RESUMEN
As the life expectancy of AIDS patients continues to increase due to improved anti-retroviral therapy less of these patients die of HIV-related illnesses. Dysphagia is a common complaint in AIDS patients and usually results from a fungal esophagitis. While cancer of the esophagus is occasionally found in AIDS patients, we report our experience with an AIDS patient diagnosed with a squamous cell esophageal malignancy who received pre-operative radiation and chemotherapy, followed by transhiatal esophagectomy. The patient is alive 16 months post-operatively. The transition of HIV/AIDS from an acute fulminant disease to a chronic condition mandates that these patients should receive full and standard therapy for their esophageal malignancies.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Carcinoma de Células Escamosas/terapia , Trastornos de Deglución/cirugía , Neoplasias Esofágicas/terapia , Esofagectomía , Anciano , Carcinoma de Células Escamosas/diagnóstico , Trastornos de Deglución/etiología , Neoplasias Esofágicas/diagnóstico , Humanos , MasculinoRESUMEN
Atypical adenomatous hyperplasia (AAH) is a probable forerunner of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma (AC) of mixed type. The present study analysed four low-grade AAHs, 13 high-grade AAHs, two BACs, nine mixed ACs, and one squamous cell carcinoma derived from 13 patients using comparative genomic hybridization. The average number of chromosomal aberrations was 1.2 in low-grade AAH, 9.6 in high-grade AAH, and 12.5 in AC. A high degree of overlap of genetic changes was found in high-grade AAH, BAC, and AC within individual patients. The high number of aberrations and the degree of shared aberrations found in high-grade AAH and AC raises questions about the separation of these two entities. In addition, in view of the monoclonal origin of multiple foci within the same patient, AAH may not be a precursor of AC in some cases, but rather may represent intraepithelial spread.
Asunto(s)
Adenocarcinoma Bronquioloalveolar/genética , Adenoma/genética , Neoplasias Pulmonares/genética , Lesiones Precancerosas/genética , Adenocarcinoma Bronquioloalveolar/patología , Adenoma/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Cromosomas Humanos X/genética , ADN de Neoplasias/genética , Humanos , Hibridación Genética/genética , Hiperplasia/patología , Neoplasias Pulmonares/patología , Invasividad Neoplásica/genética , Reacción en Cadena de la Polimerasa/métodos , Lesiones Precancerosas/patología , Aberraciones Cromosómicas SexualesRESUMEN
A potent role for memory CD8+ T cells in heterologous immunity was shown with a respiratory mucosal model of viral infection. Memory CD8+ T cells generated after lymphocytic choriomeningitis virus (LCMV) infection were functionally activated in vivo to produce interferon-gamma (IFN-gamma) during acute infection with vaccinia virus (VV). Some of these antigen-specific memory cells selectively expanded in number, which resulted in modulation of the original LCMV-specific T cell repertoire. In addition, there was an organ-selective compartmental redistribution of these LCMV-specific T cells during VV infection. The presence of these LCMV-specific memory T cells correlated with enhanced VV clearance, decreased mortality and marked changes in lung immunopathology. Thus, the participation of pre-existing memory T cells specific to unrelated agents can alter the dynamics of mucosal immunity and disease course in response to a pathogen.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica , Pulmón/patología , Coriomeningitis Linfocítica/inmunología , Virus de la Coriomeningitis Linfocítica/inmunología , Mucosa Nasal/inmunología , Infecciones del Sistema Respiratorio/inmunología , Subgrupos de Linfocitos T/inmunología , Virus Vaccinia/inmunología , Vaccinia/inmunología , Administración Intranasal , Animales , Antígenos Virales/inmunología , Linfocitos T CD8-positivos/clasificación , Células Cultivadas/inmunología , Células Cultivadas/metabolismo , Citocinas/biosíntesis , Humanos , Inmunización , Interferón gamma/biosíntesis , Pulmón/inmunología , Activación de Linfocitos , Coriomeningitis Linfocítica/patología , Coriomeningitis Linfocítica/virología , Virus de la Coriomeningitis Linfocítica/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos C57BL , Especificidad de Órganos , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología , Linfocitos T Citotóxicos/inmunología , Vaccinia/patología , Vaccinia/virología , Virus Vaccinia/aislamiento & purificaciónRESUMEN
