Intraorbital Pathology (Tumors) and Management Strategies

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.

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.

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.