Clinicopathologic Report
October 1999

Orbital Metastasis Due to Interval Lobular Carcinoma of the BreastA Potential Mimic of Lymphoma

Author Affiliations

From the Dental Hospital, The Heath, Cardiff, Wales (Dr Wolstencroft); the Departments of Maxillofacial Surgery (Dr Hodder and Mr Sugar), Histopathology (Dr Griffiths), and Radiology (Dr Jones), Morriston Hospital, Swansea, Wales; and Singleton Hospital, Swansea (Dr Askill).




Copyright 1999 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.1999

Arch Ophthalmol. 1999;117(10):1419-1421. doi:10.1001/archopht.117.10.1419

A 53-year-old woman had an orbital mass composed of a neoplastic small round cell infiltrate and no apparent extraorbital primary tumor. Although the initial diagnosis was primary orbital lymphoma, a combination of mucin histochemistry and immunohistochemical staining for cytokeratin and estrogen receptors led to the discovery of an impalpable lobular carcinoma of the breast. We discuss how detailed histopathological assessment can lead to beneficial therapy.

In most large series of orbital metastases, the breast is a major source. The histological type of breast carcinoma, however, is rarely recorded. We report a case of lobular carcinoma presenting 6 months after a mammogram screening that showed no abnormalities and in which the clinical and histological findings were potentially misleading, initially suggesting a diagnosis of lymphoma rather than metastatic carcinoma of the breast.


A 53-year-old woman had an 8-month history of painless swelling of the left cheek and upper eyelid and infraorbital paresthesia. Initial treatment was directed at her left maxillary sinus polyps and retained dental roots. Computed tomographic and magnetic resonance imaging scans 6 months later revealed an intraorbital tumor, both intraconal and extraconal, extending from the apex. Anteriorly, it became a superolateral, extraglobal mass (Figure 1). Biopsy specimens of supramedial and supralateral orbital tissue revealed infiltration by neoplastic cells with relatively bland, monomorphic, round nuclei and a thin rim of cytoplasm, an appearance closely mimicking malignant lymphoma, which is enhanced by the tendency of cells to infiltrate in single file (Figure 2). However, immunohistochemical staining for cells of lymphoid lineage (CLA, UCHL1 and L26) revealed no abnormalities. There was strong positivity for cytokeratin cell adhesion molecule 5.2 (Figure 3, left). A subsequent Alcian blue/periodic acid–Schiff stain revealed an occasional intracytoplasmic mucin droplet with a bull's-eye pattern, blue with a central red dot, a feature highly suggestive of lobular carcinoma of the breast. Immunohistochemistry for estrogen receptor revealed strong nuclear staining, again highly suggestive of a primary tumor of the breast (Figure 3, right).

Figure 1.
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Magnetic resonance imaging scan of orbit showing a superolateral, extraglobal neoplasm (arrow).

Figure 2.
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Small, uniform, noncohesive cells with scanty cytoplasm and bland, monomorphic nuclei infiltrate in single file through fibrous connective tissue (hematoxylin-eosin, ×250).

Figure 3.
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Left, Strong immunopositivity for the epithelial marker cell adhesion molecule 5.2 identifies these as metastatic carcinoma cells (streptavidin-biotin immunohistochemical, original magnification ×400). Right, Dense nuclear staining for estrogen receptor (streptavidin-biotin immunohistochemical, original magnification ×400).

No breast mass was palpable, but an ultrasound scan revealed a lesion 0.6 cm in diameter in the upper quadrant deep to the areola of the left breast, and a fine-needle aspirate confirmed the diagnosis of lobular carcinoma (Figure 4). She was treated with orbital radiotherapy, chemotherapy (cyclophosphamide, fluorouracil, and methotrexate), and tamoxifen citrate. She remains alive but with evidence of persistent orbital disease, enopthalmos, and reduced visual acuity 4 years after the initial visit.

Figure 4.
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Cells obtained by fine-needle aspiration from the breast mass are consistent with a lobular carcinoma (Giemsa, original magnification ×1000).


Metastatic tumors account for up to 13% of orbital masses, most frequently from breast, lung, prostate, and gut.13 The histological nature of metastases from the breast is seldom discussed in reports. Most primary carcinomas of the breast are ductal (80%), while 3% to 14% are lobular.

Scirrhous carcinoma, ie, ductal carcinoma with a high collagen content, may produce enophthalmos, blepharoptosis, and ocular palsy,3 presumably due to a mechanism similar to scar contracture. Lobular carcinoma has been noted to metastasize to the eyelid where it exhibits a foamy cytoplasmic appearance mimicking histiocytes, leading to confusion with the benign entity of xanthelasma.4 Van der Heijden et al5 reported a case of lobular carcinoma 5 years after mastectomy, with diplopia due to isolated infiltration of right inferior rectus and inferior oblique muscles. Reifler and Davison6 described the use of fluorescent immunohistochemistry to demonstrate estrogen and progesterone receptors in a 62-year-old with pain, ptosis, and ophthalmoplegia due to a metastatic lobular carcinoma. A palpable breast mass and axillary nodes were present.

Our patient was initially thought to have malignant lymphoma on the basis of the high nucleocytoplasmic ratio, nuclear uniformity, the single file and discohesive pattern of infiltration, and the absence of a known primary tumor. In the series by Shields et al1, orbital metastasis was the initial complaint in 9 (25%) of 35 cases of metastatic tumors of the orbit. In 4 a primary tumor was never found, 2 were from the breast, 2 from the lung, and 1 from the prostate. Both breast cases had a palpable mass. In the series by Font and Ferry,3 61% of the cases had isolated metastasis to the orbit, and in 10 of these 17 cases the primary site was never found. Goldberg et al,2 in their more recent review, report that slightly more than 25% of cases of breast cancer metastatic to the orbit have an orbital tumor as the first sign of cancer.

Median survival after surgery for orbital metastasis from all primary sites has been estimated at 15.6 months.3 In the series by Shields et al,1 patients with orbital metastases from the breast survived for an average of 21 months, compared with 4 months for lung and a combined average of 13 months for metastases from all primary sites. In the series of Goldberg et al,2 median survival for breast cancer first noted by an orbital tumor was 12 months.

This case is unusual in that, although the breast has been identified as the primary source of orbital metastatic disease, there has never been a palpable lesion. This, combined with the histological appearance of a small round cell infiltrate, could lead the unwary into a mistaken diagnosis of primary lymphoma, and this case illustrates the contribution that modern histological diagnostic procedures can make in evaluating metastatic disease. The relatively long survival also emphasizes the benefits of referral to a specialist oncological service.

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Article Information

Accepted for publication June 14, 1999.

Corresponding author: A. P. Griffiths, BSc, MBBS, MRCPI, MRCPath, Morriston Hospital, Histopathology, Swansea 6A6NL, Wales.

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