BACKGROUND: When resting cells are stimulated by growth factors, an increase in protein synthesis follows that depends in part on two key eukaryotic translation initiation factors, 4E and 2alpha (eIF-4E and eIF-2alpha, respectively). In the normal cell, expression and activity of both factors are increased transiently, whereas they become elevated constitutively in oncogene-transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study, the authors investigated an association between the expression of these translation initiation factors and lung carcinogenesis. METHODS: The authors analyzed the expression of the protein synthesis initiation factors eIF-4E and eIF-2alpha by immunohistochemistry in bronchioloalveolar (BA) and squamous cell (SC) carcinomas of the lung. Western blot analysis was performed to validate the specificity of antibodies in detecting their cognate proteins. RESULTS: Both eIF-4E and eIF-2alpha were increased frequently in BA carcinomas, whereas only rarely did SC carcinomas demonstrate elevation of these translation initiation factors. An analysis of cyclin D1 expression did not show a strict correlation with the expression of eIF-4E and eIF-2alpha. CONCLUSIONS: Increased expression of either one or both translation initiation factors may facilitate accelerated growth and division of neoplastic cells in BA carcinoma of the lung. However, the current findings suggest a possibility that increased cell growth and proliferation in SC carcinoma may be achieved through a mechanism independent of increases in eIF-4E and eIF-2alpha expression.
Asunto(s)
Adenocarcinoma Bronquioloalveolar/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Neoplasias Pulmonares/metabolismo , Factores de Iniciación de Péptidos/metabolismo , Adenocarcinoma Bronquioloalveolar/patología , Western Blotting , Carcinoma de Células Escamosas/patología , Ciclina D , Ciclinas/metabolismo , Factor 4E Eucariótico de Iniciación , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patologíaRESUMEN
An increasingly large body of work suggests that atypical adenomatous hyperplasia (AAH) of the lung may be a forerunner of pulmonary adenocarcinoma. Recognizing this fact, the World Health Organization now acknowledges the existence of AAH while noting difficulties that may be encountered in distinguishing AAH from the nonmucinous variant of bronchioloalveolar carcinoma. Regrettably, a universally acceptable definition of morphologic criteria for the diagnosis of AAH has not been achieved. This review of the literature examines the epidemiology, gross appearance, light microscopic findings, morphometry, immunohistochemistry, and molecular features of AAH and suggests a set of histopathologic features that may help the practicing pathologist identify this intriguing lesion. These features include the following: irregularly bordered focal proliferations of atypical cells spreading along the preexisting alveolar framework; prominent cuboidal to low columnar alveolar epithelial cells with variable degree of atypia but less than that seen in adenocarcinoma; increased cell size and nuclear-cytoplasmic ratio with hyperchromasia and prominent nucleoli, generally intact intercellular attachment of atypical cells with occasional empty-looking spaces between them without high cellularity and without tufting or papillary structures; and slight thickening of the alveolar walls on which the AAH cells have spread, with some fibrosis but without scar formation or significant chronic inflammation of the surrounding lung tissue. Several lines of evidence indicate that AAH is a lesion closely associated with adenocarcinoma of the lung, suggesting AAH may be involved in the early stage of a complex multistep carcinogenesis of pulmonary adenocarcinoma.
