Histological Analysis of Vascular Involvement Suggests an Invasion-Independent Metastatic Mechanism in Alveolar Soft Part Sarcoma
Nokitaka Setsu, Akihiko Yoshida, Hirokazu Chuman, Hitoshi Tsuda. National Cancer Center Hospital, Tokyo, Japan
Background: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor characterized by pseudoalveolar growth of polygonal cells associated with abundant sinusoidal vessels. ASPS has a high proclivity to blood-borne metastasis and is resistant to standard chemotherapy. Recently, an invasion-independent mechanism of metastasis has been postulated for a subset of human carcinomas (Am J Pathol. 2002;160(6):1973), in which cancer cells are shed into vessels, whilst being completely enveloped by endothelial cells, and are subsequently entrapped at recipient organs. This contrasts with the canonical pathway of metastasis, in which cancer cells actively break through vascular walls without being enveloped by endothelial cells. A previous study (BMC Med. 2004;2:9) showed that invasion-independent metastasis tends to occur in carcinomas with sinusoidal vessels. Because ASPS harbors abundant sinusoidal vessels, we hypothesized that the invasion-independent metastatic mechanism may play a role in this disease. To test this, we examined ASPS surgical specimens, paying particular attention to the mode of vascular involvement.
Design: A total of 32 ASPSs surgically resected from 27 patients were retrieved. All the H&E-stained slides were reviewed, and the detailed morphology of vascular involvement was analyzed. Vascular involvement was defined as tumor cells lying completely within vascular spaces. For objective evaluation, we limited analysis to vascular involvement located outside the contour of tumor mass; intratumoral events were excluded from analysis. All vascular involvements were immunostained for CD31.
Results: A total of 191 instances of unequivocal vascular involvement were identified in 84 slides from 20 ASPSs. In almost all (185/191, 97%) of the observed instances of vascular involvement, the intravascular tumor cells were in the form of variously sized cohesive clusters that were tightly enveloped by endothelial cells. Complete endothelial envelopment was confirmed by CD31 immunostaining. Dyscohesive intravascular tumor cells without endothelial wrapping were extremely rare.
Conclusions: Our findings suggest that, in ASPS, the canonical invasive pathway is not followed for vascular involvement, but instead, the invasion-independent mechanism is employed for entry into circulation. 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 ASPS.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 9, Monday Afternoon