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Color as a Risk Factor in Iris Melanoma
COLOR AS A RISK FACTOR IN IRIS MELANOMA JACK R O O T M A N , M . D . ,
AND R I C H A R D P. G A L L A G H E R ,
Vancouver, British Columbia,
M.A.
Canada
We reviewed 23 iris melanomas for iris color and gross tumor pigmentation. Patients with iris melanoma had lighter irides than both population controls (χ2 = 58.0; P <.0001) and other patients with uveal melanoma (χ2 = 17.1; P =.002). Amelanotic and lightly melanotic tumors occurred predominantly in the patients with light irides.
When we learned that iris color was a significant risk factor in a study of ocular melanoma (R. P. Gallagher, J. M. Elwood, J. Rootman, J. J. Spirelli, G. B. Bell, and J. Birdsell, unpublished data), we decided to conduct a retrospective clinical review of all iris melanomas seen in a single ocular oncology practice. We were particularly interested in whether the same trend of higher risk for lighter eye colors in ocular melanoma would be more pronounced in iris melanoma. S U B J E C T S AND M E T H O D S
We reviewed all ocular melanomas seen at the ocular oncology clinic of the University of British Columbia from 1977 to 1983. The catchment area for the clinic includes the entire province of British Columbia with a population of some 2.6 million. Of 93 ocular melanomas, 23 were iris melanomas with only one of these cases being a referral from outside the province. Color photographs were available for 20 patients and chart de scriptions and drawings were available for the remaining three. Iris color was classi fied as blue, gray, green, hazel, or brown and gross tumor pigmentation was re-
Accepted for publication May 21, 1984. From the Department of Ophthalmology, Eye Care Center, Vacouver, British Columbia, Canada. Reprint requests to Jack Rootman, M.D., Depart ment of Ophthalmology and Pathology, Eye Care Centre, 2550 Willow, Vancouver, B.C., Canada. 558
corded as amelanotic, moderately mela notic, or highly melanotic. We did a retrospective color assess ment of the eyes with iris melanoma using photographs taken at the time of diagnosis. Diagnosis of the iris melano mas was based on histologie evidence in eight cases and on the clinical appearance defined by Shields, Sanborn, and Augsberger, 1 that is, on the basis of size, evidence of infiltration, vascularity, doc umented progression, or secondary ocu lar changes in 15 cases. The Figure illus trates 18 of the 23 cases. The group with iris melanoma was compared for iris color with two compari son groups. The first group consisted of the 62 non-iris ocular melanomas ana lyzed in our case-control study of risk factors for ocular melanoma (R. P. Galla gher and associates, unpublished data). The second group was a randomly se lected sample of 687 individuals who served as controls for our study of cutane ous malignant melanoma. 2 Iris color for both comparison groups had previously been recorded by observation on a stan dard form by interviewers conducting these case-control studies. The inter viewers were unaware of the case-control status of the comparison subjects being interviewed. Categories for eye color in the comparison groups were identical to those used to classify the iris melanomas. We used a simple test of proportions (2 by 5 chi-square with 4 degrees of freedom)
©AMERICAN JOURNAL OF OPHTHALMOLOGY 98:558-561, 1984
IRIS MELANOMA
VOL. 98, NO. 5
559
Figure (Rootman and Gallagher). Retrospective analysis of 18 eyes with iris melanoma giving iris color (blue, gray, or hazel [B, G, or H], tumor pigmentation (amelanotic, moderately melanotic, or highly melanotic [A, MM, or HM]), and method of diagnosis (clinical or histopathologic [C or H]). Row 1, left to right: B-A-C; B-A-C; B-MM-C. Row 2, left to right: B-A-H; B-HM-C; G-HM-C. Row 3, left to right: B-HM-C; G-HM-H; G-MM-C. Row 4, left to right: G-MM-C; G-HM-H; G-HM-H; Row 5, left to right: G-MM-H, G-HM-H, G-HM-C; Row 6, left to right: G-HM-C; G-HM-H; H-HM-C.
