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1.
Oral Oncol ; 94: 115-120, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178206

RESUMO

OBJECTIVES: Achieving complete tumour resection is one of the main goals of surgery for head and neck squamous cell carcinoma (HNSCC) tumours. Whether biological characteristics of tumours contribute to the surgical resectability and the presence of positive surgical margins (SM) after resection of HNSCC is unclear. We aimed to address this issue. MATERIALS AND METHODS: We used data from The Cancer Genome Atlas (TCGA) to relate the SM status of 356 HNSCC tumours covering five major primary locations (tongue, larynx, tonsils, floor of mouth and buccal mucosa) with data from multiple omics approaches (transcriptomic, genomic and proteomic analyses). RESULTS: We identified three differentially expressed genes whose expression was significantly associated with the presence of positive SM in tongue tumours (n = 144). The three genes (CCDC66, ZRANB2 and VCPKMT) displayed significantly higher mRNA levels in tongue tumours with positive SM compared to tumours with negative SM. The corresponding gene expression signature identified tongue tumours with a positive SM with high sensitivity and specificity (85% and 76%, respectively, Area Under the Curve (AUC) = 0.84). Tongue tumours with this signature were characterised by a high grade, elevated proliferation levels and a tumour stroma with fewer fibroblasts and endothelial cells. CONCLUSION: Positive SM were found to be strikingly associated with tumour biology in tongue tumours. These findings offer interesting perspectives for biomarker identification and precision surgery in these tumours.

2.
Hum Pathol ; 89: 51-61, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054893

RESUMO

Childhood pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease. Its pulmonary histopathology, according to comprehensive clinical-radiological findings and BRAFV600E mutation status, has not yet been thoroughly documented. From the 167 childhood PLCH cases entered in the French National Histiocytosis Registry (1983-2016), we retrieved lung biopsies from a consecutive retrospective series of 17 patients, diagnosed when they were 2 weeks to 16 years old (median, 9.4 years), and report the clinical and histopathological findings herein. Histological analyses of biopsies (16 surgical and 1 postmortem) found the following features, alone or associated: Langerhans cell (LC) nodules with cavitation (9/17), cysts (14/17), fibrotic scars (2/17), peribronchiolar topographic distribution of the lesions (10/17), and accessory changes, like stretch emphysema (7/17). Those characteristics closely resemble those describing adult PLCH. However, unusual findings observed were 2 large nodules and a diffuse interstitial LC infiltrate. BRAFV600E mutation was detected in 4 of 12 samples tested, notably in the 3 with unusual features. In conclusion, childhood PLCH mostly shares the common histology features already described in adult PLCH, regardless of age. Because smoking is considered the major trigger in PLCH pathogenesis, the findings based on this series suggest other inducers of bronchiolar LC recruitment, especially in very young patients.

3.
Int J Pediatr Otorhinolaryngol ; 123: 33-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31059930

RESUMO

INTRODUCTION: Desmoid-type fibromatosis (DF) is a rare benign lesion known for its local aggressiveness. The tumor management still remains under debate. Primary head and neck (HN), represents the second most prevalently affected sitein children with DF. This study aims to analyze the specificity of HN-DF in children, focusing on long-term effects of the tumor and therapies. METHODS: This retrospective multicenter study analyzed children treated for a HN-DF between 1993 and 2013. All medical files were reviewed and their outcomes analyzed according to the initial therapies provided. RESULTS: Sixteen children were selected. Mandibular and submandibular areas were the main locations (11 cases). Eight children underwent chemotherapy as first-line therapy with tumor control in 3 cases and 5 cases needing additional treatment. Six children underwent primary surgery: isolated in 3 cases and with additional treatment after tumor progression in 3 cases. A wait-and-see attitude was adopted for 2 children without any additional treatment in 1 case, and followed by additional chemotherapy in the other case. Total burden of treatment to control the disease was a biopsy (1 case), surgery (3 unique cases, 1 multiple case), surgery with chemotherapy (6 cases), and exclusive medical therapies (5 cases). Surgical postoperative sequelae were facial palsy (cases of parotid gland affection), XIth cranial nerve sacrifice or sensory impairment. CONCLUSION: HN-DF is a local and extensive disease that is difficult to control with surgery alone. Sequelae are frequent due to the initial tumor location or therapies. Initial conservative strategies need to be discussed in a multidisciplinary way in order to try to control the disease with the minimal morbidity.

