general [8, 13–17]. Being a systemic treatment, monoclonal antibody therapy not only may be effective in local control but also may offer better overall systemic control of lymphoma. It may also be less toxic to the ocular structures compared to radiation therapy [10, 18]. Rituximab alone may yield good initial response but is associated with a 50% chance of distant relapse [17]. Rituximab in combination with chemotherapy or radioimmunotherapy may be associated with a higher durable response rate [17, 19]. Surgical excision is typically not a viable option for orbital lymphoma because of the infiltrative nature of the tumor. Rituximab may also be a good treatment option for orbital benign lymphoid hyperplasia [20].

1.1.3 Follow-up

Regardless of treatment, response to therapy should be monitored via conventional imaging; positron emission tomography could also be used as an adjunct [21]. Because the lymphoproliferative diseases show substantial overlap in terms of clinical behavior, all patients should be followed indefinitely by an oncologist and have periodic systemic workups. Workups should include examination for lymphadenopathy, complete blood cell count with differential, and body imaging.

1.2 Mesenchymal Tumors

Approximately 2% of tumors detected on orbital biopsy are tumors of fibrous connective tissue, cartilage, or bone [22]. The tumors in this group arise from primitive mesenchymal stem cells capable of developing into a variety of cell types.

1.2.1 Fibrous Histiocytoma

Fibrous histiocytoma (fibroxanthoma) may be the most common primary orbital mesenchymal neoplasm in adults. The median age at presentation is 43 years, and the superior nasal orbit is the most common site [23]. Fibrous histiocytoma is usually slow growing and characteristically very firm, displacing normal structures. The most common clinical signs are proptosis and mass effect with decreased vision; less common signs are diplopia, pain, lid edema, tearing, ptosis, and ophthalmoplegia [24]. Both fibroblastic and histiocytic cells in a storiform (mat-like) pattern are found in these locally aggressive tumors [24]. Although most are benign, intermediate and malignant varieties exist, but fewer than 10% have metastatic potential [23]. It is often difficult to distinguish this tumor clinically or microscopically from hemangiopericytoma (see Section 1.2.3). Management is surgical excision supplemented by adjuvant post operative radiation therapy or possibly chemotherapy.

1.2.2 Solitary Fibrous Tumor

A relatively new entity, solitary fibrous tumor, has been described. Unlike fibrous histiocytoma, the other major entity that has to be considered in the differential diagnosis, solitary fibrous tumor is composed of spindle-shaped, strongly CD34positive cells [24]. Solitary fibrous tumors can occur anywhere in the orbit, are well circumscribed, lack a capsule, and may recur and undergo malignant transformation if incompletely excised. Their characteristic magnetic resonance imaging feature is heterogeneity and low T2 signal intensity [24]. Before the typical immunohistochemical features of solitary fibrous tumors were described, a number of these mesenchymal tumors were likely misclassified as fibrous histiocytoma, hemangiopericytoma, and schwannoma [23]. However, many pathologists believe that solitary fibrous tumor is a very close entity to hemangiopericytoma from the standpoint of its biological and clinical behavior.

1.2.3 Hemangiopericytoma

Hemangiopericytomas are rare, encapsulated, cellular tumors typically located in the superior orbit, which appear in middle-aged adults (median age, 42 years) [25]. Hemangiopericytomas can manifest with proptosis, pain, diplopia, decreased vision, ophthalmoplegia, conjunctival prolapse, and prominent blood vessels in the fornix. These tumors may resemble cavernous hemangiomas on imaging, appearing as homogeneously enhancing, well-defined masses. Histologically, tumors are composed of a rich capillary network in a staghorn pattern surrounded by pericytes. Tumors may be benign, intermediate, or malignant. It is difficult to predict biological activity on the basis of histology; histologically benign lesions may recur and metastasize, whereas malignant lesions may remain localized [25]. Complete excision with long-term patient follow-up is a must as one-third of these tumors recur. Hemangiopericytomas may undergo malignant transformation, and 10–15% metastasize [25]. Tumors with a biologically aggressive behavior are handled with a more radical approach, including preoperative embolization, wider excision, and preor post operative radiation therapy [25]. Preoperative radiation therapy may lead to a decrease in the size of the tumor, making complete surgical excision easier and decreasing the risk of recurrence after surgical removal (unpublished observations, Dr. Bita Esmaeli) (Fig. 1.5).

1.2.4 Other Mesenchymal Tumors

Various types of malignant mesenchymal tumors, such as liposarcoma, fibrosarcoma, chondrosarcoma, synovial sarcoma (Fig. 1.6), Ewing sarcoma, and osteosarcoma, can present in the orbit. Combined-modality treatment with a combination of chemotherapy, surgery, and radiation therapy is the most common approach to treatment of these rare but aggressive tumors of the orbit [7].