PubMed Health⌕ Search

Biomedical subjects

T V Colby

Publications and source records attributed to T V Colby.

At least 19 recordsLinked to original sources
PubMed1998

Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer.

The fragile histidine triad (FHIT) gene at chromosome 3p14.2 is a candidate tumor suppressor gene linked to cancers of the lung, breast, colon, pancreas, and head and neck. Reports of frequent allelic deletion and abnormal transcripts in primary lung tumors plus recent evidence that it is targeted by tobacco smoke carcinogens suggest that it plays an important role in lung carcinogenesis. Non-small cell lung carcinoma still maintains a poor 5-year survival rate with the stage of disease at presentation as a major determinant of prognosis. We examined for allelic deletion at the FHIT locus in a series of 106 non-small cell lung carcinomas for which a full clinical, epidemiological, and 5-year survival profile was available. We found an allelic deletion frequency of 38% at one or two intragenic microsatellites. Allelic deletion of FHIT was related to tumor histology with 4 of 20 adenocarcinomas (20%) displaying loss of heterozygosity (LOH) compared with 12 of 22 (55%) nonadenocarcinomas (P = 0.03). We found that 63% of tumors with LOH of FHIT also had p53 missense mutations whereas only 26% with LOH had wild type p53 negative sequence (P = 0.02). We also found a significant trend toward poorer survival in patients with LOH of at least one locus of the FHIT gene (log rank, P = 0.01). This survival correlation is independent of tumor stage, size, histological subtype, degree of differentiation, and p53 mutation status. Our data support the hypothesis that the loss of the FHIT contributes to the molecular pathogenesis of human lung cancer and is an indicator of poor prognosis.

Acid Anhydride Hydrolases↗
PubMed1998

Reproducibility of neuroendocrine lung tumor classification.

For a tumor classification scheme to be useful, it must be reproducible and it must show clinical significance. Classification of neuroendocrine lung tumors is a difficult problem with little information about interobserver reproducibility. We sought to evaluate the classification of typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell carcinoma (SCC) tumors as proposed by W.D. Travis et al (Am J Surg Pathol 15:529, 1991). Forty neuroendocrine tumors were retrieved from the Armed Forces Institute of Pathology (AFIP) files and independently evaluated by five lung pathologists and classified as TC, AC, LCNEC, or SCC (pure SCC, mixed small cell/large cell, and combined SCC). A single hematoxylin and eosin-stained slide from each case was reviewed. Each participant was provided a set of tables summarizing the criteria for separation of the four major categories. Agreement was regarded as unanimous if all five pathologists agreed, a majority if four agreed, and a consensus if three or more pathologists agreed. The kappa statistic was calculated to measure the degree of agreement between two observers. A consensus diagnosis was achieved in all 40 cases (100%), a majority agreement in 31 of 40 (78%), and unanimous agreement in 22 of 40 (55%) of cases. Unanimous agreement occurred in seven of SCC (70%), seven of TC (58%), four of AC (50%), and four of LCNEC (40%). A majority diagnosis was achieved in 11 of 12 (92%) of TC, 9 of 10 (90%) of SCC, 6 of 8 (75%) of AC, and 5 of 10 (50%) of LCNEC. Most of the kappa values were 0.70 or greater, falling into the substantial agreement category. The most common disagreements fell between LCNEC and SCC, followed by TC and AC, and AC and LCNEC. The highest reproducibility occurred for SCC and TC, with disagreement in 8% and 10% of the diagnoses, respectively. For TC, 10% of the diagnoses rendered were AC. For AC, 15% of the diagnoses were rendered as TC, with 2.5% called LCNEC and 2.5% called SCC. For LCNEC, 18% and 4% of the diagnoses were called SCC and AC, respectively. For SCC, 4% of the diagnoses were called AC and 4% were called LCNEC. Thus, using the classification scheme tested, a consensus diagnosis can be achieved for virtually all neuroendocrine lung tumors with substantial agreement between experienced lung pathologists. Classification of NE tumors is most reproducible for classification of TC and SCC but less reproducible for AC and LCNEC. These results indicate a need for more careful definition and application of criteria for TC versus AC and SCC versus LCNEC.

