American Academy of Ophthalmology Web Site: www.aao.org
Ophthalmic Pearls: Pediatrics
Review of Capillary Hemangioma
Capillary hemangioma is a hamartoma—an abnormal, localized proliferation of vascular endothelial cells. One of the most common benign orbital tumors in children, capillary hemangioma affects up to 2 percent of all infants, with a female predilection (3:2 ratio). The incidence of eyelid and orbital hemangiomas is about onetenth that of systemic infantile hemangiomas, which occur in about 10 percent of all children by 1 year of age.1 Approximately one-third of capillary hemangiomas are apparent at birth, while the remaining two-thirds manifest by 6 months of age.
Clinically, capillary hemangioma may present as a cutaneous, subcutaneous or deep orbital lesion or a combination of the three. The superficial cutaneous lesion, or “strawberry nevus,” is initially evident as a confluence of telangiectasias, which later progresses to a red, raised nodular lesion that blanches with pressure. The subcutaneous lesion typically has a bluepurple hue and a spongy consistency. The deeper orbital lesion may present with proptosis and globe displacement.
The diagnosis is usually clinical, especially in superficial cutaneous lesions. A benign-appearing subcutaneous lesion may be associated with a much larger orbital component; thus, orbital imaging is warranted (ultrasound, MRI or CT). All patients with suspected or known deep orbital lesions should be imaged. On ultrasound, the lesion is often asymmetric and shows high internal reflectivity with an irregular acoustic structure (caused by the multiple interfaces of vascular walls). On CT, the lesion may appear as a poorly circumscribed mass, with no bony erosion, that enhances with intravenous contrast. On MRI, a capillary hemangioma appears hypointense on T1 and hyperintense on T2 and shows moderate to intense enhancement after gadolinium administration. Biopsy may be useful in equivocal cases where imaging is not diagnostic.
Histologic appearance varies with the growth phase. Early in the course, enlarged endothelial cells exist in lobules separated by fibrous septa. Mitotic figures are common, as this corresponds to the greatest proliferative phase. Vascular lumina remain small and irregular. As the lesion matures, the vascular structures become more prominent as the endothelial cells flatten and decrease in number. During involution, the fibrous septa thicken, the endothelial cells are replaced by adipocytes and the vascular structures atrophy.
Systemic involvement is rare but potentially life-threatening. In Kasabach- Merritt syndrome, extensive visceral hemangiomas act as traps for circulating platelets, resulting in thrombocytopenia, microangiopathic hemolytic anemia, consumptive coagulopathy and hemorrhagic diathesis. Other studies have shown that orbital hemangiomas may be associated with other head and neck hemangiomas; thus, a full systemic workup is essential.
The prognosis is generally good. The natural history of capillary hemangioma is an initial rapid growth phase, usually within the first six to nine months of life, followed by stabilization at around 12 to 15 months of life and then protracted involution over many years. About 30 percent of lesions regress spontaneously by 3 years of age, 60 percent by 4 years and 75 percent by 7 years. Even those who do not fully regress change significantly in size and appearance over time.
Capillary hemangioma may be confused with the port-wine stain form of nevus flammeus, although the cutaneous lesion in port-wine nevus flammeus is typically flatter and darker and does not blanch with pressure. Unlike nevus flammeus, the hemangioma may demon strate long-term growth and may increase in size during Valsalva maneuvers. The differential also includes lymphangioma, encephalocele and potentially life-threatening rhabdomyosarcoma and neuroblastoma.
Since most lesions undergo spontaneous involution, treatment is reserved for those patients at risk for permanent visual impairment. Amblyopia is the leading indication and can be refractive, deprivational or strabismic. Anisometropic astigmatism is the most common cause of visual impairment and results from direct pressure on the globe by the thickened eyelid. Deprivational amblyopia occurs when the growing hemangioma occludes the visual axis. Strabismic amblyopia can be caused by either mass effect in the orbit or direct involvement of the extraocular muscles. Other indications for treatment include a large posterior lesion causing compressive optic neuropathy or proptosis with exposure keratopathy.
