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1.
PLoS One ; 14(3): e0197655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30897085

RESUMO

The pathogenesis of thymic epithelial tumors remains poorly elucidated. The PIK3/Akt/mTOR pathway plays a key role in various cancers; interestingly, several phase I/II studies have reported a positive effect of mTOR inhibitors in disease control in thymoma patients. A major limit for deciphering cellular and molecular events leading to the transformation of thymic epithelial cells or for testing drug candidates is the lack of reliable in vitro cell system. We analyzed protein expression and activation of key players of the Akt/ mTOR pathway namely Akt, mTOR, and P70S6K in eleven A, B and AB thymomas as well as in normal thymuses. While only Akt and phospho-Akt were expressed in normal thymuses, both Akt and mTOR were activated in thymomas. Phospho-P70S6K was expressed in all thymic tumors whatever their subtypes, and absent in normal thymus. Interestingly, we report the activation of Akt, mTOR and P70S6 proteins in primary thymic epithelial cells maintained for short period of time after their derivation from seven AB and B thymomas. Finally, we showed that rapamycin (100 nM) significantly reduced proliferation of thymoma- derived epithelial cells without inducing cell death. Our results suggest that the activation of the Akt/ mTOR pathway might participate to the cell proliferation associated with tumor growth. Ultimately, our data enhance the potential role of thymic epithelial cells derived from tissue specimens for in vitro exploration of molecular abnormalities in rare thymic tumors.

2.
Am J Hum Genet ; 104(2): 213-228, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30639323

RESUMO

Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n = 14), congenital alveolar dysplasia (n = 2), and other lethal lung hypoplasias (n = 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n = 8 and n = 2, respectively) or FGF10 (n = 2 and n = 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping ∼2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung.

3.
Am J Surg Pathol ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30451731

RESUMO

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with an aggressive clinical course and specific genetic alterations of the BAF chromatin remodeling complex. In the present study, we reviewed the clinical and pathologic features of 30 cases of SMARCA4-DTS, discussed its main differential diagnoses and the challenging diagnostic scenarios that the average pathologist may face. In addition, we tested the specificity of the "SMARCA4-DTS immunohistochemical signature" (co-loss of SMARCA4 and SMARCA2 with overexpression of SOX2) in a large cohort of intrathoracic malignancies. Patients ranged from 28 to 90 years of age (median: 48 y), with a marked male predominance (male:female=9:1) and they were usually smokers. Tumors were generally large compressive masses located in the mediastinum (n=13), pleura (n=5), lung (n=2) or in 2 or more of these topographies (n=10). Treatment strategies were varied, including 1 case treated with EZH2 inhibitors. Median overall survival was 6 months. Histologically, tumors were poorly differentiated frequently showing rhabdoid features. A subset of cases showed a focal myxoid stroma (7%, n=2/30) and rare cases displayed a previously unreported pattern simulating desmoplastic small round cell tumors (7%, n=2/30). Making a diagnosis was challenging when dealing with biopsy material from massively necrotic tumors and in this setting the expression of SOX2, CD34, and SALL4 proved useful. All tested cases displayed concomitant loss of SMARCA4 and SMARCA2 and most tumors expressed epithelial markers (Pan-keratin or EMA) (n=29/30), SOX2 (n=26/27), and CD34 (n=17/27). SMARCB1 expression was retained in all cases (23/23). SALL4 and Claudin-4 were expressed in a subset of cases (n=7/21 and 2/19, respectively). TTF-1 and P63 were focally expressed in 1 case each. P40 and NUT were not expressed (0/23 and 0/20, respectively) The SMARCA4-DTS immunohistochemical signature was both sensitive and specific, with only a subset of small cell carcinoma of the ovary hypercalcemic type showing overlapping phenotypes. Our study confirms and expands the specific features of SMARCA4-DTS, emphasizing the fact that they can be straightforwardly identified by pathologists.

4.
Ann Thorac Surg ; 2018 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-30253161

RESUMO

Several surgical procedures, from debulking to extra pleural pneumonectomy, may be applied for stage IVa Masaoka thymomas but their efficiency is still controversial. Case studies favored R0 resection as the cornerstone of multimodal therapy for loco-regional metastatic extension. We report our standardized procedure associating cytoreductive surgery and intra thoracic chemo hyperthermia on a 46-years old patient presenting B2 thymoma and synchronous unilateral pleural metastasis.

