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JAMA Oncology Clinical Challenge
July 2015

A Red and Swollen Eyelid

Author Affiliations
  • 1Department of Ophthalmology, University of Michigan Medical School, Ann Arbor
  • 2Visual Sciences, W. K. Kellogg Eye Center, University of Michigan Medical School, Ann Arbor
  • 3Department of Pathology, University of Michigan Medical School, Ann Arbor
  • 4University of Michigan Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor
  • 5Division of Ophthalmology, Surgical Service, Veterans Administration Ann Arbor Healthcare System, Ann Arbor
JAMA Oncol. 2015;1(4):537-538. doi:10.1001/jamaoncol.2015.0461
Case

A woman in her 80s complained of fullness near her left eye for 2 months. She denied pain, trauma, or changes in vision. Her right eye had been enucleated 40 years before for choroidal melanoma, and she had been fitted with an ocular prosthesis (Figure 1). Twenty-six years before presentation, she had received a diagnosis of moderately differentiated, estrogen and progesterone receptor–positive, invasive ductal carcinoma of the left breast (stage II, T2N1M0). At that time, she underwent modified radical mastectomy, and 3 lymph nodes were positive for carcinoma. She was then treated with 6 cycles of cyclophosphamide, doxorubicin hydrochloride, and fluorouracil, followed by daily tamoxifen citrate for nearly 5 years. There was no evidence of recurrent disease after this treatment. External examination revealed mild edema, erythema, and ptosis of the left upper lid (Figure 1). Left cervical lymphadenopathy was present. Best-corrected visual acuity was 20/25, and left ocular motility was full.

Figure 1.
Photographs of the upper face show the ocular prosthesis (black arrowheads) and asymmetric enlargement, erythema, and ptosis of the left upper eyelid (white arrowheads). A, Front view. B, Left side. C, Right side.

Photographs of the upper face show the ocular prosthesis (black arrowheads) and asymmetric enlargement, erythema, and ptosis of the left upper eyelid (white arrowheads). A, Front view. B, Left side. C, Right side.

Box Section Ref ID

What Would You Do Next?

  1. Recommend eyelid scrubs to the left eyelid for blepharitis.

  2. Refer for ophthalmologic examination and orbital computed tomography.

  3. Prescribe oral amoxicillin sodium–clavulanate potassium for infectious preseptal cellulitis.

  4. Obtain positron-emission tomographic scan to identify metastases.

Read the Discussion.

Discussion
Diagnosis

Breast carcinoma metastasis to left lacrimal gland

What to Do Next

B. Refer for ophthalmologic examination and orbital computed tomography.

The key feature in this case is to recognize that cancer is part of the differential diagnosis. The patient had a history of breast cancer and choroidal melanoma. Because metastatic cancer is the most common ocular malignant neoplasm in adults, a complete examination by an ophthalmologist, including orbital computed tomography (CT), is the recommended initial step.

She was referred to an ophthalmologist, who found a palpable, nontender, nodular mass near the superolateral orbital rim. Funduscopic examination was unremarkable. No blepharitis was present. Orbital CT revealed left lacrimal gland enlargement. Left lacrimal gland and subbrow tissue biopsy revealed discohesive tumor cells with high nuclear to cytoplasmic ratios in an infiltrating pattern. These cells were immunoreactive for estrogen (Figure 2) and progesterone receptors and negative for human epidermal growth factor receptor 2/neu. The diagnosis was consistent with metastasis of poorly differentiated breast carcinoma to the lacrimal gland.

Figure 2.
Immunostains demonstrated estrogen-positive tumor cells (black arrowhead), often in single file, invading lacrimal (white arrowhead) and orbital tissue, indicating metastasis of breast carcinoma (original magnification ×400).

Immunostains demonstrated estrogen-positive tumor cells (black arrowhead), often in single file, invading lacrimal (white arrowhead) and orbital tissue, indicating metastasis of breast carcinoma (original magnification ×400).

The differential diagnosis includes infectious preseptal cellulitis and inflammatory conditions such as blepharitis and sarcoidosis, as well as primary and metastatic tumors. The nonneoplastic etiologies were unlikely, given the absence of pain, infection, trauma, and meibomian gland dysfunction.1 Sarcoidosis, lymphoid disorders, lacrimal tumors, and metastatic lesions should also be considered.2,3 A histopathological diagnosis is often the most helpful in establishing the diagnosis, especially to distinguish neoplastic from inflammatory causes.

Breast cancer is the most common type of orbital metastases, accounting for 29% in a recent series, followed by melanoma (20%). One center noted that of 300 patients with metastatic breast cancer, only 2 patients received a diagnosis of orbital metastases (0.67%).4 Eighty-nine percent of patients with breast cancer metastases to the orbit had a previous diagnosis of breast cancer.5 Metastases of choroidal melanoma to the contralateral orbit remain rare. The duration from diagnosis of primary breast cancer to orbital metastases ranges from 4.5 to 6.5 years.5 Most breast cancer metastases occur in the extraocular muscles, orbital fat, and bone (91%), and thus patients can present with double vision, decreased vision, and pain.5,6 Breast cancer metastatic to the orbit can also present with an unusual feature not characteristic of other types of orbital metastases: enophthalmos, which can be seen in 10% of cases.5 Orbital breast metastases can be treated with radiotherapy, chemotherapy, and hormonal therapies.6 Breast cancer metastatic to the lacrimal gland is rare: to our knowledge this report is only the third case, and the first with histopathological findings described.6,7

Systemic investigation revealed evidence for distant metastases. Serologic workup showed elevated levels of carcinoembryonic antigen (9 ng/mL; reference range, <2.5 ng/mL) and cancer antigen 15-3 (112.5 U/mL; reference range, <30 U/mL), and circulating tumor cells (>5 per 7.5 mL of blood). A right breast biopsy showed lobular carcinoma in situ. A PET scan revealed abnormal uptake in multiple posterolateral ribs and the thoracic spine, indicating bony metastases. The patient began receiving anastrozole daily with intravenous bisphosphonate but was switched to denosumab therapy because of acute renal failure. Over the next 9 months, she experienced worsening fatigue, abdominal discomfort, and decreased appetite. She began 3 biweekly injections of fulvestrant. On follow-up, nodular hepatomegaly was noted, liver enzyme levels were elevated, and CT showed diffuse liver metastases. She decided to proceed with palliative care, and she died roughly 2 months later.

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Article Information

Corresponding Author: Rajesh C. Rao, MD, W. K. Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105 (rajeshr@med.umich.edu).

Published Online: April 9, 2015. doi:10.1001/jamaoncol.2015.0461.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by a grant from the National Eye Institute (K12EY022299) to Dr Rao.

Role of the Funder/Sponsor: The National Eye Institute had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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