RESUMO
Congenital mesoblastic nephroma (CMN) is a rare pediatric renal tumor with low malignant potential that most commonly occurs early in infancy. Treatment strategies are based on the few published CMN series, while a significant number of CMN patients have been described in case reports. The aim of this narrative review was to create an up-to-date overview of the literature. Complete surgical removal is curative in most cases. The risk of treatment-related mortality (both surgery- and chemotherapy-related) is relatively high in the first weeks of life, indicating that these young patients deserve special attention with respect to timing and type of treatment.
Assuntos
Neoplasias Renais , Nefroma Mesoblástico , HumanosRESUMO
BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is an uncommon paediatric renal tumour. Relapses occur in about 15% of the patients. Since detailed clinical information on relapsed CCSK is scarce, the current study aims to describe outcome of patients with relapsed CCSK treated according to recent European protocols. PATIENTS AND METHODS: We analysed prospectively collected data of all CCSK patients who developed a relapse after complete remission at the end of primary treatment, entered onto SIOP and AIEOP trials between 1992 and 2012. RESULTS: Thirty-seven of 237 CCSK patients (16%) treated according to SIOP and AIEOP protocols developed a relapse. Median time from initial diagnosis to relapse was 17 months (range, 5.5 months - 6.6 years). Thirt-five out of thirty-seven relapses (95%) were metastatic; the most common sites of relapse were the brain (n=13), lungs (n=7) and bone (n=5). Relapse treatment consisted of chemotherapy (n=30), surgery (n=19) and/or radiotherapy (n=18), followed by high-dose chemotherapy and autologous bone marrow transplantation (ABMT) in 14 patients. Twenty-two out of thirty-seven patients (59%) achieved a second complete remission (CR); 15 of whom (68%) developed a second relapse. Five-year event-free survival (EFS) after relapse was 18% (95% CI: 4%-32%), and 5-year overall survival (OS) was 26% (95% CI: 10%-42%). CONCLUSIONS: In this largest series of relapsed CCSK patients ever described, overall outcome is poor. Most relapses are metastatic and brain relapses are more common than previously recognised. Intensive treatment aiming for local control, followed by high dose chemotherapy and ABMT, seems to be of benefit to enhance survival. Novel development of targeted therapy is urgently required.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Sarcoma de Células Claras/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Neoplasias Renais/patologia , Masculino , Estadiamento de Neoplasias , Estudos Prospectivos , Sarcoma de Células Claras/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Ovarian teratoma (OT) is the most common ovarian neoplasm in children. Oophorectomy has been the standard treatment but may impair fertility. The aim of this study was to investigate the feasibility and outcome of ovarian-sparing surgery (OSS) for OT. PROCEDURE: We retrospectively studied all children treated for OT at a pediatric teaching hospital in Paris, France, between March 1992 and July 2006. OSS was performed when deemed technically feasible in patients who had no lymphadenopathy by preoperative imaging or surgical exploration, normal tumor marker levels, and calcifications on radiographs. RESULTS: We identified 30 patients, including 29 with unilateral OT and 1 with synchronous bilateral OT. Emergent surgery was performed in five patients, among whom four had ovarian torsion requiring oophorectomy and one underwent OSS. Of the 26 OTs in the 25 remaining patients, 10 were managed with OSS and 16 with oophorectomy. Subsequently, ultrasound monitoring detected OT development in the contralateral ovary in 4 (14%) patients, after a median of 3 years (range, 1-14 years); OSS was performed in all four cases. The patient with bilateral synchronous OT, managed by OSS initially, underwent unilateral oophorectomy 3 years later for a recurrence. Overall OSS was performed for 15 (42%) OTs. CONCLUSIONS: Our results suggest recommendations for preserving fertility whenever possible without compromising the oncological prognosis. In particular, OSS should be reserved for patients who meet all criteria for localized mature teratoma. Long-term follow-up is crucial.