5.
Ann Pathol ; 38(3): 202-205, 2018 Jun.
Artigo em Francês | MEDLINE | ID: mdl-29555057

RESUMO

Multiple lung carcinomas are 5 to 11,5% of lung carcinomas. The distinction between primary lung carcinomas from carcinomas with intrapulmonary metastasis is essential for optimal patient management. The histopathological analysis is very useful but it has to be completed by genotypic assessment using molecular biology (NGS). Molecular biology can also identify genetic alterations with therapeutic implications. We present the case of a patient with a history of surgery for multiple lung carcinomas diagnosed from 2013 to 2017.

6.
Lung Cancer ; 118: 62-68, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29572005

RESUMO

INTRODUCTION: The systematic assessment of anti-programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in lung adenocarcinomas is becoming standard practice. However, the assessment of PD-L1 expression on small tissue specimens needs to be evaluated and the association with other features more thoroughly analyzed. METHODS: This retrospective single center study evaluated the immunohistochemical expression of the SP263 anti-PD-L1 antibody on tissue microarrays (TMA) of 152 surgically resected lung adenocarcinomas, using a 25% positivity threshold. The positive cases and 50 randomly chosen negative cases in tissue microarray (TMA) were reassessed on whole tissue sections. The results were correlated to clinical, histopathological and to molecular data obtained through the screening of 214 mutations in 26 genes (LungCarta panel, Agena Biosciences). RESULTS: Among 152 primary lung adenocarcinomas, 19 cases (13%) showed PD-L1 expression. The agreement between TMA and whole tissue sections was 89%, specificity was 97%. PD-L1 expression was correlated to RAS mutations (p = .04), RAS/TP53 co-mutations (p = .01) and to the solid or acinar subtype (p = .048). CONCLUSIONS: With the SP263 PD-L1 antibody, small samples appear as a reliable means to evaluate the PD-L1 status in lung adenocarcinoma. The association between PD-L1 expression and RAS/TP53 mutations may have clinical relevance to predict the efficacy of PD-1/PD-L1 immune checkpoints inhibitors.

7.
J Thorac Oncol ; 12(10): 1571-1581, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28694035

RESUMO

INTRODUCTION: Thymic epithelial tumors (TETs) are rare intrathoracic malignancies that are categorized histologically according to the WHO classification, which was recently updated in 2015 on the basis of a consensus statement of the International Thymic Malignancy Interest Group (ITMIG); at the same time, the standard Masaoka-Koga staging system is scheduled to be replaced by the eighth edition of the TNM staging classification by the American Joint Committee on Cancer/Union for International Cancer Control consortium. Our objectives were to analyze the feasibility of assessing ITMIG consensus major and minor morphological and immunohistochemical criteria and the eighth edition of the TNM staging classification in a routine practice setting. METHODS: This is a single-center study conducted at the Louis-Pradel Hospital of Lyon University, one of the largest centers for TETs in France. Overall, a large surgical series of 188 TETs diagnosed in 181 patients between 2000 and 2014 at our center were analyzed. RESULTS: There were 89 men (49%) and 92 women (51%); 57 patients (31%) presented with myasthenia gravis at time of diagnosis. According to the WHO classification, there were nine type A thymomas (5%), 67 type AB thymomas (36%), 19 type B1 thymomas (10%), 46 type B2 thymomas (24%), 27 type B3 thymomas (14%), and 20 thymic carcinomas (11%). ITMIG consensus major criteria were identified in 100% of type A, AB, B1, and B2 thymomas. After restaging according to the eighth edition of the TNM staging classification, there were 127 stage I (84%), three stage II (2%), 17 stage IIIa (11%), no stage IIIb, two stage IVa (1%), and three stage IVb (2%) thymomas. Significant correlation between histological type and stage at diagnosis was maintained after restaging according the TNM classification. CONCLUSION: Comprehensive analysis of our well-characterized surgical series of 188 TETs indicates the feasibility and the diagnostic value of the ITMIG consensus statement on WHO histological classification and highlights the major switch in staging when the eighth edition of the TNM staging classification is applied.


Assuntos
Neoplasias Epiteliais e Glandulares/classificação , Neoplasias do Timo/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/patologia , Organização Mundial da Saúde
8.
Nanoscale ; 9(46): 18246-18257, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-28726968

RESUMO

Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic X-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. In particular, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R2 = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R2 = 0.93). TEM results were in agreement with the imaging and ICP-OES in that much higher concentrations of AuNPs were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT can be used for repetitive and non-invasive determination of the biodistribution of gold nanoparticles in vivo.