Carcinoid Tumor↗
PubMed1998

Bcl-2 immunohistochemistry in a surgical series of non-small cell lung cancer patients.

The bcl-2 gene is implicated in oncogenesis by its ability to prolong cell survival through the inhibition of apoptosis, without increasing cell proliferation. An association between immunohistochemical staining for bcl-2 protein and the histological type and prognosis of non-small cell carcinoma was hypothesized by Pezzella et al. (N Engl J Med 329:690-694, 1993). In a case series, we stained formalin-fixed, paraffin-embedded tumor tissue from 106 surgical non-small cell lung cancer patients with an antibody to bcl-2 protein (DAKO clone 124, Carpinteria, CA). The resulting bcl-2 staining data were evaluated for associations with demographic, histological, immunohistochemical, and genetic features, including p53 mutations. Bcl-2 staining was observed in tumors from 29 of 106 (27%) of subjects, but was significantly less frequent in subjects' adenocarcinoma histology (8 of 55, 14.6%) (P = .007). This finding persisted after adjustment for age, gender, stage, grade, smoking history, and disease-free survival. In univariate analyses, no association was seen with age, weight, body mass index, gender, or pack-years smoking; tumor grade, stage, or patient performance status; p53 or c-erbB2 immunohistochemical staining, or p53 mutations. These data agree with earlier reports that bcl-2 staining is less common in adenocarcinomas; however, our data do not support the hypothesis that bcl-2 staining confers a better prognosis overall, in squamous cell carcinoma, or in an older patient population.

Adenocarcinoma↗
PubMed1998

Bronchiolitis. Pathologic considerations.

Bronchiolitis represents a cellular and mesenchymal reaction involving bronchioles. The interplay between the cellular infiltrate and the mesenchymal reaction affects the lumen size, lamina propria, muscular layer, and bronchiolar adventitia. The result is a variety of clinical, radiologic, and functional patterns of bronchiolar disease. The anatomy of the small airways is discussed, and a pathologic classification applicable to the surgical pathology of bronchiolitis is presented. The classification is practical and includes asthma, chronic obstructive pulmonary disease, cellular bronchiolitis, respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, bronchiolitis obliterans (including bronchiolitis obliterans with intraluminal polyps and constrictive bronchiolitis), dust-related small airway fibrosis, and (postinflammatory) bronchiolar scarring and peribronchiolar fibrosis.

Asthma↗
PubMed1998

Micronodular pneumocyte hyperplasia.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.

Adult↗
PubMed1998

Chronic diffuse interstitial fibrosis of the lung in uranium miners.

Many uranium miners have been disabled by and died of pulmonary fibrosis that was not recognized as an occupational disease. A review of animal studies, complications from whole body irradiation, pulmonary function, and mortality studies of uranium miners led us to suspect radiation-induced chronic diffuse interstitial fibrosis in miners who had inhaled excessive radon progeny. A selected group of uranium miners (22) with severe respiratory disease (but no rounded nodules in chest films) were studied. Lung tissue from five disclosed severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had small anthrasilicotic nodules and birefringent crystals. Although quartz crystals probably contributed, we concluded that the predominant injurious agent in these cases was alpha particles from radon progeny. This disease, after a long latent period, usually results in pulmonary hypertension, shortness of breath, and death by cardiopulmonary failure.

Adult↗
PubMed1998

Pulmonary mycotoxicosis: a clinicopathologic study of three cases.

