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Lynch Syndrome — SCE Medical Oncology MCQ

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HardGI CancersLynch SyndromeSCE Medical Oncology

Universal mismatch-repair immunohistochemistry on a colorectal cancer shows isolated loss of MSH6; MLH1, PMS2 and MSH2 are retained. Staining controls are satisfactory. Which Lynch-syndrome test pathway follows NICE DG27?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: D — Refer for germline testing of MSH6 through clinical genetics

Explanation lettering: C = shown as A · A = shown as B · D = shown as C · E = shown as D · B = shown as E

E is correct. Isolated loss of MSH6 with valid controls is an abnormal non-MLH1 pattern and prompts germline testing through an appropriately counselled genetics pathway. BRAF V600E and MLH1 promoter methylation are triage tests for tumours with MLH1 loss, not isolated MSH6 loss. Microsatellite instability can support mismatch-repair deficiency but does not classify the cause as sporadic. Repeating IHC annually does not establish heritable status. Paired tumour-germline analysis may later clarify double-somatic disease when germline testing is negative. The original simultaneous MSH6-PMS2 loss was not a canonical heterodimer pattern and did not justify an MSH6-only conclusion.

Reference: NICE DG27 Lynch-syndrome testing recommendations: https://www.nice.org.uk/guidance/dg27/chapter/1-Recommendations