Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

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.

Features, management, and outcomes of pediatric scalp melanomas.

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.

Neurobehavioral follow-up of children exposed to selective serotonin reuptake inhibitors in utero.

BACKGROUND: Systematic data regarding long-term neurobehavioral effects of maternal antidepressant use during pregnancy are sparse. The aim of this study was to evaluate the impact of gestational exposure to antidepressants on later neurodevelopmental function. METHODS: This study describes a cohort of mother-child dyads (44 mothers, 54 children) in which maternal depressive symptoms and medication exposures were prospectively collected across pregnancy and the postpartum period. Children age 6 to 17 were assessed using validated instruments across domains of childhood behavior and executive memory and functioning. RESULTS: No associations were found between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and atypical neurodevelopment of children. Borderline clinical or clinical ranges of internalizing symptoms were associated with exposure to a higher maternal depressive symptom burden during pregnancy compared with those in the normal range. Compared with age- and sex-matched controls, the SSRI-exposed group showed superior performance on executive function tasks; findings did not demonstrate elevated risk for abnormal neurodevelopment in children age 6 to 17 exposed to SSRIs in utero. Deviations from the norm were instead associated with higher in utero exposure to maternal depression burden. CONCLUSIONS: This study highlights the need for rigorous studies of long-term outcomes after fetal antidepressant exposure.

Genomic comparison of malignant melanoma and atypical Spitz tumor in the pediatric population.

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.

Engaging in advocacy during medical training: assessing the impact of a virtual COVID-19-focused state advocacy day.

PURPOSE: The physician voice is crucial to shaping health policy and public health guidelines, particularly during COVID-19. However, there are gaps in health policy and advocacy education within graduate medical education. This study sought to characterise the impact of a virtual COVID-19 focused advocacy day among medical trainees in Massachusetts. STUDY DESIGN: The half-day event featured speakers drawn from government relations experts, physician advocates, and state and federal legislators as well as breakout discussions among attendees. A 25-question Redcap survey and list of resources/opportunities for continued advocacy was administered to all participants at event's conclusion on 19 May 2020. RESULTS: There were 60 responses from 141 participants (43% response rate). One-third reported no prior formal health policy instruction, and over half reported getting information from news publications, social media and peers. 58% believed physician involvement in advocacy to be 'extremely important' prior to COVID-19; 83% believed the same after onset of COVID-19 (p<0.0001). The most common barriers to advocacy engagement were lack of time and knowledge. Most attendees felt participation increased their knowledge and likelihood to engage in the COVID-19 response, imparted useful skills/knowledge for continued advocacy, increased their interest in future similar events, and that such events should be available to all trainees. CONCLUSIONS: Trainees recognise the importance of health policy and advocacy and value opportunities to gain the necessary skills/knowledge to effect tangible change. Virtual advocacy days can be replicated nationwide to help trainees learn about advocacy efforts and find their legislative voices during COVID-19 and beyond.

Topical corticosteroids for noninvasive treatment of pyogenic granulomas.

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.

Language-centered approach to care improvement in a pediatric dermatology clinic.

Language-congruent care can improve clinical outcomes. As a quality improvement initiative supported by the Department of Dermatology at Massachusetts General Hospital, the American Academy of Dermatology, and the Society for Pediatric Dermatology, our group established monthly pediatric dermatology "Spanish clinics" that scheduled Spanish-speaking patients on the same day and utilized a dedicated, live interpreter who stayed with the clinical team throughout the clinic. Patients reported high satisfaction scores, averaging 9.8 out of 10, and 90.5% of patients preferred this model to traditional appointments. Our participating physician found "Spanish clinics" allowed for more efficient care not only in the monthly pilot clinics, but in all clinics occurring during the time period.

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.

BACKGROUND: Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. OBJECTIVE: To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. METHODS: A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. RESULTS: From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. LIMITATIONS: Registry analysis does not measure incidence. Morphologic misclassification is possible. CONCLUSIONS: We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

Fatal GNAQ-mutated CNS melanoma in an adolescent with nevus of Ota.

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.

Trends in pediatric skin cancer.

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.

A retrospective multicenter study of fatal pediatric melanoma.

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.

Congenital melanocytic nevi.

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.

A pediatric approach to management of skin growths in basal cell nevus syndrome.

Little guidance on management of basal cell nevus syndrome in children exists. We report a case series of four patients diagnosed with BCNS in early childhood, in whom several highly suspicious lesions were biopsied, but several smaller and questionably concerning lesions were treated with therapies that are more tolerable for children, including topical imiquimod, 5-fluorouracil, cryotherapy, or touch electrodessication following topical anesthetic cream. These therapies were well tolerated, and all residual or persistent lesions were subsequently biopsied and found to be benign. This approach is often preferable for pediatric BCNS patients, in whom concerning lesions can be identified clinically and managed compassionately. However, any lesion that exhibits growth, bleeding, or symptoms should be biopsied for definitive diagnosis.

Course of major depressive disorder after pregnancy and the postpartum period.