Assuntos
Infertilidade Feminina/prevenção & controle , Neoplasias Ovarianas/cirurgia , Teratoma/cirurgia , Criança , Pré-Escolar , Feminino , Fertilidade , Seguimentos , Humanos , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico por imagem , Estudos Retrospectivos , Taxa de Sobrevida , Teratoma/diagnóstico por imagem , Resultado do Tratamento , UltrassonografiaRESUMO
PURPOSE: The purpose of this study was to assess the performance of magnetic resonance imaging (MRI) in children and adolescents with suspected adnexal torsion (AT) after inconclusive initial ultrasound examination. MATERIALS AND METHODS: Twenty-eight girls with a mean age of 12±4 (SD) years (range: 1 month to 18years) were included. All had clinically suspected AT and inconclusive initial ultrasound findings followed by pelvic MRI as a second-line imaging modality. The final diagnosis was obtained by surgery or follow-up. Two radiologists blinded to the clinical, ultrasound and surgical data, retrospectively and independently reviewed MRI examinations. Clinical and MRI features associated with AT were searched for using univariate analyses. RESULT: Among the 28 patients, 10/28 patients (36%) had AT and 22/28 (79%) had an ovarian or tubal mass. AT was associated with an age<13years (OR: 10.7; 95% CI: 1.3-148.2) (P=0.022) and a whirlpool sign at MRI (OR: 61.0; median unbiased estimate, 7.2) (P<0.0001). When a mass was present, the best quantitative MRI criteria for AT were mass volume and ovary-corrected volume≥30cm3 (κ=0.72 and 0.61, respectively), mass axis length≥5cm (κ=0.90), and mass surface area≥14 cm2 (κ=0.58), with moderate to almost perfect interobserver agreement. The overall sensitivity, specificity and accuracy of MRI for the diagnosis of AT were 100% (10/10; 95% CI: 69-100), 94% (17/18; 95% CI: 73-100) and 96% (27/28; 95% CI: 82-100) respectively, with perfect interobserver agreement (κ=1). CONCLUSION: In pediatric patients with suspected AT and inconclusive initial ultrasound examination, a strategy including MRI as a second-line imaging modality should be considered if MRI does not delay a potential surgery.
Assuntos
Doenças dos Anexos , Torção Ovariana , Doenças dos Anexos/diagnóstico por imagem , Adolescente , Criança , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Anormalidade Torcional/diagnóstico por imagem , UltrassonografiaRESUMO
Chronic intervillositis is a rare condition, which is associated with severe obstetrical outcome and high recurrence rate. Obstetrical adverse events are intrauterine growth restriction, recurrent early miscarriages, intrauterine deaths and prematurity by placental insufficiency. The determination of the extension and the intensity of the chronic intervillositis are not currently standardized. High rates of recurrence have been described, but actually there is no reliable predictive biomarker. No treatment is currently validated, but the use of immunomodulatory drugs could be justified by the possible autoimmune or allo-immune origin. The treatment should be particularly discussed in patients with recurrent and severe obstetrical adverse events and in the presence of severe and massive histological lesions.
