British7ournalofOphthalmology, 1990,74,373-376

Mucinous adenocarcinoma metastatic to the iris,ciliary body, and choroid

Wolfgang E Lieb, Jerry A Shields, Carol L Shields, George L Spaeth

AbstractA 67-year-old woman presented with signsof severe intraocular inflammation andsecondary glaucoma. The initial diagnosis wasuveitis, and an anterior chamber paracentesiswith cytological study of the aspirate failedto establish an aetiological diagnosis. Afterthree trabeculectomies had failed to controlthe intraocular pressure, the blind eye wasenucleated. On histopathological examinationa mucinous adenocarcinoma was found tocover diffusely the iris surface and to involvethe ciliary body and peripheral choroid. Thepatient subsequently developed evidence ofwidespread metastatic disease and died shortlythereafter. Although a primary tumour wasnever found, histochemical and immuno-histochemical studies of the enucleated eyesuggested that the lesion originated in thegastrointestinal tract. In cases of intractableglaucoma and anterior chamber inflammation,metastatic carcinoma should be included inthe differential diagnosis, and efforts shouldbe made to substantiate the diagnosis by asystemic examination or a biopsy.

Wills Eye Hospital,Jefferson MedicalCollege, ThomasJefferson University,Philadelphia, PA, USA,Oncology ServiceW E LiebJ A ShieldsC L Shields

Glaucoma ServiceG L SpaethCorrespondence to:Jerry A Shields, MD,Director, Oncology Service,Wills Eye Hospital, Ninth andWalnut Streets, Philadelphia,PA 19107, USA.Accepted for publication11 January 1990

The commonest primary tumours to meta-stasise to the anterior uvea are breast, lung, andgastrointestinal tract carcinomas. 1-5 Raretumours such as bronchial carcinoid, renal cellcarcinoma, and squamous cell carcinoma of thecervix have been reported to metastasise to theanterior uvea./0 However, in 9%4 to 18%2 ofcases the primary tumour location is unknowndespite extensive investigation.Most metastatic carcinomas occur in the

posterior choroid, and only 5%14 to 1 1%2 occurin the iris and/or ciliary body. Metastatictumours to the anterior segment often present assolitary or multiple nodules on the iris or in theanterior chamber angle, with a diffuse sheddingof cells into the anterior chamber simulating asevere anterior uveitis." `'4 Metastatic tumours tothe iris present with glaucoma in 7% of cases andlater develop increased intraocular pressure inabout half the cases.315 We report a case of a

metastatic carcinoma to the anterior segment ofthe eye that simulated uveitis and producedsevere secondary glaucoma.

Case reportIn December 1984 a 67-year-old woman pre-sented with an inflamed left eye. She was foundto have an 'idiopathic iritis' and was treated withtopical corticosteroids. Several weeks later shedeveloped an intraocular pressure of 62 mmHgin the left eye. The glaucoma did not respond toconventional therapy, and the patient subse-

quently underwent trabeculectomy in March1985. This procedure failed to control theelevated intraocular pressure in her left eye.The patient was seen in consultation at

another hospital in June 1985. The right eye wasentirely normal. The intraocular pressures were15 mmHg in the right eye and 40 mmHg in theleft. The cornea was diffusely oedematous.Unusual translucent material was present on theanterior iris surface near the iridectomy site. Asecond trabeculectomy was performed duringwhich translucent material was removed fromthe anterior chamber. Histological examinationof the material disclosed fibrinous strands withacute inflammatory cells and macrophages. Nobacteria, fungi, or malignant cells were found.

Despite the two prior trabeculectomies thepatient continued to have a painful left eye with araised intraocular pressure and was sent forfurther examination to the Glaucoma Service ofWills Eye Hospital. The intraocular pressurescould not be controlled by conservative medicalmeasures such as oral carbonic anhydraseinhibitors, IB blockers, or topical corticosteroids.Cyclocryotherapy to 1800 of the ciliary body wasperformed. Despite frequent topical cortico-steroid therapy the anterior chamber inflamma-tion could not be controlled. Postoperativelyultrasonography demonstrated inferonasaland inferotemporal choroidal detachments.Although the intraocular pressure was relativelywell controlled, white debris continued toaccumulate in the anterior chamber. An intra-ocular tumour was suspected, and the patientwas referred to the Ocular Oncology Service atWills Eye Hospital.The patient had a history of a breast biopsy for

