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Arch Ophthalmol. 1999;117:1247-1249.

Intravascular papillary endothelial hyperplasia (IPEH) is an unusual condition characterized by a benign proliferation of vascular endothelial cells that form papillary projections in the lumen of a blood vessel. It is not a specific neoplasm, but is generally believed to be a reactive response that develops secondary to a thrombus in vascular lesions such as varices or hemangiomas.^1-3 It most often occurs as a painless, reddish purple lesion in the dermis or subcutis of the head and neck region or extremities.^4-6 Intravascular papillary endothelial hyperplasia has been recognized to occur rarely in the ocular area, usually in the eyelid^7-10 and less often in the orbit.^9-11 In reported ocular cases, IPEH has occurred in association with a unilateral, solitary vascular lesion.^7-11 We report a case of IPEH that developed in association with multiple bilateral orbital vascular tumors, thus expanding the known ocular spectrum of this condition.

Report of a Case
In August 1991, an 80-year-old woman was seen with a 6-month history of slowly progressive, painless proptosis of the right eye. She had a history of successfully treated uterine cervical cancer many years earlier and a cataract extraction in the right eye 6 years earlier, but had no other systemic or ocular problems. Specifically, she had no history of trauma, ocular inflammation, cutaneous hemangioma, or prior episodes of proptosis.

Her visual acuity was 20/20 OD and 20/30 OS and intraocular pressures were normal. There was bilateral fullness of the upper and lower eyelids and 5 mm of proptosis of the right eye (Figure 1). The proptosis was not exacerbated by head position or Valsalva maneuver. Most of the fullness seemed to be caused by anterior displacement of orbital fat, as there was no distinctly palpable mass. Ocular motility was normal. The remainder of her ocular examination revealed normal findings.

View larger version (72K): [in this window] [in a new window] Figure 1. Facial appearance showing bilateral fullness of eyelids and proptosis of the right eye.

Orbital computed tomography disclosed bilateral orbital masses. In the right orbit there was an intraconal mass that measured 17 x 17 x 15 mm (Figure 2) and displaced the optic nerve superiorly. Lesions in the left orbit were not clearly delineated. However, on subsequent computed tomograpic examination, a second separate tumor, measuring 12 x 12 x 12 mm, was noted in the region of the superior orbital fissure of the right orbit with posterior extension into the middle cranial fossa (Figure 3). In the left orbit was an irregular mass nasal to the globe with ill-defined extension toward the orbital apex (Figure 3). Our differential diagnosis included metastatic carcinoma, lymphoma, multiple orbital cavernous hemangiomas, and orbital varices.

View larger version (60K): [in this window] [in a new window] Figure 2. Axial computed tomographic scan of orbits showing large circumscribed right intraconal mass. The lesion in the right orbitral apex and the lesions in the left orbit were not clearly delineated.

View larger version (57K): [in this window] [in a new window] Figure 3. Axial computed tomographic scan of orbits done 5 months later, better delineating an irregular mass in right muscle cone with extension into the cranial cavity and a mass in the nasal aspect of the left orbit. The lateral bony wall of the right orbit is missing following the lateral orbitotomy.

We elected to perform an excisional biopsy of the larger, symptomatic, intraconal mass in the right orbit by a superolateral orbitotomy through a cutaneous incision with an extraperiosteal approach and lateral osteotomy (Kronlein approach).¹² A reddish blue mass was identified and removed intact. The patient had an uneventful postoperative course.

Pathologic Findings
Grossly, the slightly deflated, irregular, dark-red mass measured 17 x 15 x 10 mm. Microscopically, the lesion was a vascular mass composed of large, thin-walled, blood-filled channels lined by benign endothelial cells. There were localized areas of chronic inflammation. Approximately 70% of the mass was composed of slender fibrous trabeculae lined by benign endothelial cells that projected into the lumen of large vascular channels (Figure 4). The final diagnosis was IPEH, arising in a thrombosed varix.

