Clinicopathologic Features of Synchronous Colorectal Carcinoma: A Distinct Subset Arising from Multiple Sessile Serrated Adenomas and Associated with High-Levels of Microsatellite Instability and Favorable Prognosis
Huankai Hu, Daniel T Chang, Marina N Nikiforova, Shih-Fan Kuan, Reetesh K Pai. University of Pittsburgh, Pittsburgh, PA; Stanford University, Stanford, CA
Background: Synchronous colorectal carcinomas (CRCs) provide insight into the common causative genetic factors in colorectal neoplasia. We analyzed the clinicopathologic and molecular features of synchronous CRCs compared with solitary CRCs.
Design: 58 consecutive synchronous CRCs were retrospectively identified between January 2002 and June 2012 and analyzed for grade, stage, tumor-infiltrating lymphocytes (TILs), Crohn's-like peritumoral reaction, mucinous/signet ring differentiation, and precursor and synchronous polyps. CRCs were grouped based on the type of precursor lesion and microsatellite instability (MSI) status. BRAF V600E mutation status was performed in all MSI-H CRCs. Overall survival was compared between synchronous CRCs and 109 consecutively resected solitary CRCs.
Results: Compared with solitary CRCs, synchronous CRCs were often MSI-H (36% vs. 12%; p=0.0005) and right-sided (72% vs. 43%; p=0.0003); displayed TILs (34% vs. 11%; p=0.0004), mucinous histology (52% vs. 17%; p=0.0001), and precursor sessile serrated adenomas (SSA) (21% vs. 2%; p=0.0001); and had an improved 5-year survival (92% vs. 56%, p=0.02). There was no difference in survival between MSI-H and MSS synchronous CRCs. A unique group of 12 synchronous CRCs had CRCs arising from SSAs. All 12 SSA-associated synchronous CRCs were MSI-H and BRAF positive, seen in patients >60 years, and right-sided. SSA-associated CRCs occurred in women (11/12, 92%), were stage I/II (9/12, 75%) and low grade (10/12, 83%), and exhibited mucinous histology (10/12, 83%), TILs (10/12, 83%), and Crohn's-like reaction (8/12, 67%). 5/12 (42%) patients with SSA-associated CRCs harbored additional SSAs, ranging from 1 to 6. Clinical follow-up for 10/12 SSA-associated synchronous CRCs demonstrated all patients alive with no evidence of disease.
Conclusions: A distinct subset of synchronous CRC arises from multiple SSAs and is MSI-H and BRAF V600E positive. SSA-associated synchronous CRCs account for 21% of synchronous CRCs, occur in elderly women, and have a favorable prognosis. The high proportion of SSA-associated synchronous CRCs contributes to the improved overall survival of synchronous CRCs compared with solitary CRCs. The increased frequency of SSA-associated synchronous CRCs provides support that SSAs are high-risk lesions and suggests that patients with SSAs have a “field defect” resulting in increased risk for synchronous and likely metachronous CRC.
Monday, March 4, 2013 8:15 AM
Proffered Papers: Section D, Monday Morning