Idiopathic Orbital Inflammation/Orbital Pseudotumor
This is a challenging disease to diagnose with certainty, since it is a diagnosis of exclusion. There is no sex predilection, with peak incidence between the fourth and sixth decades. An aching discomfort, typically associated with unilateral proptosis, is an important part of the clinical presentation. Clinical findings are often characterized by the sudden onset of inflammatory features, including erythema and skin warmth from increased vascularity, and pain on passive and forced eye ductions, in addition to proptosis from tissue swelling. Typical findings, as demonstrated in Figure 1a, include swelling of the upper eyelid and lacrimal gland, and may involve the adjacent Tenon capsule, orbital fat, and trochlea. Visual loss is rare unless inflammation involves the orbital apex. Figures 1b and 1c demonstrate typical CT findings.
Initial treatment with high-dose steroids (typically 60 to 80 mg daily), followed by a slow taper, may be augmented by steroid-sparing agents such as methotrexate if steroid-dependence (prednisone >10 mg/day) or disease recrudescence occurs. High-dose intravenous steroids and local forms of augmented therapy—including intralesional steroids or external beam radiotherapy—can be considered in recalcitrant or recrudescent cases. Promising treatment options include the use of rituximab (chimeric anti-CD20 antibody), and anti-tumor necrosis factor agents such as infliximab, etanercept, or adalimumab have also been used successfully in cases of steroid dependency. As with all immune-modulators, care should be exercised in the use of these agents, and they should be administered in the setting of a multidisciplinary team.
Surgical debulking of lesions may be considered after medical treatment is completed, when there are residual anterior orbital lesions, and more cautiously considered for posterior lesions. Exenteration is reserved only for pain relief in blind, proptotic, and immobile eyes.
Recently, a subgroup of orbital pseudotumor has been reported in association with an uncommon subtype of IgG4-related sclerotic disease. An association with autoimmune pancreatitis and systemic sclerosing disease, along with de novo or secondary orbital lymphoma, has been reported in this subtype of orbital pseudotumor.
Lacrimal Gland Epithelial Tumors
These tumors are uncommon, but need to be differentiated from other disorders that involve the lacrimal gland, including Wegener granulomatosis, inflammatory dacryoadenitis, or various lymphoid lesions. Epithelial tumors commonly present as a firm enlargement of the lacrimal gland, causing globe indentation, with the disease duration proportional to tumor mass-effect. The neoplastic cell is usually derived from secretory or ductal epithelium.
Symptoms of pain or pressure-sensation are nonspecific; however, rapid progression of symptoms, as well as identification of adjacent bone lysis is helpful in distinguishing a malignant lesion from a benign one. The presence of calcific densities and tumor nodularity is nonspecific.
Pleomorphic adenomas are characterized by oval, smooth tumors in the lacrimal fossa with surface bosselation (protuberances) and internal cystic degeneration. Malignant mixed tumors arise de novo or represent malignant transformation of pleomorphic adenoma, and histologic diagnosis is necessary to differentiate them. Incisional biopsy should be avoided if pleomorphic adenoma is suspected, as late tumor recurrence with malignant transformation has been described.
Adenoid cystic carcinoma is the most common primary epithelial malignancy of the lacrimal gland. It occurs in all age groups with equal sex distribution and has varying survival rates, presumably related to its slow direct spread via perineural and bone routes. Any basaloid (containing cells that resemble basal cells) features on histopathology are associated with a worse prognosis.
Adenocarcinoma arises from the glandular structures of the lacrimal gland and is observed typically in middle-age males. Its aggressive nature with early lymphatic dissemination is reflected in its reduced median survival times.
When histopathological diagnosis is confirmed, treatment of malignant epithelial tumors of the lacrimal gland involves wide surgical resection with adjuvant chemotherapy and radiation therapy.
Lymphoma is a heterogeneous group of hematopoietic tumors and is typified by the non-Hodgkin, B-cell lineage and only rarely by the non-Hodgkin T-cell lineage or Hodgkin lymphoma. The non-Hodgkin lymphoma (NHL) subgroup alone comprised almost 10% of orbital tumors treated in the Mayo Clinic. Typical patients with NHL orbital tumors are past middle age, have equal sex predilection, and present with diplopia, epiphora, and painless proptosis or displacement of globe position. Clinical signs, demonstrated in Figures 2a and 2b, include eyelid swelling, mechanical ptosis, variable amounts of proptosis, and a conjunctival salmon-patch. An orbital or subconjunctival mass may be found on clinical or radiographic examination, as seen in Figure 2c. The frequency of palpable orbital masses in lymphomas of the orbit reflects the tendency for these tumors to extend anteriorly along fascial planes, and not to form circumscribed orbital masses that can compromise optic nerve function.
Follicular, small lymphocytic lymphoma subtypes and mucosa-associated lymphoid tissue (MALT) are the predominant forms encountered, and diagnosis is increasingly dependent on immunophenotyping for expressed immunoglobulins and cluster-defined (CD) antigens. In general, mature B-cell phenotypes express the corresponding surface antigens including IgM/D, CD5, 19, 20, 22, and 79a. Cyclin D1-gene expression is associated with poor-prognosis mantle cell lymphoma.
