Several cellular and extracellular markers that distinguish the phases of t
he hemangioma life cycle have been described previously. However, details o
f the phenotypic changes of the various cellular elements during hemangioma
development have not been fully reported, and the extracellular matrix com
position, especially in the vicinity of the proliferating endothelial cells
, is poorly described. This study examined the expression of cellular and e
xtracellular molecules and cytokines in the proliferative, involuting, and
involuted phases of hemangioma.
Paraffin-embedded hemangioma specimens, four from each phase, were examined
histochemically and immunohistochemically. Throughout the three phases, va
scular endothelial cells stained positive for CD31 and von Willebrand facto
r, although in the involuted phase, not all vessels in the tissue expressed
these endothelial markers. Proliferating cell nuclear antigen was expresse
d by the majority of endothelial cells and pericytes in the proliferative a
nd early involuting phases, but its expression was negligible in the involu
ted phase. In addition to finding that the total number of mast cells was h
ighest in the involuting phase, the authors observed that the proportion of
chymase-positive mast cells decreased with the progression of hemangioma a
nd that virtually all mast cells expressed the biogenic amine phenotype thr
oughout the hemangioma life cycle. The localization of vascular endothelial
growth factor predominantly to the pericytes and endothelial cells during
the proliferative phase and of basic fibroblast growth factor to the endoth
elial cells in both the proliferative and early involuting phases is consis
tent with previous reports, although the latter growth factor was also obse
rved in mast cells. Type TV collagen and the beta(2) chain of laminin and p
erlecan were detected in the basement membranes in all phases. Interestingl
y, collagen types I, III, and V were present in basal membranes throughout
the phases and with increasing density in the stromal areas with involution
, although type I collagen was less prominent during the proliferative phas
e. Short-chain collagen type VIII was localized extracellularly throughout
the development of hemangioma but, during the early proliferative phase, it
was also detected within mast cells.
The expression of specific cytokines and cellular and extracellular markers
may help distinguish the different clinical phases of the hemangioma life
cycle. These results provide further insight into the biology of hemangioma
.