4.
BMC Infect Dis ; 19(1): 302, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943907

RESUMO

BACKGROUND: Staphylococcus aureus has emerged as a leading cause of invasive severe diseases with a high rate of morbidity and mortality worldwide. The wide spectrum of clinical manifestations and outcome observed in staphylococcal illness may be a consequence of both microbial factors and variability of the host immune response. CASE PRESENTATION: A 14-years old child developed limb ischemia with gangrene following S. aureus bloodstream infection. Histopathology revealed medium-sized arterial vasculitis. The causing strain belonged to the emerging clone CC1-MSSA and numerous pathogenesis-related genes were identified. Patient's genotyping revealed functional variants associated with severe infections. A combination of virulence and host factors might explain this unique severe form of staphylococcal disease. CONCLUSION: A combination of virulence and genetic host factors might explain this unique severe form of staphylococcal disease.


Assuntos
Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/genética , Vasculite/diagnóstico , Adolescente , Amputação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Encéfalo/diagnóstico por imagem , Cefotaxima/farmacologia , Cefotaxima/uso terapêutico , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Humanos , Perna (Membro)/cirurgia , Imagem por Ressonância Magnética , Masculino , Meticilina/farmacologia , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Vasculite/complicações , Vasculite/microbiologia
6.
Mod Pathol ; 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30401946

RESUMO

The prognosis of malignant pediatric adrenocortical tumors is closely related to disease stage, which is used to guide perioperative treatment recommendations. However, current scoring systems are inadequate to distinguish between benign and malignant adrenocortical tumors. Robust microscopic prognostic features that could help determine perioperative therapy are also lacking. The aim of this national study was to review the prognostic value of the Wieneke scoring criteria and Ki67 labeling index in unselected pediatric adrenocortical tumors. Using strict definitions previously defined by expert pathologists, a Wieneke score was re-attributed to each tumor after an independent and centralized review. In addition, Ki67 proliferation index was performed and reviewed for each case. A total of 95 cases were selected; all were treated between 2000 and 2018 and had histopathologic material and sufficient outcome-related information available. Localized disease was found in 88% of patients. Among those with advanced disease, 6% had tumor extension into adjacent organs and 5% had metastases at diagnosis. Median follow-up was 5 years and 3 months. The 5-year PFS was 82%, 95% CI [73%-91%]. Tumor stage significantly correlated with PFS (p < 0.0001). Tumor weight up to 200 g, extra-adrenal extension and initial non-complete surgical resection were statistically associated with worse outcomes. No recurrences nor metastases occurred when the Ki67 index was < 15%. Up to two of the following five factors including tumor necrosis, adrenal capsular invasion, venous invasion, mitotic count > 15/20 high-power fields, and Ki67 index > 15%, significantly correlated with worse outcomes. We propose a pathological scoring system incorporating the Ki67 index as part of a two-step approach after disease staging to guide adjuvant treatment in pediatric adrenocortical tumors, especially after incomplete resection. These results should be validated in an independent cohort.

