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Summary: Background: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. Objectives: To develop and validate a model for incident first‐primary cutaneous melanoma using clinically assessed risk factors. Methods: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case–Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole‐body naevi and solar lentigines, and self‐assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age‐ and sex‐adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer–Lemeshow test. Results: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six‐level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71–4·54] in the Australian study and 2·56 (95% CI 2·23–2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76–0·83) in the Australian study and 0·73 (95% CI 0·70–0·75) in the Leeds study. The Hosmer–Lemeshow test P‐value was 0·30 in the Australian study and < 0·001 in the Leeds study. Conclusions: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels.For reasons of feasibility, time and cost many melanoma prediction models use self‐assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically‐assessed whole‐body naevi and solar lentigines, and self‐assessed risk factors including pigmentation phenotype and history of keratinocyte cancer.This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions. Linked Comment: Toland. Br J Dermatol 2020; 182:1089–1090. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem‐like cells, a source of post‐treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM‐infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)‐β‐mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single‐cell transcriptomics demonstrated that both tumour and haematopoietic‐derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co‐expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti‐tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways. [ABSTRACT FROM AUTHOR]

Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings. [ABSTRACT FROM PUBLISHER]

The article offers information on the 2010 review and revision of Great Britain guidelines related to the aspects of cutaneous melanoma management, including its prevention, diagnosis, and initial treatment. It mentions several measures to prevent melanoma, such as the limit of sun exposure in people at risk of the disease. It discusses several factors that can help in the prognosis of melanoma, including perineural infiltration, detection of microsatellites, and presence of melanocytic naevus.

Background Atypical naevi are common benign skin lesions but are also recognized both as precursors of and risk factors for melanoma. It is therefore imperative to excise those lesions that are either likely to progress or are already progressing to melanoma. Clinically, however, it may be difficult to distinguish these from benign atypical naevi with bland histology. Objectives To analyse the clinical characteristics of excised melanocytic lesions and to identify the predictors of severe histological atypia/melanoma in situ and invasive melanoma. Methods The case notes of 434 patients who had melanocytic lesions removed at a pigmented lesion clinic were studied retrospectively. A single pathologist reviewed the excised lesions and clinical characteristics predictive of malignancy were identified. Results The best predictors of melanoma were older age, history of change and site on an extremity, but only older age was predictive of severe histological atypia/melanoma in situ as opposed to mild to moderate atypical histology. Conclusions These results confirm the difficulty of differentiating accurately between benign atypical naevi and borderline lesions or early melanoma in a clinical setting. It is therefore necessary to have a sufficiently low threshold for excision to avoid missing early melanomas, particularly in older patients presenting with lesions on the extremities. [ABSTRACT FROM AUTHOR]

Laryngo-onychocutaneous syndrome (LOCS) is a condition characterized by erosive or ulcerative skin lesions associated with excessive granulation tissue, at sites of trauma such as the digits, elbows and knees. Similar lesions can occur within the conjunctival mucosa, leading to corneal scarring and blindness. The main complications, however, occur in the respiratory tract, where a similar process of erosions and subsequent formation of granulation tissue causes airway obstruction which may lead to premature death. LOCS is now believed to be a nonblistering variant of junctional epidermolysis bullosa and to date there are no efficacious treatments available. We report a 16-year-old girl with LOCS who failed to respond to methylprednisolone and cyclophosphamide, but had a partial response to oral thalidomide with marked decrease in granulation tissue and tracheal secretions. Interruption of treatment resulted in prompt resurgence of the granulation tissue which was again controlled by reintroduction of thalidomide. We propose that in the absence of effective therapies for LOCS, a trial of thalidomide in these patients should be considered. [ABSTRACT FROM AUTHOR]

