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BACKGROUND Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma occurring mainly in the anogenital region. Traditional management with wide local excision has shown high recurrence rates, thus Mohs micrographic surgery (MMS) has emerged as a promising treatment option. OBJECTIVE To compare long-term outcomes after treatment with MMS or excision for primary EMPD. METHODS AND MATERIALS Retrospective cohort review was conducted for 207 patients with EMPD treated at Mayo Clinic in Rochester, MN, between 1961 and 2012. RESULTS Of the 25 patients treated with MMS, 19 primary tumors were included for outcome analysis, with an estimated 5-year recurrence-free survival rate of 91% (95% confidence interval [CI], 75–100) using Kaplan–Meier curve analysis. Of 158 patients treated with local excision, 124 were included for the analysis, with an estimated 5-year recurrence-free survival rate of 66% (95% CI, 56–78). The hazard ratio (HR) for association of treatment was 0.4 (95% CI, 0.10–1.65; p = .20). Estimated 5-year overall survival rates were 79% for MMS (95% CI, 61–100) and 68% for excision (95% CI, 59–78) (HR, 1.39 [95% CI, 0.69–2.82]; p = .36). CONCLUSION Although treatment of primary EMPD with MMS versus excision did not show statistical difference, MMS demonstrated favorable long-term outcomes and was associated with a higher recurrence-free survival rate.

Objective To identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods A genome‐wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta‐analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their impact on gene expression and/or protein function. Results Among the genome‐wide significant associations identified, the largest effect on risk of AAV came from the single‐nucleotide polymorphism variants rs141530233 and rs1042169 at the HLA–DPB1 locus (odds ratio [OR] 2.99 and OR 2.82, respectively) which, together with a third variant, rs386699872, constitute a triallelic risk haplotype associated with reduced expression of the HLA–DPB1 gene and HLA–DP protein in B cells and monocytes and with increased frequency of complementary proteinase 3 (PR3)–reactive T cells relative to that in carriers of the protective haplotype. Significant associations were also observed at the SERPINA1 and PTPN22 loci, the peak signals arising from functionally relevant missense variants, and at PRTN3 , in which the top‐scoring variant correlated with increased PRTN3 expression in neutrophils. Effects of individual loci on AAV risk differed between patients with GPA and those with MPA or between patients with PR3‐ANCAs and those with myeloperoxidase‐ANCAs, but the collective population attributable fraction for these variants was substantive, at 77%. Conclusion This study reveals the association of susceptibility to GPA and MPA with functional gene variants that explain much of the genetic etiology of AAV, could influence and possibly be predictors of the clinical presentation, and appear to alter immune cell proteins and responses likely to be key factors in the pathogenesis of AAV.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

Objective: To present an unusual case of a temporal bone meningioma with intrafascicular spread throughout the temporal facial nerve from cerebellopontine angle (CPA) to stylomastoid foramen. Patient: Four-year-old female with progressive facial weakness and normal hearing. Main Outcome Measure: Clinical, radiological, and histopathological findings of temporal bone meningiomas. Results: A patient presented with progressive facial weakness and normal hearing. Imaging demonstrated a mass within the left internal auditory canal radiologically consistent with a schwannoma. Asymmetric enlargement with enhancement of the left facial nerve from CPA to the stylomastoid foramen suggested facial schwannoma. At surgery, gross tumor was noted in the internal auditory canal, the fallopian canal seemed expanded and the facial nerve was enlarged and had an irregular contour. Resection of the facial nerve from the CPA to just proximal to its exit at the stylomastoid foramen was necessary to achieve negative margins. Cable grafting was performed. The histopathologic diagnosis was transitional meningioma with intraneural growth throughout the length of the resected facial nerve segment. Conclusion: Meningiomas involving the temporal bone are exceedingly rare. We report a rare case of a child presenting with progressive facial weakness due to a presumed facial schwannoma spreading along the facial nerve throughout its intratemporal course that at surgery was found to be an intrafascicular CN VII meningioma.

AbstractChildren are at risk of developing allergic contact dermatitis to fragrances. Personal hygiene products, even those labeled hypoallergenic or considered all natural, may be a significant source of fragrance exposure in this population.