Louise Galmiche

High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses

Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAF(V600) mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAF(V600E) mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAF(V600E) in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAF(V600E) histiocytosis.

The Calcineurin Inhibitor Tacrolimus as a New Therapy in Severe Cherubism

Cherubism is a rare genetic disorder characterized by extensive growth of a bilateral granuloma of the jaws, resulting in facial disfigurement. Cherubism is caused by gain‐of‐function mutations in the SH3BP2 gene, leading to overactivation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)‐dependent osteoclastogenesis. Recent findings in human and mouse cherubism have suggested that calcineurin inhibitors might be drug candidates in cherubism medical treatment. A 4‐year‐old boy with aggressive cherubism was treated with the calcineurin inhibitor tacrolimus for 1 year, and clinical, radiological, and molecular data were obtained. Immunohistologic analysis was performed to compare preoperative and postoperative NFATc1 staining and tartrate resistant acid phosphatase (TRAP) activity. Real‐time PCR was performed to analyze the relative expression levels of OPG and RANKL. After tacrolimus therapy, the patient showed significant clinical improvement, including stabilization of jaw size and intraosseous osteogenesis. Immunohistologic analyses on granuloma showed that tacrolimus caused a significant reduction in the number of TRAP‐positive osteoclasts and NFATc1 nuclear staining in multinucleated giant cells. Molecular analysis showed that tacrolimus treatment also resulted in increased OPG expression. We present the first case of effective medical therapy in cherubism. Tacrolimus enhanced bone formation by stimulating osteogenesis and inhibiting osteoclastogenesis.

Pediatric salivary gland carcinomas: Diagnostic and therapeutic management

To analyze clinical presentations, treatment modalities, and evolution of pediatric cases of salivary gland carcinomas to standardize care for these rare diseases.

Le syndrome de Lynch existe en pédiatrie: À propos d’un cas

Resume Un cas de carcinome duodenal centre sur l’ampoule de vater chez une enfant de 15 ans est rapporte dans le cadre du syndrome de Lynch. L’observation montre qu’il existe des cas pediatriques et pose le probleme du depistage des tumeurs chez ces patients.A duodenal carcinoma centered on the vater ampulla is reported in a child of 15 years with Lynch syndrome. This case illustrates the problem of early diagnosis and treatment of Lynch syndrome associated tumors.

[Lynch syndrome pediatric: about a case].

Resume Un cas de carcinome duodenal centre sur l’ampoule de vater chez une enfant de 15 ans est rapporte dans le cadre du syndrome de Lynch. L’observation montre qu’il existe des cas pediatriques et pose le probleme du depistage des tumeurs chez ces patients.A duodenal carcinoma centered on the vater ampulla is reported in a child of 15 years with Lynch syndrome. This case illustrates the problem of early diagnosis and treatment of Lynch syndrome associated tumors.

Le syndrome de Lynch existe en pédiatrie

Resume Un cas de carcinome duodenal centre sur l’ampoule de vater chez une enfant de 15 ans est rapporte dans le cadre du syndrome de Lynch. L’observation montre qu’il existe des cas pediatriques et pose le probleme du depistage des tumeurs chez ces patients.A duodenal carcinoma centered on the vater ampulla is reported in a child of 15 years with Lynch syndrome. This case illustrates the problem of early diagnosis and treatment of Lynch syndrome associated tumors.