Benign Orbital Tumors

Etiology

Classification

Primary orbital tumors can be classified by tissue of origin (Table 1).[1]

Table 1. Benign Orbital Tumors and Tissues of Origin

Cystic Tumors

Epidermoid cysts: Epidermoid cysts rarely form in the orbit but must be considered in the differential diagnosis for deep orbital cystic lesions. Epidermoid cysts may present as primary congenital lesions or may form following traumatic displacement of the surface epithelium.[2] Histologically, epidermoid cysts are lined by stratified squamous epithelium and contain desquamated keratin lamellae. Epidermoid cysts should not be confused with dermoid cysts, which are characterized by the presence of mesodermal elements. Dermoid cysts account for nearly half of childhood orbital tumors but are rarely diagnosed in adulthood.[3] 

Mucoceles: Mucoceles are cystic cavities that contain sterile mucus. Mucoceles typically form secondary to outflow obstruction of the frontal and ethmoidal sinuses. The masses grow slowly; however, sufficiently large mucoceles can invade the orbit and cause symptoms similar to those seen with other orbital masses. Mucoceles have been reported more often in patients with a history of trauma or sinus surgical procedures.[4] Histologically, these tumors are lined by simple epithelium and may include acute or chronic inflammatory material.

Hematic pseudocysts: Hematic pseudocysts are rarely reported orbital lesions. The most common presentation of a hematic pseudocyst is acute-onset proptosis following remote trauma to the orbit.[5] Chronic orbital hematic pseudocysts have also been reported and are histologically similar to chronic subdural hematomas.[6][7] Hematic pseudocysts contain blood or blood breakdown products. Depending on the chronicity of the mass, products of inflammatory or granulomatous reactions may also be present.

Meningoencephaloceles: Defects in the orbital roof allow intracranial tissue to herniate into the orbit, forming meningoencephaloceles. Although rare, meningoencephaloceles are important to consider in patients presenting with signs of a superior or superonasal orbital mass. Meningoencephaloceles are included in the differential diagnosis of pulsatile proptosis, along with carotid-cavernous fistulas and vascular tumors.[8] Radiographic studies are crucial in diagnosing these masses because inappropriate biopsy or resection can lead to devastating outcomes.

Apocrine hidrocystomas: Apocrine hidrocystomas are common eyelid lesions but are rarely reported inside the orbit.[9] Apocrine hidrocystomas are cystic lesions characterized histologically by a capsule composed of bilaminar columnar epithelium with outpouchings of the lumen (apocrine snouts). The lesions are prone to recurrence if the capsule is not completely excised.[10] 

Additionally, colobomatous cysts of the orbit are rare congenital anomalies that result from embryological abnormalities. Colobomatous cysts appear at birth and are diagnosed in infancy or childhood; therefore, these lesions will not be discussed in detail here. Table 2 summarizes the features of cystic orbital tumors.

Table 2. Key Features of Cystic Orbital Tumors

Vasculogenic Tumors

Tumors of vasculogenic origin constitute approximately 17% of all orbital masses (Table 3).[3] The Orbital Society has classified certain vascular lesions based on the type of vascular flow.[3][11] Contrast imaging is especially helpful in the diagnosis of vascular lesions because they are often characterized by specific vascular flow and filling patterns.

Cavernous hemangioma: The cavernous hemangioma, also known as a cavernoma, is the most common benign primary orbital tumor in adults.[3] Cavernous hemangiomas have slow vascular flow and low pressure, resulting in a lower risk of hemorrhage than other vascular lesions. The lesions often present in middle age with slowly progressive proptosis and vision changes. Presentation during pregnancy is common due to hormone-associated growth and an increased risk of hemorrhage.[12] Histologically, these tumors are encapsulated lesions characterized by dilated vascular spaces separated by connective tissue. 

Lymphangiomas: Lymphangiomas, also known as lymphatic malformations, involve both vascular and lymphatic systems. They have no vascular flow and are most prevalent in the first and second decades of life.[3][11] Loose connective tissue stroma surrounds the lymphatic channels on histology. 

