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The article discusses the granulomatous reaction to hyaluronic acid filler occurring during the use of neratinib. It examines facial swelling of a woman with metastatic adenocarcinoma. It presents the Computed tomography results which reveals facial soft tissue infiltration consistent with sequelae of cosmetic procedures.

We report four previously undescribed families with germline BRCA1-associated protein-1 gene ( BAP1) mutations and expand the clinical phenotype of this tumor syndrome. The tumor spectrum in these families is predominantly uveal malignant melanoma ( UMM), cutaneous malignant melanoma ( CMM) and mesothelioma, as previously reported for germline BAP1 mutations. However, mutation carriers from three new families, and one previously reported family, developed basal cell carcinoma ( BCC), thus suggesting inclusion of BCC in the phenotypic spectrum of the BAP1 tumor syndrome. This notion is supported by the finding of loss of BAP1 protein expression by immunochemistry in two BCCs from individuals with germline BAP1 mutations and no loss of BAP1 staining in 53 of sporadic BCCs consistent with somatic mutations and loss of heterozygosity of the gene in the BCCs occurring in mutation carriers. Lastly, we identify the first reported recurrent mutation in BAP1 (p. R60X), which occurred in three families from two different continents. In two of the families, the mutation was inherited from a common founder but it arose independently in the third family. [ABSTRACT FROM AUTHOR]

UV light is regarded as a major pathogenic factor for melanoma. However, melanoma can arise in anatomic sites that are relatively or completely sun protected. We have analyzed 126 primary melanomas from anatomic sites in different sun exposure [skin with (n = 30) or without (n = 40) chronic sun damage (CSD), glabrous (non-hair bearing acral skin, n = 36), and mucosa (n = 20)] for DNA copy number aberrations using array CGH and for the mutational status in BRAF, NRAS, HRAS, and KRAS. We found significant differences in the type of genomic instability, regional DNA copy number changes, mutation frequencies in BRAF and NRAS between the four groups. Melanomas arising on the relatively or absolutely sun protected glabrous skin or mucosa, respectively, showed significantly a higher degree of chromosomal instability as assessed by the overall proportion of genome altered, copy number transitions in chromosomes, and total number of amplifications. Melanomas on glabrous skin showed higher frequencies of amplifications of the cyclin D1 locus, losses of 10p, and gains affecting 6p. Mucosal melanomas had higher frequencies of gains of 1q, and losses affecting 4q, 8p, 11p, 21q. When melanomas on the skin with or without CSD were compared, cases with no CSD had significantly more losses affecting 10q and gains of 20q, whereas cases with CSD showed more frequent losses of 4q, 11p, and gains of 22. Based on chromosomal aberrations alone samples could be correctly classified with 63% accuracy into the four groups. Mutations in BRAF were found more commonly in cases with no CSD (18/27 or 67%) and were significantly less frequent in other types (2/15 in CSD, 3/26 in glabrous, 1/17 in mucosa). Mutation in ras genes occurred exclusive of mutations in BRAF and most commonly affected the NRAS gene. Only one mutation in HRAS and no mutations in KRAS were found. Mutations were slightly more frequent in melanomas with CSD (3/14) than in melanomas on skin without CSD (2/21). However, a significant proportion of melanomas showed mutations in neither BRAF nor ras genes. Melanomas with mutations of BRAF more frequently showed increased copy number of the BRAF locus on chromosome 7 and selectively targeting the mutated allele. Melanomas with BRAF mutations also had significantly more losses of chromosome 10q including the PTEN region, than melanomas with ras mutations or melanomas with no mutations, possibly suggesting cooperation between these two events. Interestingly, melanomas with mutations in BRAF or ras genes frequently showed losses of the CDKN2A region on 9p, whereas melanomas without mutations did not. If confirmed, this suggests that the oncogene active in melanomas that are BRAF and ras wild-type does not require loss of p16 and thus may operate outside of the MAP kinase pathway. In summary, the divergent pattern of genetic alterations in melanomas of different anatomic sites and sun exposure patterns suggest distinct genetic pathways likely to require distinct targeted interventions in the future. More detailed comparisons are necessary to identify potential candidate genes in cases with no detectable mutations in the MAP kinase pathway. Work supported by NCI grants RO1CA94963 and R33CA95300. [ABSTRACT FROM AUTHOR]

Background: Nevus-associated melanomas (NAM) account for 30% of all melanomas and are associated with younger age and with thinner Breslow thickness. Previous studies of NAM dermoscopy found conflicting results., Objective: To compare the clinical and dermoscopic features of NAM and de novo melanomas (DNM), stratified by melanoma thickness, in a relatively large cohort of patients., Methods: A cross-sectional study of all melanomas biopsied between 2004 and 2019 at a large cancer centre. Lesions were categorized as in situ and invasive NAM or DNM. Dermoscopic images were reviewed and annotated. Associations between melanoma subtype and dermoscopic features were analysed via logistic regression modelling. Bivariate analyses were conducted using non-parametric bootstrap and chi-squared methods., Results: The study included 160 NAM (86 in situ and 74 invasive) and 218 DNM (109 in situ and 109 invasive). NAM were associated with younger age, greater likelihood of being present on the torso, and thinner Breslow thickness. NAM were 2.5 times more likely to show a negative pigment network than DNM. In situ NAM were 2.1 and two times more likely to display dermoscopic area without definable structures and tan structureless areas than DNM, respectively. In situ melanomas were more likely to present a pigment network, and invasive melanomas more commonly presented scar-like depigmentation and shiny white structures. Streaks, blotches and shiny white structures were associated with deeper Breslow depth., Conclusions: Even though the nevus component of NAM could not be identified dermoscopically in the current series, negative pigment network, tan structureless areas and areas without definable structures are dermoscopic clues for NAM., (© 2021 European Academy of Dermatology and Venereology.)