Pulmonary mycotoxicosis (PM), also termed organic dust toxic syndrome or silo unloader's syndrome, is an acute illness resulting from massive inhalation of microbial toxins in organic dusts. It has not been well described histologically. Three cases of PM are presented in this report. Open lung biopsies were examined in each case. All of the patients were farmers with no prior lung disease. One had burning in his eyes, throat, and chest after exposure to moldy silage; chills, fever, dry cough, malaise, and weakness developed within 24 hours. Two patients presented with fever, progressive dyspnea, cough, and fatigue within 24 hours of emptying a corncrib, cleaning a chicken coop, and baling hay. Bilateral alveolar and interstitial infiltrates on chest roentgenograms and leukocytosis with neutrophilia were observed in all of the three patients. Two patients became hypoxemic and required mechanical ventilation. Histologic examination showed acute and organizing diffuse alveolar damage in two biopsy specimens and an acute bronchopneumonia in the third. One specimen had 1- to 10-microm ovoid organisms demonstrable with methenamine silver stains; cultures grew Fusarium and Penicillium species. The other two biopsy specimens had negative tissue cultures and special stains for organisms, although Penicillium species were grown from a preoperative bronchoalveolar lavage in one case. The two patients on mechanical ventilation recovered completely with high-dose steroids. The third patient recovered without steroids. No patient had residual functional deficits or chest radiographic abnormalities. PM can be distinguished from allergic and infectious diseases common in individuals exposed to large amounts of organic dust by its clinicopathologic features.

Adult↗
PubMed1997

Multicentric endobronchial smooth muscle tumors associated with the Epstein-Barr virus in an adult patient with the acquired immunodeficiency syndrome: a case report.

BACKGROUND: The incidence of benign and malignant smooth-muscle tumors (leiomyomas and leiomyosarcomas) is increased in children with the acquired immunodeficiency syndrome (AIDS). Epstein-Barr virus (EBV) infection has been implicated in the pathogenesis of these tumors. Smooth muscle tumors in adults with AIDS are extremely rare, with only six cases involving extrapulmonary sites reported in the literature. METHODS: Multifocal smooth walled endobronchial tumors were removed from a 35-year-old man with AIDS using rigid bronchoscopic laser resection. The tumor tissues were processed for routine histology, immunohistochemical stainings, and EBV in situ hybridization using an EBV-encoded RNA- 1 RNA oligonucleotide probe. RESULTS: Histologic features and immunohistochemical profiles were characteristic of smooth muscle tumors. EBV gene expression was detected in > 90% of tumor cell nuclei. Although overt histopathologic evidence of malignancy was lacking, some of the histopathologic findings, along with multifocality of the tumors and the rapid appearance of new tumors, suggested an unfavorable prognosis in this case. CONCLUSIONS: To the authors' knowledge, this is the first reported case of multicentric smooth muscle tumors involving the bronchi and lungs of an adult patient with AIDS. Diffuse EBV gene expression in the tumor tissue supports the hypothesis that EBV infection contributes to the pathogenesis of tumors of smooth muscle origin in immunocompromised hosts.

AIDS-Related Opportunistic Infections↗
PubMed1997

Silica-induced pleural disease: an unusual case mimicking malignant mesothelioma.

A 57-year-old man with a history of exposure to silica for 32 years presented with pleural thickening of the lower lobe of the left lung and a chronic right-sided pleural effusion without any radiographic evidence of parenchymal nodules in either lung. Light microscopic examination of a left visceral pleural biopsy specimen revealed markedly thickened pleura with fibrosis and macrophages containing birefringent silica and silicates. Occasional rounded intrapleural silicotic nodules were present. The underlying lung tissue did not show fibrosis or silicotic nodules. An energy-dispersive x-ray analysis confirmed the presence of silica. In the absence of lung involvement, this case represents a very unusual pathologic reaction caused by silica and silicates and adds to the clinical differential diagnosis of chronic pleuritis and malignant mesothelioma.

Diagnosis, Differential↗
PubMed1997

Organizing pneumonia. Features and prognosis of cryptogenic, secondary, and focal variants.

