Orbital Tumors in Adults

Frank A. Nesi, MD, FACS · César A. Sierra, MD

Introduction

Thyroid-related orbitopathy is the most common cause of referral of patients with orbital disease. Other causes include neoplasia, structural, inflammatory, and vascular lesions.

Tumors can be histopathologically classified into benign, benign with local destruction, or malignant. Neoplasia can also be classified by origin into primary, secondary, or with direct extension from adjacent structures, and metastatic from a distant site.

Advances in computed tomography (CT) scanning and magnetic resonance imaging (MRI) have revolutionized the evaluation and management of patients with orbital disease. Improved modalities such as high-resolution magnetic resonance fat saturation programs and gadolinium enhancement, as well as CT-guided biopsy, have contributed to the diagnostic efficacy. This powerful neuroimaging technology is used in conjunction with clinical history and physical examination to narrow down the differential diagnosis and to guide the course of management.

Clinical Findings

In contrast to children, orbital disease in the adult is rarely an emergent threat. Although the majority of these diseases are chronic, acute and hyperacute orbital processes can be catastrophic. Therefore, all patients must be evaluated promptly, especially in the presence of any neurologic symptom.

Evaluation of such patients must include:

• Visual acuity
• Presence of relative afferent pupillary defect
• Color vision
• Color desaturation test
• Visual fields
• Extraocular motility
• Diplopia fields
• Intraocular pressure
• Anterior and posterior segment biomicroscopy
• Evaluation of the eyelids, skin, and oral cavity
• Exophthalmometry
• Globe displacement
• Palpation of the orbit and lymph nodes
• Retropulsion
• Auscultation
• Valsalva and postural maneuvers
• Evaluation of cranial nerves
• Neuroimaging and ultrasonography

A good way to remember all the components of the evaluation in such patients is to take into account the six P’s of orbital disease: proptosis, progression, pain, palpation, pulsation and postural changes, and periorbital changes.

• Proptosis. Mass effect is the most typical presentation. Proptosis, displacement, or resistance to retropulsion of the globe are all characteristic of an orbital mass. The Hertel exophthalmometer is used to accurately measure and follow any degree of proptosis. Normal variations in measurement between race and gender should be kept in mind. The clinician should investigate in detail Hertel measurements that show: (1) asymmetry of more than 2 mm, (2) white patients with measurements of more than 21 mm, and (3) black patients with measurements of 23 mm or more. Proptosis can be congestive, intermittent, axial, and nonaxial. Congestive proptosis is usually acute or subacute. Thyroid-related orbitopathy, orbital cellulitis, and metastasis are included in the differential diagnosis. The clinical presentation includes congestion of conjunctival and episcleral vessels, lid swelling, chemosis, diminished ocular motility, and pain. Retinal venous congestion is apparent in cases of carotid-cavernous fistula or as a sign of optic nerve compression. Less commonly, patients present with enophthalmos rather than proptosis.
• Progression. Although the progression of the disease is important and provides the clinician with clues to help formulate a differential diagnosis, it can be confusing when dealing with orbital disorders. Acute processes tend to be inflammatory, although aggressive neoplasia must always be ruled out. The opposite is true for chronic disorders. Chronic inflammation can pose a diagnostic dilemma due to its insidious, infiltrative, and cicatrizing characteristic behavior mimicking chronic neoplasia. A thorough ocular and orbital examination should always follow the clinical history. In most cases, neuroradiologic imaging is necessary to further evaluate and confirm the diagnosis.
• Pain. Tenderness and sharp pain are typically associated with an acute inflammatory process, whereas deep, aching pain is classically experienced in patients with chronic neoplastic infiltration. Compression by a mass may be perceived as pressure-like pain. The evolution of pain presents important clues. Acute pain commonly leads to a worse clinical course and prognosis if not dealt expeditiously. Causes include orbital hemorrhage, infection including mucormycosis in immunocompromised patients, inflammatory disease, thrombosis, and aggressive tumors such as malignant lacrimal gland tumors and nasopharyngeal carcinoma.
• Palpation. Examination of the fornices with eversion of the lids and palpation of the orbital structures unveils anterior orbital masses. Size, consistency, vascularity, conjunctival, and dermatological changes should be examined. Sometimes the location of a mass helps to narrow down the differential diagnosis. The clinician should be suspicious of lymphoma, lymphangioma, neurofibroma, or dermoid cyst if the mass is palpated in the superomedial quadrant. Masses in the superotemporal quadrant include dermoid cysts, prolapsed lacrimal gland, lymphoma, lacrimal gland tumors, and idiopathic orbital inflammatory disease. Inferior tumors are less indicative of a particular diagnosis although lymphangioma and lacrimal sac tumors are included in the differential diagnosis.
• Pulsation and postural changes. Signs of arterial lesions such as carotid-cavernous fistula or arteriovenous malformations include pulsations with or without bruits, vascular congestion of periorbital tissues with increased episcleral, and intraocular pressure. On the other hand, venous lesions such as orbital varices are non-pulsatile but respond to postural changes that increase venous pressure (i.e., Valsalva maneuvers).

