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The rate of breast cancer incidence has increased by ap-
proximately 33% over the past 30 years [1,2]. In patients with
ocular metastasis, the primary tumor is generally diagnosed
prior to ocular manifestation. The average interval between
primary diagnosis and discovery of the metastatic lesion is
generally 4.5 to 6.5 years, but delays of over 20 years have been
reported . Breast cancer generally metastasizes to the orbit
via hematogenous spread and predominantly involves the
choroid , whereas only a limited number of conjunctival
breast cancer metastasis cases have been reported. To our
knowledge, cases of subconjunctival breast cancer metastasis
have not been previously described in the literature, so we
present the first reported case of a metastatic subconjunctival
mass associated with primary breast cancer.
A 41-year-old woman visited our clinic complaining of con-
junctival injection and a foreign body sensation in the left eye,
with no other systemic symptoms. She was treated with antibi-
otics and steroid eye solutions at a local eye hospital, and was
later referred to our clinic because of disease progression. She
had a history of breast cancer and had been treated 2 years pre-
viously with modified radical mastectomy followed by adju-
vant radiotherapy (50.4 Gy, 28 cycles; 1,411.2 Gy in total) and
six cycles of chemotherapy (cyclolphosphamide, methotrexate,
and 5-fluorouracil). Pathological examination revealed an in-
vasive ductal carcinoma (stage T2N1M0) that was moderately
differentiated, negative for estrogen receptor/progesterone re-
ceptor expression, cytokeratin 5/6, and c-erb-B2, and positive
for p53 (positive reaction in more than 51% of tumor cells)
and Ki-67 expression (labeling index of 31% in tumor cells).
Axillary lymph node metastasis was found in 1 out of 18 re-
The best-corrected visual acuity was 20/20 in the right eye
and 16/20 in the left eye, with an intraocular pressure of 9 mm
Hg and 7 mm Hg in the right and left eyes, respectively. A slit
lamp bi-microscopic examination showed a cystic mass under
Metastatic Breast Cancer Presenting as a Subconjunctival Mass
Young Min Park, Jong Ho Park, Seung Uk Lee1, Jong Soo Lee
Department of Ophthalmology, Pusan National University School of Medicine, and Medical Research Institute, Pusan National University Hospital, Busan;
1Department of Ophthalmology, Institute of Medicine, Kosin University College of Medicine, Busan, Korea
J Breast Cancer 2014 March; 17(1): 88-90 http://dx.doi.org/10.4048/jbc.2014.17.1.88
Breast cancer is the most common primary source of orbital me
tastasis. Metastasis occurs through hematogenous spread and
predominantly involves the choroid. We present a case of a meta
static subconjunctival mass associated with primary breast can
cer. To our knowledge, this is the first reported case of its kind. A
41yearold woman presented with complaints of conjunctival in
jection and a foreign body sensation in the left eye. She had a
history of breast cancer and had been treated 2 years previously
with modified radical mastectomy followed by adjuvant radio
therapy and chemotherapy. Slitlamp examination showed a
cystic mass under the temporal bulbar conjunctiva, associated
with dilated overlying conjunctival vessels. An excisional biopsy
revealed a poorly differentiated adenocarcinoma. Positron emis
sion tomography examination for systemic malignancy revealed
multiple systemic metastasis. Metastatic disease should be con
sidered in the differential diagnosis of subconjunctival lesions,
and ophthalmic manifestations can play an important role in the
detection of metastatic spread of a known primary breast cancer.
Key Words: Adenocarcinoma, Breast neoplasms, Conjunctival neoplasms,
Correspondence to: Jong Soo Lee
Department of Ophthalmology, Pusan National University School of
Medicine, and Medical Research Institute, Pusan National University
Hospital, 179 Gudeok-ro, Seo-gu, Busan 602-739, Korea
Tel: +82-51-240-7323, Fax: +82-51-242-7341
Received: November 5, 2013 Accepted: January 6, 2014
Subconjunctival Breast Cancer Metastasis
the temporal bulbar conjunctiva, associated with dilated over-
lying conjunctival vessels (Figure 1). The anterior chamber,
lens, and media were clear, no signs of choroid or retina in-
volvement were observed, and extraocular muscle movement
was not limited. Informed consent was obtained from the pa-
tient before the surgery. An excisional biopsy revealed a poor-
ly differentiated adenocarcinoma positive for carcinoembry-
onic antigen and p53, and negative for gross cystic disease flu-
id protein 15, thyroid transcription factor-1, and estrogen re-
ceptor (Figure 2). Positron emission tomography examination
for systemic malignancy revealed multiple bony metastasis
with bone marrow infiltration, multiple muscular and subcu-
taneous metastasis, multiple lung metastasis with metastatic
subcarinal and left hilar lymph nodes, mesenteric metastasis,
and pancreatic metastasis.
Metastasis to the eye develop most commonly from cancer
of the breast (40%) and the lung (29%) . Freedman and
Folk  reviewed the charts of 112 patients (141 eyes) who
presented with metastasis to the eye or orbit and revealed that
breast cancer was the most common primary tumor (49.1%).
Approximately 5.8% to 9.2% of visually asymptomatic patients
with advanced or metastatic breast cancer develop ocular me-
tastasis, which typically develop 2 to 5 years after the primary
tumor has been detected [7-9]. In our case, an ocular metasta-
sis was found 2 years after the primary tumor was detected.
