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Clinical Survey of 3680 Iris Tumors Based on Patient Age at Presentation
Clinical Survey of 3680 Iris Tumors Based on Patient Age at Presentation Carol L. Shields, MD, Swarupa Kancherla, BA, Jinali Patel, BS, Priya Vijayvargiya, BS, Mayerling M. Suriano, MD, Emily Kolbus, BS, Ami Badami, BS, Priya Sharma, BS, Emily Jacobs, BS, Matt Voluck, BS, Zina Zhang, MD, Rishav Kansal, MD, Patrick W. Shields, BS, Carlos G. Bianciotto, MD, Jerry A. Shields, MD Objective: To report the spectrum of iris lesions based on patient age at presentation. Design: Retrospective, nonrandomized, single-center case series. Participants: We included 3680 iris tumors in 3451 patients. Methods: Chart review. Main Outcome Measures: Diagnostic category based on age. Results: The mean age at presentation was 48 years and there were 449 (12%) tumors in children (ⱕ20 years), 788 (21%) in young adults (21– 40 years), 1308 (36%) in mid adults (41– 60 years), and 1135 (31%) in senior adults (⬎60 years). Of 3680 tumors, the diagnostic category was cystic (n ⫽ 768; 21%) or solid (n ⫽ 2912; 79%). The cystic tumors originated from iris pigment epithelium (IPE; n ⫽ 672; 18%) or iris stroma (n ⫽ 96; 3%). The solid tumors included melanocytic (n ⫽ 2510; 68%) and nonmelanocytic (n ⫽ 402; 11%). The melanocytic tumors comprised nevus (n ⫽ 1503; 60%), melanocytoma (n ⫽ 68; 3%), melanoma (n ⫽ 645; 26%), and melanocytosis (n ⫽ 64; 3%). Of 2510 melanocytic tumors, the first and second most common diagnoses by age (children, young adult, mid adult, senior adult) were nevus (53%, 57%, 63%, and 63%, respectively) and melanoma (17%, 27%, 26%, and 27%, respectively). The nonmelanocytic tumors included categories of choristomatous (n ⫽ 4; ⬍1%), vascular (n ⫽ 57; 2%), fibrous (n ⫽ 2; ⬍1%), neural (n ⫽ 3; ⬍1%), myogenic (n ⫽ 2;, ⬍1%), epithelial (n ⫽ 35; 1%), xanthomatous (n ⫽ 8; ⬍1%), metastasis (n ⫽ 67; 2%), lymphoid (n ⫽ 12; ⬍1%), leukemic (n ⫽ 2; ⬍1%), secondary (n ⫽ 12; ⬍1%), and nonneoplastic simulators (n ⫽ 198; 5%). The median age (in years) at diagnosis included cystic (39), melanocytic (52), choristomatous (0.7), vascular (56), fibrous (53), neural (8), myogenic (42), epithelial (63), xanthomatous (1.9), metastasis (60), lymphoid (57), leukemic (25.5), secondary (59), and nonneoplastic simulators (49). Overall, the 3 most common specific diagnoses (children, young adult, mid adult, senior adult) were nevus (25%, 36%, 47%, and 47%, respectively), IPE cyst (28%, 30%, 15%, and 14%, respectively), and melanoma (8%, 16%, 20%, and 19%, respectively). Conclusions: In an ocular oncology practice, the spectrum of iris tumors includes cystic (21%) and solid (79%) tumors. The solid tumors were melanocytic (68%) or nonmelanocytic (11%). At all ages, the most common specific diagnoses were nevus (42%), IPE cyst (19%), and melanoma (17%). Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2012;119:407– 414 © 2012 by the American Academy of Ophthalmology.
Tumors of the iris are relatively uncommon and there are few published data on this subject. According to Duke and Dunn, “the accumulation of a sizable number of cases requires considerable time.”1 There have been only few reported series of iris tumors since the 1958 report by Duke and Dunn on 43 cases. In 1963, Ashton from London described 145 iris tumors, and in 1964 Heath from Boston reported on 232 iris tumors.1–3 These 3 series emanated from pathology laboratories so they represented iris tumors managed with surgical resection or enucleation. There are no comprehensive clinical studies on the relative frequency of the various iris tumors, particularly based on age. Comparative clinical features have been described in textbooks.4,5 Several subset studies on specific diagnoses have been published such as iris melanoma, melanocytoma, me© 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.
tastasis, vascular tumors, and cysts, as well as iris pigment epithelial tumors and cysts.6 –24 We herein have reported a single-center, 4-decade, comprehensive clinical experience on the overall spectrum of iris tumors, and provide perspective based on patient age at presentation.
