D I A G N O S I S O F M E T A S T A T I C T U M O R S O F T H E

A N T E R I O R O C U L A R S E G M E N T *

W I L L I A M H . MIDDLETON, M.D. Alton, Illinois

Metastatic tumors of the anterior ocular segment may arise through blood-stream me-tastases from a primary tumor elsewhere in the body or by implantation from a neoplasm of the posterior segment. Involvement of the anterior part of the eye by blood-borne me­tastasis is rare, there being only 35 recorded cases in the literature. According to Greear1

there are no more than six cases of proved metastatic carcinoma to the iris without other ocular involvement.

Although in most cases the patient with a metastatic lesion of the eye is suffering from a known malignancy, occasionally the ocular metastasis is the first sign of neoplastic dis­ease. In such instances the differential diag­nosis between a primary and a metastatic tumor of the iris is difficult. In many cases metastatic tumors may simulate inflammatory nodules or hypopyon. Three cases will be presented to illustrate these difficulties in di­agnosis.

CASE REPORTS

CASE 1

This case illustrates the simultaneous in­volvement of iris and choroid by metastatic carcinoma.

E. H., a 50-year-old woman, noticed a pinkish-white mass on the iris of her left eye one morning while looking in the mirror. Her general health at this time was good except for some vague abdominal distress.

Vision in the left eye was 2 0 / 2 0 ; tension and f undus were normal. No other ocular ab­normalities were found other than the small pinkish-white tumor which appeared very prominent on a blue iris. The eye was enu-

* From the Department of Ophthalmology, Uni­versity of Illinois School of Medicine, and the Illinois Eye and Ear Infirmary, Chicago, Illinois. Read before the Chicago Ophthalmological Society, April, 1951.

cleated within three weeks after the tumor was first discovered. The patient died two months subsequently. Unfortunately, no in­formation is available concerning her final illness and no autopsy was done.

Microscopic examination of the eye re­vealed the iris and ciliary body on one side to be replaced by a tumor mass which infiltrated

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mM^^tM"-'"" ■* Fig. 1 (Middleton). Metastatic adenocarcinoma of

iris (Case 1).

the trabeculum and Schlemm's canal in this region. The tumor was composed of large pale-staining cells containing large round or oval nuclei which varied considerably in size and staining density and contained prominent nucleoli. The cells were arranged around cen­tral lumina in crude glandular formation (fig. 1) . Two small nests of tumor cells were present in the choroid, one on each side of the optic nerve (fig. 2 ) .

The metastatic tumors in this case are adenocarcinomas, but without additional in­formation it is impossible to state the origin of the primary tumor with exactness.

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1330 W I L L I A M H. M I D D L E T O N

Fig. 2 (Middleton). One oi the metastic nodules to the choroid (Case 1).

tuberculin skin test, and normal X-ray films of the left orbit and hands and feet. Chest X-ray studies were reported as "suspicious," although a definite X-ray diagnosis was not made at this time.

In two weeks the iris nodule had enlarged to six mm. in diameter and was touching the posterior cornea. Vision had dropped to 20/200. The sclera showed intense conges­tion, the cornea was edematous, aqueous ray was positive, tension was 18 mm. Hg (Gradle) (fig. 3). Transillumination showed the nodule to be solid. The fundus could be seen with fair clearness and appeared normal.

In view of the sudden onset, rapid progres­sion, and intense inflammatory symptoms, it was felt that the iris nodule was inflammatory in nature. The patient received atropine, systemic penicillin, foreign-protein therapy, and streptomycin iontophoresis without bene­fit. The eye rapidly deteriorated and pain became so intense that enucleation was pre­formed on May 8th.

Shortly thereafter the patient developed weakness of the right arm and leg, severe headaches, and papilledema of the right disc.

CASE 2

F. H., a 37-year-old man, was seen for the first time April 14, 1948, complaining of pain and tenderness in the left eye. There was no history of a blow or injury of any kind.

