Prominent eye, double vision, and decreased vision, may be asymptomatic.

• Primarily intraconal/optic nerve:
  1. Cavernous venous malformation (cavernous hemangioma): Most common benign orbital mass in adults. Middle-aged women most commonly affected, with a slow onset of orbital signs. Growth may accelerate during pregnancy (see Figure 7.4.2.1).
  2. Mesenchymal tumors: Orbital lesions with varying degrees of aggressive behavior. The largest group is now labeled solitary fibrous tumor (SFT) and includes fibrous histiocytoma and hemangiopericytoma. These lesions cannot be distinguished clinically or radiographically. May occur at any age. Immunohistochemical staining for STAT6 is usually diagnostic.
  3. Neurilemmoma (schwannoma): Progressive, painless proptosis. Rarely associated with neurofibromatosis type II. Malignant schwannoma has been reported but is rare.
  4. Neurofibroma: See 7.4.1, ORBITAL TUMORS IN CHILDREN.
  5. Meningioma: Optic nerve sheath meningioma (ONSM) typically occurs in middle-aged women with painless, slowly progressive visual loss, often with mild proptosis. An afferent pupillary defect may be present. Ophthalmoscopy can reveal optic nerve swelling, optic atrophy, or abnormal collateral vessels around the optic nerve head (optociliary shunts).
  6. Other optic nerve lesions: Optic nerve glioma, optic nerve sarcoid, malignant optic nerve glioma of adulthood (MOGA). The second most common lesion of the optic nerve (excluding optic neuritis) after ONSM is optic nerve sarcoid, which may be difficult to distinguish from ONSM clinically and radiologically. The ACE level may be normal in cases of isolated optic nerve sarcoid. MOGA is a rapidly progressive optic nerve lesion of the elderly akin to glioblastoma multiforme; it carries a poor prognosis and is often misdiagnosed as a “progressive NAION.”
  7. Lymphangioma: Usually discovered in childhood. See 7.4.1, ORBITAL TUMORS IN CHILDREN.

  7-4.2.1 MRI of cavernous venous malformation.

  

  Note the heterogeneous contrast enhancement in two lower images.

• Primarily extraconal:
  1. Mucocele: Often presents with a frontal headache and a history of chronic sinusitis or sinus trauma. Usually located nasally or superonasally, emanating from the frontal and ethmoid sinuses. See Figure 7.4.2.2.
  2. Localized neurofibroma: Occurs in young- to middle-aged adults with the slow development of orbital signs. Eyelid infiltration results in an S-shaped upper eyelid. Some have neurofibromatosis type I, but most do not.
  3. SPA or spontaneous hematoma: See 7.3.2, SUBPERIOSTEAL ABSCESS.
  4. Dermoid cyst: See 7.4.1, ORBITAL TUMORS IN CHILDREN.
  5. Others: Tumors of the lacrimal gland (pleomorphic adenoma [well circumscribed], adenoid cystic carcinoma [ACC] [variably circumscribed with adjacent bone destruction]), sphenoid wing meningioma (commonly occurring in middle-aged females and a cause of compressive optic neuropathy), secondary tumors extending from the brain or paranasal sinuses, primary osseous tumors, and vascular lesions (e.g., varix and arteriovenous malformation including CCF).

  7-4.2.2 T-1-weighted MRI of a large frontoethmoidal mucocele.

  

  Note extension through left orbit and anterior cranial fossa with frontal lobe compression.