  Slide 1a

• Periorbital changes. Irritation, swelling, pain, warmth, and eventually loss of function suggest inflammatory diseases of the orbit. Nevertheless, the clinician should recognize that masquerading neoplastic lesions may behave in the same manner. Extraocular movement may be impaired by pain, sclerosis, infiltration, and ischemia. Examination of the eyelids may reveal anterior masses, vascular changes, inflammation, and ptosis. On biomicroscopy, generalized episcleral vascular congestion and arterialization should be distinguished from injection over the muscle insertions. A conjunctival “salmon patch” is suggestive of lymphoma. Optic nerve swelling or atrophy, optociliary shunt vessels, and choroidal folds should all be noted on fundus examination.

Neurologic changes such as loss of vision, diplopia, pain, and motor deficit are the result of one or a combination of several insults. Neoplastic infiltration, sclerosis, chronic inflammation, and mass effect can result in direct destruction, ptosis, entrapment, diplopia, pain, paresthesia, vascular, and optic nerve compromise.

Vascular Lesions

Cavernous Hemangioma

Slide 1b

Cavernous hemangiomas are the most common benign orbital neoplasms in adults. Histopathologically, cavernous hemangiomas are hamartomas composed of large vascular spaces containing low blood flow. The most common presentation is slow progressive proptosis in adulthood that can accelerate during pregnancy.

Symptoms may include diplopia and pain. Mass effect against the globe can produce acquired hyperopia, increased intraocular pressure, chorioretinal folds, and decreased visual acuity. Classically, cavernous hemangiomas lie in the intraconal space. Optic nerve compression may ensue if the orbital apex is involved. Diagnosis is made with computed tomography and ultrasonography. The CT scan will typically show a round and well-circumscribed lesion that is most commonly located in the retrobulbar space. Phleboliths are frequently detected in orbital CT scans. High internal reflectivity is typical when analyzed with ultrasonography. The lack of direct arteriovenous shunting in these lesions makes arteriography an inefficient diagnostic tool. This same element produces a characteristic pooling of contrast soon after its administration in both CT scan and MRI. Treatment is surgical, usually with a lateral approach to adequately expose the intraconal lesion (Slide 1A and Slide 1B).

Slide 2

Lymphangioma
Lymphangiomas are large serous-filled spaces lined with endothelium, containing lymphoid follicles. These tumors are known to be infiltrative and poorly circumscribed. Lymphangiomas may be superficial (i.e., eyelid, conjunctiva), orbital, or a combination of both. The majority of orbital lymphangiomas usually present superficially during childhood. Posterior lesions usually present later in adulthood as slow, progressive proptosis. Spontaneous hemorrhage within the tumor can produce abrupt onset proptosis, as well. Blood may become loculated into a “chocolate cyst,” which may subsequently regress. A CT scan and an MRI are helpful in localizing these tumors. Unlike hemangiomas, cysts can be seen within the lesions. Another distinguishing element is the absence of phleboliths (Slide 2). These lesions are friable, bleed easily and infiltrate adjacent structures. Therefore, indications for surgery are limited to large tumors or threatened vision secondary to sudden expansion by a hemorrhage.

Hemangiopericytomas
Hemangiopericytomas are rare lesions arising from pericytes. They are well-circumscribed lesions in a CT scan and are included in the differential diagnosis of cavernous hemangiomas. As opposed to hemangiomas, these lesions will grow rapidly and may have extensive shunting vessels. A large percentage of these lesions can transform and metastasize; therefore, complete surgical excision is the treatment of choice and long-term follow-up is required.

Vascular Abnormalities

Slide 3

Arteriovenous Fistulas
Arteriovenous fistulas may mimic neoplasia, presenting with similar signs such as proptosis and congestion of periocular tissues. There are two types of fistulas, low flow and high flow. The caliber of the artery involved will dictate the type of lesion, as well as the signs and subsequent treatment. Low-flow fistulas typically occur spontaneously due to degeneration of vessels from hypertension, atherosclerosis, and other vascular diseases. The clinical presentation is milder in low-flow fistulas including mild congestion of orbital tissues and dilation of the venous side.