Assuntos
Doenças Placentárias/diagnóstico , Placenta/patologia , Doença Crônica , Feminino , Histiócitos/patologia , Humanos , Fatores Imunológicos/uso terapêutico , Doenças Placentárias/terapia , Gravidez , PrognósticoRESUMO
BACKGROUND: Microphthalmia Transcription Factor (MITF)family translocation renal cell carcinoma (tRCC) is a rare RCC subtype harboring TFE3/TFEB translocations. The prognosis in the metastatic (m) setting is poor. Programmed death ligand-1 expression was reported in 90% of cases, prompting us to analyze the benefit of immune checkpoint inhibitors (ICI) in this population. PATIENTS AND METHODS: This multicenter retrospective study identified patients with MITF family mtRCC who had received an ICI in any of 12 referral centers in France or the USA. Response rate according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. Genomic alterations associated with response were determined for 8 patients. RESULTS: Overall, 24 patients with metastatic disease who received an ICI as second or later line of treatment were identified. Nineteen (82.6%) of these patients had received a VEGFR inhibitor as first-line treatment, with a median PFS of 3 months (range, 1-22 months). The median PFS for patients during first ICI treatment was 2.5 months (range, 1-40 months); 4 patients experienced partial response (16,7%) and 3 (12,5%) had stable disease. Of the patients whose genomic alterations were analyzed, two patients with mutations in bromodomain-containing genes (PBRM1 and BRD8) had a clinical benefit. Resistant clones in a patient with exceptional response to ipilimumab showed loss of BRD8 mutations and increased mutational load driven by parallel evolution affecting 17 genes (median mutations per gene, 3), which were enriched mainly for O-glycan processing (29.4%, FDR = 9.7 × 10- 6). CONCLUSIONS: MITF family tRCC is an aggressive disease with similar responses to ICIs as clear-cell RCC. Mutations in bromodomain-containing genes might be associated with clinical benefit. The unexpected observation about parallel evolution of genes involved in O-glycosylation as a mechanism of resistance to ICI warrants exploration.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/genética , Imunomodulação/efeitos dos fármacos , Neoplasias Renais/genética , Fator de Transcrição Associado à Microftalmia/genética , Família Multigênica , Translocação Genética , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Feminino , Genômica/métodos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Fator de Transcrição Associado à Microftalmia/antagonistas & inibidores , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Cytokines produced at the fetal-maternal interface play a key role in regulating maternal tolerance to the fetus and successful pregnancy. Previously, we showed that EBV-induced gene 3 (EBI3), an interleukin (IL)-12 p40 homologue, was expressed at very high levels by syncytiotrophoblasts and extravillous trophoblasts throughout human pregnancy. EBI3 was recently shown to associate with a novel ligand, p28, to form a new heterodimeric cytokine with important immunoregulatory functions, IL-27. In this study, we investigated whether EBI3 expression by trophoblast cells is associated with that of p28 to form IL-27. We found that genes encoding IL-27 (EBI3 and p28) and its receptor (IL-27R and gp130) were expressed in the placenta at various stages of pregnancy. Co-immunoprecipitation experiments performed from placental lysates, and ELISA of culture supernatants from placental explants, showed that IL-27 heterodimer was produced and released from placental cells. In situ studies of placentae of first, second and third trimester of pregnancy, and of choriocarcinomas, demonstrated that syncytiotrophoblast cells co-expressed EBI3 and p28. Similarly, extravillous trophoblast cells invading the decidua were found to co-express both subunits of IL-27. These data suggest that IL-27 may be part of the cytokine network regulating local immune responses and angiogenesis during human pregnancy.
Assuntos
Interleucina-17/metabolismo , Placenta/imunologia , Trofoblastos/imunologia , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/imunologia , Idade Gestacional , Humanos , Imuno-Histoquímica , Interleucina-17/genética , Interleucinas/genética , Interleucinas/metabolismo , Antígenos de Histocompatibilidade Menor , Gravidez , RNA/biossíntese , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos/citologiaRESUMO
The literature is rich in case reports of intraosseous haemangioma, although most of these are actually cases of venous or capillary malformations. To illustrate this confusion in terminology, we present three cases of slow-flow vascular malformations misnamed as intraosseous haemangioma. A retrospective study of children diagnosed with intraosseous haemangioma was conducted. Clinical and radiological data were evaluated. Histopathological examinations and immunohistochemical studies were redone by three independent pathologists to classify the lesions according to the International Society for the Study of Vascular Anomalies (ISSVA) and World Health Organization (WHO) classifications. Three children who had presented with jaw haemangiomas were identified. Computed tomography scan patterns were not specific. All tumours were GLUT-1-negative and D2-40-negative. The lesions were classified as central haemangiomas according to the WHO, and as slow-flow malformations according to the ISSVA. The classification of vascular anomalies is based on clinical, radiological, and histological differences between vascular tumours and malformations. Based on this classification, the evolution of the lesion can be predicted and adequate treatment applied. The binary ISSVA classification is widely accepted and should be applied for all vascular lesions.