Asunto(s)
Adenocarcinoma/patología , Adenomatosis Pulmonar/patología , Neoplasias Pulmonares/patología , Pulmón/patología , Lesiones Precancerosas/patología , Adenomatosis Pulmonar/química , Adenomatosis Pulmonar/epidemiología , Adenomatosis Pulmonar/genética , Animales , Biomarcadores de Tumor , ADN de Neoplasias/análisis , Modelos Animales de Enfermedad , Humanos , Hiperplasia , InmunohistoquímicaRESUMEN
STUDY OBJECTIVES: Asbestos bodies (ABs) form as asbestos fibers become coated by a cellular iron- and protein-rich matrix. ABs have been reported in lymph nodes and a few extrapulmonary sites, but no data exist as to their formation outside of the lung. It is not clear whether the AB found in these extrapulmonary areas have been transported as mature structures from the lung or formed at the extrapulmonary site. This study was designed to determine if ABs are produced in extrapulmonary sites. The guinea pig efficiently forms ferruginous bodies in the lung and so it was chosen as a model to test the coating efficiency of amosite asbestos fibers in lung, liver and spleen. DESIGN: Sized amosite asbestos (5 mg) was administered either endotracheally into lung (n = 2) or directly into liver (n = 4) and spleen (n = 4) of healthy 10-week-old male guinea pigs. The lung, liver and splenic tissues were removed at 40 and 180 days post inoculation and were examined histologically for the presence of AB via light microscopy. Uncoated fibers isolated from the tissues were characterized by electron microscopy. The coating efficiency was calculated as a ratio of uncoated/coated fibers per organ. RESULTS: The coating efficiency ratios of fibers that were collected at 40 days post-injection from the individual sites were: lung - 350:1, liver - 4200:1, and spleen - 220,000:1. At 6 months post-injection the ratios for the individual sites consisted of: lung - 176:1, liver - 11,000:1, and spleen - 1000:1. CONCLUSION: This study indicates that AB can be formed in extrapulmonary sites and that the coating efficiency in the lung is much greater than that within the liver or spleen.
Asunto(s)
Asbesto Amosita/efectos adversos , Cuerpos Extraños/etiología , Cuerpos Extraños/patología , Hígado , Pulmón , Bazo , Animales , Asbestosis/etiología , Modelos Animales de Enfermedad , Ferritinas/análisis , Cobayas , Masculino , Fibras Minerales/efectos adversosRESUMEN
Each cough involves a complex reflex arc beginning with the stimulation of sensory nerves that function as cough receptors. There is evidence, primarily clinical, that the sensory limb of the reflex exists in and outside of the lower respiratory tract. Although myelinated, rapidly adapting pulmonary stretch receptors (RARs), also known as irritant receptors, are the most likely type of sensory nerve that stimulates the cough center in the brain, afferent C-fibers and slowly adapting pulmonary stretch receptors (SARs) also may modulate cough. RARS, C-fibers, and SARs have been identified in the distal esophageal mucosa; however, studies have not been performed to determine whether they can participate in the cough reflex. Although gastroesophageal reflux disease can potentially stimulate the afferent limb of the cough reflex by irritating the upper respiratory tract without aspiration and by irritating the lower respiratory tract by micro- or macroaspiration, there is evidence that strongly suggests that reflux commonly provokes cough by stimulating an esophageal-bronchial reflex. Theoretically, the pathways of this reflex may be modeled in a variety of ways, and these are speculated upon in this article. The predominant role of acid in triggering cough by means of this reflex is unclear because of conflicting results from provocative challenge studies. It is interesting to speculate that a distal esophageal-bronchial reflex evolved as an early warning defense so that coughing could be started, just in case the refluxate were to reach the inlet of the lower respiratory tract. That is, thinking teleologically, it is possible that an esophageal-bronchial reflex evolved as one of several mechanisms designed to protect the lungs from aspiration of gastric contents.
Asunto(s)
Tos/fisiopatología , Reflujo Gastroesofágico/fisiopatología , Reflejo , Bronquios/fisiopatología , Tos/etiología , Tos/patología , Esófago/fisiopatología , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/patología , HumanosRESUMEN
STUDY OBJECTIVES: Workers in the nylon flocking industry recently have been found to be at increased risk of chronic nongranulomatous interstitial lung disease. Although a spectrum of cytologic and histopathologic abnormalities has been observed, nonspecific interstitial pneumonia, lymphoid nodules, and lymphocytic bronchiolitis predominated in the 19 previously reported cases of flock worker's lung. Here we describe five additional patients who appear to expand the histopathologic spectrum and add to the evidence suggesting a causative role for respirable-sized nylon fragments. METHODS: We studied all North American patients (n = 5) found in 1998 to satisfy our previous case definition of flock worker's lung. Two pulmonary pathologists independently reviewed each biopsy specimen. RESULTS: All five patients reported cough and dyspnea. Only one patient had crackles on chest auscultation. High-resolution CT scan, interpreted with attention to subtle ground-glass attenuation, remained a highly sensitive diagnostic test. Pulmonary function tests and plain chest radiograph were less sensitive. One patient's wedge biopsy showed previously described prototypical findings. Two others had transbronchial biopsies showing some of the same features. The fourth patient's wedge biopsy showed desquamative interstitial pneumonia. The fifth patient had bilateral synchronous adenocarcinoma but with radiographic evidence of diffuse interstitial fibrosis. These 5 patients and the 19 patients studied previously were exposed to nylon flock manufactured by a rarely used cutting technology. CONCLUSION: Findings in these five patients appear to broaden the spectrum of the clinicopathology of flock worker's lung and add to the evidence incriminating respirable-sized nylon particulates produced during the manufacture and use of rotary-cut nylon flock.
