Challenging cases encountered in colorectal cancer screening for Lynch syndrome reveal novel findings: nucleolar MSH6 staining and impact of prior chemoradiation therapy

SummaryMany pathology laboratories have developed specific screening protocols to detect patients with Lynch syndrome. With recent recommendations to test all patients with newly diagnosed colorectal cancer for Lynch syndrome, the volume of testing will increase, and the most economic and reliable screening test will prevail. Although the detection of microsatellite instability by polymerase chain reaction and the detection of loss of the mismatch repair proteins by immunohistochemistry can each be used as a screening tool, each methodology has its strengths and weaknesses. During the time of our study, we used both polymerase chain reaction and immunohistochemistry to screen for Lynch syndrome in colorectal cancer specimens. We encountered 21 cases that posed significant interpretive challenges. A previously unpublished pattern of nucleolar MSH6 staining and potential spurious results induced by chemoradiation therapy are described. We feel that it is important to report these cases so that potential pitfalls in screening for Lynch syndrome can be avoided.