The subconjunctival space is a potential space between the
conjunctiva and sclera that does not normally contain blood
Figure 1. The slit lamp bi-microscopic finding of subconjunctival mass.
A cystic mass was discovered under the temporal bulbar conjunctiva,
associated with dilated overlying conjunctival vessels.
Figure 2. Histopathologic examination of the biopsy specimen. (A) Section of biopsy specimen lined by adjacent sclera (H&E stain, ×40). Sclera stromal
vessels containing red blood cells were also noted (arrow). (B) Increased nuclear size with increased nuclear/cytoplasmic ratio. Increased pleomorphism.
Lack of differentiation (H&E stain, ×400). (C) Immunohistochemical staining of tumor cells, suggesting a metastatic adenocarcinoma from breast cancer
(immunohistochemical staining for carcinoembryonic antigen, ×200). (D) Immunohistochemical staining of tumor cells, suggesting a metastatic adeno-
carcinoma from breast cancer (immunohistochemical staining for p53, ×200). (E) Immunohistochemical staining of tumor cells, suggesting a metastatic
adenocarcinoma from breast cancer (immunohistochemical staining for gross cystic disease fluid protein 15, ×200). (F) Immunohistochemical staining
of tumor cells, suggesting a metastatic adenocarcinoma from breast cancer (immunohistochemical staining for estrogen receptor, ×200).
Young Min Park, et al.
vessels. Further, unlike the well-vascularized conjunctiva, the
scleral stroma mostly consists of bundles of collagen fibers, oc-
casionally accompanied by blood vessels and fibroblasts. As
breast cancer metastasizes via the bloodstream, ocular metas-
tasis tend to be located preferentially in the posterior uvea .
Metastatic subconjunctival masses are therefore very rare and,
consequently, they can be easily mischaracterized as benign
masses that are independent of the breast cancer. Although the
precise mechanism is unclear, a sclera stromal blood vessel
might have played a role in the metastasis case reported here.
Cancer metastasis to the eye are associated with a poor clin-
ical prognosis, regardless of the type of primary cancer, with an
average survival rate of only 15 months [6,11]. When breast
cancer metastasizes to the eye, the risk of it spreading to the
brain or central nervous system increases significantly. Al-
though many patients die due to systemic disease, up to half of
the patients die due to intracranial progression. The prognosis
of patients with brain metastasis is poor, with a median survival
time of 1 to 2 months in untreated patients and 3 to 6 months
in patients treated with radiotherapy . If the metastasis is
detected early, metastatic lesions can be treated successfully
with modalities such as external beam radiotherapy, radioac-
tive plaque brachytherapy, and immunotherapy . Although
our patient did not have brain metastasis, the treatment time
was delayed due to a late diagnosis. Therefore, metastatic dis-
ease should be considered in the differential diagnosis of sub-
conjunctival lesions, and ophthalmic manifestations can play
an important role in the detection of metastatic spread of a
known primary breast cancer.
CONFLICT OF INTEREST
The authors declare that they have no competing interests.
1. Tijl J, Koornneef L, Eijpe A, Thomas L, Gonzalez DG, Veenhof C. Meta-
static tumors to the orbit: management and prognosis. Graefes Arch
Clin Exp Ophthalmol 1992;230:527-30.
2. Kang E, Kim SW. The Korean hereditary breast cancer study: review
and future perspectives. J Breast Cancer 2013;16:245-53.
3. Stevens RJ, Rusby JE, Graham MD. Periorbital cellulitis with breast can-
cer. J R Soc Med 2003;96:292-4.
4. Wickremasinghe S, Dansingani KK, Tranos P, Liyanage S, Jones A,
Davey C. Ocular presentations of breast cancer. Acta Ophthalmol
5. Ferry AP, Font RL. Carcinoma metastatic to the eye and orbit. I. A clini-
copathologic study of 227 cases. Arch Ophthalmol 1974;92:276-86.
6. Freedman MI, Folk JC. Metastatic tumors to the eye and orbit: patient
survival and clinical characteristics. Arch Ophthalmol 1987;105:1215-
7. Fenton S, Kemp EG, Harnett AN. Screening for ophthalmic involve-
ment in asymptomatic patients with metastatic breast carcinoma. Eye
8. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to the eye. I.
Incidence in 213 adult patients with generalized malignancy. Am J
9. Mewis L, Young SE. Breast carcinoma metastatic to the choroid: analy-
sis of 67 patients. Ophthalmology 1982;89:147-51.
10. Frank KW, Sugar HS, Sherman AI, Beckman H, Thoms S. Anterior seg-
ment metastases from an ovarian choriocarcinoma. Am J Ophthalmol
11. Font RL, Ferry AP. Carcinoma metastatic to the eye and orbit. III. A
clinicopathologic study of 28 cases metastatic to the orbit. Cancer 1976;
12. Tsao MN, Lloyd NS, Wong RK, Rakovitch E, Chow E, Laperriere N, et
al. Radiotherapeutic management of brain metastases: a systematic re-
view and meta-analysis. Cancer Treat Rev 2005;31:256-73.
13. Wong ZW, Phillips SJ, Ellis MJ. Dramatic response of choroidal metas-
tases from breast cancer to a combination of trastuzumab and vinorel-
bine. Breast J 2004;10:54-6.