Histogenesis of nonurothelial carcinomas in the human and rat urinary bladder

The histogenesis of nonurothelial carcinomas (squamous cell carcinoma, common adenocarcinoma, clear cell adenocarcinoma, signet ring cell adenocarcinoma and undifferentiated carcinomas) of the urinary bladder is difficult to understand, since the bladder is normally lined exclusively by transitional cell epithelium and contains no otherwise specified epithelia. In the present study we analysed the morphology and development of nontransitional cell carcinomas of the human and comparatively of the rat urinary bladder in an attempt to elucidate their histogenetic derivation. There is strong evidence that the underlying histogenetic principle consists in the well-known pluripotent metaplastic potency (squamous, columnar, goblet and signet ring cell, glandular and so-called nephrogenic metaplasia) of the normal and neoplastic urothelium as well, due to the complex embryologic origin of the bladder. Our findings indicate that squamous cell carcinomas, common and clear cell adenocarcinomas, and signet ring cell adenocarcinomas mainly arise secondarily from preexisting, predominantly solid transitional cell carcinomas by focally beginning and diffusely progressing metaplastic changes of various types. The second histogenetic pathway consists in the formation from primary metaplasias of the transitional cell epithelium in situ. Undifferentiated carcinomas (small, large and sarcomatoid subtypes) develop from preexistent solid urothelial carcinomas by a cellular dedifferentiation. Recognition of transitional cell carcinomas characterised by focal metaplastic processes or cellular dedifferentiation seems to be important from a clinical point of view, because of their probably more malignant biologic behaviour compared with uniformly differentiated pure urothelial carcinomas. Our comparative morphologic analysis of nonurothelial carcinomas and their histogenesis has demonstrated that the findings in the human and rat urinary bladder are largely identical. The experimental models used permit reliable extrapolation of the results obtained to the situation in man.