Clinicopathologic, misdiagnosis, and survival differences between clinically amelanotic melanomas and pigmented melanomas.

BACKGROUND: Amelanotic malignant melanoma (AMM) is challenging to diagnose. Clinical risk factors for AMM are not well defined. OBJECTIVE: To investigate clinicopathologic, misdiagnosis, and survival differences between patients with AMM and those with pigmented malignant melanoma (PMM). METHODS: A cross-sectional retrospective medical record review at a tertiary academic medical center. RESULTS: A total of 933 patients with melanoma with known presenting tumor color were identified (342 with AMM vs 591 with PMM). AMM was associated with older age, history of nonmelanoma skin cancer, and red hair, whereas AMM was inversely associated with a family history of melanoma, more than 50 nevi, and a history of dysplastic nevi. Compared with PMM, AMM was more likely to be located on the head and/or neck, had more aggressive pathologic features (greater Breslow depth and/or mitoses, ulceration, nodular subtype), and was less likely to be associated with a precursor nevus or regression. Finally, patients with AMM were more likely to be misdiagnosed than were patients with PMM (25% vs 12% clinically and 12% vs 7% pathologically), and they had poorer melanoma-specific survival (5-year overall survival rate, 0.77 [95% confidence interval, 0.72-0.82] vs 0.84 [95% confidence interval, 0.80-0.87]). LIMITATIONS: Retrospective study design, single-institutional study. CONCLUSION: Greater clinician awareness, lower biopsy thresholds, and increased patient education may be useful to enhance AMM detection in patients with certain characteristics.

Regioselective Synthesis, NMR, and Crystallographic Analysis of N1-Substituted Pyrazoles.

A systematic study of the N-substitution reactions of 3-substituted pyrazoles under basic conditions has been undertaken. Regioselective N1-alkylation, -arylation, and -heteroarylation of 3-substituted pyrazoles have been achieved using K2CO3-DMSO. The regioselectivity is justified by the DFT calculations at the B3LYP/6-31G**(d) level. A consistent steric effect on chemical shift has been observed for N-alkyl pyrazole analogues. Twenty-five X-ray crystallographic structures have been obtained to confirm the regiochemistry of the major products.

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.