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T V Colby

Publications and source records attributed to T V Colby.

At least 109 records · Page 6Linked to original sources

Gender comparisons in human lung cancer: analysis of p53 mutations, anti-p53 serum antibodies and C-erbB-2 expression.

Little is known about the molecular mechanisms of lung carcinogenesis in women. We initiated an investigation of the role of gender in pulmonary carcinogenesis by analysis of p53 mutations, immunohistochemistry, serum antibodies and c-erbB-2 expression in a series of 63 male and 44 female lung cancer patients whose tumors were resected at the Mayo Clinic between 1991 and 1992. There were 102 smokers and 5 never smoked. Adenocarcinoma was the more frequent histological type in women (62%) than in men (41%). Sequence analysis of exons 5-8 in 42 females and 49 males identified 44 p53 mutations in 42 tumors (46%). Base substitution mutations showed a preponderance of G:C-->T:A transversions, which were more frequent in women than men (40 versus 25%) and in individuals exposed to asbestos. c-erbB-2 immunohistochemical staining was identified more frequently in females (nine cases) than males (two cases). Marked immunohistochemical staining for p53 positively correlated with the presence of missense mutations in exons 5-8 (81%, P < 0.001). Seven missense mutations (four in exon 5, two in exon 6, one in exon 8) were identified in five of nine patients who had serum antibodies recognizing p53; tumors from these patients were also strongly positive for p53 by immunohistochemistry. These and other results indicate gender differences in the genetic and biochemical alterations in lung cancer and generate hypothesis regarding gender differences in lung cancer susceptibility.

Adenocarcinoma↗

Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?

OBJECTIVE: The authors review their recent experience with resected pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Ductal adenocarcinoma of the pancreas has traditionally had a 5-year survival rate less than 10% after curative resection. Recently, several groups have reported markedly improved 5-year survival rates (approaching 25%) for patients undergoing curative resection. METHODS: Institutional experience with 186 consecutive patients (1981-1991) with pathologic diagnoses of ductal adenocarcinoma undergoing pancreatic resection was reviewed. Histologic specimens of all 3-year survivors (n = 31) were re-reviewed by two pathologists, one internal and one external; nonductal pancreatic cancers then were excluded. RESULTS: After histologic re-review, 12 patients did not have ductal adenocarcinoma, leaving a total of 174 patients for analysis (102 men, 72 women; mean age 63 years, range 34-82 years). Mean follow-up was 22 months (range 4-109). Classical pancreaticoduodenectomy was performed in 71%, pylorus-preserving resection in 9%, and total pancreatectomy in 20%. Hospital mortality was 3%. Twenty-eight patients (16%) had macroscopically incomplete resections; 98 (56%) had lymph node metastases within the resected specimens, and 21 patients (12%) had extensive perineural invasion. Overall actuarial 5-year survival was 6.8%. Five-year survival was greater for node-negative versus node-positive patients (14% vs. 1%, p < 0.001), and for smaller (< 2 cm) versus larger tumors (20% vs. 1%, p < 0.001). The 5-year survival for the subset of patients with negative nodes and no perineural or duodenal invasion (69 patients) was 23% (p < 0.001). Mean survival of the 12 excluded patients was 53 +/- 7 months compared with 17.5 +/- 1 months in the 174 patients with ductal pancreatic cancer. CONCLUSIONS: Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically "curable" intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%. Survival is greater (23%) in the subset of patients with negative nodes and no duodenal or perineural invasions. Pathologic review of all patients with pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be meaningful.

Adult↗

Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material.

PURPOSE: To determine if the degree of enhancement of pulmonary nodules is directly related to the likelihood of malignancy and to the vascularity of the nodule. MATERIALS AND METHODS: Uncalcified 6-40-mm-diameter pulmonary nodules were studied in 163 patients with malignant neoplasm (n = 111), granuloma (n = 43), and benign neoplasm (n = 9). Serial thin-section computed tomography (CT) was performed before and after injection of 100 mL of nonionic contrast material at 2 mL/sec. The maximum level of enhancement was recorded. Eighteen histologic specimens were graded after vascular staining. RESULTS: Malignant neoplasms enhanced (median, 40.0 HU; range, 20-108 HU) significantly more than granulomas and benign neoplasms (median, 12.0 HU; range, -4 to 58 HU) (P < .001). With 20 HU as the threshold for a positive test, sensitivity was 100%; specificity, 76.9%; positive predictive value, 90.2%; negative predictive value, 100%; and accuracy, 92.6% (prevalence of malignancy, 68.1%). Degree of enhancement was significantly related to amount of central vascular staining (P = .003). CONCLUSION: Enhancement is an indicator of malignancy and vascularity.

