Pathologic aspects of bronchiolitis obliterans organizing pneumonia.
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Biomedical subjects
Publications and source records attributed to T V Colby.
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BACKGROUND: The role of resection in the treatment of carcinoma of the distal pancreas remains unclear. The less frequent occurrence of tumor in the distal gland, advanced tumor stage at diagnosis, and a lack of reported success have combined to produce therapeutic nihilism in the minds of many surgeons. The goal of this review was to assess long-term survival after distal pancreatectomy for carcinoma of the pancreas. METHODS: The records of all patients undergoing distal pancreatectomy at the Mayo Clinic for a primary pancreatic malignant tumor during the 25-year period from 1963 to 1987 were reviewed. Forty-four patients undergoing potentially curative distal pancreatectomies were identified: 26 patients for ductal adenocarcinoma, 12 patients for islet cell carcinoma, and six patients for cystadenocarcinoma. RESULTS: Major postoperative morbidity occurred in 9% of the patients and operative death in 2% of the patients. Patients with ductal adenocarcinoma frequently were admitted with advanced disease (stage II or III). The median overall survival for patients with ductal adenocarcinoma was 10 months. Fifteen percent of the patients survived 2 years after operation, and 8% of the patients survived 5 years. In contrast, the 5-year survival after resection of islet cell carcinomas and cystadenocarcinomas was excellent (83% and 100%, respectively). CONCLUSION: The prognosis for patients with ductal adenocarcinoma in the distal pancreas who were treated with potentially curative distal pancreatectomy is poor; however, the results are not substantially different from those reported after pancreaticoduodenectomy for malignant tumors of the proximal pancreas. Some patients with adenocarcinoma of the distal pancreas who were treated with resection may be long-term survivors. We recommend resection of carcinoma of the distal pancreas when the disease is limited to the gland and believe that all patients with ductal adenocarcinoma should be considered for postoperative adjuvant radiation and chemotherapy.
Eosinophilia has long been associated with endomyocardial fibrosis, but the involvement of the eosinophilia in fibrosis of other organs is unclear. To investigate this question, the authors tested whether tissue eosinophilia and eosinophil degranulation are present in syndromes associated with fibrosis. The authors used an indirect immunofluorescent technique to localize eosinophil granule major basic protein (MBP) in formalin-fixed, paraffin-embedded tissue specimens from 50 patients. Thirty-four specimens were obtained from patients with inflammatory fibrosis: 12 with idiopathic retroperitoneal fibrosis, seven with sclerosing mediastinitis, four with sclerosing cholangitis, and 11 with pulmonary fibrosis. The remaining 16 specimens were obtained from patients with noninflammatory fibrous proliferations: four with keloids, six with scars, three with Dupuytren's contracture and three with dense stromal fibrosis of the breast. Eosinophil infiltration and/or extracellular MBP deposition were observed in 28 of the 34 specimens (82%) from patients with inflammatory fibrosis, including 11 of the 12 cases of retroperitoneal fibrosis, five of the seven cases of sclerosing mediastinitis, all four cases of sclerosing cholangitis, and 8 of the 11 cases of pulmonary fibrosis. In contrast, eosinophil infiltration and MBP deposition were not observed in specimens from the 16 patients with noninflammatory fibrous proliferation (P less than 0.001). These results indicate that eosinophil infiltration and release of a granule protein, namely MBP, commonly occur in inflammatory fibrotic lesions.
Idiopathic pulmonary fibrosis is an inexorably fatal disorder characterized by connective tissue deposition within the terminal air spaces resulting in loss of lung function and eventual respiratory failure. Previously, we demonstrated that foci of activated fibroblasts expressing high levels of fibronectin, procollagen, and smooth muscle actin and thus resembling those found in healing wounds are responsible for the connective tissue deposition and scarring in idiopathic pulmonary fibrosis. Using in situ hybridization and immunohistochemistry, we now demonstrate the presence of transforming growth factor beta 1 (TGF-beta 1), a potent profibrotic cytokine, in the foci containing these activated fibroblasts. These results suggest that matrix-associated TGF-beta 1 may serve as a stimulus for the persistent expression of connective tissue genes. One potential source of the TGF-beta 1 is the alveolar macrophage, and we demonstrate the expression of abundant TGF-beta 1 mRNA in alveolar macrophages in lung tissue from patients with idiopathic pulmonary fibrosis.
Salivary gland involvement is a rare clinical feature of Wegener's granulomatosis. We report a series of five cases in which submandibular or parotid gland swelling was part of the initial manifestation of the disease. All patients had limited forms of Wegener's granulomatosis. The value of determination of serum anti-neutrophil cytoplasmic autoantibodies is demonstrated in four of the cases, and its use as a new diagnostic adjunct and promising tool to monitor disease activity is discussed. The use of trimethoprim-sulfamethoxazole as part of alternative treatment regimens for limited Wegener's granulomatosis is advocated.
