A purple plaque in a patient with systemic sclerosis

We present the case of a 43-year old woman with anti-U3 ribonucleoprotein antibody-positive systemic sclerosis presenting with an enlarging purple plaque on the left upper arm. The skin was not sclerotic; however, there had been a cluster of long-standing telangiectases preceding the plaque. Histology and immunohistochemistry confirmed an angiosarcoma. There are five reported cases in the literature about angiosarcoma arising in the skin of patients with systemic sclerosis; however, to our knowledge, this is the first to have arisen from non-sclerotic skin. We would urge clinicians to adopt a high index of suspicion for atypical vascular tumours presenting in patients with systemic sclerosis

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Follicular porokeratosis of Mibelli on the buttocks.

We report a case of follicular porokeratosis of Mibelli affecting the natal cleft in a 42-year-old white man. To our knowledge, this is the first report in the English-language literature of follicular porokeratosis of Mibelli limited to the genitogluteal area

An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients

Sebaceous carcinomas are rare cutaneous appendageal tumors that may occur sporadically or in association with an internal malignancy in Muir–Torre syndrome. In Muir–Torre syndrome microsatellite instability can often be demonstrated in tumor DNA as a result of an inherited mutation in one of several known mismatch repair genes; however, the role of microsatellite instability in sporadic sebaceous carcinomas has not been previously studied. In this report we describe the clinicopathologic characteristics of a series of unselected sebaceous carcinomas and examine them for the presence of microsatellite instability. Of 10 consecutive tumors identified over a 10 y period, only one was from a patient known to have Muir–Torre syndrome. Of the nine presumed sporadic cases, five were from four renal transplant recipients and four from otherwise healthy individuals. Microsatellite instability was demonstrable in three cases: in the Muir–Torre syndrome-associated tumor and in two tumors from transplant patients. Microsatellite instability was subsequently also found in a sebaceous carcinoma from a further transplant patient prospectively sought from another institution. The presence of microsatellite instability in post-transplant sebaceous carcinomas was associated with loss of expression of the mismatch repair protein hMSH2. In summary, sebaceous gland carcinomas, while characteristic of Muir–Torre syndrome, are commonly found outside this context. Among presumed sporadic cases, our data suggest they may be over-represented in immunosuppressed renal transplant recipients. The presence of microsatellite instability in transplant-associated lesions, together with loss of hMSH2 expression suggests that immunosuppression might unmask a previously silent Muir–Torre syndrome phenotype in some cases. Alternatively, there is experimental evidence to suggest that immunosuppressive drugs, most plausibly azathioprine, could select for the emergence of a mutator phenotype and thus predispose to the development of sebaceous carcinomas. The role of mismatch repair defects in other post-transplant skin malignancies remains to be established

Dermatological surgery: a comparison of activity and outcomes in primary and secondary care

BACKGROUND Dermatological surgery is carried out by a variety of practitioners in primary and secondary care. OBJECTIVES To explore the activity and histopathological outcomes among different groups of dermatological surgeons dealing with skin cancers. METHODS Reports for all new skin tumour specimens processed by our histopathology department over a continuous 3-month period were reviewed retrospectively. RESULTS One thousand, one hundred and eleven new skin tumour specimens were identified. General practitioners (GPs) were least accurate in clinical diagnosis, with 42.8% (59/138) of their request forms including the eventual histological diagnosis, compared with 69.5% (328/472) for dermatologists (odds ratio, OR 0.33, 95% confidence interval, CI 0.22-0.48). Inappropriate procedures were most often performed by plastic surgeons, usually involving large excision biopsies for benign lesions in elderly patients [6.6% (20/305) of their specimens vs. 0% for dermatologists, exact P < 0.001]. Excision biopsies performed by GPs had the highest rate of margin involvement by tumour of any specialty [68% (15/22) of such specimens vs. 8% (9/116) for dermatologists; OR 25.47, 95% CI 8.26-78.53]. As per National Institute for Health and Clinical Excellence guidance, 13.8% (19/138) of tumours operated on by GPs should instead have been referred to secondary care for initial surgical management. CONCLUSIONS This study presents a strong case for dermatologists to continue to provide the lead in diagnosis of skin lesions, and in selection and execution of dermatological surgical procedures