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T V Colby

Publications and source records attributed to T V Colby.

At least 127 records · Page 7Linked to original sources
PubMed1993

p53 protein accumulates frequently in early bronchial neoplasia.

p53 mutations are common in human lung cancer and frequently generate levels of p53 protein that are detectable by immunohistochemistry. For this reason, p53 protein accumulation is a candidate biomarker, but little is known about its timing or frequency in multistage bronchial carcinogenesis. We studied human lung tissues containing preinvasive squamous neoplasms from 34 donors with and without lung cancer. Nuclear p53 protein was present in 0% of normal mucosas, 6.7% of squamous metaplasias, 29.5% of mild dysplasias, 26.9% of moderate dysplasias, 59.7% of severe dysplasias, 58.5% of carcinomas in situ, 67.5% of microinvasive carcinomas, and 79.5% of invasive tumors. These data indicate that (a) p53 protein accumulates in about 30% of the earliest recognized neoplastic lesions (i.e., mild dysplasia), (b) there is an increasing frequency of p53 protein accumulation starting with mild dysplasia, and (c) p53 protein accumulates infrequently in normal or metaplastic mucosa. In a subset of six patients whose most advanced lesion was carcinoma in situ without evidence of invasive cancer, p53 protein was detected in 0% of normal mucosas, 8.3% of squamous metaplasias, 37.5% of mild dysplasias, 12.5% of moderate dysplasias, 93.8% of severe dysplasias, and 55% of carcinoma in situ lesions. These data show clearly that p53 alterations can occur before invasion and suggest that the frequency is similar to that observed in the full series. Since two-thirds or more of lung cancers have p53 alterations, the timing and frequency of p53 protein accumulation make the p53 tumor suppressor gene an attractive marker for early diagnosis and evaluation of chemoprevention agents.

Biomarkers, Tumor↗
PubMed1993

Diffuse pulmonary lymphangiomatosis.

Angiomatous lesions of the lung are uncommon and not well characterized. We describe nine cases of a distinct lymphatic vascular lesion that we have termed "diffuse pulmonary lymphangiomatosis." Extrathoracic lymphangiomatous lesions were not identified. The patients comprised seven males and two females with a mean age at presentation of 10 years (age range, 1 month to 33 years). Six patients were younger than 10 years of age. Symptoms included "wheezing" or "asthma" (44%) and dyspnea (22%) present for 3 months to 20 years. Chest radiographs showed bilateral interstitial infiltrates, often greatest in the lower lobes. Pleural or pericardial effusions were present or developed in six patients. Pulmonary function tests showed in two patients and mixed obstruction and restriction in five patients. Open lung biopsies (nine patients) and autopsy (one patient) showed anastomosing endothelial lined spaces along pulmonary lymphatic routes (especially pleural and interlobular septal) accompanied by asymmetrically spaced bundles of spindle cells, which were prominent in six cases. Hemosiderin deposition often was present in the spindle cell areas and in the adjacent lung. The lining cells were positive for factor VIII-related antigen (eight cases) and Ulex europaeus I agglutinin (four cases). The spindle cells were reactive with antibodies to vimentin (nine cases), desmin (six cases), actin (seven cases), progesterone receptor (seven cases), and proliferating cell nuclear antigen (one case); they were negative for estrogen receptor (seven cases), keratin, (eight cases), and HMB-45 (eight cases). Diffuse pulmonary lymphangiomatosis was progressive in eight cases and was most aggressive in the youngest children. Two of the children have died, one of pulmonary hemorrhage and the other after heart-lung transplantation. Diffuse pulmonary lymphangiomatosis is distinct from lymphangiectasis, lymphangioleiomyomatosis, pulmonary capillary hemangiomatosis, Kaposi's sarcoma, and kaposiform hemangioendothelioma. Due to its distribution and histology, a lymphatic origin of the lesion is favored.

Adolescent↗
PubMed1993

Thymoma.

