Mohs for Melanoma: A Review of MART-1 Frozen Section Interpretation.

BACKGROUND: Mohs surgery for melanoma has been performed for many decades, but advances in the use of immunohistochemistry with frozen sections during Mohs surgery have allowed for more accurate, reliable, and efficient margin assessment with improved local control of the disease. OBJECTIVE: To describe the use of MART-1 in treating melanoma with Mohs surgery and serve as a primer for the Mohs surgeon adding melanoma cases to their repertoire. MATERIALS AND METHODS: Review of the literature and discussion of experience with Mohs for melanoma. RESULTS: Practical approach and pitfalls when assessing margins using MART-1 immunohistochemistry during Mohs surgery for the treatment of melanoma. CONCLUSION: Mohs for melanoma is an expanding field-education of Mohs surgeons and increasing the practice of this technique has the potential to improve patient outcomes.

Correlation of basal cell carcinoma subtype with histologically confirmed subclinical extension during Mohs micrographic surgery: A prospective multicenter study.

BACKGROUND: Traditionally "aggressive" histologic subtypes (HSs) of basal cell carcinoma (BCC) are more likely to quantitatively exhibit subclinical extension (SCE), requiring more stages during Mohs micrographic surgery (MMS) and, therefore, larger margins upon excision. However, the tendency for SCE has never been compared between HSs of BCC in a prospective manner. OBJECTIVE: To prospectively correlate the HS of BCC with the likelihood of SCE as defined by the number of MMS stages required to clear the tumor. METHODS: In a prospective, multicenter study involving 17 Mohs surgeons in 16 different practices across the United States, data regarding 1686 cases of BCC undergoing MMS were collected. Patient demographics, tumor characteristics, number of MMS stages required for tumor clearance, and specific BCC subtypes noted on both index biopsy and the final MMS stage were recorded. RESULTS: Analysis of the average number of MMS stages for each HS required to clear tumor revealed 2 distinct degrees of SCE (P < .0001): high (higher than average) risk of SCE (1.9 stages, 1.0 SD) and low (lower than average) risk of SCE (1.6 stages, 0.9 SD). Subtypes of BCC within the high category were morpheaform (2.1), infiltrative (1.9), metatypical (1.9), mixed (1.8), and superficial (1.8). The low category included BCC subtypes of basosquamous (1.6), micronodular (1.6), nodular (1.6), and unspecified (1.5). Three hundred twenty-four cases (22.0%) manifested HS drift or a change in subtype from index biopsy to the final MMS stage. Superficial BCC was the only subtype that showed an increase in prevalence from index biopsy to the final MMS stage (from 16.0% to 25.8%; P < .0002). LIMITATIONS: HSs from index biopsy may not be representative of all HSs present, resulting in sampling bias. CONCLUSION: SCE of superficial BCC was as likely as SCE of BCC subtypes that are considered "aggressive" and are deemed "appropriate" for MMS by the appropriate use criteria. Our study also found that when HS drift occurs, the most likely subtype to extend subclinically is superficial BCC.

Risk factors for keratinocyte carcinoma skin cancer in nonwhite individuals: A retrospective analysis.

BACKGROUND: Because most of the US population will consist of nonwhite individuals by the year 2043, it is essential that both physicians and patients are educated about skin cancer in nonwhite persons. OBJECTIVE: To update the epidemiology, investigate specific risk factors, and facilitate earlier diagnosis and intervention of keratinocyte carcinoma in nonwhite individuals. METHODS: Institutional review board-approved retrospective chart review of all nonwhite patients who had received a biopsy-proven diagnosis of skin cancer at Drexel Dermatology during June 2008-June 2015. RESULTS: Squamous cell carcinoma (SCC) was the most commonly diagnosed skin cancer in black and Asian populations, and basal cell carcinoma was the most common skin cancer in Hispanics. Black persons exhibited the majority of their SCC lesions in sun-protected areas, particularly the anogenital area. On average, current smokers received skin cancer diagnoses 12.27 years earlier than former smokers and 9.36 years earlier than nonsmokers. LIMITATIONS: Single-center design and interpractitioner variability of skin examination. CONCLUSION: The importance of lesions in photoprotected areas in nonwhite individuals should not go overlooked. However, emphasis should also be placed on active examination of sun-protected areas in nonwhite persons and recognition of the relationship between human papillomavirus and genital SCC lesions. Smoking cessation should be integrated in dermatologic counseling of all patients. Interventions tailored to each of these ethnic groups are needed.