Orbital varices: In contrast to lymphangiomas, orbital varices typically present with intermittent proptosis or diplopia during Valsalva maneuvers due to their venous flow. These vascular malformations can bleed and are the most common cause of spontaneous orbital hemorrhage.[13][14] These lesions account for fewer than 2% of all orbital masses and are most often diagnosed before the third decade of life.[14] Secondary orbital varices may form in the setting of intracranial arteriovenous malformations and carotid-cavernous fistulas. Imaging, in conjunction with the clinical examination, is often sufficient to diagnose orbital varices; histologically, the lesions consist of dilated venous channels lined by endothelial cells. Chronic inflammatory changes and fibrosis may also be present on histology.

Masson tumor: Another rare vascular mass with a propensity to bleed during resection is a Masson tumor, also known as intravascular papillary endothelial hyperplasia. Masson tumors have rarely been reported in the orbit and typically require histopathologic confirmation. Histologically, Masson tumors are characterized by papillary proliferation of vascular endothelial cells, both on the surface of the mass and within the lumens of blood vessels.[15][16] 

Additionally, capillary hemangiomas are rarely diagnosed in adulthood. Capillary hemangiomas are typically lobular masses that enhance on imaging and contain well-developed capillary channels on histology.

Table 3. Key Features of Vasculogenic Orbital Tumors

Neural Tumors

Neural orbital tumor characteristics are summarized in Table 4. 

Orbital schwannomas: Orbital schwannomas, also known as neurilemomas, are peripheral nerve sheath tumors and account for only 1% of all orbital tumors.[3] Patients with neurofibromatosis are more likely to have head and neck schwannomas with orbital involvement; however, the risk of orbital schwannomas in patients with neurofibromatosis is only slightly higher than that in the general population. Schwannomas present in 1 of 4 histologic subtypes, each of which stains positively for S-100, SOX10, p16, and neurofibromin. The four histologic variants include cellular, melanotic, plexiform, and neuroblastoma.[17] 

Neurofibroma: Another peripheral nerve sheath tumor more commonly associated with neurofibromatosis is the neurofibroma. The plexiform neurofibroma, a mass composed of large, tortuous nerve fascicles, is the most common subtype diagnosed in the orbit, accounting for 2% of orbital tumors.[18] In contrast to schwannomas, neurofibromas are histologically composed of transformed Schwann cells within a fibrous, nonneoplastic stroma.

Granular cell tumors: Modified Schwann cells have also been reported as the origin of granular cell tumors (GCTs).[19] These tumors are immunoreactive for S100 and myelin basic protein.[20] GCTs are rare tumors, and approximately 3% arise in orbit.[21][22] Within the orbit, GCTs most often arise inferiorly and may involve the extraocular muscles. Although often well-circumscribed and considered benign, infiltrative GCTs have been reported. Therefore, excision is often recommended.

Meningiomas: Meningiomas are common primary intracranial tumors that rarely arise from within the orbit. Orbital meningiomas account for approximately 4% of all orbital masses.[3] Optic nerve sheath meningiomas arise in the orbit, often present during middle age, and are 3 times more common in women.[23] Optic nerve sheath meningiomas are among the few orbital tumors that can cause optociliary shunt vessels, which are collaterals formed in the setting of chronic central retinal vein occlusion. Sphenoid wing meningiomas are the most common intracranial tumors that can directly extend into the orbit.[24] Histologically, meningiomas arise from the leptomeninges, specifically from arachnoid cap cells. Histologic features classically associated with meningiomas include psammoma bodies, whorl formations, and nuclear pseudoinclusions.[25]

Optic nerve glioma: Another orbital tumor commonly seen in patients with neurofibromatosis is the optic nerve glioma, which is histologically consistent with a pilocytic astrocytoma and is most often low grade, with variable cytology and cellularity. Optic nerve glioma is important to consider in the differential diagnosis when a young patient presents with acute-onset vision loss. Although generally considered benign, optic nerve gliomas can have malignant potential and may behave more aggressively, and distinguishing between reactive and neoplastic resection margins is often difficult.[26] Optociliary shunt vessel formation may be seen in patients with optic nerve gliomas, though less commonly than in patients with optic nerve sheath meningiomas. 