One hundred thirty-four consecutive patients (65 men and 69 women) underwent pulmonary resection for bronchoalveolar carcinoma. Mean age was 65 years. Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and wedge excision in 19. Only 10 patients had lymph node metastases (7.5%). The neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in stage II, 9 were in stage IIIa, and 1 was in stage IIIb. There were two operative deaths (1.5%). Thirty-nine complications occurred in 31 patients. Median follow-up was 5.1 years. Recurrent bronchoalveolar carcinoma developed in 45 patients. Five- and 10-year survival for patients in stage I was 75.2% and 62.0%, respectively. Survival for patients with T1 N0 M0 neoplasms was identical to expected survival and was 90.5% at 5 years, as compared with 55.4% for patients with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease, and 0.0% for patients with bilateral disease (p less than 0.0001). Other significant factors adversely affecting survival included the presence of signs and symptoms, diffuse malignant invasion, mucin-producing tumors, and the histological absence of scar. We conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases. Early aggressive pulmonary resection is safe and offers the potential for cure. The presence of bilateral cancer, however, is ominous.
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In 35 cases of pulmonary blastomycosis, the roentgenologic features were as follows: consolidation 26%, mass 31%, intermediate-sized nodules 6%, miliary pattern 11%, solitary cavity 9%, fibrotic and cavitary changes 6%, interstitial pattern 6%, diffuse alveolar involvement 3%, and mixed alveolar and interstitial infiltrate 3%. All symptomatic cases of consolidation were acute (symptoms for less than 1 month), and most were in young patients (mean age, 34 years). Consolidation constituted 58% of the acute cases in this series. Two of the nine cases of consolidation were asymptomatic epidemic cases detected by screening. A pulmonary mass was the most common initial manifestation in this series; it tended to occur in patients with chronic symptoms (more than 1 month). The mass was considered suggestive enough of bronchogenic carcinoma to necessitate resection in 55% of cases. The military form of pulmonary blastomycosis occurred in older patients with disseminated disease. Fibrotic and cavitary disease was chronic in nature. The presence of intermediate-sized nodules elsewhere in the lung proved to be a helpful diagnostic finding in several patients with consolidation, mass, or cavitary disease. Hilar adenopathy, postinfectious calcification, chest wall invasion, and pleural effusion occurred infrequently or not at all in this series.
The therapeutic options in the treatment of lung neoplasia usually have not included hormonal therapy, unlike those for primary tumors of other sites (e.g., breast). However, two mesenchymal proliferations of lung, lymphangioleiomyomatosis and epithelioid hemangioendothelioma (EHE), and one epithelial tumor, sclerosing hemangioma (SH), have a significant female predilection and may benefit from such hormonal therapy. The authors investigated five cases each of EHE and lymphangioleiomyomatosis and four cases of SH for expression of estrogen and progesterone receptors and 17-beta estradiol in paraffin-embedded tissue. Only one case each of lymphangioleiomyomatosis and EHE expressed 17-beta estradiol. All of the other cases were negative. These findings are contrary to the viewpoint held in published literature, especially in case reports of lymphangioleiomyomatosis, describing patients with positive estrogen and progesterone receptor results. Consequently, a number of issues must be considered in the clinical and immunohistochemical evaluation of the estrogen and progesterone receptor status of these rare pulmonary neoplasms.
The diagnosis and classification of most interstitial lung diseases requires histologic evaluation of lung tissue, obtained by an open lung biopsy to confirm the diagnosis. In addition, it is generally accepted that response to therapy in idiopathic pulmonary fibrosis (IPF) is related to the relative degree of cellularity and fibrosis present. Because only a qualitative assessment of the relative extent and severity of these changes is generally provided, correlation with clinical and physiologic alterations is difficult. This report describes results of a semiquantitative assessment by four pathologists of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, in addition to an overall assessment of cellularity and fibrosis in 50 patients with IPF. In 10 randomly selected biopsies examined twice in a blinded fashion, absolute agreement between assessments for a given pathologist varied between 54 and 64% (mean = 57.5%) and in the majority of instances the agreement was greater than would have occurred by chance. There was good agreement for most variables across the four raters on the 101 samples. The mean score for some of the parameters reported by a given rater deviated occasionally from those of the other raters, but no single rater was consistently different from the other raters. A principal component factor analysis revealed that the pathologic features fell into four general groupings: alveolar wall metaplasia, fibrosis, honeycombing, smooth muscle, and vascular changes fell into one group; severity and extent of cellularity in the alveolar wall into a second group; severity and extent of cellularity in the alveolar space into a third group; and interstitial young connective tissue along with granulation tissue in the airways formed the fourth group.(ABSTRACT TRUNCATED AT 250 WORDS)
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The experience of the US/Canadian Mesothelioma Panel with its first 200 cases is reviewed. The light microscopic diagnosis, histochemical findings, immunohistochemical findings, and electron microscopic features of malignant mesotheliomas are reviewed in the context of differential diagnosis. Reasons for referral of case material to the panel and lessons from follow-up of difficult and controversial cases are reported. Recommendations to general pathologists are made regarding evaluation and review of possible mesotheliomas.
