Histological analysis suggests an invasion-independent metastatic mechanism in alveolar soft part sarcoma

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor characterized by pseudoalveolar growths associated with abundant sinusoidal vessels. It has a high proclivity to blood-borne metastasis, but the exact mechanism of spread has not been widely discussed, and detailed histological analysis of vascular involvement is still lacking. In this study, we histologically analyzed 32 surgically resected ASPSs, with particular attention to the mode of vascular involvement. Among 188 instances of unequivocal vascular involvement, 184 (98%) were in the form of variously sized cohesive clusters that were completely enveloped by endothelial cells, confirmed by CD31 immunostaining. Discohesive intravascular tumor cells without endothelial wrapping were rare (2%). The clinical relevance of vascular involvement was supported by survival analysis where the average number of vascular involvements per slide was an independent risk factor for shorter progression-free survival. Our findings suggest that ASPSs do not actively break through the vascular walls to initiate the metastatic process. They instead suggest that ASPSs almost exclusively follow the recently postulated "invasion-independent mechanism" for entry into circulation, in which cancer cells are shed into vessels, while being completely enveloped by endothelial cells, and are subsequently entrapped at recipient organs. Because the latter mechanism is reportedly dependent on tumor angiogenesis and vascular remodeling, our data provide a morphological rationale for the use of anti-angiogenic therapy to treat ASPSs.