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The hypothesis that biologic aggressiveness of bladder cancer is determined by carcinogen dose was tested using heterotopically transplanted rat urinary bladders (HTBs). Young male Fischer rats, which were recipients of normal bladders, were divided into three groups; the first group received 0.5 mg of N-methyl-N-nitrosourea (MNU) into HTBs for six doses, a second, 0.05 mg for six doses and the third, 1 mg for three doses. Separately, a group of animals received bladders from rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in drinking water for 4 weeks; the transplanted bladders then were treated with 0.5 mg of MNU for six doses. Treatment with the larger dose of MNU resulted in a significant increase in tumor incidence and frequency of invasive carcinomas. The combination carcinogen treatment induced more invasive carcinomas than the single treatment. The data suggest that deeply invasive carcinomas may develop in two ways: the first is by emergence of a more anaplastic cell population within a pre-existing noninvasive carcinoma and the second is by the de novo development of an invasive carcinoma directly from a severely dysplastic urothelium, which is acceptable as carcinoma in situ. Squamous differentiation was characteristic of deeply invasive carcinomas. The dose of carcinogen(s) is a determinant of aggressiveness of bladder carcinomas.

A 57-year-old man underwent a right pneumonectomy for a bronchogenic carcinoma following bronchoscopy and bronchial biopsy. The tumor was a polypoid mass arising from the lower lobe bronchus. Microscopically it was characterized by mononuclear cells mixed with randomly distributed multinucleated giant cells similar to those seen in giant-cell tumor of bone. Also found were portions showing typical squamous cell and spindle cell carcinoma. Based on the light and electron microscopic findings, we suggest that the current case represents a metaplastic squamous carcinoma showing mesenchymal cell differentiation. A hypothesis on the histogenesis of pleomorphic carcinomas was presented. The problems of histological diagnosis generated by such a tumor should be emphasized.