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Competing Interests: Conflicts of interest Dr Hawryluk discloses unrelated conflicts of Apogee (advisory board), UpToDate (author/reviewer-honorarium), Skin Analytics (consultant, ended 2023). Authors Ugwu and Weiss have no conflicts of interest or financial disclosures.

Cutaneous BAP1-inactivated melanocytomas (BIM) are melanocytic proliferations defined histopathologically by an epithelioid, predominantly dermal melanocytic proliferation with loss of BAP1, and have been largely characterized in adult patients but less well-described in pediatric cohorts. BIM share overlapping histological features with those seen in Spitz nevi; however, unlike Spitz nevi, the majority of BIM carry both BAP1 and BRAF V600E mutations. This study investigated the potential overlap of BIMs with pediatric Spitz nevi by performing immunohistochemical staining of BAP1 and BRAF V600E on pediatric melanocytic tumors with banal Spitz and dermal features. None of the stained tumors in our study exhibited the concurrent BAP1 loss and BRAF V600E positivity that are characteristic of adult BIM, suggesting that this is a low-frequency mutation among banal tumors in the pediatric population., (© 2024 Wiley Periodicals LLC.)

Background: Pediatric longitudinal melanonychia (LM) can exhibit atypical features that mimic red-flag signs for subungual melanoma in adults and lead to diagnostic uncertainty. Nail biopsy may be unnecessary if clinical inspection and dermoscopy suggest a benign nature., Methods: We searched PubMed and Embase from inception to February 2023 for studies of any design reporting either the number or proportion of clinical and dermoscopic features in at least five children (≤18 years) with LM. Non-English articles, reviews, and abstracts were excluded. We performed a systematic review and meta-analysis to collate all existing data., Results: A total of 1218 articles were screened and 24 studies with 1391 pediatric patients were included. Nevus was the most common diagnosis (86.3%). The most prevalent sites were fingernails (76.2%) and first digits (45.4%). Pooled proportions of common features were: dark-color bands (69.8%), multi-colored bands (47.6%), broad bandwidth (41.1%), pseudo-Hutchinson sign (41.0%), irregular patterns (38.1%), Hutchinson sign (23.7%), dots and globules (22.5%), nail dystrophy (18.2%), and triangular sign (10.9%). Outcomes included progression (widening or darkening, 29.9%), stability (23.3%), and spontaneous regression (narrowing or fading, 19.9%). Only eight cases of subungual melanoma in situ were reported, and no invasive melanomas were identified., Conclusion: Although atypical characteristics are common in pediatric LM, the probability of malignant transformation is exceedingly low. Appropriate evaluation and management of pediatric LM includes careful clinical and dermoscopic inspection with attention to benign features followed by long-term interval follow-up., (© 2024 Wiley Periodicals LLC.)

Background: Pediatric melanoma presents with distinct clinical features compared to adult disease., Objective: Characterize risk factors and negative outcomes in pediatric melanoma., Methods: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers., Results: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls., Limitations: Retrospective nature, cohort size, control selection, and potential referral bias., Conclusion: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma., Competing Interests: Conflicts of interest SH reports honorarium from Elsevier and past consulting for Novan Pharmaceuticals., (Copyright © 2024. Published by Elsevier Inc.)

Pediatric melanoma of the scalp has the highest mortality of any anatomic location. We describe five pediatric patients with a diagnosis of scalp melanoma receiving care at Massachusetts General Hospital and/or Boston Children's Hospital from 2018 through 2022. Melanoma presented in diverse contexts: cellular blue nevus-associated, compound nevus-associated, spitzoid, nodular, and superficial spreading subtypes. This study describes a range of melanoma presentations and emphasizes the need for additional compilation of data on pediatric scalp melanomas to promote their recognition and improve patient care., (© 2023 Wiley Periodicals LLC.)