Paragangliomas: Paragangliomas of the orbit are extremely rare neoplasms of neuroendocrine tissue. Similar to other slow-growing orbital masses, patients in reported cases have presented with gradually worsening proptosis.[27] Paragangliomas characteristically have a salt-and-pepper appearance on MRI due to their high vascularity and flow voids.[28]

Table 4. Key Features of Neural Orbital Tumors

Abbreviations: EOM, extraocular muscle; MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1; NF2, neurofibromatosis type 2; P0, myelin protein zero; S-100, S-100 protein.

Fibrocystic Tumors

An assortment of benign and malignant mesenchymal tumors can arise within the orbit (Table 5). 

Solitary fibrous tumors: Solitary fibrous tumors encompass a spectrum of lesions with similar histopathologic morphology. Solitary fibrous tumors include fibrous histiocytoma, hemangiopericytoma, and giant cell angiofibroma.[29] Histologically, this group of tumors contains cellular and stromal components arranged in what has been called a "patternless pattern" with staghorn vessels.[30] Importantly, solitary fibrous tumors may be malignant neoplasms or invasive and locally destructive lesions. Histologic evaluation is often crucial for distinguishing benign from malignant lesions. For example, more indolent, fat-forming solitary fibrous tumors contain mature adipose tissue and few to no mitotic cells. Dedifferentiated solitary fibrous tumor signifies a more aggressive lesion.[30]

Fibrous histiocytoma: In adults, fibrous histiocytoma is considered the most common mesenchymal tumor of the orbit.[31] Fibrous histiocytoma is most often benign, though it has malignant potential, and is commonly diagnosed in middle-aged adults. Malignant fibrous histiocytomas should be considered in the differential diagnosis, especially in patients with a history of orbital radiation. Malignant fibrous histiocytomas contain the histologic features mentioned above. Immunohistochemical staining is essential to rule out other neoplasms, including schwannoma and melanoma.

Giant cell angiofibromas: Giant cell angiofibromas are benign, highly vascularized soft tissue tumors found in the head and neck region and rarely arise within the orbit. While they may have an indolent course, some grow more rapidly and can resemble malignant neoplasm.[32] Hemangiopericytomas account for about 1% of all orbital tumors and most often occur around middle age. Up to nearly half of hemangiopericytomas can metastasize, and their malignant potential is difficult to predict.[33]

Myofibroma: Another rare soft tissue mass that can arise in the orbit is the myofibroma. These tumors are more often seen in children, but cases have been reported in adults.[34] On imaging, these tumors are well-circumscribed and enhance with contrast. Histopathologic characteristics of myofibroma include spindle cells arranged in short fascicles with scant cytoplasm and thin-walled, branching vessels.

Table 5. Key Features of Fibrocystic Orbital Tumors

Abbreviations: CD34, cluster of differentiation 34; EOM, extraocular muscle; SFT, solitary fibrous tumor.

Osseous and Fibro-osseous Tumors

Osseous and fibro-osseous tumors of the orbit constitute about 2% of all orbital masses (Table 6).[3] 

Fibrous dysplasia: Fibrous dysplasia is a disorder of bone that can affect the craniofacial skeleton. Fibrous dysplasia represents up to 7% of all primary orbital bone tumors.[35] Patients often present with progressive pain and disfigurement at the affected site. The bony growth can lead to mass effect within the orbit, increasing the risk of optic nerve compression and injury.[36] Optic nerve decompression may be indicated to preserve vision in affected patients. Symptomatic fibrous dysplasia is often treated with surgical intervention. Histologically, the affected bone is dysplastic, revealing dense fibrous stroma with low to moderate cellularity.

