Section 4 -

Orbital Metastases Abelardo A. Rodríguez-Reyes Ophthalmic Pathology Service Asociacion Para Evitar la Ceguera en Mexico' I.A.P. Hospital ''Dr Luis Sanchez Bulnes'' Mexico

Metastatic tumors to the orbit were first described by Horner [1] in 1864 and Perl [2] in 1872. Metastatic disease to the periorbital region in children is almost exclusively orbital, in contradistinction to metastatic disease in adults, in whom uveal involvement predominates. [3] In adults, metastatic carcinoma occur to orbit about one tenth as often as to the eyeball. [4, 5] Metastasis is a rare cause of orbital mass, comprising 3-7% of the cases. [6] Their clinical presentations are as diverse as the biology of the underlying primary tumors, and this wide range of manifestations has been the root, of misdiagnoses and lengthy delays to diagnosis. Although with today's sophisticated diagnostic tools, lack of suspicion and protean presentation can lead to difficulty in properly and efficiently diagnosing orbital metastatic disease. In infants, the classic clinical manifestation of both neuroblastoma and Ewing's sarcoma is a rapidly developing proptosis, which may be associated with ecchymosis in the eyelids caused by necrosis as it rapidly grows and outstrip its blood supply. [7, 8] The orbital metastases may be bilateral in up to 40% of neuroblastoma patients, although they are more often unilateral in the Ewing's sarcoma. Metastatic tumors to the orbit are more likely to be found in middle aged-individuals, with a mean age in different series around 60 years, both orbits are equally affected, and occasional bilateral metastases can occur. [7] As a general rule, metastatic tumors to the orbit produce disproportionately severe complaints in comparison with primary orbital tumors. The patients most commonly present with proptosis or diplopia. [6, 9, 10] Other signs and symptoms at presentation include pain, decreased vision, ptosis, and enophthalmos. The most common orbital metastases are carcinomas, with the primary sources being breast carcinoma in females and lung and prostate carcinomas in males. Less common metastatic tumors are from gastrointestinal tract, kidney and cutaneous melanoma. Metastatic carcinomas to the orbit are frequently a diagnostic challenge because they may occur long after primary tumor has apparently been successfully treated or may even occur as the first sign of an undetected primary neoplasm. It is not infrequent to have an orbital metastasis with an occult primary, as seen in one third of the cases. [6, 10] Radiographic and CT evaluations of orbits with metastases provide a multiform set of results. [11, 12]T he lesions may be well circumscribed or may disclose diffusely infiltrative growth pattern. Bone erosion may be quite considerable with the metastatic lesions of the orbit of tumors such as prostatic, mammary, pulmonary and renal carcinomas. The histopathology of metastatic orbital carcinoma is as varied as that of the primary tumors and the diagnosis is mainly based on morphologic features. Special stains, immunohistochemistry, electron microscopy and other molecular biology techniques, are very useful tools to establish the diagnosis of metastatic orbital tumors. Orbital metastases can be confused with inflammatory processes, pseudotumors and other primary or secondary orbital tumors. Certain pitfalls in the diagnosis of metastatic carcinoma to the orbit should be pointed out. The histopathology of metastatic orbital carcinoma is as varied as that of primary neoplasms. The histiocytoid mucus-producing variant of metastatic breast carcinoma can be mimicked by primary adnexal carcinomas of the eyelid, which have virtually indistinguishable histopathologic and ultrastructural findings. [13] With respect to both metastatic histiocytoid carcinoma and the primary adnexal carcinoma, frequent mistaken diagnoses include granular cell tumor, histiocytosis, inflammatory pseudotumor, and xantelasma. In tumors with similar morphologic features originated in the paranasal sinuses, a clinicopathologic correlation and long-term follow-up are required to rule out a metastatic process. In the histiocytoid variant of breast carcinoma, [14] individual neoplastic cells immerse in the fibrous stroma resemble histiocytes, except that their nuclei are hyperchromatic and atypical, and their cytoplasm have a central vacuole, which may be shown by special stains (alcian blue, colloidal iron or mucicarmin) to contain a mucinous material. The work-up of a patient with an orbital metastasis not known to have a primary tumor, should consist of a complete physical examination by an oncologist, laboratory tests and imaging studies. The treatment of orbital metastases is commonly nonsurgical, although rarely circumscribed tumors may be completely excisable. There are rare causes of orbital mass lesion, when histopathology is of primary importance in diagnosis, in those cases, a biopsy should be taken. [15, 16] Systemic chemotherapy for the primary tumor may have as well a beneficial effect on orbital tumors. Localized orbital radiotherapy with protection of the globe, can have excellent results. Orbital metastases of systemic cancer appear to be increasing in frequency. This finding may reflect the overall increase in the volume of medical literature more than it does the frequency of site specific metastatic disease. It might represent an increased longevity and changing metastatic patterns in today's cancer patients, whose survival has been extended and there immunological status being altered by modern treatment methods. [17] References Horner F: Carcinoma der Dura Mater. Exophthalmus. Carcinoma der Musculi Recti. Allgemeine Carcinose. Klin Monatsbl Augenheilkd 1864;2:186-190. Perl M: Contributions to pathology of tumors. Virchows Arch A 1872;56:437-467. Volpe NJ, Jakobiec FA: Pediatric orbital tumors. Int Ophthalmol Clin 1991;31:201-221. Ferry AP, Font RL: Carcinoma metastatic to the eye and orbit: I. A clinicopathologic study of 227 cases. Arch Ophthalmol 1974;92:276-286. Shields CL, Shields JA, Peggs M: Tumors metastatic to the orbit. Ophthal Plast Reconstr Surg 1988;4:73-80. Char DH, Miller T, Kroll S: Orbital metastases: diagnosis and course. Br J Ophthalmol 1997;81:386-90. Jakobiec FA, Rootman J, Jones IS: Secondary and metastatic tumors of the orbit. In: Jones IS, Jakobiec FA (eds): Diseases of the Orbit. Hagerstown, Md: Harper & Row;1979. Musarella MA, Chen HSL, DeBoer G, Gallie BL: Ocular involvement in neuroblastoma: Prognostic implications. Ophthalmology 1984;92:1758-1762. Font RL, Ferry AP: Carcinoma metastatic to the eye and orbit III. A clinicopathologic study of 28 cases metastatic to the orbit. Cancer 1976;38:1326-35. Günalp I, Gündüz K: Metastatic orbital tumors. Jpn J Ophthalmol 1995;39:65-70. Hesselink JR, David KR, Weber AL, et al: Radiological evaluation of orbital metastases, with emphasis on computed tomography. Radiology 1980;137:363-366. Healy JF: Computed tomographic evaluation of metastases to the orbit. Ann Ophthalmol 1983;15:1026-1029. Jakobiec FA, Austin P, Iwamoto T, et al: Primary infiltrating signet ring carcinoma of the eyelids. Ophthalmology 1983;90:291-299. Hood CI, Font RL, Zimmerman LE: Metastatic mammary carcinoma in the eyelid with histiocytoid appearance. Cancer 1973;31:793-800. Souza-Filho JP, Odashiro AN, Al-Boloushi A, et al: Orbital metastasis of urinary bladder carcinoma: A clinicopathologic report and review of the literature. Orbit 2005;24:269-271. Gupta R, Honavar SG, Vemuganti GK: Orbital metastasis from hepatocellular carcinoma. Surv Ophthalmol 2005;50:485-489. Goldberg RA, Rootman J, Cline RA: Tumors metastatic to the orbit: A changing picture. Surv Ophthalmol 1990;35:1-24.