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined., Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM., Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45)., Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status., Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Cutis verticis gyrata (CVG), characterized by cerebriform overgrowth of the scalp, is rarely observed in congenital melanocytic nevi (CMN). We describe a 13-year-old male with autism and a large CMN of the scalp with numerous satellite nevi whose scalp nevus exhibited evolution with poliosis and CVG. Given the potential association of CVG (independent of CMN) with seizures, neuropsychiatric, and ophthalmologic disorders, and nevus-associated CVG (cerebriform intradermal nevus) with melanoma, multidisciplinary evaluation of CMN patients with CVG is important to guide management and treatment., (© 2022 Wiley Periodicals LLC.)

Background: High-risk congenital melanocytic nevi (CMN) are associated with abnormalities of the central nervous system (CNS), prompting magnetic resonance imaging (MRI) screening guidelines., Objective: Describe MRI brain and spine abnormalities in children with CMN and report trends between nevus features, MRI findings, and neurologic outcomes., Methods: Retrospective review of individuals aged ≤18 years with an MRI of the brain and/or spine and at least 1 dermatologist-diagnosed CMN., Results: Three hundred fifty-two patients were identified. Forty-six children had CMN that prompted an MRI of the brain and/or spine (50% male, average age at first image, 354.8 days). In these children, 8 (17%) had melanin detected in the CNS, of whom all had >4 CMN. One developed brain melanoma (fatal). In patients without CNS melanin, 4 had concerning imaging. Concerning MRI patients had more neurodevelopmental problems, seizures, neurosurgery, and death than individuals with unremarkable imaging. Three hundred six patients received MRIs for other reasons; none detected melanin. No children with only multiple small CMN (n = 15) had concerning imaging., Limitations: Lack of a control group, cohort size, and retrospective methods., Conclusion: MRI of the brain and spine is useful for detecting intervenable abnormalities in high-risk children. Healthy infants with few small CMN may not require screening MRI., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi., Competing Interests: Declaration of interests D.E.F. has a financial interest in Soltego, a company developing salt inducible kinase inhibitors for topical skin-darkening treatments that might be used for a broad set of human applications. The interests of D.E.F. were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict-of-interest policies. C.L.C. has a financial interest in 4Immune, a company developing cell therapy treatments that can be used for a broad set of human applications. The interests of C.L.C were reviewed and are managed by Mass General Brigham in accordance with their conflict-of-interest policies. X.S.L. is a cofounder, board member, SAB member, and consultant of GV20 Oncotherapy and its subsidiaries; stockholder of BMY, TMO, WBA, ABT, ABBV, and JNJ; and received research funding from Takeda, Sanofi, Bristol Myers Squibb, and Novartis. M.C.M. discloses consulting relationship with Novartis, Advisory Board with BioCoz and Caliber ID, and author royalties with Wiley & Sons., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Background/objectives: The diagnostic distinction between atypical Spitz tumor (AST) and malignant melanoma (MM) in pediatric tumors is challenging. Molecular tests are increasingly used to characterize these neoplasms; however, limited studies are available in pediatric patients. This study aimed to provide a genomic comparison of pediatric MM and AST in the context of comprehensive clinical annotation., Methods: Pediatric patients diagnosed with MM (n=11) and AST (n=12) were compared to a cohort of 693 adult melanoma patients. DNA next-generation sequencing assessed kinase gene fusions, tumor mutational burden, sequence variants, copy number alterations, structural variants, microsatellite instability, and mutational signatures., Results: Seven AST cases and eight MM cases were successfully sequenced. Kinase gene fusions were identified in both the MM and AST cohorts (NTRK1, ROS1, and MET). MM cases had TERT, BRAF, and CDKN2A alterations, which were not identified in the AST cohort. Tumor mutational burden (TMB) analysis showed pediatric ASTs had an average of 2.82 mutations/Mb, pediatric MM had an average of 5.7 mutations/Mb, and adult MM cases averaged 18.8 mut/Mb. One pediatric MM case had an elevated TMB of 15 mutations/Mb and a UV mutational signature., Conclusions: These data expand our understanding of pediatric malignant melanoma. The differences between the molecular signatures for AST and MM are not statistically significant, and histopathology remains the gold standard for the diagnosis of pediatric AST and MM at this time. With more data, molecular studies may provide additional support for diagnosis and targeted therapeutics., (© 2022 Wiley Periodicals LLC.)