The choice of therapy is dependent on tumor location and histological subtype, with excellent responses to external beam radiation therapy being the norm. Total fractionated doses <35 Gy are recommended to avoid serious long-term complications, including keratoconjunctivitis sicca, cataract, keratitis, and radiation retinopathy, while adequately achieving local control. Survival rates for the most common lymphoma subtypes are excellent; however, certain clinical scenarios, including relapsing low-grade, de novo intermediate, or high-grade lymphomas, require a combination of chemotherapy and radiation therapy. Current new treatments include biologically active agents like rituximab, radioactive-labeled biologic and chemotherapeutic agents such as iodine131, β-emitting isotope yttrium 90, and other forms of immunotherapy directed at β-cell antigens Cyclin D1, CD20, or CD22.
Meningiomas are common neurogenic tumors that may arise from the optic nerve sheath or sphenoid ridge. They are slow-growing (Figure 3a) and create symptoms by compression of normal structures. Visual loss is not uncommon and is seen early with tumors located posteriorly and in close proximity to the optic nerve. This tumor is more common in females (hormone receptors, including progesterone receptors, have been identified on tumor cells), in patients with past exposure to ionizing radiation, and NF-2 (in the setting of multiple meningiomas, or pediatric patients).
With regard to optic nerve meningiomas, diffuse-calcification is associated with indolent tumor behavior. Gadolinium-enhanced MRI scans accurately delineate intracranial involvement of tumors. Optic nerve meningiomas demonstrate a fine nodular surface that reflects its typical extradural growth pattern, and this is distinct from the smooth, well-defined surface of optic nerve gliomas.
When invading soft tissues, sphenoid meningiomas extend along fascial planes through foramina and adventitial spaces. CT imaging demonstrates bony reactive changes often with hyperostosis while the soft tissue component is well demonstrated on MRI (Figures 3b and 3c) as a defined, homogeneous lesion that enhances uniformly with gadolinium. Calcification may be seen in psammomatous lesions.
Treatment options for orbital meningiomas include observation, surgery, and/or irradiation, and are ultimately influenced by patient age as well as tumor size, location, and extent. The management of optic nerve sheath meningiomas involves external beam radiation therapy with an attempt to preserve vision. Surgery is usually deferred until clinical or imaging characteristics suggest extension of tumor into vital intracranial structures, or loss of useful vision. In contrast, orbital meningiomas arising from the sphenoid wing are treated with surgical excision and, in certain cases, followed by adjunctive radiation therapy to delay tumor recurrences. More recently, stereotactic radiosurgery with a gamma knife has demonstrated an excellent response rate for meningiomas at the base of the skull. As expected, surgery for tumors of the optic nerve sheath or lesser wing of the sphenoid would be associated with poorer visual prognoses as compared to surgery for tumors of the greater sphenoid wing.
Hormonal therapy with anti-progestogenic agents has shown mixed results, with side effects of partial cortisol antagonism and stimulation of the hypothalamic-pituitary-adrenal (HPA) axis, limiting their use. Interestingly, progestogen agonists have not been shown to accelerate tumor growth, and anti-estrogenic compounds have no reported benefit in tumor treatment. Irradiation of orbital meningiomas at high doses of irradiation (50 Gy) involves potential risks, including that of "malignant" conversion of a seemingly benign meningioma, inducing secondary orbital tumors, and neuro-ophthalmic and retinal complications.
This is the most common benign orbital tumor in adults and has a predilection for middle-age women. The common use of orbital imaging for headaches or other nonrelated causes has increased the frequency of diagnosis of this painless, unilateral, non-pulsatile, slowly progressive orbital tumor (Figure 4a). The most common presenting symptoms and signs are related to mass effects, including proptosis or displacement of the globe, and visual disturbance from induced hyperopia, choroidal folds, optic nerve compression, motility defects, and gaze-evoked amaurosis. Figures 4b and 4c illustrate typical radiological findings.
Most patients opt for observation, as these benign tumors grow slowly. Surgical treatment is excision and may require lateral or anteromedial orbitotomy. Unusual sites including apical or postero-medial orbital locations may require combined approaches for surgical access.
This malformation of the orbital venous circulation consists of a rich network of anomalous veins directly connected to the orbital venous system. The presence of deep venous anomalies is suspected in patients with a combination of vascular engorgement, and intermittent dynamic proptosis (Figures 5a–f). Similar venous malformations can also affect the eyelids, conjunctiva, and other periorbital or intracranial tissues.
Most patients do not require any intervention, but embolization or surgery may be considered for progressive pain and enlargement, or cosmetic concerns. Surgical intervention is difficult and preoperative measures to induce intralesional thrombosis with micro-coils or cyanoacrylate glue are often employed to minimize intraoperative hemorrhage.