9.
Lung Cancer ; 108: 1-6, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28625619

RESUMO

BACKGROUND: Pleural recurrences are a hallmark of thymomas, and represent a challenge for multidisciplinary management. The purpose of this study was to assess the feasibility and the results in terms of morbidity, mortality and survival rates, of Intra-Thoracic Chemo-Hyperthermia (ITCH) for the treatment of pleural recurrences of thymomas. METHODS: Retrospective analysis of 19 consecutives patients between 1997 and 2015 treated by surgical cytoreduction (pleurectomy) followed by ITCH with 25mg/m2 of mitomycin, and 50mg/m2 of Cisplatin. RESULTS: There were 8 men and 11 women with a median age of 44 years. ITCH was combined with pleurectomy alone in 4 (22%) patients, pleurectomy and wedge resections in 14 (74%) patients; 1 (5%) patient had a pleuropneumonectomy. There were no perioperative deaths, and 5 patients (26%) presented with postoperative complication, including 3 (16%) cases related to chemotherapy (one case of reversible grade 2 bone marrow aplasia, and 2 cases of reversible, acute kidney failure). The median length of stay in intensive care unit and hospital were 1day and 10days, respectively. After a median follow-up period of 39 months (range 10-127 months), median disease-free survival was 42 months. Five patients (26%) died during follow-up. CONCLUSIONS: Our data indicate that ITCH is a feasible option for selected patients with pleural recurrence of thymomas. ITCH clearly provides long local control, without major safety issues, and prolonged survival may be achieved in selected patients. This therapeutic option should be discussed at a multidisciplinary tumor board.


Assuntos
Quimioterapia Adjuvante , Hipertermia Induzida , Neoplasias Pleurais/secundário , Neoplasias Pleurais/terapia , Timoma/patologia , Adulto , Idoso , Terapia Combinada , Comorbidade , Procedimentos Cirúrgicos de Citorredução , Feminino , Seguimentos , Humanos , Hipertermia Induzida/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Timoma/diagnóstico , Timoma/mortalidade , Resultado do Tratamento , Adulto Jovem
10.
Hematol Oncol ; 35(4): 510-519, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27140394

RESUMO

Primary cardiac lymphoma (PCL) represents a rare subset of extranodal lymphomas for which the primary lesion arises from the heart and/or the pericardium. Fundamental characteristics of PCL remain uncertain, regarding optimal diagnosis strategy, pathological features, treatments, as well as prognostic factors. This is a single-institution retrospective study of patients with histologically proven lymphoma, presenting with exclusive or predominant myocardial invasion at time of diagnosis. Thirteen patients were included, all of whom had symptoms related to cardiac tumour location with chronic chest pain in six (46%), dyspnea in seven (54%) and arythmia in three (23%). Sub-acute and acute congestive heart failure were noticed in respectively nine (70%) and one (9%). PCL was identified at transthoracic echocardiography and computed tomography scan in 80 and 100% of patients, respectively. Most frequent location was the right atrium in 10 (77%) patients. Pericardial effusion was identified in 10 (77%). Pathological diagnosis-diffuse large B-cell lymphoma in 12 cases and Burkitt in 1 case-was made on cardiac surgical biopsies in 9 cases and by intravascular procedure in 2 cases. All patients received first-line chemotherapy, with a complete response rate of 62%. Recurrences occurred in 55% of patients, mostly at extracardiac extranodal sites. Our data confirm that PCL harbours specific clinical and anatomical features. The aggressiveness of PCL mainly results from the possible onset of acute cardiac events. Further molecular characterization may help to further individualize PCL among diffuse and intrathoracic lymphomas. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Neoplasias Cardíacas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Neoplasias Cardíacas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Ann Pathol ; 36(3): 214-7, 2016 Jun.
Artigo em Francês | MEDLINE | ID: mdl-27234518