Adult↗

Tracheobronchial involvement in Wegener's granulomatosis.

This study was designed to characterize the clinical spectrum and course of tracheobronchial involvement in Wegener's granulomatosis (WG). Of the 51 patients with biopsy-proven WG who underwent bronchoscopy at least once at our institution between January 1982 and November 1993, 30 (59%) had endobronchial abnormalities due to WG. Initial findings included subglottic stenosis in five (17%), ulcerating tracheobronchitis with or without inflammatory pseudotumors in 18 (60%), tracheal or bronchial stenosis without inflammation in four (13%), and hemorrhage without identifiable source in two (4%) patients. Nine patients with ulcerating tracheobronchitis on initial study had subsequent bronchoscopies for continued symptoms, which in seven cases documented the progression from ulcerating tracheobronchitis to stenosis without inflammation. Bronchoscopic interventions included dilation by rigid bronchoscope in three, YAG-laser treatment in one, and placement of silastic airway stents in three patients. Only the stents provided persistent airway patency. Endobronchial biopsies were performed on 21 occasions in 17 patients. Half of the specimens were helpful in establishing the diagnosis and in all but three in assessing disease activity. While antineutrophil cytoplasmic antibody titers reflect overall disease activity, no correlation with endobronchial inflammatory activity was apparent.

Adult↗

Increased expression of type VI collagen in lung fibrosis.

Pulmonary fibrosis is characterized by disturbances of extracellular matrix protein deposition resulting from fibroblast activation and proliferation. Collagen VI, forming microfibrillar meshworks separate from major fibrillar systems, is thought to serve as an anchoring element between collagen I/III fibrils and basement membranes and as a cell binding substrate. We report on the expression of collagen VI in normal and in fibrotic lungs. Collagen VI is present in vascular and bronchial walls and in the interstitial space of normal lungs. Its turnover is too low to generate a mRNA signal by in situ hybridization. Collagen VI expression is increased in lung fibrosis, and its degree appears independent of the etiology of fibrosis. There was no evidence for differential regulation of gene expression for the alpha 1(VI) and alpha 3(VI) constitutive peptide chains of collagen VI. Collagen VI mRNA is expressed by fibroblasts, mostly with myofibroblast characteristics. Collagen VI was coexpressed with collagen III rather than collagen I in idiopathic bronchiolitis obliterans with organizing pneumonia, acute interstitial pneumonitis of the Hamman-Rich type, and bleomycin-induced fibrosis, but collagen VI overlapped with collagen types I and III in idiopathic pulmonary fibrosis. These coexpression data suggest that collagen VI expression may be an early rather than a late phenomenon in pulmonary fibrosis.

Collagen↗

Correlation of structure and function in idiopathic pulmonary fibrosis.

The early stage of idiopathic pulmonary fibrosis (IPF) is thought to involve a smaller number of alveoli and to be characterized predominantly by cellularity and minimal fibrosis, whereas advanced disease involves a large number of alveoli and is characterized predominantly by fibrosis with minimal cellularity. In addition, correlative studies have indicated that prognosis and response to therapy is determined in part by the extent of fibrosis and cellularity. This study was undertaken to determine whether pulmonary function assessment would help distinguish between the cellular and fibrotic phases of this disorder, as determined by a semiquantitative pathology scoring system that comprised four factor scores: fibrosis, cellularity, granulation/connective tissue, and desquamation. Ninety-six untreated patients with biopsy-confirmed IPF (27 never smokers, 32 current smokers, and 37 ex-smokers) were evaluated. In the group as a whole, there was no significant relationship between the fibrosis or the connective/granulation tissue factor scores and any of the physiologic parameters. The DLCO correlated with the "desquamation" and the total pathology scores, whereas the TLC and FVC correlated with the cellularity factor score. In the current smokers, the coefficient of elastic retraction, DLCO/VA, and FEV1/FVC ratio were significantly lower than in never smokers and ex-smokers, and TLC and FVC were higher than in never smokers. Also, the mean cellularity and granulation/connective tissue factor scores were significantly lower, and the desquamation factor score was significantly higher than those in never smokers and ex-smokers. Both age and smoking status were significant for the cellularity factor score, whereas for the connective/granulation tissue factor score, age was not significant but smoking status was.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chronic eosinophilic pneumonia and idiopathic bronchiolitis obliterans organizing pneumonia: comparison of eosinophil number and degranulation by immunofluorescence staining for eosinophil-derived major basic protein.

