Marta Feito

Pigmentation-related genes and their implication in malignant melanoma susceptibility

Abstract:  Human pigmentation appears to be one of the main modulators of individual risk of developing malignant melanoma (MM). A large number of genes are known to be involved in rare pigmentary disorders and explain most of the variation in pigmentation phenotypes seen in human populations. This Spanish case–control study included 205 patients with melanoma and 245 control subjects. Thirty‐one single nucleotide polymorphisms (SNPs) in genes that had been mainly associated with congenital pigmentation syndromes (ADTB3A, ATRN, CHS1, EDNRB, HPS, KIT, MGRN1, MITF, MLANA, MYO5A, MYO7A, OA1, OCA2, PAX3 and SOX10) were selected. We found that the variant allele of OCA2 R419Q (rs1800407) was associated with increased risk of MM (OR 1.55, 95% CI 1.04–2.31, P = 0.03). This effect on melanoma risk appeared to be stronger among individuals with solar lentigines, or at least 50 nevi. We also describe, for the first time, an association with the variant S1666C (rs2276288) in the MYO7A gene (OR 1.35; 95% CI 1.04–1.76; P = 0.03). Again, this association appeared to be stronger in several phenotypic groups such as individuals with fair skin and those with childhood sunburns. We also found that several variants in the pigmentation genes considered were associated with intermediate phenotypic characteristics. Our findings highlight the potential importance of pigmentation genes in sporadic MM susceptibility.

Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2

Please cite this paper as: Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Experimental Dermatology 2010; 19: 836–844.

rs12512631 on the group specific complement (vitamin D-binding protein GC) implicated in melanoma susceptibility.

Background Solar radiation should be avoided in melanoma patients. Nevertheless, this is the main means by which the body produces vitamin D. Evidence suggests a protective role against cancer for vitamin D. Since vitamin D performs its function by binding the receptor encoded by the vitamin D-receptor gene (VDR), most studies have focused on polymorphisms (SNPs) within this gene. However, the gene encoding the vitamin D-binding protein (GC) appears in recent studies as a major player in the role of a serum vitamin D level regulator and in Cutaneous Melanoma (CM) predisposition. Methods We performed a case-control study of 12 polymorphisms on GC and 9 on VDR among 530 cases and 314 controls from Spanish population. Results We found association between SNP rs12512631, located 3′downstream of GC, and risk of CM that seems to fit a dominant model (OR 1.63 95%CI 1.23–2.17 p-value 7×10−4). This association remained Bonferroni’s correction and after adjustment for potential confounders (p-value 3×10−3) and even after increasing the sample size to 1729 individuals (p-value 0.0129). Moreover, we confirmed evidence of an association between CM susceptibility and the linkage disequilibrium block marked by tag-SNP rs222016 (p-value 0.032). This block covers the GC intron 1 region, with probable regulatory functions. Conclusion To our knowledge, this is the first vitamin D pathway-related polymorphism study in melanoma risk conducted in the Spanish population. Furthermore, we show an association between polymorphisms in GC and melanoma risk, confirming recent studies in different populations.

Pediatric Dermatofibrosarcoma Protuberans in Madrid, Spain: Multi-institutional Outcomes

Little is known about the incidence and management of dermatofibrosarcoma protuberans (DFSP) in children. We conducted a retrospective review of all patients younger than 18 years of age treated for DFSP over a period of 11 years (2000–2011) in Madrid, Spain. The sample consisted of 13 children. The average annual incidence of DFSP in the pediatric population corresponded to 1.02 cases per million person‐years (95% confidence interval 0.55, 1.73). Sites of involvement were diverse, with 15.3% of tumors found in acral locations. The median tumor size was 3.5 cm × 3 cm and the median time from apparent onset to diagnosis was 36 months. Histopathologic examination revealed conventional (77.0%), pigmented (15.4%), and myxoid (7.6%) variants. The mitotic index was consistently <5 per 10 high‐power fields. All lesions were removed using surgical excision. One patient developed a local recurrence because of initial affected margins; none developed metastases. The median duration of clinical follow‐up was 70.5 months. This study estimated the average annual incidence rate of DFSP in a population of patients younger than 18 years and reviewed the experience of several hospitals in the management of this tumor.