BACKGROUND: Organizing pneumonia (OP) is a non-specific response to many types of lung injury. Clinicians frequently encounter pathology reports of OP in patients with no underlying condition (cryptogenic OP, also known as BOOP or bronchiolitis obliterans OP) or in association with drugs or nonpulmonary disease. The goals of this study are to describe the clinical course and outcomes in patients with 3 clinical variants of OP. METHODS: A retrospective study of patients with OP seen at the Mayo Clinic, Rochester, Minn, from January 1, 1984, through June 30, 1994, was conducted. Initial features were obtained from medical records. Chest radiographs and pathology specimens were reviewed for this study. Resolution, relapse, and survival were obtained from medical records and a follow-up patient questionnaire. RESULTS: Seventy-four patients had pathologically confirmed OP. Organizing pneumonia was classified into 3 clinical groups: symptomatic cryptogenic OP; symptomatic OP related to underlying hematologic malignant neoplasm, collagen vascular disease, or drugs (secondary OP); and asymptomatic OP presenting as a focal nodule (focal OP). Thirty-seven patients (50%) had cryptogenic OP and 27 patients (36%) had secondary OP. No difference was found between cryptogenic and secondary OP in type or severity of symptoms, signs, laboratory and pulmonary function tests, or radiologic or pathologic findings. Corticosteroids were given at a similar initial dose (prednisone, about 50 mg/d). Resolution of symptoms was more frequent in patients with cryptogenic OP than those with secondary OP. Relapse was infrequent in both of these groups. Five-year survival was higher in patients with cryptogenic OP (73%) than in secondary OP (44%), and respiratory-related deaths were more frequent in patients with secondary OP. Organizing pneumonia was an asymptomatic focal rounded opacity in 10 patients (14%), most often detected on chest radiograph and diagnosed on lung biopsy done for suspicion of lung cancer. Patients with focal OP required no treatment and had no relapse or respiratory-related deaths. CONCLUSIONS: Clinical classification of OP is useful to predict clinical course and outcome. Cryptogenic OP most often was a symptomatic bilateral lung process that had an overall favorable prognosis with prolonged corticosteroid therapy. Patients with secondary OP had a high mortality rate when the disease was associated with predisposing conditions or drugs. Patients with asymptomatic focal OP had an excellent prognosis.

Aged↗
PubMed1997

Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel disease.

Basidiobolus ranarum is a fungus belonging to the Entomophthoraceae family and is mainly associated with subcutaneous soft tissue infection. The disease is usually characterized by an insidious onset of massive induration of the subcutaneous tissue involving the limbs, trunk, or buttocks. Most cases of basidiobolomycosis have been reported from Africa, South America, and tropical Asia. Visceral involvement is extremely rare. Only 4 cases with involvement of the gastrointestinal tract, including 1 fatal case originating in the United States, have been well documented in the English-language literature. This case report describes the first successfully treated patient residing in the United States who had B. ranarum infection involving the gastrointestinal tract.

Colonic Diseases↗
PubMed1997

Organizing diffuse alveolar damage associated with progressive systemic sclerosis.

Diffuse alveolar damage (DAD) is a relatively nonspecific pattern of acute lung injury that can be observed in a wide range of clinical circumstances. DAD has often been recognized in association with various connective tissue diseases; however, to our knowledge, it has not been previously reported in the setting of progressive systemic sclerosis. Herein we describe two patients with established diagnoses of progressive systemic sclerosis who had development of the acute respiratory distress syndrome. Open-lung biopsy specimens from both patients showed a histologic pattern of DAD with no identifiable cause other than their progressive systemic sclerosis. Our results suggest that DAD should be added to the list of pleuropulmonary complications of progressive systemic sclerosis.

Aged↗
PubMed1997

Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone.

We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim-Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a+ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim-Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim-Chester disease, are discussed.

