Analysis Of Clinicopathological Histomorphological And Molecular Differences In Right And Left Sided Colonic Carcinoma

BackgroundColorectal carcinoma (CRC) remains a significant cause of cancer morbidity and mortality worldwide. Right- and left-sided tumours differ in clinical, morphological, and molecular features. Microsatellite instability-high (MSI-H) tumours, often right-sided, are associated with distinct histopathological characteristics and prognostic implications. In Sri Lanka, molecular MSI testing is currently unavailable, highlighting the need for alternative predictive approaches. ObjectivesGeneral Objective: To describe the clinical and histopathological characteristics of right- and left-sided colorectal cancers in a Sri Lankan cohort and evaluate their usefulness in predicting MSI-H tumours. Specific ObjectivesTo compare clinicopathological features between right- and left-sided colorectal cancers. To predict MSI-H tumours based on clinicopathological features, including assessment of the MsPath score and histological parameters. To determine interobserver agreement for MsPath score application in selecting cases for MSI assessment. MethodsA retrospective analytical study was conducted on 156 colorectal carcinoma resections diagnosed between 2019 and 2021 at the National Hospital of Sri Lanka. Histopathological evaluation included tumour differentiation, mucinous and medullary features, tumour-infiltrating lymphocytes (TILs), and Crohn-like reaction. MsPath scores were calculated based on age, tumour site, and histological parameters. Immunohistochemistry (IHC) for PMS2 and MSH6 was performed on 46 selected cases to assess mismatch repair (MMR) status. ResultsOf 156 cases, 41 (26%) were right-sided and 115 (74%) left-sided. The majority were moderately differentiated adenocarcinomas (89%). Histological features suggestive of MSI-H including TILs (29%) and Crohn-like lymphoid reaction (23%) were more frequent in right-sided tumours. MsPath scores ranged from 0.0 to 5.9, with 50% of cases scoring below 1. Among the 46 cases evaluated by IHC, MMR deficiency was observed predominantly in higher MsPath score categories, and a significant association was found between MsPath score category and MMR status ({chi}{superscript 2} = 13.76, df = 2, p = 0.001). Interobserver agreement for MsPath scoring was substantial (Kappa = xx, indicating reproducibility). ConclusionRight-sided colorectal carcinomas in this Sri Lankan cohort more frequently exhibited histological features suggestive of MSI-H, including mucinous differentiation, TILs, and Crohn-like lymphoid reaction. MsPath scoring correlated with MMR deficiency in the IHC-tested subset, but its predictive value is limited without immunohistochemical confirmation. IHC using a two-antibody panel (PMS2 and MSH6) proved to be a feasible, cost-effective, and reliable method for MSI screening in resource-limited settings. This study is the first comprehensive evaluation of right-versus left-sided colorectal carcinomas and MsPath utility in Sri Lanka, underscoring the need for expanded IHC capacity, larger cohorts, and integration of molecular testing for MSI validation.