Genetic disorder characterized by the presence of
abnormal nevi that predispose to melanoma development.
BK Mole Syndrome; Familial Atypical Mole Melanoma (FAMM)
Syndrome; Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome;
Hereditary Dysplastic Nevus Syndrome; Nevoid Melanoma Syndrome.
First reported in 1820 by W. Norris.
Prevalence in white population of America and Europe is
approximately 2 to 5%. In Sweden, 18% of white adults have atypical
moles clinically but only 8% have the typical histologic features. No sex
predilection. Atypical moles are rare in black, Asian, and Middle Eastern
Clinical history and family examinations
suggest an autosomal dominant mode of inheritance. A first proposed
assignment of a melanoma gene (CMM1) chromosome 1p36 was not confirmed. A
second proposed gene (cell cycle regulator CDKN2A [P16], a cyclin-dependent
kinase) has been mapped to chromosome 9p21, and this gene assignment has
been confirmed. Germline mutations in this gene occur in approximately
20% of kindreds with familial atypical mole syndrome. Penetrance is
variable. Exposure to ultraviolet light plays a role in the phenotypic
expression of the syndrome.
Dysplastic nevi appear to be histogenetic
precursors of melanomas.
Clinically based on the presence and specific appearance
of nevi. The National Institutes of Health Consensus Conference requires the
following criteria to establish the diagnosis:
1. First-degree (e.g., parent, sibling or child) or second-degree
relative (e.g., grandparent, grandchild, aunt, uncle) with malignant
2. Large number of nevi, often more than 50, some of which are atypical nevi
3. Nevi that demonstrate certain microscopic features
Histologic examination of dysplastic nevi shows compound nevi with evidence
of abnormal growth. Nevus cell nests within the epidermis may be enlarged
and show abnormal coalescence with adjacent nests. As part of this process,
single nevus cells begin to replace the normal basal cell layer along the
dermoepidermal junction. Cytologically, the atypical features consist of
irregular, often angulated, nuclear contours frequently combined with
hyperchromasia. Associated alterations occur in the superficial dermis, with
sparse lymphocytic infiltrate, loss of melanin pigment from presumably
destroyed nevus cells, phagocytosis of melanin pigment by dermal
macrophages, and linear fibrosis surrounding the involved epidermal rete
ridges. This atypical nevus syndrome phenotype is the most potent risk
factor for melanoma in families and in the general population. Although most
dysplastic nevi are stable lesions, transition to melanoma is well known and
can occur within a few months. Atypical mole syndrome (AMS) represents the
highest risk factor known for malignant melanoma. A 7-year followup of
14 families indicated affected individuals having at least two relatives with
malignant melanoma have a 100% lifetime risk of developing a melanoma,
whereas all other affected persons have a lifetime risk
of approximately 18%. An increased risk for development of
pancreatic cancer has been reported for some mutations. The synonymous name
BK moles is derived from the initials of the surnames of the ...