Patients are commonly referred to pediatric dermatology for the evaluation of pigmented lesions. For families, pediatricians, and dermatologists alike, malignancy is the main fear. In the past few decades, there has been evolving literature to inform diagnosis and management. This article provides an update on the clinical, histopathologic, and ancillary testing for 3 categories of particularly challenging pigmented lesions: congenital melanocytic nevi, spitzoid neoplasms, and pediatric melanoma., Competing Interests: Disclosure D.W. Bartenstein: MRK (stock, self); DVA (stock, spouse); ANTM (stock, spouse); PRSC (stock, spouse); AMAG (stock, spouse). E.B. Hawryluk: UpToDate, Inc. (royalty, author/reviewer); Purity Brands, LLC (consultant); Gritstone Oncology, Inc. (salary, stock spouse); PathAI (stock and advisory board, spouse)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A pediatric dermatology expert working group performed a narrative review to describe care related to congenital melanocytic nevi (CMN) in neonates and infants. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. Few guidelines exist for surgical management; newer recommendations favor conservative practice. Emerging evidence contributes to recommendations for screening MRI to evaluate for neural melanosis and related central nervous system complications, however, more research is needed. Risk for melanoma is generally low, but those with large, giant, or multiple CMN have a higher risk. Multidisciplinary care, with a focus on family and patient preferences, is of paramount importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including full or partial excision, timing and frequency of imaging, melanoma risk, and assessment for neural melanosis. This review highlights the current state of knowledge concerning care of patients with CMN, reveals gaps in the literature surrounding skin care, and provides management recommendations. We additionally discuss cutaneous complications of CMN, such as pruritus, hypertrichosis, and wound healing. Resources and references for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, we contribute expert care recommendations to the current body of literature as a foundation for the development of future, more comprehensive care guidelines., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Marla N. Jahnke discloses conflicts with Sanofi (consultant), which are not relevant to the content of this article. Elena B. Hawryluk discloses conflicts with Gritstone Oncology (spouse employment, stock), PathAI (spouse stock), Purity Brands LLC (consultant), and UpToDate (author, reviewer), which are not relevant to the content of this article. Kimberly A. Horii discloses conflicts with UpToDate (author, reviewer), which are not relevant to the content of this article. Ilona J. Frieden discloses conflicts with Pfizer (Chair, Data Safety Monitoring Boards), Novartis (advisory board, consultant), and Venthera/Biobridge (consultant), which are not relevant to the content of this article. The other authors have no conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Pyogenic granulomas are benign vascular proliferations of the skin and mucous membranes that tend to bleed easily. They typically require procedural treatments that can be difficult for patients with intellectual disabilities or behavioral concerns to tolerate. In our practice, we have found the use of topical clobetasol to be effective to induce regression of cutaneous pyogenic granulomas. We present here a case of an adolescent patient with autism and two bleeding pyogenic granulomas who poorly tolerated a biopsy of the first lesion and could not tolerate subsequent procedures. Topical therapy with clobetasol effectively managed the second pyogenic granuloma, an approach representative of a noninvasive practice utilized in our clinic., (© 2021 Wiley Periodicals LLC.)

Nevus of Ota is an uncommon benign mesodermal melanosis that involves the first and second divisions of the trigeminal nerve. Primary non-cutaneous melanoma often involves distinct genetic mutations compared to cutaneous melanoma. In primary central nervous system (CNS) melanomas associated with nevus of Ota, somatic mutations most commonly occur at the Q209 and R183 residues of GNAQ and likely induce tumorigenesis through upregulation of the MAP kinase pathway. This case underscores the importance of elucidating neurologic symptoms early in patients with nevus of Ota, as a delayed presentation of CNS melanoma could portend a devastating outcome., (© 2021 Wiley Periodicals LLC.)

