Dermoscopy, reflectance confocal microscopy and histopathology of an amelanotic melanoma from an individual heterozygous for MC1R and tyrosinase variant alleles

Curchin, Claudia; Wurm, Elisabeth M. T.; Jagirdar, Kasturee; Sturm, Richard A.; Soyer, H. Peter

doi:10.1111/j.1440-0960.2012.00882.x

Cited by 15 publications

(22 citation statements)

References 23 publications

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“…reported that 100% of their 75 amelanotic melanoma cases had moderate levels of tyrosinase expression, suggesting that the lack of melanin was not because of the lack of melanin‐producing enzymes but due to other functional impairments. Our findings suggest that TYR R402Q may be significantly associated with the reduced pigment in these melanocytic lesions …”

Section: Discussionmentioning

confidence: 61%

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients

Rayner

McMeniman

Duffy

et al. 2019

Acad Dermatol Venereol

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Background Amelanotic/hypomelanotic melanoma is associated with poorer outcomes due to a more advanced disease stage at diagnosis. Objective To determine phenotypic risks and genotypic associations with amelanotic/hypomelanotic melanoma to develop a clinical and genetic profile that could assist in identifying high‐risk individuals. Methods The Brisbane Naevus Morphology Study conducted from 2009 to 2016 has recruited a core of 1254 participants. Participants were drawn from a combination of volunteers from dermatology outpatient clinics, private dermatology clinics, the Brisbane Longitudinal Twin Study and QSkin study. Case participants had a personal history of melanoma and control participants no personal history of melanoma. We specifically examined seven known candidate pigmentation and melanoma genes and pigmentary phenotypic characteristics in participants with amelanotic/hypomelanotic melanoma compared to pigmented melanomas. This assayed single nucleotide polymorphisms in MC1R, TYR, HERC/OCA2, IRF4, MTAP, PLA2G6 and MITF. Results Forty‐seven participants had at least one amelanotic/hypomelanotic melanoma, and 389 had pigmented melanomas, with amelanotic/hypomelanotic melanoma patients significantly older than pigmented melanoma participants (63.3 ± 13.0 vs. 54.6 ± 15.3 years; P < 0.001). Amelanotic/hypomelanotic melanoma patients were more likely than pigmented melanoma patients to have red hair (34% vs. 15%; P = 0.01), severe hand freckling (13% vs. 5%; P = 0.01) and propensity to sunburn (63% vs. 44%; P = 0.01). MC1R R/R genotype was much more frequent in our amelanotic/hypomelanotic melanoma population (31.1% vs. 11%; P < 0.001; OR 26.4 vs. 5.9; control 1.0). Amelanotic/hypomelanotic melanoma was associated with TYR rs1126809*A/A [OR (CI 95%) 2.7 (1.1–6.8) vs. 1.2 (0.8–1.9)] and PLA2G6 rs11570734*A/A [OR (CI 95%) 3.7 (1.0–13.6) vs. 1.3 (0.9–2.0)]. The MTAP melanoma risk SNP genotype, associated with darker pigmentation, (rs4636294*A/A) was less common in amelanotic/hypomelanotic melanoma patients [OR (CI 95%) 0.8 (0.3–2.1) vs. 2.0 (1.3–3.1)]. Conclusions Knowledge of phenotypic and genotypic associations of amelanotic/hypomelanotic melanoma can help predict risks and associations of this difficult to diagnose melanoma, which may ultimately assist clinical management and patient skin self‐examination.

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Section: Discussionmentioning

confidence: 61%

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients

Rayner

McMeniman

Duffy

et al. 2019

Acad Dermatol Venereol

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“…Unfortunately, the pathology reports detailing the pigmentation status of the five melanoma lesions for patient 176SP, who was also of this MC1R genotype, were not available to confirm this observation. Previous association of the MC1R RHC alleles with amelanotic melanoma and depigmented nevi lends support to this interaction (Zalaudek et al, 2009;Curchin et al, 2012), and possibly for the high number of multiple primaries. Moreover, a genetic interaction has earlier been described for the high-penetrance familial melanoma gene CDKN2A and co-carriers of homozygous MC1R RHC alleles for the increasing incidence of multiple primary melanomas (Peris et al, 2004;Goldstein et al, 2005;Eliason et al, 2007;Pastorino et al, 2008).…”

Section: Discussionmentioning

confidence: 83%

Phenotypic Characterization of Nevus and Tumor Patterns in MITF E318K Mutation Carrier Melanoma Patients

Sturm

Fox

McClenahan

et al. 2014

Journal of Investigative Dermatology

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A germline polymorphism of the microphthalmia transcription factor (MITF) gene encoding a SUMOylation-deficient E318K-mutated protein has recently been described as a medium-penetrance melanoma gene. In a clinical assessment of nevi from 301 volunteers taken from Queensland, we identified six individuals as MITF E318K mutation carriers. The phenotype for 5 of these individuals showed a commonality of fair skin, body freckling that varied over a wide range, and total nevus count between 46 and 430; in addition, all were multiple primary melanoma patients. The predominant dermoscopic signature pattern of nevi was reticular, and the frequency of globular nevi in carriers varied, which does not suggest that the MITF E318K mutation acts to force the continuous growth of nevi. Excised melanocytic lesions were available for four MITF E318K carrier patients and were compared with a matched range of wild-type (WT) melanocytic lesions. The MITF staining pattern showed a predominant nuclear signal in all sections, with no significant difference in the nuclear/cytoplasmic ratio between mutation-positive or -negative samples. A high incidence of amelanotic melanomas was found within the group, with three of the five melanomas from one patient suggesting a genetic interaction between the MITF E318K allele and an MC1R homozygous red hair color (RHC) variant genotype.

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“…In our study, these lesions occurred in the youngest population, and no characteristic phenotypic pattern was identifiable. A recent report describes a similar clinical case .…”

Section: Discussionmentioning

confidence: 86%

Distinct melanoma types based on reflectance confocal microscopy

Pellacani

Pace

Reggiani

et al. 2014

Experimental Dermatology

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Distinct melanoma types exist in relation to patient characteristics, tumor morphology, histopathologic aspects and genetic background. A new diagnostic imaging tool, reflectance confocal microscopy (RCM), allows in vivo analysis of a given lesion with nearly histologic resolution while offering a dynamic view of the tissue in its 'natural' environment. The aim of this study was to analyse cell morphology of consecutive melanomas as they appear on RCM and to correlate morphology with tumor and patient characteristics. One hundred melanomas were visualized by RCM before excision. Clinical data, confocal features and histologic criteria were analysed. Four types of melanomas were identified as follows: (i) Melanomas with a predominantly dendritic cell population ('dendritic-cell melanomas') typically were thin by Breslow index; (ii) Melanomas typified by roundish melanocytes were smaller in size than dendritic cell MMs, but thicker by Breslow index, and predominantly occurred in patients with a high nevus count; (iii) Melanomas characterized by dermal nesting proliferation usually were thick by Breslow index at the time of diagnosis, although frequently smaller in size compared with the other types; and (iv) combined type melanomas may represent an evolution of dendritic cell and/or round cell types. Integration of confocal microscopy with clinical and histologic aspects may help in identifying and managing distinct tumors.

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Dermoscopy, reflectance confocal microscopy and histopathology of an amelanotic melanoma from an individual heterozygous for MC1R and tyrosinase variant alleles

Cited by 15 publications

References 23 publications

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients

Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients

Phenotypic Characterization of Nevus and Tumor Patterns in MITF E318K Mutation Carrier Melanoma Patients

Distinct melanoma types based on reflectance confocal microscopy

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