Risk of Subsequent Cutaneous Melanoma in Moderately Dysplastic Nevi Excisionally Biopsied but With Positive Histologic Margins.

Importance: Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins). Objective: To determine outcomes and risk for the development of subsequent cutaneous melanoma (CM) from moderately dysplastic nevi with positive histologic margins observed for 3 years or more. Design, Setting, and Participants: A multicenter (9 US academic dermatology sites) retrospective cohort study was conducted of patients 18 years or older with moderately dysplastic nevi with positive histologic margins and 3 years or more of follow-up data collected consecutively from January 1, 1990, to August 31, 2014. Records were reviewed for patient demographics, biopsy type, pathologic findings, and development of subsequent CM at the biopsy site or elsewhere on the body. The χ2 test, the Fisher exact test, and analysis of variance were used to assess univariate association for risk of subsequent CMs, in addition to multivariable logistic regression models. To confirm histologic grading, each site submitted 5 random representative slide cases for central dermatopathologic review. Statistical analysis was performed from October 1, 2017, to June 22, 2018. Main Outcomes and Measures: Development of CM at a biopsy site or elsewhere on the body where there were moderately dysplastic nevi with positive histologic margins. Results: A total of 467 moderately dysplastic nevi with positive histologic margins from 438 patients (193 women and 245 men; mean [SD] age, 46.7 [16.1] years) were evaluated. No cases developed into CM at biopsy sites, with a mean (SD) follow-up time of 6.9 (3.4) years. However, 100 patients (22.8%) developed a CM at a separate site. Results of multivariate analyses revealed that history of CM was significantly associated with the risk of development of subsequent CM at a separate site (odds ratio, 11.74; 95% CI, 5.71-24.15; P < .001), as were prior biopsied dysplastic nevi (odds ratio, 2.55; 95% CI, 1.23-5.28; P = .01). The results of a central dermatopathologic review revealed agreement in 35 of 40 cases (87.5%). Three of 40 cases (7.5%) were upgraded in degree of atypia; of these, 1 was interpreted as melanoma in situ. That patient remains without recurrence or evidence of CM after 5 years of follow-up. Conclusions and Relevance: This study suggests that close observation with routine skin surveillance is a reasonable management approach for moderately dysplastic nevi with positive histologic margins. However, having 2 or more biopsied dysplastic nevi (with 1 that is a moderately dysplastic nevus) appears to be associated with increased risk for subsequent CM at a separate site.

Leuprolide acetate-induced generalized papular eruption.

Leuprolide acetate, a gonadotropin-releasing hormone agonist, is used in the treatment of prostate cancer. We report a unique case of a disseminated papular rash following leuprolide acetate injections in a 65-year-old man that shares clinical and histopathological features of papuloerythroderma of Ofuji. Leuprolide-induced papuloerythroderma, as well as a limited number of other disseminated cutaneous eruptions caused by this drug, is extremely rare, with only one case previously reported. Our case calls attention to this uncommon side effect in a commonly used hormonal therapy.

Non-nearest-neighbor dependence of stability for group III RNA single nucleotide bulge loops.