Background: Pediatric melanoma is rare and diagnostically challenging., Objective: To characterize clinical and histopathologic features of fatal pediatric melanomas., Methods: Multicenter retrospective study of fatal melanoma cases in patients younger than 20 years diagnosed between 1994 and 2017., Results: Of 38 cases of fatal pediatric melanoma identified, 57% presented in white patients and 19% in Hispanic patients. The average age at diagnosis was 12.7 years (range, 0.0-19.9 y), and the average age at death was 15.6 years (range, 1.2-26.2 y). Among cases with known identifiable subtypes, 50% were nodular (8/16), 31% were superficial spreading (5/16), and 19% were spitzoid melanoma (3/16). One fourth (10/38) of melanomas arose in association with congenital melanocytic nevi., Limitations: Retrospective nature, cohort size, and potential referral bias., Conclusions: Pediatric melanoma can be fatal in diverse clinical presentations, including a striking prevalence of Hispanic patients compared to adult disease, and with a range of clinical subtypes, although no fatal cases of spitzoid melanoma were diagnosed during childhood., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To update pediatric providers on new developments in our understanding of the clinical presentation, genetics, and systemic risks associated with congenital melanocytic nevi (CMN)., Recent Findings: CMN are primarily caused by sporadic postzygotic somatic mutations, most frequently in NRAS, and studies of the genetic underpinnings of CMN have demonstrated a diverse array of genetic drivers. The primary complications of large and giant CMN include neurocutaneous melanocytosis and malignant melanoma. Abnormalities in CNS MRI may predict a worse clinical course for patients and increased risk of melanoma. Targeted therapies of the MEK pathway have begun to be studied for the treatment of CMN and prevention of associated complications., Summary: Patients with large and giant CMN should be managed by an interdisciplinary care team for the monitoring of dermatologic, neurologic, and psychosocial concerns. Ongoing research is underway to better characterize the genetic drivers of CMN and to better guide development of targeted therapeutics.

Purpose of Review: To inform pediatric providers of the clinical characteristics, underlying genetic drivers, and therapeutic options for skin cancer arising in childhood and adolescence., Recent Findings: The incidence of melanoma in pediatric patients has been declining in the past decades. Pediatric-specific diagnostic criteria should be utilized when assessing lesions concerning for melanoma to better account for the different presentations seen in pediatric disease compared with adults, such as an increased prevalence of amelanotic melanoma or frequent mimic of benign pediatric lesions. Pediatric melanoma often presents with a higher histopathologic stage and a higher Breslow depth as compared with adult melanoma. Pediatric nonmelanoma skin cancer including basal cell carcinoma and squamous cell carcinoma are associated with genetic conditions and immunosuppression, both iatrogenic and inherited., Summary: Melanoma in pediatric patients often presents differently from conventional adult melanoma, including Spitz melanoma and melanoma associated with congenital melanocytic nevi. Pediatric patients with nonmelanoma skin cancers should be evaluated for predisposing risk factors. More research on therapeutic options for pediatric skin cancer is vital to understanding the tolerance and response of our pediatric patients to therapies that are more frequently utilized in adult disease.

Background/objective: Pediatric hematopoietic stem cell transplantation (HSCT) patients are at an increased risk for skin cancers. Sun exposure is a significant modifiable environmental risk factor. While patient education on sun protection and avoidance behaviors with regular dermatology evaluations are crucial for pediatric HSCT patients, the real-life practice of these sun-protection recommendations in this patient population compared to their peers is unknown., Methods: A survey-based cross-sectional cohort study was performed in pediatric HSCT patients seen at the Dana-Farber Cancer Institute and Boston Children's Hospital over a 1.5-year period compared with age/sex/Fitzpatrick skin phototype-matched healthy controls. Study participants were surveyed using the validated Glanz survey for pediatric sun protection behavioral research., Results: Eighty-five pediatric HSCT patients and 85 controls completed the study. Pediatric HSCT patients more frequently used sunscreen, hats, umbrellas, and sunglasses and obtained full-body skin exams compared to controls. No difference was observed in sun exposure during hours of peak sun intensity, frequency of purposeful tanning, tanning bed use, and the number of painful sunburns received between pediatric HSCT patients and controls., Conclusions: Although pediatric HSCT patients practice more sun protection behaviors, they experienced harmful sunburns and intentional tanning behaviors at the same rate as their peers. Patient-directed counseling and strategies to improve patient adherence to optimal sun protection behaviors could have a significant impact on the dermatology quality of life in pediatric HSCT patients., (© 2019 Wiley Periodicals, Inc.)