7.
Orphanet J Rare Dis ; 13(1): 166, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30236129

RESUMO

BACKGROUND: Cherubism is a rare autosomal dominant disorder of the jaws caused by mutation of the SH3BP2 gene. The bone is replaced by a fibrous granuloma containing multinucleated giant cells. Cells of the cherubism granuloma have never been systematically analyzed. Hence, the aim of this study was to characterize the cells in human cherubism granulomas, to determine the osteoclastic characteristics of the multinucleated giant cells and to investigate the potential role of TNF-α in human cherubism. RESULTS: Seven granulomas were analyzed in pathology, molecular biology and immunohistochemistry. Granulomas were composed mainly of macrophages or osteoclasts within a fibroblastic tissue, with few lymphoid cells. Myeloid differentiation and nuclear NFATc1 localization were both associated with disease aggressiveness. OPG and RANKL immunohistochemical expression was unexpected in our specimens. Five granuloma cells were cultured in standard and osteoclastogenic media. In culture, cherubism cells were able to differentiate into active osteoclasts, in both osteoclastogenic and standard media. IL-6 was the major cytokine present in the culture supernatants. CONCLUSION: Multinucleated giant cells from cherubism granulomas are CD68 positive cells, which differentiate into macrophages in non-aggressive cherubism and into osteoclasts in aggressive cherubism, stimulated by the NFATc1 pathway. This latter differentiation appears to involve a disturbed RANK-L/RANK/OPG pathway and be less TNF-α dependent than the cherubism mouse model.

8.
Hum Pathol ; 2018 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-30130629

RESUMO

Solid pseudopapillary neoplasms of the pancreas (SPN) are classified as "exocrine" pancreatic tumors by the World Health Organization. However, despite numerous studies using immunohistochemistry, electron microscopy, animal models and molecular biology, the histogenesis of SPN remains unclear. At the same time, our knowledge of human pancreas development has significantly increased. It is now well known that the undifferentiated PDX1+ pancreatic progenitors proliferate and differentiate into endocrine, ductal, and acinar cells, thanks to the expression of numerous transcription factors, which can be used to better characterize pancreatic tumors. In a series of 14 pediatric SPN, we investigated the expression of four transcription factors associated with pancreatic development (PDX1, SOX9, PTF1A and NKX2.2) to obtain new insights into the pathogenesis of SPN. In addition, we tested the expression of different markers of epithelial, endocrine, exocrine, and neural differentiation, using both immunohistochemical and immunofluorescence analyses. All tumors displayed the typical histological features of SPN, with both pseudopapillary and solid patterns. The immunoprofile was characterized by immunoreactivity for ß-catenin (100%), progesterone receptor (100%), cyclin D1 (100%), synaptophysin (65%) and S100 (15%). In all cases, tumor cells were negative for the following markers: PDX1, SOX9, PTF1A, NKX2.2, chromogranin A, glucagon, insulin, somatostatin, ghrelin, pancreatic polypeptide, amylase, GFAP, calretinin, EPCAM and estrogen receptor α. To conclude, SPN do not express major transcription factors involved in pancreatic development and differentiation, which does not allow to precise pancreatic lineage of tumor cells. Thus additional studies are still required to determine origin of SPN.

9.
Eur J Hum Genet ; 26(8): 1217-1221, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29706636

RESUMO

Osteosarcoma is the most common malignant bone tumor in adolescents and young adults. Most osteosarcomas are sporadic but the risk of osteosarcoma is also increased by germline variants in TP53, RB1 and RECQL4 genes. ATRX germline variations are responsible for the rare genetic disorder X-linked alpha-thalassemia mental retardation (ATR-X) syndrome characterized by severe developmental delay and alpha-thalassemia but no obvious increased risk of cancer. Here we report two children with ATR-X syndrome who developed osteosarcoma. Notably, one of the children developed two osteosarcomas separated by 10 years. Those two cases raise the possibility that ATRX germline variant could be associated with an increased risk of osteosarcoma.

