Forty-five bronchioloalveolar carcinomas were studied, including 27 cases by electron microscopy. Bronchioloalveolar carcinomas can be classified by routine sections or by diastase-digested periodic acid-Schiff (PAS) stains, but electron microscopy is useful in confirming Clara cell or type II pneumocyte (nonmucinous) differentiation and excluding metastases. Mucinous bronchioloalveolar carcinoma can mimic metastatic adenocarcinoma histologically and ultrastructurally. Of the nine tumors with mucinous differentiation, eight had aerogenous dissemination (multifocal or with pneumonic spread), and seven of those eight were fatal. Twenty-four of 36 nonmucinous bronchioloalveolar tumors had aerogenous spread; all of the 24 patients died or were living with distant metastases. The 12 nonmucinous tumors without aerogenous dissemination had a 5-year survival rate of 61%. Among these, the smaller tumors had a better prognosis. The presence of alveolar spread, rather than cell type, was the most important feature predicting survival.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819860415%2957%3A8%3C1555%3A%3AAID-CNCR2820570820%3E3.0.CO%3B2-N

Bronchioloalveolar carcinomas. Cell types, patterns of growth, and prognostic correlates

This study is to examine the potential usefulness of immunohistochemical staining for carcinoembryonic antigen (CEA)-like material in the differential diagnosis of mesotheliomas (12 cases) from other lung cancers (14 cases) that had been previously diagnosed by transmission and scanning electron microscopy and conventional light microscopy. Indirect immunofluorescent staining for CEA was carried out on formalin-fixed paraffin-embedded sections, and the slides were examined under code. All 9 cases of diffuse mesothelioma were negative, and all 12 cases of adenocarcinoma and bronchioloalveolar carcinoma were positive for CEA-like material. Three localized mesotheliomas and a carcinoid tumor were also negative. A squamous cell carcinoma was positive. A positive immunohistochemical result for CEA-like material in lung cancers will raise the possibility of its being of bronchial epithelial origin.

Absence of carcinoembryonic antigen-like material in mesothelioma: an immunohistochemical differentiation from other lung cancers.

A review of the pathologic material from 34 patients having bronchioloalveolar carcinoma has demonstrated two histopathologic types that have a bearing on the prognosis. Type 1 is associated with gross and microscopic mucus production, and is likely to be multicentric. Type 2 has lesser amounts of mucus, and is likely to be solitary. The 5-year survival of type 1 is 26%, and that of type 2 is 72%.

Bronchioloalveolar carcinoma: The significance of two histopathologic types.

Formalin-fixed paraffin-embedded tumor tissues from North American (N = 12) and Japanese (N = 11) patients with lung carcinomas were stained by the immunoperoxidase method for surfactant-specific apoprotein. Cytoplasmic and focal nuclear staining was seen in three "bronchioloalveolar carcinomas" occurring in Japanese patients. We refer to these three tumors as carcinomas of Type II pneumocytes. These neoplasms formed discrete masses with minimal growth along the alveolar septa at margins of the tumors. Papillary growth with lymphocytic infiltrates in the stalks of the papillary processes was the usual growth pattern. Focal noncaseating granulomas were seen in the stroma of 2 cases, and similar granulomas in the draining lymph nodes were noted in 1. The abundant cytoplasm was foamy, and the nuclei were generally vacuolated with frequent eosinophilic inclusions in the vacuoles. By electron microscopy, osmiophilic lamellar bodies or whorled lamellas were seen in the cytoplasm of the 3 tumors staining for surfactant apoprotein. The nuclei in 2 of the 3 cases contained tubular inclusions; the tubules had a diameter of 60 nm and a 20-nm core.

Carcinoma of type II pneumocytes: immunodiagnosis of a subtype of "bronchioloalveolar carcinomas".

Peritumoral and intratumoral macrophages are associated with human and mouse lung cancer. The mouse model allows manipulation of the macrophage population to experimentally evaluate its contribution to tumor growth. Genetic and pharmacologic strategies also permit testing the involvement of specific inflammatory mediators in tumor progression. Among those endogenous mediators thus identified are interleukin (IL)-10, glucocorticoids, prostacyclin, nitric oxide, and surfactant apoprotein D (SP-D); serum SP-D levels are a useful biomarker to monitor tumor growth rate. The importance of understanding the mutually antagonistic roles of individual prostaglandins downstream from cycloxygenase (COX) and how this affects the efficacy of COX-inhibitory drugs is discussed. Promising drug candidates include synthetic glucocorticoids such as budesonide and the sulfone derivative of sulindac, apotosyn.

Role of inflammation in mouse lung tumorigenesis: a review.

Ultrastructural features were correlated with a series of special staining reactions in eight cases of bronchiolo-alveolar carcinoma. Ultrastructural, all tumors were similarly composed of large cells with abundant cytoplasm and small nuclei in close contact with each other. Straight membranes or complex interdigitations occurred within adjacent tumor cells, attached to each other by scattered desmosomes. Microvilli or cilia abutted from free surfaces of the cells, and were noted in different stages of evolution. Numerous organelles were seen in the cytoplasm, including prominent mitochondria and single or coalescent secretory vacuoles with granular matrix resembling mucin. Other cytosomes less commonly found were irregular, partially lamellated inclusions and dark, homogeneous structures without limiting membranes. The stroma of the tumors was rich in elastin and collagen. Both the number of secretory vacuoles in the cytoplasm of tumor cells and the amount of connective tissue fibrils in the stroma of the tumors correlated well with the findings in the series of special staining reactions. No definite ultrastructural feature was present to identify the tumors as orginating from Type II alveolar epithelial cells, but the possibility exists that they arose in the bronchiole, from undifferentiated basal cells or mucinous cells per se. Our impression in these eight cases studied is consistent with the view that bronchiolo-alveolar carcinomas are indistinguishable at the ultrastructural level from other bronchogenic adenocarcinomas.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197510%2936%3A4%3C1399%3A%3AAID-CNCR2820360432%3E3.0.CO%3B2-S

David C. Bentinck

Papers

Ultrastructure of human bronchiolo-alveolar cell carcinoma.