Can a gastrointestinal pathologist identify microsatellite instability in colorectal cancer with reproducibility and a high degree of specificity

Clinical features usually initiate evaluation for Lynch Syndrome (LS) but some colorectal cancer (CRC) histopathology findings are compatible with high microsatellite instability (MSI-H) that also occurs in LS. This led to the suggestion that pathologists request MSI analysis, which is an expensive addition to routine histology. We aimed to see if a Gastrointestinal Pathologist could identify MSI-H features with reproducibility and high (95%) specificity (MSI-H 95%). Histopathology of all CRCs received during 2005 and 4 MSI-H controls were scored using 2 published methods, “MsScore” and “PathScore”. MSI analysis was performed on CRCs scored by either method as probable MSI-H 95% and results compared. To examine reproducibility of histopathology, 100 coded slides, including 25 scored MSI-H 95% and 75 scored low, were re-examined to now identify those needing MSI analysis. Costs were evaluated for identifying MSI-H with or without scoring. All 227 CRCs were scored for possible MSI-H 95%; 24 had high scores and MSI analysis. DNA analysis proved 14 MSI-H, PathScore identified 13 (95%), MsPath identified 9 (64%), histopathology alone identified 7 (50%). Reproducibility for identifying histopathology characteristics of MSI-H at re-examination, without scoring, was “moderate agreement” (Kappa statistic = 0.4615). Costs for identifying MSI-H by PathScore were the lowest, $436/identification. Conclusions; PathScore identified the most proven MSI-H CRCs at lowest cost and even an experienced gastrointestinal pathologist has difficulties identify MSI-H without scoring. So, scoring can be facilitated by a computerized evaluation form for routine CRC histology, prompting score computation and recommendation for MSI analysis with high specificity.