Mismatch repair screening in sebaceous carcinomas may aid in cancer prevention, treatment

Key takeaways:

• Mismatch repair (MMR) screening showed MMR deficiency in one-third of sebaceous carcinoma (SC) cases.
• Rates of Lynch syndrome-associated cancers among patients with SC are high, primarily among extraocular SC.

Incorporating mismatch repair screening into daily practice for the management of sebaceous carcinomas may help identify patients with Muir-Torre/Lynch syndrome, which causes genetic predisposition to certain cancers, according to a study.

Muir-Torre syndrome (MTS), a type of Lynch syndrome (LS), is characterized by the presence of sebaceous carcinomas (SC). According to the study, MTS/LS occurs when germline pathogenic variants are found in one of four mismatched repair (MMR) genes. Therefore, screening SC for MMR could potentially aid in early LS detection and preventative interventions.

“Sebaceous tumors are the most strongly associated marker of all LS associated cancers, with 18.8% to 33.3% of patients with sebaceous tumors having LS,” Sam Cook, MBChB, FRCPath, of the department of pathology at the Royal Victoria Infirmary in Newcastle upon Tyne, U.K., and colleagues wrote. “MMR screening of SC samples to aid detection of LS is currently not standard practice in England, and may represent a missed opportunity for LS detection for both SC patients and their families.”

In this retrospective study, researchers identified the proportion of SC screened for MMR and MMR deficiencies in order to establish the need for this screening for early LS detection.

A total of 1,077 SC cases across England — 739 extraocular and 338 periocular — were analyzed in this study from January 2008 to December 2018.

Results showed that men had higher age standardized incidence rates per 1,000,000 person-years compared with women (2.74; 95% CI, 2.52-9.69 vs. 1.47; 95% CI, 1.4-1.62). Of the total number of patients, 19% developed a minimum of one malignancy associated with MTS/LS.

MMR immunohistochemical screening was reported in 20% of patients with annual increases from 4% in 2008 to 34% in 2018. Of these screened cases, 32% of the SC tumors showed MMR deficiency. Patients with tumors that had MMR deficiency were aged younger compared with those with tumors that were MMR proficient (67 years vs. 78 years).

The authors also found that rates of LS-associated cancers were higher in extraocular vs. periocular SC (39% vs. 11%). Therefore, the authors suggested that practitioners should focus efforts on patients with extraocular SC in MMR screening if there are limited testing resources.

“In this national study of SC with genetic testing data and cancer diagnoses, we found that one-third of SC cases tested had MMR deficiency, and that cancer risk among patients with SC is high,” the authors concluded. “Currently, MMR screening is infrequent among patients with SC, and our findings provide data to recommend that all patients with SC tumors should be offered MMR screening.”