Benign Orbital Tumors

Etiology

Classification

Primary orbital tumors can be classified according to the tissue of origin (Table 1).

Table 1. Benign orbital tumors and their tissues of origin.

Cystic Tumors 

• Epidermoid cyst

• Dermoid cyst

• Mucocele

• Hematic pseudocyst

• Meningoencephalocele

• Apocrine hidrocystoma

• Colobomatous cyst

Epidermoid cysts rarely form in the orbit but must be considered in the differential for deep orbital cystic lesions. They may present as primary congenital lesions or form following the traumatic displacement of surface epithelium.[1] 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.[2] 

Mucoceles are cystic cavities that contain sterile mucus. They typically form secondary to outflow obstruction of the frontal and ethmoidal sinuses. These masses rarely form and are slow-growing. However, when large enough, they can invade the orbit and cause symptoms similar to those seen in other orbital masses. Mucoceles have been more often reported in patients with a history of trauma or sinus surgery.[3] Histologically, these cysts are lined by simple epithelium and may include acute or chronic inflammatory material.

Hematic pseudocysts are also rarely-reported orbital lesions. The most common presentation of a hematic cyst is acute-onset proptosis following remote trauma to the orbit.[4] Chronic orbital hematic cysts have also been reported and are histologically similar to chronic subdural hematomas.[5][6] These lesions are cystic and contain blood and/or blood breakdown products. Depending on the chronicity of the mass, products of inflammatory or granulomatous reactions may also be present.

Defects in the orbital roof allow for the herniation of intracranial tissue into the orbit, forming meningoencephaloceles. Although rare, these intraorbital masses are important to consider in patients presenting with signs of a superior or superonasal orbital mass. Meningoencephaloceles are on the differential for pulsatile proptosis, along with carotid-cavernous fistulas and vascular tumors.[7] Radiographic studies are crucial in diagnosing these masses since inappropriate biopsy or resection can lead to devastating outcomes.

Apocrine hidrocystomas are common lid lesions but rarely reported inside the orbit.[8] They are cystic lesions characterized histologically by a capsule composed of bilaminar, columnar epithelium with outpouchings of the lumen ("apocrine snouts"). These lesions are prone to recurrence if the capsule is not completely excised.[9]

Colobomatous cysts of the orbit are rare, congenital anomalies that occur secondary to embryogenesis abnormalities. Since these cysts appear at birth and are diagnosed in infancy or childhood, they will not be discussed in detail here.  

Table 2. Key features of cystic orbital tumors.

Vasculogenic Tumors

• Cavernous hemangioma
• Lymphangioma
• Orbital varix
• Intravascular papillary endothelial hyperplasia
• Capillary hemangioma

Tumors of vasculogenic origin constitute approximately 17% of all orbital masses.[2] The Orbital Society has classified certain vascular lesions based on the type of vascular flow.[2][10] The use of imaging with contrast is especially helpful in the diagnosis of these lesions, as they are often characterized by vascular flow with specific filling patterns.

The cavernous hemangioma, also known as a cavernoma, is the most common benign primary orbital tumor in adults.[2] These lesions have slow vascular flow and low pressure, which makes their risk of hemorrhage lower than other vascular lesions. They often present in middle age with slowly progressive proptosis and vision changes. Presentation during pregnancy is common due to hormonal-associated growth and increased risk of hemorrhage.[11] Histologically, these are encapsulated lesions characterized by dilated vascular spaces separated by connective tissue. 

Lymphangiomas, also known as lymphatic malformations, involve both vascular and lymphatic systems. They have no vascular flow and are most prevalent in the 1st-2nd decade of life.[2][10] Loose connective tissue stroma surrounds the lymphatic channels on histology. 

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.[12][13] They account for less than 2% of all orbital masses and are most often diagnosed before the 3rd decade of life.[13] 

Secondary orbital varices may form in the setting of intracranial arteriovenous malformation and carotid-cavernous fistulas. Imaging in conjunction with the clinical exam is often sufficient to diagnose orbital varices, and these lesions are classified histologically as dilated venous channels lined by endothelial cells. Chronic inflammatory changes and fibrosis may also be present on histology.  

Another rare vascular mass with a propensity to bleed during resection is a Masson tumor, also known as intravascular papillary endothelial hyperplasia. These tumors have been rarely reported in the orbit and typically require histopathologic confirmation. Histologically, the lesion is characterized by papillary proliferation of vascular endothelial cells, both on the surface of the mass and within lumens of blood vessels.[14][15]

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

Table 3. Key features of vasculogenic orbital tumors.