Examination of the eye revealed a small white nodule on the anterior surface of the iris at the 4-o'clock position near the base. The globe showed pericorneal injection and tenderness to pressure over the region of the ciliary body. Vision was 20/20. The right eye was normal.

Laboratory work-up showed a negative blood Wassermann and spinal tap, negative

Fig. 3 (Middleton). External photograph, Case 2, showing large iris tumor. Note intense congestion of globe.

TUMORS OF THE ANTERIOR SEGMENT 1331

Fig. 4 (Middleton). Metastatic carcinoma of iris and ciliary body (Case 2).

X-ray studies of the chest now revealed a definite tumor of the left upper lung. The patient died on May 30th.

Microscopic examination of the eye showed that the iris on one side had been re­placed by a large tumor mass composed of undifferentiated cells growing in sheets and columns (fig. 4 ) . The tumor extended into the ciliary processes and the trabeculum. Within the tumor were large a reas . of necrosis containing masses of leukocytes (fig. 5 ) .

An autopsy report, kindly furnished by Dr. Horace K. Giffen, directory of laboratories, Youngstown Hospital Association, Youngs-town, Ohio, revealed a bronchogenic cari-noma of the left upper lobe with metastases to the peribronchial lymph nodes and the brain. The lung tumor was characterized by moderately large cells with poorly defined cell borders, pale, finely granular cytoplasm, and vesicular, moderately large round or oval nuclei, thus corresponding closely to the cells found in the iris tumor (fig. 6 ) .

CASE 3

This case illustrates involvement of the anterior segment by intraocular metastases from a tumor in the posterior segment. An unusual feature is the inflammatory symp­toms which obscured the diagnosis.

J. B., a nine-year-old Negro, was first seen at the Illinois Eye and Ear Infirmary on May

10, 1948. Three months previously he had been kicked in the left temple, following which the eye had become inflamed and vision declined. Five years previously he had had a squint operation at Cook County Hospital.

Examination showed the right eye to be normal ; left eye: vision 20/70, tension 51 mm. H g (Schip'tz). The bulbar conjunctiva was slightly injected. The lower portion of the anterior chamber was filled with a white exudate, and there were clumps of the same material on the anterior surface of the iris, the anterior lens capsule, and floating free in the chamber. A space of about one mm. between the iris and anterior lens capsule was noted. The lens was clear. The vitreous con­tained floating opacities. The fundus could not be seen except for a dull red reflex.

Laboratory work including tuberculin skin and X-ray studies of the skull, orbit, and chest were all normal. Three aspirations of the anterior chamber were performed and in

Fig. 5 (Middleton). Higher-power view of tumor in Figure 4, showing massive necrosis and leukocytic infiltration.

1332 W I L L I A M H. M I D D L E T O N

Fig. 6 (Middleton). Primary bronchogenic carcinoma (Case 2 ) .

one instance the chamber was irrigated. Cul­tures and guinea pig inoculations of the as­pirated material were negative. The vision of the left eye declined to light perception. Tumor was suspected, and on June 9, 1948, the eye was enucleated.

Shortly thereafter the patient developed swelling of the cervical lymph glands and biopsy of one of these showed metastatic tumor. He received X-ray therapy to the left socket and cervical regions without benefit. Before death, a metastatic lesion in the right upper humerus developed.

Microscopic sections of the eye revealed a retinoblastoma just posterior to the ora ser-rata, with multiple intraocular metastases. Over the iris a thick layer of tumor cells was arranged around blood or lymph spaces. From here the tumor had invaded the iris, trabeculum, canal of Schlemm, and ciliary body (fig. 7).

DISCUSSION

Primary tumors of the iris such as malig­

nant melanomas, epithelial tumors, and leio-miomas may be very difficult to distinguish from metastatic lesions or from each other. Metastatic nodules to the iris may be single or multiple, and present in one or both eyes. They may be located at the base of the iris or at the pupillary margin, and their size may vary from pinpoint to a large mass filling the anterior chamber. Their color may be white, yellowish-white, pink, red, brown, or gray.