Methods We reviewed the computer-coded clinical records of all patients with an iris mass or lesion (tumor), examined and managed by members of the Ocular Oncology Service at Wills Eye Institute between July 1974 and August 2010. Institutional review board approval was obtained. Clinical data were gathered retrospectively regarding features of the patient and tumor. The clinical data was ISSN 0161-6420/12/$–see front matter doi:10.1016/j.ophtha.2011.07.059
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Ophthalmology Volume 119, Number 2, February 2012 Table 1. Clinical Survey of 3680 Iris Tumors in 3451 Patients: Diagnostic Category Patients
Tumor
Diagnostic Category
No. of Patients (n ⫽ 3451)
% of All Patients
No. of Tumors (n ⫽ 3680)
% of All Iris Tumors
Cystic Solid Melanocytic Nonmelanocytic Choristomatous Vascular Fibrous Neural Myogenic Epithelial Xanthomatous Metastatic Lymphoid Leukemic Secondary Nonneoplastic simulating lesion
718 2733 2375 358 4 53 2 2 2 35 8 65 11 2 12 162
21 79 69 10 ⬍1 2 ⬍1 ⬍1 ⬍1 1 ⬍1 2 ⬍1 ⬍1 ⬍1 5
768 2912 2510 402 4 57 2 3 2 35 8 67 12 2 12 198
21 79 68 11 ⬍1 2 ⬍1 ⬍1 ⬍1 1 ⬍1 2 ⬍1 ⬍1 ⬍1 5
then analyzed with regard to tumor classification and tumor diagnosis, and then compared with patient demographics. The data included patient demographics such as age, race, and gender. The tumor data included laterality, eye involved, iris color, lesion color, number of lesions, and location by radial site, clockhour site, quadrant site, and anteroposterior site. The tumor size in basal dimension (millimeters) and thickness (millimeters) was recorded. The tumor was coded according to diagnostic category including cystic, melanocytic, choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid, leukemic, secondary tumor, and nonneoplastic lesion simulating tumor. The specific diagnoses were listed. The tumor was then classified according to benign versus malignant and categorized based on age at presentation, race, and gender.
Results Over a 36-year period, there were 3451 patients with 3680 iris tumors referred for evaluation and management by the Ocular Oncology Service at Wills Eye Institute. There were 3302 Caucasians (96%), 76 African Americans (2%), 35 Hispanics (1%), 28 Asians (⬍1%), and 10 others (⬍1%). There were 1423 males (41%) and 2028 females (59%). The mean age at presentation was 48 years (median, 50; range, 2 weeks to 95 years). There were 449
(12%) tumors in children (ⱕ20 years), 788 (21%) in young adults (21– 40 years), 1308 (36%) in mid adults (41– 60 years), and 1135 (31%) in senior adults (⬎60 years). The major diagnostic categories for the 3680 iris tumors are listed in Table 1. There were 768 (21%) cystic and 2912 (79%) solid tumors. The solid tumors (n ⫽ 2912) comprised melanocytic tumors in 2510 (68%) and nonmelanocytic tumors in 402 (11%). The diagnostic categories were then evaluated separately for specific clinical diagnoses by age (children, young adults, mid adults, and senior adults). They are detailed in tables by category as follows: Cystic (Table 2), melanocytic (Table 3), vascular (Table 4), epithelial (Table 5), metastatic (Table 6), lymphoid/leukemic (Table 7), choristomatous, fibrous, neural, myogenic, xanthomatous, secondary (Table 8), and nonneoplastic simulators (Table 9, available