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]

Overview

Development of hemangioma is the result of genetic mutations, overexpression of angiogenic fators and downregulation of inhibitors of angiogenesis. Hemangioma may be associated with POEMS syndrome and Castleman disease. On gross pathology, spongy with vascular compartments of various sizes separated by fibrous tissue are findings of hemangioma. On microscopic histopathological analysis, channels lined by benign endothelium containing red blood cells are findings of hemangioma.

Pathophysiology

The pathogenesis of 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:
  • Vascular endothelial growth factor
  • Basic fibroblast growth factor
  • Matrix metalloproteinases
• And there is downregulation of some inhibitors of angiogenesis such as:
  • Tissue inhibitor of metalloproteinase-I

Second theory

• The second theory is that the presence of liver hemangiomas involves a genetic background of mutations.
• Genetic errors in growth factor receptors have also been shown to affect development of hemangiomas.
• Metalloproteinases can accumulate in the endoplasmic reticulum of the tumor cells causing:
  • Self-digestion
  • Vacuole formation
• Cavernous hemangioma cell can 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.
• 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:
  • Chorionic villus sampling
  • Placenta previa
  • Preeclampsia

Growth Pattern

• Hemangiomas follow a predictable course with three distinct developmental phases:
  • Proliferation phase
  • Quiescence phase
  • Involution phase

Proliferation phase

• In most hemangiomas, eighty percent of proliferation occurs by three months of life but may last longer.
• During proliferation, rapid growth can lead to exhaustion of blood supply with resulting ischemia, necrosis, ulceration, and bleeding.

Quiescence phase

• Following proliferation, hemangiomas enter a slower or no growth phase, known as quiescence.
• This phase typically lasts from nine to twelve months of age.

Involution phase

• The final and unique phase of the hemangioma lifecycle is involution.
• This phase is marked by graying of the overlying skin and shrinking of the deeper components.
• At the final stages of involution, a fibrofatty protuberance may remain.

Associated Conditions

Hemangioma may be associated with:

• POEMS syndrome
• Castleman disease
• PHACES syndrome

Gross Pathology

• Grossly hemangiomas are described as “spongy” with vascular compartments of various sizes separated by fibrous tissue.

• Thrombi may be present and are well separated from the normal liver parenchyma despite the absence of a fibrous capsule.

Microscopic Pathology

On microscopic histopathological analysis channels lined by benign endothelium containing red blood cells are findings of hemangioma.

Gallery

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  _{Intermediate magnification micrograph of a capillary hemangioma. H&E stain.}

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  _{Very high magnification micrograph of a capillary hemangioma. H&E stain.}

• 

  _{Histopathological image representing a cavernous hemangioma of the liver. Surgical excision of the lesion for the impending risk for rupture. H&E stain.}

• 

  _{Histopathological image reprsenting a cavernous hemangioma of the liver. H&E stain.}

Immunohistochemistry

Hemangioma is demonstrated by positivity to:

• CD31 positive
• D2-40 negative