ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.

Revisiting the initial diagnosis and blood staging of mycosis fungoides and Sézary syndrome with the KIR3DL2 marker.

BACKGROUND: The early diagnosis of Sézary syndrome (SS) is challenging. Loss of CD7 and CD26 expression on CD4+ T cells is the currently used criterion in the initial diagnosis and staging of patients with SS. OBJECTIVES: Our aim was to evaluate the respective value of CD26, CD7 and KIR3DL2 expression on CD4+ T cells and total lymphocytes at initial diagnosis of SS. METHODS: This prospective study included 254 patients with clinical features consistent with cutaneous T-cell lymphoma seen at our institution between March 2014 and February 2019. Peripheral blood analysis by flow cytometry was performed for each patient at the time of diagnosis and during follow-up. The diagnosis of SS was based on ISCL/EORTC criteria. RESULTS: The presence of KIR3DL2+ Sézary cells (SCs) ≥ 200 µL-1 correlated with the diagnosis of SS, with sensitivity of 88·6% and specificity of 96·3%. All 154 patients with either inflammatory skin disease or other haematological disease had KIR3DL2+ cells < 200 µL-1 , while eight of them had CD4+ CD26- T cells ≥ 1000 µL-1 . Of five patients with SS and lymphopenia, four had CD4+ CD7- T cells < 1000 µL-1 and three had CD4+ CD26- T cells < 1000 µL-1 . However, all of them had KIR3DL2+ CD4+ T cells ≥ 200 µL-1 . Among patients with available samples during evolution, all B1-staged patients with ≥ 200 µL-1 KIR3DL2+ SCs at diagnosis evolved to B2 stage within 7 months. CONCLUSIONS: KIR3DL2 expression on T cells is highly specific and helps the early diagnosis of SS, especially in those patients with lymphopenia. What's already known about this topic? In the ISCL/EORTC cutaneous T-cell lymphoma (CTCL) categorization of blood involvement (B0-B2), B2 is defined as a T-cell receptor clonal rearrangement in blood, associated with high blood-smear Sézary cell (SC) count. Flow cytometry was developed to circumvent interobserver variability of SC manual counts; however, it mostly relies on detection of cells lacking CD7 and/or CD26 expression. We previously reported the reliability of KIR3DL2 as the first positive SC marker. What does this study add? Based on our analysis of 254 patients, we propose that KIR3DL2 be added to the ISCL/EORTC criteria for initial diagnosis of Sézary syndrome (SS) and B2 staging. This marker improved sensitivity of SS B2-stage CTCL diagnosis with a specificity > 95%, especially for patients with lymphopenia. We found KIR3DL2 helped early diagnosis of SS and was more reliable than CD26 in assessing blood tumour burden during therapy. What is the translational message? SC quantification is the major means of staging at initial diagnosis and monitoring blood tumour burden in a clinical trials setting. We recommend using a threshold value of KIR3DL2+ SCs ≥ 200 µL-1 or KIR3DL2+ SCs/lymphocytes ≥ 10% in the diagnostic criteria of SS and propose a novel algorithm for CTCL B2 blood staging.

[Managing late-effects after allogeneic stem cell transplantation in children: recommendations from the SFGM-TC]. / Prise en charge des séquelles après greffe de cellules souches hématopoïétiques chez l'enfant : recommandations de la SFGM-TC.

In this report, we address the issue of late-effects after allogeneic stem cell transplantation in children. In an effort to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille.

[New developments in Sézary syndrome]. / Actualités sur le syndrome de Sézary.

Sézary syndrome (SS) represents 3% of cutaneous T-cell lymphomas (CTCL). It is an aggressive epidermotropic CTCL with a 5-year survival rate of 24%. According to EORTC (European organization for research and treatment of cancer), SS is defined by erythroderma, diffuse lymphadenopathy, atypical T lymphocytes (>1000/mm(3)), and the presence of a major blood, cutaneous and nodal T cell clone. A specific marker for atypical tumoral T lymphocytes known as Sézary cells was identified in 2001, namely KIR3DL2 (CD158k) receptor, which allows more specific diagnosis of SS; levels of this marker are highly correlated with the clinical course of the disease. In therapeutic terms, clinical trials are being conducted on new molecules that point towards an improved prognosis for this disease. We propose a review of Sézary syndrome, which is currently the subject of scientific papers concerning both physiopathology and therapeutics, with new prospects of targeted therapy.

SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation.

T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain-containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain-containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor- and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.

T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane.

The molecular mechanisms regulating recruitment of intracellular signaling proteins like growth factor receptor-bound protein 2 (Grb2), phospholipase Cgamma1, or phosphatidylinositol 3-kinase (PI3-kinase) to the plasma membrane after stimulation of the T cell receptor (TCR)- CD3-zeta complex are not very well understood. We describe here purification, tandem mass spectrometry sequencing, molecular cloning, and biochemical characterization of a novel transmembrane adaptor protein which associates and comodulates with the TCR-CD3-zeta complex in human T lymphocytes and T cell lines. This protein was termed T cell receptor interacting molecule (TRIM). TRIM is a disulfide-linked homodimer which is comprised of a short extracellular domain of 8 amino acids, a 19-amino acid transmembrane region, and a 159-amino acid cytoplasmic tail. In its intracellular domain, TRIM contains several tyrosine-based signaling motifs that could be involved in SH2 domain-mediated protein-protein interactions. Indeed, after T cell activation, TRIM becomes rapidly phosphorylated on tyrosine residues and then associates with the 85-kD regulatory subunit of PI3-kinase via an YxxM motif. Thus, TRIM represents a TCR-associated transmembrane adaptor protein which is likely involved in targeting of intracellular signaling proteins to the plasma membrane after triggering of the TCR.

Absolute CD3+ CD158k+ lymphocyte count is reliable and more sensitive than cytomorphology to evaluate blood tumour burden in Sézary syndrome.

Background CD158k/KIR3DL2 is a specific marker for Sézary cells which can be used to diagnose Sézary syndrome (SS) in erythrodermic patients with abnormal circulating T cells. Objectives To evaluate the suitability of CD158k/KIR3DL2 for detecting and evaluating blood tumour load during the follow up of patients with SS. Methods The absolute CD3+ CD158k+ lymphocyte count was compared with the absolute count of cytomorphological Sézary cells and was correlated with clinical flares in a cohort of patients with SS. Twenty-five patients were included in the study and 48 blood samples were analysed. Results The absolute count of CD3+ CD158k+ cells strongly correlated with the absolute count of atypical circulating cells (r = 0.97, P < 10(-15)). The CD3+ CD158k+ lymphocyte cell count was in eight cases more sensitive than cytomorphology for detecting atypical circulating cells especially for small-sized tumour cells. The tumour burden evaluated by CD3+ CD158k+ immunostaining was significantly associated with clinical flare (P < 10(-4)). Conclusions CD3+ CD158k+ phenotyping is a reliable and objective test to monitor the blood tumour burden in patients with SS under systemic therapy.

Functional analysis of young patients with desmoid-type fibromatosis: Initial surveillance does not jeopardize long term quality of life.