Osteomas: Osteomas are common paranasal sinus tumors that can involve the orbit. Primary orbital osteomas are very rare, accounting for less than 1% of orbital tumors. Depending on the location of the mass, surgical intervention may include sculpting or repair of the bone to restore the natural orbital contour.[37]

Ossifying fibromas: Ossifying fibromas are benign bone lesions with 3 different variants: cemento-ossifying fibroma, juvenile trabecular ossifying fibroma, and juvenile psammomatoid ossifying fibroma. Cemento-ossifying fibromas and juvenile trabecular ossifying fibroma are almost exclusively present in the jaw. Juvenile psammomatoid ossifying fibromas often present by the third decade and can involve the orbit.[38] Psammomatoid bodies are small ossicles that resemble psammoma bodies. Histologically, they are seen embedded in the stroma with spindle and stellate cells.  

Chondromas: Chondromas are benign cartilaginous tumors that very rarely occur in the head and neck region and constitute less than 1% of all orbital tumors. Orbital chondromas may arise from the trochlea, which is the only purely cartilaginous structure present in the orbit.[39] Their potential for malignant transformation is not well-defined.

Giant cell (reparative) granulomas are defined as benign fibro-osseous proliferations and are most commonly reported in the jaw. Rarely, these lesions can arise in the orbit.[40] Although benign, these lesions can potentially be locally aggressive and destructive.[41] Giant cell granulomas are more often diagnosed in women within the first 2 decades of life.[42] Treatment of these tumors has included sculpting the bone and removing the abnormal tissue without sharp excision.[41]

Table 6. Key Features of Osseous and Fibro-Osseous Orbital Tumors

Abbreviations: JPOF, juvenile psammomatoid ossifying fibromas

Lipomatous Tumors

Dermolipomas: Dermolipomas account for approximately 3% of orbital tumors and may be mistaken for orbital fat prolapse, as both occur in the lateral canthal area. Dermolipomas are often unilateral and occur in younger patients.[43] Dermolipomas should be distinguished from orbital lipomas, which account for less than 1% of all orbital tumors, because the treatment approaches differ.

Lipomas: Lipomas are often excised in full; however, surgical excision of dermolipomas is typically conservative and confined to readily visible portions of the mass.[44] Table 7 summarizes the lipomatous orbital tumors.

Table 7. Key Features of Lipomatous Orbital Tumors

Lymphoid Tumors

Plasmacytomas: Plasmacytomas are plasma cell tumors that can arise from soft tissue or bone. More commonly, secondary metastatic plasmacytomas arise secondary to multiple myeloma. Importantly, primary plasmacytomas cannot be differentiated from metastatic lesions on histopathology.[45] Plasmacytomas have heterogeneous plasma cell morphology with multinucleated cells and scant stroma. Patients diagnosed with plasmacytoma should undergo further workup for systemic disease.

Benign reactive lymphoid hyperplasia: Lymphocyte proliferation in the orbit can present as one of several entities. The first is benign reactive lymphoid hyperplasia, which has been categorized as an inflammatory or granulomatous process rather than a neoplasm.[46] Benign reactive lymphoid hyperplasia most often presents as a salmon-colored lesion on the nasal conjunctiva.[47] Histologically, this tumor can be distinguished from orbital inflammatory syndrome and is typically characterized by slow proliferation of lymphocytes without other markers of malignant neoplasm (eg, BCL-2).[48] When evaluating benign reactive lymphoid hyperplasia, clinicians must also consider more aggressive processes, such as atypical lymphoid hyperplasia, lymphoma, and other malignant neoplasms, in the differential diagnosis. Treatment involves corticosteroids, external beam radiation therapy, and rituximab.[48] Table 8 summarizes the features of lymphoid orbital tumors.

Table 8. Key Features of Lymphoid Orbital Tumors

Epidemiology

The incidence of primary orbital tumors is low, affecting approximately 1 in 100,000 people.[49] Most primary orbital tumors are benign, with an increased risk of a malignant neoplasm in patients older than 60 years.[50] In adults, most primary benign orbital tumors are diagnosed equally in men and women, although some subtypes, including cavernous hemangiomas and meningiomas of the optic nerve sheath and sphenoid wing, are more common in women. Please see StatPearls' companion references, "Optic Nerve Sheath Meningioma," "Orbital Vascular Anomalies," and "Meningioma," for further information. Geographic location as well as race and ethnicity have not yet been established as risk factors for primary orbital tumors in adults.

