Chapter 1
Primary Orbital Cancers in Adults
Roman Shinder and Bita Esmaeli
Abstract Neoplasms of the orbit in adults may be primary tumors, secondary tumors extending from adjacent structures, or metastatic tumors. The incidence of primary malignant orbital neoplasms is low. A computed tomography scan is usually the initial radiographic modality employed to investigate suspicious lesions. Biopsy is usually undertaken to establish a diagnosis and formulate a treatment plan. Prognosis depends on the type of tumor and extent of local or systemic disease at presentation. This chapter is not intended to provide an exhaustive discussion of all possible primary orbital cancers; rather, it focuses on the management of tumors most commonly encountered at a tertiary cancer center. Benign tumors of the orbit in adults, lacrimal gland tumors, and pediatric orbital tumors are also covered in Chapters 2, 7, and 3, respectively.
1.1 Lymphoproliferative Disorders
Lymphoproliferative disorders, a heterogeneous group of neoplasms of the lymphoid system, account for greater than 20% of all orbital masses and are the most common orbital malignancies in adults [1, 2]. The majority of primary orbital lymphomas are B-cell non-Hodgkin lymphomas. The incidence of orbital lymphomas has been increasing in recent years, although the factors responsible for this rise are poorly understood. Recognized risk factors include chronic autoimmune diseases and occupations that involve exposure to bioactive solvents and reagents.
R. Shinder (B)
Section of Ophthalmology, Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
e-mail: romanshinder@hotmail.com
B. Esmaeli (ed.), Ophthalmic Oncology, M.D. Anderson Solid Tumor |
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Oncology Series 6, DOI 10.1007/978-1-4419-0374-7_1,
C Springer Science+Business Media, LLC 2011
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R. Shinder and B. Esmaeli |
1.1.1Presenting Signs and Symptoms, Histopathologic and Molecular Genetic Characteristics, and Diagnosis
Over the past 20 years, our understanding of orbital lymphoproliferative lesions has undergone profound change. This is primarily due to the development of increasingly sophisticated and specific immunodiagnostic and molecular techniques in tissue pathology. Historically, lymphoid tumors were classified as either benign reactive lymphoid hyperplasias or malignant lymphomas. More recently, it has been accepted that lymphoproliferative lesions represent a spectrum and that ultimate behavior is challenging to predict. Patients with microscopically benign lymphoid infiltrates eventually may develop systemic lymphoma, while malignant lymphomas may be well circumscribed and respond to local therapy without subsequent extraorbital involvement. At present, 70–80% of lymphoproliferative lesions are considered malignant on the basis of monoclonal cell-surface markers, whereas 90% are found to be malignant through molecular genetic testing [2]. With further advances in diagnostic techniques, the proportion of cases classified as benign reactive lymphoid hyperplasia is likely to continue to diminish.
Typically, lymphoproliferative lesions of the orbit present as progressive, painless masses in the sixth to eighth decades of life [1]. The tumors are often located anteriorly in the extraconal orbital space and may present as a palpable, rubbery mass. Lesions typically mold themselves around orbital structures rather than invading them; therefore, disturbances of extraocular motility or vision are unusual. Orbital lymphomas may be associated (22% of cases) with a salmon-colored, fleshy, subconjunctival extension that molds to the shape of the globe, commonly referred to as a salmon patch (Fig. 1.1) [2]. There is usually a history of slow growth over
Fig. 1.1 Orbital and conjunctival MALT lymphoma with a “salmon patch” infiltrate on the ocular surface
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Fig. 1.2 Unusual presentation of diffuse large B-cell lymphoma of orbit with bony invasion in the orbital apex and extension intracranially
a period of months to years. Orbital imaging displays a characteristic, cohesive, putty-like molding of the tumor around structures, and bone erosion or infiltration is unusual except in high-grade malignant lymphomas (Fig. 1.2). The most common site involved is the lacrimal fossa, where up to 50% of lymphoproliferative lesions occur [3]. Approximately 17% of lymphoid lesions occur bilaterally in the orbits; while bilateral involvement markedly increases the risk for systemic disease, it does not, by itself, signify systemic involvement [3].
An open biopsy is recommended for all lesions confined to the orbit to obtain adequate tissue to establish a diagnosis. If systemic disease is present, biopsy of an accessible lymph node is preferred over orbital biopsy because nodal architecture is helpful in diagnosis and the procedure may be safer [4]. The majority of the specimen should be sent fresh to the laboratory for flow cytometry and immunohistochemistry; the remainder of the specimen may be fixed for microscopic analysis. Histologically, a continuum is seen ranging from benign reactive hyperplasia to atypical lymphoid hyperplasia to low-grade lymphoma to high-grade lymphoma. All variants are characterized by a hypercellular lymphoid proliferation with a scant stromal component; thus, it is difficult to categorize a lesion solely by light microscopy. Immunopathology and molecular studies are therefore used as aids in tumor categorization.