online at http://aaojournal.org). The 768 cystic iris lesions were grouped according to a published classification of iris cysts.19 –22 The most common were peripheral cyst of the iris pigment epithelium (IPE; 55%) and mid zonal IPE cyst (24%; Table 2; Fig 1). Of the 96 iris stromal cysts, congenital stromal cyst was most common in children (25/35 cases; 71%) and acquired stromal cyst was most common in senior adults (19/49 cases; 39%). Of 2510 melanocytic iris tumors, the most common were nevus (n ⫽ 1534; 61%) and melanoma (n ⫽ 645; 26%; Table 3; Fig 2). Throughout the 4 age categories, nevus and melanoma prevailed,
Table 2. Cystic Iris Tumors in 768 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 768 tumors), n (%)
Children, 0–20 Years (n ⴝ 159 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 241 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 196 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 172 tumors), n (%)
IPE cyst, pupillary IPE cyst, mid zonal IPE cyst, peripheral IPE cyst, dislodged Iris stromal cyst, congenital Iris stromal cyst, acquired Epithelial downgrowth
49 (6) 188 (24) 424 (55) 11 (1) 35 (5) 49 (6) 12 (2)
18 (11) 29 (18) 78 (49) 2 (1) 25 (16) 6 (4) 1 (⬍1)
16 (7) 30 (12) 181 (75) 2 (1) 2 (1) 10 (4) 0 (0)
11 (6) 50 (26) 112 (57) 3 (2) 4 (2) 14 (7) 2 (1)
4 (2) 79 (46) 53 (31) 4 (2) 4 (2) 19 (11) 9 (5)
IPE ⫽ iris pigment epithelium.
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Shields et al 䡠 Clinical Survey of Iris Tumors Table 3. Melanocytic Iris Tumors in 2510 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 2510 tumors), n (%)
Children, 0–20 Years (n ⴝ 212 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 487 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 981 tumors), n (%)
Senior Adults >60 Years (n ⴝ 830 tumors), n (%)
Nevus Tapioca nevus Melanocytoma Melanocytosis Lisch nodules Melanoma Other
111 (4) 1503 (60) 31 (1) 68 (3) 64 (3) 70 (3) 645 (26) 18 (⬍1)
8 (4) 108 (51) 4 (2) 14 (7) 22 (10) 12 (6) 36 (17) 8 (4)
20 (4) 271 (56) 6 (1) 25 (5) 14 (3) 17 (3) 131 (27) 3 (⬍1)
33 (3) 606 (62) 10 (1) 24 (2) 18 (2) 29 (3) 258 (26) 3 (⬍1)
50 (6) 518 (62) 11 (1) 5 (⬍1) 10 (1) 12 (1) 220 (27) 4 (⬍1)
Table 4. Vascular Iris Tumors in 57 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 57 tumors), n (%)
Children, 0–20 Years (n ⴝ 4 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 10 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 18 tumors), n (%)
Senior Adults >60 Years (n ⴝ 25 tumors), n (%)
Varix Racemose hemangioma Capillary hemangioma Cavernous hemangioma Microhemangiomatosis Arteriovenous malformation
5 (9) 37 (65) 2 (4) 7 (12) 3 (5) 3 (5)
0 (0) 3 (75) 0 (0) 1 (25) 0 (0) 0 (0)
2 (20) 7 (70) 1 (10) 0 (0) 0 (0) 0 (0)
1 (6) 13 (72) 1 (6) 2 (11) 0 (0) 1 (6)
2 (8) 14 (56) 0 (0) 4 (16) 3 (12) 2 (8)
Table 5. Epithelial Iris Tumors in 35 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 35 tumors), n (%)
Children, 0–20 Years (n ⴝ 4 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 5 tumors), n (%)
Mid Adults, 41– 60 Years (n ⴝ 10 tumors), n (%)
Senior Adults >60 Years (n ⴝ 16 tumors), n (%)
IPE adenoma Medulloepithelioma IPE adenocarcinoma
31 (89) 3 (9) 1 (3)
1 (25) 3 (75) 0 (0)
4 (80) 0 (0) 1 (20)
10 (100) 0 (0) 0 (0)
16 (100) 0 (0) 0 (0)
IPE ⫽ iris pigment epithelium.