to test differences in eye color between subjects with iris melanomas and those in each of the comparison groups. RESULTS
Eyes with iris melanoma seen at the ocular oncology clinic were overwhelm
ingly blue or gray, with 21 of 23 subjects having light irides (Table 1). None had brown irides. Gross pigmentation of the tumors varies with iris color as amelanotic and moderately melanotic tumors ap peared predominantly in blue-eyed pa tients. Table 2 shows a comparison of the
560
AMERICAN JOURNAL OF OPHTHALMOLOGY TABLE 1
IRIS COLOR AND GROSS MELANOTIC PIGMENTATION
Gross Melanoma Pigmentation Iris Color
Blue Gray Green Hazel Brown
Amelanotic
Moderately Melanotic
Highly Melanotic
3 0 0 0
6 2 0 0
2 8 1 1
proportional distribution of eye color in the eyes with iris melanomas, in those with uveal melanomas from our casecontrol study, and eyes in a randomly chosen group of 687 normal healthy pop ulation controls previously chosen for a study of cutaneous malignant melanoma. 3 Not only was the color distribution in eyes with iris melanoma significantly dif ferent from that of the population con trols (χ2 = 58.0; P <.00001) but it also differed significantly from that in eyes with uveal melanoma (χ2 = 17.1; P = .002), indicating a higher proportion of gray irides in the group with iris mel anoma. DISCUSSION
Based on population rates from our overall study of incident ocular melano ma, we would have expected about 125
NOVEMBER, 1984
melanomas at the ocular oncology clinic from 1977 to 1983 if we had seen all newly diagnosed cases. Several United States studies 3,4 and one Scandinavian 5 incident study led us, therefore, to antici pate a maximum of 12 iris melanomas. The disproportionate numbers of iris melanomas in the present study probably represented a tendency of ophthalmolo gists to refer iris lesions selectively, and may also have reflected the slow growth of iris melanomas. Our clinical review of iris melanomas was prompted by our finding that individ uals with light irides have an increased risk of ocular melanoma (R. P. Gallagher and associates, unpublished data). The predominance of lighter irides appears to be even more pronounced in iris melano mas than in other uveal melanomas. Al though our finding may have been an artifact of the small numbers, we note that Makley, 7 discussing the management of iris melanoma, described 12 cases, ten of which were in blue or blue-green irides. Because of the unusual predominance of lighter irides in this group, it is of interest to speculate on whether shortwavelength light (ultraviolet) or light in general is an inductive factor for this tumor. It may be that predisposed or previously transformed melanocytes may be more intensely stimulated by light in a
TABLE 2 IRIS C O L O R DISTRIBUTION
color Blue Gray Green Hazel Brown Total
Iris Melanomas % No.
Uveal Melanomas* No. %
11 10 1 1 0 23
35 5 4 8 10 62
47.8 43.4 4.4 4.4
—
100
56.5 8.1 6.4 12.9 16.1 100
Population Controls No. % 283 37 66 123 178 687
41.2 5.4 9.6 17.9 25.9 100
*The original ocular melanoma study contained 65 cases. We eliminated the three patients with iris melanomas all of whom had blue eyes.
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IRIS MELANOMA
pale iris without protective pigmentation. Further, the relatively benign course of iris melanomas may in some instances reflect a reactive neoplastic process rath er than a frank malignant transformation. A larger series of iris melanomas needs to be studied to confirm our observations concerning the tumor. REFERENCES 1. Shields, J. A., Sanborn, G. E., and Augsberger, J. J.: The differential diagnosis of malignant melanoma of the iris. Ophthalmology 90:716, 1983.
561
2. Elwood, J. M., Gallagher, R. P., Hill, G. B., Spinelli, J. J., Pearson, J. C. G., and Threlfall, W. J.: Pigmentation and skin reaction to sun as risk factors for cutaneous melanoma. Western Canada Melanoma Study. Br. Med. J. 288:99, 1984. 3. Rones, B., and Zimmerman, L. E.: The prog nosis of primary tumors of the iris treated by iridectomy. Arch. Ophthalmol. 60:193, 1958. 4. Reese, A. B.: Tumors of the Eye, 3rd ed. Hagerstown, Harper & Row, 1976, pp. 226-229. 5. Jensen, O. A.: Malignant melanoma of the human uvea, 25 year follow-up of cases in Denmark 1943-1952. Acta Ophthalmologica 60:161, 1982. 6. Makley, T. A., Jr.: Management of melanomas of the anterior segment. Surv. Ophthalmol. 19:135, 1974.