It is thought that malignant lymphomas represent clonal expansions of abnormal precursor cells. Immunologic studies of lymphocyte cell-surface markers may be used to classify tumors as containing B or T cells and as being monoclonal (malignant) or polyclonal (benign). DNA hybridization is more sensitive than cell-surface marker typing in assessing clonality, but the DNA hybridization technique is more time consuming and expensive [5]. Importantly, monoclonality established by either immunophenotyping or molecular genetic testing does not predict which tumors will
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lead to systemic disease. Approximately 90% of lymphomas show monoclonality by molecular genetic studies.
Marginal zone lymphomas, also known as mucosa-associated lymphoid tumor (MALT), represent the largest group of orbital lymphomas, accounting for 40–60% [6]. It was previously thought that low-grade MALT-type lymphomas rarely undergo systemic spread. However, recent studies demonstrate that at least 50% of patients will develop systemic disease within 10 years [6]. MALT lymphomas undergo histologic transformation to a more aggressive lymphoma in 15–20% of patients, usually after several years, and the risk of transformation is unrelated to therapy [7].
Prior, concurrent, or future systemic spread may occur in patients with ocular adnexal lymphomas. In a recent report from our center, more than half of patients with orbital and ocular adnexal lymphoma were found to have extraorbital involvement at the time of diagnosis [8]. This is higher than previously reported rates, in part because of the more aggressive lymphomas seen at our tertiary cancer center and likely because of the uniform staging workup performed here, which included total-body positron emission tomography in the majority of patients and bone marrow biopsies in all patients. The anatomic location of the tumor may help predict the risk of developing systemic disease; risk is lowest for conjunctival lymphomas (20% of cases), greater for orbital lymphomas (35% of cases), and highest for eyelid lymphomas (67% of cases) [9]. Although most cases of primary orbital lymphoma are low grade, secondary orbital lymphomas in patients with prior or concurrent disease are typically intermediate or high grade [10]. Secondary orbital lymphoma may appear at any time after initial diagnosis of non-Hodgkin’s lymphoma and may occur as either a manifestation of disseminated relapse or the only site of active recurrence [10].
An important option to consider in the differential diagnosis of patients with orbital lymphoproliferative lesions is idiopathic orbital inflammation. Inflammatory disorders can be differentiated from lymphoma on the basis of their acute presentation, rapid response to steroids, and polymorphic infiltrate on histopathology.
1.1.2 Treatment
Important determinants of the optimal management of orbital lymphoma are the stage at presentation, histologic classification, extent of disease, patient comorbidities, and potential ocular toxicity of treatment. Proper initial staging is critical and should include total-body positron emission tomography, bone marrow biopsy, and, for MALT lymphoma and mantle cell lymphoma, gastrointestinal endoscopy [9].
Radiation therapy has classically been the treatment of choice for patients with localized low-grade ocular adnexal lymphoma as it achieves local control in greater than 90% of cases [11]. However, radiation therapy is a form of local therapy and thus does not address the risk of systemic relapse. Also, it may cause immediate and delayed ocular side effects, including dry-eye syndrome, keratopathy, cataract, and retinopathy. Furthermore, since careful staging proves that more than 50% of patients have systemic disease on presentation, systemic
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Fig. 1.3 Magnetic resonance imaging of orbital lymphoma before (a) and after (b) radioimmunotherapy using ibritumomab tiuxetan (Zevalin)
Fig. 1.4 Magnetic resonance imaging of benign lymphoid hyperplasia of orbit before (a) and after (b) treatment with rituximab. From Hao HH, Savar A, Samaniego F, et al. Treatment of benign lymphoid hyperplasia of the orbit with rituximab. Ophthal Plast Reconstr Surg 2010;26:11–13. Reprinted with permission
therapy, such as monoclonal antibody immunotherapy or radioimmunotherapy, can be considered as an alternative to radiation therapy (Figs. 1.3 and 1.4). Systemic combination chemotherapy regimens, such as cyclophosphamide, doxorubicin, vincristine, and prednisone or similar protocols, are used for more aggressive histologic varieties of lymphoma, such as diffuse large B-cell lymphoma or mantle cell lymphoma [12].
Recently, there has been a trend toward the use of monoclonal antibody therapy or radioimmunotherapy directed against CD20 (rituximab or ibritumomab tiuxetan) to treat not only ocular adnexal lymphoma but also non-Hodgkin’s lymphoma in