Thirty-five RNA duplexes containing single nucleotide bulge loops were optically melted and the thermodynamic parameters for each duplex determined. The bulge loops were of the group III variety, where the bulged nucleotide is either a AG/U or CU/G, leading to ambiguity to the exact position and identity of the bulge. All possible group III bulge loops with Watson-Crick nearest-neighbors were examined. The data were used to develop a model to predict the free energy of an RNA duplex containing a group III single nucleotide bulge loop. The destabilization of the duplex by the group III bulge could be modeled so that the bulge nucleotide leads to the formation of the Watson-Crick base pair rather than the wobble base pair. The destabilization of an RNA duplex caused by the insertion of a group III bulge is primarily dependent upon non-nearest-neighbor interactions and was shown to be dependent upon the stability of second least stable stem of the duplex. In-line structure probing of group III bulge loops embedded in a hairpin indicated that the bulged nucleotide is the one positioned further from the hairpin loop irrespective of whether the resulting stem formed a Watson-Crick or wobble base pair. Fourteen RNA hairpins containing group III bulge loops, either 3' or 5' of the hairpin loop, were optically melted and the thermodynamic parameters determined. The model developed to predict the influence of group III bulge loops on the stability of duplex formation was extended to predict the influence of bulge loops on hairpin stability.

Perioral lesions and dermatoses.

The purpose of this article is to review the common neoplasms, infections, and inflammatory dermatoses that may present around or near the mouth. Dental professionals are well positioned to evaluate perioral skin conditions, further contributing to patients' general health. This article includes a review of seborrheic keratosis, warts, actinic keratoses, actinic cheilitis, and squamous cell carcinoma, among several other perioral cutaneous lesions.

A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice.

Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr (-/-) mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr (-/-) Scarb1 (I179N) mice, respectively, when compared to gender-matched Ldlr (-/-) control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr (-/-) Scarb1 (I179N) mice compared to Ldlr (-/-) control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr (-/-) Scarb1 (I179N) mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis.

Differential binding of the related transcription factors Pho4 and Cbf1 can tune the sensitivity of promoters to different levels of an induction signal.

Transcription factors that belong to the same family typically have similar, but not identical, binding specificities. As such, they can be expected to compete differentially for binding to different variants of their binding sites. Pho4 is a yeast factor whose nuclear concentration is up-regulated in low phosphate, while the related factor, Cbf1, is constitutively expressed. We constructed 16 GFP-reporter genes containing all palindromic variants of the motif NNCACGTGNN, and determined their activities at a range of phosphate concentrations. Pho4 affinity did not explain expression data well except under fully induced conditions. However, reporter activity was quantitatively well explained under all conditions by a model in which Cbf1 itself has modest activating activity, and Pho4 and Cbf1 compete with one another. Chromatin immunoprecipitation and computational analyses of natural Pho4 target genes, along with the activities of the reporter constructs, indicates that genes differ in their sensitivity to intermediate induction signals in part because of differences in their affinity for Cbf1. The induction sensitivity of both natural Pho4 target genes and reporter genes was well explained only by a model that assumes a role for Cbf1 in remodeling chromatin. Our analyses highlight the importance of taking into account the activities of related transcription factors in explaining system-wide gene expression data.

Stability of single-nucleotide bulge loops embedded in a GAAA RNA hairpin stem.

Forty-six RNA hairpins containing combinations of 3' or 5' bulge loops and a 3' or 5' fluorescein label were optically melted in 1 M NaCl, and the thermodynamic parameters ΔH°, ΔS°, ΔG°(37), and T(M) for each hairpin were determined. The bulge loops were of the group I variety, in which the identity of the bulge is known, and the group II variety, in which the bulged nucleotide is identical to one of its nearest neighbors, leading to ambiguity as to the exact position of the bulge. The fluorescein label at either the 3' end or 5' end of the hairpin did not significantly influence the stability of the hairpin. As observed with bulge loops inserted into a duplex motif, the insertion of a bulge loop into the stem of a hairpin loop was destabilizing. The model developed to predict the influence of bulge loops on the stability of duplex formation was extended to predict the influence of bulge loops on hairpin stability. Specifically, the influence of the bulge is related to the stability of the hairpin stem distal from the hairpin loop.