Phenomena of Intussusceptive Angiogenesis and Intussusceptive Lymphangiogenesis in Blood and Lymphatic Vessel Tumors

Intussusceptive angiogenesis (IA) and intussusceptive lymphangiogenesis (IL) play a key role in the growth and morphogenesis of vessels. However, there are very few studies in this regard in vessel tumors (VTs). Our objective is to assess the presence, characteristics, and possible mechanisms of the formation of intussusceptive structures in a broad spectrum of VTs. For this purpose, examples of benign and malignant blood and lymphatic VTs were studied via conventional procedures, semithin sections, and immunochemistry and immunofluorescence microscopy. The results demonstrated intussusceptive structures (pillars, meshes, and folds) in benign (lobular capillary hemangioma or pyogenic granuloma, intravascular papillary endothelial hyperplasia or Masson tumor, sinusoidal hemangioma, cavernous hemangioma, glomeruloid hemangioma, angiolipoma, and lymphangiomas), low-grade malignancy (retiform hemangioendothelioma and Dabska tumor), and malignant (angiosarcoma and Kaposi sarcoma) VTs. Intussusceptive structures showed an endothelial cover and a core formed of connective tissue components and presented findings suggesting an origin through vessel loops, endothelialized thrombus, interendothelial bridges, and/or splitting and fusion, and conditioned VT morphology. In conclusion, the findings support the participation of IA and IL, in association with sprouting angiogenesis, in VTs, and therefore in their growth and morphogenesis, which is of pathophysiological interest and lays the groundwork for in-depth molecular studies with therapeutic purposes.