Pigmented onychomatricoma: a rare mimic of subungual melanoma.
Clin Exp Dermatol. 2018 Feb 23;:
Authors: Isales MC, Haugh AM, Bubley J, Zarkhin S, Bertler D, Hanson E, Verzi AE, Brieva J, Guitart J, Gerami P
PMID: 29473193 [PubMed - as supplied by publisher]
Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation analysis.
Int J Cancer. 2018 Feb 22;:
Authors: Liyanage UE, Law MH, Ong JS, Cust AE, Mann GJ, Ward SV, Melanoma Meta-analysis Consortium, Gharahkhani P, Iles MM, MacGregor S
Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk - putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomised controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma. To perform MR we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark "large" predicted change in PUFAs in which, for example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17th percentile to the median. Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only negligibly changed melanoma risk - Odds Ratio [OR] = 1.03 (95% Confidence Interval [CI] = 0.96 - 1.10). Other PUFAs yielded similar results as DPA. Our MR analysis suggests that the effect of PUFA levels on melanoma risk is either zero or very small. This article is protected by copyright. All rights reserved.
PMID: 29473154 [PubMed - as supplied by publisher]
Melanoma cases demonstrate increased carrier frequency of Phenylketonuria/hyperphenylalanemia mutations.
Pigment Cell Melanoma Res. 2018 Feb 23;:
Authors: Arbesman J, Ravichandran S, Funchain P, Thompson CL
Identifying novel melanoma genetic risk factors informs screening and prevention efforts. Mutations in the phenylalanine hydroxylase gene (the causative gene in phenylketonuria) lead to reduced pigmentation in untreated phenylketonuria patients, and reduced pigmentation is associated with greater melanoma risk. Therefore, we sought to characterize the relationship between phenylketonuria carrier status and melanoma risk. Using National Newborn Screening Reports, we determined the United States phenylketonuria/hyperphenylalanemia carrier frequency in Caucasians to be 1.76%. We examined three publically available melanoma datasets for germline mutations in the phenylalanine hydroxylase gene associated with classic phenylketonuria and/or hyperphenylalanemia. Mutations were identified in 29/814 melanoma patients, with a carrier frequency of 3.56%. There was a two-fold enrichment (p-value=3.4 x 10-5 ) compared to the Caucasian frequency of hyperphenylalanemia/phenylketonuria carriers. These data demonstrate a novel association between phenylalanine hydroxylase carrier status and melanoma risk. Further functional investigation is warranted to determine the link between phenylalanine hydroxlase mutations and melanomagenesis. This article is protected by copyright. All rights reserved.
PMID: 29473999 [PubMed - as supplied by publisher]
Primary Cervical Malignant Melanoma: 2 Cases and a Literature Review.
Int J Gynecol Pathol. 2018 Feb 22;:
Authors: Yin C, Yang A, Zhang Y, Tao L, Zou H, Ren Y, Liang W, Jiang J, Zhao J, Zhang W, Li F, Jia W
Primary cervical malignant melanoma (MM) is an extremely rare tumor, and we are only aware of 44 reported cases. Further information is needed with regard to this disease's clinicopathologic features. Two patients (55 and 81 yr old) with postmenopausal vaginal bleeding were diagnosed with primary cervical MM on the basis of hematoxylin-eosin staining and immunohistochemistry findings. Our literature review revealed that the average age in cases of primary cervical MM was 59 yr (range, 34-81 yr); 93% of patients presented with vaginal bleeding, and 82% of patients were diagnosed at an early clinical stage (International Federation of Gynecology and Obstetrics stages I-II). Primary cervical MM is an extremely rare cervical tumor and is associated with a poor prognosis. Histologic morphology and immunohistochemistry are very important considerations for diagnosing this disease, which must be differentiated from cervical undifferentiated carcinoma, leiomyosarcoma, and malignant peripheral schwannoma.
PMID: 29474317 [PubMed - as supplied by publisher]
CXCL5 facilitates melanoma cell-neutrophil interaction and lymph node metastasis.
J Invest Dermatol. 2018 Feb 20;:
Authors: Soler-Cardona A, Forsthuber A, Lipp K, Ebersberger S, Heinz M, Schossleitner K, Buchberger E, Gröger M, Petzelbauer P, Hoeller C, Wagner E, Loewe R
Chemokines influence tumor metastasis by targeting tumor, stromal and hematopoietic cells. Characterizing the chemokine mRNA expression profile of human primary melanoma samples, we found CXCL5 significantly upregulated in stage T4 primary melanomas when compared to thin melanomas (T1 stage). To characterize the role of CXCL5 in melanoma progression, we established a metastasizing murine xenograft model using CXCL5 overexpressing (CXCL5ox) human melanoma cells. CXCL5 had no effect on melanoma proliferation in vitro and on primary tumor growth in vivo, but CXCL5ox tumors recruited high amounts of neutrophils and exhibited significantly increased lymphangiogenesis in our SCID mouse model. Recruited neutrophils were found in close proximity to or within lymphatic vessels, often in direct contact with melanoma cells. Clinically, CXCL5ox melanomas had significantly increased lymph node metastases. We were able to translate these findings to human patient samples and found a positive correlation between CXCL5 expression, numbers of neutrophils in stage T4 primary melanoma and the occurrence of subsequent locoregional metastasis.
PMID: 29474942 [PubMed - as supplied by publisher]