OBJECTIVE: To undertake additional assessment of the possible overlap between bronchiolitis obliterans organizing pneumonia (BOOP) and chronic eosinophilic pneumonia (CEP). DESIGN: We retrospectively reviewed open-lung biopsy specimens from six patients with CEP, five patients with idiopathic BOOP, and four patients with secondary BOOP, encountered during the 5-year period 1986 through 1991, for the presence of eosinophils and extent of eosinophil degranulation. MATERIAL AND METHODS: Using previously described immunofluorescence methods for detection of intact eosinophils and extracellular deposition of eosinophil-derived major basic protein, we counted the number of eosinophils per x160 microscopic field and evaluated the extent of eosinophil degranulation semiquantitatively. RESULTS: The median numbers of eosinophils were 221 (range, 26 to 343) in cases of CEP, 7 (range, 1 to 65) in cases of idiopathic BOOP, and 7.5 (range, 1 to 39) in cases of secondary BOOP. More eosinophils were found in CEP than in idiopathic BOOP or all cases of idiopathic and secondary BOOP. We found no differences in the extent of eosinophil degranulation among the three groups, although a tendency for more degranulation was noted in cases of CEP. CONCLUSION: Even though clinical and histologic overlap may exist between CEP and idiopathic BOOP, the exact relationship and the role of the eosinophil in idiopathic BOOP remain to be determined.

Adolescent↗

Neurologic manifestations of Churg-Strauss syndrome.

OBJECTIVE: To determine the frequency and the types of neurologic involvement in a series of patients with Churg-Strauss syndrome (CSS). DESIGN: We reviewed the medical records of 47 consecutive patients with CSS who were examined at the Mayo Clinic between January 1974 and June 1992. MATERIAL AND METHODS: The study patients were classified into two groups: (1) those with a histopathologically confirmed diagnosis of CSS who had evidence of either vasculitis or Churg-Strauss granuloma, the presence of asthma, and peripheral eosinophilia (more than 10% eosinophils) on at least one differential leukocyte count (N = 33) and (2) those with a clinical diagnosis of CSS who had evidence of vasculitis based on either multiple mononeuropathy or necrotizing cutaneous lesions, the presence of asthma, and peripheral eosinophilia (more than 10% eosinophils) on at least one differential leukocyte count (N = 14). RESULTS: Of the 47 patients, 29 (62%) had neurologic involvement. Peripheral neuropathy was detected in 25 patients: 17 had multiple mononeuropathy, 7 had distal symmetric polyneuropathy, and 1 had an asymmetric polyneuropathy. Three patients had cerebral infarctions. Less commonly identified problems included radiculopathies, ischemic optic neuropathy, and bilateral trigeminal neuropathy. Asthma preceded the onset of neurologic involvement in all cases (mean duration, 6.7 years. Follow-up data, when available, showed that corticosteroid therapy usually yielded improvement or stabilization. CONCLUSION: Neurologic involvement is common in CSS, usually manifesting as peripheral neuropathy. In this series of patients, asthma preceded the neurologic manifestations.

Adolescent↗

Lymphomatoid granulomatosis. Evidence of immunophenotypic diversity and relationship to Epstein-Barr virus infection.

We studied open-lung biopsies from 17 patients with pulmonary lymphomatoid granulomatosis (LYG) using paraffin-section immunostains and Epstein-Barr virus (EBV) RNA in situ hybridization to assess the phenotype of these unique tumors and to clarify the role of EBV infection. Histologically, all cases demonstrated the characteristic mixed mononuclear cell infiltrate of lymphomatoid granulomatosis with variable numbers of cytologically atypical large lymphoid cells in a background of small lymphocytes. Paraffin-section immunostains in all cases showed a predominance of T lymphocytes. A minor population of CD20-positive large B lymphocytes was identified in 11 cases; immunoglobulin light-chain restriction was demonstrated in four of these and immunoglobulin gene rearrangements in another case. Nuclear labelling for EBV RNA was detected in 10 of these 11 cases and was confined to the population of large B lymphocytes. Staining for CD20 was absent in the remaining six cases, as was nuclear labeling for EBV RNA. However, the large atypical lymphoid cells stained for T-cell-lineage-specific antibodies in three of these cases. We conclude that some cases of lymphomatoid granulomatosis are B-cell lymphoma associated with EBV infection, whereas others are of T-cell origin and are probably unrelated to EBV infection.

Adult↗

Malignancies in the lung and pleura mimicking benign processes.

