[Heterogeneity of malignant bronchial tumors. Problems of histogenesis]

The 1981 WHO classification of bronchial carcinoma, based on light microscopic analysis, proposed 4 principal classes: epidermoid carcinoma, adenocarcinoma, small cell carcinoma and large cell undifferentiated carcinoma. This apparently simple nosology underestimates the difficulties of classifying a good number of these tumors, due to a great diversity in appearance within the same histologic group. Experimental studies on the regeneration of bronchial epithelium, on lesions induced by irritants and carcinogens, suggest one undifferentiated cell line as the origin of all malignant proliferations, including neuro-endocrine tumours. To support this histogenetic hypothesis, an ultra-structural analysis of the carcinomas shows the existence and frequency of heterogenous forms, multi-differentiated, up to the level of individual cells. The same cell line may express several ways of differentiation simultaneously (bi or tri-partite differentiation). Equally immunohistochemical methods reveal antigenic differentiation (intermediary filaments, neuro-endocrine antigens) and establish a means of identifying different cellular constituents. These two methods have allowed real progress in the diagnosis of neuro-endocrine tumours, placing them firmly with bronchial tumours and seem particularly helpful in the analysis of undifferentiated small and large cell carcinomas. By another way, one finds in the majority of bronchial tumours the different antigens expressed, certainly following their histological type in variable degrees, yet with an antigenic (phenotypic) profile showing great similarity. This is a reflection of multi-differentiation in these tumours and appears as a direct consequence of their common histogenetic origin. Bronchial carcinomas are placed along a continuous spectrum of three parallel and/or simultaneous differentiations. They represent a single tumour having a tendency to express one or several ways of differentiation.