title: Vascular invasion and herniation by hepatocellular carcinoma in cirrhosis: A wolf in sheep's clothing?
abstract: BACKGROUND
  Vascular invasion is an important diagnostic and prognostic feature of hepatocellular carcinoma (HCC) in cirrhosis. Intravascular free-floating tumor clusters (IvCs) of HCC are found histologically in the vicinity of HCC. Thrombus formation is not seen morphologically in association with these IvCs, which are usually covered by endothelium.
  
  
  OBJECTIVE
  Our hypothesis is that these IvCs are the result of a nondestructive form of vascular invasion by HCC, and we tried to define this aspect of microvascular invasion more accurately.
  
  
  METHODS
  Tissue sections were stained with hematoxylin-eosin, and consecutive sections were stained for fibrin (Martius scarlet blue, fibrinogen), platelets (factor XIIIa), smooth muscle actin, and endothelium (CD34). We studied cirrhotic livers removed at transplantation between 1997 and 1999. Of the livers studied, 35 of 81 consecutive cirrhotic livers contained HCC, and 17 showed microscopic vascular invasion. Five of these 17 cases showed IvCs and were subjected to the study.
  
  
  METHODS
  Presence or absence of thrombus formation in association with IvC.
  
  
  RESULTS
  Usually, IvCs were covered by endothelium, and no associated thrombus formation was seen. In 1 case of HCC, thrombus formation was seen focally in association with disruption of the endothelial coating.
  
  
  CONCLUSIONS
  We propose that the endothelial-lined trabecular structure of HCC everts, frondlike, via vascular structures within the tumor capsule into peritumoral vascular lumens without destruction of the endothelial coating. This may protect these HCC tumor projections from thrombus formation but may also act as a barrier to tumor extravasation, and this may be exploited from a therapeutic point of view.
authors.affiliation: Department of Histopathology, Royal Free Hospital, London, United Kingdom. alberto.quaglia@royalfree.nhs.uk
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.forename: Nazanin
authors.initials: N
authors.lastname: Etessami
authors.forename: Rosalind
authors.initials: R
authors.lastname: Sim
authors.forename: John
authors.initials: J
authors.lastname: Difford
authors.forename: A P
authors.initials: AP
authors.lastname: Dhillon
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D026122:Factor XIIIa / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D017463:Receptors, Complement 3b / Q000378:metabolism
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D017463:Receptors, Complement 3b; D005337:Fibrin; D005340:Fibrinogen; D026122:Factor XIIIa