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Importance: Shared gene variants in benign-malignant process pairs, such as BRAF mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships., Objective: To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing., Design, Setting, and Participants: In a single-center case series, 10 formalin-fixed, paraffin-embedded cherry angioma specimens from biopsies performed at Massachusetts General Hospital in Boston from July 10, 2016, to January 23, 2018, were obtained and underwent sequencing across a panel of 323 genes most relevant to cancer. Somatic mutations were curated by excluding variants that were presumed to be germline or of low mapping quality., Main Outcomes and Measures: Identification of somatic mutations associated with cherry angiomas., Results: In 10 cherry angioma tissue samples originating from 6 female and 4 male patients with a median (range) age of 54 (26-79) years, 5 samples (50%) revealed somatic missense mutations in GNAQ (Q209H, Q209R, and R183G) and GNA11 (Q209H). Individually, these mutational hot spots are known to be involved in entities that include congenital and anastomosing hemangiomas, hepatic small-vessel neoplasms (Q209), port-wine stains, and Sturge-Weber syndrome (R183). Both hot spots are associated with blue nevi, melanoma associated with blue nevus, and uveal melanoma., Conclusions and Relevance: In this case series study, the high prevalence of 5 known genetic drivers within the benign cherry angioma entity appears to support the context-dependent role of gene alterations in both benign and malignant proliferations from various cellular origins.

Objective: Loss of participants in longitudinal data collection can affect the validity of outcomes in rheumatoid arthritis (RA) registries. Prior research indicates that demographics and socioeconomic and psychosocial factors contribute to attrition. This study analyzed the characteristics of an RA registry that may contribute to attrition in a hospital-based population., Methods: Subjects consisted of RA patients enrolled in the Brigham and Women's Rheumatoid Arthritis Sequential Study. Demographics and clinical and psychological factors were evaluated in univariate analyses to determine differences between participants who dropped out and those who completed 5 years of followup. Univariate factors with a P value <0.1 were used in a survival analysis to determine significant factors associated with attrition. A secondary analysis looked at patients who dropped out during the first year., Results: A total of 1,144 RA participants were enrolled (509 completed 5 years of followup, 227 were still actively enrolled, and 408 dropped out). The attrition rate was 4.31% per 6-month cycle. Shorter disease duration, higher disease activity (3-variable Disease Activity Score in 28 joints using the C-reactive protein level), less education, RA drug therapy, and lower arthritis self-efficacy were statistically significant in multivariate survival analyses. In a secondary analysis, sex and age were the only additional factors found that contributed to attrition., Conclusion: The attrition rate for this registry was similar to rates reported by other registries. Shorter disease duration, higher disease activity, and several other socioeconomic factors were associated. Men and younger patients tended to drop out during the first year. Population differences in each registry may result in different attrition patterns and ultimately, each longitudinal registry should consider conducting its own analyses., (Copyright © 2013 by the American College of Rheumatology.)

The utility of sectioning at multiple levels in the histopathologic analysis of sentinel lymph nodes (SLNs) for melanoma and the correlation of metastasis size with risk of subsequent metastasis were investigated. Metastatic melanoma was identified in SLNs from 91 of 475 (19%) melanoma patients with SLN sampling at the Massachusetts General Hospital between 2004 and 2008. All SLNs were evaluated by a 9-slide protocol: sets of MART-1, hematoxylin and eosin, and S100 stains at 3 distinct levels separated by 80 μm. The location and size of the tumor deposits were evaluated in the context of subsequent metastasis and overall survival. Of the 91 patients with positive sentinel nodes, all 9 protocol slides were available for review in 61 (67%). Eleven of 61 patients had no tumor present in the first set of levels; 2 of these patients died of metastatic melanoma. Patients in whom 11 or more tumor cells were detected in the sentinel node had a greater chance of developing subsequent metastases when compared with patients in whom 10 or fewer tumor cells were detected (P=0.05). Of those with either metastases >2 mm in diameter or extracapsular extension, 50% developed metastases beyond the SLN basin. Eliminating 1 of the 3 levels in the SLN detection protocol would have led to a false-negative diagnosis in 18% of patients.

Objective: Despite recent advances in our molecular understanding of Spitz-type tumors, the clinical behavior of these lesions remains unclear. We thus set out to define the clinical outcome of classic Spitz nevi, atypical Spitz tumors (ASTs), and spitzoid melanomas., Design: From 1987 through 2002, data on all lesions containing the term "Spitz" or "Spitz" [AND] "melanoma" were retrieved from the pathology database at Massachusetts General Hospital, and the cases were followed up for their outcome., Setting: The study was performed at a university-affiliated tertiary health care center in Boston, Massachusetts., Patients: A total of 157 patients with Spitz-type melanocytic lesions and follow-up information were identified., Main Outcome Measures: Sentinel lymph node biopsy results, metastases, or fatality were assessed., Results: There were 68 classic Spitz nevi, 76 ASTs, 10 spitzoid melanomas, and 3 melanomas that arose in Spitz nevi. Spitz nevi were diagnosed at a younger age than ASTs (mean age, 26.4 years vs 33.7 years) (P = .01), though both occurred earlier than melanomas (mean age, 50.4 years, P < .001). Sentinel lymph node biopsy findings were positive in 1 of 6 and 4 of 8 patients with ASTs and spitzoid melanomas, respectively. After a median follow-up of 9.1 years, only 1 patient with an AST, who had a separate intermediate-thickness melanoma, developed distant metastasis. There were 6 documented invasive melanomas among 144 patients with classic Spitz nevi or ASTs (observed/expected ratio, 8.03) (P = .01)., Conclusions: Atypical Spitz tumors are associated with minimal lethal potential, an increased melanoma risk, and a moderate risk of metastasis to regional nodes. It makes clinical sense to minimize aggressive treatment but to offer careful surveillance for rare relapses and subsequent melanomas.