Thymomas and thymic carcinomas are thymic epithelial tumors that constitute approximately 15% of all mediastinal masses. From 28 to 66% of thymomas cause chest symptoms as the initial manifestation; the rest are discovered on routine chest roentgenograms or during investigations prompted by the presence of a paraneoplastic syndrome. Forty percent of patients with thymoma have one or more paraneoplastic syndromes, including myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia. Extrathymic malignant lesions develop in up to 20% of patients. Traditional histologic classifications have not accurately predicted tumor behavior; a recently developed classification based on cellular differentiation toward thymic medullary or cortical epithelium may correlate better with prognosis. Nevertheless, the prognosis is best predicted by stage of the tumor determined intraoperatively and is poorer in patients with incomplete resection than in those with complete resection of the thymoma. In addition to surgical intervention, irradiation and chemotherapy have important roles in the management of thymomas, particularly in advanced stages. In this article, the clinical manifestations, diagnosis, pathologic features, staging, and treatment of thymomas are reviewed, and the prognosis of affected patients is discussed.

Humans↗
PubMed1993

Pulmonary capillaritis. The association with progressive irreversible airflow limitation and hyperinflation.

We report two patients with systemic necrotizing vasculitis (microscopic polyarteritis) and associated recurrent pulmonary capillaritis, in whom progressive irreversible airway dysfunction began approximately 10 yr after disease onset. Their course was characterized by repeated episodes of diffuse alveolar hemorrhage, glomerulonephritis, palpable purpura, and splinter hemorrhages. The lung revealed intraalveolar hemorrhage, neutrophilic infiltration and cellular fragmentation, fibrinoid necrosis of the alveolar interstitium, and parenchymal hemosiderin deposits. No medium-sized vessel involvement, granulomatous inflammation, or bronchiolar obliteration were seen. Renal biopsies revealed focal segmental necrotizing glomerulonephritis, and a cutaneous biopsy in one case showed a leukocytoclastic vasculitis. Immunofluorescent studies of lung and kidney showed minimal or no immunoreactivity. The clinical course and serologic tests did not support another systemic vasculitis, connective tissue disease, or antiglomerular basement membrane antibody disease. The acute episodes responded to antiinflammatory and immunosuppressive therapy. Symptoms, serial pulmonary function tests, and chest imaging documented the development of a progressive irreversible obstructive airway disease. No other predisposing factors were identified. These cases demonstrate the unexpected appearance of an irreversible obstructive airway disease with lung parenchymal hyperinflation after systemic necrotizing vasculitis associated with recurrent pulmonary capillaritis and diffuse alveolar hemorrhage.

Adult↗
PubMed1993

Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?

To determine the histologic differences in the airways of patients who died from sudden-onset asthma and the more common slow-onset asthma, we studied seven cases of fatal asthma. The numbers of eosinophils and neutrophils, as well as extracellular deposition of their respective granule contents in the airway mucosa and submucosa, were determined and statistically analyzed. Four of the seven patients had slow-onset asthma attacks in which the time interval between onset of asthma and death was more than 2.5 h. In contrast, three patients had sudden-onset asthma in which the time interval between onset of asthma attack and death was less than 1 h. The four patients with slow-onset fatal asthma had more eosinophils (34.1 +/- 6.3 in slow-onset; 9.7 +/- 3.5 in sudden-onset; p = 0.002) and fewer neutrophils (4.8 +/- 2.0 in slow-onset; 16.8 +/- 5.4 in sudden-onset; p = 0.008) in the airway submucosa than did patients with sudden-onset fatal asthma. In addition, within the slow-onset fatal asthma group, eosinophils exceeded neutrophils in the airway submucosa (eosinophils > neutrophils, p = 0.002). By contrast, within the sudden-onset fatal asthma group, neutrophils exceeded eosinophils (neutrophils > eosinophils, p = 0.04). We suggest that sudden-onset fatal asthma is immunohistologically distinct from slow-onset fatal asthma and that it is characterized by a relative paucity of eosinophils in the face of an excess of neutrophils in the airway submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Cryptogenic constrictive bronchiolitis. A clinicopathologic study.