Cutaneous granulomas are uncommon in primary immunodeficiency disorders. We report cutaneous granulomas in a child with ataxia telangiectasia (AT) and compare the clinical course with similar lesions in an adult with common variable immunodeficiency (CVI). A 4-year-old female with AT developed cutaneous granulomas as erythematous plaques. The largest lesion appeared on her left cheek and continued to progress despite treatment with topical and intralesional steroids. Disease control was obtained initially with oral antibiotics and low-dose oral steroids. On cessation of oral steroids, significant relapse of the facial granuloma occurred. Pulsed and then oral steroids were required to stop the disease process leaving significant scarring. The second case is of cutaneous granulomas in a 66-year-old man, with CVI, who presented with an erythematous reticulate rash on the legs. We consider it useful to report this patient here as disease control was obtained in a similar way with systemic immunosuppression. In this patient a combination of oral steroids and azathioprine was used. These cutaneous granulomas are thought to be a manifestation of immune dysregulation. No infectious cause has been found so far. We recommend the use of broad-spectrum antibiotics in conjunction with systemic steroids for progressive granulomas, as these patients are immunosuppressed and infection with an unidentified organism cannot be excluded. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy (SLNB) is a minimally invasive procedure used accurately to stage nodal basins at risk of occult metastases. There are no data as yet to show a survival benefit from SLNB and its use remains controversial. If Breslow thickness of the tumour correlates well with positive SLNB, it could be used to select patients for SLNB. Methods: A quantitative systematic review of published studies on SLNB in patients with melanoma available by September 2001 was performed. Results: Twelve studies containing 4218 patients with stage I and II melanoma were identified; 17·8 (95 per cent confidence interval 16·7 to 19·0) per cent of patients had nodal micrometastases detected by SLNB. The incidence of micrometastasis in sentinel nodes correlated directly with Breslow tumour thickness; it was 1·0 per cent for lesions of less than or equal to 0·75 mm, 8·3 per cent for 0·76–1·50 mm, 22·7 per cent for 1·51–4·0 mm and 35·5 per cent for more than 4·0 mm. Conclusion: The Breslow thickness of primary melanoma predicts the presence of a sentinel node metastasis. The published data are not sufficient to demonstrate a correlation between other known prognostic indicators and a positive SLNB. [ABSTRACT FROM AUTHOR]

Summary: 黑色素瘤是一种在黑素细胞(皮肤的色素细胞)中发生的癌症。黑色素瘤发生率(表示其常见程度)在皮肤白皙人群中增加,其中澳大利亚、新西兰、北美和欧洲的发病率最高。 在澳大利亚,14 名男性中有 1 名和 24 名女性中有 1 名将在其一生中被诊断患有黑色素瘤。黑色素瘤的危险因素包括日晒、日光浴、皮肤上痣的数量、皮肤对阳光的敏感度、雀斑数量、肤色、眼睛颜色、头发颜色、家族史和许多易感基因(使您面临更高风险的基因)。 黑色素瘤风险预测模型(将许多个体黑色素瘤危险因素结合到总体风险中)可能有助于通过匹配预防策略(干预)与患者的黑色素瘤风险水平来预防黑色素瘤。 许多黑色素瘤风险预测模型使用自我评估的危险因素,因为与临床(医学)危险因素评估相比,这样更快且成本更低,但很多人低估了他们的痣数。本研究旨在推导一个黑色素瘤风险预测模型,其中包括身上痣的数量和日光性雀斑痣(阳光引起的深色皮肤斑)作为临床评估的危险因素,以及色素(肤色)特征、日晒、家族史和皮肤癌病史作为自我评估的危险因素。 痣的数量是模型中最强的危险因素。该模型在识别能力(模型区分患有和未患黑色素瘤的个体的能力)方面表现出色。在临床环境中,该模型可能有助于临床医生根据患者的黑色素瘤风险确定适合针对性预防策略的患者。 本摘要涉及研究:一项关于纳入临床评估的痣和日光性雀斑痣的黑色素瘤风险预测模型的开发和外部验证研究 Linked Article: Vuong et al. Br J Dermatol 2020; 182:1262–1268 [ABSTRACT FROM AUTHOR]

Summary: Melanoma is a cancer that develops in the melanocytes, the pigment cells of the skin. Melanoma incidence rates, which show how common it is, have been increasing in people with fair skin, with the highest rates in Australia, New Zealand, North America and Europe. In Australia, one in 14 men and one in 24 women will be diagnosed with melanoma during their lifetime. Risk factors for melanoma include sun exposure, sunbed use, the number of moles on the skin, the skin's sensitivity to the sun, the number of freckles, skin colour, eye colour, hair colour, family history and a number of susceptibility genes (genes that place you at higher risk). Melanoma risk prediction models, which combine many individual melanoma risk factors into an overall risk, may be useful in the prevention of melanoma by matching prevention strategies (interventions) to the patient's melanoma risk levels. Many melanoma risk prediction models use self‐assessed risk factors because it is quicker and less costly compared to the clinical (medical) assessment of risk factors, but many people underestimate the number of moles they have. This study aims to derive a melanoma risk prediction model, which includes the number of moles on the body and solar lentigines (darker skin patches caused by the sun) as clinically‐assessed risk factors, and pigmentation (skin colour) characteristics, sun exposure, family history and history of skin cancer as self‐assessed risk factors. The number of moles is the strongest risk factor in the model. The model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma. In a clinical setting, this model may help clinicians identify patients for targeted prevention strategies based on the patient's melanoma risk. This is a summary of the study: Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines Linked Article: Vuong et al. Br J Dermatol 2020; 182:1262–1268 [ABSTRACT FROM AUTHOR]

Presents a letter to the editor related to a case of Bazex–Dupré–Christol syndrome associated with multiple genital trichoepitheliomas.