As pathologists, we are most concerned about overcalling reactive changes in the lung as carcinoma and the fact that malignant processes may be misinterpreted as benign processes in the lung is less well recognized. This review covers five such lesions. Well-differentiated adenocarcinomas, especially bronchioloalveolar carcinomas, are frequently undercalled, particularly in small biopsy and cytology specimens. In such cases, one must pay particular attention to the uniformity and monotony of the epithelium even though it may be extremely well differentiated. Spindle cell carcinomas may have necrosis and cavitation, interstitial growth, and a reactive fibroblastic reaction, and thus be mistaken as organizing inflammatory processes. Careful attention to the atypical cytological features, prominent vascular invasion, and getting immunohistochemical supports helps in recognizing them. Lymphoid lesions of the lung present a number of problems; small lymphocytic lymphomas and Hodgkin's disease are often misinterpreted as inflammatory processes. Intravascular lymphomatosis in the lung may be misinterpreted as an interstitial pneumonia if one does not appreciate the atypical lymphoid cells within the capillaries. The desmoplastic variant of sarcomatous mesothelioma may be extremely difficult to diagnose, because large portions of the tumors are composed of bland-appearing fibrous tissue. A case of desmoplastic mesothelioma presenting predominantly as a mediastinal mass is discussed, and problems in differential diagnosis are outlined. Angiosarcomas are rare tumors, but an appreciable percentage of them present as pulmonary metastases which may be interpreted as pulmonary hemorrhage or organizing infarction. The clinical and radiographic pattern, usually mimicking metastatic disease, and the fact that atypical spindle cells occlude small pulmonary arteries with surrounding alveolar hemorrhage are clues to the recognition of these lesions.

Adenocarcinoma↗

Diffuse panbronchiolitis: diagnosis and distinction from various pulmonary diseases with centrilobular interstitial foam cell accumulations.

Diffuse panbronchiolitis (DPB) is a clinicopathologic entity characterized histologically by chronic inflammation principally affecting the respiratory bronchioles. Few pathologists outside Japan are familiar with this entity. The most distinctive pathologic feature of DPB is chronic inflammation and an accumulation of foam cells in the walls of the respiratory bronchioles, adjacent alveolar ducts, and alveoli (PB unit lesion). The differential diagnosis is important both clinically and histologically because of the similarity of DPB to other chronic airway diseases. We report seven cases of DPB and 20 examples of a histologically similar lesion (PB-like lesion) found in a large review of cases of bronchiolitis, cystic fibrosis, bronchiectasis, aspiration pneumonia, extrinsic allergic alveolitis. Wegener's granulomatosis, bronchocentric granulomatosis, and malignant lymphoma. The results indicate that the PB-like lesion is a nonspecific histologic finding; the diagnosis of DPB can be made only in the appropriate clinical setting and when other conditions have been carefully ruled out.

Adult↗

Pathologic features of lung biopsy specimens from influenza pneumonia cases.

Most histopathologic descriptions of influenza pneumonia are based on autopsy findings in fatal cases during epidemics and pandemics of influenza. We describe the histologic findings of influenza pneumonia observed in biopsy material derived from six sporadic cases of influenza (influenza A, four cases; influenza B, one case; and influenza A and B, one case). Four patients recovered completely, one patient died, and one was lost to follow-up. In addition to confirming previously published pathologic descriptions of influenza pneumonia, we also document a spectrum of less severe histologic findings with mild acute lung injury and bronchiolitis obliterans with organizing pneumonia.

Adult↗

Immunohistochemical localization of transforming growth factor-beta 1 in the nonnecrotizing granulomas of pulmonary sarcoidosis.

Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by the formation of nonnecrotizing granulomas in affected tissues, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming growth factor-beta 1 (TGF-beta 1) is a potent cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha 5 beta 1 fibronectin receptor. The role of TGF-beta 1 in promoting lung fibrosis in the setting of pulmonary sarcoidosis has not yet been investigated. Accordingly, we determined the extent and distribution of TGF-beta 1 in lung tissue obtained from seven patients with clinical and histologic features of pulmonary sarcoidosis. The tissue distributions of TGF-beta 1, the TGF-beta 1 binding proteoglycan decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor were assessed immunohistochemically. In all cases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta 1. We further demonstrated decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue surrounding the lesions. TGF-beta 1 staining was also observed in bronchiolar epithelial cells, hyperplastic Type II pneumocytes, and occasional alveolar macrophages. This study demonstrates enhanced tissue localization of TGF-beta 1 and related extracellular matrix proteins associated with the nonnecrotizing granulomas of pulmonary sarcoidosis. Through its actions on matrix protein synthesis, TGF-beta 1 may modulate the fibrotic repair process accompanying granuloma healing in sarcoidosis.