RESUMO

Primary cardiac tumors are extremely rare and mainly benign. The majority of these are myxomas (40%). Myxoma are generally sporadic tumors which occur most commonly in adult females between 30 and 40 years, and are seldom found in the paediatric population (5%). Seven percent are associated with igenetic diseases. We report the case of an eight-year-old boy presenting a recurrent glandular cardiac myxoma. In 2011, he presented a deterioration of the general state. An echocardiography highlighted a left atrial mass on the interatrial septum, with a pedicular insertion. On the microscope, it consisted of a proliferation of stellate cells isolated or clustered in rudimentary vessels in a myxoid stroma presenting haemorrhage changes. These cells expressed CD34 and calretinine. Glandular elements without atypia were clustered within the myxomatous proliferation. They expressed cytokeratin (CK) 7. Surgical resection was macroscopically complete. In 2014, the boy had a sudden neurological deficit during a football match. An echocardiography revealed a recurrence at the same location. The lesion was excised and addressed in several fragments. Classical myxoma was associated with glands without atypia. This last component expressed CKAE1/AE3 and CK7. Ki67 index of proliferation was low. The surgical reintervention was macroscopically complete. The final diagnosis was glandular cardiac myxoma. A genetic survey was conducted, showing the presence of Carney complex. This is the first description in the litterature of a recurrent glandular cardiac myxoma occuring in a child.


Assuntos
Neoplasias Cardíacas/diagnóstico , Mixoma/diagnóstico , Criança , Átrios do Coração/patologia , Neoplasias Cardíacas/terapia , Humanos , Masculino , Mixoma/terapia
12.
Ann Pathol ; 36(2): 111-9, 2016 Apr.
Artigo em Francês | MEDLINE | ID: mdl-26995100

RESUMO

INTRODUCTION: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD. MATERIALS AND METHODS: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis. RESULTS: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation. DISCUSSION AND CONCLUSION: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect.


Assuntos
Biomarcadores Tumorais/análise , Mesotelioma/química , Proteínas de Neoplasias/análise , Neoplasias Pleurais/química , Proteínas Supressoras de Tumor/análise , Ubiquitina Tiolesterase/análise , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Aconselhamento Genético , Humanos , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologia , Sensibilidade e Especificidade
13.
Pathol Res Pract ; 211(12): 996-1002, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26534878

RESUMO

OBJECTIVES: Glucose-transporter-1 (Glut-1) may be a useful marker for differentiating B3 thymomas and thymic carcinomas. Since the literature is limited, we undertook a study to evaluate its diagnostic value in a series of thymic epithelial tumors. MATERIALS AND METHODS: Glut-1 expression was studied by the group of pathologists linked to the French national oncological network RYTHMIC. Immunostaining was performed on a whole section of one paraffin block in a series of 92 successive surgical specimens. Patterns (focal, zonal, diffuse) and intensity of Glut-1 expression were assessed and compared with WHO histological subtypes. RESULTS: Expression was mainly restricted to epithelial cells. Immature T-lymphocytes were negative. A diffuse, moderate or strong staining was observed in most thymic carcinomas (15/16). In B3 thymomas (10/11) and in B3 thymomas borderline to thymic carcinomas (5/6), a moderate to strong zonal staining was observed at distance from vessels and fibrous septa. This pattern sometimes created the aspect of an anastomosing network in large cellular lobules. In B1 thymomas, immunostaining highlighted foci of medullary differentiation (7/8). B2 thymomas (n=25) were heterogeneous, with a spectrum of patterns ranging between those of B1 and B3 thymomas. Type A thymomas (n=5) mostly presented a weak positivity but one aggressive case showed zonal moderate/strong positivity. Most AB thymomas (15/17) showed weak to moderate immunostaining in spindle cell areas. In micronodular thymomas (n=3), epithelial cells and B-lymphocytes were weakly positive while follicular dendritic cells were strongly highlighted. One metaplastic thymoma displayed diffuse and moderate positivity. CONCLUSION: Glut-1 expression globally depended on histological subtypes and the staining patterns (diffuse or zonal) were different between thymic carcinomas and type B3 thymomas. A comparative study of Glut-1 expression in atypical versus conventional type A thymomas appears warranted. Otherwise, restriction to epithelial cells makes likely a correlation with clinical assessment of glucose uptake in lymphocyte-poor tumors.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/patologia , Transportador de Glucose Tipo 1/biossíntese , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias do Timo/patologia , Transportador de Glucose Tipo 1/análise , Humanos , Imuno-Histoquímica
14.
Ann Pathol ; 35(6): 515-8, 2015 Dec.
Artigo em Francês | MEDLINE | ID: mdl-26608111