Four women with a chronic respiratory illness characterized by chronic cough, dyspnea, mild to severe physiologic abnormalities, relatively normal chest radiographs, and lack of response to bronchodilators or prednisone were identified and prospectively evaluated. Constrictive bronchiolitis, defined as concentric narrowing of the bronchiolar lumen, mural scarring, smooth muscle hyperplasia, and mucus stasis, was the major histologic finding on open lung biopsy in all cases. Each presented with an illness clinically distinct from asthma, connective tissue disorders, occupational or environmental lung disease, bronchiectasis, diffuse panbronchiolitis, cystic fibrosis, and emphysema. None of the patients smoked cigarettes. None had clinical evidence of a recent viral lower respiratory tract infection. The physical examinations were normal except for rales heard on chest examination in two patients. Chest radiographs showed increased bronchovascular markings in three patients. Lung function was normal in one patient, two of the patients had a reduced diffusing capacity associated with moderate hypoxemia and an obstructive ventilatory defect, and one patient exhibited a mixture of restrictive and obstructive defects. None have experienced significant progression of their disease over 1 to 5 yr of follow-up. However, complete return to normal function did not occur. We hypothesize that patients with the constellation of findings described represent a distinct and definable clinicopathologic entity and further clarifies the spectrum of "small airways disease." Establishing the diagnosis appears important for prognostic and possibly therapeutic reasons.

Adult↗
PubMed1993

Wegener's granulomatosis in the 1990s--a pulmonary pathologist's perspective.

The diagnosis and classification of vasculitic syndromes in general requires a correlation of clinical histologic and serologic data. Classifications based solely on clinical or histologic features have proven unsatisfactory. WG is no exception, and proper diagnosis and management of patients with WG requires careful correlation of all available clinical, radiographic, serologic, and histologic data by experienced individuals. Active discourse between the clinician and pathologist frequently helps in the decision as to how to proceed in an individual case and whether or not further diagnostic tests are necessary.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Pathologic manifestations of bronchiolitis, constrictive bronchiolitis, cryptogenic organizing pneumonia, and diffuse panbronchiolitis.

This article reviews the histopathological findings in a variety of inflammatory bronchiolar diseases. The emphasis is on differentiating syndromes of idiopathic airflow limitation (constrictive bronchiolitis and diffuse panbronchiolitis) from cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia). The histopathological findings in each of these conditions are relatively nonspecific; therefore, it is imperative that pathological findings are correlated with clinical and roentgenographic information before a specific diagnosis is made.

Acute Disease↗
PubMed1993

Tryptophan-induced lung disease: an immunophenotypic, immunofluorescent, and electron microscopic study.

L-tryptophan (LT) has been implicated as a causal agent in the recently recognized eosinophilia-myalgia syndrome (EMS). Pulmonary complications occur in up to 60% of patients. Lung biopsies have shown chronic interstitial pneumonia, mild eosinophilia, vasculitis and perivasculitis, and hypertensive pulmonary arteriopathy. Open lung biopsies from two women who developed respiratory symptoms associated with LT EMS were studied with a panel of antibodies to lymphoid cells, by transmission electron microscopy and by direct immunofluorescence for immunoglobulin and complement. The majority of the cells infiltrating the interstitium and around vessels were T-cells, with a predominance of CD8+ cells. Numerous alveolar macrophages were also identified. Rare polyclonal B-cells were also present. Ultrastructural studies confirmed the presence of interstitial and perivascular lymphocytes as well as occasional eosinophils. The inflammatory cells were also present in vessel cells. Fibrointimal thickening was not observed in the sections studied ultrastructurally. Immunofluorescent staining for IgG, IgA, C3, C4, albumin, kappa, and lambda was negative. There was scattered staining for fibrinogen in alveolar spaces. The etiology of LT EMS is still under investigation, although a contaminant acting in conjunction with host factors is the favored hypothesis. The results of this study indicate that T cytotoxic/suppressor cells may be intimately involved in the pathogenesis of the lung injury.

Adult↗
PubMed1993

The lung in inflammatory bowel disease.