a.mass that had proved to be benign. There wasno history of cancer. Visual acuity was 6/9 inthe right eye and light perception in the left.Applanation intraocular pressures were 7 mmHgin the right eye and 13 mmHg in the left eye. Theright eye was entirely normal. The left eye had aclear cornea and mild conjunctival injection. Inthe anterior chamber a diaphanous yellowishwhite material covered most of the anterior irissurface, and a moderate amount of cell materialand flare were noted as well as a small hyphaema(Fig 1). There were no nodules in the iris oranterior chamber angle. The fundus could notbe visualised because of the anterior chamberreaction and posterior synechiae.The chronically inflamed, blind painful eye

was enucleated in October 1985.

MACROSCOPIC EXAMINATIONThe specimen consisted of a soft left eyemeasuring 24x24x24 mm, with a short sectionofoptic nerve attached. The cornea was clear and

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Figure 1: Slit-lampphotograph ofthe anteriorsegment after a repeatedtrabeculectomy. There is asmall hyphaema inferiorly.Nasally white fluffymaterial can be seen.

measured 12*5 x 11 5 mm. The anterior chamberwas almost completely filled with a fluffy whitematerial (Fig 2). There was good transillumina-tion, with no shadows seen.The eye was opened vertically to include the

prior iridectomy sites. On opening the globe theperipheral choroid and ciliary body were foundto be thickened superiorly and covered withwhite material. There was also condensation ofthe vitreous in a funnel shaped pattern from thedisc to the posterior surface of the lens.

MICROSCOPIC EXAMINATIONThe cornea appeared normal except in itsinferior part, where a layer of cuboidal cells wasgrowing on to its posterior surface (Figs 3, 4).The cells had vacuolar cytoplasm and ratherlarge atypical nuclei. This monolayer of cellsgrew along the surface of all structures in theanterior chamber and covered most of thetrabecular meshwork. It reflected over theanterior iris surface where it assumed a papillaryfrond pattern (Fig 5). In some sections these cellsgrew around the pupillary margin on to theposterior surface of the iris and extended back tothe pars plicata and the pars plana. In the ciliarybody the mucin-producing cells formed smallcysts containing mucinous material. In theanterior part of the choroid tumour cells werealso seen forming duct-like structures with acentral area of mucin. The remainder of thechoroid, retina, and sclera was normal. Themucinous material stained positive with Alcianblue and was resistant to hyaluronidase. Thematerial also stained positive with periodic acid

Figure 2: Gross specimenshows white material andhaemorrhage in the anteriorchamber, a dense cataract,thickening ofthe ciliarybody, and vitreoushaemorrhage.

Figure 3: Low-power photomicrograph showing parts oftheanterior segment. There is a monolayer ofcells growing on theback surface ofthe cornea, covering the anterior chamberangle, the anterior and posterior iris surface, and extending upto the pars plana. Posterior synechiae are present.(Haematoxylin-eosin, xS.)

Schiff and mucicarmine stains. Immunoperoxi-dase stains for carcinoembryonic antigen (CEA)were highly positive, suggesting that the primarytumour probably originated from the gastro-intestinal tract.

Subsequently the patient underwent a com-plete evaluation for a primary malignancy.The results of the physical examination, includ-ing a breast examination, computed tomographyof the head and abdomen, upper and lowergastrointestinal (GI) tract, proctoscopy, liverfunction studies, electrolytes, and completeblood count were normal. The only abnormalityfound was on the computed tomograph of thechest, in which a small pleural effusion and twopleural nodules were discovered. Aspiration ofthe pleural fluid revealed mucin producingadenocarcinoma cells with a high CEA level of390 ng/ml (normal <5-0 ng/ml).Owing to these findings the patient was re-

examined for a primary tumour in the gastro-intestinal tract, but none was found. She died sixmonths later of pulmonary and cardiac failuresecondary to widespread metastases. Permissionfor a necropsy was not granted.

DiscussionMetastatic tumours to the eye are probably thecommonest intraocular malignant tumours ofadults. As has been shown in several series, theymost commonly involve the posterior choroid.A4Ophthalmological studies do not reflect the trueincidence of these tumours because many meta-stases are never clinically discovered owing totheir occurrence in patients with end stagedisease, who do not undergo ocular examination.

