Primary gastric squamous cell carcinoma in a young adult with immunotherapy complications: a case report.

Background: Primary gastric squamous cell carcinoma (GSCC) is a rare and aggressive malignancy, accounting for less than 0.1% of all gastric cancers. Its clinical presentation and management remain a challenge due to the lack of standardized treatment protocols and limited understanding of its molecular profile.

Case description: We report the case of a 33-year-old male presented with significant weight loss, severe acid reflux, and progressive subcutaneous masses. Diagnostic imaging and biopsies confirmed stage IV GSCC, with no evidence of other potential metastatic origins. Genetic analysis revealed pathogenic variants in the phosphatase and tensin homolog gene (PTEN), ataxia telangiectasia mutated gene (ATM), and Fanconi anemia, complementation group M (FANCM), along with intermediate tumor mutational burden (TMB). The patient was treated with a combination of leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy and nivolumab. Despite aggressive treatment, the patient experienced rapid disease progression and severe thrombocytopenia likely resulting from multifactorial causes, including severe sepsis, liver dysfunction, chemotherapy effects, tumor progression, and possible immune checkpoint inhibitor-related thrombocytopenia (irTCP). The severe complications led to death following palliative extubation.

Conclusions: This case highlights the complexity of diagnosing and managing GSCC, especially in younger patients. Identifying genetic alterations provides valuable insights into the disease's molecular profile. Further research is needed to develop effective and standardized treatment strategies for this rare malignancy.