These guidelines for the management of patients up to 18 years with Langerhans cell histiocytosis (LCH) have been set up by a group of experts involved in the Euro Histio Net project who participated in national or international studies and in peer reviewed publications. Existing guidelines were reviewed and changed where new evidence was available in the literature up to 2012. Data and publications have been ranked according to evidence based medicine and when there was a lack of published data, consensus between experts was sought. Guidelines for diagnosis, initial clinical work‐up, and treatment and long‐term follow‐up of LCH patients are presented. Pediatr Blood Cancer 2013;60:175–184. © 2012 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.

Background. The purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chem

In Fanconi anemia (FA) C mice tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) have key roles in the pathogenesis of bone marrow failure. In FA subjects TNF-α was found to be increased in the serum and overproduced by patient-derived B-cell lines. In acquired aplastic anemia, a disease in which, similarly to FA, marrow failure occurs, TNF-α and IFN-γ act as late mediators of the stem cell damage and are overexpressed in patient marrow lymphocytes. This study evaluated in marrow mononuclear cells (MNCs) of patients with FA, the expression of negative modulators of the hematopoiesis, such as TNF-α, IFN-γ, macrophage inflammatory protein 1α (MIP-1α), and surface Fas ligand, and the role of TNF-α on FA erythropoiesis in vitro. TNF-α and IFN-γ were significantly overexpressed in stimulated marrow MNCs of FA patients as compared to healthy controls. MIP-1α and Fas ligand were undetectable in patients and controls. In bone marrow cultures, the addition of anti–TNF-α increased the size and significantly increased the number of erythroid colony-forming units and erythroid burst-forming units grown from FA patients but not from healthy controls. This indicates that FA subjects have a marrow TNF-α activity that inhibits erythropoiesis in vitro. TNF-α has a relevant role in the pathogenesis of erythroid failure in FA patients.

Purpose: To review a historical cohort of childhood ganglioneuroma (GN), the benign representative of the peripheral neuroblastic tumor (PNT) family. Patients and Methods: Of 2,286 PNTs enrolled between 1979 and 2005, 146 (6.4%) were registered as GN. Histological revision was carried out on 76 tumors. Diagnosis was confirmed in 45, while 27 were reclassified as ganglioneuroblastoma intermixed (GNBI) and four were reclassified as other PNT subtypes. Results: GNs differed from other PNTs for sex, age, tumor site, stage, tumor markers, and scintigraphic results. Characteristics of 76 reviewed and 70 nonreviewed patients were comparable. Reviewed GN and GNBI patients were comparable except for homovanillic acid excretion, metaiodobenzylguanidine scintigraphy, and DNA content. Seven patients were only biopsied and 139 underwent surgery. Twenty-two patients suffered surgery-related complications, of which two were fatal and seven were severe. Radical tumor resection and surgery-related complication rates were comparable for GN, GNBI, and nonreviewed instances. Six patients developed tumor progression but survived. Two patients developed a late malignancy but survived. None of the 146 patients received chemotherapy. Of 146 patients, two died of surgery-related complications and 144 survived. Conclusion: Diagnosis was changed to GNBI for approximately one third of 76 reviewed tumors. Patients with confirmed GN, reclassified as GNBI, and nonreviewed histology presented with comparable clinical, biochemical, and biologic features. Surgical results, complication rate, number of progressions, and outcome were similar for the three groups. Surgery was associated with significant risk of complications. Survival was not influenced by extent of tumor resection. Aggressive surgical approach should not be recommended for childhood GN and GNBI.