Assuntos
Hemangioma/classificação , Neoplasias Maxilomandibulares/classificação , Crânio/anormalidades , Coluna Vertebral/anormalidades , Terminologia como Assunto , Malformações Vasculares/classificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.
Assuntos
Neoplasias Renais/tratamento farmacológico , Tumor de Wilms/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Resultado do Tratamento , Tumor de Wilms/mortalidade , Tumor de Wilms/patologiaRESUMO
Interstitial duplications of chromosomal region 1q are rarely seen. We report the first prenatal diagnosis of pure partial trisomy 1q. The fetus was karyotyped for polyhydramnios, micrognathia, and flexion of fingers of both hands. Conventional and molecular cytogenetics showed a de novo direct duplication of the chromosomal region 1q23.1q31.1 leading to a partial trisomy 1q. At autopsy, the fetus showed Pierre Robin sequence (PRS) and camptodactyly. The main histological finding was a decreased number of motoneurons with apoptotic features in the anterior horn of the spinal cord. A literature review and our observations suggest that genetic material mapping to chromosome 1q25 could be responsible for PRS with distal arthrogryposis when this is in triple dose.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , Deformidades Congênitas da Mão/genética , Síndrome de Pierre Robin/genética , Bandeamento Cromossômico , Evolução Fatal , Morte Fetal , Duplicação Gênica , Humanos , Hibridização in Situ Fluorescente , CariotipagemRESUMO
Wegener's granulomatosis (WG) is an inflammatory, destructive, angiotropic lesion. The inflammatory process involves accumulation of macrophages, lymphocytes, and polymorphonuclear neutrophils. We studied 6 lung biopsy specimens from patients with WG to characterize the cellular infiltrate and to analyze the mechanism of immune cell recruitment. We show that lymphocytes accumulating in WG lesions are mostly memory CD4(+)CD45RO(+) T lymphocytes and, although less numerous, CD8(+)CD45RO(+) T lymphocytes. Few if any B lymphocytes or natural killer cells are present within lesions. The chemokine RANTES (regulated upon activation in normal T cells, expressed and secreted) has been reported to recruit memory T lymphocytes and macrophages selectively. We used reverse-transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry to study its production in WG. RANTES was expressed at a higher level in WG lungs than in normal controls, especially around microabscesses. As visualized immunohistochemically in serial sections with anti-RANTES monoclonal antibody, RANTES production was produced mainly by macrophages. Expression of the gene coding for interferon-gamma (IFN-gamma), a potent RANTES inducer, was also studied. Its expression was also much stronger in WG than in controls. Our observations are consistent with a cascade of events leading to the recruitment of immune cells in WG, sequentially involving production of IFN-gamma by T lymphocytes and RANTES production by macrophages, leading to the homing of memory T-helper lymphocytes and macrophages. HUM PATHOL 32:320-326.
