Nasal ala V-Y island flap with a superior vascular pedicle based on inferior perforators of the superior alar artery.

For small defects of the anterior nasal ala, a V-Y pedicle advancement flap within the subunit is a useful repair option. Here we propose a modification of this technique, utilising careful dissection to identify inferior perforators of the superior alar artery. Basing this flap on a visualised vascular pedicle aims to prevent common complications of internal mucosal buckling and free margin notching, by allowing more extensive dissection without compromising the vascularity of the flap.

Curettage and colour-A technique for defining tumour depth on the ear in the Mohs and non-Mohs setting.

For tumours of the ear that are suspected to involve auricular cartilage, precise definition of the extent of involved deep margin can be difficult. As large resections of cartilage can be cosmetically disfiguring with limited repair options, we propose a simple and effective technique to facilitate a targeted deep margin resection using a curette and a surgical marking pen.

Melanoma genetics.

Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other medium to high penetrance melanoma predisposition genes have been associated with renal cell carcinoma (MITF, BAP1) and glioma (POT1). These associations between melanoma and other cancers hint at the possibility of common pathways for oncogenesis, and better knowledge of these pathways may improve understanding of the genetic basis underpinning familial melanoma. It is likely that 'melanoma' risk genes will impact on mutation screening and genetic counselling not only for melanoma but also a range of other cancers.

Pediatric Erythema Multiforme in the Emergency Department: More Than "Just a Rash".

OBJECTIVES: Erythema multiforme (EM) is characterized by symmetrical acrally distributed target lesions; however, other conditions can mimic the clinical features of EM. Although it is typically self-limiting, alternative diagnoses may be life-threatening and require immediate identification and treatment. This study aimed to investigate the clinical spectrum and accuracy of diagnosis of pediatric EM in the emergency department (ED). METHODS: A retrospective, descriptive study of all pediatric patients with an ED information system diagnosis of EM at 2 EDs in Southeast Queensland between January 2010 and July 2013. Cases were evaluated using previously established EM classification criteria. RESULTS: Seventy patients (34 males and 36 females) with a diagnosis of EM were identified. From 57 cases where a diagnosis could be established, 9 cases fulfilled the classification criteria for EM. No patients had mucosal involvement, and therefore, all 9 cases were classified as EM minor, with the majority (89%) attributed to viral infection. Of the 48 cases that did not fit the criteria, the most common condition misdiagnosed as EM was urticaria multiforme (n = 20). CONCLUSIONS: In the ED setting, EM in children is frequently misdiagnosed. Greater awareness of diagnostic factors for EM may improve diagnostic accuracy. Teledermatology and incentives to include clinical pictures in the (electronic) medical record may be useful adjuncts for patients with suspected EM and other dermatological conditions.

Recent advances in cutaneous melanoma: towards a molecular model and targeted treatment.

Melanoma is an aggressive disease process, with a heterogeneous aetiology linked to environmental and genetic risk factor profiles. Overall prognosis for advanced disease remains poor, and a lack of effective systemic therapies has prompted investigation into alternative strategies. The identification of novel mutations that instigate and perpetuate melanocyte transformation has offered insight into new treatment approaches, and the subsequent development of targeted treatments appears to be integral to improving melanoma survival. This article reviews the mechanisms of melanoma oncogenesis and classic molecular signalling pathways, targeted treatment approaches based on the molecular model and immunotherapy, and the advent of next-generation sequencing technologies in understanding the complexity of the melanoma pathogenome. In addition to the known somatic activating mutations BRAF and NRAS, exome sequencing has recently identified RAC1, a novel UV-signature gain-of-function mutation. Germline mutations associated with familial melanoma have added a further dimension to the molecular underpinnings of melanoma, implicating BAP1 and MITF as melanoma predisposition genes. Advances in understanding melanoma and implementing targeted treatment strategies will be of increasing importance in this era of personalised medicine.

Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma.

Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency < 0.01) in families with multiple members affected by these cancers. Whole-genome or exome sequencing was performed on 160 CM and/or UM families from Australia, the Netherlands, Denmark and Sweden. Between one and five cases were sequenced from each family, totalling 307 individuals. Sanger sequencing was performed to validate BRCA1 and BRCA2 germline variants and to assess carrier status in other available family members. A nonsense and a frameshift mutation were identified in BRCA1, both resulting in premature truncation of the protein (the first at p.Q516 and the second at codon 91, after the introduction of seven amino acids due to a frameshift deletion). These variants co-segregated with CM in individuals who consented for testing and were present in individuals with pancreatic, prostate and breast cancer in the respective families. In addition, 33 rare missense mutations (variant allele frequency ranging from 0.00782 to 0.000001 in the aggregated ExAC data) were identified in 34 families. Examining the previously reported evidence of functional consequence of these variants revealed all had been classified as either benign or of unknown consequence. Seeking further evidence of an association between BRCA1 variants and melanoma, we examined two whole-genome/exome sequenced collections of sporadic CM patients (total N = 763). We identified one individual with a deleterious BRCA1 variant, however, this allele was lost (with the wild-type allele remaining) in the corresponding CM, indicating that defective BRCA1 was not a driver of tumorigenesis in this instance. Although this is the first time that deleterious BRCA1 mutations have been described in high-density CM families, we conclude that there is an insufficient burden of evidence to state that the increased familial CM or UM susceptibility is because of these variants. In addition, in conjunction with other studies, we conclude that the previously described association between BRCA2 mutations and UM susceptibility represents a rare source of increased risk.

Increased incidence of bladder cancer, lymphoid leukaemia, and myeloma in a cohort of Queensland melanoma families.

Familial cancer risk has been proposed as a shared feature of many cancers, and overall susceptibility is influenced by combinations of low to moderate risk polymorphisms, rare high penetrance germline mutations, and modulation of risk by environmental and genetic factors. Clustering of melanoma occurs in approximately 10 % of families, and an over-representation of additional cancers has been noticed in some 'melanoma' families. The degree to which other cancers aggregate in families affected by melanoma has not been well defined. Therefore, this study aimed to assess the risk of cancers other than melanoma in a cohort of 178 'intermediate risk' melanoma families, not selected for specific genetic mutations. Families designated as 'intermediate risk' had two first degree relatives (FDRs) affected by melanoma when ascertained between 1982 and 1990, and were followed up over a 33 year period to assess new occurrences of cancer. We included 414 melanoma cases and 529 FDRs, comprising 25,264 person years of observation. Standardised incidence ratios and their 95 % confidence intervals were calculated for all invasive cancers, comparing observed to expected cases of cancer based on age and sex specific incidence rates for the Queensland population. Statistically significant increases were found for bladder cancer in females (observed, 7; expected, 1.99; SIR, 3.52; 95 % CI 1.41-7.25), lymphoid leukaemia in females (observed, 6; expected, 1.75; SIR, 3.43; 95 % CI 1.26-7.46), and myeloma in female melanoma cases (observed, 4; expected, 0.82; SIR, 4.89; 95 % CI 1.33-12.52). Over-representation of bladder cancer, lymphoid leukaemia, and myeloma in females of the cohort may suggest sex-dependent co-modifiers, and it is possible that specific combinations of polymorphisms predispose to certain cancer types.