hamartoma of the retinal pigment epithelium

HAMARTOMA O F T H E RETINAL PIGMENT EPITHELIUM

E D W A R D B. M C L E A N , M.D.

Seattle, Washington

An unusual turrior of the ocular fundus has been characterized as a distinct clini­cal entity and confirmed histopatholo-gically as a hamartoma of the retinal pigment epithelium with secondary in­volvement of retina and vitreous.1 - 8 Con­fusion in the diagnosis of such clinically diverse lesions as choroidal malignant melanoma and retinoblastoma has led to enucleation in several cases.

C A S E REPORT

A 9-year-old boy had decreased visual acuity in the right eye of one year's duration. In 1968, at 2 years of age, the patient had herpetic keratitis of the right eye with minimal tortuosity of the retinal vasculature. Family history was noncontributory for ocular abnormalities.

On April 8, 1975, abnormalities were confined to the right eye; the left eye was normal. Corrected visual acuity was R.E.: 20/400, and L.E.: 20/20. A Marcus Gunn pupillary response was present on the right, and a small right hypotropia was evident. No exophthalmos was present and extraocular move­ments were normal. Faint geographic opaciflcation of the right cornea was secondary to previous her­petic infection. The anterior chamber, iris, and lens were normal. The vitreous was clear. The major lesion of the posterior pole was slightly elevated and occupied the entire macula (Fig. 1). The substance of the lesion was pale, whereas the borders were hyperpigmented and faded into normal coloration near the periphery. There was no evidence of in­flammatory response associated with the lesion. The overlying macular retina was distorted by surface contracture and there was marked secondary tortu­osity of retinal arterioles and veins without conges­tion. The cortical vitreous was clear; however, a fine preretinal membrane was evident and several tufts of condensed vitreous were noted over the disk. The appearance of the optic disk was normal. The elec-troretinogram (ERG) was normal in both eyes. The electro-oculogram (EOG) was asymmetric with a light/dark ratio in the right eye of 1.5 and in the left eye 2.1. The lower limit of normal for the EOG in

From the Department of Ophthalmology, Univer­sity of Washington School of Medicine, Seattle, Washington.

Reprint requests to Edward B. McLean, M.D., Department of Ophthalmology, RJ-10, University of Washington School of Medicine, Seattle, WA 98195.

our laboratory is 1.7. A fluorescein angiogram re­vealed normal retinal vascular flow dynamics and tortuosity of the retinal vessels, but there was no leakage of fluorescein. Choriocapillaris fluorescence was completely blocked by the lesion in the posteri­or pole while peripherally, the angiographie pattern was normal (Fig. 2).

DISCUSSION

By analyzing 20 previously reported cases,1 - 8 we characterized these lesions into two clinically distinct groups based on their location. The first group com­prises 15 juxtapapillary lesions1 - 8 and the second group comprises five cases with more peripherally located tumors.6

The juxtapapillary lesions occurred predominantly in males (13 males, two females) with onset of visual symptoms in most between 20 to 45 years of age. The lesion appeared clinically as a solitary gliotic mass adjacent to the disk with variable amounts of vascularity and black pigmentation surrounding the base of the lesion. With time the lesions developed overlying retinal contracture involving the macula and subsequent impairment of vision. The initial clinical diagnosis in most cases has been juxtapapillary malig­nant melanoma of the choroid, retinoblas­toma, or unspecified malignant neoplasm. Before the Vogel, Zimmerman, and Gass report5 in 1969, these various diagnoses had led to enucleation of five eyes. In each case histopathologic examination demonstrated the benign cytologie char­acteristics of the lesions despite their bi­zarre ophthalmoscopic appearances.

In contrast to the juxtapapillary lesions, the more peripherally located lesions in five patients became symptomatic at an earlier age (3 months to 8 years), and the sex distribution was approximately equal in these few patients.6 Compared to the

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juxtapapillary lesions, the peripherally lo­cated lesions tended to be more extensive, only slightly elevated, and had a broader border of hyperpigmentation. These are only quantitative differences and do not imply etiologic or significant morpholog­ic differences between juxtapapillary and peripheral lesions clinically. The periph­eral tumors were benign and none have been enucleated. The basis for designat­ing the peripheral lesions as hamartomas rests on the reported histology of similar juxtapapillary lesions in the five enucleat­ed eyes. In addition, Gass6 supported this conclusion by citing the report by Duke and Maumenee of a comparable peripher­al lesion with histologie examination.

