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Familial melanoma

Synonym(s) -
Prevalence Unknown
Inheritance Autosomal dominant
or Multigenic/multifactorial
Age of onset Adult
  • C43
MeSH -
MedDRA -


Malignant melanoma is a neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus. Melanoma is defined as familial if it is described either in a family with three melanoma patients (irrespective of their relationship) or in a family in which two first-degree relatives are diagnosed with melanoma.

The incidence of familial melanoma is about 1.5/100 000 and the prevalence is unknown.

Other cancers, besides melanoma, may also be associated: pancreatic carcinoma, other gastrointestinal cancers and breast cancer. In several families, the co-occurrence of eye and skin melanoma has been reported. The association of melanoma and atypical nevi within families has been named familial atypical multiple mole-melanoma (FAMMM, see this term). Melanoma is hereditary in approximately 10% of cases.

Studies of families with a high incidence of melanoma culminated in the identification of two susceptibility genes - CDKN2A (located at 9p21) and CDK4 (located at 12q13) - the products of which are known to be components of tumor-suppression pathways. CDKN2A has an unusual and complex genomic organization: it encodes two distinct tumor-suppressor proteins in alternative reading frames, INK4A (also known as p16) and ARF (also known as p14). The incidence of CDKN2A mutations among melanoma-prone families ranges from 25 to 40%. Mutations in these gene products are inherited in an autosomal dominant fashion. The mutation in the CDK4 gene was identified in two melanoma families.

Treatment depends on the stage of cancer. Cancerous lesions must be surgically removed in stage 0 melanoma. Recently, Imiquimod (an immune response modifier) therapy or dynamic phototherapy have been proposed in the treatment of lentigo maligna (or Hutchinson's freckle). In stage I cancer, excision of a margin of normal skin is performed in addition to the tumour excision. In stage II melanoma, sentinel lymph node biopsy may be also recommended, especially if lymph nodes are enlarged. Lymph node dissection is required in all stage III cancers. Interferon immunotherapy can be prescribed, as well as other adjuvant therapies such as radiation therapy or chemotherapy. In stage IV cancer, treatment essentially aims at alleviating symptoms. When a family has been diagnosed with familial melanoma, melanoma patients and their first-degree relatives should undergo yearly skin examinations from the age of 10.

Expert reviewer(s)

  • Dr Paolo CARLI
  • Dr Camilla SALVINI

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