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The lungs have an important role in the synthesis of angiotensin I converting enzyme (ACE). In BAL fluid and serum the ACE activity was determined in 18 patients with sarcoidosis (11 with high intensity and 7 with low intensity alveolitis), 14 patients with lung cancer and 16 with acute bronchitis. The activity of ACE was examined by a reagent set produced by Boehringer Mannheim Biochemica Test-Combination ACE cat. no. 789/011. The ACE activity in the high intensity alveolitis group of sarcoidosis patients was significantly increased in BAL fluid and serum in comparison to other observed patients. On the other hand, in patients with lung cancer the ACE activity was also increased in comparison to acute bronchitis and referred norms, especially in BAL fluid. This findings suggest a role of neoplastic process in ACE secretion in the airways. Very low correlation observed between ACE activity in serum and BAL fluid indicates a separate mechanism of secretion.
Sixty-six human lung neoplasms of different histological types and normal bronchial epithelial cells of newborn babies and adults were studied histochemically using ConA and PSA and the result was compared with that of CEA. Normal mucosal epithelium could bind to ConA, and the location of ConA receptors was related to the maturation of mucosal epithelial cells. Normal mucosal epithelium in adult bronchi failed to be stained with PSA and anti-CEA, and most of lung neoplasms could bind to PSA and positive for CEA, indicating that new glycoconjugate and CEA-glycoprotein could be synthesized after malignant transformation of mucosal epithelium. The binding of ConA, PSA and anti-CEA to cell membrane and nucleus membrane was characteristic of squamous cell lung cancer while lung adenocarcinoma mainly showed cytoplasmic staining. The weak staining of ConA, PSA and anti-CEA in small cell carcinoma and negative staining in carcinoid and malignant melanoma help testify that their origin may differ from that of squamous cell carcinoma and adenocarcinoma.
Two unusual primary carcinomas of the lung are described. One occurred in a 31-year-old man and was composed of large, undifferentiated, ovoid to polygonal cells. The other occurred in a 72-year-old man, was composed of spindle-shaped cells, and was initially diagnosed as a localized fibrous mesothelioma. The neoplastic cells of these tumors expressed only vimentin intermediate filaments and showed no other immunohistochemical features of epithelial neoplasms, although they exhibited a metastatic pattern characteristic of lung carcinomas. These two malignant neoplasms further expand the spectrum of unusual lung neoplasms, and suggest that there are pulmonary carcinomas that contain only vimentin intermediate filaments.
Neoplasms of the lungs showing neuroendocrine differentiation are classified histologically into the following groups: (1) carcinoid, (2) atypical carcinoid (well-differentiated neuroendocrine carcinoma and malignant carcinoid, (3) small cell neuroendocrine carcinoma (small cell undifferentiated carcinoma and oat cell carcinoma), and (4) large cell neuroendocrine carcinoma (atypical endocrine tumor of the lung and intermediate neuroendocrine carcinoma). Nine examples of neuroendocrine lung carcinomas are discussed that have unusual histologic features that make it difficult to assign them to one of the above groups, have unusual immunohistochemical features, have unusual ultrastructural features, or exhibit a biologic behavior different from what one would have predicted from their morphologic appearance. The findings in these nine cases suggest that the present classification of neuroendocrine lung neoplasms may be too precise and that these neoplasms, like other nonneuroendocrine pulmonary tumors, exhibit a wider morphologic and biologic spectrum than previously appreciated.
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This article has presented information concerning the ultrastructural features and, to a lesser degree, the immunohistochemical characteristics of lung neoplasms. Electron microscopy and immunohistochemistry are useful techniques for diagnosing and understanding common and rare lung tumors. Electron microscopy is particularly helpful in accurately diagnosing undifferentiated lung tumors such as large-cell undifferentiated and small-cell undifferentiated carcinomas. Ultrastructural studies of lung tumors have also aided in overall understanding of the histogenesis of these tumors. Electron microscopy and immunohistochemistry are techniques that can be applied to tiny specimens, including those obtained via fine-needle aspiration biopsy, and to cells obtained from pleural fluid. An intelligent use of electron microscopy and immunohistochemistry aids in the diagnosis and understanding of lung neoplasms.
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We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR). In this study, we investigated the expression of transforming growth factor alpha (TGF-alpha), a ligand for EGFR, to determine if an autocrine mechanism for growth stimulation was present in these tumors. As determined by immunohistochemistry, 59% (26/44) of the lung neoplasms examined had increased expression of TGF-alpha. Expression of TGF-alpha was not related to the etiology of the tumor, e.g., spontaneous or plutonium-induced; however, it was related to the phenotype of the tumor. Statistical analysis of the correlation of EGFR and TGF-alpha expression within the same tumor did not show a positive association; however, specific phenotypes did have statistically significant expression of EGFR or TGF-alpha, suggesting that overexpression of either the ligand or its receptor conferred a growth advantage to the neoplasm. Twenty-seven percent (32/117) of radiation-induced proliferative epithelial foci expressed TGF-alpha, and a portion of those foci (8/32) expressed both EGFR and TGF-alpha. This supports the hypothesis that these foci represent preneoplastic lesions, and suggests that those foci exhibiting increased expression of the growth factor or its receptor are at greater risk for progressing to neoplasia.
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Systemic tumor embolization during pulmonary resection for lung neoplasms is an uncommon but potentially catastrophic complication. In recent months, two patients undergoing pulmonary resection for bronchogenic carcinoma were found at operation to have tumor extending into a pulmonary vein. Both patients had systemic tumor embolization, one with a fatal outcome because of occlusion of the superior mesenteric artery. The possibility of systemic tumor embolization should be considered in patients with large, central tumors and particularly those that abut the pulmonary veins. The implications of such pulmonary vein involvement is reviewed, and an algorithm for postoperative evaluation and management of these patients is presented.
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