Background: As melanoma rates increase, and the supply of dermatologists remains suboptimal to meet demand for services, detection of early melanoma has become an increasingly difficult challenge. Some authors advocate for shifting dermatologic resources from routine appointments to urgent visits for those with lesions concerning for melanoma., Objective: We sought to investigate the potential of an urgent access track (UAT) embedded within a pigmented lesion clinic to improve early melanoma detection., Methods: We conducted a retrospective review of patient records from a tertiary care hospital's pigmented lesion clinic and the associated UAT. Results of procedures for all 4495 patient visits to the routine track and all 316 visits to the UAT during the 21-month study period were included, as were detailed chart reviews of all UAT patient visits., Results: UAT visits were more than 4 times as likely (4.1% vs 1.0%) to yield a diagnosis of melanoma as routine track visits (odds ratio 4.24; 95% confidence interval 2.28-7.88; P < .0001), and almost 25 times as likely (2.2% vs 0.1%) to yield a diagnosis of metastatic melanoma (odds ratio 25.4; 95% confidence interval 7.4-87.4; P < .0001)., Limitations: This was a preliminary analysis with only limited data extracted from the routine track pigmented lesion clinic patient visits., Conclusion: This initial analysis of UAT strategy suggests that UATs have potential to detect patients with earlier melanomas; further research is needed to specifically delineate how resources should be best allocated between routine surveillance and urgent care to maximize melanoma early detection and survival., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Heritable alterations in CDKN2A account for a subset of familial melanoma cases although no robust method exists to identify those at risk of being a mutation carrier., Methods: We set out to construct a model for estimating CDKN2A mutation carrier probability using a cohort of 116 consecutive familial cutaneous melanoma patients evaluated at Massachusetts General Hospital Pigmented Lesion Center between April 2001 and September 2004. Germline CDKN2A and CDK4 status on the familial melanoma cases and clinical features associated with mutational status were then used to build a multiple logistic regression model to predict carrier probability and performance of model on external validation., Results: From the 116 kindreds prone to melanoma in the Boston area, 13 CDKN2A mutation carriers were identified and 12 were subsequently used in the modeling. Proband age at diagnosis, number of proband primaries, and number of additional family primaries were most closely associated with germline mutations. The estimated probability of the proband being a mutation carrier based on the logistic regression model (MELPREDICT) is given by e(L)/(1 + e(L) where L = 1.99+[0.92x(no. of proband primaries)]+[0.74x(no. of additional family primaries)]-[2.11xln(age)]. The mean estimated probabilities for subjects in the Boston dataset were 55.4% and 5.1% for the mutation carriers and non-carriers respectively. In a receiver operator characteristic analysis, the area under the curve was 0.881 (95% confidence interval 0.739 to 1.000) for the Boston model set (n = 116) and 0.803 (0.729 to 0.877) for an external Toronto hereditary melanoma cohort (n = 143)., Conclusions: These results represent the first-iteration logistic regression model to approximate CDKN2A carrier probability. Validation of this model with an external dataset revealed relatively robust performance.

Background: Over the past two decades, cutaneous melanoma (CM) and non-Hodgkin's lymphoma (NHL) have both experienced unabated increases in incidence. Population-based studies have documented an elevated risk of subsequent NHL among patients with CM and vice versa., Methods: To better characterize the clinical features of patients who have had both malignancies, we retrospectively identified all patients with CM at the Massachusetts General Hospital (MGH) who subsequently had NHL and all NHL patients who later developed CM., Results: A total of 2461 CM and 2708 NHL patients were registered at MGH between 1973 and 1998. Out of these groups, 10 CM patients (0.4%) eventually developed NHL and 11 NHL patients (0.4%) subsequently had CM. The mean age at the first CM diagnosis was 56 years, wheras the mean age at the first NHL diagnosis was 67 years. The mean interval to NHL among the CM group was 119 months, whereas the mean interval to CM among the NHL patients was 36 months. All primary CMs were relatively thin (0.95 mm, first diagnosis; 1.07 mm, second diagnosis), and most NHL subtypes were indolent in nature., Conclusion: The rates of developing a second NHL among CM patients and vice versa are low. Any interactions between CM and NHL may be due to factors such as detection bias, shared environmental ultraviolet carcinogenesis, or possibly, posttreatment effects.

Background: Although the survival benefits of early stage melanoma have been clearly documented, the potential economic impact of early versus late stage disease has not been assessed., Objective: Our purpose was to estimate the annual direct cost of diagnosing and treating melanoma, based on the number of projected cases of melanoma entering each stage in 1997., Methods: A model was constructed with assumptions derived from the literature and clinical experience at the Massachusetts General Hospital Melanoma Center and the Boston University Medical Center. Cost estimates were based on 1997 Boston area Medicare reimbursements., Results: The annual direct cost of treating newly diagnosed melanoma in 1997 was estimated to be $563 million. Stage I and II disease each comprised about 5% of the total cost; stage III and stage IV disease consumed 34% and 55% of the total cost, respectively. About 90% of the total annual direct cost of treating melanoma in 1997 was attributable to less than 20% of patients (those patients with advanced disease, that is, stage III and stage IV)., Conclusion: In addition to the potential survival advantages, aggressive primary prevention through sun protection and intensive screening to enhance earlier detection should reduce the economic burden of melanoma care.