View larger version (119K): [in this window] [in a new window] Figure 4. Photomicrograph shows intravascular papillary endothelial hyperplasia filling lumen of an orbit varix. (Left, hematoxylin-eosin, original magnification x10; right, hematoxylin-eosin, original magnification x100.)

Three years after surgery, the patient's visual acuity was 20/40 OD and 20/30 OS. There was 2 mm of right proptosis and slight pallor of the right optic disc. Orbital computed tomography disclosed that all of the remaining lesions were stable.

Comment
Intravascular papillary endothelial hyperplasia usually occurs in the head and neck region and the extremities.^4-6 Ocular involvement is exceptionally rare. In the series of 44 cases reported by Clearkin and Enzinger,⁴ 17 cases reported by Kuo et al,⁵ and the 91 cases reported by Hashimoto et al,⁶ there was no mention of specific lesions in the eyelids or orbit.

To our knowledge, the first reported bona fide case of eyelid IPEH was by Wolter and Lewis⁷ in 1974. Although these authors cited 3 prior eyelid cases, these subsequently were not accepted by Font et al,⁹ who considered the patient of Wolter and Lewis⁷ to be the first acceptable case. Additional eyelid cases were recorded by Sorenson et al⁸ and Font et al⁹ in 1983. In 1997, Werner et al¹⁰ compiled the experience of several surgeons and added 4 eyelid cases, one of which extended to the lateral orbital rim.

Even fewer cases of deeper orbital involvement with IPEH have been recorded. The first case was reported by Weber and Babel¹¹ in 1981. In 1983, Font et al⁹ added 3 orbital cases from the files of the Armed Forces Institute of Pathology. A similar histopathologic response was also observed in a patient with a variant of the Sturge-Weber syndrome.¹³ Based on the aforementioned reports, it seems that there have been approximately 8 reported cases of eyelid IPEH and 5 reported cases of orbital IPEH in the English-language literature.

Our case of IPEH is unusual for 2 reasons. First, it occurred in bilateral orbital vascular lesions, presumably varices. Second, it was associated with another lesion that extended through the superior orbital fissure into the cranial cavity. Recently, a few cases of IPEH have been recognized to arise from intracranial vascular lesions, and these were summarized by Werner et al.¹⁰ It has also been recognized in the region of the superior orbital fissure,¹⁴ as occurred in our case.

Based on the histopathologic findings, the IPEH in our patient probably arose in a thrombosed varix. Orbital varices usually are primary lesions, but they occasionally can arise secondary to an intracranial arteriovenous communication that shunts arterial blood to the venous system, causing secondary dilation of orbital veins.² The fact that the vascular lesions in our patient were bilateral and multiple raised the possibility of secondary orbital varices. However, our patient had no history of trauma or clinical signs of carotid-cavernous fistula. Therefore, the pathogenesis of the underlying vascular lesion in our case remains obscure. It is possible that the presumed varices in our patient had been present for many years and that IPEH was a response to thrombosis in the larger lesion in the right orbit that contributed the progressive proptosis.

Intravascular papillary endothelial hyperplasia can be found histopathologically in vascular lesions of the eyelid and orbit, such as varix, cavernous hemangioma, and lymphangioma. Small intraluminal foci of IPEH are not uncommon, which attests to the reactive nature of the process. Many patients who have presumed benign vascular lesions of the orbit are diagnosed with computed tomography or magnetic resonance imaging and are followed up without treatment. If such a patient with a previously dormant lesion develops acute or progressive proptosis, however, the possibility of IPEH, rather than tumor growth or malignant transformation, should be considered. In IPEH, the proptosis can be gradual or rapid in onset, the latter possibly resulting from inflammation associated with an acute thrombus.

The histopathologic differential diagnosis includes angiosarcoma and angiolymphoid hyperplasia with eosinophilia (Kimura disease). Angiosarcoma is particularly difficult to differentiate from IPEH. However, it has more malignant cytologic features and invades tissue outside the vascular lumen.^2-4 Kimura disease has a predominance of lymphocytes and eosinophils.^2-4

In summary, this case demonstrates that orbital IPEH can occur in patients with multiple orbital vascular tumors, as well as solitary lesions. Intravascular papillary endothelial hyperplasia should be included in the differential diagnosis of acquired progressive proptosis in adults.

