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Histopathology of Documented Growth in Small Melanocytic Choroidal Tumors
Arch Ophthalmol. 2004;122:1876-1878.
Differentiation of a choroidal nevus from a small choroidal melanoma can be difficult. Choroidal nevi are generally asymptomatic lesions1 that are less than 6 mm in diameter and less than 1.5 mm in height. The presence of drusen or areas of atrophy of the overlying retinal pigment epithelium generally indicate a chronic, inactive choroidal nevus.1 Orange pigment and subretinal fluid are more commonly present in choroidal melanomas.2 Echography usually demonstrates medium to high internal reflectivity in nevi and low reflectivity in melanomas. Documented growth3-4 is widely interpreted as evidence of malignancy.
We provide the histopathology of 2 small choroidal melanocytic tumors that became symptomatic, developed orange pigment, and showed documented growth. One lesion was an epithelioid malignant melanoma; the other was a benign nevus.
Report of Cases
Case 1
A 45-year-old man was examined in May 1996 at the Ocular Oncology Clinic of the University of Michigan Kellogg Eye Center, Ann Arbor, for an enlarging, small juxtapapillary choroidal lesion in his right eye. A photograph from 1994 (Figure 1) showed a flat, brown 3.0 x 1.8-mm choroidal lesion, superior to the disc, without drusen or orange pigment. The lesion had increased to 3.0 x 3.0 mm and developed extensive orange pigment over its surface. Echography revealed a maximal height of 1.5 mm with a medium internal acoustic pattern. The initial diagnosis was a probable melanoma, but a decision was made to observe for evidence of continued growth before initiating therapy. In July 1996, the patient complained of blurred vision in his right eye. Results of an examination showed that the base had further increased to 3.3 x 3.2 mm (Figure 2). Repeat echography revealed that tumor height had increased to 1.7 mm. The patient was advised that the lesion was malignant. He subsequently underwent an unremarkable evaluation for metastatic disease. After reviewing possible options, the patient decided to have his eye removed.
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Figure 1. Fundus photograph of the right eye of case 1 shows a flat, pigmented choroidal lesion superior to the disc.
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Figure 2. Fundus photograph of the right eye of case 1 shows a symptomatic, enlarged choroidal lesion 2 years after the photograph in Figure 1.
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Case 2
A 47-year-old man was examined in April 1995 in the Ocular Oncology Clinic for an enlarging, small pigmented choroidal mass beneath his left macula. A photograph from March 1991 (Figure 3) showed a flat, pigmented 4.3 x 3.2-mm lesion beneath the inferior macula. The lesion had no drusen, orange pigment, or adjacent subretinal fluid. The lesion had increased to 6.0 x 4.0 mm and had focal orange pigment over the surface of the lesion. Echography revealed a maximum height of 2.0 mm with medium internal reflectivity. Because the growth had occurred over a 4-year period, the initial decision was to follow the lesion. In February 1996, the patient complained of constant flickering in the central aspect of his left visual field. The lesion now showed increased orange pigmentation, and the base had increased to 6.5 x 4.5 mm (Figure 4). Repeat echography showed that the internal acoustic pattern and height were unchanged. The patient was advised that the lesion showed evidence of malignancy and underwent a metastatic evaluation, which was unremarkable. After reviewing possible options, the patient elected to have his eye removed.
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Figure 3. Fundus photograph of the left eye of case 2 shows a flat, pigmented choroidal lesion beneath the inferior macula.
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Figure 4. Fundus photograph of the left eye of case 2 five years later shows a clinically symptomatic, enlarged pigmented choroidal lesion beneath the inferior macula.
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Histopathological Findings
Histopathological examination of the right eye of patient 1 (Figure 5) showed a epithelioid cell–type malignant melanoma of the choroid, arising from a preexisting nevus.
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Figure 5. Cross section of the peripapillary choroidal tumor of case 1 shows an epithelioid cell–type malignant melanoma (hematoxylin-eosin, original magnification x100).
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Histopathological examination of the left eye of patient 2 (Figure 6) showed a benign spindle nevus of the choroid with numerous melanophages within the lesion. Multiple histopathological sections through various portions of the tumor failed to show any evidence of melanoma. The clinically apparent orange pigment of the tumor appeared to correlate with the presence of melanophages.
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Figure 6. Cross section of the central aspect of the macular tumor of case 2 shows a benign spindle nevus of choroid with scattered melanophages within the lesion (hematoxylin-eosin, original magnification x100).