Neural Tumors

• Schwannoma

• Neurofibroma

• Meningiomas

• Optic nerve glioma

• Paraganglioma

Orbital Schwannomas, also known as neurilemomas, are peripheral nerve sheath tumors and account for only 1% of all orbital tumors.[2] While patients with Neurofibromatosis (NF) are more likely to have head and neck schwannomas with orbital involvement, the risk of orbital schwannomas in these patients is only slightly higher than in the general population. Schwannomas present in one of four histologic subtypes, all stain positively for S-100, SOX10, p16, and neurofibromin. The four histologic variants include cellular, melanotic, plexiform, and neuroblastoma.[16]

Another peripheral nerve sheath tumor that is more classically associated with NF is the neurofibroma. The plexiform neurofibroma, a mass of large tortuous nerve fascicles, is the most common subtype diagnosed within the orbit, accounting for 2% of orbital tumors.[17] In contrast with schwannomas, neurofibromas are histologically composed of transformed Schwann cells within the fibrous, non-neoplastic stroma.

Modified Schwann cells have also been reported as the origin of granular cell tumors (GCTs).[18] These tumors are immunoreactive for S100 and myelin basic protein.[19] GCTs are rare tumors, of which about 3% rise in orbit.[20][21] Within the orbit, they most often arise inferiorly and may involve the extraocular muscles. Although often well-circumscribed and considered benign, there have been reports of infiltrative GCTs. Thus, excision is often recommended.

Meningiomas are common primary intracranial tumors that rarely arise from within the orbit. Orbital meningiomas account for approximately 4% of all orbital masses.[2] Optic nerve sheath meningiomas (ONSM) arise in orbit, often present during middle age, and are three times more common in females.[22] They are one of 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 to the orbit.[23] Histologically, meningiomas arise from the leptomeninges, specifically from arachnoid cap cells. Certain features classically associated with meningiomas include psammoma bodies, whorl formations, and nuclear pseudoinclusions.[24]

Another orbital tumor commonly seen in NF is the optic nerve glioma (ONG), which is histologically consistent with a pilocytic astrocytoma, most often low-grade with variable cytology and cellularity. ONG is important to consider as the differential when a young patient presents with acute-onset vision loss. Although generally considered benign, it is often difficult to distinguish between reactive and neoplastic resection margins, as these tumors are more aggressive with malignant potential.[25] Optociliary shunt vessel formation may be seen in patients with ONG, though less commonly than in patients with ONSM. 

Paragangliomas of the orbit are extremely rare neoplasms of neuroendocrine tissue. Similar to other slow-growing orbital masses, the reported cases presented with gradually worsening proptosis.[26] These tumors are characteristically present with a "salt and pepper" appearance on MRI due to their high vascularity and flow voids.[27]

Table 4. Key features of neural orbital tumors.

Fibrocystic Tumors

• Fibrous histiocytoma

• Giant cell angiofibroma

• Hemangiopericytoma

• Myofibroma

An assortment of benign and malignant mesenchymal tumors can arise within the orbit. Solitary fibrous tumors (SFT) encompass a spectrum of lesions with similar histopathologic morphology. These include fibrous histiocytoma, hemangiopericytoma, and giant cell angiofibroma.[28] Histologically, this group of tumors contains cellular and stromal components arranged in what has been called a "patternless pattern" with "staghorn" vessels.[29] Importantly, SFTs may b, e malignant, invasive, and locally destructive lesions. Often the histologic evaluation is crucial in distinguishing between a benign and malignant lesion. For example, more indolent, fat-forming STFs contain mature adipose tissue and few to no mitotic cells. Dedifferentiated SFT signifies a more aggressive lesion.[29]

In adults, fibrous histiocytoma is considered the most common mesenchymal tumor of the orbit.[30] It 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, especially in patients who have previously undergone radiation to the orbit. They contain the histologic features mentioned above. Immunohistochemical staining is essential to rule out other neoplasms, including schwannoma and melanoma. 

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 malignancy.[31]

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.[32]

Another rare soft tissue mass that can arise in the orbit is the myofibroma. These are more often seen in children, but cases have been reported in adults.[33] 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.

