Cuong V Nguyen1, Kevin J Gaddis2, Michael R Stephens3, John T Seykora3, Emily Y Chu3. 1. Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 2. Department of Dermatology, University of Minnesota, Minneapolis. 3. Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia.
Abstract
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.
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.
Authors: Rachel M Roth; Sigurdis Haraldsdottir; Heather Hampel; Christina A Arnold; Wendy L Frankel Journal: Am J Clin Pathol Date: 2016-06-29 Impact factor: 2.493
Authors: M M Entius; J J Keller; P Drillenburg; K C Kuypers; F M Giardiello; G J Offerhaus Journal: Clin Cancer Res Date: 2000-05 Impact factor: 12.531
Authors: Maegan E Roberts; Douglas L Riegert-Johnson; Brittany C Thomas; Colleen S Thomas; Michael G Heckman; Murli Krishna; David J DiCaudo; Alina G Bridges; Katherine S Hunt; Kandelaria M Rumilla; Mark A Cappel Journal: J Genet Couns Date: 2012-12-06 Impact factor: 2.537
Authors: Anna Maria Cesinaro; Alessandro Ubiali; Pamela Sighinolfi; Gian Paolo Trentini; Francesca Gentili; Fabio Facchetti Journal: Am J Dermatopathol Date: 2007-08 Impact factor: 1.533
Authors: Mujde Z Erten; Luca P Fernandez; Hank K Ng; Wendy C McKinnon; Brandie Heald; Christopher J Koliba; Marc S Greenblatt Journal: Dig Dis Sci Date: 2016-07-06 Impact factor: 3.199
Authors: Michael R Sargen; Gabriel J Starrett; Eric A Engels; Elizabeth K Cahoon; Margaret A Tucker; Alisa M Goldstein Journal: Clin Cancer Res Date: 2020-09-09 Impact factor: 13.801