Asunto(s)
Enfermedades Pulmonares Intersticiales/etiología , Nylons/efectos adversos , Enfermedades Profesionales/etiología , Exposición Profesional/efectos adversos , Industria Textil , Adulto , Anciano , Biopsia , Enfermedad Crónica , Diagnóstico Diferencial , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/patología , Masculino , Enfermedades Profesionales/diagnóstico por imagen , Enfermedades Profesionales/patología , Radiografía Torácica , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Flocking is a widely used industrial process in which short lengths of synthetic fibers are applied to backing fabric to produce plush material. In response to an apparent outbreak of interstitial lung disease in flock workers, the Centers for Disease Control hosted a clinical-pathological workshop to identify the defining characteristics of the disease and possible etiologic agents. Six pathologists reviewed 15 biopsies of 15 cases (out of a clinical caseload of 20 patients) and assessed the pattern, extent and degree of pulmonary inflammation, fibrosis, and other changes. A consensus clinical-pathologic diagnosis was reached for each patient and correlated with clinical and radiologic findings. Four of eight open lung biopsies and one of seven closed (transbronchial) lung biopsies demonstrated a characteristic pattern to which the descriptive terminology lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia was applied. The other biopsies showed nonspecific inflammatory changes, airspace organization, and diffuse alveolar damage. One open lung biopsy demonstrated respiratory bronchiolitis with lymphoid hyperplasia. None of the lung biopsies showed more than mild interstitial fibrosis and no granulomas were identified. The consensus of the workshop was that lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia was a characteristic and distinctive pattern of injury in the flock workers' lung biopsies. Although the etiology of this disease remains undefined at present, the injury pattern and environmental studies suggest a chronic immunologic response to inhaled material.
Asunto(s)
Bronquiolitis Obliterante/patología , Pulmón/patología , Enfermedades Profesionales/patología , Exposición Profesional/efectos adversos , Industria Textil , Adulto , Contaminantes Ocupacionales del Aire , Biopsia , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/etiología , Femenino , Humanos , Hiperplasia , Linfocitos/patología , Tejido Linfoide/patología , Masculino , Persona de Mediana Edad , Nylons/efectos adversos , Enfermedades Profesionales/tratamiento farmacológico , Enfermedades Profesionales/etiologíaRESUMEN
A case of low thyroid radioactive iodine uptake (RAIU) thyrotoxicosis due to a large struma ovarii comprising pure thyroid tissue is presented, including a detailed diagnostic evaluation, histopathology, and demonstration of rapid recovery of native thyroid function after surgical excision. In addition, the first comprehensive analysis of thyroglobulin obtained from an ovarian struma is reported.