Biomarkers↗
PubMed1997

p53 and K-ras mutational genotyping in pulmonary carcinosarcoma, spindle cell carcinoma, and pulmonary blastoma: implications for histogenesis.

In an attempt to understand the molecular pathogenesis of biphasic pulmonary neoplasms, the authors studied 25 cases of carcinosarcoma, spindle cell carcinoma, and pulmonary blastoma using a combined immunohistochemical and topographic genotyping approach for the presence of p53 abnormalities within the different epithelial and mesenchymal components of these tumors. Genotyping involved a search for point mutational damage in p53 exons 5-8, which was correlated with p53 immunoreactivity. This analytical approach demonstrated p53 missense point mutations in four of nine cases of spindle cell carcinoma with a 100% concordance rate between p53 immunopositivity and the presence of DNA mutational damage. One of six carcinosarcomas, heterologous in type, exhibited a p53 mutation. The concordance rate among carcinosarcomas was also 100%. However, the concordance rate among classic biphasic pulmonary blastomas was only 43%, with one of seven cases demonstrating a p53 mutation by DNA genotyping. The lack of concordance in pulmonary blastomas was possibly due to the existence of genotypically distinct subsets of tumor cells likely bearing mutations among largely nonmutated cells. In a similar fashion, among three well-differentiated fetal type adenocarcinomas, no p53 mutations were detected despite the presence of focal p53 immunopositivity in one of the cases. No K-ras mutations were detected in any of the 25 tumors examined. Monoclonal histogenesis from a single totipotential cell in a subset of these neoplasms (six of 22 cases) was supported by the finding of p53 overexpression and identical p53 mutational genotype in both the epithelial and spindle elements of the tumors. Furthermore, the finding of a small percentage of p53-positive tumor cells within one or both components suggests late acquisition of p53 mutational change in a subset of pulmonary blastomas.

Aged↗
PubMed1997

Pathology of lung cancer.

In this review, we focus on a number of developments pertaining to lung cancer diagnosis, entirely restricted to those parameters assessable by light microscopy. A number of discrete areas of interest stand out in 1996 related to the pathology of lung cancer. Aberrant p53 expression continues to be debated as an independent prognostic factor in nonsmall cell carcinoma. Neuroendocrine differentiation may be an independent prognostic factor in nonsmall cell carcinoma and new associations with the protein product of the bcl-2 oncogene have been described. Angiogenesis continues to arise as a predictor of metastatic potential in lung cancer. Finally, we review conceptual aspects of carcinogenesis from atypical adenomatous hyperplasia to bronchioloalveolar carcinoma, in addition to a variety of individual tumor-related issues associated with progression, response to chemotherapy, and survival.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1997

Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis.

We conducted a multicenter case-control study of clinically and histologically diagnosed idiopathic pulmonary fibrosis (IPF), a chronic diffuse interstitial lung disease of unknown cause. The study included 248 cases, and 491 control subjects identified through random-digit dialing, matched to cases in sex, age, and geographic region. Telephone interviews were conducted with both cases and controls to collect information on potential risk factors for IPF, including smoking and household, occupational, and environmental exposures. Pulmonary function tests, X-rays, computed tomographic (CT) scans of the chest, and lung biopsy reports were submitted by referring centers to support the diagnoses. An a priori hypothesis that smoking is associated with IPF was examined with conditional logistic regression analyses. More cases (72%) than control subjects (63%) had a history of ever smoking. The odds ratio (OR) for ever smoking was 1.6 (95% CI: 1.1 to 2.4). Risk was significantly elevated for former smokers (OR = 1.9; 95% CI: 1.3 to 2.9) and for smokers with 21 to 40 pack-yr (OR = 2.3; 95% CI: 1.3 to 3.8). A history of smoking is associated with an increased risk for the development of IPF. Although there was no clear exposure-response pattern with cumulative consumption of cigarettes, there was a trend for time since cessation of smoking, with the highest risk for those who had most recently quit.

Adult↗