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Comment
In the Collaborative Ocular Melanoma Study,5 histopathological examination of 413 eyes with a clinical diagnosis of choroidal melanoma demonstrated a misdiagnosis rate of 0.48%. In contrast to our cases, however, all of those tumors had a height of greater than 2.5 mm. With lesions less than 2 mm in height, it is more difficult to distinguish a nevus from a melanoma.
Recent studies6-8 have documented that certain clinical features are predictive of growth of small melanocytic choroidal tumors. These features include visual symptoms, greater tumor thickness and diameter, presence of orange pigment, absence of drusen, absence of retinal pigment epithelial changes adjacent to the tumor, posterior tumor margin adjacent to the disc, and subretinal fluid. In those studies, growth was presumed to be the key indicator of malignant transformation, as those small lesions were generally treated with globe-preserving therapies with no histopathological confirmation of the malignancy.
The 2 lesions described in this report exhibited many of the clinical features predictive of growth and documented growth, but only one of the lesions was malignant. With the exception of one feature, posterior margin adjacent to the disc, the benign choroidal nevus demonstrated the same array of predictive factors for growth8 as the malignant melanoma did. Moreover, the nevus showed the greater growth in height (2.0 mm vs 1.7 mm), but over a longer period (5 years vs 2 years). On a clinical basis, it was not possible to distinguish this enlarging nevus from a growing melanoma.
Augsburger and colleagues9 have advocated the use of transvitreal biopsy of small melanocytic choroidal tumors to achieve an accurate diagnosis. With their technique, they were able to obtain a sufficient aspirate for cytodiagnosis in 65% of cases, but in 18% of those cases, the biopsy specimen showed intermediate cells consistent with either atypical nevus or low-grade melanoma.
Growth or enlargement of choroidal nevi has been previously documented.1, 10 Our report demonstrates that documented growth is not an unequivocal indicator of melanoma for small melanocytic tumors.
AUTHOR INFORMATION
Correspondence: Dr Vine, University of Michigan Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105 (akv{at}umich.edu).
Financial Disclosure: None.
Victor M. Elner, MD, PhD;
Andrew Flint, MD;
Andrew K. Vine, MD
REFERENCES
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1. Gass JD. Problems in the differential diagnosis of choroidal nevi and malignant melanoma: XXXIII Edward Jackson Memorial lecture. Trans Sect Ophthalmol Am Acad Ophtalmol Otolaryngol. 1977;83:19-48.
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2. Shields JA, Rodrigues MM, Sarin LK, Tasman WS, Annesley WH Jr. Lipofuscin pigment over benign and malignant choroidal tumors. Trans Sect Ophthalmol Am Acad Ophtalmol Otolaryngol. 1976;81:871-881.
3. Augsburger JJ, Schroeder RP, Territo C, Gamel JW, Shields JA. Clinical parameters predictive of enlargement of melanocytic choroidal lesions. Br J Ophthalmol. 1989;73:911-917.
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4. Gass JD. Observation of suspected choroidal and ciliary body melanomas for evidence of growth prior to enucleation. Ophthalmology. 1980;87:523-528.
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5. Collaborative Ocular Melanoma Study Group. Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma study: COMS report No. 1 [published correction appears in Arch Ophthalmol. 1990;108:1708]. Arch Ophthalmol. 1990;108:1268-1273.
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6. Shields CL, Shields JA, Kiratli H, De Potter P, Cater JR. Risk factors for growth and metastasis of small choroidal melanocytic lesions. Ophthalmology. 1995;102:1351-1361.
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7. Collaborative Ocular Melanoma Study Group. Factors predictive of growth and treatment of small choroidal melanoma: COMS report No. 5. Arch Ophthalmol. 1997;115:1537-1544.
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8. Shields CL, Cater JC, Shields JA, Singh AD, Santos MC, Carvalho C. Combination of clinical factors predictive of growth of small choroidal melanocytic tumors. Arch Ophthalmol. 2000;118:360-364.
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9. Augsburger JJ, Corrêa ZM, Schneider S, et al. Diagnostic transvitreal fine-needle aspiration biopsy of small melanocytic choroidal tumors in nevus versus melanoma category. Trans Am Ophthalmol Soc. 2002;100:225-234.
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10. MacIlwaine WA IV, Anderson B Jr, Klintworth GK. Enlargement of a histologically documented choroidal nevus. Am J Ophthalmol. 1979;87:480-486.
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SECTION EDITOR: W. RICHARD GREEN, MD
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