Orbital and Eyelid Lymphangioma

Kathleen M. Zielinski, MD · Mark R. Levine, MD, FACS · David S. Bardenstein, MD

Introduction

Lymphangioma is a rare, diffusely infiltrating, benign, nonencapsulated vascular tumor most commonly diagnosed in the first or second decade of life. Despite a congenital nature and low proliferative potential, lymphangiomas often show some degree of progressive enlargement or growth. Lymphangiomas are distinct, however, from capillary hemangiomas because of the lack of significant communication with the vascular system and lack of spontaneous regression. Lymphangiomas arise in many soft tissue sites of the body, including the eyelids, conjunctiva, and orbit.

Lymphangioma comprised 0.3% to 1.5% of all histopathologically diagnosed orbital tumors in five major series.¹ The actual frequency may be higher because some asymptomatic and mildly symptomatic patients do not undergo a biopsy procedure. No significant race or sex predilection exists, although lymphangiomas are reported slightly more often in female patients.

The pathogenesis of orbital lymphangioma is controversial. Wright and colleagues suggested that most lymphangiomas represent venous anomalies or varicies because a connection of these tumors to the venous system can be demonstrated by venography.² Harris and colleagues considered lymphangioma channels isolated from the normal orbital vasculature. They found that, unlike a varix, a lymphangioma was not affected by postural change, except for the dependency-related diffusion that affects all tissues. They also found that neither arteriography nor venography filled lymphangiomas.³

Jones suggested that the human orbit may have lymphatic channels when he demonstrated in animals that India ink injected into the extracellular space of the orbit appeared in the cervical lymph nodes.⁴ Therefore, lymphangioma may represent a hamartomatous abnormality of existing orbital lymph vessels. Features that indicate a lymphatic origin include a simple layer of endothelial cells lining the channels, lymph-like fluid, and a thin septal stroma that may hold lymphocyte aggregates. However, lymphoid follicles are frequently absent, and electron microscopy has shown features of both lymphatic channels and venous channels.³ Studies using tritiated thymidine have shown that the endothelial lining has a turnover rate similar to that of normal mature cells, suggesting that lymphangiomas represent areas of maldevelopment rather than actively proliferating and growing true neoplasias.¹

Orbital lymphangiomas are associated with an orbital and/or intracranial arterovenous malformation. Katz and researchers attempted to explain this by stating that lymphangiomas represent a spectrum of multicentric venous lymphatic vascular malformations, depending on the time of occurrence during embryonal development.⁵

Clinical Features

The most common initial complaint reported by patients with a lymphangioma was progressive swelling or a mass affecting the eyelids, with or without ptosis (Slide 1). Proptosis and hemorrhage were the next two most commonly reported symptoms. In one study by Wright and colleagues, 61% of patients had proptosis at rest, which increased with the Valsalva maneuver.² Acute proptosis may also occur secondary to lymphoid hypertrophy within the tumor after upper respiratory tract infections (Slide 2, Slide 3, Slide 4, Slide 5).

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Orbital hemorrhage occurred in 55% of patients in Wright's study. Although hemorrhage was a major factor in the enlargement of the lesions, bleeding into the surrounding tissues and cyst formation was also frequent.² Without a tumor capsule or a substantial stroma between the adjacent channels, the expansion of blood cysts is relatively unrestrained and proptosis can be dramatic (Slide 6). Mild anisometropic amblyopia has occurred in patients whose cysts indented the globe and went untreated.⁴

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Hemorrhage in conjunction with cyst formation has been termed chocolate cyst. Hemorrhages are frequently associated with pain and sudden proptosis and, in children, by nausea and vomiting. Additional symptoms reported include pain, reduction in vision, and tearing (Table). Signs include eyelid and brow thickening, ptosis, diplopia, tearing, recurrent epistaxis, conjunctival cysts, and soft and hard palate cysts (Slide 7).

Clinical features, treatment, and prognosis are correlated with the location of the lymphangioma.

• The superficial lymphangioma typically presents as a small multilobulated cystic mass of bulbar conjunctiva and/or the lid that neither affects vision nor displaces the globe. When cosmetically unacceptable, superficial lymphangiomas can be removed with good results (Slide 8, Slide 9, Slide 10, Slide 11, Slide 12).
• The orbital lymphangioma is located behind the orbital septum and involves the intraconal and/or extraconal space. Usually, orbital lymphangiomas present with a sudden proptosis and occasionally with pain due to spontaneous intralesional hemorrhage or to lymphoid proliferation in the connective tissue of the tumor during an upper respiratory infection. Other signs of an orbital lymphangioma may include ptosis, eye movement restriction, and compressive optic neuropathy with papilledema and secondary glaucoma.
• The combined lymphangioma consists of the superficial and deep form and involves the intraconal, extraconal preseptal, and postseptal spaces. It has an anterior component with multiple conjunctival or lid cysts. Similar cystic lesions of mucous membrane of the mouth and palate are often observed in patients with combined lymphangiomas. Spontaneous intratumoral hemorrhage may result in periorbital ecchymosis, ptosis, and amblyopia. Optic nerve dysfunction may occur as the result of an acute expanding tumor. The patient may require surgery, either on urgent basis in cases of acute retrobulbar hemorrhage with optic nerve compression, or on elective basis for cosmetic problems.
• An isolated intracranial vascular venous anomaly associated with a cavernous hemangioma has been reported in patients with combined lymphangioma and related cerebral hemorrhage.⁶

