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Branch Retinal Artery Occlusion Caused by an Embolus of Metastatic Gastric Adenocarcinoma
Arch Ophthalmol. 2002;120:1209-1211.
We report a case of branch retinal artery occlusion caused by an embolus
of metastatic gastric adenocarcinoma. A 67-year-old man sought treatment for
sudden visual loss in his left eye. He had a medical history of gastric cancer
with liver metastasis. Findings on funduscopic examination included localized
edema of the inner retina consistent with a supratemporal branch retinal artery
occlusion and a yellowish-white subretinal mass surrounded by shallow retinal
detachment superior to the equator. Histopathological and immunohistochemical
examinations of the eye obtained post mortem showed positive staining of the
choroidal tumor for epithelial membrane and carcinoembryonic antigens. In
addition, an embolus of tumor cells was found to cause occlusion of the retinal
artery.
Occlusion of the retinal artery is mostly ascribed to either embolus,
thrombus, or vasculitis. It is strongly associated with carotid atheromatous
plaque or cardiac valvular diseases with vegetation. Other causes, such as
atrial myxoma, temporal arteritis, periarteritis nodosa, and systemic lupus
erythematosus, have been described but are relatively rare.1
Embolism caused by neoplastic cells is extremely rare.2-3
We report a case of gastric adenocarcinoma that metastasized to the choroid
and occluded a branch retinal artery with an embolus of carcinoma cells.
Report of a Case
A 67-year-old man was referred to our clinic for sudden visual loss
in his left eye. He had been diagnosed with gastric adenocarcinoma and metastatic
liver cancer 2 years previously and had undergone total gastrectomy and partial
resection of the liver. He had no history of hypertension, diabetes mellitus,
heart disease, or cerebral infarction. On examination, the corrected visual
acuity was 20/30 OD and light perception OS. Intraocular pressures were 13
mm Hg OD and 10 mm Hg OS. A relative afferent pupillary defect was observed
in the left eye. External and slitlamp examinations were unremarkable bilaterally.
Funduscopic examination revealed milky-white retinal edema consistent with
branch retinal artery occlusion in the supratemporal quadrant and a yellowish-white
subretinal mass surrounded by shallow retinal detachment in the superior quadrant
of the left eye (Figure 1).
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Figure 1. A funduscopic photograph shows
milky-white retinal edema in the supratemporal quadrant, which is compatible
with branch retinal artery occlusion. Note also the yellowish-white subretinal
mass surrounded by shallow retinal detachment superior to the equator of the
left eye.
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Ultrasonography disclosed a mass with strong internal echoes in the
same region, suggestive of a subretinal tumor. The provisional diagnosis of
the mass lesion was metastatic adenocarcinoma to the choroid associated with
branch retinal artery occlusion. Fluorescein angiographic and computed tomographic
examinations could not be performed because of the patient's poor general
condition. Laboratory values included a carcinoembryonic antigen level of
722 ng/mL (reference level, <5 ng/mL) and a carbohydrate antigen 19-9 level
of 2567 U/mL (reference level, <37 U/mL). Cultures of arterial blood were
negative for bacteria, and splenomegaly was absent. A chest radiograph showed
no concrete evidence of a metastatic tumor. Three weeks after admission, the
patient died because of the deterioration of his general condition. Both eyes
were obtained post mortem, fixed in formaldehyde, and processed routinely
for light microscopy. Macroscopic examination disclosed a solid tumor with
a mottled dark-brown color that measured 12 mm x 6 mm in the choroid
of the left eye. Microscopic examination of the tumor disclosed extensive
infiltration of the choroidal stroma by cords and lobules of a malignant epithelial
neoplasm consistent with metastatic mucin-secreting adenocarcinoma. The tumor
cells formed tubules and glandular structures (Figure 2A), and the periodic acid–Schiff and alcian blue stains
confirmed the presence of numerous intracytoplasmic vacuoles of mucin (Figure 2B). Immunohistochemical stains showed
intense positive immunoreactivity for epithelial membrane antigen (Figure 3A) and carcinoembryonic antigen (Figure 3B). The histopathological findings
of the choroidal metastasis resembled the patient's primary tumor (Figure 4) and were consistent with a moderately
well-differentiated gastric adenocarcinoma. A micrometastasis was also identified
in the ciliary body inferior to the muscle. In addition, an embolus of tumor
cells was found to totally occlude the lumen of the supratemporal retinal
arteriole near the optic disc (Figure 5). The cytological characteristics of the tumor embolus were quite similar to
those of the choroidal tumor. The right eye was normal on gross examination,
and there were no particular histopathological changes.
