Dabrafenib for Pilocytic Astrocytoma With BRAF V599ins.

This report highlights the first pediatric case of pilocytic astrocytoma with BRAF V599ins mutation, successfully treated with dabrafenib.

Infantile Hemangioma of the Breast: Long-Term Assessment of Outcomes.

Background: The literature is meager regarding the natural history and outcomes of infantile hemangiomas (IHs) in the breast. Treatment in childhood may be considered due to psychosocial and physical concerns with breast development. Early surgical intervention may cause iatrogenic breast asymmetry and possibly impair lactation later in life. This study characterizes the clinical presentation, management, and long-term outcomes of IHs arising in the breast. Methods: Female patients aged 11 years or older at presentation were included in a retrospective review of the Vascular Anomalies Center database for patients with IHs of the breast seen at our institution between 1980 and 2020. Breast development was ascertained by a structured telephone interview, physical examination, or photographs. Results: A total of 10 patients met criteria for inclusion in this study. The median age at enrollment was 14 years (11-36 years). Breast asymmetry was noted in 60% of patients (n = 6). Of the four patients who underwent subtotal excision of breast IH, three developed ipsilateral breast hypoplasia. Breast asymmetry was also noted in three of five patients who did not receive medical treatment: two with hypoplasia and one with hyperplasia. No asymmetry was noted in the single patient who received corticosteroid. Conclusions: IHs involving the nipple-areola complex can be associated with breast asymmetry. Hypoplasia was noted in patients not treated with corticosteroid or resection in childhood. These findings suggest that systemic treatment should be considered. Longitudinal follow-up on patients treated with propranolol will elucidate its possible benefits in minimizing breast asymmetry.

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy.

Cancer remains a leading cause of morbidity and mortality among children. Targeted therapies may improve survivorship; however, unique side-effect profiles have also emerged with these novel therapies. Changes in hair, skin, and nails-termed dermatologic adverse events (AEs)-are among the most common sequelae and may result in interruption or discontinuation of therapy. Though dermatologic AEs have been detailed in adults, these findings are not well described in the pediatric population. We reviewed the literature to characterize dermatologic AEs to anticancer targeted therapies available as of July 2020 and summarized the spectrum of clinical findings as well as treatment recommendations for children. Dermatologic AEs are among the most common AEs reported in pediatric patients receiving targeted therapy, but morphologic and histologic descriptions are often lacking in current publications. Pediatric dermatologists are uniquely poised to recognize specific morphology of dermatologic AEs and make recommendations for prevention and treatment that may improve quality of life and enable ongoing cancer therapy.

Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

Cutaneous reactions to pediatric cancer treatment: Part I. Conventional chemotherapy.

Chemotherapies often cause side effects of the skin, nails, and mucosal surfaces. These mucocutaneous toxicities contribute to morbidity and affect quality of life. Identification and management of these drug-induced eruptions is vital to allow for continuation of essential therapies. This review demonstrates the wide range of chemotherapy-induced cutaneous toxicities in children and includes clues for diagnosis as well as tips for counseling and management.

Utilizing immediate preoperative n-BCA in the resection of head and neck venous and lymphatic malformations.

PURPOSE/OBJECTIVE: To add to the current literature on single stage excision of head and neck vascular malformations with preoperative n-butyl cyanoacrylate (n-BCA) glue. Unlike previous studies, this series includes pediatric and adult patients, highlights a single stage partial excision of a complex venous malformation, and describes the first description of using glue prior to resection of a macrocystic lymphatic malformation. STUDY DESIGN: Case series with chart review. SETTING: Tertiary-care adult and pediatric hospital. SUBJECTS AND RESULTS: Four patients (3 males - 9, 13, 25 years, 1 female - 61 years) underwent same day excision of head and neck vascular malformations utilizing immediate preoperative n-BCA glue embolization performed by interventional radiology and otolaryngology, as described by Tieu et al. The indications for resection included bleeding (1/4), pain (3/4), cosmetic deformity (3/4), and discomfort with denture wear (1/4). Prior interventions included none (1/4), cautery and primary closure to control acute hemorrhage (1/4), and sclerotherapy (2/4). Treatments included complete embolization and resection of simple venous malformation (VM)s of the oral cavity/lip (2/4), partial embolization and resection of a complex hemifacial venous malformation (VM) (1/4), and complete embolization and resection of a lymphatic malformation (LM) (1/4). On average, 97 min of anesthesia time was added for the preoperative embolization procedure (range, 94-104 min). All patients had a successful embolization without need for coils. Operative time ranged from 28 to 44 min for the simple cases and was 6 h and 30 min for the complex case. There was minimal blood loss in all cases. There were no associated complications, lesion recurrences, or long-term deficits at an average follow-up of 5 months. The patient with the complex hemifacial VM demonstrated subtle lower facial weakness post-operatively, which completely resolved within two months. CONCLUSIONS: Treatment of head and neck vascular malformations with preoperative n-BCA glue and subsequent surgical excision is a viable method for both simple and complex lesions. The safety and efficacy of this technique has been demonstrated in the past in a limited number of studies. This study further supports the use of this technique to address patient concerns such as pain or discomfort and cosmetic deformity, even if the lesion is only partially resectable. In our series a lymphatic malformation refractory to sclerotherapy was treated with a similar technique of glue and resection, following aspiration of the mucoid LM fluid. Our series emphasizes that pediatric vascular malformations carry functional and cosmetic deficits into adulthood that can and should be addressed in this patient population. Therefore, same-day embolization and resection should be coordinated when possible, in order to optimize patient safety and convenience.

Fibrillin-1 in the Vasculature: In Vivo Accumulation of eGFP-Tagged Fibrillin-1 in a Knockin Mouse Model.