Slide 4

In contrast, high-flow fistulas such as carotid-cavernous fistulas most commonly develop after trauma. Basal skull fractures with tears in the intracavernous portion of the carotid artery are the most common cause of high-flow fistulas. The large degree of shunting will result in increased venous pressure with arterialization of episcleral vessels causing secondary glaucoma. Other signs and symptoms include pain, exposure keratopathy, bruit, pulsatile exophthalmos, swelling of the periocular, and orbital tissues, signs of decreased perfusion, and variable cranial nerve involvement with sixth cranial nerve palsy being the most common (Slide 3). Detailed, high-resolution arteriovenous imaging and occasionally arteriography are required in the diagnosis of such lesions (Slide 4). Treatment of high-flow shunts involves embolization of the fistula by interventional radiology because they are less likely than low-flow fistulas to spontaneously thrombose.

Orbital Varices
Orbital varices are venous dilations that can present at any age. Non-pulsatile, intermittent proptosis that increases with Valsalva is characteristic. Bruits are absent in varices. A superficial periocular lesion is commonly seen. A CT scan of the orbits is the diagnostic tool of choice. Hyperextension of the neck in the coronal views places the head in a dependent position while Valsalva maneuvers decrease the venous return. The employment of both of these strategies shows the characteristic enlargement of these lesions on a CT scan.

Dermoid Cysts

Slide 5

Dermoid cysts are choristomas also known as benign cystic teratomas. The fibrous walls are lined with dermal appendages and filled with keratin. There are two types of dermoids — superficial and deep. Usually a deeper orbital lesion is found in adulthood as the cyst slowly and progressively grows displacing the globe. Dermoids may erode bone and even create bony defects with intracranial extension (Slide 5). Differential diagnosis may include mucoceles and encephaloceles medially and lacrimal tumors laterally in the lacrimal fossa. Treatment consists of total surgical excision of the cyst. Generally, deeper cysts are more challenging to excise. Failure to extirpate the lesion en bloc without rupture results in chronic inflammation and fibrosis of contiguous structures. Therefore, the key in management of orbital dermoid cysts is detailed preoperative neuroimaging to precisely delineate the extent of the lesion.

Lymphoid Tumors

Slide 6a

Orbital lymphoproliferative disorders are best described as a continuum of lesions from localized benign to malignant. As a group, these comprise the most common primary orbital lesions of the orbit accounting for up to 20% of all orbital biopsies. Adult patients after their sixth decade are almost exclusively affected. The classic presentation is a slow, progressive, and painless mass effect. Lymphoid lesions may present under the conjunctiva as a fleshy mass, also known as a “salmon patch,” in the lacrimal gland or deeper in the orbit (Slide 6A). Displacement of the globe occurs late due to its typical molding quality that spreads around the ocular and orbital structures. CT scan shows the putty-like molding appearance and defines the extension of these lesions (Slide 6B).

Slide 6b

A biopsy is required to identify the tumor. The specimens should be sent in formalin for permanent histologic section analysis and a different sample submitted for immunopathologic studies. Histopathologic classification is difficult and confusing, making the clinical course variable and unpredictable. Patients with studies suggesting reactive lymphoid hyperplasia may develop malignant lymphoma. Conversely, patients thought to have a malignant process can occasionally respond to steroids or regress spontaneously. As a general rule, the presence of lymphoid tumor cells suggests the possibility of a malignancy elsewhere regardless of the histological classification. It is therefore recommended that every patient diagnosed with a benign or malignant lymphoid disorder be consulted and evaluated indefinitely by a team that includes an ophthalmologist, an oncologist, and a radiation oncologist. Most cases of orbital lymphoma respond to radiotheraphy, whereas chemotherapy is commonly required in patients with systemic disease.

Neuronal Tumors

Optic Nerve Glioma or Glioblastoma
As a rule of thumb, optic nerve tumors occurring in an unusual age group will act more aggressive. Optic nerve gliomas in the adult are the perfect example. Although extremely rare, this tumor typically occurs in middle-aged men presenting with signs similar to optic neuritis. The aggressive behavior of glioblastomas leads to a rapid progression of blindness, neurological decline, and death.