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Figure 2. A, Hematoxylin-eosin staining
shows the tumor to be a moderately well-differentiated adenocarcinoma based
on the presence of tubulelike or glandlike structures. B, Positive periodic
acid–Schiff staining is indicative of mucin production by carcinoma
cells, especially by cells forming glandlike structures (original magnification
x180).
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Figure 3. A, Positive immunostaining for
epithelial membrane antigen on the membrane of cells is related to the tubulelike
or glandlike structures of the tumor. B, Diffuse and strongly positive immunostaining
for carcinoembryonic antigen of the tumor is shown (original magnification
x180).
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Figure 4. A representative microphotograph
shows moderately well-differentiated adenocarcinoma of the stomach. The section
was taken from the surgical specimen (original magnification x180).
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Figure 5. The retinal artery is completely
occluded by a tumor embolus (original magnification x180).
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Comment
The present study clearly shows that the choroidal tumor was metastatic
adenocarcinoma. Histopathological examination also confirmed that the supratemporal
retinal arteriole was occluded by an embolus of tumor cells. The histopathological
and immunohistochemical studies, including positive immunoreactivity markers
for epithelial membrane antigen and carcinoembryonic antigen, are consistent
with metastatic gastric adenocarcinoma; a primary tumor with known hepatic
metastasis had been treated 2 years earlier. The patient is presumed to have
died from widespread systemic metastases because postmortem examination was
limited to the eyes.
To our knowledge, retinal artery occlusion caused by an embolism of
tumor cells is very rare, and there are only a few reports that clearly describe
this condition. Occlusion of the central retinal artery by chondrosarcoma
and bronchial carcinoma cells was described by Burde and Henkind2
and Tarkkanen et al,3 respectively. Zamora
et al4 reported a case of branch retinal
artery occlusion in a patient with papillary fibroelastoma of the mitral valve,
but there was no histopathological demonstration of the embolus. Metastasis
of carcinoma cells to the retina alone appears to be a rare event. Smoleroff
and Agatston5 reported a case of gastroesophageal
carcinoma that metastasized into the nerve fiber layer of the retina. Shields
et al6 studied 520 eyes with uveal metastasis
and found only 5 to have metastatic lesions in the retina.
However, there was no description of arterial occlusion in their series.
In patients with end-stage disease, particularly those with malignancies,
embolism due to bacterial endocarditis, nonbacterial thrombotic endocarditis,
or thrombi formed with disseminated intravascular coagulation syndrome may
be encountered in the retinal artery.7-8
In the present case, there was no strong clinical or laboratory evidence of
infection, valvular diseases, or disseminated intravascular coagulation. Complete
obstruction of the arterial lumen by the tumor embolus as shown in our case
is uncommon, whereas venous and lymphatic invasion by malignant cells is more
common because it can be observed in routine surgical specimens. A major factor
that contributes to the formation of tumor emboli is the expression of adhesion
molecules,9 but emboligenic factors such
as those mentioned above may accelerate their formation.
In conclusion, we report a clinicopathological correlation of a case
of metastatic gastric adenocarcinoma to the choroid that had branch retinal
artery occlusion due to a tumor embolus. Ophthalmologists should be aware
of this cause of acute visual loss in their differential diagnoses of retinal
artery occlusion in patients with a history of malignancy.
AUTHOR INFORMATION
The authors have no proprietary interest in any aspect of this report.
Hisashi Masuda, MD;
Akihiro Ohira, MD, PhD;
Yuzo Shibuya, MD;
Taiji Takanashi, MD;
Liliam Pineda, MD;
Takayuki Harada, MD, PhD
Izumo, Japan
Corresponding author and reprints: Akihiro Ohira, MD, PhD, Department
of Ophthalmology, Shimane Medical University, 89-1 Enya, Izumo, Shimane 693-8501,
Japan (e-mail: aohira{at}shimane-med.ac.jp).
REFERENCES
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4. Zamora RL, Adelberg DA, Berger AS, et al. Branch retinal artery occlusion caused by a mitral valve papillary
fibroelastoma. Am J Ophthalmol. 1995;119:325-329.
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5. Smoleroff JW, Agatston SA. Metastatic carcinoma of the retina: report of a case, with pathologic
observations. Arch Ophthalmol. 1934;12:359-365.
FULL TEXT
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6. Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes with uveal metastases. Ophthalmology. 1997;104:1265-1276.
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7. Deppisch LM, Fayemi AO. Non-bacterial thrombotic endocarditis. Am Heart J. 1976;92:723-729.
FULL TEXT
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8. Cogan DG. Ocular involvement in disseminated intravascular coagulopathy. Arch Ophthalmol. 1975;93:1-8.
ABSTRACT
9. Weiss L. Cell adhesion molecules: a critical examination of their role in metastasis. Invasion Metastasis. 1994-95;14:192-197.
SECTION EDITOR: W. RICHARD GREEN, MD
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