Malignant Melanoma Arising From a Large Uveal Melanocytoma in a Patient With Oculodermal Melanocytosis

A 51-year-old man with ocular melanocytosis was seen with a pigmented uveal mass that extended from the iris to the macular region in the ipsilateral left eye. Diffuse uveal melanoma was suspected, and multiple foci of extrascleral pigment were discovered at enucleation. Histopathologically, the lesion was a diffuse uveal tumor composed mostly of cells identical to a melanocytoma. In the center of the mass was an island of amelanotic malignant melanoma cells. The extraocular component was consistent with benign melanocytoma. The patient is alive and well after 20 years. Based on observations in this case, we discuss the relationship between ocular melanocytosis and melanocytoma and emphasize that they may represent different clinical expressions of the same congenital pigmentary abnormality.

Ocular melanocytosis is a congenital condition characterized by hyperpigmentation of the uveal tract, sclera, and episclera. When the periocular skin is involved, it is termed ocular melanocytosis or nevus of Ota.¹(pp46-59) Melanocytoma is a deeply pigmented variant of uveal nevus that was originally described in the optic disc but is now known to occur in all parts of the uveal tract.¹(pp101-115), ^2-10 Although both ocular melanocytosis and melanocytoma can give rise to uveal melanoma, there has been a tendency among ophthalmologists to consider them as different entities. We describe a patient with ocular melanocytosis and a large diffuse uveal melanocytoma that gave rise to melanoma.

In April 1979, a 51-year-old white man was referred to one of us (J.A.S.) because of a pigmented lesion in his left eye. His visual acuity was 20/15 OS and intraocular pressure was 8 mm Hg OU. The right eye was normal. The patient had a congenital cutaneous blue nevus, 2 cm in diameter, near the lateral aspect of the left eyebrow but not periocular cutaneous pigmentation. There were several well-defined patches of gray pigmentation on the sclera inferiorly (Figure 1). A dark brown lesion was present in the iris inferotemporally (Figure 2). Gonioscopy revealed that the inferior aspect of the trabecular meshwork was deeply pigmented.

Findings from fundus examination disclosed a pigmented, sectorial, inferotemporal ciliochoroidal mass that measured 15 mm in diameter and 8 mm in thickness. It was contiguous with the pigmented lesion of the iris and trabecular meshwork. The remainder of the choroid inferiorly was deeply pigmented with extension of the flat pigmentation into the central macular region (Figure 3). Fluorescein angiography of the mass demonstrated relative hypofluorescence in the venous phase and mild late hyperfluorescence. A-scan ultrasonography showed a solid mass with gradually diminishing internal reflectivity, and B-scan ultrasonography showed a peripheral choroidal mass with low internal reflectivity.

Based on clinical findings and ancillary studies, our diagnosis was ocular melanocytosis with sector uveal melanocytosis, giving rise to diffuse choroidal melanoma, and enucleation was advised. Inspection of the globe immediately after enucleation disclosed multiple, deeply pigmented nodules on the posterior aspect of the globe inferotemporally and around the optic nerve (Figure 4).

The sectioned globe showed a diffuse, elevated, deeply pigmented uveal mass, measuring 20 × 20 × 8 mm in the inferotemporal quadrant with patches of black pigmentation in the corresponding episcleral tissue (Figure 5). Low magnification microscopy showed cystic degeneration in the peripheral part of the pigmented choroidal mass and a large focus of depigmentation in the postequatorial region (Figure 6). Review of bleached sections showed that the deeply pigmented portions of tumor and the extrascleral nodules were composed of bland, ovoid cells with uniform small nuclei, compatible with the diagnosis of ocular melanocytosis or melanocytoma (Figure 7).² In contrast, the less pigmented foci were composed of spindle cells and a few epithelioid cells, compatible with a mixed-cell type melanoma (Figure 8). No mitotic activity was identified in the numerous sections studied.

Based on the clinical and histopathologic findings, the diagnosis was ocular melanocytosis with segmental uveal melanocytosis forming a melanocytoma with foci of amelanotic choroidal melanoma. The patient is alive and well after 20 years with no local recurrence or metastasis.

Although it was originally described as a lesion of the optic disc,² melanocytoma subsequently has been recognized to occur in the uveal tract, including the iris, ^6,7 ciliary body,^8,9 and choroid. ¹⁰ Patients with ocular melanocytosis have an increased risk of developing uveal melanoma.²(pp46-59), ^2,11,12 Similarly, melanocytoma of the optic disc or uveal tract can spawn melanoma. ¹³ Zimmerman ² has stressed the microscopic similarities shared by ocular melanocytosis and melanocytoma of the optic disc. He coined the term melanocytoma for the pigmented lesions of the optic disc because he observed that the cells comprising such lesions were nearly identical to the cells that diffusely involve the uveal tract in ocular melanocytosis. ²

Based on our experience, we believe that most ophthalmologists consider melanocytoma and ocular melanocytosis to be 2 distinctly different pigmentary conditions. However, in our practice of ocular oncology, we have seen patients who had a melanocytoma of the optic disc that was contiguous with a widespread area of choroidal pigmentation identical to the choroidal changes of ocular melanocytosis.

Our belief that melanocytosis and melanocytoma represent different expressions of the same congenital pigmentary process is also supported by the case reported here. Our patient, who had ocular melanocytosis, also had marked uveal thickening, which was composed of cells identical to those seen in melanocytoma. In 1986, Haas et al ¹⁴ reported a similar case in a 10-year-old boy. They also observed that the cells that comprised the choroidal thickening were identical to those seen in a melanocytoma of the optic disc. In contrast to our case, the tumor in their patient did not have histopathologic evidence of a malignant component.

We believe that there is a variant of ocular melanocytosis characterized by marked thickening of the uveal tract by cells that have features typical of those seen with melanocytoma of the optic disc. This large uveal melanocytoma can undergo malignant transformation into melanoma, as shown in our case. A curious feature of this malignant transformation is that the malignant portion is only minimally pigmented whereas the primary benign lesion is deeply pigmented. We have documented 2 other cases in which a clone of relatively amelanotic melanoma cells was present in a deeply pigmented melanocytoma of the ciliary body.

In summary, our patient with ocular melanocytosis was atypical in that the uveal tract was markedly thickened and assumed tumorous proportions. The deeply pigmented uveal mass was composed of cells identical to those found in melanocytoma of the optic nerve. The melanocytosis contained an area of malignant transformation into amelanotic melanoma cells. The patient is alive and well after 20 years, suggesting that he may have a favorable prognosis. This unusual case underscores the similarity between ocular melanocytosis and melanocytoma and suggests that they may represent variations of the same entity.

This study was supported in part by the Eye Tumor Research Foundation, Philadelphia, Pa; the Paul Kayser Award of Merit in Retina Research, Houston, Tex (Dr J. Shields); the Macula Foundation, New York, NY (Dr C. Shields); CAPES, Brasilia, Brazil (MCMS) (Dr Santos); and the Noel T. and Sarah L. Simmonds Endowment for Ophthalmic Pathology, Wills Eye Hospital, Philadelphia (Dr Eagle).

Presented by Dr J. Shields at the annual meeting of the Eastern Ophthalmic Pathology Society, New York, NY, October 12, 1979.

Reprints: Jerry A. Shields, MD, Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA 19107.