Orbital tumors encompass a heterogenous range of lesions, from congenital cystic masses to both benign and malignant neoplasms, and can originate from a variety of tissue types. In a large 30-year study of orbital tumors, 64% of masses were benign and 36% were malignant. The most common orbital tumors by category are vascular, secondary or metastatic, and lymphoid. Rhabdomyosarcoma is the most common malignancy in children (3% of cases), and lymphoma is the most common malignancy in older patients (10% of cases). The percentage of malignant orbital tumors increases with age, with malignancies three times more common in older patients owing to the higher incidence of lymphoma and metastasis in this population.
This chapter reviews the most important and common intraorbital tumors and simulating lesions that are encountered in clinical practice. We review the associated demographics, clinical presentation, diagnosis, and management of each tumor.
Lymphoproliferative Tumors
The majority (> 90%) of orbital lymphoproliferative tumors are B-cell non-Hodgkin lymphoma, with increasing incidence in the United States. The most common subtype is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, a low-grade B-call malignancy that represents 40% to 50% of all orbital lymphomas. High-grade (large cell) lymphoma is far less likely to present in the orbit. Orbital lymphoma tends to occur in older patients and may be associated with systemic lymphoma, with a 10-year systemic incidence of 33% for patients with unilateral disease and 72% for those with bilateral disease.
Orbital lymphoma usually presents as a painless, slowly progressive mass in the anterior orbit that may feel rubbery to palpation. Conjunctival involvement may have a salmon-patch appearance. Orbital imaging demonstrates a moderately enhancing ovoid mass that tends to mold to adjacent structures without bone involvement ( Fig. 25.1 ). If orbital lymphoma is suspected, open biopsy is preferred to adequately sample the lesion, and a systemic evaluation by an oncologist is indicated to rule out remote lymphoma. When biopsy is performed biopsy, fresh tissue should be sent for flow cytometry analysis in addition to formalin-fixed tissue study. Histopathologic analysis reveals a characteristic polymorphous appearance of small round lymphocytes and plasma cells with mitotically active germinal centers. Hypercellular proliferation with sparse stroma may be similarly seen in benign lesions; molecular studies can be useful to further characterize the lesion as benign, intermediate, or malignant in these cases. Molecular analysis revealing a monoclonal proliferation is consistent with a malignant process.
Management depends on the extent and nature of the histopathologic subtype of lymphoma. In patients with localized ocular adnexal involvement with extranodal marginal zone lymphoma, low-dose radiotherapy (25 Gy) is the treatment of choice. Given the infiltrative nature of lymphoid tumors, a surgical cure is usually not achieved. More aggressive diffuse large B-cell lymphoma requires a combination of radiation and chemotherapy. Co-management with a medical oncologist is crucial.
Burkitt Lymphoma
Burkitt lymphoma is a rare orbital non-Hodgkin B-cell lymphoma that typically presents in the jaw or abdomen of African children. Orbital involvement usually occurs secondary to spread from the maxillary bone and may also extend into the globe. A particularly aggressive form of Burkitt lymphoma may develop in patients with AIDS. A clinical presentation of a proptotic child with an abdominal and orbital mass and upward globe displacement is typical. Diagnostic orbital imaging demonstrates a maxillary bone or paranasal sinus lesion with secondary orbital invasion. Histopathology shows B-lymphocyte proliferation and a classic “starry-sky” appearance. Other features include translocation of chromosomes 8 and 14 as well as an association with Epstein-Barr virus. Burkitt lymphoma is typically chemosensitive. As such, management involves attempted debulking and chemotherapy, with external radiation for chemoresistant cases.
Plasma Cell Tumors
Tumors composed of mature plasma cells include plasmacytoma (monoclonal proliferation of plasma cells) and localized plasma cell–rich pseudotumor. Plasmacytoma may rarely present as a primary orbital tumor involving bone (solitary plasmacytomas of bone) or soft tissue (extramedullary plasmacytoma). Secondary orbital plasmacytoma is more common and is associated with multiple myeloma. Systemic workup to rule out multiple myeloma is crucial before the diagnosis of primary orbital plasmacytoma can be made. Patients typically present with nonspecific orbital signs, including painless proptosis, ptosis, and eyelid swelling. Orbital imaging shows a posterior extraconal orbital mass with possible bony destruction. Multiple myeloma–associated masses tend to occur in the superotemporal quadrant. Definitive diagnosis requires histopathologic analysis of tumor tissue. Treatment is usually external beam radiation or chemoradiation. Underlying multiple myeloma is treated by a medical oncologist with chemoradiation and/or stem cell transplant.
Histiocytic Tumors
Histiocytic disorders can be divided into two broad categories: Langerhans cell histiocytosis (LCH) and non-LCH.
