Histological and fine structural features of pancreatic ductal adenocarcinomas in relation to growth and prognosis: studies in xenografted tumours and clinico-histopathological correlation in a series of 75 cases


Address for correspondence: Dr G. Klöppel, Institute of Pathology, University of Hamburg, Martinstr. 52, D-2000 Hamburg 20, FRG.


Histology and fine structure of pancreatic ductal adenocarcinomas were assessed with respect to their significance for tumour growth and prognosis. The histological parameters included glandular differentiation, nuclear anaplasia, nuclear size, and mitotic activity (number of mitoses per high power field). Using these criteria three grades of malignancy were distinguished. They correlated well with the growth kinetics of seven human pancreatic ductal adenocarcinomas transplanted into nude mice. The tumour doubling time of a G3 carcinoma was about half that of a G1 carcinoma. On electron microscopy the tumour grade was reflected in the degree of functional differentiation of the neoplastic duct cells. In an additional clinicopathological evaluation of 75 patients operated upon for ductal adenocarcinoma of the pancreatic head, a positive relationship was found between grade and duration of symptoms until diagnosis. Moreover, the G1 tumours showed generally a lower stage at the time of surgery than G2 and G3 carcinomas. Finally, the median survival times correlated significantly with the tumour grade. From the various parameters used nuclear grade proved to be the most significant prognostic criterion, since a separate morphometric study revealed a very close correlation between median nuclear size of the tumours and survival time.