Asunto(s)
Neoplasias Ováricas/complicaciones , Estruma Ovárico/complicaciones , Tirotoxicosis/etiología , Anciano , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/diagnóstico por imagen , Cintigrafía , Estruma Ovárico/diagnóstico , Estruma Ovárico/diagnóstico por imagen , Tiroglobulina/metabolismo , Tirotoxicosis/diagnóstico por imagen , Triyodotironina/sangreRESUMEN
Invasion of vascular walls by cancer cells is a well-known phenomenon in lymphoid malignancies. However, its occurrence in epithelial tumors is less well known. This report documents the occurrence of such invasion of vascular walls by an adenocarcinoma of the stomach in a 68-year-old woman. This rare event differs histopathologically from inflammatory vasculitis associated with malignant disease, lymphangitis carcinomatosa, and carcinomatous arteriopathy. In inflammatory vasculitis associated with malignant disease, the main histopathologic feature is fibrinoid necrosis and ordinary pan arteritis-like vasculitis. In lymphangitis carcinomatosa, the main feature is plugging of vascular lumina by tumor cells, a finding not encountered in our case, while in carcinomatosa arteriopathy, the main event is an obliterative fibrointimal hyperplasia, apparently resulting from arterial tumor emboli. In none of these three conditions has direct invasion of vascular walls by tumor cells been previously reported.
Asunto(s)
Adenocarcinoma/patología , Arteritis/patología , Neoplasias Gástricas/patología , Anciano , Arteritis/etiología , Femenino , Humanos , Invasividad NeoplásicaRESUMEN
STUDY OBJECTIVES: To determine the bronchoscopist's ability to predict specimen quality at the time of transbronchial biopsy and to determine the influence of biopsy specimen size and alveolar content on diagnostic value. DESIGN: Prospective, blinded, observational analysis. SETTING: Tertiary care academic hospital-based pulmonary practice. PATIENTS: Forty-three adult patients who underwent transbronchial lung biopsy. INTERVENTIONS: Each of 170 biopsy specimens was rated as to likelihood of containing diagnostic tissue, size and ability to float, tissue types present, number of alveoli, and pathologic diagnosis. RESULTS: Fifteen percent of biopsy specimens were small and 40% were large. Seventy-six percent of specimens floated; 61.8% of the 170 biopsy specimens contained abnormal lung tissue; and 14.7% of individual specimens were diagnostic. Fifty-two percent of specimens contained >20 alveoli. Larger biopsy specimens were more likely to contain diagnostic tissue (r=0.29, p=0.001). Cup forceps retrieved smaller pieces of tissue (p=0.007) and were less likely to obtain diagnostic tissue (p=0.06). Physician ratings of specimen quality (mean+/-SD) did not differ between specimens containing normal and abnormal tissue (5.98+/-2.3 vs 5.46+/-5.5; p=0.24) or between specimens containing diagnostic vs nondiagnostic tissue (5.56+/-2.5 vs 6.25+/-2.1; p=0.14). Specimens that floated were no more likely to be diagnostic or abnormal than specimens that sank (p<0.05). Diagnosis when established was made by the first biopsy specimen in 53.3% and the second in 33.3% CONCLUSIONS: Physician estimate of biopsy specimen quality and the float sign are not helpful in predicting that the biopsy specimen contains abnormal or diagnostic tissue. Diagnostic biopsy specimen will likely be obtained if the size of the specimen fills the forceps, 2 to 4 biopsies are performed, and toothed forceps are used.
Asunto(s)
Biopsia/métodos , Broncoscopía , Pulmón/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), and the lymphocyte function-associated antigen (LFA-1) are cell adhesion molecules thought to play an important role in the complex process of airway inflammation and tumor cell growth. The aim of this study was to examine the distribution of ICAM-1, VCAM-1, and LFA-1 in adenocarcinoma of lung and in major cellular compartments of non-neoplastic lung tissue. We examined cellular compartments in tissue from five bronchoalveolar carcinomas, three acinar adenocarcinomas, and one colon cancer metastatic to the lung. The compartments in neoplasms included the tumor cells proper, endothelial cells within the tumor vasculature, tumor stromal cells, and tumor-infiltrating lymphocytes. The compartments in non-neoplastic lung tissue included lung endothelial cells, pulmonary lymphocytes, interstitial fibroblasts, Type II alveolar pneumocytes, and bronchial epithelial cells. ICAM-1 was expressed in tumor cells from all of the nine adenocarcinomas. In contrast, VCAM-1 expression was not identified in tumor cells from any of the nine adenocarcinomas. ICAM-1 was expressed in all cellular compartments of the non-neoplastic lung tissue, whereas VCAM-1 was expressed only in pulmonary lymphocytes and interstitial fibroblastic cells. LFA-1 was uniformly expressed in tumor-infiltrating lymphocytes from each of the nine tumors and all of the lymphocytes in non-neoplastic lung tissue. This study showed major differences in the expression of ICAM-1 and VCAM-1 in tumor cells from pulmonary adenocarcinoma and also provided evidence for a wider distribution of ICAM-1, compared with VCAM-1, in non-neoplastic cellular compartments of the lung. ICAM-1 expression was particularly noticeable in bronchial and alveolar epithelial cells. Upregulation of ICAM-1 in pulmonary adenocarcinoma might foster binding by LFA-1-bearing lymphocytes, with a possible impact on the vulnerability of tumor cells to host defense mechanisms.