RESUMO

Calcifying fibrous tumor is a rare soft tissue benign tumor (OMS 2002). Some pleural localisations are described, which affect slightly older individuals than the other soft tissue forms. The calcifying fibrous tumor is included in the 2004 World Health Organization classification of pleural tumors. A pleural tumor located in the right inferior pulmonary lobe is diagnosed in a 59-year-old man. This pleural tumor is macroscopically well-circumscribed. Histologically, the rare spindle tumoral cells are located between bundles of a collagenous tissue, sometimes hyalinized, with psammomatous or dystrophic calcifications. The tumoral cells have a fibrohistiocytic origin. They stain positively for antibodies against vimentin, factor XIIIa, CD68, CD163, CD34. Antibodies against smooth muscle actin, desmin, PS100, ALK1 and EBV are negative. Main differencial diagnoses are other benign pleural tumors (solitary fibrous tumor, inflammatory myofibroblastique tumor), some malignant tumors (desmoplastic malignant pleural mesothelioma) and pleural pseudotumors (calcified pleural plaques, chronic fibrous pleuritis, amylose, hyalinizing granuloma). Our case is the 15th pleural calcifying fibrous tumor being reported.


Assuntos
Calcinose/diagnóstico , Neoplasias de Tecido Fibroso/diagnóstico , Neoplasias Pleurais/diagnóstico , Antígenos CD/análise , Biomarcadores Tumorais/análise , Calcinose/metabolismo , Calcinose/patologia , Diagnóstico Diferencial , Fator XIIIa/análise , Granuloma de Células Plasmáticas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Miofibroblastos/química , Miofibroblastos/patologia , Neoplasias de Tecido Fibroso/química , Neoplasias de Tecido Fibroso/patologia , Neoplasias Pleurais/química , Neoplasias Pleurais/patologia , Tumores Fibrosos Solitários/diagnóstico , Vimentina/análise
15.
Ann Diagn Pathol ; 19(4): 269-76, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26025258

RESUMO

Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia, with typical high-resolution computed tomography (HRCT) features and histologic pattern of usual interstitial pneumonia (UIP); its main differential diagnosis is fibrotic nonspecific interstitial pneumonia (F-NSIP). Usual interstitial pneumonia was mainly described from lung biopsies, and little is known on explants. Twenty-two UIP/IPF explants were analyzed histologically and compared with previous open lung biopsies (OLBs; n = 11) and HRCT (n = 19), when available. Temporospatial heterogeneity and subpleural and paraseptal fibrosis were similarly found in UIP/IPF explants and OLB (91%-95%). Fibroblastic foci were found in 82% of OLBs and 100% of explants, with a higher mean score in explants (P = .023). Honeycombing was present in 64% of OLBs and 95% of explants, with a higher mean score in explants (P = .005). Almost 60% of UIP/IPF explants showed NSIP areas and 41% peribronchiolar fibrosis; inflammation, bronchiolar metaplasia, and vascular changes were more frequent in UIP/IPF explants; and Desquamative Interstitial Pneumonia (DIP)-like areas were not common (18%-27%). Numerous large airspace enlargements with fibrosis were frequent in UIP/IPF explants (59%). On HRCT, honeycombing was observed in 95% of the cases and ground-glass opacities in 53%, correlating with NSIP areas or acute exacerbation at histology. Six patients had combined IPF and emphysema. Lesions were more severe in UIP/IPF explants, reflecting the worsening of the disease. Usual interstitial pneumonia/IPF explants more frequently presented with confounding lesions such as NSIP areas, peribronchiolar fibrosis, and airspace enlargements with fibrosis sometimes associated with emphysema.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Inflamação/patologia , Transplante de Pulmão/métodos , Masculino , Metaplasia/patologia , Pessoa de Meia-Idade , Fibrose Pulmonar/cirurgia , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
16.
J Thorac Oncol ; 10(2): 309-15, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25319181

RESUMO

BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) refer as to a heterogeneous group of mesenchymal malignancies with various anatomic and histology features. Upfront surgical resection is the standard approach, but recurrences may be aggressive and difficult to treat. The most widely accepted staging system has been proposed by De Perrot et al. Because SFTPs are rare, evidence to support a role for perioperative chemotherapy is scarce. Likewise, the predictive or prognostic relevance of the De Perrot system may be questioned. METHODS: Multicenter retrospective study of patients with histologically proven SFTP with complete follow-up from surgical diagnostic to tumor recurrence and death. RESULTS: Sixty-eight patients were included. Tumor stage was 0/I for 29 (43%) patients, II for 23 (34%) patients, III for seven (10%) patients, and IV for nine (13%) patients. Postoperative chemotherapy was given to seven patients, mostly with stage III/IV SFTP, mostly consisting of doxorubicin-based regimen. Recurrence rate and median relapse-free survival after surgery were 3%, 52%, 71%, and 80% (p < 0.001), and 107, 70, 29, 11 months (p < 0.001) for stage 0/I, II, III, and IV tumors, respectively. At time of tumor recurrence, 14 patients received exclusive chemotherapy. Highest disease control rates were observed with trabectedin, and gemcitabine-dacarbazine combination. CONCLUSION: Our study confirms the prognostic value of the De Perrot staging system, as well as its possible predictive value for perioperative chemotherapy decision-making, whereas the efficacy of currently available regimens to significantly reduce the risk of tumor recurrence remains questionable. Trabectedin may be of interest for recurrent tumors.