Adult↗

Diffuse alveolar hemorrhage due to antibasement membrane antibody disease appearing with a polyglandular autoimmune syndrome.

We describe a patient with type 3-C polyglandular autoimmune syndrome who presented with diffuse alveolar hemorrhage and normal renal function. The diagnosis of antibasement membrane antibody disease was established by immunofluorescent staining of transbronchial biopsy specimens. We suggest the incorporation of antibasement membrane antibody disease into the spectrum of diseases that define the polyglandular autoimmune syndromes.

Adult↗

Agnogenic myeloid metaplasia with extramedullary hematopoiesis and fibrosis in the lung. Report of two cases.

Agnogenic myeloid metaplasia (AMM) is a chronic hematologic disorder with a long clinical course, characteristically accompanied by extramedullary hematopoiesis (EMH) in various organs, most commonly the spleen and liver. We describe two cases of AMM with clinically significant and ultimately fatal EMH and associated fibrosis in the lung and pleura. The literature on AMM and EMH involving the lung and pleura is reviewed. Three similar cases were found.

Aged↗

Rhodococcus equi pneumonia and pulmonary malakoplakia in acquired immunodeficiency syndrome. Pathologic features.

Pulmonary infection with Rhodococcus equi is rare, and most cases are seen in immunocompromised patients, particularly those with acquired immunodeficiency syndrome. We describe the pathologic features in four cases of culture-positive R equi pneumonia occurring in patients infected with human immunodeficiency virus. All four patients had a solitary cavitary pulmonary mass that was resected (n = 3) or had undergone biopsy (n = 1). Pathologically, all specimens revealed sheets of histiocytes with abundant foamy to eosinophilic cytoplasm with numerous phagolysosomes that were positive for periodic acid-Schiff, Gomori methenamine silver, and Grocott stains. Occasional histiocytes contained Michaelis-Gutmann bodies, diagnostic of malakoplakia. The Michaelis-Gutmann bodies yielded positive results with periodic acid-Schiff, Gomori methenamine silver, Grocott, Giemsa, and von Kossa stains (three of three cases studied) and with alizarin red and Prussian blue stains (two of three cases studied). Many gram-positive coccobacilli within histiocytes and associated with neutrophils were found in one case. Ultrastructural study of one case showed histiocytes containing abundant phagolysosomes with degenerated bacterial components and Michaelis-Gutmann bodies. The latter had a targetoid appearance with variegated phagolysosome cores that were mineralized by deposition of electron-dense spicules surrounded by peripheral rings of granular and membranous material. Based on our observations and reports in the literature, there appears to be a more than coincidental association between pulmonary R equi infection, malakoplakia, and human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome↗

Mesothelial/monocytic incidental cardiac excrescences: cardiac MICE.

We have identified four new cases of the cardiac lesion resembling a histiocytoid (epithelioid) hemangioma from the consultation and surgical pathology files of the Mayo Clinic from 1979 to 1992. The lesions occurred in two men and two women, mean age 60 yr (range, 55 to 63), three of whom had undergone previous cardiac catheterization. All were found incidentally, two as separate tissue fragments obtained by right ventricular endomyocardial biopsy during investigations for dilated cardiomyopathy, and two during mitral valve replacement (one free floating in the left atrium and the other attached to the mitral valve). The latter two lesions measured 1.0 and 0.8 cm. All were composed of histiocytes (macrophages) focally admixed with cuboidal cells which formed strips and tubular arrays in three cases. Immunohistochemistry (two cases) confirmed their biphasic nature with cytokeratin positivity of the cuboidal cells and CD68 (KP-1) positivity (macrophage-myeloid lineage) of the histiocytes. Carcinoembryonic antigen and Leu-M1 were negative for both cell types. Transmission electron microscopy (two cases) showed macrophage-like cells and cuboidal cells with intracytoplasmic intermediate filaments, desmosome-like cellular junctions, and rough endoplasmic reticulum consistent with mesothelial cells. All four patients had a benign clinical course (range, 2 mo to 13 yr). This mesothelial and monocytic (histiocytic) process is postulated to relate to previous cardiac catheterization (applicable in three of our patients). The importance of these nodules, which are likely reactive, is their potential confusion with metastatic adenocarcinoma. We propose the name mesothelial/monocytic incidental cardiac excresences (cardiac MICE) for these lesions.

Antigens, CD↗