An Intrapatient Concordance Study of Mismatch Repair Protein Immunohistochemical Staining Patterns in Patients With Muir-Torre Syndrome

Question  Is there intrapatient concordance of mismatch repair protein (MMRP) immunohistochemical (IHC) staining pattern between different sebaceous neoplasms in patients with known Muir-Torre syndrome (MTS)?

Findings  In this case series of 11 patients with MTS, there was high intrapatient concordance of MMRP IHC staining between different sebaceous neoplasms of individual patients (range, 2-4 lesions per patient), with 36 of 38 lesions matching the confirmed germline mutation (sensitivity, 94.7%; 95% CI, 82.3%-99.4%). Extrafacial lesions (n = 16) corresponded to patients’ known germline mutation in 100% of cases.

Meaning  These findings may suggest that MMRP IHC has high reproducibility across sebaceous lesions within an individual patient with MTS, and that this test may be used to support a diagnosis of MTS when clinical suspicion is strong.

Importance  Appropriate use criteria for Muir-Torre syndrome (MTS) screening suggest that mismatch repair protein (MMRP) immunohistochemical (IHC) testing is usually appropriate in patients with 2 or more sebaceous neoplasms (SNs). While MTS is known to be caused by a germline mutation in mismatch repair genes, data are limited as to whether individual sebaceous tumors in these patients with multiple lesions show identical MMRP IHC staining patterns.

Objective  To determine concordance of MMRP IHC staining patterns in lesions of patients with MTS who have multiple SNs.

Design, Setting, and Participants  This retrospective single-center case series evaluated 38 SNs in 11 patients with MTS confirmed by genetic testing for MMRP IHC staining patterns. Tumor sites were classified as either facial or extrafacial. Data were collected between January 1, 2007, and January 1, 2018.

Main Outcomes and Measures  In each patient, MMRP IHC staining patterns for SNs were compared with one another to evaluate intrapatient concordance between lesions, and to the patient’s known germline mutation.

Results  A total of 11 patients (7 women and 4 men) with MTS, with a mean (SD) age of 59.3 (10.6) years at time of SN biopsy, were identified. There was high concordance between MMRP IHC staining results (2-4 lesions per patient) and the patient’s mutation status, with 36 of 38 total lesions (95%) matching (sensitivity, 94.7%; 95% CI, 82.3%-99.4%). Extrafacial site tumors represented 16 of 38 total lesions (42%) and demonstrated 100% concordance of IHC results to germline mutation. Only 1 of 11 patients (9%) demonstrated discordant results, with both lesions in this patient occurring on a facial site.

Conclusions and Relevance  In patients with known MTS, SNs present with highly concordant MMRP IHC staining profiles across multiple lesions. There is also a strong association with underlying germline mutations. A diagnosis of MTS might be supported by MMRP IHC when the pretest probability is high.