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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–computed 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® 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–mesenchymal 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's 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. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a significant health problem associated with several risk factors, increasingly driven by non-alcoholic steatohepatitis and metabolic syndrome. This association poses a challenge for the primary treatments of HCC, which may include immune checkpoint inhibitors and vascular endothelial growth factor inhibitors, due to their potential cardiotoxic effect. Therefore, it is imperative to balance the therapeutic effects of these agents with their potential cardiovascular adverse events., Case Description: We describe the case of a man in his seventies with advanced HCC and significant cardiovascular comorbidities who was treated with atezolizumab and bevacizumab. Despite achieving a clinical and radiologic complete response, the patient experienced a deterioration in cardiac function after 16 months, necessitating the discontinuation of bevacizumab. The patient continued to respond well to atezolizumab, but unfortunately, he passed away due to a cardiac event after 4 years of follow-up., Conclusions: Careful risk stratification and optimization of modifiable risk factors is of uttermost importance in management of HCC. Close monitoring, comprehensive patient management in a cardio-oncology clinic is also vital, particularly for patients at high risk of developing cardiovascular adverse events. The delicate balance between the efficacy of cancer treatments and their potential cardiotoxicity is one of the principal determinants of outcomes of patients diagnosed with HCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-359/coif). P.S. reports that he is the owner of Ladprao General Hospital with stock less than 5%. J.S. reports receiving consulting fee from Paige AI and having professional activities in Paige AI. G.K.A.A. reports receiving research grant support from Agenus, Arcus, Astra Zeneca, BioNtech, BMS, Elicio, Genentech/Roche, Helsinn, Parker Institute, Pertzye, Puma, QED, Servier, and Yiviva, and consulting support from Abbvie, Alligator Astra Zeneca, Autem, Berry Genomics, BioNtech, Boehringer Ingelheim, BMS, Eisai, Exelixis, Genentech/Roche, Incyte, Ipsen, J-Pharma, Merck, Merus, Neogene, Novartis, Servier, Tango, Tempus, Vector, and Yiviva. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)