Dataset Information

Histologic features of melanoma associated with CDKN2A genotype.

ABSTRACT: Inherited susceptibility genes have been associated with histopathologic characteristics of tumors.We sought to identify associations between histology of melanomas and CDKN2A genotype.This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations.Compared with CDKN2A(-) cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (Ptrend = .02) and increased pagetoid scatter (Ptrend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A(-) (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation.Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype.Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.

SUBMITTER: Sargen MR

PROVIDER: S-EPMC4333073 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Histologic features of melanoma associated with CDKN2A genotype.

Sargen Michael R MR Kanetsky Peter A PA Newton-Bishop Julia J Hayward Nicholas K NK Mann Graham J GJ Gruis Nelleke A NA Tucker Margaret A MA Goldstein Alisa M AM Bianchi-Scarra Giovanna G Puig Susana S Elder David E DE

Journal of the American Academy of Dermatology 20150113 3

<h4>Background</h4>Inherited susceptibility genes have been associated with histopathologic characteristics of tumors.<h4>Objective</h4>We sought to identify associations between histology of melanomas and CDKN2A genotype.<h4>Methods</h4>This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations.<h4>Results</h4>Compared with CDKN ...[more]

PMID: 25592620

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Project description:ImportanceLentigo maligna (LM) presents an invasive component in up to 20% of biopsied cases, but to date the histologic features useful in detecting this invasive component have not been described. Some histologic characteristics are hypothesized to contribute to the progression of LM invasion.ObjectiveTo identify the histologic characteristics associated with lentigo maligna melanoma (LMM) in patients with LM diagnosed by a partial diagnostic biopsy.Design, setting, and participantsA retrospective cross-sectional study of patients treated between January 1, 2000, and December 31, 2017, was conducted in a referral oncology center in València, Spain. Data and specimens of patients (n = 96) with a diagnosis of primary cutaneous melanoma in the form of either LM or LMM who had undergone surgical treatment, a complete histologic examination of the whole tumor, and an initial diagnostic partial biopsy of LM were included in the study. Histologic assessment was blinded to the presence of an invasive component.InterventionsAll biopsy specimens were evaluated for the presence of certain histologic characteristics.Main outcomes and measuresComparisons between invasive samples and samples without an invasive component were performed. The differences in the distribution of variables between the groups were assessed using the χ2 and Fisher exact tests, and the degree of association of the relevant variables was quantified by logistic regression models. A classification and regression tree analysis was performed to rank the variables by importance.ResultsIn total, 96 patients had sufficient histologic material that could be evaluated. The patients were predominantly male (56 [58.3%]) and had a mean (SD) age at diagnosis of 72 (12) years. Of these patients, 63 (65.6%) had an LM diagnosis and 33 (34.4%) had an LMM diagnosis (an invasive component). The histologic variables associated with the presence of an invasive component were melanocytes forming rows (odds ratio [OR], 11.5; 95% CI, 1.4-94.1; P = .02), subepidermal clefts (OR, 2.8; 95% CI, 1.0-7.9; P = .049), nests (OR, 3.0; 95% CI, 1.1-8.6; P = .04), and a lesser degree of solar elastosis (OR, 0.4; 95% CI, 0.1-1.1; P = .07). A classification and regression tree analysis of the relevant histologic features was able to accurately identify lentigo maligna with an invasive component (LMM) in more than 60% of patients.Conclusions and relevanceThese findings may be useful in classifying early LM specimens at higher risk of invasion, which may eventually be relevant in identifying the most appropriate management for LM.

Project description:BackgroundSeveral algorithms are available for the dermoscopic diagnosis of pigmented skin lesions. The MC1R gene is a key determinant of pigmentation characteristics that are established host-related melanoma risk factors.ObjectivesTo investigate the association of dermoscopic features of sporadic cutaneous melanomas with clinical characteristics of patients and corresponding tumours and with genetic changes in the MC1R and BRAF genes.MethodsA total of 64 dermoscopic images of 62 patients were scored by ABCD rule and modified pattern analysis. Detailed patients' and melanomas' characteristics were collected. Patients were screened for germline MC1R variants and related melanomas for somatic V600 BRAF mutations.ResultsA lower total dermoscopic score (TDS) was observed in melanomas of patients with red hair (P = 0.019), due to reduced dermoscopic structures (P < 0.0001). Thicker melanomas showed higher TDS values (P = 0.021) due to sharper borders (P < 0.0001) and higher number of colors (P = 0.004). An atypical pigment network was prevalent in superficial spreading melanomas (P = 0.010), in individuals with dark skin (P = 0.043) and hair color (P = 0.001). An atypical vascular pattern was more frequent in nodular (P < 0.0001) and thick (P < 0.0001) melanomas, in individuals with skin type I-II (P = 0.037), blond or red hair color (P = 0.032) and blue or green eyes (P = 0.014). Melanomas of MC1R R carriers showed lower TDS value (P = 0.037), reduced dermoscopic structures (P = 0.001) and lower prevalence of atypical pigment network (P = 0.001). No differences were identified between BRAF-mutated or wild-type melanomas.ConclusionsWe suggest a phenotypic/MC1R profile for melanoma patients and their tumours. Melanomas of MC1R R carriers show a significant lower TDS value, with reduced dermoscopic structures, and a lower prevalence of an atypical pigment network. Non-carriers of MC1R R variants develop melanomas dermoscopically characterized by an atypical pigment network which is prevalent in superficial spreading melanomas, in patients with dark complexion and less frequent in red-haired individuals.

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Histologic features of melanoma associated with CDKN2A genotype.

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Histologic features of melanoma associated with CDKN2A genotype.

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