• Intraconal or extraconal:
  1. Lymphoproliferative disease (lymphoid hyperplasia and lymphoma): More commonly extraconal. About 50% are well circumscribed on imaging, and 50% are infiltrative. Ocular adnexal lymphoma is typically of the non-Hodgkin B-cell type (NHL), and about 75% to 85% follow an indolent course (extranodal marginal zone lymphoma [EMZL] or mucosa-associated lymphoid tissue lymphoma, grade I or II follicular cell lymphoma, and chronic lymphocytic leukemia [small cell lymphoma]). The remainder are aggressive lesions (diffuse large B-cell lymphoma and mantle cell lymphoma, among others). May occur at any adult age; orbital NHL is rare in children. Slow onset and progression unless there is an aggressive subtype. Pain may occur in up to 25% of orbital NHL. Typically develops superiorly in the anterior aspect of the orbit, with about 50% occurring in the lacrimal gland. May be accompanied by a subconjunctival salmon-colored lesion. Most orbital NHL (especially if indolent subtype) occurs without evidence of systemic lymphoma (Stage IE). Orbital NHL may be confused with IOIS, especially when it presents more acutely with pain. Note that NHL frequently responds dramatically to systemic corticosteroids, as does IOIS.
  2. Metastases: Usually occurs in middle-aged to elderly people with a variable onset of orbital signs. Common primary sources include the breast (most common in women), lung (most common in men), and genitourinary tract (especially prostate). Twenty percent of orbital breast cancer metastases are bilateral and frequently involve extraocular muscles. Enophthalmos (not proptosis) may be seen with scirrhous breast carcinoma. Metastatic prostate adenocarcinoma has a propensity for bone and often involves the zygoma or greater sphenoid wing. Note that uveal metastases are far more common than orbital lesions by a 10 to 1 ratio.
  3. Others: Mesenchymal tumors and other malignancies.

Workup

1. History: Determine the age of onset and rate of progression. Headache or chronic sinusitis? History of cancer? Trauma (e.g., mucocele, hematocele, orbital foreign body, or ruptured dermoid)? Classic lymphoma symptoms including fever, night sweats, or unintentional weight loss.
2. Complete ocular examination, particularly visual acuity, pupillary response, ocular motility, dyschromatopsia testing, an estimate of globe displacement and proptosis (Hertel exophthalmometer), IOP, optic nerve evaluation, and automated perimetry of each eye if concerned about an optic neuropathy. Examine conjunctival surface and cul-de-sacs carefully for salmon patches if lymphoma is suspected.
3. CT (axial, coronal, and parasagittal views) of the orbit and brain or orbital MRI with fat suppression/gadolinium, depending on suspected etiology and age. See 14.2, Computed Tomography and 14.3, MAGNETIC RESONANCE IMAGING.
4. Orbital US with color Doppler imaging as needed to define the vascularity of the lesion. Conventional B-scan has a limited role in the diagnosis of orbital pathology because of the availability and resolution of CT and MRI, but may provide some data on anterior orbital lesions.
5. When a metastasis is suspected and the primary tumor is unknown, the following should be performed:
   • Incisional biopsy to confirm the diagnosis, with estrogen receptor assay if breast adenocarcinoma is suspected.
   • Breast examination and palpation of axillary lymph nodes by the primary physician.
   • Medical workup (e.g., chest imaging, mammogram, prostate examination, PSA testing, and colonoscopy).
   • If the patient has a known history of metastatic cancer and is either a poor surgical candidate or has an orbital lesion that is difficult to access, empiric therapy for the orbital metastasis is a reasonable option.
6. If lymphoproliferative disease (lymphoma or lymphoid hyperplasia) is suspected, a biopsy for definitive diagnosis is indicated. Include adequate fixed tissue (for permanent sectioning and immunohistochemistry) and fresh tissue (for flow cytometry). If lymphoproliferative disease is confirmed, the systemic workup is almost identical for polyclonal (lymphoid hyperplasia) and monoclonal (lymphoma) lesions (e.g., CBC with differential, serum protein electrophoresis, lactate dehydrogenase, and whole-body imaging [CT/MRI or positron emission tomography/CT]). Based on recent data, bone marrow biopsy is indicated in all cases of orbital lymphoma, even indolent subtypes. Close surveillance with serial clinical examination and systemic imaging is indicated over several years in all patients with lymphoproliferative disease, regardless of clonality. A significant percentage of patients initially diagnosed with orbital lymphoid hyperplasia will eventually develop systemic lymphoma.

