Case report: Orbital metastasis an early sign of prostatic cancer

Discovery of a lesion in a patient’s orbit led ophthalmologists to a diagnosis of prostate cancer in a patient with no urinary symptoms.

Issue: June 1, 2003

ByMark R. Levine, MD, FACS

ByJohn Y. Choi, MD

ByDavid S. Bardenstein, MD

Right eye proptosis and superior orbit fullness.

Right eye showing upgaze restriction.

A 53-year-old man presented with sudden onset of diplopia, right eye proptosis and headaches. The patient had no history of urinary tract problems, neoplasia or thyroid disease. Initial uncorrected vision was 20/30 in the right eye and 20/15 in the left. Exophthalmometry with a base of 100 mm was 25 mm for the right eye and 20 mm for the left. The right orbit was full and firm to palpation from the mid-superior orbit temporally (figure 1). The right superior rectus had limited motion in its field of action (figure 2). The rest of the examination including pupils, anterior segment, applanation tonometry and the fundus were within normal limits.

Diagnosis and treatment

Computed tomography revealed a hyperostotic lesion of the greater wing of the right spheroid bone with intracranial and intraorbital extension, which was interpreted as an atypical spheroid ridge meningioma (figure 3). The patient was referred to the neurosurgery service and underwent an orbital zygomatic craniotomy with complete tumor resection.

On frozen section evaluation, the tumor was diagnosed as prostate adenocarcinoma. Microscopic specimen examination revealed sheets of epithelial cells arranged in various patterns. Some fields showed glandlike structures with cells arranged in tubes and cords (figure 4). Others demonstrated infiltrative clusters of cells.

Cytologically, cells showed round nuclei with prominent and sometimes multiple nucleoli surrounded by pale cytoplasm. Other cells showed pleomorphism and eosinophilic cytoplasm (figure 5). Mitotic figures were not seen. On immunohistochemical analysis, most of the tumor cells expressed markers for both prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP).

Postoperative systemic evaluation for metastatic prostate carcinoma showed a serum PSA of 35.3 µg/dL (normal is less than 5 µg/dL). Bone scan and CT of chest, abdomen and pelvis were negative for metastasis. Genitourinary evaluation included a prostate biopsy, which was positive for prostate adenocarcinoma with a Gleason’s score of 7. The patient was clinically assessed as having stage IV prostate adenocarcinoma with orbital metastasis.

Medical therapy was instituted with bicalutamide 50 mg orally per day and leuprolide 7.5 mg orally per month in combination with adjuvant radiation of 45 Gray over 5 weeks. The patient is alive and well 2 years later without recurrence.

Retrospective CT analysis revealed that the lesion was osteolytic and the foci of calcification were more likely fragments of lysed greater spheroid wing displaced by the growth of the metastasis, simulating osteoblastosis.

Axial CT scan showing a mass involving the greater wing of the right spheroid with intracranial and intraorbital extension. Foci of calcification are seen in the lesion. The globe is displaced forward.

Low-power photomicrograph of carcinoma with glandular and invasive patterns (hematoxylin-eosin, original magnification ×100).

High-power photomicrograph of prostate carcinoma cells with large nucleoli (hematoxylin-eosin, original magnification ×400).

Discussion

Prostate carcinoma is the third most common male cancer after non-melanoma skin and lung cancers. It ranks third after lung and colon cancers in male cancer deaths. Seventy to eighty percent of prostate carcinomas metastasize distantly, most frequently to the bony pelvis and vertebra.

Prostate carcinoma is more likely to metastasize to the bony orbit than the globe by a 4.4:1 ratio, contrasting sharply with metastatic tumors as a whole, which favor ocular metastasis by a 7:1 ratio.

Prostatic orbital metastases occur in an older age group compared to metastases from other sites. In their meta-analysis of orbital metastases, Goldberg et al noted a mean age at onset of 70 years, as did Carriere et al. Goldberg and Rootman from their series of metastatic orbital tumors had four prostate metastases with an average age at presentation of 74.3 years.

In their series of 100 cases of orbital metastases, Shields et al noted that 75% of prostate metastases occurred in the 60- to 79-year-old age group. The average age of presentation for metastases from all sites, including prostate, was 53.6 years according to Font and Ferry and 56 years per Goldberg et al.

The most frequent orbital signs are proptosis, limited extraocular motility and globe displacement. The most common symptoms are pain, diplopia and decreased vision.

Detecting orbital metastases

Prostatic orbital metastases frequently are detected before the primary neoplasm. Boldt and Nerad presented eight cases of prostatic carcinoma metastatic to the orbit. Three patients had no prior diagnosis of prostate cancer. In Goldberg and Rootman’s series, only 25% of prostate metastases were detected before the primary tumor.

