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.

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.

with bortezomib by her oncologist. Despite paraprotein levels remaining stable for six months following chemotherapy, the rash did not resolve. Oral montelukast 10mg daily was added and, on review three months later, the patient had complete clinical resolution of the rash and its symptoms. Blood eosinophil levels normalised to 0.26x10^9/L. Her skin remained clear with ongoing montelukast after twelve months of follow-up.

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.

INTRODUCTION Closed degloving injuries are often overlooked in the acute setting and may not be apparent until later presentation as an evolving contour deformity.1 Trauma with an oblique shearing force can avulse skin and subcutaneous tissues from the underlying fascia, creating a potential space for seroma accumulation, and subsequent Morel-Lavallée lesion. Morel-Lavallée first described posttraumatic seroma in 1853, reporting several patients who sustained traumatic injuries of the lumbosacral region, buttocks, and thigh.2 CASE REPORT Case 1 A 60-year-old man presented with fluctuant masses of his right buttock and thigh, on a background history of trauma to the area when he was run over by a bus many years ago (Fig. 1). Computed tomography scan demonstrated multiple communicating cystic collections (44 × 20 × 12 cm), consistent with a Morel-Lavallée lesion. The lesion and capsule were excised and 2-0 Vicryl quilting sutures placed between the flap and fascia. After surgery and compression, drain output was nearly 5 L over 10 days. A small seroma occurred after drain removal but settled with conservative management. There has been no recurrence after nearly 3 years postsurgery.Fig. 1.: Contour deformity of the right buttock and thigh as described in case 1.Case 2 A 56-year-old man presented with increasing swelling and pain in his left thigh, 11 days after a car drove over his thighs and pelvis. Approximately 1600mL of serosanguineous fluid was aspirated, and over the next month he represented several times for drainage of a presumed "simple seroma." Computed tomography scan subsequently showed a 38 × 11 × 10 cm multiseptated fluid collection. The encapsulated lesion was resected, and the flap was quilted with 3-0 Vicryl sutures (Fig. 2). Postoperatively, a bandage was used for compression, and drain output over 4 days was 300 mL. Some seroma reaccumulation was evident at day 10 and 1 month after surgery, but at 10 months postsurgery there was no recurrence.Fig. 2.: Intraoperative surgical resection of the left thigh Morel-Lavallée lesion described in case 2, demonstrating the extent of the surrounding fibrous capsule.DISCUSSION Following closed degloving, a large dead space is created between the deep fascia and avulsed subcutaneous tissues. Ongoing discordant movement between the surfaces of these tissue planes prevents tissue adherence, thereby promoting seroma accumulation and pseudocyst formation. The presence of an encapsulated lesion, or pseudocyst, implies that conservative management with repeated aspiration will be ineffective. However, seroma may also recur after surgical resection, as simple excision addresses the pseudocyst but does not adequately treat the main issues of dead space and discordant movement between tissue layers. Quilting sutures aim to eliminate dead space and reduce motion between adjacent tissue planes, as demonstrated in elective surgical procedures that feature controlled degloving.3,4 Wide undermining in latissimus dorsi muscle flap harvest and mastectomy results in a dead space with potential movement between tissue layers, and the use of quilting sutures in these procedures is associated with reduced risk of postoperative seroma and reduced total seroma volume.3,4 The utility of quilting sutures for seroma prevention has also been explored in a series of 22 patients with degloving injuries.5 In addition to resection and compression, routine use of quilting sutures is a useful surgical adjunct to close dead space, reduce movement and promote adherence between tissue layers, and prevent reaccumulation of seroma in resected Morel-Lavallée lesions. STATEMENT OF CONFORMITY The authors confirm that the principles outlined in the Declaration of Helsinki have been followed.

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.

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.

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.