Clinical Factors Associated With Skin Neoplasms in Individuals With Lynch Syndrome





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• In this retrospective analysis involving 607 Lynch syndrome (LS) carriers, 9.2% had LS-associated skin neoplasia (sebaceous carcinomas, sebaceous adenomas, and keratoacanthomas) and 15.0% had non–LS-associated skin neoplasia. In this cohort, skin neoplasms were the third most common form of malignancy, following colorectal and endometrial cancers. Factors associated with LS-associated skin neoplasms included male sex, age, race, MLH1 and MSH2/EPCAM pathogenic germline variants, and a personal history of non–LS-associated skin neoplasms.
• Patients with LS should receive regular dermatologic screening starting in early adulthood, as skin neoplasms are observed in approximately 20% of patients.

–  Katherine M. Stiff, MD

Written by

 

 

Walter Liszewski MD

Lynch syndrome is a genetic disease which predisposes individuals to a variety of cutaneous and internal malignancies. Cutaneous tumours associated with Lynch syndrome include sebaceous neoplasms and keratoacanthomas. Lynch syndrome is due to a mutation in one of several genes that are responsible for DNA mismatch repair. These genes include MLH1, MLH2, MSH6, and PMS2.

This 20-year, retrospective study from Dana-Farber looks at rates and risk factors for developing a Lynch-associated skin neoplasm, as well as non–Lynch-associated skin neoplasms, including basal cell and squamous cell carcinoma in adults with germline mutations in Lynch syndrome–associated genes.

Overall, 21.1% of patients in the study had a documented history of a skin cancer. Among all individuals, 9.2% developed a Lynch syndrome–associated cancer and 15.0% develop a skin cancer that is not classically associated with Lynch syndrome. The most common skin cancer in the cohort was basal cell carcinoma (9.9%), followed by sebaceous adenoma (7.2%). In a multivariate regression analysis, factors associated with a greater likelihood of developing a Lynch-associated skin cancer included MLH1 (aOR, 6.67; P < .001) or MSH2 (aOR, 15.33; P < .001) germline mutations.

Limitations of the study include the single-site nature of the case review; however, the number of cases and granularity of patient demographics is impressive. Overall, dermatologists should be aware that Lynch patients are at an increased risk of skin cancer; however, in this cohort, only around 20% developed at least one. The significance is that not all Lynch syndrome patients are destined to develop skin cancer, and, even if they do, it appears that basal cell carcinoma is more common than sebaceous neoplasms. Still, routine screening of these patients is important because they display higher rates of skin cancer than the general population.

Abstract 

BACKGROUND

Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch syndrome (LS).

OBJECTIVE

Identify clinical factors associated with development of skin neoplasms in LS.

METHODS

Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from January 2000 to March 2020. Multivariable logistic regression was performed to evaluate clinical factors associated with skin neoplasia.

RESULTS

Of 607 LS carriers, 9.2% had LS-associated skin neoplasia and 15.0% had non-LS-associated skin neoplasia; 58.2% (353/607) had documentation of prior dermatologic evaluation; 29.7% (38/128) with skin neoplasms lacked a history of visceral LS-associated malignancy. LS-associated skin neoplasms were significantly associated with male sex, age, race, MLH1 pathogenic germline variants, MSH2/EPCAM pathogenic germline variants, and personal history of non-LS skin neoplasms. Non-LS-associated skin neoplasms was significantly associated with age, number of first- and second-degree relatives with non-LS-associated skin neoplasms, and personal history of LS-associated skin neoplasms.

LIMITATIONS

Single-institution observational study; demographic homogeneity.

CONCLUSIONS

Skin neoplasms are common in individuals with LS. We identified clinical factors associated with LS- and non-LS-associated skin neoplasms. Regular dermatologic surveillance should be considered for all LS carriers.

Journal of the American Academy of Dermatology

Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort

J Am Acad Dermatol 2023 Feb 08;[EPub Ahead of Print], CS Zhong, M Horiguchi, H Uno, C Ukaegbu, A Chittenden, NR LeBoeuf, S Syngal, VE Nambudiri, MB Yurgelun 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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