However, in this case, the patient’s young age, absence of urinary tract disease and a CT suggestive of osteoblastosis, in combination with his symptoms and proptosis from a mass involving the bony orbit, were more suggestive of meningioma than of prostate metastasis.

Neuroimaging is important in the evaluation of these lesions. On CT, 66% to 90% of bony prostatic lesions are osteoblastic, characterized by hyperostotic bone with irregular, often spiculated, new bone involving a surrounding soft tissue mass.

This differs from osteolytic lesions from other primary sites of metastasis. Other entities that can cause osteoblastic orbital changes are usually distinguished by history and CT. These include meningioma en plaque, osteomas, Paget’s disease, osteogenic sarcoma, fibrous dysplasia, ossifying fibromas, neurofibromatosis and osteoblastoma.

In this case, the lesion on CT was initially interpreted to be osteoblastic with osteogenic foci. On subsequent review, the foci were determined to be bone fragments from an area of osteolysis.

Metastatic prostate carcinoma can be diagnosed specifically with immunohistochemistry. Prostate tissues express PSA and several acid phosphatase isozymes, of which isozyme 2 is prostate-specific. Prostatic acid phosphatase isoenzyme immunoperoxidase labeling has been demonstrated to be more sensitive and specific than other immunohistochemical techniques in determining prostatic origin.

History and prognosis

The natural history and prognosis of orbital prostate metastasis have not been studied extensively. Boldt and Nerad noted a mean survival time of 26 months for their eight patients. Relapse and progression to death often occur by 2 to 3 years, and the 10-year survival rate is 10%. Telera et al noted that prostate metastasis to the spheroid with cranial nerve deficits was associated with a median survival of 5 months.

Treatment is palliative. Hormonal therapy is effective in 70% to 80% of patients, with an average response of 18 months. Luteinizing hormone-releasing hormone agonists such as leuprolide inhibit gonadotropin release, suppressing testicular steroidogenesis needed for prostate growth.

Bicalutamide is an androgen antagonist, competing for prostatic androgen receptors. Osteoblastic lesions are sensitive to it; late-stage osteolytic lesions are less responsive.

As with many other metastases, local radiation is effective. In a series of 37 patients receiving 30-56 Gray for ocular or orbital metastatic carcinoma, 89.9% experienced tumor regression and improvement of symptoms.

Our patient is instructive because of his young age, the absence of urinary tract disease and a CT suggestive of osteoblastosis, in combination with his symptoms and proptosis from a mass involving the bony orbit, leading to attribution of his findings to meningioma. The lesion was later determined to be osteolytic, unlike the majority of prostatic orbital metastases. Histologic evaluation led to the proper diagnosis.

For Your Information

David S. Bardenstein, MD, is an associate professor of ophthalmology and pathology, Department of Ophthalmology, Case Western Reserve University.

John Y. Choi, MD, is a resident in the Department of Ophthalmology, Case Western Reserve University.

References:

Boldt HC, Nerad JA. Orbital metastases from prostate carcinoma. Arch Ophthalmol. 1998;106:1403-1408.

Goldberg RA, Rootman J. Cline RA. Tumors metastatic to the orbit: A changing picture. Surv Ophthalmol. 1990;35:1-24.

Carriere VM, Karcioglu ZA, et al. A case of prostate carcinoma with bilateral orbital metastases and the review of the literature. Ophthalmology. 1982;89:402-406.

Goldberg RA, Rootman J. Clinical characteristics of metastatic orbital tumors. Ophthalmology. 1990;97:620-624.

Shields JA, Shields CL, et al. Cancer metastatic to the orbit: The 2000 Robert M. Curts Lecture. Ophthal Plast Reconstr Surg. 2001;17:346-354.

Font RL, Ferry AP. Carcinoma metastatic to the eye and orbit III. A clinicopathologic study of 28 cases metastatic to the orbit. Cancer. 1976;38:1326-1335.

Wolter JR, Hendrix RC. Osteoblastic prostate carcinoma metastatic to the orbit. Am J Ophthalmol. 1981;91:648-651.

Long MA, Husband JES. Features of unusual metastases from prostate cancer. Br J Radiol. 1999;72:933-941.

Winkler CF, Goodman GK, et al. Orbital metastasis from prostatic carcinoma. Identification by an immunoperoxidase technique. Arch Ophthalmol. 1981;99:1406-1408.

Telera S, Carloia S, et al. Sphenoidal metastasis from prostate carcinoma. Neurochirurgie. 2001;47:61-65.