Hereditary melanoma: Update on syndromes and management

Abstract

Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis.

Germline Variation at CDKN2A and Associations with Nevus Phenotypes among Members of Melanoma Families

“…However, an adolescent twin study from the UK found no evidence for D9S942 as a quantitative-trait locus influencing nevus density (Barrett et al , 2003) and a familial-based investigation of a potentially nevogenic variant (A148T) near D9S942 also found no association with common acquired nevus counts (Bertram et al , 2002). Germline mutations in CDKN2A are strongly associated with FAMMM syndrome, and individual members of these families often have abundant numbers of atypical and common nevi (Gruis et al , 1995; Hussussian et al , 1994; Soura et al , 2016). However, not all individuals with CDKN2A mutations present with excessive or even higher nevus counts.…”

Major Hereditary Gastrointestinal Cancer Syndromes: a Narrative Review

“…Around 20-40% of people with familial melanoma worldwide have a germline mutation in the CDKN2A gene, whereas germline mutations in another gene, CDK4, are seen in only about 1% of melanoma-prone families [20]. FAMMM should be considered in people with multiple nevi (more than 50), history of cutaneous melanoma in first and second-degree relatives with early onset or a family history of melanoma, pancreatic cancer and astrocytoma [20,21].…”

Unilateral Unique Primary Melanomas

“…occurs more frequent in patients with FAMMM syndrome (familial or sporadic form) or hereditary melanoma [1,2]. About 10% of all melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare [1]. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common [1].…”

“…primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases [1]. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives [1,2].…”

“…The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives [1,2].…”