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.

Spitz nevus with EHBP1-ALK fusion and distinctive membranous localization of ALK.

ALK rearrangements define a histopathologically distinctive yet diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of gene partners, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13-year-old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next-generation RNA sequencing revealed an in-frame EHBP1-ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5' ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK-rearranged melanocytic tumors.

Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.

ABSTRACT: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.

Cutaneous body image: A window into the adolescent experience of dermatologic disease.

BACKGROUND/OBJECTIVES: Cutaneous body image (CBI) is a self-reported measure of an individual's satisfaction with their hair, skin, and nails using a psychometric survey described and validated in adult dermatology patient populations. As the CBI's clinical utility for pediatric dermatology patients has not yet been examined, we assessed the relationship between CBI scores, demographic, and clinical parameters among adolescents. METHODS: Retrospective cohort of 293 patients ages 13-18 seen at the UCSF pediatric dermatology clinic from June 2017 to February 2019. An 11-question CBI survey was administered as part of routine clinical care, querying patient satisfaction with their skin, hair, and nails on a 10-point Likert-type scale, and experience with embarrassment, bullying, and mental health care. RESULTS: Satisfaction with overall skin, skin of face, and hair significantly varied by patient age (P < .05), decreasing among subjects ages 13-16, and comparatively higher among patients ages 17-18. Mean total CBI scores did not significantly vary by sex, ethnicity, diagnosis, or new versus established patients. Mean total CBI scores were significantly higher among patients who did not report embarrassment (27.5) than among those who did (20.5) (P < .01), and among patients who had not experienced bullying (25.7) than among those who had (22.0) (P < .01). CONCLUSIONS: Objective CBI scores among adolescents correlate with reported negative experiences of skin disease (embarrassment and bullying) and with age. The CBI provides insight into the psychosocial impact of skin disease among adolescents, validates the patient's subjective perspective of their disease, and informs patient-centered discussions and management in the pediatric dermatology clinic setting.

Diagnosing Calciphylaxis: A Review With Emphasis on Histopathology.

Calciphylaxis is a cutaneous vasculopathy with high morbidity and mortality characterized by vascular intimal fibrosis, calcification, stenosis, thrombosis, and eventual tissue death due to ischemia. Histopathologic diagnosis is often difficult, frequently necessitating multiple tissues samples due to lack of specific histopathologic features and subtle changes on biopsies of early lesions. In this study, we review the reported clinical and histopathologic features of calciphylaxis, correlating them with relevant imaging, ancillary studies, and pathophysiology. Although many histopathologic changes seen in calciphylaxis are also reported in other conditions (eg, Mönckeberg sclerosis, lupus panniculitis, pancreatic panniculitis, and peripheral artery disease), calcification of subcutaneous small vessels, thrombosis and/or ischemic changes, pseudoxanthoma elasticum-like changes in the subcutis, and perieccrine calcification may serve as helpful clues. von Kossa and Alizarin red stains can assist in the identification of subtle calcification. Netlike calcification of the affected blood vessels on imaging further supports the diagnosis. Studies into the pathophysiology of calciphylaxis are ongoing and will hopefully facilitate the development of additional diagnostic adjuncts to increase sensitivity and specificity for the diagnosis of this disease.

Risk Factors and Outcomes of Nonmelanoma Skin Cancer in Children and Young Adults.

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.

Innovative use of chemodenervation in the treatment of postoperative genital hyperhidrosis-like symptoms.

Postoperative complications present in many forms and can cause great morbidity and even mortality in patients who experience them. Frey syndrome is an example of a postoperative complication in which aberrant nerve regeneration following parotidectomy leads to hyperhidrosis induced by gustatory stimuli. We present a unique but similar case of aberrant nerve regeneration and resulting hypersecretion that emerged 6-7 months following perineoplasty and labial reduction for lichen sclerosus in a 53-year-old woman. An exhaustive investigation ruled out genitourinary causes of her symptoms. Pads, tampons, and surgical procedures provided no relief. We propose that the mechanism of her excessive watery secretions is similar to that which causes Frey syndrome: iatrogenic damage to nerves that aberrantly regenerate to innervate local structures involved in secretory control. The parallels between our patient's condition and Frey syndrome are evident in the duration between surgery and onset of symptoms and the response to treatment with onabotulinum toxin, highlighting a shared cholinergic pathway. Onabotulinum injections are well tolerated by patients with localized hyperhidrosis and symptom control typically lasts several months. In this manuscript we present a novel mode of delivery of onabotulinum toxin topically to a mucosal region. With these treatments, the patient's hyperhidrosis-like symptoms remain well controlled for 3-4 months, at which point she returns to clinic for treatment. The patient did not experience symptomatic relief until this unique treatment plan was initiated. Her case illustrates the need for further understanding of recalcitrant postoperative complications involving local structures controlling liquid secretion, such as sweat glands and vascular plexuses.

Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy.

The success of messenger RNA therapeutics largely depends on the availability of delivery systems that enable the safe, effective and stable translation of genetic material into functional proteins. Here we show that extracellular vesicles (EVs) produced via cellular nanoporation from human dermal fibroblasts, and encapsulating mRNA encoding for extracellular-matrix α1 type-I collagen (COL1A1) induced the formation of collagen-protein grafts and reduced wrinkle formation in the collagen-depleted dermal tissue of mice with photoaged skin. We also show that the intradermal delivery of the mRNA-loaded EVs via a microneedle array led to the prolonged and more uniform synthesis and replacement of collagen in the dermis of the animals. The intradermal delivery of EV-based COL1A1 mRNA may make for an effective protein-replacement therapy for the treatment of photoaged skin.

Ki-67 and p16 Immunostaining Differentiates Pagetoid Bowen Disease From "Microclonal" Seborrheic Keratosis.

OBJECTIVES: We observed keratoses with "clonal" nests present as numerous tiny collections, in which cells in "pagetoid" array are found, a configuration we termed microclonal seborrheic keratosis (MSK). To better distinguish MSK from pagetoid Bowen disease (PBD), we investigated use of immunohistochemical staining. METHODS: Biopsy specimens of 26 MSKs, 17 PBDs, and 11 borderline cases were reviewed for histopathology and stained with p53, Ki-67, and p16. RESULTS: High expression of Ki-67 and p16 was observed in 12 (80%) of 15 PBDs and in one (4%) of 23 MSKs. Low expression of p16 and high expression of Ki-67 were observed in 16 (70%) of 23 MSKs and in two (13%) of 15 PBDs. Expression of p16 was elevated in 12 (80%) of 15 PBDs and in three (13%) of 23 MSKs (P < .0001). CONCLUSIONS: We describe a "microclonal" variant of seborrheic keratosis with morphology sometimes challenging to distinguish from PBD. High expression of p16 and Ki-67 or p16 alone favors the diagnosis of PBD over MSK.

Disseminated Cutaneous and Osteoarticular Sporotrichosis Mimicking Pyoderma Gangrenosum.

Disseminated sporotrichosis may present with inflammatory arthritis and cutaneous ulcerations that mimic noninfectious skin conditions such as pyoderma gangreonsum (PG). Sporotrichosis must therefore be ruled out before administering immunosuppressive agents for PG. Furthermore, dimorphic fungi such as sporotrichosis may grow as yeast in bacterial cultures, even before fungal cultures become positive. We present a case of disseminated cutaneous and osteoarticular sporotrichosis mimicking PG and describe the differential diagnosis and the diagnostic and treatment approach to this condition.

Cutaneous Adverse Effects of Neurologic Medications.

Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.