Origin of Familial Malignant Melanomas From Heritable Melanocytic Lesions

Clark, Wallace H.

doi:10.1001/archderm.1978.01640170032006

Cited by 677 publications

(140 citation statements)

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“…Since the histological description of a type of atypical nevus by Clark et al (2)(3)(4)(5)(6)(7)(8), considerable controversy has surrounded the interpretation of the histological changes, regarding their correlation with familial melanoma and with melanoma risk for the individual. Subsequent work has emphasized two types of clinical settings associated with these atypical nevi, one being in patients with large numbers of such nevi and a familial or personal history of melanoma, called familial dysplastic nevus syndrome.…”

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confidence: 99%

Grading of Atypia in Nevi: Correlation with Melanoma Risk

2003

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Nevi with architectural disorder and cytologic atypia of melanocytes (NAD), aka "dysplastic nevi," have varying degrees of histologic abnormalities, which can be considered on a spectrum of grades of atypia. Somewhat controversial and subjective criteria have been developed for grading of NAD into three categories "mild," "moderate," and "severe." Grading involves architectural and cytological features, which often correlate with each other. Architectural criteria were intraepidermal junctional extension beyond any dermal component, complex distortion of rete ridges, and dermal fibrosis. Cytological criteria were based on nuclear size, dispersion of chromatin, prominence of nucleoli, hyperchromasia and variation in nuclear staining. Few tests have been made of the relationship between specific grades of atypia and patient risk for melanoma. Retrospective review of pathology reports was performed on 20,275 nevi examined between 1989 and 1996. From the total, 6,275 were diagnosed as NAD, which were in 4,481 patients. These patients were divided into those whose worst NAD was mild (2,504), moderate (1,657), or severe (320). Review of accession data revealed that a personal history of melanoma was present in 5.7% of patients with mild, 8.1% with moderate, and 19.7% with severe atypia. The male/female ratios were similar in each group. In the three groups, the mean ages of men were similar and of women were similar, but the mean age of men tended to be 6 -11 yrs. older than women in each group. Family histories of melanoma were not considered. The odds ratio as a measure of association between NAD and personal history of melanoma, shows an odds ratio of 4.08 (2.91-5.7) for NAD-severe versus NAD mild, odds ratio 2.81 (2-3.95) for NAD-severe versus NADmoderate and odds ratio 1.45 (1.13-1.87) for NAD moderate versus NAD-mild. These data show that the probability of having personal history of melanoma, for any given NAD patient, correlates with the NAD grade. Likewise, the risk of melanoma is greater for persons who tend to make nevi with high grade histological atypia.

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confidence: 99%

Grading of Atypia in Nevi: Correlation with Melanoma Risk

2003

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“…In the subsequent 4 decades, several additional kindreds have been described [8,[14][15][16][17][18][19][20][21][22][23][24], but the precise molecular basis for familial sus ceptibility to melanoma remains elusive. A major ad vance in defining genetic predisposition to melanoma came in 1978, when Clark et al [25] and Lynch et al [26] defined clinical and histologic features of a melanocytic precursor to cutaneous melanoma. The disorder was des ignated the B-K mole syndrome (named after families B. and K., the first two kindreds studied).…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Controlling Human Melanoma Progression and Metastasis

Welch

Goldberg

1997

Pathobiology

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Progression from normal melanocyte to metastatic melanoma is a multistep, multigenic process. While relatively easy to conceptualize, the stages of melanoma progression are not necessarily discrete, nor are they unambiguously defined at the morphologic or molecular levels. The ability to stage the lesions more precisely would afford clinicians a greater confidence when designing therapeutic strategies. Unfortunately, a molecular definition of cells at each stage does not yet exist. Toward that end, the purpose of this review is twofold: (1) to highlight recent advances in our understanding of the molecular genetics of human cutaneous melanoma predisposition, and (2) to construct a molecular model of melanoma progression toward metastasis.

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“…Dysplastic nevi (DN), as first described in 1978 (Clark et al, 1978), are recognized as important precursors for malignant melanoma (N1H Consensus Conference, 1984). However, uni form criteria tor histologic diagnosis of DN are not yet being applied in practice as evidenced by the widely differing estimates in the prevalence of DN in the population [i.e., from 2% (Rhodes et al, 1980) to 53-60% (Piepkorn et al, 1989)].…”

Section: Introductionmentioning

confidence: 99%