Familial melanoma: genetic, clinical, and dermoscopic insights and follow-up

Our plain-English summary of Familial melanoma: genetic, clinical, and dermoscopic insights and follow-up, by A.E. Raika, M.E. de Las Heras Alonso, D. Sproge, et al (Frontiers in Medicine, 2026).

The study

• Authors: A.E. Raika, M.E. de Las Heras Alonso, D. Sproge, E. Bataraga
• Journal: Frontiers in Medicine
• Published: 2026;13:1906952
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

Familial melanoma accounts for approximately 5-10% of all melanoma cases. It is characterized by an earlier age of onset. Multiple primary melanomas occur in up to a fifth of patients with a positive family history, compared to 5% in sporadic cases. Pathologically, familial melanomas tend to present at thinner Breslow depths and show a higher proportion of in situ lesions compared to their sporadic counterparts, with a predilection for the lower limbs. The genetic landscape of familial melanoma is heterogeneous. CDKN2A and CDK4 mutations act through UV-dependent and cell cycle disruption pathways, while BAP1, POT1, and TERT mutations are considered UV-independent. Beyond cutaneous melanoma, germline mutations confer an increased risk for additional malignancies, including pancreatic cancer, renal cell carcinoma, mesothelioma, and neural system tumors, necessitating multidisciplinary surveillance and genetic counseling for affected families. Dermoscopically, CDKN2A mutation carriers predominantly present with superficial spreading melanoma, displaying atypical pigment networks, irregular dots and globules, regression structures, and a blue-white veil. Co-occurrence of MC1R variants may produce more subtle, structureless presentations with a lower total dermoscopy score, posing additional diagnostic challenges. Sequential digital dermoscopy and total body photography remain the cornerstones of surveillance, with follow-up every 3-6 months recommended for mutation carriers. All patients should receive structured education on photoprotection, including the use of broad-spectrum SPF50+ sunscreen and sun avoidance measures.

Copyright © 2026 Raika, de las Heras Alonso, Sproge and Bataraga.

In plain English

This article was a review, not a new study. The authors summarized published research on familial melanoma, meaning melanoma skin cancer that runs in families. It did not study asbestos. Citing earlier work, the review reported that about 5 to 10% of melanoma cases involve a family history, and that roughly 20% of these familial cases are linked to high-risk inherited gene changes. It described CDKN2A as the most clinically significant of these genes. The review stated that inherited changes in the BAP1 gene are associated with an increased risk of uveal melanoma, cutaneous melanoma, malignant mesothelioma and renal cell carcinoma. It listed a personal or family history of mesothelioma among the indications for genetic testing. It also described what these melanomas look like under a skin microscope (dermoscopy) and reported published follow-up schedules, with checks every 3 to 6 months for people with inherited gene changes. The authors concluded that about half of melanoma families remain genetically unexplained, suggesting that more susceptibility genes remain to be found. They noted that regions such as Asia and Africa are underrepresented in the research.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature on familial melanoma; no new data were collected
• Who was studied: No patients were studied directly. The review drew on previously published studies and guidelines. The authors are from the Department of Dermatology and Venereology, Riga Stradins University, Latvia, and from Madrid, Spain.
• Exposure: Inherited (germline) gene variants linked to melanoma risk: CDKN2A, CDK4, BAP1, POT1, TERT, ACD/TERF2IP, MC1R and MITF p.E318K. UV exposure was discussed as a contributing factor for some of these genes. Asbestos exposure was not discussed.
• Main results:
  • Citing earlier studies, the review reported that about 20% of familial melanoma cases are attributable to high-risk, high-penetrance germline mutations.
  • The review cited Cust et al. as reporting an 87-fold increased melanoma risk among CDKN2A mutation carriers in the United Kingdom, compared with the general population, and a 31-fold increased risk in Australia.
  • The review reported CDKN2A penetrance of approximately 30% by age 50 and 67% by age 80.
  • The review stated that BAP1 mutations are associated with an increased risk of uveal melanoma, cutaneous melanoma, malignant mesothelioma and renal cell carcinoma.
  • The review stated that an estimated 63% of patients with germline BAP1 variants develop at least one of these cancers before age 53.
  • The review listed a personal or family history of mesothelioma among the indications for genetic testing when familial melanoma is suspected.
  • Citing earlier studies, the review reported that multiple primary melanomas occur in about 5% of patients with sporadic melanoma, compared with 19% of patients with a family history of melanoma.
  • The review reported studies finding up to a 40-fold increased risk of pancreatic cancer in patients with CDKN2A mutations, compared with the general population.
  • Citing earlier studies, the review reported that familial melanomas were more often found on the lower limbs than sporadic melanomas.
  • The review reported that patients with germline CDKN2A mutations have significantly more superficial spreading melanomas than nodular or lentigo maligna melanomas.
  • The review reported that follow-up every 3 to 6 months is recommended for patients with germline mutations or multiple primary melanomas.
• The authors' conclusion: The authors concluded that familial melanoma accounts for 5 to 10% of melanoma cases and has distinctive features. Because about half of melanoma families remain genetically unexplained, they suggested that additional susceptibility genes remain to be discovered.
• Limitations the authors state:
  • The authors noted that some regions, particularly Asia and Africa, are underrepresented in the literature, which may affect how well the regional diagnostic thresholds apply there.
  • The authors noted that follow-up intervals are not strictly standardized.

Topics

Medical terms in this study, explained in our Lexicon: CDKN2A, BAP1, Germline Mutation, Carcinoma, Mesothelioma, Genetic Counseling.

Related studies

• BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives — S. Cedres, A. Valdivia, et al. (2025)
• Risk of other Cancers in Families with Melanoma: Novel Familial Links — C. Frank, J. Sundquist, et al. (2017)
• Genetic susceptibility to malignant mesothelioma and exposure to asbestos: the influence of the familial factor — D. Ugolini, M. Neri, et al. (2008)
• Melanoma genetics — J. Read, K.A. Wadt, et al. (2016)
• Identification, genetic testing, and management of hereditary melanoma — S.A. Leachman, O.M. Lucero, et al. (2017)
• Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition — K.A. Wadt, L.G. Aoude, et al. (2015)

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