Asunto(s)
Adenocarcinoma/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Antígeno-1 Asociado a Función de Linfocito/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Adenocarcinoma/patología , Anciano , Femenino , Secciones por Congelación , Humanos , Técnicas para Inmunoenzimas , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/patología , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
Paraneoplastic pemphigus (PNP) is an autoimmune disease associated with leukemia and non-Hodgkin's lymphoma. A patient with stage IVB poorly differentiated lymphocytic lymphoma developed characteristic upper and lower airway involvement with profound mucocutaneous erosion and tracheobronchial epithelial desquamation. Immunofluorescence testing confirmed autoantibody deposition along the basement membrane of bronchial epithelium. Disruption of the cellular adhesion mechanisms, including desmosomes, hemidesmosomes, and possibly the integrin subunits, is presumed to have led to disruption and desquamation of the tracheobronchial epithelial barrier, severe obstruction of the airways and hypoxia, and possibly bacterial superinfection. As far as can be determined, the feature of airflow obstruction occurring in association with PNP has not been described. Physicians should be aware that these complications of PNP may rapidly lead to hypoxic respiratory failure and death.
Asunto(s)
Obstrucción de las Vías Aéreas/diagnóstico , Enfermedades Autoinmunes/diagnóstico , Bronquitis/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Pénfigo/diagnóstico , Traqueítis/diagnóstico , Obstrucción de las Vías Aéreas/etiología , Enfermedades Autoinmunes/complicaciones , Biopsia , Bronquios/patología , Bronquitis/complicaciones , Diagnóstico Diferencial , Humanos , Hipoxia/diagnóstico , Hipoxia/etiología , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/diagnóstico , Masculino , Persona de Mediana Edad , Necrosis , Síndromes Paraneoplásicos/complicaciones , Pénfigo/complicaciones , Piel/patología , Traqueítis/complicacionesRESUMEN
Laminin, a glycoprotein component of basement membrane, and cathepsin B, a lysosome-derived proteinase, are thought to play a role in the complex process of tumor invasion and metastasis. This study evaluates the possible prognostic significance of laminin degradation and cathepsin B expression in Stage I (T1NO, T2NO) human non-small cell lung cancer. Archival, formalin-fixed, paraffin-embedded lung tissue from patients with documented Stage I non-small cell cancer was studied in a series of 31 patients (14 men, 17 women; ages 40-82 yr; mean age, 67 yr) by using polyclonal antibodies against laminin and cathepsin B. The immunoexpression of laminin was assessed with respect to a continuous versus discontinuous pattern, whereas that of cathepsin B was semiquantitated according to a four-tiered grading scale: 0, 0% positive cells; 1, 1 to 9%; 2, 10 to 49%; and 3, more than 50% positive cells. Cox proportional hazards models and Kaplan-Meler survival analysis were used to evaluate the association of possible risk factors, including laminin and cathepsin B, with survival. Univariate analysis looking at possible associations of survival with age, sex, histologic type, degree of tumor differentiation, and tumoral stage (T1NO, T2NO) did not show significant association. Likewise, degradation of laminin and immunoexpression of cathepsin B did not show significant association with survival. Although previous studies suggested improved survival with increased laminin expression and decreased survival with high expression of cathepsin B, the results applying to intrastage (Stage I) non-small cell cancer suggest that the expression of laminin and cathepsin B has little prognostic significance.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Catepsina B/análisis , Laminina/análisis , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/análisis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/química , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/química , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
A precursor lesion of pulmonary adenocarcinoma has not been clearly defined. Previous studies suggested that atypical alveolar cell hyperplasia (AACH) might represent such a precursor lesion. Most previous studies showed an association between AACH and adenocarcinoma in surgical resection specimens. In this study, we searched for the prevalence of AACH and nonatypical alveolar cell hyperplasia (ACH) in a general autopsy population. Cases in which there was clinical or anatomic evidence of pulmonary neoplasia were excluded from the study. In the 100 consecutive autopsies examined, we found four cases of ACH and two cases of AACH. The two AACH lesions showed cytologic atypia and stained positively for p53 and c-erb-2. These findings suggest a possible role for AACH as a precursor lesion of adenocarcinoma of the lung.