BACKGROUND: With recent conservative strategies, prognosis of patients with desmoid-type fibromatosis (DTF) is about function preservation. We analyzed the long-term quality of life (QoL) of pediatric patients with DTF. METHODS: All French young patients (<21years) treated between 2005 and 2016 for a DTF in the EpSSG NRSTS-05 study were analyzed. A first wait-and-see strategy was recommended. Patients' QoL was analyzed with the internationally validated Child Health Questionnaire (CHQ). We focused on the relevant subscales scores: physical functioning (PF), role social limitations physical (RP), bodily pain (BP), general health perception (GH) and physical (PhS) and psychosocial (PsS) summary measures. RESULTS: Among the 81 patients, 52 families answered the CHQ (median delay since diagnosis = 6.2years; min2.2-max13.3 years). Median age at diagnosis was 11.5 years. Primary site: limbs (52%), head/neck (27%), or trunk (21%). Five year-Progression Free Survival was 39.1% (95%CI: 27.7-50.5%). As initial management for these 52 patients, 30 patients were first observed (57%), 13 had surgery (25%) and 9 received chemotherapy (18%). Total burden of therapy was exclusive surgery (9pts/18%), exclusive chemotherapy (18pts/35%), surgery + chemotherapy (13pts/25%), chemotherapy + radiotherapy (1 pt), surgery + chemotherapy + radiotherapy (1 pt), wait and see (10 pt). Regarding the parent forms, patients have significant lower PF (86.0vs.96.1; p = 0.03), RP (82.0vs.93.6; p = 0.04), GH (60vs.73; p < 0.005) and PhS (46.2 vs.53; p = 0.02) scores compared to healthy population. Comparison of QoL subscales scores according to initial strategy (wait-and-see vs.surgery/chemotherapy) did not reveal any difference (PF = 87.3vs.84.9; p = 0.80/RP = 83.4vs.78.7; p = 0.72/BP = 78.9vs.78.2; p = 0.95/GH = 59.7vs60; p = 0.97). Similar results were found using the children or adult forms. CONCLUSIONS: Initial wait-and-see strategy does not affect long term functional impairment.

Protocadherin 15 (PCDH15): a new secreted isoform and a potential marker for NK/T cell lymphomas.

Natural killer cells are well known to play an important role in immune defense against tumor development and viral infections. To further characterize new functionally relevant structures in these cells, we studied a series of monoclonal antibodies that we have raised against the NK cell line YT. One of these antibodies previously described as AY19, recognizes a 85 kD surface glycoprotein. Here we report the identification of a new secreted isoform of protocadherin 15, PCDH15C, which represents a potential associated protein for p85. Importantly, whereas protocadherins are absent from the surface of normal hematopoietic cells, we describe, for the first time, that PCDH15 is expressed in cytotoxic tumor-derived T- and NK-cell lines as well as in biopsies of nasal NK/T-cell lymphomas.

SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages.

Inhibitory immunoreceptors downregulate signaling by recruiting Src homology 2 (SH2) domain-containing tyrosine and/or lipid phosphatases to activating receptor complexes [1]. There are indications that some inhibitory receptors might also perform other functions [2] [3]. In adherent macrophages, two inhibitory receptors, SHPS-1 and PIR-B, are the major proteins binding to the tyrosine phosphatase SHP-1. SHPS-1 also associates with two tyrosine-phosphorylated proteins (pp55 and pp130) and a protein tyrosine kinase [4]. Here, we have identified pp55 and pp130 as the adaptor molecules SKAP55hom/R (Src-kinase-associated protein of 55 kDa homologue) and FYB/SLAP-130 (Fyn-binding protein/SLP-76-associated protein of 130 kDa), respectively, and the tyrosine kinase activity as PYK2. Two distinct SHPS-1 complexes were formed, one containing SKAP55hom/R and FYB/SLAP-130, and the other containing PYK2. Recruitment of FYB/SLAP-130 to SHPS-1 required SKAP55hom/R, whereas PYK2 associated with SHPS-1 independently. Formation of both complexes was independent of SHP-1 and tyrosine phosphorylation of SHPS-1. Finally, tyrosine phosphorylation of members of the SHPS-1 complexes was regulated by integrin-mediated adhesion. Thus, SHPS-1 provides a scaffold for the assembly of multi-protein complexes that might both transmit adhesion-regulated signals and help terminate such signals through SHP-1-directed dephosphorylation. Other inhibitory immunoreceptors might have similar scaffold-like functions.

Endostatin variations in childhood acute lymphoblastic leukaemia--comparison with basic fibroblast growth factor and vascular endothelial growth factor.

Angiogenic factors such as basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) were previously studied in childhood acute lymphoblastic leukaemia (ALL) but little is known concerning the anti-angiogenic response in ALL. At diagnosis, the plasma levels of the anti-angiogenic factor endostatin were significantly higher in 33 children with ALL than in controls (median values 17.7 and 7.6 ng/ml, respectively, p=0.0192) but no relationship was observed with plasma bFGF or VEGF levels. The highest levels were observed in patients with an hyperdiploïd karyotype. Expression of mRNA for collagen XVIII/endostatin in lymphoblasts was detected in 19/24 cases but protein secretion was found only in 14/28 supernatants of cultured lymphoblasts. No direct relationship appeared between secretion of endostatin by lymphoblasts and plasma levels. In addition, endostatin levels remained elevated in remission, suggesting that endostatin could have a stromal origin as well. No prognostic value of plasma endostatin could be assessed. In conclusion, the present data indicate that an anti-angiogenic response is observed in some ALL children, but its physiopathological importance remains to be established.

