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Multiple Bilateral Extraocular Muscle Metastases as the Initial Manifestation of Breast Cancer

Spitzer, Stephen G. MD; Bersani, Thomas A. MD; Mejico, Luis J. MD

Journal of Neuro-Ophthalmology: March 2005 - Volume 25 - Issue 1 - p 37-39
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A 75-year-old woman had gradually progressive binocular diplopia and 2 months later had breast cancer diagnosed. Examination showed bilateral external ophthalmoplegia with lid retraction and lag and no pupillary abnormalities. Orbital magnetic resonance imaging showed enlargement and enhancement of all extraocular muscles bilaterally. A right orbital biopsy was consistent with metastatic breast carcinoma. Positron emission tomography, bone scan, and computed tomography of the chest, abdomen, and pelvis failed to disclose other evidence of breast cancer metastases. It is unusual to encounter metastatic breast cancer affecting every extraocular muscle before the diagnosis of the primary carcinoma.

From the Departments of Neurology (LJM) and Ophthalmology (SGS, TAB, LJM), SUNY Upstate Medical University, Syracuse, New York.

Address correspondence to Luis Mejico, MD, Department of Neurology, 90 Presidential Plaza, Syracuse, NY 13202; E-mail:

Supported by unrestricted grants from Research to Prevent Blindness, Inc, New York City, NY, and Lions District 20-Y1.

A 75-year-old woman had blurred vision on upgaze in January 2003 and diplopia on extreme right gaze in February 2003. In March 2003, she began having binocular diplopia in extreme lateral gaze to either side. There was no daily fluctuation in the diplopia or relationship to rest or exercise. She had occasional eye discomfort and tearing. There had been no change in the appearance of her eyes. Other than a recently decreased appetite, she felt well. Examination by her ophthalmologist at that time was remarkable for impaired abduction and adduction of the OD.

In subsequent days, she noticed dimpling of one of her nipples. A breast incisional biopsy revealed grade 3 breast cancer.

On neuro-ophthalmic evaluation within days of the diagnosis of breast cancer, best-corrected visual acuities were 20/30 OU without improvement with pinhole. Color vision was 8/10 OD and 8.5/10 OS using Hardy-Rand-Rittler color plates, brightness sense was symmetric, and the Amsler grid test was normal. Tangent visual field testing was also normal. The pupils were of equal size and reacted briskly to light. There was no relative afferent pupil defect. The orbital repositus was soft and non-tender and there were no ocular bruits. There was bilateral upper eyelid retraction and eyelid lag but no Cogan lid-twitch sign, fatigue with prolonged upgaze, or seesaw ptosis. Exophthalmometry with a base of 92 was 17 mm OU. Ocular motility examination disclosed that the OD had no abduction, 50% of normal adduction and supraduction, and full infraduction. The OS had full range of motion except for 50% of normal supraduction. The slit-lamp and ophthalmoscopic examinations were normal. Spontaneous venous pulsations were clearly seen ophthalmoscopically. The neurologic examination was normal. Subsequent work-up included normal thyroid function tests and negative anti-Hu and anti-Ri antibodies. A magnetic resonance imaging of the brain and orbits showed no brain abnormalities, but there was dramatic bilateral extraocular muscle enlargement and enhancement (Fig. 1). There was also enhancement of the intraconal fat in the right orbit. Whole-body positron emission tomography scan, bone scan, and computed tomography scans of the chest, abdomen, and pelvis failed to disclose any evidence of metastasis. A right orbital biopsy revealed poorly differentiated breast carcinoma in the retrobulbar fat and medial rectus muscle (Fig. 2).

FIG. 1

FIG. 1

FIG. 2

FIG. 2

The patient completed six cycles of cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), and letrozole (Femara) treatment. Split-beam x-irradiation with 3,000 centigray to the orbits resulted in a full range of ocular motion except for limited abduction OD secondary to postbiopsy scarring of the right medial rectus muscle.

Metastatic cancer has a prevalence of 1% to 13% of all orbital tumors (1). The orbital bone and fat are the most common locations for breast cancer metastasis, although extraocular muscle metastasis is well-documented (2). Although bilateral orbital metastasis is common in breast carcinoma (10% to 61% of cases), rarely are more than two extraocular muscles involved (2-5). Bilateral orbital metastasis affecting all the extraocular muscles, as in our patient, has been reported only twice (6,7).

A primary tumor is typically known at the time that orbital metastasis of breast cancer is discovered. Most reports cite a long interval between diagnosis of the primary tumor and the first orbital metastasis. In a 2002 review, Reeves et al (8) found that the average interval from primary diagnosis to orbital metastasis varied from 4.5 to 6.5 years but could be as long as 20 to 25 years. Furthermore, they concluded that although not uncommon, orbital metastasis secondary to breast carcinoma usually occurs in the context of multi-system end-stage disease in patients with already known primary cancer. Our patient is very unusual in having had manifestations of orbital metastasis before her diagnosis of breast cancer.

Interestingly, our patient had bilateral eyelid lag and retraction in the absence of proptosis. In a comprehensive classification of the various causes of eyelid retraction, Bartley (9) included orbital neoplasms only when there was proptosis. Our patient's findings may be explained by sclerosing carcinomatous muscle infiltration, potentially involving the levator muscles as well. Pathologic shortening of the levator muscle fibers is thought to be the cause of eyelid retraction in patients with thyroid orbitopathy (10).

Our case illustrates that metastatic breast cancer affecting many extraocular muscles could account for ophthalmoplegia even if a diagnosis of the primary cancer has not been made.

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