Diagnostic Accuracy of Immunohistochemistry Testing on Sebaceous Gland Neoplasms for Muir-Torre Syndrome: A...

Muir-Torre syndrome (MTS) is a hereditary tumor predisposition syndrome associated with sebaceous neoplasms. Immunohistochemistry (IHC) for loss of mismatch repair (MMR) proteins in these tumors is used as a screening test, but its diagnostic accuracy has not been rigorously assessed.

We conducted a meta-analysis of 25 studies involving 692 patients who underwent IHC testing for MMR protein loss in sebaceous neoplasms.

The pooled sensitivity was 0.84 (95% CI: 0.75-0.90) and specificity was 0.46 (95% CI: 0.28-0.66), with significant inter-study heterogeneity in specificity (I ², 77%). Restricting the meta-analysis to more rigorous studies with exposure-based designs and germline mutation as the reference standard yielded higher sensitivity (0.91; 95% CI: 0.83-0.96) and lower specificity (0.14; 95% CI: 0.06-0.27). Hypothetically restricting testing to patients under 60 years or tumors outside the head/neck locations increased specificity (0.87 and 0.88, respectively) but reduced sensitivity (0.60 and 0.37, respectively). A two-antibody panel (MSH6 and PMS2) performed equivalently to a four-antibody panel (MLH1, MSH2, MSH6, and PMS2).

IHC testing can discriminate between sporadic and MTS-associated sebaceous neoplasms, but diagnostic utility is limited by low specificity. Most MMR-deficient cases are not due to MTS.