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We report four patients who had intravascular lymphomatosis (IVL) that presented as interstitial lung disease. All four patients had progressive shortness of breath, weight loss, fever, and diffuse interstitial infiltrates on chest radiographs. Open lung biopsy samples showed an interstitial pneumonia except for the intravascular proliferation of large lymphoid cells associated with irregular congestion, fibrin microthrombi, and intimal proliferation in vessels. This appearance corresponded to an intravascular large cell lymphoma (malignant angioendotheliomatosis [MAE], angiotropic lymphoma). The differential diagnosis of IVL with other pulmonary lymphoproliferations and intravascular malignancies is reported.
It is widely believed that thoracotomy is necessary to obtain biopsy specimens adequate for the histopathologic demonstration of pulmonary Wegener's granulomatosis (WG). We report five patients with WG who were diagnosed by transbronchial biopsy (TBB). In three cases, a diagnosis of WG was made by TBB alone. In the other two patients, subsequent open lung biopsies confirmed the TBB findings but did not add essential diagnostic information. Our experience suggests TBB may be appropriate as the initial diagnostic procedure in selected cases of suspected WG. This approach requires an understanding of the diverse histologic features of WG and the correlation of clinical and pathologic data.
In this article, we retrospectively review 29 cases of Hamman-Rich syndrome. As in some other recent reports, we have used the term "acute interstitial pneumonia" to emphasize the clinical and pathologic features of these cases and to distinguish them from the more common chronic interstitial pneumonias, particularly idiopathic pulmonary fibrosis. Of the 29 patients, 12 survived, some after a long and complicated hospitalization. The histologic features were those of organizing diffuse alveolar damage, and some patients, including survivors, had extensive fibroblastic distortion of lung parenchyma. The overall survival among these patients was not appreciably different from the survival of patients with the adult respiratory distress syndrome in general.
We describe two adults with multiple cystic fibrohistiocytic tumors of the lung that manifested as bilateral nodular opacities, cystic lesions, or both on chest roentgenograms. One patient had recurrent episodes of pneumothorax and intermittent shortness of breath; the other was asymptomatic. Open-lung biopsy specimens showed identical histologically benign fibrohistiocytic proliferations associated with formation of cysts that were lined by metaplastic bronchiolar, squamous, or type II alveolar epithelium and old hemorrhage in the cysts. In both patients, the lesions grew slowly over a period of years. These unusual multiple bilateral fibrohistiocytic tumors of the lung should be included in the differential diagnosis of bilateral cystic lesions in the lung.
We studied eight clear cell tumors of the lung (CCTL) to better define their clinical, immunohistochemical, and ultrastructural features, and to clarify their distinction from other neoplasms, particularly metastatic renal cell carcinoma. Patients ranged in age from 31 to 67 years (mean, 51 years). Seven patients had clinically benign, asymptomatic lesions measuring less than 2 cm in diameter that were devoid of necrosis. The eighth patient had a symptomatic, partially necrotic CCTL 4.5 cm in diameter that metastasized to the liver and peritoneum; the patient died of tumor 17 years after diagnosis. Ultrastructural study of seven CCTL showed interdigitating cell processes (all cases), primitive cell junctions (five of seven cases), intracytoplasmic glycogen (all cases), and rare dense core granules (two of seven cases). Immunohistochemically, paraffin-embedded sections from all eight CCTL were negative for cytokeratin (CK), epithelial membrane antigen (EMA), chromogranin, and vimentin. Focal staining was seen for S-100 protein (three of eight cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu 7 (one case). Although these findings suggest that at least some CCTL exhibit neuroendocrine differentiation, the tumor's histogenesis remains uncertain. Of more practical importance, the combined absence of CK, EMA, and vimentin in formalin-fixed, paraffin-embedded CCTL virtually precludes confusion with renal cell carcinoma. Although traditionally considered benign, CCTL larger than 2 cm that are symptomatic, and focally necrotic should be regarded as potentially malignant neoplasms.