Asunto(s)
Disnea/etiología , Fibrosis Pulmonar Idiopática/diagnóstico , Pulmón/patología , Anciano , Alveolitis Alérgica Extrínseca/diagnóstico , Biopsia , Diagnóstico Diferencial , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/patología , Indoles/uso terapéutico , Pulmón/diagnóstico por imagen , Masculino , Piridonas/uso terapéutico , Radiografía Torácica , Sarcoidosis/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
AIMS: Pulmonary Langerhans cell histiocytosis (PLCH) is an idiopathic cigarette smoking-related disorder of the lung. Molecular changes in cellular or fibrotic stages of PLCH have not been investigated. We studied the prevalence of extracellular signal-regulated kinase (ERK) pathway mutations in different PLCH stages and other non-PLCH smoking-related lung diseases. METHODS AND RESULTS: The cohort included 28 PLCH with cellular (n = 10), mixed cellular/fibrotic (n = 4) and fibrotic histology (n = 14). Seven cases had concurrent multi-focal/multi-lobar tumours. Respiratory bronchiolitis interstitial lung disease (RB-ILD, n = 2), desquamative interstitial pneumonia (DIP, n = 4) and mixed RB-ILD/DIP (n = 2) were included for comparison. BRAF(V) (600E) immunohistochemistry, next-generation sequencing (NGS) and peptide nucleic acid (PNA) clamp polymerase chain reaction (PCR) with high analytical sensitivity (<0.1-0.2%) were used to analyse RAS, BRAF and MAP2K1 genes. Of 26 cases with gene mutation data, BRAF(V) (600E) was identified in eight of 12 (67%) cellular cases and in one of 14 (7%) fibrotic cases. MAP2K1 or KRAS mutations were observed in four of 14 (29%) fibrotic cases and three of the 12 (25%) cellular cases. Multi-focal/multi-lobar specimens carried identical BRAF (n = 5) or non-hotspot MAP2K1 (n = 2) mutations. The other smoking-related disorders were negative for mutations. Patients with cellular lesions or BRAF mutation were significantly younger than patients with fibrotic or BRAF wild-type PLCH. CONCLUSION: The presence of identical but mutually exclusive ERK pathway mutations in multi-focal PLCH supports a neoplastic/clonal origin for this disease. Patient age and mutation type differed between cellular and fibrotic histology and may indicate a natural progression or a mutation-specific pathogenicity.
Asunto(s)
Histiocitosis de Células de Langerhans/genética , Enfermedades Pulmonares/genética , Sistema de Señalización de MAP Quinasas/genética , Adolescente , Adulto , Anciano , Análisis Mutacional de ADN , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Histiocitosis de Células de Langerhans/etiología , Histiocitosis de Células de Langerhans/patología , Humanos , Inmunohistoquímica , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , MAP Quinasa Quinasa 1/genética , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas B-raf/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Fumar/efectos adversos , Adulto Joven , Proteínas ras/genéticaAsunto(s)
Filaminas/genética , Heterotopia Nodular Periventricular/diagnóstico , Anomalías Múltiples , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Ecocardiografía , Insuficiencia de Crecimiento/etiología , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X , Trastornos del Crecimiento/etiología , Corazón/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Hemangioma/complicaciones , Hemangioma/diagnóstico , Humanos , Lactante , Pulmón/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Mutación , Linaje , Heterotopia Nodular Periventricular/complicaciones , Heterotopia Nodular Periventricular/genética , Radiografía Torácica , Insuficiencia Respiratoria/etiologíaAsunto(s)
Pulmón/patología , Eosinofilia Pulmonar/patología , Anciano , Alveolitis Alérgica Extrínseca/diagnóstico , Biopsia , Enfermedad Crónica , Diagnóstico Diferencial , Fiebre/etiología , Humanos , Hipoxia/etiología , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico , Masculino , Eosinofilia Pulmonar/complicaciones , Eosinofilia Pulmonar/diagnóstico por imagen , Recurrencia , Tomografía Computarizada por Rayos XAsunto(s)
Bronquiolitis Obliterante/patología , Disnea/etiología , Pulmón/patología , Bronquiectasia/complicaciones , Bronquiectasia/diagnóstico por imagen , Bronquiolitis Obliterante/complicaciones , Diagnóstico Diferencial , Femenino , Volumen Espiratorio Forzado , Humanos , Trasplante de Pulmón , Persona de Mediana Edad , Tomografía Computarizada por Rayos XAsunto(s)
Apéndice Atrial/patología , Cardiomiopatía Hipertrófica/patología , Tabiques Cardíacos/patología , Sarcoidosis/patología , Anciano , Amiloidosis/diagnóstico , Apéndice Atrial/cirugía , Cardiomiopatía Hipertrófica/complicaciones , Diagnóstico Diferencial , Disnea/etiología , Ecocardiografía , Edema/etiología , Humanos , Pierna , Pulmón/diagnóstico por imagen , Pulmón/patología , Ganglios Linfáticos/patología , Enfermedades Linfáticas/diagnóstico , Masculino , Radiografía , Sarcoidosis/complicaciones , Síncope/etiologíaAsunto(s)
Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Anciano , Bronquios/diagnóstico por imagen , Bronquios/patología , Femenino , Humanos , Fibrosis Pulmonar Idiopática/patología , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Mesothelioma is considered a signal tumor for exposure to asbestos (fibrous materials) and can occur decades after first exposure. The present case study reports on tissue burden of fibrous dust in a person who used a vermiculite material (Zonolite) as an attic insulator some 50 years prior to her death. The exposure occurred in two construction/renovation projects in her private residencies. She potentially had exposures to wall board/joint compounds during renovations. She additionally was reported to occasionally be involved in occupational activity, including drilling holes in presumed asbestos-containing electrical boxes. The tissue burden analysis revealed the presence of noncommercial amphibole asbestos fibers and consistent presence in the lung and lymph samples of Libby amphibole fibers. The findings of Libby amphibole fibers in human tissue can be attributed to exposure to Libby vermiculite. This study illustrates that analytical transmission electron microscopy can distinguish these structures from "asbestos" fibers. Further, the findings indicate that a population of these structures is biodurable and retained in the tissue years after first/last exposure.
Asunto(s)
Asbestos Anfíboles/efectos adversos , Neoplasias Pulmonares/inducido químicamente , Mesotelioma/inducido químicamente , Anciano de 80 o más Años , Femenino , Humanos , Microscopía Electrónica de TransmisiónAsunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Fibrosis Pulmonar Idiopática/patología , Pulmón/patología , Pleura/patología , Diagnóstico Diferencial , Disnea/etiología , Tolerancia al Ejercicio , Femenino , Humanos , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico , Persona de Mediana Edad , Tomografía Computarizada por Rayos XAsunto(s)
Hipercalcemia/etiología , Enfermedades Renales/patología , Riñón/patología , Insuficiencia Renal/etiología , Sarcoidosis/patología , Anciano , Diagnóstico Diferencial , Disnea/etiología , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Radiografía , Sarcoidosis/complicacionesAsunto(s)
Actinomicosis/patología , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Empiema/patología , Infecciones por Pasteurellaceae/patología , Derrame Pleural/etiología , Pared Torácica/patología , Traqueostomía/efectos adversos , Actinomyces/aislamiento & purificación , Actinomicosis/complicaciones , Niño , Diagnóstico Diferencial , Empiema/complicaciones , Empiema/diagnóstico por imagen , Femenino , Humanos , Inflamación/diagnóstico , Neoplasias/diagnóstico , Infecciones por Pasteurellaceae/complicaciones , Derrame Pleural/diagnóstico por imagen , Pared Torácica/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tráquea/lesiones , Traqueítis/complicacionesAsunto(s)
Vacuna BCG/efectos adversos , Pulmón/patología , Mycobacterium bovis/aislamiento & purificación , Tuberculosis/patología , Anciano , Alveolitis Alérgica Extrínseca/diagnóstico , Vacuna BCG/uso terapéutico , Biopsia , Carcinoma de Células Transicionales/complicaciones , Carcinoma de Células Transicionales/tratamiento farmacológico , Diagnóstico Diferencial , Fiebre/etiología , Humanos , Leucopenia/etiología , Pulmón/diagnóstico por imagen , Masculino , Radiografía , Tuberculosis/diagnóstico por imagen , Tuberculosis/etiología , Neoplasias de la Vejiga Urinaria/complicaciones , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by (32) P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced-111.3% (95% CI, -3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Aductos de ADN/genética , Ácido Fólico/administración & dosificación , Neoplasias Pulmonares/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Adenocarcinoma/patología , Anciano , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Fumar/genéticaAsunto(s)
Neoplasias Pulmonares/patología , Mesotelioma/patología , Pleura/patología , Derrame Pleural Maligno/diagnóstico , Dolor en el Pecho/etiología , Diagnóstico Diferencial , Humanos , Enfermedades Pulmonares/diagnóstico , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Mesotelioma/complicaciones , Mesotelioma/diagnóstico por imagen , Persona de Mediana Edad , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/etiología , Derrame Pleural Maligno/etiología , Radiografía Torácica , Fumar/efectos adversosAsunto(s)
Enfermedad de Crohn/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Pulmón/patología , Trastornos Necrobióticos/diagnóstico , Niño , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Granulomatosis con Poliangitis/complicaciones , Humanos , Infecciones/diagnóstico , Nódulos Pulmonares Múltiples/etiología , Trastornos Necrobióticos/complicaciones , Tomografía de Emisión de PositronesRESUMEN
Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib. Defining distinctive features of ALK-rearranged (ALK+) lung adenocarcinomas may help identify cases that merit molecular testing. However, data describing the morphologic features of ALK+ lung adenocarcinomas are conflicting and are primarily based on analysis of resected primary lung tumors. It is unclear whether the findings from prior studies are applicable to metastatic lung tumors or to small biopsy/cytology specimens. To address these issues, we examined resection, excision, small biopsy, and cytology cell block specimens from 104 ALK+ and 215 ALK- lung adenocarcinomas from primary and metastatic sites. All cases were evaluated for ALK rearrangements by fluorescence in situ hybridization. The predominant histologic subtypes and distinctive cytomorphologic features were assessed in each case. Primary ALK+ lung adenocarcinomas showed a significant association with solid, micropapillary, and papillary-predominant histologic patterns and tumor cells with a signet ring or hepatoid cytomorphology. Among metastatic lung tumors and small biopsy/cytology specimens, the only distinguishing morphologic feature of ALK+ tumors was the presence of signet ring cells. Based on these results, we developed a morphology-based scoring system for predicting ALK rearrangements in lung adenocarcinomas. The scoring system predicted ALK rearrangements in a new cohort of 78 lung adenocarcinomas (29 ALK+ and 49 ALK-) with a sensitivity of 88% and a specificity of 45%. In conclusion, ALK+ lung adenocarcinomas have distinctive morphologic features, with signet ring cells showing a significant association with ALK rearrangements irrespective of tumor site (primary vs metastatic) or specimen type. However, morphologic screening alone will not detect a minority of ALK+ lung adenocarcinomas, and the routine use of ancillary studies may be warranted to identify all patients who may benefit from crizotinib treatment.
Asunto(s)
Adenocarcinoma/genética , Adenocarcinoma/secundario , Reordenamiento Génico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteínas Tirosina Quinasas Receptoras/genética , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/enzimología , Adenocarcinoma del Pulmón , Adenocarcinoma Papilar/enzimología , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/secundario , Adulto , Anciano , Anciano de 80 o más Años , Quinasa de Linfoma Anaplásico , Antineoplásicos/uso terapéutico , Biopsia , Carcinoma de Células en Anillo de Sello/enzimología , Carcinoma de Células en Anillo de Sello/genética , Carcinoma de Células en Anillo de Sello/secundario , Crizotinib , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hibridación Fluorescente in Situ , Modelos Logísticos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Selección de Paciente , Fenotipo , Medicina de Precisión , Valor Predictivo de las Pruebas , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Adulto JovenRESUMEN
Wegener granulomatosis is an uncommon necrotizing vasculitis that classically manifests as a clinical triad consisting of upper and lower airway involvement and glomerulonephritis. Other less frequently involved organ systems include the central and peripheral nervous system and large joints. The diagnosis is based on a combination of clinical and laboratory findings. Because thoracic involvement often predominates, chest radiographic findings are often the first to suggest the diagnosis. However, chest computed tomography (CT) has superior sensitivity and specificity for evaluation of the airways, lung parenchyma, and mediastinum, particularly with the use of multiplanar reformatted and three-dimensional images. Common pulmonary radiologic findings include waxing and waning nodules, masses, ground-glass opacities, and consolidation. Airway involvement is usually characterized by circumferential tracheobronchial thickening, which can be smooth or nodular. Pleural effusions are the most common manifestation of pleural disease and can result from primary involvement or be secondary to renal failure. Mediastinal lymphadenopathy is a nonspecific finding and is usually reactive. Uncommon thoracic radiologic manifestations include involvement of the heart and great vessels. CT is the imaging modality of choice for diagnosis, surveillance, and follow-up in patients with Wegener granulomatosis.
Asunto(s)
Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico , Radiografía Torácica/métodos , Enfermedades Torácicas/complicaciones , Enfermedades Torácicas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Raras/diagnóstico por imagen , Enfermedades Raras/patología , Estadística como AsuntoRESUMEN
BACKGROUND: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. METHOD: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. RESULTS: Pathologists were being able to use the system comfortably after 0-15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. CONCLUSIONS: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.
Asunto(s)
Diagnóstico por Imagen/instrumentación , Procesamiento de Imagen Asistido por Computador/instrumentación , Telepatología/instrumentación , Presentación de Datos , Diseño de Equipo , Humanos , Factores de TiempoRESUMEN
Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.