Assuntos
Quimiocina CCL5/genética , Expressão Gênica , Granulomatose com Poliangiite/metabolismo , Pneumopatias/metabolismo , Adulto , Idoso , Anticorpos Monoclonais , Linfócitos B/química , Linfócitos B/patologia , Biópsia , Linfócitos T CD4-Positivos/química , Linfócitos T CD4-Positivos/patologia , Quimiocina CCL5/análise , Feminino , Granulomatose com Poliangiite/patologia , Humanos , Imuno-Histoquímica , Hibridização In Situ , Interferon gama/genética , Antígenos Comuns de Leucócito/análise , Pneumopatias/patologia , Macrófagos/química , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/química , Linfócitos T/patologiaRESUMO
The usefulness of post-mortem microbiology in the assessment of sudden unexpected deaths in infants and children has been debated by many pathologists. In our centre, microbiological investigations have been part of the post-mortem protocol for investigation of sudden deaths in infants and children for the past 12 years. The objective of this study was to review the microbiological findings for infants and children examined by our unit during the past 4 years in relation to gross and histological findings of the autopsy and the medical and social histories of the children. We reviewed 57 consecutive sudden deaths in infants and children examined by our Referral Centre between November 1994 and October 1998. These 57 sudden deaths were aged from 1 day to 4 years and 9 months including 40 cases of sudden infant death syndrome (SIDS) and 17 non-SIDS deaths. Results of the microbiological investigations of tissues and body fluids were assessed during the case review with reference to histological shock signs, severe gastric aspiration, and signs of acute thymic involution. Bacteria alone or in association with viruses were identified in 45/57 (79%) cases including 34/40 (85%) SIDS. The most frequent bacterial isolate was Escherichia coli (27), and the virus identified most frequently was enterovirus (8). C-reactive protein was increased in 10 out of the 42 cases tested including 8/32 (25%) SIDS. Significant gastric content aspiration was found in 17/57 (29.8%) including 13/40 (32.5%) SIDS. Histological signs of shock were present in 33/55 (60%) cases including 22/39 SIDS (56.4%). The microbiological findings were positive for 27/33 (81.8%). We conclude that post-mortem microbiology is essential in sudden death investigation. The conclusion that a death is unexplained if no microbiology was done is not valid, even if in some cases it may be difficult to know precisely in what way the pathogen contributed to the death.
Assuntos
Microbiologia , Morte Súbita do Lactente/etiologia , Autopsia , Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Viroses/virologia , Vírus/classificação , Vírus/isolamento & purificaçãoRESUMO
Chondrolipoma is a rare condition; especially in the oral cavity. The authors described a giant chondrolipoma of the tongue, associated with mandibular and lower lip overgrowth, in a 14-year-old boy. After tumour excision, histopathological examination showed mature cartilage within lobules of mature adipocytes. This is the first case of giant chondrolipoma associated with facial overgrowth. The aetiology and the association with a localized Proteus syndrome are discussed.
Assuntos
Hiperostose/diagnóstico , Doenças Mandibulares/diagnóstico , Mesenquimoma/diagnóstico , Neoplasias da Língua/diagnóstico , Adipócitos/patologia , Adolescente , Cartilagem/patologia , Diagnóstico Diferencial , Crescimento Excessivo da Gengiva/diagnóstico , Humanos , Macroglossia/diagnóstico , Masculino , Mordida Aberta/diagnóstico , Síndrome de Proteu/diagnósticoRESUMO
Castleman disease (CD) is a benign lymphoproliferative disorder, rare in children. Head and neck localizations are found only in 14 % of the cases. Two forms have been described: a hyaline vascular type and a plasma cell type. It can also be monocentric or multicentric. Both young patients were affected with an isolated neck localization of Castleman disease. Preoperative diagnosis can be difficult with a thymoma or a lymphoma. CT and MRI can help in the diagnosis, which is confirmed by histopathological assessment. The pathological features and the therapeutic management of CD are discussed. While surgery is the treatment for localized lesions, steroids and chemotherapy are indicated in the multicentric type. Because of the risk of relapse and malignant transformation, long-term follow-up is mandatory.