Osseous and Fibro-osseous Tumors

• Fibrous dysplasia

• Osteoma

• Ossifying fibroma

• Chondroma

• Giant cell granuloma 

Osseous and fibro-osseous tumors of the orbit constitute about 2% of all orbital masses.[2]

Fibrous dysplasia is a disorder of bone that can affect the craniofacial skeleton. It represents up to 7% of all primary orbital bone tumors.[34] 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.[35] Optic nerve decompression may be indicated to preserve vision in these cases. 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 are common paranasal sinus tumors that can involve the orbit. Primary orbital osteomas are very rare, making up 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.[36]

Ossifying fibromas (OF) are benign bone lesions with three different variants: cemento-OF (COF), juvenile trabecular OF (JTF,) and juvenile psammomatoid OF (JPOF). Of these, COF and JTOF are almost exclusively present in the jaw. JPOF often presents by the 3rd decade and can involve the orbit.[37] Psammomatoid bodies are small ossicles that resemble psammoma bodies. Histologically, they are seen embedded in the stroma with spindle and stellate cells.  

Chondromas are benign cartilaginous tumors that very rarely occur in the head and neck region and constitute less than 1% of all orbital tumors. Chondromas may arise within the orbit from the trochlea, which is the only purely cartilaginous structure present.[38] Their potential for malignancy is not well-defined.

Giant cell (reparative) granulomas (GCRG) have been defined as benign fibro-osseous proliferation and are most often reported in the jaw. Rarely these lesions can rarely arise in the orbit.[39] Although benign, these lesions can potentially be locally aggressive and destructive.[40] Giant cell granulomas are more often diagnosed in women within the first two decades of life.[41] Recent studies have treated GCRG by sculpting the bone and removing the abnormal tissue without sharp excision.[40]

Table 6. Key features of osseous and fibro-osseous orbital tumors.

Lipomatous Tumors

• Dermolipoma

• Lipoma 

Dermolipomas constitute approximately 3% of all 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.[42] They should be distinguished from orbital lipomas, which account for less than 1% of all orbital tumors due to the difference in management. While lipomas are often excised in full, surgical excision of dermolipomas is often conservative and confined to portions of the mass that are readily visible.[43]

Table 7. Key features of lipomatous orbital tumors.

Lymphoid Tumors

• Plasmacytoma

• Benign reactive lymphoid hyperplasia

Plasmacytomas are plasma cell tumors that can arise from soft tissue or bone. More commonly, secondary metastatic plasmacytomas arise as a consequence of multiple myeloma. Importantly, primary plasmacytomas cannot be differentiated from metastatic lesions on histopathology.[44] The plasma cell morphology is heterogeneous with the presence of multinucleated cells and scant stroma. Patients diagnosed with plasmacytoma should undergo further work-up for systemic disease.

Lymphocyte proliferation in the orbit can present in one of a few entities. The first is benign reactive lymphoid hyperplasia (BRLH), which has been categorized under inflammatory or granulomatous as opposed to neoplastic.[45] It most often presents as a salmon-colored lesion on the nasal conjunctiva.[46] Histologically, BRLH has been distinguished from orbital inflammatory syndrome and is typically characterized by slow proliferation of lymphocytes without other markers of malignancy (e.g., Bcl-2 marker).[47] 

When considering the diagnosis of BRLH, it is crucial to consider more aggressive processes such as atypical lymphoid hyperplasia, lymphoma, and other malignancies on the differential. Treatment of BRLH involves corticosteroids, external beam radiation therapy, and rituximab.[47]

Table 8. Key features of lymphoid orbital tumors.

Epidemiology

The incidence of primary orbital tumors is low, affecting approximately 1 in 100,000 people.[48] Most primary orbital tumors are benign, with an increased risk of malignancy in patients over 60 years of age.[49] In adults, most primary benign orbital tumors are diagnosed equally in male and female patients, although some subtypes, including cavernous hemangiomas and meningiomas of the optic nerve sheath and sphenoid wing, are more common in females.[50][51][52] Geography and race have not yet been established as risk factors for primary orbital tumors in adults.

A large retrospective series of 2,480 orbital lesions referred to a specialized center for tissue diagnosis identified benign masses in 68% of cases.[49] 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 malignant disease. Additional patterns were identified, with different lesions presenting most commonly in different anatomic locations. 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 made up the highest number in the lower inner quadrant. The most common central orbital masses were meningiomas.

Pathophysiology

The orbital masses discussed in this article are tumors. These tumors are categorized by the origin of cell type. The differential for these orbital masses includes those that arise due to inflammation, infections, or other pathologic processes.

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 can be found in Tables 2-8.