Metastatic tumours to the iris and ciliary bodymay simulate an inflammatory process. In oneseries 10 out of 26 patients with metastases tothe anterior segment presented with uveitis.3Anterior segment metastasis led to secondaryglaucoma in 56%, and many of these casesunderwent antiglaucomatous surgery.3 Themechanism of the glaucoma in these cases isoften two-fold. Besides the thin sheet of tumourcells covering the surface of the iris, the anteriorchamber angle, and the posterior surface of thecornea, the production of mucus leads to a

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Mucinous adenocarcinoma metastatic to the iris, ciliary body, and choroid

Figure 4: high-power photomicrograph showing single layer oftumour cellsforming aretrocorneal membrane and covering the peripheral cornea. (Alcian blue, x 150.)

'mucogenic glaucoma'. 16 In some insttumour induced iris neovascularisation canocclusion of the anterior chamber angleincrease of intraocular pressure. In a fewthe diagnosis was made clinically or bylogical examination of the specimenanterior chamber paracentesis.'7 '9 The ma

of anterior segment metastases were diagafter enucleation for severe late complicatedinflammation and secondary glaucoma, as cred in our case. In several cases an aq

specimen showed only a non-specific inflatory reaction. However, since a large numlprimary tumours that arise from thebreast, or gastrointestinal system producemeasuring the serum level and levels o

antigen in the aqueous should be consimore often.'7 2-22

In our specimen the carcinoma cells coN

the anterior and posterior iris surface stpositive for CEA. This, in combination wiexcessive mucin production and the parfrond-like pattern, suggested the gastrointetract as the most likely site of the pr

)}

Figure 5: High-power photomicrograph showing adenocarcinoma cells growing in a fro;pattern on the anterior iris surface, resembling colonic mucosa. (Alcian blue, x 150.)

tumour. A similar case with the primarycarcinoma located in the caecum has beenreported.'

Several conditions should be included in theace differential diagnosis of metastatic cancer to

the iris and ciliary body. They include irismelanoma, adenoma of the ciliary pigmentepithelium, and granulomatous uveitis. In con-trast to amelanotic melanomas of the iris orciliary body, iris metastases are generally moregelatinous, friable, and yellow. A metastasis maynot present as a solid tumour nodule but ratheras a diffuse sheath of cells covering the anterioriris surface. Only rarely do metastases infiltratethe deep iris stroma or break through the irispigment epithelium into the posterior chamber.Two-thirds of all uveal metastases are purelycellular and do not have stroma vessels thatcould be demonstrated on biomicroscopy orfluorescein angiography.23

Lances Primary adenomas and adenocarcinomas ofcause the non-pigmented ciliary epithelium aree and extremely rare, and metastases have not beencases known to occur."" As Jakobiec et al26 havecyto- pointed out, primary ciliary mucinous tumoursfrom tend to grow in strings and garlands and do not

ljority form complete lumina.nosed Iris metastases can seed cells into the anteriorons of chamber forming a tumour-induced pseudo-)ccur- hypopyon.' Other lesions which may be con-ueous fused with anterior segment metastases includemma- granulomatous uveitis (sarcoidosis or syphilis)ber of and retained foreign bodies. The examinationlung, should be directed to exclude these lesions.CEA, In cases of intractable glaucoma with severeIf this persistent anterior segment inflammation a com-

dered plete systemic examination should be under-taken to exclude a primary malignancy. If that

vering shows nothing, an anterior chamber aspiratetained and/or a peripheral iridectomy may be per-th the formed at the time of the filtering procedure andpillary sent for histological examination. If the diagnosis~stinal of a mucin-producing tumour is made, a distantimary primary tumour should be suspected, and a more

extensive diagnostic examination should beundertaken. If no primary tumour is found andthe patient is systemically well, then radio-therapy to the eye should be administered,approximately 3000 cGy-4000 cGy beinggiven.27 If a primary tumour is found, ocularradiotherapy may be withheld until a response tochemotherapy or hormonal therapy is assessed.28

This work was supported in part by the Ocular Oncology Fundand the Oncology Research Fund, Wills Eye Hospital, and in partby the Black Patch Invitational Golf Tournament, Downington,

PA.

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