Assuntos
Hiperplasia do Linfonodo Gigante/diagnóstico , Doenças do Colo do Útero/patologia , Adolescente , Hiperplasia do Linfonodo Gigante/classificação , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Doenças do Colo do Útero/diagnóstico , Doenças do Colo do Útero/terapiaAssuntos
Quimiocinas CXC/metabolismo , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta/metabolismo , Âmnio/metabolismo , Quimiocina CXCL12 , Feminino , Idade Gestacional , Humanos , Imuno-Histoquímica , Placenta/citologia , Gravidez , Complicações Infecciosas na GravidezRESUMO
Epstein-Barr virus (EBV)-induced gene 3 (EBI3) is expressed by tumour cells in several EBV-associated malignancies. EBI3 was recently found to associate with a novel peptide, p28, to form a new heterodimeric cytokine, called interleukin-27. In this study, we investigated EBI3 and p28 expression in normal human B lymphocytes and in non-EBV-associated B-cell lymphomas. Low levels of EBI3 were detected in purified tonsillar B cells and expression was upregulated upon anti-CD40 or anti-micro stimulation via NF-kappaB activation. In non-neoplastic tissues, EBI3 expression by lymphocytes was largely restricted to a subset of germinal centre (GC) B cells located at the margin of the light zone, in close contact with CD3+ T lymphocytes. Over 50% of EBI3+ GC B cells were engaged in cell proliferation as assessed by Ki67 expression, and 10-30% expressed MUM1, an early marker of plasma cell differentiation expressed by late centrocytes. Many EBI3+ GC B cells had downregulated bcl-6 expression, which further suggests that these cells correspond to late CD40-activated centrocytes. Immunohistochemical analysis of 64 B-cell lymphomas showed that the highest EBI3 levels were detected in follicular lymphomas and in diffuse large B-cell lymphomas of both GC B-cell-like or non-GC B-cell-like types. No or rare p28 expression was detected in normal or tumour B cells. This constitutive expression of EBI3 by neoplastic B cells may be involved in lymphomagenesis, and may be a useful marker for lymphoma diagnosis.
Assuntos
Linfócitos B/virologia , Interleucinas/biossíntese , Linfoma de Células B/virologia , Linfócitos B/citologia , Linfócitos B/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Interleucinas/genética , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Linfoma Folicular/metabolismo , Linfoma Folicular/virologia , Antígenos de Histocompatibilidade Menor , Tonsila Palatina/virologia , Subunidades Proteicas/biossíntese , Subunidades Proteicas/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
In human pregnancy, trophoblasts are the only cells of fetal origin in direct contact with the maternal immune system: syncytiotrophoblasts are in contact with maternal blood, whereas extravillous trophoblasts are in contact with numerous maternal uterine natural killer (NK) cells. Therefore, trophoblasts are thought to play a key role in maternal tolerance to the semiallogeneic fetus, in part through cytokine production and NK cell interaction. Epstein-Barr virus-induced gene 3 (EBI3) encodes a soluble hematopoietin receptor related to the p40 subunit of interleukin-12. Previous studies indicated that EBI3 is expressed in the spleen and tonsils, and at high levels in full-term placenta. To investigate further EBI3 expression throughout human pregnancy, we generated monoclonal antibodies specific for EBI3 and developed an EBI3 enzyme-linked immunosorbent assay. Immunohistochemical experiments with EBI3 monoclonal antibody on first-, second-, and third-trimester placental tissues demonstrated that EBI3 was expressed throughout pregnancy by syncytiotrophoblasts and extravillous trophoblasts (cytotrophoblast cell columns, interstitial trophoblasts, multinucleated giant cells, and trophoblasts of the chorion laeve). EBI3 expression was also induced during in vitro differentiation of trophoblast cell lines. In addition, large amounts of secreted EBI3 were detected in explant cultures from first-trimester and term placentae. Consistent with these data, EBI3 levels were strongly up-regulated in sera from pregnant women and gradually increased with gestational age. These data, together with the finding that EBI3 peptide is presented by HLA-G, suggest that EBI3 is an important immunomodulator in the fetal-maternal relationship, possibly involved in NK cell regulation.
Assuntos
Glicoproteínas/metabolismo , Gravidez/metabolismo , Receptores de Citocinas , Trofoblastos/fisiologia , Anticorpos Monoclonais , Diferenciação Celular/fisiologia , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Técnicas de Cultura , Feminino , Idade Gestacional , Glicoproteínas/sangue , Humanos , Imuno-Histoquímica/métodos , Interleucinas , Antígenos de Histocompatibilidade Menor , Trofoblastos/citologia , Células Tumorais Cultivadas , Regulação para Cima , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologiaRESUMO
We report the first case of obstructive cholangitis after laparoscopic cholecystectomy, related to intraperitoneal retained gallstones.
Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Icterícia/etiologia , Idoso , Humanos , MasculinoRESUMO
Fractalkine is the only member of the CX3C chemokine family. Polymorphism of the fractalkine receptor gene may influence the prognosis of human immunodeficiency virus (HIV) infection, but the nature of the cells expressing fractalkine or its receptor in HIV-infected patients remains unknown. We show that, in contrast to HIV-uninfected individuals, a large number of cells expressed fractalkine in T-cell zones of lymph nodes from HIV-infected patients. CD83(+) mature and CD123(+) plasmacytoid dendritic cells as well as plasma cells are involved in this increased expression of fractalkine. Increased numbers of plasmacytoid dendritic cells and plasma cells were present in T-cell zones of HIV-infected patients. CD83(+) dendritic cells were present in similar number in HIV-infected patients and controls, but an increased fraction of these cells produced fractalkine in HIV-infected patients. Many plasma cells in the gut-associated lymphoid tissue from HIV-infected patients also produced fractalkine, whereas few cells produced fractalkine in the gut of controls. The fraction of CD45RO(+) and CD45RO(-) T helper (Th) cells expressing the fractalkine receptor CX3CR1 was higher in HIV-infected patients than in healthy individuals, and these cells were abnormally sensitive to fractalkine stimulation. This increased response correlated with HIV viremia, and it returned to normal levels in patients successfully treated with antiretroviral drugs. The increased expression of the fractalkine/fractalkine receptor complex associated with HIV infection may affect adhesion and migration of Th lymphocytes and their interaction with dendritic cells. Thus, it may influence the equilibrium between depletion and renewal of the Th lymphocyte compartment.
Assuntos
Quimiocinas CX3C/biossíntese , Infecções por HIV/imunologia , HIV-1 , Proteínas de Membrana/biossíntese , Receptores de Citocinas/metabolismo , Receptores de HIV/metabolismo , Antígenos CD , Contagem de Linfócito CD4 , Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Quimiocinas CX3C/genética , Células Dendríticas/química , Células Dendríticas/imunologia , Duodeno/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/crescimento & desenvolvimento , Humanos , Imunoglobulinas/análise , Interleucina-2/farmacologia , Subunidade alfa de Receptor de Interleucina-3 , Linfonodos/imunologia , Glicoproteínas de Membrana/análise , Proteínas de Membrana/genética , Plasmócitos/imunologia , RNA Mensageiro/biossíntese , Receptores de Citocinas/fisiologia , Receptores de HIV/fisiologia , Receptores de Interleucina-3/análise , Linfócitos T Auxiliares-Indutores/imunologia , Transcrição Gênica , Regulação para Cima , Carga Viral , Antígeno CD83RESUMO
Expression and function of the fractalkine receptor CX3CR1 by T lymphocyte subpopulations was evaluated in healthy individuals. In CD8(+) T lymphocytes, CX3CR1 was expressed by and functional in both CD45RO(-) and CD45RO(+) cells. In CD4(+) T lymphocytes, CX3CR1 was expressed mainly by CD45RO(+) cells, and almost exclusively by activated HLA-DR(+) T lymphocytes. This receptor was functional in CD45RO(+) cells, but not in CD45RO(-) cells. Expression of fractalkine was detected by in situ hybridization and immunohistochemistry in endothelial cells of normal lung and thymus. In hyperplastic lymph nodes, fractalkine was expressed by endothelial cells of high endothelial venules and of subcapsular vessels, by follicular dendritic cells (FDC) and by some follicle lymphocytes. Fractalkine mRNA was constitutively present in the HK FDC-like cell line, and it was induced in vitro in B lymphocytes stimulated by an anti-micro or by a CD40 mAb. These findings indicate that fractalkine may contribute to the recruitment of effector T helper lymphocytes, either in peripheral tissues or in lymphoid organs. In these tissues, fractalkine and its receptor may favor contact within follicles between activated T helper lymphocytes, activated B lymphocytes and FDC, thus contributing to the maturation of the B lymphocyte response.