{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T20:36:18Z","timestamp":1785875778265,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T00:00:00Z","timestamp":1731110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography\u2013computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence\u00ae revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial\u2013mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient\u2019s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation.<\/jats:p>","DOI":"10.3390\/diagnostics14222512","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T08:46:54Z","timestamp":1731314814000},"page":"2512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An Atypical Case of Pancreatic Cancer with Mesenchymal Differentiation in a Patient with Primary Lung Adenocarcinoma: Insights into Tumor Biology and Novel Therapeutic Pathways"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2894-4524","authenticated-orcid":false,"given":"Noura","family":"Abbas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Riad El Solh, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama","family":"Zahreddine","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Riad El Solh, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Tawil","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Riad El Solh, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1976-8370","authenticated-orcid":false,"given":"Mustafa","family":"Natout","sequence":"additional","affiliation":[{"name":"Department of Radiology, American University of Beirut Medical Center, Riad El Solh, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3725-8403","authenticated-orcid":false,"given":"Ali","family":"Shamseddine","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Riad El Solh, Beirut 1107-2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1016\/S0140-6736(20)30974-0","article-title":"Pancreatic cancer","volume":"395","author":"Mizrahi","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","unstructured":"(2024, March 06). SEER*Explorer: An Interactive Website for SEER Cancer Statistics [Internet]. 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