Tn approximately one half of the reported

Fig. 7 (Middleton). Involvement of anterior segment by retinoblastoma (Case 3 ) . Note tumor-cell hypopyon.

cases the iris nodules are extensively vascu-larized, a feature which McKee2 stated was also characteristic of primary malignant mel­anoma of the iris. In general metastatic iris tumors grow more rapidly than primary ones and pain and secondary glaucoma are almost always present.

The dark color of most primary iris tumors is a valuable point of differentiation although a melanoma without pigment (leukosarcoma) may simulate exactly a metastatic lesion.

TUMORS OF THE ANTERIOR SEGMENT 1333

Cysts of the iris can usually be diagnosed by transillumination.

It is usually stated that inflammatory symp­toms are rare with metastatic tumors, but in 40 percent of the 35 reported cases of blood-borne metastases to the anterior ocular segment definite signs of iridocyclitis were present, such as in the second case reported here. In several of these cases the marked iridocyclitis temporarily obscured the diag­nosis.

Thus, in the case reported by Stallard3 the patient gave a history of syphilis, the Wasser-mann reaction was positive, and there was a typical Argyll Robertson pupil in the right eye. The left eye showed circumcorneal injec­tion, and a pink-buff colored mass was pres­ent in the iris root between the 9- and 11-o'clock position and contained dilated vessels on the surface. The aqueous ray was positive. Punctate keratic precipitates and broad pos­terior synechias were present.

The first diagnosis was syphilitic iritis and gumma of the iris. However, four weeks later the patient died of carcinoma of the lung and the iris tumor proved to be a metastatic carcinoma. Stallard states that inflammatory features are more evident in metastatic car­cinoma of the iris than when the choroid is involved.

In Kreibig's4 case the first eye symptoms were those of iridocyclitis. A strongly posi­tive tuberculin reaction seemed to confirm the diagnosis of tuberculous nodular iritis, but the nodule later proved to be metastatic from a bronchogenic carcinoma. Kreibig called attention to the recurrent hemorrhages into the anterior chamber in this case and considered them an important diagnostic point as they practically never occur with nodular iritis.

Several cases of retinoblastoma with meta­static seeding of tumor cells into the anterior chamber resembling an inflammatory hypo­pyon have been reported. Walker5 described such a case in a boy, aged four years, in whom a yellow-brown hypopyon was present (from tumor cells). The eye was painful,

injected, and the tension was elevated. The lens was clear but only a dull-brown retinal reflex was present. A paracentesis and irriga­tion of the anterior chamber were performed.

Another case reported by von der HoeveG

also contained a tumor-cell hypopyon. In the discussion of von der Hoeve's paper, Dr. Friedenwald mentioned another case of retinoblastoma which was confused with tuberculous iritis, and in which the preauric-ular glands were enlarged due to tumor metastasis, which he stated, is very rare. This is strikingly similar to the third case pre­sented here.

It is very unsual for carcinoma to spread within the eye by seeding, although in one of Greear 's1 cases a small nest of tumor cells was growing on the anterior iris surface, pre­sumably engrafted there from a large meta­static carcinoma of the ciliary body on the opposite side. Goldsmith7 has reported car-cinomatous cells growing free in the anterior chamber in the manner of a tissue culture.

Of the 35 cases of blood-borne metastatic tumor involving the anterior segment re­ported to date, 31 were carcinoma, three were metastatic melanoma, and one a sarcoma. In approximately one third of these cases cho-roidal lesions were also present, and in others the iris and ciliary body were simultaneously affected. The primary tumor was known in 32 cases. Breast carcinoma accounted for 14, lung carcinoma five, cancer of the gastro­intestinal tract four, hypernephroma two, malignant melanoma of the opposite eye two, skin melanoma one, sarcoma of the ovary one, and carcinoma of the thyroid, prostate, and epididymis one each. The duration of life after discovery of the ocular lesion varied from two to seven months in the reported cases.