BACKGROUND: Maternal major depressive disorder (MDD) has an adverse effect on child development and increases risk for child psychopathology. It is paramount to understand the course of maternal depression during the childhood years particularly before, during, and after pregnancy. OBJECTIVE: To follow the course of MDD in women with prior histories of depression followed during an index pregnancy. METHODS: Subjects were women with histories of MDD who had participated in prior prospective, observational studies during pregnancy. In the follow-up, participants completed a structured interview that addressed (1) the course of MDD since their index pregnancy, (2) new psychiatric diagnoses, and (3) the course of MDD and treatment across subsequent pregnancies. RESULTS: Out of 129 eligible women, 48.8% participated (N = 63) with an average/mean time of 12.9 years (SD = 1.9, 8.8-16.7) elapsed since participation in the prior pregnancy studies. Although approximately one third reported sustained remission from MDD since the pregnancy during which they had been originally followed, of the remaining two thirds of women who reported subsequent depressive episodes, almost one fifth (∼12% of the total sample) endorsed depression more than 50% of the time following their index pregnancy. A total of 6.3% of the women with previous validated diagnoses of MDD reported new diagnoses of bipolar disorder. Women reported similar treatment choices regarding the use of antidepressants during pregnancies subsequent to the one followed in the previous study. CONCLUSION: Women with MDD experienced high rates of recurrent depression across the childbearing years. This represents a critical variable for clinical care and research.

Gestational Weight Gain and Pre-pregnancy Body Mass Index Associated With Second-Generation Antipsychotic Drug Use During Pregnancy.

BACKGROUND: Obesity during pregnancy is the most common high-risk obstetric condition, resulting in increased rates of adverse maternal and neonatal outcomes. Individuals with psychiatric disorders have a higher risk of obesity than the general population, but data regarding implications of obesity in women with psychiatric disorders are sparse. OBJECTIVE: The objective of this study was to assess pre-pregnancy weights and gestational weight gain in women who were exposed to second-generation antipsychotics (SGAs) during pregnancy compared to controls. METHODS: We assessed pre-pregnancy weights and gestational weight gain from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics for patients exposed to SGAs and controls unexposed to these medicines during pregnancy. Both groups experienced similar psychiatric morbidity. RESULTS: A total of 403 participants had evaluable data for these analyses (N = 279 exposed to SGAs; N = 124 controls). The mean pre-pregnancy weight, body mass index (BMI), and likelihood to begin pregnancy with an obese BMI were significantly higher in the exposed group compared to controls (p = 0.0003, p < 0.0001, and p < 0.0001 respectively), as were the mean weight and BMI at delivery (p < 0.0001). The mean weight gain did not differ significantly between groups. Across pre-pregnancy BMI categories, both groups gained more than the recommended amount of weight during pregnancy. CONCLUSION: We found that women exposed to SGAs began pregnancy with higher BMIs than controls. Both exposed and unexposed groups experienced similar weight gain during pregnancy. Strategies are needed to prevent excessive gestational weight gain and to reduce pre-pregnancy obesity in women with psychiatric disorders, especially those treated with SGAs.

Vortioxetine for major depressive disorder, vasomotor, and cognitive symptoms associated with the menopausal transition.

BACKGROUND: In a preliminary trial, we assessed the efficacy of vortioxetine for major depressive disorder (MDD) during the menopausal transition. Secondary outcomes included hot flashes (HFs), anxiety, and cognitive complaints. METHODS: Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary outcome measure. Secondary measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause-Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI), Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol Substitution Test (DSST), and Cogstate testing. RESULTS: Of the 27 women, 24 (88.8%) were evaluated (≥1 follow-up), and 21 (77.8%) completed the study; 1 discontinued because of adverse effects. The mean MADRS score decreased significantly (P = .0001) from 31.3 (standard deviation [SD] = 5.5) at pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate (≥50% reduction in MADRS) and remission rate (final MADRS ≤10) were 75% and 70.8%, respectively. GCS, MEN-QOL, BAI, CPFQ, and DSST scores improved significantly (P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133, respectively); Cogstate test scores did not. Frequency and severity of HFs improved significantly (P = .0291 and P = .0299, respectively). CONCLUSIONS: These data support further study of vortioxetine for treating menopausal depression and associated symptoms.

Reproductive Safety of Second-Generation Antipsychotics: Current Data From the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

OBJECTIVE: Second-generation antipsychotics are used to treat a spectrum of psychiatric illnesses in reproductive-age women. The National Pregnancy Registry for Atypical Antipsychotics was established to determine the risk of major malformations among infants exposed to second-generation antipsychotics during pregnancy relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity. METHOD: Women were prospectively followed during pregnancy and the postpartum period; obstetric, labor, delivery, and pediatric medical records were obtained. Eligible enrollees were pregnant women ages 18-45. The Registry is based at the Center for Women's Mental Health at Massachusetts General Hospital. Women were recruited through provider referral, self-referral, and the Center's web site. RESULTS: As of December 2014, 487 women were enrolled: 353 who used second-generation antipsychotics and 134 comparison women. Medical records were obtained for 82% of participants. A total of 303 women had completed the study and were eligible for inclusion in the analysis. Of 214 live births with first-trimester exposure to second-generation antipsychotics, three major malformations were confirmed. In the control group (N=89), one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. The odds ratio for major malformations comparing exposed infants with unexposed infants was 1.25 (95% CI=0.13-12.19). CONCLUSIONS: The results suggest that it would be unlikely for second-generation antipsychotics to raise the risk of major malformations more than 10-fold beyond that observed in the general population or among control groups using other psychotropic medications. If the estimate stabilizes around the null with ongoing data collection, findings may be reassuring for both clinicians and women trying to make risk-benefit treatment decisions about using atypical antipsychotics during pregnancy. These findings are timely given the renewed focus of regulatory agencies on reproductive safety.