Juvenile Xanthogranuloma
Juvenile zanthogranuloma (JXG), the most common form of non-LCH, is a predominantly benign cutaneous disorder. Lesions typically appear during the first year of life as reddish-yellow cutaneous nodules that resolve spontaneously. The head and neck are the most common sites of involvement. Extracutaneous JXG occurs in a minority of patients and is most frequent, and potentially blinding, in the eye. It can also involve the brain, lungs, liver, spleen, and other sites. Management involves topical or periocular corticosteroids for ocular involvement and corticosteroids or excisional biopsy for periocular JXG. Conservative globe-sparing treatment leads to tumor control and satisfactory visual outcome in the majority of patients.
Adult Xanthogranuloma
Adult xanthogranuloma may present in isolated forms in the eyelid or anterior orbit (necrobiotic xanthogranuloma, adult-onset xanthogranuloma) or in an aggressive, potentially lethal systemic form (Erdheim-Chester disease). Xanthogranuloma presents with fibrosclerosis of the orbital tissues. In Erdheim-Chester disease, the mediastinum, pericardium, pleura, bone, and retroperitoneum may be involved, and orbital disease is more diffuse with potential for vision loss. Local lesions are treated with systemic corticosteroids and other immunosuppressants. Vemurafenib, tocilizumab, and sirolimus have shown promising results in systemic disease.
Langerhan Cell Histiocytosis
LCH is a rare condition characterized by the abnormal accumulation of proliferating dendritic histiocytes. It most often presents in children between the ages of 5 and 10 years with upper eyelid swelling. The disease spectrum ranges from acute disseminated form (Letterer-Siwe syndrome) with lethal outcomes to chronic, more benign forms (Hand-Schüller-Christian disease and eosinophilic granuloma). Clinically episodes of orbital inflammation may occur recurrently and can involve soft tissue. On orbital imaging, lytic defects of the temporal fossa or sphenoid wing can help differentiate the lesion from orbital cellulitis. Management involves a systemic workup to evaluate for extraorbital involvement, confirmatory biopsy with debulking, followed by intralesional steroid injection or low-dose radiation. Systemic disease requires chemotherapy.
Lacrimal Gland Tumors
The majority of lacrimal gland masses involve dacryoadenitis, or nonspecific inflammation. A smaller portion of lacrimal fossa masses are consistent with lymphoproliferative disease, as discussed earlier. A minority of lacrimal gland tumors are of epithelial origin: 50% are pleomorphic adenomas and 50% are carcinomas.
Dacryops
Dacryops is a lacrimal gland fluid–filled cyst of epithelial origin associated with normal lacrimal tissue. It typically presents in young adults and middle-aged patients. Dacryops most frequently arises from the palpebral lobe of the lacrimal gland and presents as a slow-growing conjunctival mass in the superotemporal fornix. Although typically painless, dacryops may become inflamed or infected and cause pain. Imaging reveals a localized cystic mass in the lacrimal fossa. In symptomatic cases, localized resection may be performed through a superotemporal conjunctival approach, taking care to avoid damaging additional lacrimal ductules and thereby causing dry eye.
Pleomorphic Adenoma
Pleomorphic adenoma (benign mixed tumor) is the most frequently occurring lacrimal gland epithelial tumor. It is slightly more common in men and typically presents during the fourth or fifth decade of life. Clinically the patient presents with painless proptosis from a slowly growing, progressive mass that displaces the globe inferonasally ( Fig. 25.2 ). A firm, potentially nodular mass may be palpated in the lacrimal gland region. Imaging reveals a well-circumscribed mass that may be nodular in appearance. Diagnosis is confirmed by histopathologic analysis of the excised mass, which demonstrates benign-appearing epithelial cells in a spindle-shaped cellular stroma with components of cartilage, osseous, and/or mucin material present. Management involves complete excision of the tumor and its surrounding pseudocapsule without initial biopsy because the tumor frequently recurs (32% of cases) with potential for malignant degeneration.
Malignant Mixed Tumor
Malignant mixed tumor, or pleomorphic adenocarcinoma, may arise from an incompletely excised pleomorphic adenoma. Microscopically this tumor demonstrates localized areas of malignant degeneration with otherwise similar histopathologic features as pleomorphic adenoma. Surgical management is typically followed by radiotherapy and/or chemotherapy.
Adenoid Cystic Carcinoma
Adenoid cystic carcinoma is the most common lacrimal gland malignancy. Axial proptosis and inferonasal globe displacement are common, as is posterior orbital extension owing to the lack of encapsulation. In contrast to pleomorphic adenoma, patients present with a characteristic painful and rapid-growing mass over the course of less than 1 year. Histologic diagnosis reveals cells arranged in tubular, nets, or Swiss-cheese pattern with possible perineural invasion. Basaloid cellular morphology portends a poorer prognosis than cribriform morphology.