Activation of p56lck by p72syk through physical association and N-terminal tyrosine phosphorylation.

The p56lck and p59fyn protein tyrosine kinases are important signal transmission elements in the activation of mature T lymphocytes by ligands to the T-cell antigen receptor (TCR)/CD3 complex. The lack of either kinase results in deficient early signaling events, and pharmacological agents that block tyrosine phosphorylation prevent T-cell activation altogether. After triggering of the TCR/CD3 complex, both kinases are moderately activated and begin to phosphorylate cellular substrates, but the molecular mechanisms responsible for these changes have remained unclear. We recently found that the p72syk protein tyrosine kinase is physically associated with the TCR/CD3 complex and is rapidly tyrosine phosphorylated and activated by receptor triggering also in T cells lacking p56lck. Here we examine the regulation of p72syk and its interaction with p56lck in transfected COS-1 cells. p72syk was catalytically active and heavily phosphorylated on its putative autophosphorylation site, Tyr-518/519. Mutation of these residues to phenylalanines abolished its activity in vitro and toward cellular substrates in vivo and reduced its tyrosine phosphorylation in intact cells by approximately 90%. Coexpression of lck did not alter the catalytic activity of p72syk, but the expressed p56lck was much more active in the presence of p72syk than when expressed alone. This activation was also seen as increased phosphorylation of cellular proteins. Concomitantly, p56lck was phosphorylated at Tyr-192 in its SH2 domain, and a Phe-192 mutant p56lck was no longer phosphorylated by p72syk. Phosphate was also detected in p56lck at Tyr-192 in lymphoid cells. These findings suggest that p56lck is positively regulated by the p72syk kinase.

Identification of CD245 as myosin 18A, a receptor for surfactant A: A novel pathway for activating human NK lymphocytes.

CD245 is a human surface antigen expressed on peripheral blood lymphocytes, initially delineated by two monoclonal antibodies DY12 and DY35. Until now, CD245 molecular and functional characteristics remained largely unknown. We combined immunological and proteomic approaches and identified CD245 as the unconventional myosin 18A, a highly conserved motor enzyme reported as a receptor for the surfactant protein A (SP-A), that plays a critical role in cytoskeleton organization and Golgi budding. We report that the recruitment of CD245 strongly enhanced NK cell cytotoxicity. Further, we show that the enhancement of the NK lymphocytes killing ability toward CD137-ligand expressing target cells could result from the induction of CD137 expression following CD245 engagement. The SP-A receptor could therefore represent a novel and promising target in cancer immunotherapy.

Coupling the TCR to downstream signalling pathways: the role of cytoplasmic and transmembrane adaptor proteins.

Engagement of the T-cell receptor (TCR) complex initiates a cascade of intracellular events ultimately leading to T-cell proliferation and differentiation. One of the first detectable consequences of TCR triggering is the activation of cytoplasmic protein kinases which, through phosphorylation of specific substrates, couple the TCR to downstream signalling cascades. Although it is well established that activation of the Ras- and the calcium-dependent calcineurin pathway is required for the achievement of T-cell activation, the precise mechanism as to how the TCR is connected to these intracellular effector molecules is still unclear. Major progress has been made in this regard with the molecular characterization of novel cytoplasmic and transmembrane molecules called adaptor proteins which integrate TCR-mediated signals at the intracellular level thus allowing fine tuning of T-cell responses.

Induction of hyperphosphorylation and activation of the p56lck protein tyrosine kinase by phenylarsine oxide, a phosphotyrosine phosphatase inhibitor.