Table 6. Metastatic Iris Tumors in 67 Cases Based on Age at Presentation
Primary Site of Cancer Breast Lung Skin (melanoma) Kidney Gastrointestinal tract Carcinoid Other
All Ages (n ⴝ 67 tumors), n (%)
Children, 0–20 Years (n ⴝ 2 tumors), n (%)
Young Adults, 21–40 years (n ⴝ 4 tumors), n (%)
Mid Adults, 41– 60 Years (n ⴝ 31 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 30 tumors), n (%)
21 (31) 19 (28) 9 (13) 3 (4) 1 (1) 2 (3) 12 (18)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (100)
2 (50) 0 (0) 2 (50) 0 (0) 0 (0) 0 (0) 0 (0)
11 (35) 5 (17) 3 (10) 3 (10) 1 (3) 1 (3) 7 (23)
8 (27) 14 (47) 4 (13) 0 (0) 0 (0) 1 (3) 3 (10)
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Ophthalmology Volume 119, Number 2, February 2012 Table 7. Lymphoid/Leukemic Iris Tumors in 14 Cases Based on Age At Presentation
Diagnosis Benign reactive lymphoid hyperplasia Lymphoma Plasmacytoma Multiple myeloma Leukemia
All Ages (n ⴝ 14 tumors), n (%)
Children, 0–20 Years (n ⴝ 1 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 2 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 8 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 3 tumors), n (%)
1 (7)
0 (0)
1 (50)
0 (0)
0 (0)
8 (57) 2 (14) 1 (7) 2 (14)
0 (0) 0 (0) 0 (0) 1 (100)
1 (50) 0 (0) 0 (0) 0 (0)
5 (63) 2 (25) 0 (0) 1 (13)
2 (67) 0 (0) 1 (33) 0 (0)
but in children there was higher incidence of referral for melanocytosis and melanocytoma. Melanoma represented 17% (36/212 cases) of all iris tumors found in children, 27% (131/487) in young adults, 26% (258/981) in mid adults, and 27% (220/830) in senior adults. Of 57 vascular iris tumors,18 the most common were racemose hemangioma (n ⫽ 37; 65%) and cavernous hemangioma (n ⫽ 7; 12%; Table 4; Fig 3). Vascular iris tumors were more common in mid adults and senior adults (43/57 cases; 75%) compared with children and young adults (14/57 cases; 25%). Of the 35 epithelial iris tumors, the most common was IPE adenoma (n ⫽ 31; 89%; Table 5; Fig 3). Adenoma of the IPE was more common in mid and senior adults (26/31 cases; 84%) compared with children and young adults (5/31 cases; 16%). Medulloepithelioma comprised 9% (n ⫽ 3) of epithelial iris tumors and was found only in children (3/3 cases). Of the 67 metastatic iris tumors, the most common primary cancer site was in the breast (n ⫽ 21; 31%), lung (n ⫽ 19; 28%), skin (melanoma; n ⫽ 9; 13%), and kidney (n ⫽ 3; 4%; Table 6; Fig 3). Metastatic iris tumors were more common in mid adult and
senior adults (61/67 cases; 91%) compared with children and young adults (6/67 cases; 9%). Of the 14 lymphoid/leukemic iris tumors, the most common type was lymphoma (n ⫽ 8; 57%; Table 7; Fig 3). Iris lymphoma was more common in mid adult and senior adults (7/8 cases; 88%) compared with children and young adults (1/8 cases; 12%). Of the 4 choristomatous iris tumors, all occurred in children and included lacrimal gland choristoma (n ⫽ 3; 75%) and iris dermoid cyst (n ⫽ 1; 25%; Table 8). In this series, only 1 iris leiomyoma was found, occurring in a senior adult. There were 16 cases of xanthoma/xanthogranuloma, all in children. Of the 198 nonneoplastic lesions simulating iris tumors, the most common diagnoses included iris atrophy (n ⫽ 42; 21%), iridocorneal endothelial syndrome (n ⫽ 42; 21%), foreign body (n ⫽ 20; 10%), coloboma (n ⫽ 20; 10%), and heterochromia (n ⫽ 19; 10%; Table 9 [available online at http://aaojournal.org]; Fig 4). Of the 49 simulating lesions in children, the most frequent diagnoses were coloboma (17/49 cases; 35%) and congenital heterochromia (10/49 cases; 20%), compared with the 113 simulators in mid and senior adults that proved to be iris atrophy (33/113; 29%),
Table 8. Choristomatous, Fibrous, Neural, Myogenic, Xanthomatous, and Secondary Iris Tumors Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 40 tumors), n (%)
Children, 0–20 Years (n ⴝ 26 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 3 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 4 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 7 tumors), n (%)
Lacrimal gland choristoma Dermoid Fibroma Neurofibroma Rhabdomyosarcoma Leiomyoma Xanthoma Xanthogranuloma Ciliary body melanoma Retinoblastoma NPCE adenoma
3 (8) 1 (3) 2 (5) 4 (10) 1 (3) 1 (3) 2 (5) 14 (35) 2 (5) 1 (3) 9 (23)
3 (12) 1 (4) 0 (0) 4 (15) 1 (4) 0 (0) 2 (8) 14 (54) 0 (0) 1 (4) 0 (0)
0 (0) 0 (0) 1 (33) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (33) 0 (0) 1 (33)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 4 (100)
0 (0) 0 (0) 1 (14) 0 (0) 0 (0) 1 (14) 0 (0) 0 (0) 1 (14) 0 (0) 4 (57)
NPCE ⫽ nonpigmented ciliary body epithelium.
