Composite
tumors are rare
neoplasms containing a mixture of 2 different cellular components present in roughly equal proportions. It is hypothesized that composite
tumors arise from a multipotential stem cell with subsequent bidirectional differentiation. We present an unusual composite
tumor of the stomach composed equally of
signet ring cell carcinoma and low-grade
neuroendocrine carcinoma. Twenty-one additional patients with signet ring cell
carcinomas of the stomach were studied to determine the prevalence of neuroendocrine differentiation by morphology and immunohistochemistry for
synaptophysin and
chromogranin A. Immunohistochemistry for
mucins 5AC and 2 was performed to assess for divergent differentiation toward foveolar and intestinal
mucin phenotypes, respectively, and to evaluate for any potential relationship with neuroendocrine differentiation. We found morphologic evidence of
neuroendocrine carcinoma in 4 (19%) of 21 consecutive signet ring
carcinomas.
E-cadherin immunostaining was subsequently performed on these 4
tumors plus the index case. All 5
tumors demonstrated concordance between the signet ring and neuroendocrine components. There was no distinct relationship to
mucin 5AC/
mucin 2 profiles, with the exception that all 11 intramucosal signet ring cell
carcinomas from 4 patients with germ line
cadherin 1 gene mutations were composed exclusively of
mucin 5AC+ signet ring cells that lacked intestinal
mucin and neuroendocrine differentiation. The concordant
E-cadherin status in the neuroendocrine and signet ring cell
tumor components and the frequent admixture of
mucin 5AC+ cells with foveolar differentiation and
mucin 2+ cells with intestinal differentiation may support the hypothesis that composite
tumors arise from a common stem cell with bilineage or multilineage differentiation.