AND R I C H A R D P. G A L L A G H E R ,
Vancouver, British Columbia,
M.A.
Canada
We reviewed 23 iris melanomas for iris color and gross tumor pigmentation. Patients with iris melanoma had lighter irides than both population controls (χ2 = 58.0; P <.0001) and other patients with uveal melanoma (χ2 = 17.1; P =.002). Amelanotic and lightly melanotic tumors occurred predominantly in the patients with light irides.
When we learned that iris color was a significant risk factor in a study of ocular melanoma (R. P. Gallagher, J. M. Elwood, J. Rootman, J. J. Spirelli, G. B. Bell, and J. Birdsell, unpublished data), we decided to conduct a retrospective clinical review of all iris melanomas seen in a single ocular oncology practice. We were particularly interested in whether the same trend of higher risk for lighter eye colors in ocular melanoma would be more pronounced in iris melanoma. S U B J E C T S AND M E T H O D S
We reviewed all ocular melanomas seen at the ocular oncology clinic of the University of British Columbia from 1977 to 1983. The catchment area for the clinic includes the entire province of British Columbia with a population of some 2.6 million. Of 93 ocular melanomas, 23 were iris melanomas with only one of these cases being a referral from outside the province. Color photographs were available for 20 patients and chart de scriptions and drawings were available for the remaining three. Iris color was classi fied as blue, gray, green, hazel, or brown and gross tumor pigmentation was re-
Accepted for publication May 21, 1984. From the Department of Ophthalmology, Eye Care Center, Vacouver, British Columbia, Canada. Reprint requests to Jack Rootman, M.D., Depart ment of Ophthalmology and Pathology, Eye Care Centre, 2550 Willow, Vancouver, B.C., Canada. 558
corded as amelanotic, moderately mela notic, or highly melanotic. We did a retrospective color assess ment of the eyes with iris melanoma using photographs taken at the time of diagnosis. Diagnosis of the iris melano mas was based on histologie evidence in eight cases and on the clinical appearance defined by Shields, Sanborn, and Augsberger, 1 that is, on the basis of size, evidence of infiltration, vascularity, doc umented progression, or secondary ocu lar changes in 15 cases. The Figure illus trates 18 of the 23 cases. The group with iris melanoma was compared for iris color with two compari son groups. The first group consisted of the 62 non-iris ocular melanomas ana lyzed in our case-control study of risk factors for ocular melanoma (R. P. Galla gher and associates, unpublished data). The second group was a randomly se lected sample of 687 individuals who served as controls for our study of cutane ous malignant melanoma. 2 Iris color for both comparison groups had previously been recorded by observation on a stan dard form by interviewers conducting these case-control studies. The inter viewers were unaware of the case-control status of the comparison subjects being interviewed. Categories for eye color in the comparison groups were identical to those used to classify the iris melanomas. We used a simple test of proportions (2 by 5 chi-square with 4 degrees of freedom)
©AMERICAN JOURNAL OF OPHTHALMOLOGY 98:558-561, 1984
IRIS MELANOMA
VOL. 98, NO. 5
559
Figure (Rootman and Gallagher). Retrospective analysis of 18 eyes with iris melanoma giving iris color (blue, gray, or hazel [B, G, or H], tumor pigmentation (amelanotic, moderately melanotic, or highly melanotic [A, MM, or HM]), and method of diagnosis (clinical or histopathologic [C or H]). Row 1, left to right: B-A-C; B-A-C; B-MM-C. Row 2, left to right: B-A-H; B-HM-C; G-HM-C. Row 3, left to right: B-HM-C; G-HM-H; G-MM-C. Row 4, left to right: G-MM-C; G-HM-H; G-HM-H; Row 5, left to right: G-MM-H, G-HM-H, G-HM-C; Row 6, left to right: G-HM-C; G-HM-H; H-HM-C.