Results from a large retrospective series of 2480 orbital lesions referred to a specialized center for tissue diagnosis identified benign masses in 68% of cases.[50] Of these, the most common tumors were dermoid cysts (14%), followed by cavernous hemangiomas (9%). Most tumors were located in the upper outer orbital quadrant, and the authors noted that tumors in the lower inner quadrant have a higher likelihood of being malignant neoplasms. The series also identified anatomic patterns among lesion subtypes. In the upper outer quadrant, dermoid cysts were the most common tumors identified. Most masses in the upper inner quadrant were mucoceles. Cavernous hemangiomas were the most common masses found in the lower outer quadrant, and basal cell epitheliomas were the most common masses in the lower inner quadrant. The most common central orbital masses were meningiomas.

Pathophysiology

The orbital masses discussed in this article are benign neoplasms that arise from a variety of tissues within the orbit. These tumors are typically classified according to their cell or tissue of origin and demonstrate distinct clinical, imaging, and histopathologic characteristics. The differential diagnosis of an orbital mass also includes inflammatory, infectious, vascular, and malignant processes that may mimic benign tumors.

Histopathology

The histopathology of benign orbital tumors varies widely, depending on the tissue of origin. Histopathologic features of the orbital tumors discussed in this article are presented in Tables 2-8.

History and Physical

Space-occupying orbital lesions produce a variety of ocular signs and symptoms (Table 9). The most common presenting signs associated with orbital masses include proptosis, restrictive or paralytic extraocular muscle limitation, chemosis, exposure keratopathy, and optic neuropathy. Additionally, patients typically present with eye and periocular pain, vision loss, diplopia, a change in the appearance of the eye or eyelids, a pulsatile sensation, irritation, and, rarely, a visible mass. Slow-growing lesions are typically painless; however, acute changes, such as lesion rupture or hemorrhage, can cause sudden onset of pain and other orbital symptoms.

Recommended clinical examination to evaluate patients with a suspected orbital tumor includes the following:

• Visual acuity and refraction with attention to asymmetry or a hyperopic shift
• Pupillary assessment in multiple directions of gaze to assess for a relative afferent pupillary defect and dynamic optic nerve compression
• Color vision testing to assess for subtle optic neuropathy
• Intraocular pressure measurement to screen for secondary ocular hypertension due to mass effect or impaired venous drainage
• Extraocular motility testing to evaluate for restrictive or paralytic muscle limitations 
• Hertel exophthalmometry to quantify proptosis and establish a baseline for future comparison 
• Dilated fundus examination to assess for optic nerve asymmetry, pallor, and choroidal folds
• Optical coherence tomography retinal nerve fiber layer and Humphrey Visual Field 30-2 testing to further assess and quantify the degree of optic neuropathy

Table 9. Common Presenting Signs and Symptoms of Orbital Tumors and Their Potential Mechanisms

Evaluation

Many benign orbital tumors share similar clinical presentations, making imaging a critical component of the diagnostic evaluation. Although the patient history and physical examination may suggest certain diagnoses, imaging studies are often required to characterize the lesion and narrow the differential diagnosis. Computed tomography and MRI are the primary imaging modalities used to evaluate orbital masses. CT is often obtained initially because it provides excellent visualization of orbital anatomy and adjacent bony structures. Contrast-enhanced studies, including arterial-phase imaging when appropriate, can further characterize vascularity and other lesion-specific features. MRI, with or without contrast, offers superior soft tissue resolution and is frequently used when more detailed anatomical characterization is needed or when intracranial extension is suspected. Ultrasonography is used less frequently but can provide rapid, noninvasive assessment of lesions located in the anterior orbit. Ultrasonography is also useful for serial monitoring of selected slow-growing tumors, such as cavernous venous malformations (cavernous hemangiomas), when observation is the preferred management strategy.[51]

Treatment / Management

General Considerations

The presence or absence of symptoms often dictates treatment decisions for benign orbital masses. In many cases, small, asymptomatic tumors can be closely monitored with annual examinations. Exceptions include tumors with a high potential for malignant transformation.