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Diagnostic Features

To establish diagnosis, computed tomography (CT) scan and magnetic resonance imaging (MRI) of the orbit are obligatory. A CT scan usually shows a multilobulated cystic mass within the orbit and intralesional calcifications may be demonstrated. MRI is the modality of choice to identify the hemorrhagic cyst as well as the lymphatic cystic component. Hemorrhagic cyst (acute and subacute) shows increased signal on MRI T1- and T2-weighted images, whereas lymphatic cysts are hypointense on T1-weighted images and hyperintense on T2-weighted images. MRI study is most helpful in documenting fluid level within the multicystic lesion.⁷ Pathological examination of a lymphangioma reveals a non-encapsulated lesion with variably sized cystic spaces, lined by flattened endothelial cells. Pericytes and smooth muscles are absent in the vessel wall. This feature, the progression by recurrent intralesional hemorrhages, and the absence of clinical response to interferon and corticotherapy help to distinguish lymphangioma from cavernous hemangioma.

Natural Course

Lymphangiomas consist of nonencapsulated networks of endothelial-lined channels, which are separated by thin septa and filled with pale-staining fluid. Lymphatic aggregates are frequently present. Harris and colleagues found the basic lesion is a network of small caliber, malformed vascular channels that arborize irregularly throughout portions of the orbit.³ Although the lumens are not continuous with the orbital circulation, small nutrient vessels exist within the fragile walls and may be the source of hemorrhage. Bleeding into these channels or microcysts may cause hemorrhage, expansion into macrocystic lesions, and massive blood cysts, all of which may be precipitated by a viral illness or a trauma.

Subsequently, the clinical course may be variable. Small bleeds with proptosis maintaining normal vision may develop, which then may return to normal. In other instances, the proptosis may remain after the bleeding subsides. In other case reports, bleeds from days to weeks occur, resulting in visual compromise from optic nerve compression or from extreme proptosis.

Treatment

Treatment of these intertwining cystic lesions can be problematic. The mainstay of treatment is a conservative approach in hopes of aquiescence of the varying degree of bleeding into microcysts or macrocysts. Several treatment modalities have been described including observation, systemic steroids, needle decompression of cysts with imaging guidance, surgical resection, staged laser treatments, cryotherapy, and sclerotherapy. Any local intervention must be used cautiously because of possible damage to functionally important orbital structures.

Conservative management has been followed by spontaneous resolution and normalization of vision in selected patients. Wilson and colleagues described conservative management as limitation of activity or bedrest as an outpatient or inpatient, cold compresses, and monitoring of visual acuity, pupillary light reaction, and maintenance of appetite.⁸

The use of systemic steroids has generally been helpful; however, investigators have found it to be of minimal help.⁹ Sires and colleagues have recommended corticosteroids for symptomatic relief, loss of vision, and motility dysfunction, and use of corticosteroids peri- and postoperatively decreases inflammation and swelling in surgical patients.¹⁰ Theoretically, the beneficial effect of steroids in lymphangioma is a reduction of lymphoid hypertrophy and stabilization of the vasculature. Steroid treatment may have a better effect in children because of a lack of pseudo-encapsulation, which slowly develops over time.

If surgery is performed because of major macrocysts that raise the orbital pressure, compress the optic nerve, and cause extreme proptosis, then the approach should include an MRI or a CT scan to determine the best surgical location approach, followed by limited intraorbital dissection and decapitation of the offending blood cysts. An aggressive approach may result in the destabilization of multiple macrocysts and significant recurrent bleeding. If this happens, repeat orbital decompression and exploration with aggressive dissection and bipolar cauterization should be considered with a Jackson-Pratt drainage system in place. This is a controversial approach; macrocysts can continue to bleed without the Jackson-Pratt drainage system (Slide 13, Slide 14, Slide 15, Slide 16, Slide 17, Slide 18, Slide 19), but, on the other hand, suction of the system may destabilize more cysts.

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Other treatment options include injection of sclerosing agents (sodium tetradecyl sulfate), which may be a useful therapeutic option for some patients, especially those with no preceding surgery. Intralesional injection of OK-432, an immunopotentiator, has also been successful in shrinking lymphangiomas.⁶ Growth factor receptors, specifically platelet-derived growth factor receptor-alpha, are expressed by the endothelial cells lining orbital lymphangiomas. The specific role of platelet-derived growth factor receptor inhibitors, such as imatinib mesylate, is under investigation. One proposed surgical technique describes combining partially controlled decompression of the lesion with intralesional injection of fibrin glue.¹¹

Conjunctival lymphangiomas have been treated best with a carbon dioxide laser, but cryotherapy and surgical removal are options. Infiltration of the lid and levator is best treated with a combination of surgical dissection with cautery and/or carbon dioxide laser. The carbon dioxide laser removes the lymphangioma with minimal bleeding (Slide 20, Slide 21, Slide 22, Slide 23).

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Conclusion

Orbital lymphangioma should be considered in any case of childhood proptosis. Associated extraorbital localizations, particularly intracranial vascular venous anomaly, have to be ruled out. A multidisciplinary approach is needed and the treatment has to be as conservative as possible, if vision is not at risk and cosmesis is acceptable.

References

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11. Boulos PR, Harissi-Dagher M, Kavalec C, et al. Intralesional injection of Tisseel fibrin glue for resection of lymphangiomas and other thin-walled orbital cysts. Ophthal Plast Reconstr Surg. 2005;21:171-176.