Neuroendocrine and squamous colonic composite carcinoma: case report with molecular analysis.

Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Caucasian male to investigate the presence and prognostic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicarmine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromogranin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performed according to lab-developed methods, followed by capillary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squamous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophysin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar immunohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemotherapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.