Malignant lacrimal gland tumors have been associated with notoriously poor outcomes. Surgical debulking combined with radiation therapy is the recommended management strategy, as exenteration has failed to demonstrate improvement in survival rates. Neoadjuvant chemotherapy is under active investigation. Unfortunately, mortality from intracranial extension typically occurs within years after a series of recurrences.
Neurogenic Tumors
Meningioma
Meningiomas are invasive tumors originating from the arachnoid villi and represent the most common primary brain tumor. Orbital involvement may involve the optic nerve sheath or the sphenoid wing.
Sphenoid Wing Meningioma
Orbital involvement typically occurs secondarily from spread of an intracranial meningioma along the sphenoid wing. Patients are typically Caucasian women older than 50 years and present with temporal fullness, proptosis, globe dystopia, eyelid edema, and/or chemosis. Tumors near the optic nerve can cause decreased visual acuity, visual field loss, and relative afferent pupillary defect (RAPD). Cavernous sinus infiltration may lead to diplopia from cranial neuropathy. An enhancing temporal fossa mass with hyperostosis of the sphenoid wing is seen on orbital imaging ( Fig. 25.3 ). The diagnosis is secured by biopsy for histopathologic analysis, which shows whorls of meningothelial cells composed of epithelioid type cells with eosinophilic cytoplasm and calcium deposition (psammoma bodies). Sphenoid wing meningioma is usually observed unless functional deterioration occurs, at which point tumor debulking with or without postoperative radiotherapy is performed.
Optic Nerve Sheath Meningioma
Primary meningioma may arise in the orbit from the arachnoid of the optic nerve sheath. Optic nerve sheath meningioma has a gradual, painless presentation with gradual loss of vision and RAPD. The typical patient is a woman in her third or fourth decade of life. Ophthalmic examination can show a normal optic nerve head or disc edema with optociliary shunt vessels. Orbital imaging is generally diagnostic and demonstrates tubular enlargement of the optic nerve with contrast enhancement. Computed tomography (CT) may show characteristic calcification of the optic nerve sheath, known as tram-tracking. Optic nerve sheath meningioma is observed with serial magnetic resonance imaging (MRI) scans if vison is minimally affected and intracranial extension is absent. In the setting of progressive or profound vision loss, radiation therapy is administered. Surgery is typically avoided because of the risk of permanent vision loss from optic nerve blood supply compromise.
Optic Nerve Glioma
Optic nerve glioma is a type of juvenile pilocytic astrocytoma that usually occurs in children younger than 10 years and may be associated with neurofibromatosis in up to 50% of cases. Patients present with gradual, painless, unilateral axial proptosis and ipsilateral vision loss with RAPD. Optic atrophy, disc edema, strabismus, and/or nystagmus may be seen on ophthalmic examination. Diagnosis can usually be made by imaging studies, which show fusiform enlargement and kinking of the optic nerve. Biopsy is typically avoided because of the risk of additional vision loss. Optic nerve gliomas may be observed with serial MRI unless vision loss is progressive and extraorbital involvement is present. When treatment is indicated, chemotherapy is usually considered the first-line therapy. In the setting of progressive symptoms despite chemotherapy, radiation therapy can be used. Surgical debulking is considered only in exceptional cases with extreme proptosis. The rare, malignant variant (glioblastoma) is fatal within 6 to 14 months despite chemotherapy and radiation.
Neurofibroma
Neurofibroma is a Schwann cell tumor that may be discrete or associated with neurofibromatosis type 1 (plexiform neurofibroma). The patient presents with a stereotypical S -shaped lateral eyelid deformity and ptosis. In cases associated with neurofibromatosis, multiple neurofibromas may cause diffuse facial disfigurement. On examination, the mass may have a “bag of worms” consistency to palpation. Surgical management is limited to tumors that cause disfigurement or visual compromise, although recurrence is common in plexiform tumors. In contrast, discrete tumors may be excised without recurrence.
Schwannoma
Schwannoma (neurolemmoma) is a benign, slow-growing encapsulated tumor that arises from proliferation of Schwann cells. Affected patients are between the second and sixth decade of life. Schwannomas typically occupy the superior orbit and rarely undergo malignant transformation ( Fig. 25.4 ). Microscopically, tumors demonstrate a distribution of nuclear palisading (Antoni A) and myxoid (Antoni B) areas, and the appearance on MRI has a variable degree of heterogeneity. Primary treatment is complete excision with maintenance of capsular integrity.
