Carcinosarcoma of the stomach: four cases that expand the morphologic spectrum of gastric cancer with a primitive phenotype.

Carcinosarcoma of the stomach is a rare neoplasm characterized by the presence of both epithelial and mesenchymal malignant components. We describe four examples with a focus on the characterization of the epithelial components and the histogenetic implications for this unique tumor. All patients were men aged 40-79 years. All patients developed metastatic disease, and three of them died 4-19 months after the diagnosis. Sarcomatous elements included poorly differentiated spindle cell sarcoma without distinctive differentiation (n = 4), chondrosarcoma (n = 2), and rhabdomyosarcoma (n = 1). In two cases, the sarcomatous component was recognized only in metastatic lesions. Notably, carcinomatous components were characterized by multilineage and primitive cellular differentiation, including carcinoma with enteroblastic (n = 4), hepatoid (n = 3), yolk sac tumor-like (n = 1), trophoblastic (n = 1), and neuroendocrine (n = 1) differentiation, as well as conventional tubular adenocarcinoma (n = 4). On immunohistochemistry, all four cases showed varying degrees of positive expression of primitive phenotypic markers, including alpha-fetoprotein (AFP), glypican-3, or SALL4. All tumors showed mutant patterns of p53 staining, exhibiting either diffusely positive or completely negative staining. On the basis of these findings, at least some gastric carcinosarcomas are likely to be derived from carcinoma with a primitive phenotype, including AFP-producing adenocarcinoma. Our observations suggest that sarcomatous differentiation, as well as multilineage differentiation of epithelial components, may represent increased cellular plasticity of gastric carcinoma with a primitive phenotype.