Respiratory involvement in patients with inflammatory bowel disease (IBD) has been reported mainly since 1976. This form of involvement should clearly be separated from interstitial lung disease due to sulfasalazine or mesalamine, although the distinction may be difficult in some cases. We report the data of an ongoing Registry containing 33 cases (23 cases receiving no drug therapy) with ulcerative colitis or, less often, Crohn's disease, who developed varied bronchopulmonary problems. In several cases, the exact diagnosis and the relation of the bronchopulmonary disease to IBD had not been established for many years, thus delaying effective treatment with steroids. In most cases (28/33), respiratory involvement followed the onset of IBD (8 of these 28 cases were postcolectomy), and in the remainder, respiratory manifestations predated the IBD. Patterns of involvement included: 1) Airway inflammation, in the form of subglottic stenosis, chronic bronchitis, severe chronic bronchial suppuration, bronchiectasis, and chronic bronchiolitis. In cases with large airway involvement, endoscopy showed exuberant inflammatory tissue in the airways and narrowing of tracheal and/or bronchial lumen. Histologically, airways were heavily infiltrated by a dense aggregate of inflammatory cells, and there were mucosal ulcerations. 2) Varied patterns of interstitial lung disease, mainly bronchiolitis obliterans with organizing pneumonia, and pulmonary infiltrates and eosinophilia. (3) Miscellaneous other forms of involvement including striking neutrophilic necrotic parenchymal nodules (corresponding histologically to sterile aggregates of neutrophils), and serositis. Steroids were very effective in the majority of cases. Inhaled steroids were of durable benefit in patients with chronic bronchitis, but less often so in those with chronic bronchial suppuration, bronchiectasis, or chronic bronchiolitis. Steroids administered orally led to marked improvement in patients with interstitial lung disease and necrotic nodules, but lacked effectiveness in several patients with severe airway inflammation or chronic bronchiolitis. Intravenous steroids were required in the initial management of life-threatening complications such as asphyxiating subglottic stenosis or extensive interstitial lung disease. Bronchial lavages with methylprednisolone were effective in some patients with severe airway inflammation. Patients with IBD can develop varied inflammatory complications in the lung, and a sizable fraction of these complications is steroid-sensitive.

Adolescent↗
PubMed1992

Desmoplastic malignant mesothelioma masquerading as sclerosing mediastinitis: a diagnostic dilemma.

A 48-year-old woman presented with dyspnea, chest discomfort, and left vocal cord paralysis that developed 2 months after a flu-like illness. Radiographic examination showed prominence of mediastinal soft tissues and an ill-defined left upper lobe infiltrate. Dense mediastinal sclerosis was found at thoracotomy, and biopsy samples taken from the sclerotic areas showed densely hyalinized fibrotic tissue. Necrotizing granulomas containing organisms resembling Histoplasma capsulatum were present within mediastinal lymph nodes. Based on these findings, a diagnosis of sclerosing mediastinitis was made. During the next year, the patient's respiratory function deteriorated, and biopsy samples taken during a second thoracotomy 1 year later were again interpreted as sclerosing mediastinitis. The patient died postoperatively; at autopsy, the sclerotic mass involving the mediastinum was composed of a mixture of dense fibrosis and sarcomatous tissue. The final diagnosis was localized mediastinal desmoplastic malignant mesothelioma. We report it here because of its unusual clinical presentation, which mimicked sclerosing mediastinitis.

Autopsy↗
PubMed1992

Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis.

Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis-associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic. These patients were divided into two groups on the basis of treatment for the diabetes insipidus: The first group (radiation group) included 30 patients (28 of whom were evaluable for response) who received hypothalamic-pituitary radiation therapy, and the second group (control group) included 17 patients who did not. A partial response to treatment was defined as a reduction in vasopressin dosage or improvement in computed tomography (CT) or magnetic resonance imaging (MRI). A complete response was defined as no further need for vasopressin therapy or normalization of CT or MRI. End points analyzed included treatment response, patient characteristics, morbidity, dose-response relationship, and survival. Patient characteristics of the two groups were similar except for age and lung involvement, both of which were significantly less in the radiation group. Thirty-six percent of patients (10 of 28) in the radiation group responded to hypothalamic-pituitary radiation therapy (22% complete response and 14% partial response), whereas none in the control group responded. Five of the six complete responders were irradiated within 14 days of the diagnosis of diabetes insipidus. The mean dose used in the responding and nonresponding patients was 11.2 and 10 Gy, respectively. Three of five patients (60%) treated with more than 15 Gy responded compared to seven of 23 (30%) treated with less than 15 Gy. Eight of the 10 responders (80%), compared to 16 of 35 nonresponders (46%), were female. Only one in 20 patients with concomitant lung histiocytosis responded. Complications of therapy may include insufficiency in other hypothalamic-pituitary axes in the treated patients. Actuarial survivals at 5, 10, 20, and 40 years for the entire group were 80%, 78%, 75%, and 65%, respectively, with a median follow-up in living patients of 14.7 years.

Adolescent↗
PubMed1992

Immunofluorescent staining for mast cells in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase.

In many diseases, retrospective analysis for determining the presence of mast cells has been difficult because of their loss of metachromatic staining properties once tissue has undergone formalin fixation. We quantified mast cells in peribronchiolar tissue of idiopathic pulmonary fibrosis (IPF) and in normal human lung by using rabbit antiserum to human mast cell tryptase. In lung biopsy specimens from 15 patients with IPF, the mean number of mast cells per high-power field in connective tissue directly adjacent to the lumen of small airways (0.5 to 2 mm in diameter) and other fibrotic foci was 29.9 +/- 10.8 in comparison with 13.7 +/- 3.5 in 16 normal controls (P < 0.001). In addition, mast cells in cases of IPF had an altered appearance--irregularity of the plasma membrane and release of extracellular tryptase. We conclude that the number of mast cells is increased in IPF and that the altered appearance of the mast cells suggests that they are activated and undergoing degranulation.

Biopsy↗
PubMed1992

Comparison of extracellular matrix antigens in subtypes of bronchioloalveolar carcinoma and conventional pulmonary adenocarcinoma. An immunohistochemical study.

In contrast to the conventional pulmonary adenocarcinomas (CPAs), bronchioloalveolar carcinoma (BAC) grows predominantly by spreading along the existing alveolar septal framework. Within the BAC category, three subtypes have been identified: mucinous, nonmucinous, and sclerosing BAC. Of these, mucinous and sclerosing BACs have worse prognoses compared with nonmucinous BAC. However, the manifestation of aggressive behavior is different between the mucinous and sclerosing types of BACs. Multifocality is often produced by aerogenous spread, especially in the case of mucinous BACs. To study the differences between the BAC subtypes and the conventional pulmonary adenocarcinomas, we employed a battery of immunohistochemical stains marking the extracellular matrix architecture (laminin, collagen IV, fibronectin, and collagen III), a degradative enzyme against a basement membrane component (anti-type IV collagenase) and cellular receptors for laminin and collagen IV (alpha 2 integrin) on 16 BACs (5 mucinous, 5 nonmucinous, and 6 sclerosing) and 30 CPAs. The mucinous and nonmucinous BACs demonstrated neoplastic epithelial cells growing along a continuous basement membrane. A similar growth pattern with intact basement membrane was noted in the periphery of sclerosing BACs. However, in contrast to mucinous and nonmucinous BACs, all cases of sclerosing BACs showed disruption or complete absence of basement membrane components (laminin and collagen IV) around the embedded glands located centrally in the sclerotic fibrous stroma, as was seen in the basement membrane analysis of conventional adenocarcinomas. Furthermore, increased type IV collagenase activity was seen in the small centrally located embedded glands in comparison to the peripheral glands. These architectural alterations of basement membrane disruption and phenotypic expression of degradative activity may be a reflection of the invasive behavior of the sclerosing BACs and their tendency to produce lymph node metastasis. Although the mucinous BACs did not show evidence of basement membrane disruption, there was a marked increase in their levels of type IV collagenase expression along with consistently low levels of alpha 2 integrin receptor (laminin and collagen IV receptor) expression. These findings may be related to the ability of the mucinous BACs to detach from the underlying basement membrane and spread aerogenously, and is to be contrasted with the stromal infiltration and desmoplasia of sclerosing BACs and CPAs.