Background: Spitzoid proliferations range from Spitz naevi to melanomas. There are few studies describing clinical features and outcomes in the paediatric population., Objectives: To determine the clinical features and outcomes of a large paediatric cohort with histopathologically confirmed Spitz tumours., Methods: This was a retrospective cohort study of patients seen at Boston Children's Hospital who were aged < 20 years and had a histopathological diagnosis of spitzoid proliferation from 1 January 1994 to 23 October 2012., Results: In total 595 patients with 622 spitzoid proliferations were identified (median age 7·4 years, interquartile range 4·6-11·7). Overall 512 proliferations (82·3%) were typical, 107 (17·2.%) were atypical and three (0·5%) were melanomas. The median ages at biopsy were 7·4, 7·2 and 17·2 years, respectively, and there was a significant difference in age at biopsy for patients with typical or atypical proliferations vs. melanoma (P < 0·01). Among samples with positive margins (n = 153), 55% (54 of 98) of typical proliferations, 77% (41 of 53) of atypical proliferations and 100% (two of two) of melanomas were re-excised. Six patients had sentinel lymph node biopsy performed, with three patients demonstrating nodes positive for melanocytic cells. Within a median follow-up of 4·1 years for the full cohort there were no related deaths., Conclusions: Spitz tumours have strikingly benign outcomes in the paediatric population, although this study is limited by the low number of melanomas and restriction to a single paediatric institution. Aggressive management recommendations should be reconsidered for children and adolescents with banal-appearing Spitz naevi, based on the clinically indolent behaviour in this cohort., (© 2018 British Association of Dermatologists.)

Objective: To identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children., Study Design: This was a multicenter, retrospective, case-control study of patients <20 years of age diagnosed with NMSC between 1995 and 2015 from 11 academic medical centers. The primary outcome measure was frequency of cases and controls with predisposing genetic conditions and/or iatrogenic exposures, including chemotherapy, radiation, systemic immunosuppression, and voriconazole., Results: Of the 124 children with NMSC (40 with basal cell carcinoma, 90 with squamous cell carcinoma), 70% had at least 1 identifiable risk factor. Forty-four percent of the cases had a predisposing genetic condition or skin lesion, and 29% had 1 or more iatrogenic exposures of prolonged immunosuppression, radiation therapy, chemotherapy, and/or voriconazole use. Prolonged immunosuppression and voriconazole use were associated with squamous cell carcinoma occurrence (cases vs controls; 30% vs 0%, P = .0002, and 15% vs 0%, P = .03, respectively), and radiation therapy and chemotherapy were associated with basal cell carcinoma occurrence (both 20% vs 1%, P < .0001). Forty-eight percent of initial skin cancers had been present for >12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001)., Conclusions: NMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although melanoma is a rare diagnosis in the pediatric population, advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. At this time, medical management is not considered curative but may reduce the risk of recurrence or prolong survival. Surgical management remains the mainstay of treatment. Medical therapy of pediatric melanoma is not thought to have a role for in situ, early-stage, or localized disease, but adjuvant therapy may have a role in improving the prognosis of patients with positive sentinel lymph node biopsy (SLNB), spread beyond the regional lymph node basin, metastatic disease, or recurrent disease. Medical treatment options include immunotherapies, particularly checkpoint inhibitors, and targeted therapies, which have provided improved toxicity profiles compared with traditional chemotherapy regimens in the setting of advanced disease. There is a growing body of pediatric-specific data relevant to the use of adjuvant therapies for advanced melanoma in children.