Asunto(s)
Lesiones Precancerosas/patología , Alveolos Pulmonares/patología , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Predicción , Humanos , Hiperplasia/patología , Inmunohistoquímica , Antígeno Ki-67/análisis , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Alveolos Pulmonares/química , Receptor ErbB-2/análisis , Estudios Retrospectivos , Fumar , Proteína p53 Supresora de Tumor/análisisRESUMEN
OBJECTIVE: This study sought to assess the fibrogenic and carcinogenic potential of erionite (a fibrous zeolite) on the pleural mesothelium of the Fischer 344 rat (n = 24). DESIGN: The study was designed to examine rat pleural mesothelial changes by three independent observers at timed intervals, ranging from 1 to 480 days postinoculation using erionite from the Pine Valley, Nevada (USA) area. The mean length and width of the erionite fibers were 2.29 and 0.48 microns, respectively. Only microscopic observations made by majority (2/3) or unanimity (3/3) were accepted for final diagnosis. RESULTS: Pleural and lung tissue were available for examination in 21 of the 24 rats. Fibrosis, chronic inflammation, and foreign body reaction occurred in 6 of 21 rats. Mesothelial hyperplasia and dysplasia occurred in 9 and 3 of the 21 rats, respectively. A single mesothelioma was identified at 434 days in a rat that had gross nodular pleural lesions. CONCLUSIONS: The findings reported herein confirm the strong fibrogenic potential of erionite but are at variance with previous studies reporting much higher yields of mesothelioma. The reasons for the low yield of mesothelioma in this study are not known, but may be related to the study design, the strict criteria used for histopathologic diagnosis, and/or possible differences in erionite physicochemical properties, associated with its geographic distribution, most previous animal studies having used erionite from the Rome, Oregon (USA) area.
Asunto(s)
Pleura/efectos de los fármacos , Zeolitas/farmacología , Animales , Carcinógenos/farmacología , Fenómenos Químicos , Química Física , Epitelio/efectos de los fármacos , Femenino , Fibrosis , Estudios de Seguimiento , Reacción a Cuerpo Extraño/inducido químicamente , Hiperplasia , Pulmón/efectos de los fármacos , Enfermedades Pulmonares/inducido químicamente , Mesotelioma/inducido químicamente , Microscopía , Nevada , Oregon , Enfermedades Pleurales/inducido químicamente , Neoplasias Pleurales/inducido químicamente , Pleuresia/inducido químicamente , Neumonía/inducido químicamente , Fibrosis Pulmonar/inducido químicamente , Ratas , Ratas Endogámicas F344 , Zeolitas/químicaRESUMEN
Reactive atypia of alveolar epithelium occurs in many types of lung injury and may sometimes raise suspicions of adenocarcinoma or bronchioloalveolar carcinoma. To assess whether there is sufficient difference in the frequency of p53 protein immunopositivity in these lesions to provide a practical basis for differentiating malignancy from reactive atypia, we immunostained 110 malignant and inflammatory/fibrotic lung specimens for p53 protein. Paraffin-embedded sections were immunostained with p53 protein antibody (clone BP53-12; BioGenex, San Ramon, CA) and standard capillary gap (Microprobe; Fisher Scientific, Fairlawn, NJ) avidin- biotin complex technique with antigen retrieval solution. Percent of immunopositive cells was semiquantitatively categorized as follows: 0%, less than 1%, 1% to 10%, 10% to 50%, more than 50%. Of reactive atypias, 94% are negative or show p53 immunopositivity in less than 10% of cells. Of p53 positive malignancies, 86% are positive in more than 10% of cells. When p53 immunopositivity occurs in more than 10% of atypical cells, the lesion is usually a malignancy, primarily adenocarcinoma. Most reactive atypias are immunopositive in less than 10% of atypical cells. Important caveats were noted. Rare reactive atypias are p53 immunopositive in greater than 10% of cells. Bronchioloalveolar carcinomas are infrequently p53 immunopositive. Therefore, this approach would be less useful in their differentiation from reactive atypias.