History and Physical

Space-occupying orbital lesions produce a variety of ocular signs and symptoms (Table 9). Presenting signs due to orbital masses most commonly include proptosis, extraocular muscle limitation, either restrictive or paralytic, chemosis, exposure keratopathy, and optic neuropathy. Additionally, patients typically present with eye and periocular pain, loss of vision, 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, including lesion rupture or hemorrhage, can result in 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 the presence of a relative afferent pupillary defect and dynamic optic nerve compression
• Color vision testing to assess for subtle optic neuropathy
• Intraocular pressure to screen for secondary ocular hypertension due to mass effect or impaired venous drainage
• Extraocular motility to evaluate for restrictive or paralytic muscle limitations 
• Hertel exophthalmometry to quantify proptosis and establish a baseline for future comparison 
• Dilated fundus exam to assess for optic nerve asymmetry, pallor, and choroidal folds
• Optical coherence tomography retinal nerve fiber layer (OCT RNFL) and Humphrey visual field (HVF) 30-2 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 have similar clinical presentations. Although patient history and exam findings may help distinguish between certain types of orbital masses, imaging is often necessary for diagnosis. 

Computed tomography (CT) or magnetic resonance imaging (MRI) can provide important diagnostic information and guide surgical management. Initial imaging with CT is often recommended to assess orbital/bony anatomical landmarks. Using contrast and arterial phase imaging is especially helpful for characterizing masses and developing a differential diagnosis. When a more detailed anatomic definition is required, MRI, with and without contrast, is often obtained. Ultrasound imaging is less commonly used but can provide fast diagnostic information for masses located in the anterior orbit.

Treatment / Management

General Considerations

The presence or absence of symptoms often dictates management decisions for benign orbital masses. In many cases, small and asymptomatic tumors can be observed closely with annual exams. Exceptions to this include tumors with a high potential for malignancy.

Medical Management

Most primary orbital tumors cannot be treated with medical management. There have been reported cases of severe lymphatic malformations and lymphangiomas that have responded to Sildenafil (PDE-5 inhibitor) and Sirolimus (mTOR inhibitor).[53][54][55](B3)

Surgical Management

Surgical excision is warranted in orbital masses that cause symptoms, particularly vision changes, proptosis, and extraocular movement restriction. The risk of recurrence may be high with some primary orbital tumors, including lymphangiomas and incompletely-excised cavernous hemangiomas. Hemangiopericytomas should be surgically resected due to their relatively high potential for malignancy.

Certain orbital tumors, such as orbital varices and optic nerve sheath meningiomas, are difficult to resect due to the risk of hemorrhage or proximity to vital structures. More recently, embolization of vascular tumors by interventional radiology has allowed resection of these masses with a lower risk of hemorrhage.[56](B3)

Radiation Therapy

Radiation therapy is rarely used in isolation to treat benign orbital masses. In recent studies, it has been implemented in the treatment of some unresectable or recurrent primary orbital tumors, such as schwannomas and sphenoid wing meningiomas. 

Special Considerations 

Lesions of the orbital apex can result in compressive optic neuropathy and progressive, permanent vision loss. Surgical resection is often difficult in such cases due to challenging anatomy and limited surgical approaches. Orbital decompression has been described as an option in cases and can preserve vision without the need for complete tumor resection and the associated morbidity of orbital apex resection.[57](B2)

Differential Diagnosis

There are a number of other etiologies that may mimic orbital tumors in clinical presentation. The two major categories are infectious and inflammatory diseases. 

Infectious Diseases

• Orbital cellulitis
• Orbital tuberculosis
• Orbital sarcoidosis
• Histoplasmosis
• Coccidioidomycosis
• Mucormycosis/zygomycosis

Inflammatory Diseases 

• Thyroid orbitopathy/thyroid eye disease
• Idiopathic orbital inflammation (IOI)
• IgG4-related disease
• Amyloidosis
• Giant cell myositis
• Optic neuritis

Other Diseases to Consider

• Orbital fat prolapse
• Lacrimal gland prolapse
• Orbital metastasis

Prognosis

The prognosis for benign orbital tumors is often good but 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, discovered incidentally, and/or 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 location of the tumor and its proximity to vital structures can impact visual prognosis. Regarding optic nerve sheath meningiomas, for example, surgical resection is often avoided due to the risk of postoperative blindness.[58]

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. Surgical biopsy or surgical excision of orbital masses may result in orbital hemorrhage or damage to vital structures.

Surgical complications vary depending on the type, size, and location of the tumor. Incomplete excision of certain orbital tumors, such as cavernous hemangiomas, may result in recurrence.