Adenocarcinoma↗
PubMed1992

The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic, and surgical aspects.

Serous cystadenoma of the pancreas is a rare lesion thought to be almost invariably benign. Since 1978, 211 cases have been reported in the literature. Some have been recognized by computed tomography (CT) when small and asymptomatic. The authors have reviewed their experience with 40 patients (median follow-up of 1.9 years, maximum of 22.2 years) from 1936 to 1991. One third (13) were asymptomatic, of whom eight (20%) were discovered intraoperatively. Of those 20 who had CT, an unequivocal preoperative diagnosis was reached in none. Needle biopsy proved accurate in two patients. Endoscopic retrograde cholangiopancreatography (ERCP) and biopsy were performed with diagnostic success on one occasion. Three patients presented acutely. The tumor was resected in 90%, with an operative mortality rate of 10%. Enucleation of the tumor without formal anatomic pancreatectomy necessitated reoperation for complications in four of eight patients. Survival after successful resection paralleled expected survival. Serous cystadenoma may be associated with von Hippel-Lindau syndrome. The current role for conservative management remains questionable because of our current inability to reliably differentiate many of these benign neoplasms from malignant cystic neoplasms of the pancreas.

Adult↗
PubMed1992

Effect of external beam radiotherapy on prostatic carcinoma DNA content as measured by static image cytometry.

Static image cytometry was used to study the effect of radiotherapy on the DNA content of prostatic carcinoma. Feulgen-stained specimens from 50 patients before and after radiotherapy were examined. The DNA index increased significantly after treatment (p less than 0.03), and it occurred equally in those with low (less than 1.5) and high (greater than or equal to 1.5) indices. The level of the initial DNA index was significantly related to the rate of symptomatic progression (p less than 0.05). The initial change in and final DNA indices were not related to survival however. There was a significant increase in Gleason score (p = 0.001) and histological grade (p = 0.01) after irradiation and, when taken individually, the degree of change was related to survival in both, p = 0.05 and 0.004, respectively. As Gleason score, Mayo grade and clinical stage were not independent variables; none of them was related to survival when corrected for the other factors. Thus, DNA content or ploidy, as well as Mayo grade and Gleason score, increases in recurrent tumor after radiotherapy. This may be of importance when considering what treatment to use and how intensively the patients should be followed up.

Actuarial Analysis↗
PubMed1992

Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system.

The objective of this study was to determine the accuracy of a semiquantitative method of assessing the relative degree of cellularity and fibrosis compared with a morphometric analysis of specific histopathologic features in idiopathic pulmonary fibrosis (IPF). Morphometric analysis was performed on biopsy tissue from 20 patients. Morphometry showed that approximately 70% of parenchymal tissue was abnormal: 35% cellular consolidation and fibrosis, 20% honeycomb changes, 10% thick alveolar septa, and 5% small airways within abnormal parenchymal tissue. The prominent components of the abnormal parenchymal tissue were extracellular fibers, an abundance of interstitial cells, and epithelial cell hyperplasia. Correlation between four groupings of pathologic features, identified by a semiquantitative analysis, and each of the components of the parenchymal lesions showed significant correlations between (1) the fibrotic or reparative factor (alveolar wall metaplasia, fibrosis, honeycombing, and smooth muscle and vascular changes) and components of honeycomb lesions (extracellular fibers, interstitial cells, and epithelial injury and repair), and (2) the inflammatory and exudative factor and extracellular fibers in the lesions. These results support that the scoring system used by the pathology panel provides an accurate assessment of pathologic features useful in the assessment of the extent and severity of the histopathologic lesions of IPF.

Biopsy↗