The T cell protein tyrosine kinase p56lck is implicated in thymic development and mitogenic activation of T lymphocytes, and is itself regulated by reversible tyrosine phosphorylation. When phenylarsine oxide (PAO), a membrane-permeable inhibitor of phosphotyrosine phosphatases, was added to Jurkat T leukemia or LSTRA thymoma cells, the phosphate content of p56lck increased rapidly. The sites of increased phosphorylation were mapped to Tyr-192, Tyr-394 and Tyr-505. Hyperphosphorylated p56lck displayed retarded mobility on SDS gels, unaltered or marginally increased cytoskeletal association, and its catalytic activity changed in a biphasic manner; during the first 10-20 min of PAO-treatment the activity increased and then it declined to very low values within 1-2 hr. Our data suggest that p56lck contains both positive and negative regulatory sites which are constantly dephosphorylated at an unexpectedly high rate by cellular phosphotyrosine phosphatases.

Increased expression of a novel early activation surface membrane receptor in cutaneous T cell lymphoma cells.

Using a newly generated monoclonal antibody we identified the 96 kDa transmembrane receptor SC5 expressed simultaneously on a human Sezary cell line and a minor T cell subset in normal individuals. SC5 antigen was detected mostly on CD45RO+ lymphocytes from both CD4+ and CD8+ subsets as well as on natural killer and B lineage cells. SC5 surface expression increased very early after polyclonal stimulation of CD3+ cells due to the transfer of intracellular SC5 molecules to the cell membrane. Engagement of SC5 receptor by its monoclonal antibody inhibited the anti-CD3-induced proliferation and cytokine secretion of peripheral blood T cells and cell clones, whereas SC5 monoclonal antibody did not affect the cytotoxic activity of CD8+ T cell clones. Extensive phenotypic analysis revealed that the percentage of SC5+ CD4+ circulating lymphocytes in Sezary syndrome patients was significantly increased in comparison with controls (p < 0.01) and correlated with the morphologically detected percentage of Sezary syndrome cells in peripheral blood (p < 0.001). In one patient we clearly demonstrated that the circulating malignant T cells coexpress SC5 molecules. Importantly, ligation of SC5 receptor in a cutaneous T cell lymphoma cell line profoundly inhibited the anti-CD3-induced proliferation. Consequently, the expression of SC5 receptor in the peripheral blood of Sezary syndrome patients may serve not only to detect the presence of circulating malignant CD4+ cells but also as a target for immunotherapy.

SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55.

A recombinant GST-Fyn-SH2 domain was used to purify proteins from lysates of pervanadate treated EL4 cells. N-terminal sequencing and molecular cloning of one of the purified polypeptides resulted in the identification of a novel adaptor protein that shares strong structural homology to the recently cloned Fyn-associated adaptor protein SKAP55. This protein was termed SKAP-HOM (SKAP55 homologue). Despite their striking homology, SKAP55 and SKAP-HOM have distinct characteristics. Thus, unlike SKAP55, which is exclusively expressed in T lymphocytes, SKAP-HOM expression is ubiquitous. Furthermore, while SKAP55 is constitutively tyrosine phosphorylated in resting human T cells, SKAP-HOM is expressed as a non-phosphorylated protein in the absence of external stimulus but becomes phosphorylated following T cell activation. In addition, SKAP-HOM does not associate with p59fyn in T cells although it represents a specific substrate for the kinase in COS cells. Finally, we demonstrate that, as previously shown for SKAP55, SKAP-HOM interacts with the recently identified polypeptide SLAP-130.

[Cefepime-amikacin combination in febrile neutropenic children with malignant hemopathy or tumor]. / Association céfépime-amikacine chez les enfants neutropéniques fébriles atteints d'hémopathies ou de tumeurs malignes.