AUTHOR INFORMATION
Supported by the Eye Tumor Research Foundation, Philadelphia, Pa (Drs J. A. Shields and C. L. Shields); the Award of Merit in Retina Research, Houston, Tex (Dr J. A. Shields); the Macula Foundation, New York, NY (Dr C. L. Shields); and the Noel T. and Sarah L. Simmonds Endowment for Ophthalmic Pathology, Wills Eye Hospital, Philadelphia (Dr Eagle).

Ramon Font, MD, kindly provided a second opinion on the histopathology in this case.

Jerry A. Shields, MD; Carol L. Shields, MD; Ralph C. Eagle, Jr, MD; Waltenio Diniz, MD
Philadelphia, Pa

Reprints: Jerry A. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.

REFERENCES
1. Enzinger FM, Weiss SW. Reactive vascular proliferations mimicking angiosarcoma: papillary endothelial hyperplasia. In: Enzinger FM, Weiss SW. Soft Tissue Tumors. 2nd ed. St Louis, Mo: Mosby–Year Book Inc; 1988:522-525. 2. Shields JA. Vasculogenic tumors and malformations. In: Shields JA. Diagnosis and Management of Orbital Tumors. Philadelphia, Pa: WB Saunders Co; 1989:140-145. 3. Shields JA, Shields CL. Vascular tumors. In: Shields JA, Shields CL. Atlas of Orbital Tumors. Philadelphia, Pa: Lippincott/Williams & Wilkins; 1999:68-69. 4. Clearkin KP, Enzinger FM. Intravascular papillary endothelial hyperplasia. Arch Pathol Lab Med. 1976;100:441-444. ISI | PUBMED 5. Kuo TT, Sayers CP, Rosai J. Masson's "vegetant intravascular hemangioendothelioma": a lesion often mistaken for angiosarcoma: study of seventeen cases located in the skin and soft tissues. Cancer. 1976;38:1227-1236 PUBMED 6. Hashimoto H, Daimam Y, Enjoji M. Intravascular papillary endothelial hyperplasia: a clinicopathologic study of 91 cases. Am J Dermatopathol. 1983;5:539-546. ISI | PUBMED 7. Wolter JR, Lewis RG. Endovascular hemangioendothelioma of the eyelid. Am J Ophthalmol. 1974;78:727-729. PUBMED 8. Sorenson RL, Spencer WH, Stewart WB, Miller WW, Kleinhenz RJ. Intravascular papillary endothelial hyperplasia of the eyelid. Arch Ophthalmol. 1983;101:1728-1730. ABSTRACT 9. Font RL, Wheeler TM, Boniuk M. Intravascular papillary endothelial hyperplasia of the orbit and ocular adnexa. Arch Ophthalmol. 1983;101:1731-1736. ABSTRACT 10. Werner MS, Hornblass A, Reifler DM, Dresner SC, Harrison W. Intravascular papillary endothelial hyperplasia: collection of four cases and a review of the literature. Ophthal Plast Reconstr Surg. 1997;13:48-56. PUBMED 11. Weber FL, Babel J. Intravascular papillary endothelial hyperplasia of the orbit. Br J Ophthalmol. 1981;65:18-22. FREE FULL TEXT 12. Shields JA. Basic principles of management: lateral orbitotomy. In: Shields JA. Diagnosis and Management of Orbital Tumors. Philadelphia, Pa: WB Saunders Co; 1989:59-63. 13. Hofeldt AJ, Zaret CR, Jakobiec FA, et al. Orbitofacial angiomatosis. Arch Ophthalmol. 1979;97:484-488. ABSTRACT 14. Patt S, Kaden B, Stoltenberg-Didinger G. Intravascular papillary endothelial hyperplasia at the fissure orbitalis superior: a case report. Clin Neuropathol. 1992;11:128-130. PUBMED

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