Several treatment modalities exist, and no single algorithm covers all individual variations. The choice of treatment often depends on the lesion location, whether the lesion is focal or diffuse and the potential adverse effects of intervention. Some forms of treatment—cryotherapy, radiation, electrolysis and diathermy—have become obsolete.
Corticosteroids. Systemic, intralesional and topical corticosteroids may be used as treatment.
Laser photocoagulation. Laser photocoagulation, specifically pulsed-dye laser, is effective in attenuating proliferation and facilitating regression of superficial cutaneous hemangiomas. Laser also may be useful as adjunctive therapy to the first-line treatments outlined above.4
Surgical excision. Surgical excision is often difficult since most lesions are diffuse and unencapsulated. The potential for hemorrhage is also a serious concern, especially in the infant. In general, surgical excision is best for noninfiltrative, well-circumscribed lesions that are refractory to other forms of treatment. Recent case reports suggest better outcomes if excision is performed before 13 months of age.5
Immunomodulators. Immunomodulators are a viable option if more standard treatment has failed. Like systemic corticosteroids, they may be especially effective for lesions with an orbital component. Vincristine has been moderately successful in treating the diffuse visceral hemangiomas of Kasabach- Merritt syndrome. Cyclophosphamide (10 mg/kg/day) has been used as monotherapy or in combination with systemic corticosteroids since the 1970s. Interferon alfa-2a has been used as a single agent since the early 1990s. Although both cyclophosphamide and interferon alfa-2a have proven efficacy, a prolonged treatment course, often extending beyond nine months, places the patient at significant risk for adverse effects, namely myelosuppression and hepatotoxicity for cyclophosphamide and neurotoxicity (spastic diplegia) for interferon.
In an effort to shorten the treatment period, a recent retrospective case series used a combination of cyclophosphamide (10 mg/kg/day for three days, then every two weeks) and interferon alfa-2a (3 million U/m2/day subcutaneously).6 Treatment was limited to six months at most. Four of five patients had a 40 to 60 percent regression of hemangioma, with reduction in proptosis, exposure keratopathy and occlusion of the visual axis. All had mild neutropenia with uncomplicated, successfully treated infections. None had irreversible neurologic sequelae.
Primary ophthalmic care. Last, in addition to definitive treatment of the hemangioma, it is of vital importance to optimize visual rehabilitation by providing optimal refractions and initiating occlusive therapy when indicated.
Capillary hemangioma is one of the most common benign orbital tumors in children. It may present as a cutaneous, subcutaneous or deep orbital lesion. While capillary hemangioma is usually a clinical diagnosis, orbital imaging (ultrasound, CT or MRI) is especially helpful in subcutaneous and deep orbital lesions, or to make sure there is no deeper involvement. Because most hemangiomas regress spontaneously by age 7 years, treatment is indicated in cases of threatened amblyopia (refractive, deprivational, strabismic), compressive optic neuropathy or proptosis with exposure keratopathy; otherwise, observation is usually recommended. The choice of treatment modality depends on lesion location, quality and potential adverse effects. Systemic or intralesional corticosteroids are firstline treatments. Alternative treatments include topical corticosteroids, laser photocoagulation and surgical excision. Immunomodulators may be effective in cases refractory to first-line treatment and for deep orbital lesions. Although cyclophosphamide and interferon alfa-2a have been used for decades, the need for a prolonged treatment course and the subsequent adverse effects have reduced their use as monotherapy. Recent research shows promise that a combination of the two agents may be both safe and effective. Last, it is important to provide frequent refractions and occlusive therapy to maximize visual rehabilitation.
2 Schwartz, S. et al. J AAPOS 2007;11:577–583.
3 Coats, D. K. et al. Ophthalmology 2003;110:1255–1259.
4 Ceisler, E. and F. Blei. Lymph Res Biol 2003;1:321–330.
5 Levi, M. et al. J AAPOS 2007;11:230–234.
6 Wilson, M. W. et al. Ophthalmology 2007;114:1007–1011.
Dr. Peralta is a third-year resident and Dr. Glavas is a clinical assistant professor. Both are at New York University and the Manhattan Eye, Ear and Throat Hospital, New York.