These acquired arteriovenous shunts present with a constellation of symptoms and signs proportional to hemodynamic flow in the lesion. Traumatic high-flow lesions (direct fistulas) have a more pronounced effect of orbital swelling, chemosis, increased episcleral venous pressure, pulsatile proptosis and bruit, as well as variable cranial nerve palsies (Figure 6a). Figures 6b and 6c demonstrate characteristic radiographic findings of high-flow lesions, which rarely close spontaneously and benefit from elective closure by micro-coils, detachable balloon, or direct surgical exposure. In contrast, low-flow spontaneous dural shunts (indirect fistulas) often close spontaneously, and typically manifest less severe symptoms and signs of edema and vascular dilatation.
This common disorder of surgical sino-rhinology is the most common secondary-orbital tumor in the Mayo Clinic tumor survey (see "Suggested Reading"). These lesions present to the ophthalmologist with proptosis, palpable orbital masses, gaze restriction, and headache associated with chronic sinusitis and upper respiratory tract infections. Symptoms and signs depend on the location of the affected sinus(es), typically the frontal and/or ethmoid sinuses.
Management requires surgery and is usually the purview of the sinus surgeon. Often the ENT surgeon will request the assistance of an orbital surgeon, if extensive orbital involvement is present. The goal is to evacuate the cystic contents, remove diseased mucosa, and create new intranasal drainage. In severe or recurrent cases, frontal sinus ablation and packing with fat is helpful to prevent recurrence.
Most clinicians are familiar with pediatric capillary hemangiomas involving the eyelids.
Infants with tumors in the anterior orbit usually present with a unilateral, painlessly enlarging (especially when crying), and compressible swelling of the overlying eyelid. Proptosis tends to be minimal, although rapid growth with anterior protrusion of tumor and displacement of the eye can be seen. The clinical course of growth, followed by growth plateau and regression, is highly variable. During the interim, differentiation from malignant tumors and observation for complications associated with occlusion amblyopia or corneal astigmatism determine whether early intervention is warranted.
Treatment options for skin and anterior orbital lesions include intralesional or oral steroids; however, potential side effects of skin atrophy, lid necrosis, and ocular embolism can occur with the intralesional route. Recent reports have described good efficacy with systemic beta-blockers (propranolol 2 mg/kg/day), and even topical beta-blockers. Retroseptal tumors may be managed with intralesional or systemic corticosteroids (prednisone 3–5 mg/kg/day) or interferon α-2β (for resistant cases). Open biopsy with direct injection of corticosteroids may be considered if the diagnosis is in doubt, and exceptional cases may be managed with surgical excision.
Lymphangiomas are an important consideration when seeing a child with proptosis. In the consideration of acute proptosis, rhabdomyosarcoma also has to be considered. Some patients demonstrate dynamic proptosis with varying degrees of ocular motility impairment. There may be associated vascular tumors of the cheek, forehead, and nose, or straw-colored cysts in mucous membranes of the hard-palate and conjunctival fornix. Some patients have associated non-contiguous intracranial vascular lesions. There may be intermittent and transient swelling of the mass associated with intercurrent upper respiratory infections or lymphoid stimulation.
The natural course of growth is typically slower compared to that of capillary hemangiomas (unless there is intervening hemorrhage), hence patients are likely to present later in childhood with progressive proptosis correlating with tumor growth. Pain is unusual and, if present, suggests acute intralesional hemorrhage and formation of "chocolate-cysts" that may be associated with raised intraorbital pressure and consequent visual impairment. The clinical course of this tumor is variable and inconsistent, varying from benign arrest of growth, to relentless growth despite debulking surgery, with a discouraging prognosis. In between these two extremes, spontaneous episodes of hemorrhage and/or painful disfiguring proptosis may ensue.
Treatment may require surgical debulking, but generally, conservative therapy and delaying interventions until adulthood is preferable unless visual function is threatened, since surgery often directly or indirectly impairs the functionally important structures of the orbit.
As the most common primary malignant orbital tumor of young children and adolescence, rhabdomyosarcoma needs to be included in the differential diagnosis of acute, painless unilateral nonaxial proptosis (Figure 7a). If the tumor is highly malignant, the clinical picture can be confused by accompanying eyelid swelling, conjunctival chemosis, and ocular dysmotility in the direction of the tumor mass. There is rapid progression of eyelid edema and color, from blue to purple and then red, which is distinguished from orbital cellulitis by its lack of local heat and lack of signs of systemic sepsis.
CT defines tumor location, size, and lytic bone effects (Figures 7b and 7c). MRI provides excellent soft tissue delineation of the tumor and suggests irregular but defined contours and may demonstrate mild to moderate contrast enhancement depending on its blood supply. Management involves surgery with adjuvant chemotherapy and radiation therapy. As multimodal management has improved, orbital exenteration is now rarely, if ever, considered as a primary therapeutic option for this tumor. Different management protocols exist and, in general, are predicated on the histology and amount of residual tumor.