Background: Melanoma can mimic other cutaneous lesions, but the full spectrum and prevalence of these morphologic variants remain largely unknown., Objective: To classify nonacral cutaneous melanomas into distinct morphologic clusters and characterize clusters' clinicopathologic features., Methods: All pathologic melanoma diagnoses (occurring during 2011-2016) were reviewed for routine prebiopsy digital photographs (n = 400). Six dermatologists independently assigned lesions into 1 of 14 diagnostic classes on the basis of morphology. Image consensus clusters were generated by K-means; clinicopathologic features were compared with analysis of variance and χ 2 ., Results: Five morphologic clusters were identified: typical (n = 136), nevus-like (n = 81), amelanotic/nonmelanoma skin cancer (NMSC)-like (n = 70), seborrheic keratosis (SK)-like (n = 68), and lentigo/lentigo maligna (LM)-like (n = 45) melanomas. Nevus-like melanomas were found in younger patients. Nevus-like and lentigo/LM-like melanomas tended to be thinner and more likely identified on routine dermatologic examinations. NMSC-like melanomas were tender, thicker, more mitotically active, and associated with prior NMSC. Typical and SK-like melanomas had similar clinicopathologic features., Limitations: Cluster subdivision yielded diminished sample sizes. Visual assignment was performed without clinical context., Conclusion: When primary cutaneous melanomas were assigned into diagnostic groups and subjected to novel consensus clustering, recurrent morphologic patterns emerged. The spectrum of these morphologies was unexpectedly diverse, which might have implications for visual training and possibly clinical diagnosis., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pediatric melanoma is a rare disease that affects approximately 6 out of every one million children and accounts for 1-4% of all melanomas. This article reviews the epidemiology, etiology, diagnosis, treatment and prognosis of pediatric melanoma - with particular attention to recent updates in the literature. While awareness of melanoma increases among the general population, recent data suggest stable and even declining incidence rates among certain pediatric populations. Studies have examined clinical features and presentations of melanoma among the pediatric population and the conventional ABCDE criteria (asymmetrical shape, border, color, diameter, evolving lesion) used to diagnosis adult melanoma may not be entirely appropriate for pediatric melanoma; as such, additional pediatric-ABCD and CUP criteria (color changing, ulceration, pyogenic granuloma-like lesions) have been proposed. Dermoscopy serves as a valuable tool to detect suggestive patterns among pediatric skin lesions, and aids in the monitoring of skin lesions and detection of melanoma among children and adolescents. The etiology and pathogenesis of the pediatric melanoma is currently being investigated; studies have examined the genetic alterations that may be involved with the development of pediatric melanomas including TERT promoter, BRAF, and NRAS among others. While genetic testing using molecular techniques such as comparative genomic hybridization and fluorescence in-situ hybridization is helpful for diagnosis in certain contexts, molecular workup is not considered standard of care among pediatric melanoma cases, and in fact has not been proven to reliably distinguish between benign and malignant spitzoid tumors in children. Our growing understanding of melanoma has informed treatment decisions regarding management of positive sentinel lymph nodes, use of adjuvant therapy, and use of immunotherapy in treatment plans.

Background/objectives: Melanoma in children and adolescents is uncommon, and there are limited data on pediatric outcomes. Several studies have shown comparable survival rates in children and adults, but other research demonstrates that prepubescent children have more favorable outcomes. This study aims to compare childhood and adolescent melanoma., Methods: Retrospective cohort study of children who received a melanoma diagnosis at the Massachusetts General Hospital between January 1, 1995, and December 21, 2016. Childhood melanoma is defined as disease occurring in patients younger than 11 years old, and adolescent melanoma is defined as disease occurring in patients 11 to 19 years old. Patients diagnosed with ocular melanoma and borderline tumors of uncertain malignant potential were excluded. This analysis compares clinical, histopathologic, and outcome characteristics of childhood and adolescent melanoma., Results: Thirty-two children with melanoma were identified (12 children, 20 adolescents). The spitzoid melanoma subtype was significantly more common in children (6/12) than adolescents (2/20) (P = .01). Four adolescents and no children with melanoma died from melanoma, and survival was significantly different between the age groups (P = .04). Median follow-up time for survivors was 3.6 years., Conclusions: These results suggest that children and adolescents present with different melanoma subtypes and that adolescents have a more aggressive disease course than children., (© 2018 Wiley Periodicals, Inc.)

