Selective screening for Lynch Syndrome among patients with sebaceous neoplasms could improve the detection, an Australian study has found.
The systematic review, published in Australasian Journal of Dermatology, looked at studies between 2005 and 2024, analysing Lynch Syndrome prevalence among patients with sebaceous adenomas and carcinomas [link here].
“[Sebaceous neoplasms] present an opportunity for early Lynch Syndrome detection due to their association with mismatch repair (MMR) gene pathogenic variants,” wrote the investigators, led be senior author Professor Finlay Macray of The Royal Melbourne Hospital.
Professor Finlay Macrae
The prevalence of Lynch Syndrome varied across the studies from 0.8% to 29%, highlighting the need for standardised testing strategies, the research team said.
The analysis also revealed important clinical and molecular features of neoplasms associated with the syndrome, with 6.6% of patients with sebaceous neoplasms harboring MMR gene germline mutations that could benefit from genetic screening for Lynch Syndrome, the authors said.
Across the studies, those with Lynch Syndrome-associated sebaceous neoplasms were younger, more often male, and had several extra-facial tumours.
“The age of onset for sebaceous neoplasms in LS-positive individuals was considerably younger compared to sporadic cases, with median ages aligning closely with those for other LS-associated malignancies,” the authors said.
“This younger age of onset provides another rationale for early LS screening in patients presenting with sebaceous tumours, particularly in the absence of other risk factors like radiation exposure or immunosuppression.”
Tailored approach could be a low-cost screening strategy
“Early detection of [Lynch Syndrome] provides the opportunity for early prevention and intervention, including early screening for other malignancies related to [the syndrome], preventative hysterectomy and aspirin therapy for CRC prevention,” the authors added.
Current guidelines recommend universal screening in colorectal and endometrial cancers but not for less common malignancies like sebaceous neoplasms.
“Our meta-analysis demonstrates that 6.6% of patients with sebaceous neoplasms have a germline MMR mutation, a prevalence that should not be ignored,” they said.
Taking a tailored approach which considered the age of onset and number of tumours could identify which patients are good candidates for genetic testing, the authors argued.
“Patients with multiple lesions, who are of young age, have an extra-facial sebaceous neoplasm site, or a positive family history, should prompt genetics referral.”
The benefits of finding Lynch Syndrome cases in this patient group would go beyond cancer detection to treatment options, the researchers said.
“[Lynch Syndrome[ patients are candidates for immunotherapy, particularly with immune checkpoint inhibitors such as pembrolizumab which has shown efficacy in MSI-H/MMRd cancers.”
Several of the studies reviewed in the analysis were retrospective and included only a small number of patients, which was a limitation.
“Future studies should aim to establish clear immunohistochemical and genetic guidelines for [Lynch Syndrome] testing in sebaceous neoplasms and explore the potential role of universal screening in select high-risk populations,” the authors said.