T R E A T M E N T

Of course, all treatment is palliative. In many cases enucleation is necessary for the relief of pain which is often intense. Lemoine and McLeod8 reported the arrest of activity of a metastatic carcinoma to the choroid by

1334 E. RAUBITSCHEK

X-ray therapy. A solitary iris nodule may be removed by iridectomy if the diagnosis is in doubt. However, as in our Case 3 and other cases in the literature in which a para-centesis was performed for diagnosis of the cause of a hypopyon, this procedure ap­parently resulted in an extrabulbar exten­sion of the tumor and metastases to the •regional lymph nodes and the orbit. There­fore, it is doubtful whether it is ever advisa­ble to perform a paracentesis in such cases of hypopyon in children, unless perhaps the cellular material is immediately frozen, stained, and studied under the microscope at the time of operation so that enucleation can be proceeded with immediately in case tumor cells are found.

S U M M A R Y

In summary, three cases of metastatic

When I first described my astigmatic test, which is based on the use of a specially con­structed arrow,1 - 3 and demonstrated it at the Amsterdam Ophthalmological Congress in 1929, it won interest and approval and was considered a serviceable device of high sensitiveness. Some later favorable refer­ences to the test were made by Pascal4 and Gat.5

In the interval, other very delicate methods gained predominance, most of them based on the Jackson cross cylinder.6 '7 Jackson's test has been further refined by Crisp and Stine8

e tumors to the anterior ocular segment are s presented, two arising by blood-borne metas-i tasis from systemic carcinoma, one by im­

plantation of cells from a retinoblastoma. In e patients with tumors of the anterior ocular

segment a search for a primary focus else­where, particularly in the breast and lungs,

e should be made. Such metastatic tumors either from a systemic origin or from the posterior segment of the eye may simulate in-

f flammatory lesions of the anterior ocular ; segment.

427 Bluff Street. t —

I wish to express my thanks to Dr. Georgiana Theobald who kindly made available the microscopic

l" material on the three cases herein presented. I wish to express my thanks to Dr. Hedwig Kuhn

of Hammond, Indiana, for permission to report the second case. The completeness of her records, which include an autopsy report, and the interesting and unusual aspects of her case gave the stimulus for

; this paper.

using the cross-cylinder against Verhoeff's rotating cross as a target. Lebensohn9 pro­posed a modification using his "astigmome-ter" in which he adds to the cross an inverted V, the arms 60 degrees apart, to act as a pointer. Stine10 agrees to Lebensohn's modi­fications with some reluctance, claiming that the addition of more lines complicates the simplicity of the two-line cross.

Without disparaging the other tests, I believe that the "arrow test" has these special characteristics which make it a valuable test for astigmatism.

REFERENCES

1. Greear, J. N., J.: Am. J. Ophth, 33 :101S, 19S0. 2. McKee, S. H.: Arch. Ophth., 28 :197, 1942. 3. Stallard, H. B.: Brit. J. Ophth, 24 :S41, 1940. 4. Kreibig, W.: Ztschr. f. Augenh, 93 :278, 1937. 5. Walker, C. H.: Tr. Ophth., Soc. U. Kingdom, 35 :363, 1915. 6. von der Hoeve. J.: Tr. Ophth. Soc. U. Kingdom, 45 :256, 1925. 7. Goldsmith, A. J. B.: Brit. J. Ophth, 29 :136, 1945. 8. Lemoine, A. N , and McLeod, J.: Arch. Ophth, 16 :804, 1936.

T H E R A U B I T S C H E K A R R O W T E S T F O R A S T I G M A T I S M

E. RAUBITSCHEK, M.D. Baghdad, Iraq