1. Metastatic disease: Systemic chemotherapy as required for the primary malignancy. Radiation therapy is often used for palliation of the orbital mass; high-dose radiation therapy may result in ocular and optic nerve damage. Hormonal therapy may be indicated in certain cases (e.g., breast and prostate adenocarcinoma).
2. Well-circumscribed lesions: Complete surgical excision is performed when there is compromised visual function, diplopia, rapid growth, or high suspicion of malignancy. Excision for cosmesis can be offered if the patient is willing to accept the surgical risks. An asymptomatic patient can be followed every 6 to 12 months with serial examinations and imaging. Progression of symptoms and rapidly increasing size on serial imaging are indications for exploration and biopsy/excision.
3. Mucocele: Systemic antibiotics (e.g., ampicillin/sulbactam 3 g i.v. q6h) followed by surgical drainage of the mucocele, usually by transnasal endoscopic technique. Orbitotomy for excision is usually unnecessary and contraindicated in most cases as disruption of the mucocele’s mucosal lining may lead to recurrent, loculated lesions.
4. Lymphoid tumors: Lymphoid hyperplasia and indolent lymphoma without systemic involvement are treated almost identically. With few exceptions, orbital lymphoproliferations respond dramatically to relatively low doses of radiation (∼24 Gy); ocular and optic nerve complications are therefore less common than with other malignancies. Systemic lymphoma or localized aggressive lymphoma are treated with chemotherapy and in many cases with biologics (e.g., rituximab). The vast majority of orbital lymphoma is of B-cell origin and 50% to 60% are EMZL. In older individuals with few symptoms and indolent lesions, more conservative measures may be indicated, including observation alone or brief courses of corticosteroids. To date, there is no clear role for the use of systemic antibiotics in the treatment of orbital lymphoproliferative disease except possibly in certain geographic locations. There is also no clear evidence that orbital EMZL is in any way related to Helicobacter pylori-associated gastric EMZL. Remember that the specific subtype of NHL (and therefore level of aggressiveness) and stage of the disease define the ultimate treatment.
5. ONSM: The diagnosis is usually based on slow progression and typical MRI findings. MRI with gadolinium is the preferred imaging modality. CT is occasionally helpful in demonstrating intralesional calcifications. Stereotactic radiation therapy is usually indicated when the tumor is growing and causing significant visual loss. Otherwise, the patient may be followed every 3 to 6 months with serial clinical examinations and imaging studies as needed. Recent studies have shown the significant efficacy of stereotactic radiotherapy in decreasing tumor growth and in visual preservation. Stereotactic radiotherapy is not equivalent to gamma knife therapy (“radiosurgery”). Empiric stereotactic radiotherapy (i.e., without confirmatory biopsy) is a reasonable treatment option, but is reserved for typical cases of ONSM. Atypical or rapidly progressive lesions still require biopsy.
6. Localized neurofibroma: Surgical removal is performed for symptomatic and enlarging tumors. Excision may be difficult and incomplete in infiltrating neurofibromas.
7. Neurilemmoma: Same as for cavernous venous malformation (see above).
8. Mesenchymal tumors (usually SFT): Complete excision when possible. The lesion may be fixed to the surrounding normal anatomy and abut critical structures. In such cases, debulking is reasonable, with long-term follow up and serial imaging to rule out aggressive recurrence or potential malignant transformation. SFT is notoriously difficult to prognosticate. Some lesions will behave in an indolent fashion, while others may present with aggressive recurrence, regional extraorbital extension, or systemic spread.

1. In cases of isolated lesions that can be completely excised (e.g., cavernous venous malformation), routine ophthalmologic follow up is all that is necessary.
2. Other etiologies require long-term follow up at variable intervals.
3. Metastatic disease requires timely workup and management.