UNLABELLED: Our aim was to evaluate retrospectively the efficacy of a therapeutic strategy with a first line combination based on cefepime-amikacin in febrile neutropenic children treated with chemotherapy. PATIENTS AND METHODS: Sixty-five neutropenic febrile episodes in 43 children treated by the association cefepime-amikacin, were evaluated according to the clinical status, the depth and duration of neutropenia, the underlying disease and the initial treatment. RESULTS: Thirty-nine (60%) episodes were successfully treated by the association cefepime-amikacin. Among the 26 persisting febrile episodes, adjunction of vancomycin and amphotericin B was effective in 11 (76% of total rate success) and 5 (84% of total rate success) cases respectively. The efficacy of the first line antibiotherapy was not different as regards to the duration and the depth of neutropenia. Otherwise, febrile episodes after chemotherapy against solid tumours were rapidly controlled by the first and second line of the anti-microbial strategy. Children treated for haematological malignancies presented a lower response rate (P = 0.03). CONCLUSION: In febrile and neutropenic children treated with chemotherapy, the association cefepime-amikacin appeared to be a safe empirical treatment. In a neutropenic child, the immunodeficiency and possibly the clinical status should be the major factors of the infectious prognosis more than the duration of aplasia.

[Severe cutaneous Streptococcus pyogenes infections in the child: results of a multicenter survey]. / Infections cutanées sévères à Streptococcus pyogenes chez l'enfant: résultats d'une enquête multicentrique.

UNLABELLED: To assess pediatric cases of severe cutaneous infections due to Streptococcus pyogenes. Since the beginning of 1980, the incidence of cellulitis and necrotizing fasciitis due to S. pyogenes has increased in adults. Serotyping of obtained isolates are in most cases M1, M3 or M5 protein. PATIENTS AND METHOD: A retrospective (1990-2000) survey was carried out in pediatric hospital centers. RESULTS: Three cases of necrotizing fasciitis and 15 of cellulitis were observed. In 30% of the cases, vancella lesions were associated; in the other cases, minor wounds were the site of the infection. Bacteriologic diagnosis was made by local samples in 14 cases; blood cultures were positive in four cases. In 11 cases, initial intravenous treatment consisted of third generation cephalosporin, in six cases of penicillin M or G and in one case of fusidic acid. In the second time, penicillin M was perfused in the majority of the cases. Mean duration of intravenous antibiotics perfusion was 15 days. There were no sequelae or death in this survey. CONCLUSIONS: Despite this study had limited epidemiological characteristics, it confirms that these two infections are rare. The frequency is probably underestimated, due to the difficulty in performing a diagnosis. The major site of infection was the varicella lesion. These two infections are so similar that it is frequent to mistake one infection for the other. Nonsteroidal anti-inflammatory drugs and site of infections did not influence prognosis. The treatment of cellulitis is penicillinotherapy whereas in necrotizing fasciitis early major surgery is often correlated with the rate of survival.

Characteristics of endobronchial primitive tumors in children.

Primary endobronchial tumors are rare in children and they include a broad spectrum of lesions. The aim of this study was to determine the characteristic features, treatments and outcomes of these tumors. We report a retrospective analysis of all patients treated for endobronchial tumor in nine French hospitals between 1990 and 2010 and a comparison of the results with those reported in the medical literature. Twelve tumors were reported: five low grade muco epidermoid carcinomas, two inflammatory myofibroblastic tumors, two hemangiomas, one anaplastic large cell lymphoma, one carcinoid tumor, and one juvenile xanthogranuloma. The mean age of the patients was 7.5 ± 3.5 years. The most common sign revealing the disease was persistent atelectasis or recurrent pneumonia (eight cases). The other revealing signs were a persistent bronchospasm (three cases) and hemoptysis (one case). The clinical presentation, biology, serum tumor markers, and chest X-ray abnormalities were not specific to a particular histological diagnosis. Chest CT scan revealed the presence of an endobronchial tumor in 11 cases. Nine tumors could be diagnosed from a biopsy obtained by video endoscopy. Complete surgical resection was performed in seven patients. Bronchoscopic removal was performed in five cases and was successful in three. There were no deaths. Endobronchial tumors are rare in childhood and their histology is diverse. Chest CT scan and per-endoscopic endobronchial biopsies are required for diagnosis, when possible. Surgical or endoscopic treatment should be discussed by a multidisciplinary team. Despite the multiple etiologies, the prognosis of these tumors is good if diagnosis is early and if resection is complete. Long-term recurrences have been described, so long-term follow-up of these children is recommended.