Hemangioma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Nawal Muazam M.D.[2]


On microscopic histopathological analysis channels lined by benign endothelium containing RBCs are findings of hemangioma.[1]



The pathogenesis of hepatic hemangiomas has not been elucidated, but there are two competing theories.

First theory

  • The first theory supports the notion that there is overexpression of angiogenic factors such as:[2]
  • And there is downregulation of some inhibitors of angiogenesis such as:[2]

Second theory

  • The second theory is that the presence of liver hemangiomas involves a genetic background of mutations.[2]
  • Genetic errors in growth factor receptors have also been shown to affect development of hemangiomas.
  • Zhang et al. presumed that metalloproteinases accumulate in the endoplasmic reticulum of the tumor cells causing:
  • Self-digestion
  • Vacuole formation
  • Additionally, Hu et al. showed the cavernous hemangioma cell to downregulate Derlin-1.
  • Derlin-1 is a protein that when overexpressed induces the dilated endoplasmic reticulum to return to its normal size.

Third theory

  • The third theory suggests that hemangioma endothelial cells arise from disrupted placental tissue imbedded in fetal soft tissues during gestation or birth.[3]
  • Markers of hemangiomas have been shown to coincide with those found in placental tissue.
  • This is further supported by the fact that they are found more commonly in infants following:[3]
  • Chorionic villus sampling
  • Placenta previa
  • Preeclampsia


Associated Conditions

Hemangioma may be associated with:

  • POEMS syndrome
  • Castleman disease

Gross Pathology

Microscopic Pathology

On microscopic histopathological analysis channels lined by benign endothelium containing RBCs are findings of hemangioma.[1]


Hemangioma is demonstrated by positivity to:[1]

  • CD31 positive
  • D2-40 negative



  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Microscopic features of hemangioma. Librepathology (2015). http://librepathology.org/wiki/index.php/Hemangioma. Accessed on November 12, 2015
  2. 2.0 2.1 2.2 Papafragkakis, Haris; Moehlen, Martin; Garcia-Buitrago, Monica T.; Madrazo, Beatrice; Island, Eddie; Martin, Paul (2011). "A Case of a Ruptured Sclerosing Liver Hemangioma". International Journal of Hepatology. 2011: 1–5. doi:10.4061/2011/942360. ISSN 2090-3456.
  3. 3.0 3.1 Richter, Gresham T.; Friedman, Adva B. (2012). "Hemangiomas and Vascular Malformations: Current Theory and Management". International Journal of Pediatrics. 2012: 1–10. doi:10.1155/2012/645678. ISSN 1687-9740.

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