Alteration of tumour cell arrangement related to connective tissue stroma in metastatic brain tumours. Histological and immunohistochemical studies of 68 autopsy cases.

Tumour cell arrangements of a variety of 68 tumours metastatic to brain parenchyma and leptomeninges were compared histologically and immunohistochemically with those of the primary tumours in regard to their connective tissue stroma. In the brain parenchyma, more than 90% of 31 metastatic differentiated adenocarcinomas from various organs changed in cell arrangement from a tubular to a papillary pattern, in which tumour cells lined the increased perivascular connective tissue, rich in both type III collagen and fibronectin, the typical constituents of interstitial type extracellular matrices. Twelve (39%) and 3 of 31 cases were rearranged in a partially or completely tubular pattern respectively, within the metastatic nodules. Most of these neoplastic tubules were surrounded by diffusely proliferating connective tissue. Metastatic growth of carcinoma cells in the absence of supporting connective tissue in the nervous tissue was rare. A similar result was obtained for differentiated squamous cell carcinoma. In contrast, metastatic undifferentiated carcinoma and tumours with some neuro-ectodermal characteristics showed a sheet-like arrangement without pronounced connective tissue proliferation, similar to that of the primary tumours. In the leptomeninges, differentiated carcinoma cells were arranged in a tubular or a squamoid pattern and were frequently accompanied by marked stromal response. These results indicate that differentiated carcinomas require connective tissue stroma for metastatic growth, and that tumour cell arrangement in the brain varies depending upon the amount and distribution of proliferating connective tissue stroma. In undifferentiated carcinomas and tumours with neuro-ectodermal characteristics lacking stromal dependency, the tumor cell arrangement remains unchanged. The degree of stromal response to metastatic tumours in the brain parenchyma is related to the degree of epithelial differentiation.