10.
J Pediatr Hematol Oncol ; 40(4): 320-324, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29016414

RESUMO

We present the case of a woman referred to our department at 34 weeks of pregnancy with a fetal ultrasonographic scan showing a mass that had developed within the right maxilla with invasion of the orbit. A retrospective examination showed that this tumor had been present since the 12th week of pregnancy. At 39+4 weeks of gestation, a boy was born. He presented a black firm aspect in the maxilla. A computed tomographic scan and magnetic resonance imaging revealed a soft tissue swelling over the right maxilla, extending into the orbit but without invasion of the globe. Surgical biopsy confirmed a melanotic neuroectodermal tumor of infancy. The pathologic examination did not show any neuroblast-like component on the hematoxylin eosin saffron staining. Because of the extension and the size of the lesion, neoadjuvant chemotherapy was carried out. At day 21, the patient received 1 cycle of low-dose cyclophosphamide and vincristine, 2 cycles of etoposide and carboplatin, and thereafter 1 cycle of cyclophosphamide, adriamycin, and vincristin because the lesion kept growing. After stabilization of the size of the tumor, at 4 months, a maxillectomy and partial resection of the orbital floor and lateral orbital wall was performed on the patient. As a complete resection would have required orbital exenteration, surgery was performed deliberately incomplete leaving a macroscopic residue (R2). At 2.5 years of follow-up, the patient showed complete remission with no lesions evident on magnetic resonance imaging.

11.
J Craniomaxillofac Surg ; 46(2): 201-206, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29275074

RESUMO

OBJECTIVES: Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence. METHODS: A retrospective multicenter study, including 11 patients from eight centers with a confirmed diagnosis of MNTI, was conducted. Epidemiological, clinical, radiological, pathological, and immunohistochemical examinations were reviewed. A statistical analysis using a t-test was conducted to calculate parameters correlating with tumor recurrence. RESULTS: MNTIs mainly occurred in the maxilla, with a mean age at diagnosis of 3.18 months (range: 0-6 months). Primary surgery was performed on 10 patients, with a clear margin resection on two patients. Overall recurrence rate was 27% with a survival of 100% at time of follow-up. No statistical correlation between recurrence rate, age at diagnosis, localization, resection margins, and pathological and immunohistochemical characteristics could be established. CONCLUSION: In our study, locoregional tumor recurrence did not seem to correlate with resection margins, so a conservative surgical approach may need to be considered to avoid functional and aesthetic sequelae.


Assuntos
Neoplasias de Cabeça e Pescoço/etiologia , Tumor Neuroectodérmico Melanótico/etiologia , Feminino , França/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Neoplasias Mandibulares/epidemiologia , Neoplasias Mandibulares/etiologia , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/cirurgia , Neoplasias Maxilares/epidemiologia , Neoplasias Maxilares/etiologia , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Tumor Neuroectodérmico Melanótico/epidemiologia , Tumor Neuroectodérmico Melanótico/patologia , Tumor Neuroectodérmico Melanótico/cirurgia , Neoplasias Orbitárias/epidemiologia , Neoplasias Orbitárias/etiologia , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
12.
PLoS One ; 12(9): e0185190, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28945781

RESUMO

PURPOSE: This study investigated relationships between neuroblastomas (NBs) imaging phenotypes, tumor genomic profile and patient outcome. PATIENTS AND METHODS: This IRB-approved retrospective observational study included 133 NB patients (73 M, 60 F; median age 15 months, range 0-151) treated in a single institution between 1998 and 2012. A consensus review of imaging (CT-scan, MRI) categorized tumors according to both the primarily involved compartment (i.e., neck, chest, abdomen or pelvis) and the sympathetic anatomical structure the tumors rose from (i.e., cervical, paravertebral or periarterial chains, or adrenal gland). Tumor shape, volume and image-defined surgical risk factors (IDRFs) at diagnosis were recorded. Genomic profiles were assessed using array-based comparative genomic hybridization and divided into three groups: "numerical-only chromosome alterations" (NCA), "segmental chromosome alterations" (SCA) and "MYCN amplification" (MNA). Statistical analyses included Kruskal-Wallis, Chi2 and Fisher's exact tests and the Kaplan-Meier method with log-rank tests and Cox model for univariate and multivariate survival analyses. RESULTS: A significant association between the sympathetic structure origin of tumors and genomic profiles was demonstrated. NBs arising from cervical sympathetic chains were all NCA. Paravertebral NBs were NCA or SCA in 75% and 25%, respectively and none were MNA. Periarterial NBs were NCA, SCA or MNA in 33%, 56% and 11%, respectively. Adrenal NBs were NCA, SCA or MNA in 16%, 36% and 48%, respectively. Among MNA NBs, 92% originated from the adrenal gland. The sympathetic anatomical classification was significantly better correlated to overall survival than the compartmental classification (P < .0003). The tumor volume of MNA NBs was significantly higher than NCA or SCA NBs (P < .0001). Patients with initial volume less than 160 mL had significantly better overall survival (P < .009). A "single mass" pattern was significantly more frequent in NCA NBs (P = .0003). The number of IDRFs was significantly higher in MNA NBs (P < .0001). CONCLUSION: Imaging phenotypes of neuroblastomas, including tumor origin along the sympathetic system, correlate with tumor genomic profile and patient outcome.