Asunto(s)
Adenocarcinoma Bronquioloalveolar/patología , Carcinoma de Células Acinares/patología , Enfermedades Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmón/patología , Proteína p53 Supresora de Tumor/análisis , Adenocarcinoma Bronquioloalveolar/química , Adenocarcinoma Bronquioloalveolar/etiología , Anciano , Carcinoma de Células Acinares/química , Carcinoma de Células Acinares/etiología , Epitelio/química , Epitelio/patología , Humanos , Inmunohistoquímica/métodos , Inflamación/patología , Pulmón/química , Neoplasias Pulmonares/química , Neoplasias Pulmonares/etiología , Persona de Mediana Edad , Alveolos Pulmonares/química , Alveolos Pulmonares/patología , Fumar/efectos adversosRESUMEN
Calcofluor white (CFW), a chemofluorescent agent, has proven effective in the recognition of Pneumocystis carinii cysts in respiratory fluids and secretions. However, its usefulness in the recognition of P. carinii cysts in tissue preparations has not been established. We studied 68 formalin-fixed, paraffin-embedded, transbronchial tissue biopsy specimens from individuals seropositive for the human immunodeficiency virus and stained them with the CFW stain and the conventional Gomori methenamine silver (GMS) stain to determine the concordance rate of the two stains. CFW-positive specimens showed light peripheral staining and a unique double parenthesis-like structure near the center of the cysts. Thirty-six (52.9%) of the 68 specimens were CFW and GMS positive, whereas 27 (39.7%) of the specimens were negative by both techniques, yielding a concordance rate of 92.6%. Five (7.4%) of the 68 specimens showed disparate results, and, of these, four (5.9%) were CFW positive and GMS negative, whereas one (1.5%) was CFW negative and GMS positive. We conclude that the CFW stain is suitable and useful for the demonstration of P. carinii cysts in tissue preparations.
Asunto(s)
Bencenosulfonatos , Colorantes Fluorescentes , Pneumocystis/aislamiento & purificación , Neumonía por Pneumocystis/patología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Biopsia , Humanos , Pulmón/microbiología , Pulmón/patología , Adhesión en Parafina , Neumonía por Pneumocystis/diagnóstico , Tinción con Nitrato de Plata , Fijación del TejidoRESUMEN
Although most lung carcinomas and mesotheliomas are associated with well-known risk factors, these cancers develop in only a minority of persons exposed to known risk factors. On the other hand, these cancers develop in some patients without exposure to known risk factors. This indicates that other environmental factors play a role in the carcinogenesis of these tumors. Oncogenic viruses such as Epstein-Barr virus (EBC) are well-established agents in the development of certain cancers. EBV genomes have been detected by in situ hybridization in gastric adenocarcinomas and in nasopharyngeal carcinomas. To determine whether EBV infection is associated with pulmonary adenocarcinoma or mesothelioma, we performed EBV-encoded RNA-1 in situ hybridization on 80 pulmonary adenocarcinoma and 50 mesothelioma resection specimens. Sections were cut from paraffin-embedded tissue and EBV-encoded RNA-1 in situ hybridization was performed using an antisense oligoprobe. Sections were reviewed for the presence of EBV-encoded RNA-1 in tumor cells. All 80 adenocarcinomas and 50 mesotheliomas were negative for EBV-encoded RNA-1 by in situ hybridization. In conclusion, no evidence for an etiologic role for EBV in the development of pulmonary adenocarcinoma or pleural mesothelioma was found in this study.