Case Report
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 14, 2011; 17(42): 4729-4733
Published online Nov 14, 2011. doi: 10.3748/wjg.v17.i42.4729
Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis
Sabrina C Wentz, Cindy Vnencak-Jones, William V Chopp
Sabrina C Wentz, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232-2561, United States
Cindy Vnencak-Jones, Molecular Genetics Laboratory, Vanderbilt University Medical Center, Nashville, TN 37232-2561, United States
William V Chopp, Department of Pathology, Veterans Affairs Medical Center, Nashville, TN 37232-2561, United States
Author contributions: Wentz SC is the manuscript author and contributed 90% of the manuscript text and all photomicrographs; Vnencak-Jones C and Chopp WV contributed equally to the paper with histopathologic and molecular data interpretation and manuscript supervision.
Supported by Intradepartmental funds through Vanderbilt University Medical Center Department of Pathology for resident career development
Correspondence to: Sabrina C Wentz, MD, Department of Pathology, Vanderbilt University Medical Center, 1161 21st Ave S., CC3322 Nashville, TN 37232-0011, United States.
Telephone: +1-615-3434882 Fax: +1-615-3437023
Received: July 18, 2010
Revised: January 24, 2011
Accepted: January 31, 2011
Published online: November 14, 2011

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.

Keywords: Composite carcinoma, Neuroendocrine, Squamous, KRAS, BRAF, Microsatellite instability