There is a known increased risk of skin cancer in the adult population after hematopoietic stem cell transplantation (HSCT). However, late dermatologic effects that children may experience after HSCT have not been well described. The primary objective of this study was to characterize nevi and skin cancers affecting children after allogeneic HSCT. A cross-sectional cohort study of 85 pediatric HSCT recipients and 85 controls matched for age, sex and skin phototype was performed at a single institution. All participants underwent a full skin examination. Median age at study visit was 13.8 years in HSCT patients with median time post-HSCT of 3.6 years. HSCT patients had significantly more nevi than control patients (median (range): 44 (0-150) vs 11 (0-94), P<0.0001). HSCT patients also had significantly more nevi >5 mm in diameter and atypical nevi than controls. Factors associated with increased nevus count included malignant indication for HSCT, pretransplant chemotherapy, TBI exposure and myeloablative conditioning. A total of 16.5% of HSCT patients developed cancerous, precancerous lesions and/or lentigines. Our study suggests that pediatric HSCT recipients have an increased risk of benign and atypical melanocytic proliferations and nonmelanoma skin cancer that can manifest even during childhood.

Background: Voriconazole, an antifungal agent, is associated with various cutaneous reactions, including phototoxicity, accelerated photoaging, and skin cancer. Incidence and risk factors for these reactions in children have not been well described., Objective: We sought to determine the incidence of and factors associated with phototoxic reactions and nonmelanoma skin cancer in pediatric patients treated with voriconazole., Methods: This was a retrospective analysis of 430 pediatric patients treated with voriconazole between 2003 and 2013 at Boston Children's Hospital., Results: Incidence of phototoxicity was 20% in all children treated with voriconazole and 47% in children treated for 6 months or longer. Factors associated with phototoxicity included white race, cystic fibrosis, cumulative treatment time, and cumulative dose. Four patients (1%) had nonmelanoma skin cancer; all experienced a phototoxic reaction during voriconazole treatment. Of those with phototoxicity, 5% were discontinued on voriconazole, 6% were referred to dermatology, and 26% received counseling about sun protection from their primary physician., Limitations: Our study is limited by its retrospective design and potential referral bias associated with a tertiary-care center., Conclusions: Voriconazole-associated phototoxicity is relatively common in children and may lead to nonmelanoma skin cancer. However, those with phototoxic reactions are often continued on therapy, rarely referred to dermatology, and infrequently counseled on sun protection., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Recent efforts in genomic research have enabled the characterization of molecular mechanisms underlying many types of cancers, ushering novel approaches for diagnosis and therapeutics. Melanoma is a molecularly heterogeneous disease, as many genetic alterations have been identified and the clinical features can vary. Although discoveries of frequent mutations including BRAF have already made clinically significant impact on patient care, there is a growing body of literature suggesting a role for additional mutations, driver and passenger types, in disease pathophysiology. Although some mutations have been strongly associated with clinical phenotypes of melanomas (such as physical distribution or morphologic subtype), the function or implications of many of the recently identified mutations remains less clear. The phenotypic and clinical impact of genomic mutations in melanoma remains a promising opportunity for progress in the care of melanoma patients., (Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.)

Importance: Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an effective, novel treatment for patients with metastatic melanoma with the V600E BRAF mutation. This therapy is associated with squamous cell carcinomas and keratoacanthomas. Granulomatous eruptions have not been previously reported., Observations: Two patients with melanoma developed cutaneous granulomatous eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption concerning for progression of disease prompted cessation of treatment. After the histopathologic diagnosis of granulomas, the patient was treated with clobetasol ointment with resolution within days and resumption of therapy. In case 2, after 5 months of vemurafenib treatment, the patient developed a granulomatous eruption, which resolved 3 weeks after cessation of therapy., Conclusions and Relevance: We report 2 cases of cutaneous granulomatous eruptions on treatment with targeted BRAF inhibitors, a previously unreported association. Although additional investigations are necessary to better elucidate the pathogenic mechanisms, our report includes a treatment plan that prevents unnecessary discontinuation of therapy. Given the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should be aware of this possible cutaneous reaction and treatment option to optimize patient management.

