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Langerhans cell histiocytosis (LCH) is caused by the expansion of CD1a+/CD207+ cells and is characterised by a wide spectrum of organ involvement and dysfunction, affecting all ages. While almost all organs and systems can be affected, only the involvement and dysfunction of liver, spleen, and haematopoietic system influence survival. The LCH pathogenic cells are defined by universal activation of the mitogen-activated protein kinase (MAPK) signalling pathway. The most common alteration is a somatic BRAFV600E mutation, which is present in approximately two-thirds of the cases, followed by MAP2K1 mutations. Treatment of LCH is risk-adapted; patients with single lesions may respond well to local treatment, whereas patients with multi-system disease require systemic chemotherapy. While survival for patients without organ dysfunction is excellent, mortality rates for patients with organ dysfunction may reach 20%. Despite progress made in the treatment of LCH, disease reactivation rates remain above 30%, and standard second-line treatment has yet to be established. Long-term effects, including neuroendocrine dysfunction and neurodegeneration, represent a major challenge for survivors. Treatment with BRAF or MEK inhibitors results in immediate responses, but reactivations are very common after discontinuation. Their role as single agents and in combination with chemotherapy is being explored., (© 2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objectives/hypothesis: To describe our current multidisciplinary approach to pediatric malignant glomus tumors of the head and neck and review the current literature., Study Design: Retrospective chart review at a tertiary referral children's hospital and a comprehensive literature review., Methods: A comprehensive literature search of PubMed, Embase, Web of Science, Google Scholar, and EBSCO with respect to malignant glomus tumors of the head and neck was conducted. We obtained expert input from other pertinent specialties, including oncology, pathology, and radiology. To highlight the difficulty of evaluation and management of these patients, we also present a pediatric patient with a left neck malignant glomus tumor and lung metastases., Results: Only two cases of pediatric malignant glomus tumor (including our own) have been reported in the English literature. Overall, 14 malignant glomus tumors have been reported in the head and neck (11 primary and three metastatic). Surgical resection is the mainstay of treatment, but local recurrence is common (five of 11, 45%)., Conclusions: Malignant glomus tumor of the head and neck is an extremely rare tumor in children. Evaluation consists of imaging, and tissue biopsy is necessary for definitive diagnosis. Management options include surgical resection with or without an adjuvant chemotherapy protocol similar to those designed for sarcoma. Additional reports are necessary so that we may determine the utility, if any, of radiotherapy in the management of this tumor. Laryngoscope, 127:2873-2882, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To review the presentation and management of malignant tumors of the mandible in children., Study Design: Case series., Methods: Children 0 to 21 years old presenting to a tertiary pediatric hospital with a diagnosis of a malignant tumor involving the mandible were included. Comparison groups included children from the Surveillance, Epidemiology, and End Results database with malignant mandible tumors as well as a group of children with benign mandibular lesions from the same institution. Main outcome measures for the institutional malignant group included presentation, tumor characteristics, treatment modalities, and clinical outcome., Results: Sixteen patients with malignant and 183 patients with benign lesions were identified at the primary institution. The most common presentation in both groups was mandibular swelling or mass. Malignant tumors included sarcoma (n = 11), leukemia/lymphoma (n = 2), squamous cell carcinoma (n = 1), malignant spindle cell tumor (n = 1), and yolk sac tumor (n = 1). The national database identified 56 malignant cases, of which 71% were sarcomas. Thirteen patients at our institution (81%) underwent mandibulectomy and 12 were reconstructed using free tissue transfer. Eleven of the 13 (85%) were treated with adjuvant therapy. After an average follow-up of 32.8 months, seven (44%) had no evidence of disease, three (19%) were deceased, three (19%) were alive with disease, and three (19%) were lost to follow-up., Conclusions: Malignant mandibular tumors in children are most often sarcomas but can include other rare lesions. Free flap reconstruction is a reasonable option for even very young children requiring extensive mandibular surgery., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Langerhans cell histiocytosis (LCH) is a proliferative disease of cells that share phenotypic characteristics with the primary antigen presenting cells of the epidermis. Its clinical manifestations are highly variable, extending from very benign forms to a disseminated, aggressive disease that causes significant mortality. Although many of the fundamental pathogenetic features of LCH have been enigmatic, recent advances have led to a much clearer understanding of the disease. In particular, careful molecular analyses of mouse models and human LCH samples suggest that LCH's cell of origin may not be the epidermal LC itself but a myeloid-derived precursor. Advanced genomic technologies have revealed the presence of activating, somatic BRAF mutations in the majority of patient specimens. Together, these observations have produced a new picture of LCH as a myeloid neoplasm. These advances are likely to have profound implications for the use of targeted therapeutics in LCH., (© 2011 Blackwell Publishing Ltd.)

Langerhans cell histiocytosis (LCH) is a disorder characterized by proliferation of activated Langerhans cells. Immune dysregulation is believed to be part of the pathogenesis. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for patients with low-risk disease, and a significant proportion of young patients die of their disease. More effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chloro-deoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or high-risk LCH. Six patients with recurrent LCH received 2-CdA (5-7 mg/m(2)/day for 5 days, repeated every 21-28 days). All patients achieved remission. With a median follow-up of 15 months (range, 3-25 months), 5 patients remain in remission. A patient with multisystem disease who recurred after 13 months, achieved a second remission with 2-CdA. Hematologic toxicity was minimal, and no infectious complications were documented. 2-CdA is among the most effective drugs for the treatment of LCH, and this is probably due to both its anti-proliferative and immunomodulatory effects. 2-CdA needs to be considered for the treatment of recurrent LCH. However, its incorporation into front-line treatment of patients with multi-system LCH needs further study.