A Red and Swollen Eyelid

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 was diagnosed with moderately differentiated, estrogen and progesterone receptor-positive, invasive ductal carcinoma of the left breast (Stage 2, T2, N1, M0). At that time, she underwent modified radical mastectomy, and three lymph nodes were positive for carcinoma. She was then treated with 6 cycles of cyclophosphamide, doxorubicin, and 5-fluorouracil, followed by daily tamoxifen 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.

Erythema, edema, and ptosis of the left upper eyelid. Front (A), left (B), and right (B) aspects of the upper face show the ocular prosthesis (black arrowhead) and asymmetric enlargement, erythema, and ptosis of the left upper eyelid (white arrowheads).

What would you do next?

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

2. Refer for ophthalmologic examination and orbital computed tomography (CT).

3. Prescribe oral amoxicillin-clavulanate for infectious preseptal cellulitis.

4. Obtain positron emission tomography (PET) scan to identify metastases.

Diagnosis

Breast carcinoma metastasis to left lacrimal gland.

What to do next

Refer for ophthalmologic examination and orbital CT.

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

Discussion

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

Figure 2.

Multimodal imaging and histopathology of breast cancer metastases. (A) Axial CT scan shows mild asymmetric prominence of the lacrimal gland and adjacent soft tissue. (B) PET imaging shows increased Tc-99m tracer uptake in posterolateral ribs (white arrowhead) and thoracic spine (black arrowhead), suggesting osseous metastases. (C) Hematoxylin and eosin staining from the lacrimal gland biopsy showed poorly differentiated carcinoma cells with high nuclear-to-cytoplasmic ratio invading into orbital tissue and adjacent lacrimal gland structures (white arrowhead). Immunostains demonstrated estrogen (D) and progesterone (E) positive tumor cells (black arrowheads), often in single-file, invading into lacrimal and orbital tissue, indicating metastasis of breast carcinoma. (C, D, 400X original magnification; E, 200X original magnification)

The differential diagnosis includes infectious preseptal cellulitis, inflammatory conditions such as blepharitis and sarcoid, as well as primary and metastatic tumors. Infectious preseptal cellulitis is often acute or painful, related to a preceding upper respiratory infection (sinusitis) or trauma. No meibomian gland dysfunction was present. These findings made preseptal cellulitis and blepharitis unlikely.¹ A histopathological diagnosis is often the most helpful in establishing the diagnosis, especially to distinguish neoplastic from inflammatory causes. Systemic inflammation such as sarcoidosis; as well as neoplastic etiologies such as lymphoid disorders, lacrimal tumors (e.g. adenoma, pleomorphic adenocarcinoma, adenoid cystic carcinoma, primary ductal adenocarcinoma), and metastatic lesions, should also be considered, given the remote history of two primary cancers (breast carcinoma and choroidal melanoma). ^2,3 One center noted that out of 300 patients with metastatic breast cancer, only 2 patients were diagnosed with orbital metastases (0.67%).⁴

Orbital metastases comprise only 1%–13% of orbital tumors.⁵ The presence of orbital metastasis portends poor prognosis, as mean survival following diagnosis is 31 months.⁶ Orbital CT and magnetic resonance imaging are indicated to initially evaluate orbital mass lesions, while whole-body PET imaging is preferred for staging by detection of metabolically-active distant metastases.² Breast cancer is the most common type of orbital metastases, accounting for 29% in a recent series, followed by melanoma (20%), and prostate cancers (12%).⁶ Metastases of choroidal melanoma to the contralateral orbit remains rare.⁷ Eighty-nine percent of patients with breast cancer metastases to the orbit had a previous diagnosis of breast cancer.⁸

The duration from diagnosis of primary breast cancer to orbital metastases ranges from 4.5 – 6.5 years.⁸ 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.^6,8 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.^7,8 A biopsy is required to establish diagnosis, and orbital breast metastases can be treated with radiation therapy, 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.^6,9

Patient outcome

Systemic investigation revealed evidence for distant metastases. Serologic workup showed normal CA-125 (23.5 U/mL), elevated carcinoembryonic antigen (9 ng/mL, normal < 2.5 ng/mL), CA 15-3 (112.5 U/mL, normal < 30 U/mL), and circulating tumor cells (> 5 per 7.5 mL of blood). A right breast biopsy showed lobular carcinoma in situ. PET scan revealed abnormal uptake in multiple posterolateral ribs and mottled uptake in the thoracic spine (Figure 2B), indicating bony metastases. The patient began anastrozole daily with intravenous bisphosphonate, but was switched to denosumab due to acute renal failure. Over the next 9 months, she experienced worsening fatigue, abdominal discomfort, and decreased appetite. She began 3 bi-weekly injections of fulvestrant. On follow-up, nodular hepatomegaly was noted, liver function tests were elevated, and CT showed diffuse liver metastases. The patient decided to proceed with palliative care, and died approximately 2 months later (1 year following original presentation).