Assuntos
Neoplasias Pleurais/terapia , Tumor Fibroso Solitário Pleural/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pleurais/patologia , Neoplasias Pleurais/cirurgia , Padrões de Prática Médica , Prognóstico , Estudos Retrospectivos , Tumor Fibroso Solitário Pleural/patologia , Tumor Fibroso Solitário Pleural/cirurgia , Resultado do Tratamento
17.
J Thorac Oncol ; 9(5): 596-611, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24722150

RESUMO

INTRODUCTION: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. METHODS: To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. RESULTS: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. CONCLUSION: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.


Assuntos
Carcinoma/patologia , Timoma/patologia , Neoplasias do Timo/patologia , Antígenos CD20/análise , Antígenos CD5/análise , Carcinoma/química , Transportador de Glucose Tipo 1/análise , Humanos , Mucina-1/análise , Proteínas Proto-Oncogênicas c-kit/análise , Reprodutibilidade dos Testes , Timoma/química , Neoplasias do Timo/química , Organização Mundial da Saúde
18.
Ann Pathol ; 34(1): 87-91, 2014 Feb.
Artigo em Francês | MEDLINE | ID: mdl-24630641

RESUMO

Epithelial thymic tumours are rare and sometimes difficult to classify. Since 2010, the French National Cancer Institute supports a French national network, called Rythmic, devoted to the treatment of these tumours through regional and national multidisciplinary conferences using the web. All the tumours are secondarily reviewed by a French pathology national network for classification and staging. This review focuses on the presentation of the Rythmic network, and mainly to the Pathology review process.


Assuntos
Sistemas Multi-Institucionais , Patologia Clínica , Neoplasias do Timo/patologia , França , Humanos
20.
J Heart Lung Transplant ; 29(7): 792-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20456977

RESUMO

BACKGROUND: Coronary allograft vasculopathy (CAV) is the major limiting factor for long term survival after heart transplantation. The aim of this study was to identify gene candidates implicated in human CAV using a rat aortic allograft model in tandem with microarrays and quantitative real time PCR (Q-PCR). METHODS: Rat abdominal aortas were isografted (5) or allografted (5) from Brown-Norway to Lewis rats and grafts were harvested after day 8, 25 and 60. Agilent microarrays were then used to highlight differentially expressed genes between isografted and allografted rat aortas. Further investigation of a selected candidate gene was performed on human coronary arteries. RESULTS: 1829, 2582 and 1925 genes (fold changes >2 or <2 and p values <0.05) were differentially expressed at day 8, 25 and 60 respectively between isografs and allografts. Seventeen candidate genes were selected according to significant differential expression at day 60. These rat candidate genes were then validated by quantitative real time polymerase chain reaction (Q-PCR). One of these candidate genes, T-Cadherin (T-Cad) was further investigated, using immunohistochemistry (IHC), in human coronary arteries showing CAV compared to classical atherosclerosis present in ischemic cardiomyopathy (ICM) and normal coronary arteries present in dilated cardiomyopathy (DCM). Results showed an over expression of T-Cad in CAV and classical atherosclerosis compared to normal coronary arteries. CONCLUSIONS: T-Cad was found to be over expressed in CAV. T-Cad could potentially act as a trigger for smooth muscle cells (SMCs) proliferation and vascular remodelling observed in CAV leading to a diffuse narrowing of the arterial lumen.


Assuntos
Caderinas/metabolismo , Rejeição de Enxerto/metabolismo , Transplante de Coração , Doenças Vasculares/metabolismo , Adolescente , Adulto , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/transplante , Proliferação de Células , Vasos Coronários/metabolismo , Vasos Coronários/transplante , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Rejeição de Enxerto/patologia , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Estudos Retrospectivos , Transplante Homólogo , Doenças Vasculares/patologia , Adulto Jovem
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