Meningioma
Meningiomas are the most commonly occurring optic nerve tumor in adults. Middle-aged women are affected more frequently. Similar to glioblastomas, meningiomas occurring outside the typical age range are more aggressive. These tumors arise from the meningothelial cells of the arachnoid villi. Signs and symptoms depend on the location of the lesion. The clinical behavior of meningiomas differs from tumors originating outside the meninges as proptosis follows all the signs of optic nerve compression. Optic nerve sheath meningiomas typically present with early decrease in visual acuity and signs of optic nerve dysfunction including papilledema, enlarged blind spot, decreased color vision, and optic nerve atrophy. Optociliary shunt vessels in the peripapillary area are thought to develop due to compression of the retinal vessels by the tumor. These shunt vessels are classic but not pathognomonic because they can also be found in patients with optic nerve glioma and in central retinal vein occlusion. CT scan and MRI are invaluable in the diagnosis and management of meningiomas. The typical calcifications also known as "railroad tracks" are seen within the radiolucent optic nerve surrounded by a thickened high-density tumor. Patients are closely monitored with imaging studies for progression, growth, and invasion of vital structures. Preservation of functional visual acuity is almost impossible with surgical resection of the tumor. Debulking with or without radiotherapy is required in patients showing aggressive tumors, especially in those extending intracranially.

Contrary to optic nerve meningiomas, patients with meningiomas arising from the sphenoid ridge commonly present with proptosis, eyelid swelling secondary to venous congestion, and temporal mass effect. Visual changes are usually a late finding. A dense, homogeneous lesion with psammomatous calcifications, hyperostosis, and bone lysis is noted with CT scan. Treatment options include close observation, debulking, and surgical excision with radiotherapy are the treatment options. Indications for intervention are deterioration of visual acuity secondary to compression and involvement of essential structures.

Schwannoma
A schwannoma is a well-defined, encapsulated tumor arising from peripheral nerves as proliferations of Schwann cells. Schwannomas usually present in adulthood with slow, progressive, and painless proptosis with predilection for the superior orbit and inferior displacement of the globe. Diplopia frequently develops when the third, fourth, and fifth cranial nerves are involved. CT scan and MRI show a well-circumscribed heterogeneous mass similar to a cavernous hemangioma. Occasionally, a schwannoma surrounds the optic nerve and can be confused with an optic nerve sheath meningioma. Visual prognosis is good with early diagnosis and surgical excision of the tumor.

Tumors of the Lacrimal Gland

The most common cause of a lacrimal gland mass is inflammation or dacryoadenitis. Other causes include lymphoproliferative disorders and epithelial neoplasia. In this section, the most common epithelial tumors will be discussed.

Slide 7

Benign Mixed Tumor or Pleomorphic Lacrimal Gland Adenoma
The pleomorphic adenoma typically presents in the middle-aged adult with slow, progressive, painless superolateral mass causing proptosis and inferonasal displacement of the globe. Patients present months or even a year after the initial symptoms. On CT scan, the tumor appears as a round, heterogeneous and well-circumscribed mass. Classically, the lacrimal fossa is enlarged without evidence of lytic bone destruction. Because of a high recurrence rate and potential for malignant transformation, complete surgical excision through a lateral orbitotomy is recommended.

Adenoid Cystic Carcinoma
Adenoid cystic carcinomas are the most common malignant epithelial tumors of the lacrimal gland. These tumors commonly present as a sudden onset and fast growing mass in the lacrimal fossa. Pain secondary to perineural invasion, bone destruction, and aggressiveness are all distinguishing features of this lesion. Calcifications may also be seen on CT scan. Treatment consists of orbital exenteration and aggressive radiotherapy (Slide 7). Prognosis is poor due to early perineural invasion into structures adjacent to the orbit and even metastasis at the time of presentation.

Metastatic Tumors of the Orbit

Orbital metastasis is the initial presentation in up to 28% of patients with unknown systemic cancer. Breast and lung carcinomas are the leading causes. Typical manifestations of metastasis include mass effect with displacement or proptosis, pain, inflammation, bone destruction, and infiltration manifested as ptosis, diplopia, or enophthalmos. The latter is most commonly seen in sclerotic tumors such as scirrhous breast carcinoma. Orbital metastasis from bronchogenic carcinomas occur early in the disease in contrast to breast cancer that has the potential of involving the orbit even 20 years after treatment. Fine needle aspiration aids in the diagnosis of these tumors. Hormone receptor studies on fresh tissue samples are useful in directing the management of metastatic breast carcinoma. The goal in orbital metastases is palliation and the mainstay of treatment is radiotheraphy. Adjunctive hormonal therapy, chemotherapy, and even surgery may be added in select patients.

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