Cerebral cavernous malformations: congruency of histopathological features with the current clinical definition

Aim: Cerebral cavernous malformations (CCMs) are defined as a mulberry-like assembly of thin walled vascular sinusoids lined by a thin endothelium lacking smooth muscle and elastin, displaying no intervening brain parenchyma. In this study, we analyse the congruency of histopathological features with the current clinical definition on a large series of neuroradiologically verified CCMs. Methods: 87 patients who received no primary treatment prior to surgery were included. Preoperative MRIs of all patients were reviewed. 12 histopathological parameters were assessed systematically, using haematoxylin-eosin, Prussian blue, elastica van Gieson and congo red for amyloid detection. Results: 71/87 (81.6%) of the cases fulfilled the basic histological criteria of CCMs. However, the thickness of the vessel walls and the calibre of the malformed vessels were highly variable. 16/87 cases (18.4%) were histologically non-diagnostic. Non-diagnostic specimens were significantly associated with radiological signs of haemorrhage (p = 0.001). A few cases (4.6%) regionally contained capillary-like malformed vessels. Intervening brain parenchyma between malformed vessels throughout the lesion was seen in 50/71 (70.4%) diagnosable lesions. Haemosiderin deposits, gliosis, thrombosis, fibrotic changes, hyalinised vessel walls, calcification and cholesterol crystals were present in a considerable range. In addition, we found amyloid deposits in 14/87 (16.1%) specimens. Conclusion: Contrary to the current clinical definition, the absence of intervening brain parenchyma does not represent an essential histopathological criterion of CCMs in our series. Furthermore, the diameter of the vessel lumina and the thickness of vessel walls varied considerably. Based on these findings, adaptation of the current definition on the basis of interdisciplinary interaction needs to be considered.