Three different types of IPEH have been reported: (a) a primary (pure) form where changes are observed in a distended vessel; (b) a secondary (mixed) form that occurs in preexisting varices, hemangiomas, pyogenic granulomas, or lymphangiomas; and (c) an uncommon type in an extravascular location [1
The pathogenesis of IPEH is poorly understood. One possible mechanism is a benign neoplastic process involving endothelial cell proliferation and papillary formation in the vascular lumen that undergoes degeneration and necrosis in the manner of a red infract. Alternative mechanisms include a benign endothelial proliferation arising from a thrombus as a variant of angiolymphoid hyperplasia with eosinophilia; a reactive process of endothelial cells induced by blood stasis and perivascular inflammation; and a pseudotumoral lesion caused by endothelial proliferation with papillary formation proceeded by an accumulation of thrombotic material, which serves to facilitate development of the lesion [6
The benign behavior of these lesions is emphasized throughout the literature. The vast majority of lesions present as a slowly growing mass that can be cured by local excision [4
Ki-67 (MIB-1) is a large nuclear protein preferentially expressed during all active phases of the cell cycle but absent in resting cells. Avellino et al. [4
] have demonstrated the presence of a small number of Ki-67 (MIB-1) positive cells in IPEH tumors by immunohistochemistry, suggesting that these are slow-growing benign lesions and not reactive growths.
IPEH of the oral mucosa and lips occurs more commonly in females than males [3
]. A possible hormonal role has been suggested based on this gender difference, and local angiogenic growth factors may contribute to endothelial proliferation [3
]. This lesion is more common in older patients (6th decade of life) [1
]. Our patient, a 70-year-old female, is a typical example.
In the oral cavity, IPEH presents as a slow-growing, firm, reddish-blue mass with slight elevation. The most frequent locations are the lower lip, tongue, buccal mucosa, upper lip, mandibular vestibule and angle of the mouth [3
The lesion has been clinically mistaken for mucocele, hemangioma, lymphagioma, hematoma, Kaposi sarcoma, hemangioendothelioma, thrombosed vein, traumatic fibroma, pyogenic granuloma, angiosarcoma and salivary gland tumor [3
]. Since these growths lack highly specific clinical characteristics, the final diagnosis can only be made after biopsy and microscopic examination [8
]. Histologically, IPEH is characterized by a papillary proliferation of endothelial cells forming vascular channels, commonly associated with thrombus (fig. ). IPEH may be clinically and histopathologically mistaken for an angiosarcoma. Although hematoxylin and eosin staining is sufficient for the diagnosis of IPEH confined to a dilated vessel, the CD105 (named endoglin, a transmembrane protein that is highly expressed on human vascular endothelial cells) immunohistochemistry technique could be helpful in the case of extravascular location of the IPEH lesion. CD105 staining will differentiate IPEH from angiosarcoma, since this molecule is overexpressed only in angiosarcoma-associated endothelial cells [8
]. The best treatment is a total excision-biopsy with healthy margins. When resected completely, recurrence is extremely rare.