Despite the clinical differences be­tween these two groups, there are suffi­cient similarities to indicate that they are related variants of the same process. Clin­ically, all the lesions have shown eleva­tion, superficial gliosis, secondary retinal contracture with retinal vessel tortuosity, and peripheral hyperpigmentation at the level of the retinal pigment epithelium. There has been no suggestion of reactive hyperpigmentation or atrophy to imply a current or previous inflammatory process.

The differential diagnosis in young pa­tients with peripheral or macular lesions includes retinoblastoma and Toxocara larval invasion. In older patients the dif­ferential diagnosis must include choroi-dal malignant melanoma and melanocy-toma. The histology in enucleated cases1'2'3'5 has shown proliferation of reti­nal pigment epithelial cells, thickened retina, preretinal membranes, and no evi­dence of malignant change.

The correct clinical diagnosis was un­suspected in the five eyes enucleated when the gliotic component of the lesion was mistaken for retinoblastoma or the hyperpigmented portion mistaken for ma­lignant melanoma of the choroid. The lesion resembles no other common reti­

nal, epithelial, or choroidal lesion, with the possible exception of Toxocara larval invasion which may result in a focal le­sion having a gliotic central mass bor­dered by reactive hyperpigmentation and overlying vitreous changes.

The fluorescein angiographie findings in those patients with juxtapapillary le­sions are sufficiently unusual to serve as a differential point in the diagnosis. Of the 15 lesions reported, seven have been studied with fluorescein angiography. All showed a profuse network of dilated cap­illaries within the tumor and frequently leakage of fluorescein, implying altered capillary permeability. These features distinguish the lesions from melanocy-tomas and juxtapapillary melanomas. In contrast, only two of the five peripherally located lesions have been studied, and the angiographie pattern was not diagnostic. Both cases showed vascular tortuosity and dilation as anticipated, and in one of these there was leakage of fluorescein from the involved retinal vessels. Retinal vascular tortuosity and complete block­age of transmitted fluorescence from the choriocapillaris by the overlying retinal pigment epithelial tumor mass was noted on the fluorescein angiogram of the pa­tient described in this report.

ERG and EOG results were not report­ed in these cases, i _ 8 and it is probably significant that an abnormally low EOG value was obtained in the affected eye of this patient because the extensive lesion occupied most of the posterior pole and was located at the level of the retinal pigment epithelium.

SUMMARY

A 9-year-old boy had a unilateral ocular lesion characterized by a broadly elevated mass at the level of the retinal pigment epithelium. The mass showed hyperpig­mented borders, overlying retinal con­tracture, retinal vessel tortuosity, and vit-

Fig. 1 (McLean). Composite fundus photograph showing full extent of a broadly elevated lesion in the posterior pole with secondary retinal contracture and retinal vessel tortuosity.

VOL. 82, NO. 2 HAMARTOMA OF RETINAL PIGMENT EPITHELIUM 231

Fig. 2 (McLean). Fluorescein angiography, 20 seconds after the first appearance of fluorescence, shows marked retinal vessel tortuosity and complete blockage of transmitted fluorescence by the overly­ing tumor from the choriocapillaris level.

reous condensations. Electrophysiologic testing revealed an abnormal electro-oculogram.

REFERENCES 1. Roveda, J. M: Melanosis de la papila. Arch.

Ophthalmol. 27:61, 1952. 2. Theobald, G. D., Floyd, G. G., and Kirk, H. Q.:

Hyperplasia of the retinal pigment epithelium. Am. J. Ophthalmol. 45:235, 1958.

3. Machemer, R.: Die primäre retinale pigment epithelhyperplasie. Albrecht von Graefe's Arch. Klin. Ophthalmol. 167:284, 1964.

4. Cardell, B. S., and Starbuck, M. J.: Juxtapapil-lary hamartoma of retina. Br. J. Ophthalmol. 45:672, 1961.

5. Vogel, M. H., Zimmerman, L. E., and Gass, J. D. M.: Proliferation of juxtapapillary retinal pig­ment epithelium simulating malignant melanoma. Doc. Ophthalmol. 26:461, 1969.

6. Gass, J. D. M.: An unusual hamartoma of the pigment epithelium and retina simulating choroidal melanoma and retinoblastoma. Trans. Am. Ophthal­mol. Soc. 71:171, 1973.

7. Vogel, M. H., and Wessig, A.: Die proliferation des juxtapapillären retinalen pigment epithels. Klin. Monatsbl. Augenheilkd. 162:736, 1973.

8. Gass, J. D. M.: Tumors of the retinal pigment epithelium. In Differential Diagnosis of Intraocular Tumors. A Stereoscopic Presentation. St. Louis, C. V. Mosby, 1974, pp. 234-246.