Assuntos
Neuroblastoma/diagnóstico por imagem , Neuroblastoma/genética , Criança , Pré-Escolar , Aberrações Cromossômicas , Hibridização Genômica Comparativa , Feminino , França/epidemiologia , Genômica , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Neuroblastoma/mortalidade , Fenótipo , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Transcriptoma
13.
J Pediatr Hematol Oncol ; 39(8): e479-e482, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28582275

RESUMO

Ewing sarcoma (ES) infrequently affects the spine. Diagnosis is usually made several weeks following growing symptoms. In this report, we present the case of a child with ES localized at the upper thoracic level. ES was revealed by isolated acute complete paraplegia mimicking medullary stroke. The girl was operated for decompressive laminectomy and tumor removal. Afterwards, she received adjuvant therapy. Subsequently, the child showed a slow improvement of her leg sensitivity associated with a partial motor recovery. ES can affect the mobile spine. Acute symptomatology due to intratumoral hemorrhage and sudden spinal cord compression may suggest the diagnosis. Neurological outcomes following ES are generally poor.


Assuntos
Neoplasias Ósseas/complicações , Paraplegia/diagnóstico , Paraplegia/etiologia , Sarcoma de Ewing/complicações , Vértebras Torácicas/patologia , Biópsia , Neoplasias Ósseas/diagnóstico , Criança , Terapia Combinada , Descompressão Cirúrgica , Feminino , Humanos , Laminectomia , Imagem por Ressonância Magnética , Paraplegia/terapia , Sarcoma de Ewing/diagnóstico , Esteroides/uso terapêutico , Vértebras Torácicas/diagnóstico por imagem
14.
Am J Dermatopathol ; 39(6): 463-467, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28525423

RESUMO

Congenital infantile fibrosarcoma (CIFS) is a soft tissue sarcoma of infants mainly involving lower extremities and usually developing during the first year of life. At another end of the spectrum of pediatric fibroblastic lesions, lipofibromatosis is a rare benign infiltrative soft tissue tumor that affects children. The authors report in this study a particular presentation with a CIFS surrounded by lipofibromatosis-like areas. The presence of a surrounding benign tumor confused and delayed CIFS diagnosis.


Assuntos
Fibroma/patologia , Fibrossarcoma/patologia , Lipoma/patologia , Neoplasias Complexas Mistas/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Biópsia , Diagnóstico Tardio , Feminino , Fibroma/congênito , Fibroma/cirurgia , Fibrossarcoma/congênito , Fibrossarcoma/cirurgia , Humanos , Recém-Nascido , Lipoma/congênito , Lipoma/cirurgia , Imagem por Ressonância Magnética , Neoplasias Complexas Mistas/congênito , Neoplasias Complexas Mistas/cirurgia , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Natal , Neoplasias de Tecidos Moles/congênito , Neoplasias de Tecidos Moles/cirurgia , Tomografia Computadorizada por Raios X , Carga Tumoral
15.
J Med Genet ; 54(5): 324-329, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28069933