Dermoscopic findings and histological correlation of the acral volar pigmented maculae in Laugier–Hunziker syndrome

Laugier–Hunziker syndrome (LHS) is an acquired, benign, macular hyperpigmentation of the lips and oral mucosa, often associated with pigmentation of the nails. Volar acral maculae on the palms and fingertips of patients affected by LHS are a typical feature of this rare entity. Dermoscopic examination of these maculae has been described in a previous report, in which authors found a parallel‐furrow pattern. We describe two cases in which a parallel‐ridge pattern (PRP) was found on the dermoscopic examination of the pigmented acral lesions. Histological examination showed increased melanin in basal keratinocytes, which was most prominent in those located at the crista intermedia profunda, that is, in the epidermal rete ridges underlying the surface ridges. In our study, dermoscopic features of the pigmented maculae found on LHS differed from those previously described. In addition, by means of this case report, the histological features of these lesions are described for the first time, showing an excellent correlation with dermoscopy. The reported cases prove that although the PRP is very specific of melanoma, it is also possible to find it in benign lesions. Therefore, we must be familiar with the differential diagnosis of PRP, and take into consideration the clinical context in which we find it. Further studies are needed to increase our knowledge on the histological and dermoscopic features of acral pigmented maculae of LHS.

Childhood actinic lichen planus: Successful treatment with antimalarials

Actinic lichen planus (ALP) is a photosensitive variant of lichen planus, affecting mainly young adults of Middle Eastern descent. We report a case of ALP in a 9‐year‐old Colombian girl with an excellent response to hydroxychloroquine and photoprotection.

Fever and Multiple Eschars After an African Safari: Report of Three Cases

African tick‐bite fever (ATBF), a tickborne disease endemic in rural areas of sub‐Saharan Africa and the West Indies caused by Rickettsia africae, has been recognized as an emerging health problem in recent years. ATBF has been reported as the second most commonly documented etiology of fever, after malaria, in travelers who return ill from sub‐Saharan Africa. Most cases reported in the literature occurred in middle‐aged adults, so the incidence of ATBF in children is unclear. We report a cluster of three cases of ATBF that occurred in children ages 7 to 16 years after returning from a game‐hunting safari in South Africa.

Trichodysplasia Spinulosa in a 20-Month-Old Girl With a Good Response to Topical Cidofovir 1%.

Trichodysplasia spinulosa (TS) is a rare entity, characterized by a follicular digitate keratosis predominantly affecting the face and variable degrees of hair loss, most severely facial hair, that occurs in immunosuppressed individuals, and is considered to be a viral infection caused by a human polyomavirus, the “TS-associated polyomavirus.” Histologically it is characterized by hair follicles with excessive inner root-sheath differentiation and intraepithelial viral inclusions. Correlation of these findings with clinical features is required for diagnosis. Treatment with antiviral agents appears to be the most effective. We report the occurrence of TS in a 20-month-old girl with multivisceral transplantation due to short-bowel syndrome secondary to intestinal atresia and gastroschisis. The patient was treated with cidofovir 1% cream, with significant improvement and without any adverse effects. We describe the youngest patient, to our knowledge, with TS.

Diffuse Melanosis and Ascites due to Metastatic Malignant Melanoma

We present a female patient who developed mucosal and skin hyperpigmentation due to metastatic malignant melanoma. Diffuse cutaneus melanosis is a rare entity that complicates a small percentage of metastatic melanomas, confering a fatal prognosis. We discuss briefly the current evidence on pathogenesis of melanosis arising from metastatic melanoma.

Notalgia Paresthetica and Multiple Endocrine Neoplasia Syndrome 2A: A Case Report.

Notalgia paresthetica is characterized by a hyperpigmented macular pruritic skin lesion most commonly localized unilaterally in the middle and upper back region. This condition has been reported in association with multiple endocrine neoplasia syndrome type 2A (MEN 2A) in several families; it rarely affects children and it may serve as an early marker of MEN 2A. We report a 9‐year‐old girl diagnosed with MEN 2A and notalgia paresthetica.