Immunolocalization studies have shown that fibrillin-1 is distributed ubiquitously in the connective tissue space from early embryonic times through old age. When mutated, the gene for fibrillin-1 (FBN1) causes the Marfan syndrome, a common inherited disorder of connective tissue. The multiple manifestations of the Marfan syndrome reflect the known distribution of fibrillin-1 in cardiovascular, musculoskeletal, ocular, and dermal tissues. In this study, a mouse model of Marfan syndrome in which fibrillin-1 is truncated and tagged with green fluorescence was used to estimate the relative abundance of fibrillin-1 in developing tissues. In embryonic tissues, the aorta was the only tissue in which fibrillin-1 green fluorescence was detectable. Other arteries gained detectable fibrillin-1 green fluorescence just after birth. Fibrillin-1 fluorescence was observed at later postnatal times in the lung, skin, perichondrium, tendon, and ocular tissues, while other tissues remained negative. These results indicated that tissues most affected in the Marfan syndrome are the tissues in which fibrillin-1 is most abundant. Focus was placed on the aorta, since aortic disease is life threatening in the Marfan syndrome and fibrillin-1 green fluorescence was most abundant in this tissue. Fibrillin-1 green fluorescence and immunostaining showed that fibrillin-1 is within aortic medial elastic lamellae. Endothelial-specific compared to smooth muscle-specific fibrillin-1 green fluorescence, together with light microscopic analyses of fragmentation of aortic elastic lamellae, demonstrated that smooth muscle cell mutated fibrillin-1 contributed most to progressive aortic fragmentation. However, these studies also indicated that other cells, possibly endothelial cells, also contribute to this aortic pathology. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.

Understanding the cost of dermatologic care: A survey study of dermatology providers, residents, and patients.

BACKGROUND: The American Academy of Dermatology recommends dermatologists understand the costs of dermatologic care. OBJECTIVE: This study sought to measure dermatology providers' understanding of the cost of dermatologic care and how those costs are communicated to patients. We also aimed to understand the perspectives of patients and dermatological trainees on how cost information enters into the care they receive or provide. METHODS: Surveys were systematically developed and distributed to 3 study populations: dermatology providers, residents, and patients. RESULTS: Response rates were over 95% in all 3 populations. Dermatology providers and residents consistently underestimated the costs of commonly recommended dermatologic medications but accurately predicted the cost of common dermatologic procedures. Dermatology patients preferred to know the cost of procedures and medications, even when covered by insurance. In this population, the costs of dermatologic medications frequently interfered with patients' ability to properly adhere to prescribed regimens. LIMITATIONS: The surveyed population was limited to the northwestern United States and findings may not be generalizable. Cost estimations were based on average reimbursement rates, which vary by insurer. CONCLUSION: Improving dermatology providers' awareness and communication of the costs of dermatologic care might enhance medical decision-making, improve adherence and outcomes, and potentially reduce overall health care expenditures.

Effective use of mirtazapine for refractory pruritus associated with carcinoma en cuirasse.

Pruritus is a debilitating symptom that can be associated with cutaneous involvement by an underlying malignancy. We report the case of a 68-year-old woman with a history of triple-negative breast cancer who presented with extensive, localised cutaneous metastasis complicated by incapacitating, treatment-refractory pruritus localised to the anatomic regions involved by her metastatic disease. Physical examination revealed an indurated, ecchymotic, ulcerated plaque circumferentially encasing her thorax. Histopathological examination revealed substantial dermal lymphatic involvement and dilation as well as dermal collagen infiltration by tumour cells and nodules. The clinical and pathological findings were consistent with a diagnosis of carcinoma en cuirasse. Mirtazapine, a noradrenergic antidepressant with antiserotonin and antihistamine activity, was started and led to rapid, sustained relief of the patient's pruritus. Mirtazapine may be a useful systemic agent for the palliative relief of pruritus associated with cutaneous infiltration by an underlying malignancy.

Hypohidrotic ectodermal dysplasia, osteopetrosis, lymphedema, and immunodeficiency in an infant with multiple opportunistic infections.

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections.

In vivo studies of mutant fibrillin-1 microfibrils.

In humans, mutations in fibrillin-1 result in a variety of genetic disorders with distinct clinical phenotypes. While most of the known mutations in fibrillin-1 cause Marfan syndrome, a number of other mutations lead to clinical features unrelated to Marfan syndrome. Pathogenesis of Marfan syndrome is currently thought to be driven by mechanisms due to haploinsufficiency of wild-type fibrillin-1. However, haploinsufficiency-driven mechanisms cannot explain the distinct phenotypes found in other fibrillinopathies. To test the hypothesis that mutations in fibrillin-1 cause disorders through primary effects on microfibril structure, two different mutations were generated in Fbn1 in mice. One mutation leads to a truncated fibrillin-1 molecule that is tagged with green fluorescent protein, allowing visualization of mutant fibrillin-1 incorporated into microfibrils. In heterozygosity, these mutant mice demonstrate progressive fragmentation of the aortic elastic lamellae and also display fragmentation of microfibrils in other tissues. Fibrillin-2 epitopes are also progressively revealed in these mice, suggesting that fibrillin-2 immunoreactivity can serve as a marker for microfibril degradation. In contrast, a second mutation (in-frame deletion of the first hybrid domain) in fibrillin-1 results in stable microfibrils, demonstrating that fibrillin-1 molecules are not required to be in perfect register for microfibril structure and function and that the first hybrid domain is dispensable for microfibril assembly. Taken together, these results suggest that perturbation of microfibril structure may underlie one of the major features of the Marfan syndrome: fragmentation of aortic elastic lamellae.