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

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.

[1]  T. Force,et al.  Muir-Torre syndrome appropriate use criteria: Effect of patient age on appropriate use scores. , 2019 .

[2]  Jason B. Lee,et al.  Muir‐Torre syndrome appropriate use criteria: Effect of patient age on appropriate use scores , 2019, Journal of cutaneous pathology.

[3]  R. Sandford,et al.  Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a service setting , 2018, Clinical and experimental dermatology.

[4]  Jason B. Lee,et al.  Review of the current medical literature and assessment of current utilization patterns regarding mismatch repair protein immunohistochemistry in cutaneous Muir–Torre syndrome‐associated neoplasms , 2017, Journal of cutaneous pathology.

[5]  M. Greenblatt,et al.  Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience , 2016, Digestive Diseases and Sciences.

[6]  W. Frankel,et al.  Discordant Mismatch Repair Protein Immunoreactivity in Lynch Syndrome-Associated Neoplasms:  A Recommendation for Screening Synchronous/Metachronous Neoplasms. , 2016, American journal of clinical pathology.

[7]  M. Redston,et al.  Importance of universal mismatch repair protein immunohistochemistry in patients with sebaceous neoplasia as an initial screening tool for Muir-Torre syndrome. , 2016, Human pathology.

[8]  S. Gruber,et al.  Screening for germline mismatch repair mutations following diagnosis of sebaceous neoplasm. , 2014, JAMA dermatology.

[9]  I. Bissett,et al.  Immunochemistry screening for Lynch syndrome in colorectal adenocarcinoma using an initial two antibody panel can replace a four antibody panel. , 2013, The New Zealand medical journal.

[10]  M. Heckman,et al.  Screening for Muir-Torre Syndrome Using Mismatch Repair Protein Immunohistochemistry of Sebaceous Neoplasms , 2013, Journal of Genetic Counseling.

[11]  A. Cesinaro,et al.  Mismatch Repair Proteins Expression and Microsatellite Instability in Skin Lesions With Sebaceous Differentiation: A Study in Different Clinical Subgroups With and Without Extracutaneous Cancer , 2007, The American Journal of dermatopathology.

[12]  J. Keller,et al.  Microsatellite instability and expression of hMLH-1 and hMSH-2 in sebaceous gland carcinomas as markers for Muir-Torre syndrome. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  R. Schwartz,et al.  The Muir-Torre syndrome: a 25-year retrospect. , 1995, Journal of the American Academy of Dermatology.