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The British Journal of Dermatology Oct 2014Nonmelanoma skin cancer (NMSC) is the most common cancer in the U.S.A. The two most common NMSCs are basal cell carcinoma and squamous cell carcinoma. The associations... (Review)
Review
Nonmelanoma skin cancer (NMSC) is the most common cancer in the U.S.A. The two most common NMSCs are basal cell carcinoma and squamous cell carcinoma. The associations of single-nucleotide polymorphisms (SNPs) in pigmentation pathway genes with NMSC are not well characterized. There is a series of epidemiological studies that have tested these relationships, but there is no recent summary of these findings. To explain overarching trends, we undertook a systematic review of published studies. The summarized data support the concept that specific SNPs in the pigmentation pathway are of importance for the pathogenesis of NMSC. The SNPs with the most promising evidence include MC1R rs1805007(T) (Arg151Cys) and rs1805008(T) (Arg160Trp), and ASIP AH haplotype [rs4911414(T) and rs1015362(G)]. There are a few other SNPs found in TYR, OCA2 and SLC45A2 that may show additional correlation after future research. With additional research there is potential for the translation of future findings to the clinic in the form of SNP screenings, where patients at high risk for NMSC can be identified beyond their phenotype by genotypically screening for predisposing SNPs.
Topics: Cell Differentiation; Humans; Melanocytes; Melanosomes; Pigmentation; Pigmentation Disorders; Polymorphism, Single Nucleotide; Skin Neoplasms
PubMed: 25319428
DOI: 10.1111/bjd.13283 -
Journal of the American Academy of... Mar 2013Diffuse melanosis cutis (DMC) is a rare presentation of metastatic melanoma characterized by a progressive blue-gray discoloration of the skin and mucous membranes. (Review)
Review
BACKGROUND
Diffuse melanosis cutis (DMC) is a rare presentation of metastatic melanoma characterized by a progressive blue-gray discoloration of the skin and mucous membranes.
OBJECTIVE
To foster a better understanding of the clinical presentation, histological findings, and pathophysiology underlying DMC.
METHODS
A systematic review of the literature was completed utilizing MEDLINE, CINAHL, Embase, and Google. Data were extracted using a protocol-driven spread sheet with all statistical analyses completed using SPSS.
RESULTS
The review identified 68 original cases of DMC. The mean time from diagnosis of melanoma until development of DMC was 11.48 months (95% confidence interval [CI]: 0-48.16). The mean time to death following the onset of DMC was 4.43 months (95% CI: 0.00-11.11). Histological findings were relatively consistent demonstrating intracellular and extracellular melanin deposition in the dermis, with a pronounced perivascular distribution. The pathophysiological mechanisms underlying DMC could not be definitively elucidated; however, it is hypothesized that the melanin precursors, melanin, and melanosomes liberated by cytolytic metastatic melanoma deposits are phagocytosed by dermal histiocytes, manifesting clinically as diffuse melanosis.
LIMITATIONS
The cross-sectional nature of case reports, paucity of cases of DMC, and heterogeneity in reporting limit any conclusions being drawn regarding the pathophysiology of DMC definitively.
CONCLUSION
DMC heralds a poor prognosis for patients with metastatic melanoma and affected patients should be made aware of the implications of this condition on survival.
Topics: Dermis; Humans; Melanins; Melanoma; Melanosis; Melanosomes; Prognosis; Skin; Skin Neoplasms; Skin Pigmentation
PubMed: 23219556
DOI: 10.1016/j.jaad.2012.08.018