Mismatch Repair Deficiency Screening Rates Low in Sebaceous Carcinoma

Lynch syndrome is a dominantly inherited genetic condition with a 50% risk for transmission to children, highlighting the benefit of early LS detection.

Patients with sebaceous carcinoma (SC) have a significantly increased risk for Lynch syndrome (LS)-associated cancers and low rates of mismatch repair deficiency screening, according to study results published in Journal of the American Academy of Dermatology.

Researchers conducted a retrospective cohort study that comprised patients with histologically confirmed cutaneous SC in England between January 2008 and December 2018. Data were extracted from the National Cancer Registration and Analysis Service (NCRAS). Verified cases were linked to registry data for patient characteristics and germline mismatch repair status.

A total of 1077 participants had confirmed SC in the study period. The median age was 76 (IQR, 17) years, and approximately 94% were White. The European age standardized incidence rate (ASIR) was 2.11 per 1,000,000 person years. The ASIR was 2.74 per 1,000,000 person years for men and 1.47 for women.

The incidence rates were higher for extraocular SCs (1.46 per 1,000,000) vs periocular SCs (0.64 per 1,000,000). Extraocular SC represented 69% (n=739) of cases compared with 31% (n=338) for periocular SCs.

dMMR SC can be a presenting feature of MTS/LS, and thus may reveal a predisposition to other associated cancers.

At the last follow-up, 42% (n=446) of participants with known vital status were deceased, and their mean survival was 3.04 (SD, 2.28) years after diagnosis of SC. The mean follow-up was 4.15 (SD, 2.82) years. The median survival was 6.8 years for men and 7.4 years for women, according to Kaplan-Meier curves for all-cause survival.

At least 1 other recognized LS-associated cancer occurred in 19% (n=210) of participants, and 274 LS-associated cancers were diagnosed across 210 participants. Several cancers occurred at significantly higher rates, including colorectal cancers, uterine cancers, and salivary gland cancers. Approximately 29% (n=79) of LS-associated cancers occurred after the diagnosis of SC. In 27.1% (n=57) of participants. The median latency for a subsequent LS-associated cancer after SC was 2.3 years (IQR, 3.3).

Mismatch repair immunohistochemistry (IHC) screening was reported in 20% (n=220) of cases, and testing increased annually during the study period. Researchers observed that mismatch repair IHC testing increased from a low of 4% (n=2) of cases in 2008 to a high of 34% (n=44) of cases in 2018. For SC cases in which mismatch repair IHC was conducted, 32% (n=70) were mismatch repair deficient.

Cases of SC linked to germline DNA mismatch repair testing results were identified in 56 participants, of whom 25 underwent mismatch repair IHC testing of their tumor. Germline testing identified mismatch repair deficiency consistent with Muir-Torre syndrome (MTS) and LS (germline pathogenic variants of MSH2/MSH6/MLH1/PMS2) in 54% (n=30). Among participants with mismatch repair deficient tumors by IHC, 50% (n=12) had germline pathogenic variants.

Limitations of the study include possible practice variations regarding thresholds for mismatch repair deficiency testing. Linkage to germline testing is dependent on National Health Service molecular genetic laboratories that test for LS to extract retrospective data for submission to NCRAS.

The researchers conclude, “dMMR SC can be a presenting feature of MTS/LS, and thus may reveal a predisposition to other associated cancers.” “Incorporation of tumor IHC MMR screening into clinical practice guidelines for the management of SC will increase the opportunity for MTS/LS diagnoses for patients and family members who may benefit from cancer surveillance, chemoprevention with aspirin and immunotherapy treatment targeted to MTS/LS cancers.”


Cook S, Pethick J, Kibbi N, et al. Sebaceous carcinoma epidemiology, associated malignancies and Lynch/Muir-Torre syndrome screening in England from 2008 to 2018. J Am Acad Dermatol. Published online April 7, 2023. doi:10.1016/j.jaad.2023.03.046