Background: Merkel cell carcinoma (MCC) is a rare and lethal cutaneous neuroendocrine carcinoma. Imaging is crucial for accurate staging, which remains a strong predictor of survival, as well as earlier detection of recurrence and progression, which are common despite aggressive management. There is no consensus on the role of initial and subsequent imaging for MCC., Objective: We sought to evaluate the use of 2-fluoro-[(18)F]-deoxy-2-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the management of MCC., Methods: In all, 270 FDG-PET/CT studies were performed in 97 patients with pathology-proven MCC at the Dana-Farber/Brigham and Women's Cancer Center, Boston, Mass, from August 2003 to December 2010., Results: FDG-PET/CT scans were obtained as part of the initial (61 scans in 61 patients) and subsequent (209 scans in 79 patients) treatment strategies. MCCs were FDG-avid with a mean maximum standardized uptake value of primary lesions of 6.5 (range 1.3-12.9) and a mean maximum standardized uptake value of regional and distant metastases of 7.2 (range 1.5-9.9). FDG-PET/CT upstaged 16% of patients who underwent baseline scans. FDG-PET/CT studies showed that bone and bone-marrow metastases were more common than previously reported, and were often undetected by CT., Limitations: Our study is limited by its retrospective design, and potential referral bias associated with a tertiary care center., Conclusions: FDG-PET/CT performed as part of the initial management strategy tended to upstage patients with more advanced disease. FDG-PET/CT performed as part of the subsequent treatment strategy identified metastatic disease, particularly in bone/bone marrow, which was not seen on CT. FDG-PET/CT imaging is a valuable staging and restaging tool in MCC management., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Markedly pleomorphic epithelioid cells with high mitotic activity, giant cell formation, very large atypical nuclei, multiple nucleoli and abundant cytoplasm characterize 'monster' cells and may indicate aggressive tumor behavior. Very rare reports of melanomas comprised of 'monster cells' or cells with comparable histomorphological features, found in tissue samples from skin, lymph nodes, CNS, oral cavity and ileum have been published in the literature. This case is the first such description in the lung, and it is characterized with a battery of immunohistochemical stains; BRAF mutation status was negative, and fluorescence in situ hybridization analysis revealed increased copy number gains in 11q (cyclin D1), which is associated with poor prognosis in melanoma. The presence of monster cells in melanoma was associated with aggressive behavior in the reported patient., (Copyright © 2012 John Wiley & Sons A/S.)

Background: The histopathologic diagnosis of some melanocytic tumors is extraordinarily difficult. With this in mind, melanocytic tumors from patients referred to the Massachusetts General Hospital (MGH) Pigmented Lesion Clinic (PLC) are routinely reviewed in the MGH Dermatopathology Unit., Objective: We sought to determine the frequency of diagnostically challenging cases from patients treated at the MGH PLC, as measured by a change in the diagnosis upon review of the referral materials., Methods: We retrospectively reviewed the MGH and referral pathology reports for 478 consecutive cutaneous melanocytic tumors: 126 from 1996-1997 and 352 from 2010-2011. Differences in diagnosis and in therapeutic impact were evaluated., Results: Changes in diagnosis occurred in 168 of 478 cases (35%), more frequently when the original diagnostician was a general pathologist (P = .003). A similar fraction of diagnoses were changed from malignant to benign or vice versa, in both historic and contemporary cohorts. In 64 patients (13%), changes in diagnosis led to a change in therapy. Changes in stage or grading led to the most changes in therapy (78%; 50/64) versus changes from benign to malignant or vice versa (22%; 14/64)., Limitations: This is a retrospective study with the bias of a tertiary-care referral center., Conclusions: These findings demonstrate the diagnostic difficulty of a subset of melanocytic tumors and highlight the utility of review by more than one pathologist; patient treatment is affected in more than 10% of cases. Identification of melanoma prognostic factors and melanocytic nevus grading led to clinically significant changes in diagnosis leading to a change in patient management., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)