Background: Lentigo maligna/lentigo maligna melanoma (LM/LMM) poses a treatment and surgical challenge given unpredictable subclinical extension resulting in incomplete excision., Objectives: To describe the demographic, clinical and pathologic characteristics of incompletely excised LM/LMM. To evaluate the potential role of reflectance confocal microscopy (RCM)., Patients and Methods: A retrospective review of a melanoma database at a tertiary cancer centre for patients referred with 'incompletely excised LM/LMM' or 'incompletely excised melanoma' between October 2006 and July 2017. We recorded clinical and pathological data and surgical margins needed to clear the residual LM/LMM. The second part consisted of a prospective cohort of patients in which RCM was performed when presenting with incompletely excised LM/LMM., Results: We included a total of 67 patients (retrospective + prospective cohort); mean age was 64.9 (standard deviation: 11.3) years and 52.2% were males. For the retrospective cohort (n = 53), the mean scar size was 3.4 cm. The average initial margins excised prior to presentation were 4.8 mm (range 3-7 mm). The average additional margin needed to clear the residual, incompletely excised LM/LMM was 7.8 mm. For the prospective cohort (n = 14), there were no differences in age, gender or size when compared to the retrospective cohort. RCM had a diagnostic accuracy of 78.6%, a sensitivity of 90.9%, a specificity of 33.3% and a positive predictive value of 83.3% for the detection of incompletely excised LM/LMM., Conclusions: Incompletely excised LM/LMM is a poorly characterized clinical-pathological scenario that may require considerable extra margins for microscopic clearance. RCM may emerge as a valuable tool for the evaluation of patients with incompletely excised LM/LMM., (© 2020 European Academy of Dermatology and Venereology.)

Background: Determining whether repigmentation within or adjacent to lentigo maligna or lentigo maligna melanoma (LM/LMM) scars represents recurrence of melanoma is challenging. The use of reflectance confocal microscopy (RCM) and dermoscopy may aid in differentiating true melanoma recurrence from other causes of repigmentation., Objectives: To describe the characteristics of repigmentation within or adjacent to LM/LMM scars observable on RCM and dermoscopy., Methods: We retrospectively analysed patients who presented with new pigmentation within or adjacent to scars from surgically treated LM/LMM between January 2014 and December 2018. Clinical and demographic characteristics and time to recurrence were recorded. RCM was used to evaluate areas of pigmentation before biopsy. If available, dermoscopic images were also evaluated., Results: In total, 30 confocal studies in 29 patients were included in the study cohort. Twenty-one patients had biopsy-confirmed recurrent LM/LMM; the remainder had pigmented actinic keratosis (n = 4) or hyperpigmentation/solar lentigo (n = 5). RCM had sensitivity of 95.24% (95% CI, 76.18-99.88%), specificity of 77.7% (95% CI, 39.99-97.19%), positive predictive value of 90.91% (95% CI, 74.58-97.15%) and negative predictive value of 87.5% (95% CI, 50.04-98.0%). The most common dermoscopic feature observed among patients with recurrent LM/LMM was focal homogeneous or structureless areas of light-brown pigmentation (92.8% vs. 37.5% in patients with other diagnoses; P = 0.009). LM-specific dermoscopic criteria were present in only 28.5% of patients with recurrent LM/LMM., Conclusions: Reflectance confocal microscopy and dermoscopy are valuable tools for the comprehensive evaluation of repigmentation within or adjacent to LM scars., (© 2019 European Academy of Dermatology and Venereology.)

Bortezomib is the first proteasome inhibitor to be approved for use in haematological malignancies. Although a rash has been described as a common adverse event associated with the drug, it has not been well characterised. Based on three phase II studies of bortezomib in patients with non-Hodgkin lymphoma (140 assessable patients), we identified 26 patients who developed a unique erythematous maculopapular rash during treatment, six of whom underwent cutaneous biopsy. Punch biopsy in six patients revealed a perivascular lymphocytic infiltrate without evidence of lymphoma, consistent with a non-necrotising cutaneous vasculitis. The combined overall response rate was 41%. The response in the 26 patients who developed a rash was 73%, compared with 33% in patients who did not. The odds ratio for response given the development of a rash was 4.6 (95% CI, 1.7-12.4, P = 0.001). This is the first report to characterise a vasculitic rash associated with bortezomib, and to show a relationship between development of the rash and response to treatment. Unlike classic hypersensitivity type reactions, this vasculitic rash may not necessarily prompt cessation of drug. In fact, the development of an isolated cutaneous vasculitis may portend a better clinical response to bortezomib in some patients.