Serrated Polyps of the Extracolonic Gastrointestinal Tract: Histologic Findings and Genetic Alterations
Melissa W Taggart, Asif Rashid, Jeannelyn Estrella, Susan C Abraham. MD Anderson Cancer Center, Houston
Background: Serrated polyps are now recognized as precursors to a subset of colorectal carcinomas (CRC) and have been classified as hyperplastic (HP), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed adenomatous/serrated polyp (MP). HP and SSA frequently harbor BRAF mutations, while dysplastic lesions (TSA and MP) more commonly harbor KRAS mutations. CRC arising through the serrated neoplasia pathway often demonstrates high-level microsatellite instability (MSI-H) and CpG island methylator phenotype (CIMP). In contrast to serrated polyps of the colon, extracolonic serrated polyps are virtually undescribed and their genetic alterations are unknown.
Design: Fifteen serrated polyps from small bowel (n=9), stomach (n=4), and ampulla (n=2) were classified in accordance to serrated lesions of the colon as HP (n=2), SSA (n=1), TSA (n=6) and MP (n=6). Purified DNA from these lesions was subjected to pyrosequencing for BRAF (exons 11, 15) and KRAS (codons 12, 13, 61) mutations, immunohistochemistry and/or PCR for MSI status, and methylation-specific PCR for CIMP.
Results: Eleven (73%) of 15 serrated polyps were associated with invasive carcinoma, including 5 with mucinous features and 1 with signet ring cells. Oncogenic KRAS mutation was the most common abnormality, present in 8 of 14 cases (57%). MSI and CIMP were less common (Table 1). Only one polyp (duodenal HP) harbored a BRAF mutation (Fig 1).
|Stomach||TSA with fundic gland polyp||Q61H||Neg||Stable||Neg|