RESUMO

BACKGROUND: While mitochondrial DNA (mtDNA) copy number is strictly regulated during differentiation and according to cell type, very little is known regarding the mechanism which accurately controls mtDNA copy number in human. Exon 2 of the human POLG gene, encoding the catalytic subunit of the mitochondrial-specific DNA polymerase gamma, contains a CpG island, highly conserved in mice and human. Changes of DNA methylation at the POLG locus have been shown to modulate mtDNA copy number during cell differentiation in both mouse and human. METHODS: We have investigated the epigenetic modification of the POLG gene, by assessing the methylation level of its exon 2 using deep-Next Generation Sequencing analysis of bisulfite-treated DNA. Analysis were performed on various tissues at either postnatal or prenatal stages, on samples from carriers of mtDNA mutations, patients carrying two loss-of-function POLG mutations and controls. RESULTS: Very high methylation levels at POLG exon 2 were found (94±3%) and no variation was observed according to either developmental stage or tissue of origin, except for sperm samples for which lower methylation levels were found (80%). This high level of methylation was neither correlated with the presence of mtDNA mutations (94±1% of methylated alleles), nor with biallelic POLG mutations (93%±2%), even in tissues where a mtDNA depletion had been observed. CONCLUSIONS: This study suggests that, at variance with mouse and un/de-differentiated human cells, differentiated human cells control mtDNA levels irrespective of POLG methylation. The factors which actually control the mtDNA levels in such cell types remain to be identified.


Assuntos
Diferenciação Celular/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Polimerase do DNA Mitocondrial/genética , DNA Mitocondrial/genética , Éxons/genética , Mutação/genética , Adolescente , Adulto , Animais , Sequência de Bases , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Camundongos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
16.
Hum Pathol ; 62: 160-169, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28087478

RESUMO

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter. Symptoms mimic primary urea cycle defects but dysimmune symptoms are also described. Renal involvement in LPI was first described in the 1980s. In 2007, it appeared that it could concern as much as 75% of LPI patients and could lead to end-stage renal disease. The most common feature is proximal tubular dysfunction and nephrocalcinosis but glomerular lesions are also reported. However, very little is known regarding histological lesions associated with LPI. We gathered every kidney biopsy of LPI-proven patients in our highly specialized pediatric and adult institution. Clinical, biological, and histological information was analyzed. Five LPI patients underwent kidney biopsy in our institution between 1986 and 2015. Clinically, 4/5 presented with proximal tubular dysfunction and 3/5 with nephrotic range proteinuria. Histology showed unspecific tubulointerstitial lesions and nephrocalcinosis in 3/5 biopsies and marked peritubular capillaritis in one child. Glomerular lesions were heterogeneous: lupus-like-full house membranoproliferative glomerulonephritis (MPGN) in one child evolved towards monotypic IgG1κ MPGN sensitive to immunomodulators. One patient presented with glomerular non-AA non-AL amyloidosis. Renal biopsy is particularly relevant in LPI presenting with glomerular symptoms for which variable histological lesions can be responsible, implying specific treatment and follow-up.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/patologia , Rim/patologia , Adolescente , Adulto , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/genética , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Amiloidose/etiologia , Amiloidose/patologia , Biópsia , Criança , Progressão da Doença , Feminino , Imunofluorescência , Cadeias Leves da Proteína-1 Reguladora de Fusão/genética , Predisposição Genética para Doença , Glomerulonefrite Membranoproliferativa/etiologia , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Lactente , Masculino , Mutação , Nefrocalcinose/etiologia , Nefrocalcinose/patologia , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/patologia , Paris , Fenótipo , Proteinúria/etiologia , Proteinúria/patologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/patologia , Fatores de Tempo
17.
Orphanet J Rare Dis ; 12(1): 3, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28057010