Medical Management

Medical therapy has a limited role in the treatment of most primary orbital tumors. However, case reports and small case series have described clinical improvement in patients with severe orbital lymphatic malformations (lymphangiomas) treated with sildenafil, a phosphodiesterase type 5 inhibitor, or sirolimus, an mTOR inhibitor.[52][53][54](B3)

Surgical Management

Surgical excision is indicated for orbital masses that produce symptoms, particularly vision loss or other visual disturbances, proptosis, or restriction of extraocular movements. Complete excision may be challenging for some tumors, and recurrence can occur, particularly with lymphatic malformations (lymphangiomas) and incompletely resected cavernous venous malformations (cavernous hemangiomas). Solitary fibrous tumors (formerly classified as hemangiopericytomas) are typically managed with complete surgical resection because of their potential for local recurrence and malignant transformation. Certain orbital lesions, including orbital varices and optic nerve sheath meningiomas, may be difficult to resect because of their vascularity or proximity to critical neurovascular structures. Advances in interventional radiology, including preoperative embolization of select vascular lesions, have improved the safety of surgical resection by reducing the risk of intraoperative hemorrhage.[55](B3)

Radiation Therapy

Radiation therapy has a limited role in the management of benign orbital masses and is rarely used as a primary treatment modality. However, studies have demonstrated its utility in select cases of unresectable, recurrent, or surgically challenging tumors, including schwannomas and sphenoid wing meningiomas. In these situations, radiation therapy may provide local tumor control while avoiding the risks associated with surgical intervention.

Special Considerations 

Lesions involving the orbital apex can cause compressive optic neuropathy, leading to progressive and potentially irreversible vision loss. Management of these lesions is often challenging because complete surgical resection may be limited by the complex anatomy of the orbital apex and its proximity to critical neurovascular structures. In selected patients, orbital decompression may be an effective alternative, relieving pressure on the optic nerve and preserving vision without the need for complete tumor removal and the associated morbidity of orbital apex surgery.[56](B2)

Differential Diagnosis

Several nonneoplastic conditions can mimic the clinical presentation of an orbital tumor and should be considered in the differential diagnosis. These conditions can be broadly categorized as infectious, inflammatory, and other orbital disorders:

Infectious Diseases

• Orbital cellulitis
• Orbital tuberculosis
• Histoplasmosis
• Coccidioidomycosis
• Mucormycosis (zygomycosis)

Inflammatory Diseases 

• Thyroid eye disease (thyroid orbitopathy)
• Idiopathic orbital inflammation 
• IgG4-related disease
• Amyloidosis
• Giant cell myositis
• Optic neuritis
• Sarcoidosis
• Antineutrophil cytoplasmic antibody–associated vasculitis

Other Diseases to Consider

• Orbital fat prolapse
• Lacrimal gland prolapse
• Orbital metastasis

Prognosis

The prognosis for benign orbital tumors is generally favorable; however, outcomes can vary depending on the tissue of origin and the tumor location. Long-term morbidity from these lesions stems primarily from the space-occupying effect on surrounding structures, such as the optic nerve. Benign orbital tumors may be small, may be discovered incidentally, or may have an indolent course. However, certain lesions may grow large enough to cause proptosis, direct compression of the globe, optic neuropathy, or diplopia from extraocular muscle restriction. Additionally, the tumor's location and proximity to vital structures can affect the visual prognosis. For example, surgical resection of optic nerve sheath meningiomas is often avoided due to the risk of postoperative blindness.[57]

Complications

Morbidity and complications from benign orbital tumors primarily stem from their space-occupying effect. Certain vascular tumors, such as orbital varices, may cause spontaneous orbital hemorrhage. Biopsy or surgical excision of orbital masses may result in orbital hemorrhage or injury to vital structures. Surgical complications vary depending on the type, size, and location of the tumor. Additionally, incomplete excision of certain orbital tumors, such as cavernous hemangiomas, may result in recurrence.