to test differences in eye color between subjects with iris melanomas and those in each of the comparison groups. RESULTS
Eyes with iris melanoma seen at the ocular oncology clinic were overwhelm
ingly blue or gray, with 21 of 23 subjects having light irides (Table 1). None had brown irides. Gross pigmentation of the tumors varies with iris color as amelanotic and moderately melanotic tumors ap peared predominantly in blue-eyed pa tients. Table 2 shows a comparison of the
560
AMERICAN JOURNAL OF OPHTHALMOLOGY TABLE 1
IRIS COLOR AND GROSS MELANOTIC PIGMENTATION
Gross Melanoma Pigmentation Iris Color
Blue Gray Green Hazel Brown
Amelanotic
Moderately Melanotic
Highly Melanotic
3 0 0 0
6 2 0 0
2 8 1 1
proportional distribution of eye color in the eyes with iris melanomas, in those with uveal melanomas from our casecontrol study, and eyes in a randomly chosen group of 687 normal healthy pop ulation controls previously chosen for a study of cutaneous malignant melanoma. 3 Not only was the color distribution in eyes with iris melanoma significantly dif ferent from that of the population con trols (χ2 = 58.0; P <.00001) but it also differed significantly from that in eyes with uveal melanoma (χ2 = 17.1; P = .002), indicating a higher proportion of gray irides in the group with iris mel anoma. DISCUSSION
Based on population rates from our overall study of incident ocular melano ma, we would have expected about 125
NOVEMBER, 1984
melanomas at the ocular oncology clinic from 1977 to 1983 if we had seen all newly diagnosed cases. Several United States studies 3,4 and one Scandinavian 5 incident study led us, therefore, to antici pate a maximum of 12 iris melanomas. The disproportionate numbers of iris melanomas in the present study probably represented a tendency of ophthalmolo gists to refer iris lesions selectively, and may also have reflected the slow growth of iris melanomas. Our clinical review of iris melanomas was prompted by our finding that individ uals with light irides have an increased risk of ocular melanoma (R. P. Gallagher and associates, unpublished data). The predominance of lighter irides appears to be even more pronounced in iris melano mas than in other uveal melanomas. Al though our finding may have been an artifact of the small numbers, we note that Makley, 7 discussing the management of iris melanoma, described 12 cases, ten of which were in blue or blue-green irides. Because of the unusual predominance of lighter irides in this group, it is of interest to speculate on whether shortwavelength light (ultraviolet) or light in general is an inductive factor for this tumor. It may be that predisposed or previously transformed melanocytes may be more intensely stimulated by light in a
TABLE 2 IRIS C O L O R DISTRIBUTION
color Blue Gray Green Hazel Brown Total
Iris Melanomas % No.
Uveal Melanomas* No. %
11 10 1 1 0 23
35 5 4 8 10 62
47.8 43.4 4.4 4.4
—
100
56.5 8.1 6.4 12.9 16.1 100
Population Controls No. % 283 37 66 123 178 687
41.2 5.4 9.6 17.9 25.9 100
*The original ocular melanoma study contained 65 cases. We eliminated the three patients with iris melanomas all of whom had blue eyes.
VOL. 98, NO. 5
IRIS MELANOMA
pale iris without protective pigmentation. Further, the relatively benign course of iris melanomas may in some instances reflect a reactive neoplastic process rath er than a frank malignant transformation. A larger series of iris melanomas needs to be studied to confirm our observations concerning the tumor. REFERENCES 1. Shields, J. A., Sanborn, G. E., and Augsberger, J. J.: The differential diagnosis of malignant melanoma of the iris. Ophthalmology 90:716, 1983.
561
2. Elwood, J. M., Gallagher, R. P., Hill, G. B., Spinelli, J. J., Pearson, J. C. G., and Threlfall, W. J.: Pigmentation and skin reaction to sun as risk factors for cutaneous melanoma. Western Canada Melanoma Study. Br. Med. J. 288:99, 1984. 3. Rones, B., and Zimmerman, L. E.: The prog nosis of primary tumors of the iris treated by iridectomy. Arch. Ophthalmol. 60:193, 1958. 4. Reese, A. B.: Tumors of the Eye, 3rd ed. Hagerstown, Harper & Row, 1976, pp. 226-229. 5. Jensen, O. A.: Malignant melanoma of the human uvea, 25 year follow-up of cases in Denmark 1943-1952. Acta Ophthalmologica 60:161, 1982. 6. Makley, T. A., Jr.: Management of melanomas of the anterior segment. Surv. Ophthalmol. 19:135, 1974.