RESUMO

BACKGROUND: Lysinuric protein intolerance (LPI) is a rare metabolic disease resulting from recessive-inherited mutations in the SLC7A7 gene encoding the cationic amino-acids transporter subunit y+LAT1. The disease is characterised by protein-rich food intolerance with secondary urea cycle disorder, but symptoms are heterogeneous ranging from infiltrative lung disease, kidney failure to auto-immune complications. This retrospective study of all cases treated at Necker Hospital (Paris, France) since 1977 describes LPI in both children and adults in order to improve therapeutic management. RESULTS: Sixteen patients diagnosed with LPI (12 males, 4 females, from 9 families) were followed for a mean of 11.4 years (min-max: 0.4-37.0 years). Presenting signs were failure to thrive (n = 9), gastrointestinal disorders (n = 2), cytopenia (n = 6), hyperammonemia (n = 10) with acute encephalopathy (n = 4) or developmental disability (n = 3), and proteinuria (n = 1). During follow-up, 5 patients presented with acute hyperammonemia, and 8 presented with developmental disability. Kidney disease was observed in all patients: tubulopathy (11/11), proteinuria (4/16) and kidney failure (7/16), which was more common in older patients (mean age of onset 17.7 years, standard deviation 5.33 years), with heterogeneous patterns including a lupus nephritis. We noticed a case of myocardial infarction in a 34-year-old adult. Failure to thrive and signs of haemophagocytic-lymphohistiocytosis were almost constant. Recurrent acute pancreatitis occurred in 2 patients. Ten patients developed an early lung disease. Six died at the mean age of 4 years from pulmonary alveolar proteinosis. This pulmonary involvement was significantly associated with death. Age-adjusted plasma lysine concentrations at diagnosis showed a trend toward increased values in patients with a severe disease course and premature death (Wilcoxon p = 0.08; logrank, p = 0.17). Age at diagnosis was a borderline predictor of overall survival (logrank, p = 0.16). CONCLUSIONS: As expected, early pulmonary involvement with alveolar proteinosis is frequent and severe, being associated with an increased risk of death. Kidney disease frequently occurs in older patients. Cardiovascular and pancreatic involvement has expanded the scope of complications. A borderline association between increased levels of plasma lysine and poorer outome is suggested. Greater efforts at prevention are warranted to optimise the long-term management in these patients.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Adolescente , Adulto , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Criança , Pré-Escolar , Humanos , Lactente , Nefropatias/sangue , Nefropatias/metabolismo , Nefropatias/patologia , Nefrite Lúpica/sangue , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Lisina/sangue , Múltiplas Afecções Crônicas , Mutação , Infarto do Miocárdio/sangue , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Pancreatite/sangue , Pancreatite/metabolismo , Pancreatite/patologia , Proteinose Alveolar Pulmonar/sangue , Proteinose Alveolar Pulmonar/metabolismo , Proteinose Alveolar Pulmonar/patologia , Estudos Retrospectivos , Distúrbios Congênitos do Ciclo da Ureia/sangue , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Distúrbios Congênitos do Ciclo da Ureia/patologia , Adulto Jovem
18.
Laryngoscope ; 127(1): 140-147, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27497071

RESUMO

OBJECTIVES/HYPOTHESIS: To analyze clinical presentations, treatment modalities, and evolution of pediatric cases of salivary gland carcinomas to standardize care for these rare diseases. STUDY DESIGN: Multicentric, retrospective study. METHODS: We included in this retrospective study all children and adolescents (aged ≤18 years) treated from 1992 to 2012 in six pediatric centers in Paris, France. Pathological tumor specimens of these cases were reviewed. RESULTS: Forty-three children were included (sex ratio male/female = 19/24, median age = 13 years). The parotid gland was the most common (37 cases) location for tumors. Histological subtypes were mucoepidermoid carcinomas (n = 20), acinic cell carcinomas (n = 14), and other (n = 9). Initial fine-needle aspiration was performed in 15 cases (33%), and was concordant to final diagnosis in three cases (20%). Primary surgery was performed in 42 patients, leading to a complete microscopic resection in 80%. Associated lymph node dissection was performed in 28 patients (homolateral: 27, bilateral: 1) and showed lymph node metastases in only two patients. One patient had distant metastases. Adjuvant irradiation was delivered to 11 patients (median: 60 Gy; range: 50-65) and chemotherapy in five cases. After a median follow-up of 5 years, six tumors relapsed, but no deaths occurred. CONCLUSIONS: Childhood salivary gland carcinomas have a good prognosis despite possible recurrences. Treatment is mainly based on surgery, with simultaneous node dissection in cases of clinical or radiologic node enlargement. Radiation therapy seems to be restricted to inoperable high-grade tumors or after recurrence. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:140-147, 2017.


