, and systemic treatment strategies for PHC remain poorly defined. BRAF V600E is an actionable alteration with established therapeutic value in several solid tumors; however, its clinical significance in PHC remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report the case of a 64-year-old man with advanced PHC who presented with painless jaundice, dark urine, and recent weight loss. Laboratory tests showed marked cholestatic liver injury and significantly elevated AFP. Imaging revealed a pancreatic head-neck mass with portal vein tumor thrombus and regional lymph node metastases, corresponding to cT4N1M1, stage IV disease. Percutaneous transhepatic biliary drainage was first performed to relieve obstructive jaundice. Biopsy of the pancreatic lesion showed poorly differentiated carcinoma. Based on hepatoid morphology, immunophenotype, elevated serum AFP, imaging findings, and exclusion of primary hepatocellular carcinoma, the patient was diagnosed with PHC. Comprehensive genomic profiling identified a BRAF V600E mutation with a variant allele frequency of 31.89%, together with MDM2 and MYC amplification. The molecular profile was characterized by microsatellite stability, low tumor mutational burden, MGMT promoter methylation, and low PD-L1 expression. After two cycles of pembrolizumab-based first-line therapy combined with paclitaxel, S-1, and lenvatinib, AFP continued to increase and imaging showed rapid tumor enlargement, consistent with immune checkpoint inhibitor-related hyperprogressive disease. The treatment was then switched to dabrafenib plus trametinib. AFP declined rapidly and returned to the normal range within approximately two months. Imaging showed marked regression of the pancreatic primary lesion, disappearance of the portal vein tumor thrombus and metastatic lymph nodes, and conversion of peripheral blood minimal residual disease to negative. The best response was partial response. After approximately six months of targeted therapy, occult disease progression emerged. Subsequent addition of cetuximab, replacement of the MEK inhibitor, and dose escalation of targeted therapy did not restore sustained systemic disease control, although local disease remained manageable with subsequent treatment adjustments. Proton radiotherapy was then delivered to the residual pancreatic lesion, followed by CyberKnife radiotherapy for a newly detected 2.3-cm metastasis in the caudate lobe of the liver. As of April 2026, the patient\u2019s AFP level remained close to normal at 14 ng\/mL, local lesions were well controlled, peripheral blood minimal residual disease had turned positive, and the patient remained in a stable tumor-bearing state.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic analysis<\/jats:title>\n                    <jats:p>We further summarized 57 previously reported cases of PHC. The median age was 54 years, and 66.7% of patients were male. Tumors occurred at different pancreatic sites, including the pancreatic head in 21 cases, body in 8 cases, tail in 13 cases, and multifocal lesions in 15 cases. More than half of the patients had metastatic disease at initial diagnosis. The immunophenotype of PHC was highly heterogeneous. Regarding treatment, 47 patients underwent surgery, 20 received chemotherapy, and 6 received targeted therapy. The 1-year and 3-year overall survival rates were 70.7% and 43.1%, respectively, indicating an overall poor prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case suggests that BRAF V600E may represent a clinically actionable driver alteration in PHC. Dabrafenib plus trametinib induced a rapid and deep response in this patient with advanced BRAF V600E-mutant PHC. Microsatellite stability, low tumor mutational burden, low PD-L1 expression, and MDM2 amplification may be associated with limited benefit from immunotherapy and a risk of hyperprogression. After resistance to targeted therapy, local radiotherapy may serve as an important strategy for controlling oligoresidual and oligometastatic lesions. Together with the literature review, this case supports early comprehensive molecular profiling and individualized multidisciplinary management for advanced PHC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1927414","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:53Z","timestamp":1787027333000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Marked response to dabrafenib plus trametinib in a patient with BRAF V600E-mutant pancreatic hepatoid carcinoma: a case report and systematic analysis of 57 cases"],"prefix":"10.3389","volume":"16","author":[{"given":"Yingli","family":"Li","sequence":"first","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengzhi","family":"Xie","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianchang","family":"Sun","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangwei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbing","family":"Guo","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Chen","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Dang","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yang","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Ma","sequence":"additional","affiliation":[{"name":"The Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"442","DOI":"10.3892\/ol.2023.14029","article-title":"A pancreatic adenocarcinoma mimicking hepatoid carcinoma of uncertain histogenesis: a case report and literature review","volume":"26","author":"Iliesiu","year":"2023","journal-title":"Oncol Lett"},{"key":"B2","doi-asserted-by":"publisher","first-page":"75","DOI":"10.21037\/acr-24-195","article-title":"Pancreatic hepatoid carcinoma: a case report","volume":"9","author":"Wang","year":"2025","journal-title":"AME Case Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1335647","article-title":"Case report and literature analysis: pancreatic hepatoid carcinoma with multiple lymph node metastases progressing to liver metastasis after pancreaticoduodenectomy","volume":"14","author":"Huang","year":"2024","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.540030","article-title":"Targeting the mutational landscape of bystander cells: drug-promoted blood cancer from high-prevalence pre-neoplasias in patients on BRAF inhibitors","volume":"10","author":"Simnica","year":"2020","journal-title":"Front Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2012.02.047","article-title":"The dysplastic nevus: from historical perspective to management in the modern era: part I. 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