Assuntos
Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/terapia , Adolescente , Criança , Diagnóstico Diferencial , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Resultado do Tratamento
19.
Hum Pathol ; 58: 62-71, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27498064

RESUMO

Cherubism is a rare genetic disease characterized by bilateral giant cell reparative granuloma of the jaws consisting of a fibrotic stroma with giant multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is highly variable, and recurrence after surgery is the most important risk. Currently, there are no prognostic indicators. The aims of this study were to evaluate the osteoclastogenesis phenotype by histologic examination of nuclear factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid phosphatase (TRAP) activity and to correlate the results to disease aggressiveness to define prognostic indicators. Based on cherubism evolution 1 year after surgery, 3 classes of cherubism aggressiveness were identified: mild (group A), moderate (group B), and severe (group C). Histologically, in grade A and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1 nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all positive for TRAP activity and NFATc1 nuclear localization and displayed osteoclast-like features. Other histopathologic findings were not different among the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear localization are associated with aggressive cherubism and therefore could be added to routine pathologic examination to aid in prognosis and management of the disease. The finding of NFATc1 nuclear localization in aggressive tumors supports the addition of anticalcineurin treatment to the therapeutic arsenal for cherubism.


Assuntos
Núcleo Celular/química , Querubismo/diagnóstico , Células Gigantes/química , Arcada Osseodentária/química , Fatores de Transcrição NFATC/análise , Osteoclastos/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Biomarcadores/análise , Núcleo Celular/patologia , Querubismo/metabolismo , Querubismo/patologia , Querubismo/cirurgia , Criança , Feminino , Predisposição Genética para Doença , Células Gigantes/patologia , Humanos , Imuno-Histoquímica , Arcada Osseodentária/patologia , Masculino , Mutação , Procedimentos Cirúrgicos Ortognáticos , Osteoclastos/patologia , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de Doença , Fosfatase Ácida Resistente a Tartarato/análise , Fatores de Tempo , Resultado do Tratamento
20.
Arch Cardiovasc Dis ; 109(8-9): 465-75, 2016 Aug-Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27346323

RESUMO

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) using the bovine jugular vein Melody(®) valve (Medtronic Inc., Minneapolis, MN, USA) is safe and effective. However, post-procedural complications have been reported, the reasons for which are unclear. OBJECTIVE: To assess the impact of PPVI procedural steps on valvular histology and leaflet mechanical behaviour. METHODS: Three different valved stents (the Melody(®) valve and two homemade stents with bovine and porcine pericardium) were tested in vitro under four conditions: (1) control group; (2) crimping; (3) crimping plus inflation of low-pressure balloon; (4) condition III plus post-dilatation (high-pressure balloon). For each condition, valvular leaflets (and a venous wall sample for Melody(®) stents) were taken for histological analysis and mechanical uniaxial testing of the valve leaflets. RESULTS: Among the Melody(®) valves, the incidence of transverse fractures was significantly higher in traumatized samples compared with the control group (P<0.05), whereas the incidence and depth of transverse fractures were not statistically different between the four conditions for bovine and porcine pericardial leaflets. No significant modification of the mechanical behaviour of in vitro traumatized Melody(®) valvular leaflets was observed. Bovine and porcine pericardia became more elastic and less resilient after balloon expansion and post-dilatation (conditions III and IV), with a significant decrease in elastic modulus and stress at rupture. CONCLUSION: Valved stent implantation procedural steps induced histological lesions on Melody(®) valve leaflets. Conversely, bovine and porcine pericardial valved stents were not histologically altered by in vitro manipulations, although their mechanical properties were significantly modified. These data could explain some of the long-term complications observed with these substitutes.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Teste de Materiais/métodos , Pericárdio/transplante , Valva Pulmonar/patologia , Valva Pulmonar/cirurgia , Animais , Bovinos , Desenho de Prótese , Insuficiência da Valva Pulmonar/cirurgia , Estenose da Valva Pulmonar/cirurgia , Suínos
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