™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3 Figure 1. Clinical spectrum of iris cysts. A, Pupillary margin iris pigment epithelium (IPE) cyst. B, midzonal IPE cyst. C, peripheral IPE cyst. D, congenital iris stromal cyst. E, acquired iris stromal cyst. F, acquired iris stromal cyst.
™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3 Figure 2. Clinical spectrum of melanocytic iris tumors. A, Iris melanocytosis, sector involvement sparing inferior iris. B, Iris Lisch nodules, multifocal. C, Iris freckles. D, Iris sector nevus, with corectopia and mild ectropion uveae. E, Iris nevus, with trace corectopia. F, Iris melanocytoma. G, Iris nodular melanoma. H, Iris large melanoma. I, Iris diffuse melanoma. IPE ⫽ iris pigment epithelium.
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Figure 3. Clinical spectrum of non-melanocytic iris tumors. A, Iris metastasis from lung cancer. B, Iris racemose hemangioma. C, Iris lymphoma. D, Iris pigment epithelial adenocarcinoma.
iridocorneal endothelial syndrome (n ⫽ 32; 28%), and foreign body (n ⫽ 15; 13%). Among all races, melanocytic and nonneoplastic simulators prevailed as the most common iris tumors, representing 70% of iris tumors in Caucasians (2307/3302 patients), 41% in African Americans (31/76 patients), and 51% in combined Asian, Hispanic, and other races (37/73 patients; Table 10, available online at http:// aaojournal.org). Cystic lesions were found slightly more often in females (433/718 patients; 60%), as were melanocytic lesions (1382/2375 patients; 58%).
The tumor location was listed according to anteroposterior site (Table 11, available online at http://aaojournal.org), quadrant (Table 12, available online at http://aaojournal.org), and laterality (Table 13, available online at http://aaojournal.org). Melanocytic tumors were most often located inferiorly (1275/2510 cases; 51%; Table 12; available online at http://aaojournal.org). Bilaterality of tumors was found with cystic (62/718 cases; 9%), vascular (4/53 cases; 8%), and melanocytic (155/2375 cases; 7%). The bilateral melanocytic tumors were nevi in all cases and there was no case of bilateral iris melanoma.
Figure 4. Clinical spectrum of lesions that simulate iris tumors. A, Iris atrophy (along 8:00 meridian) simulating melanoma. B, Iris juvenile xanthogranuloma simulating melanoma. C, Iris foreign body granuloma simulating metastasis.
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Shields et al 䡠 Clinical Survey of Iris Tumors In the entire cohort of 3680 tumors, the most common specific diagnoses included iris nevus (n ⫽ 1503; 41%), melanoma (n ⫽ 645; 17%), IPE cyst peripheral (n ⫽ 424; 12%), IPE cyst midzonal (n ⫽ 188; 5%), ⫽ 111; 3%), Lisch nodules (n ⫽ 70; 2%), melanocytoma (n ⫽ 68; 2%), and melanocytosis (n ⫽ 64; 2%). The remaining diagnoses each represented ⱕ1% of all cases.
Discussion In 1958, Duke and Dunn reported on 43 cases of primary tumors of the iris examined at the pathology laboratory of the Wilmer Institute over a 31-year period.1 They identified malignant melanoma (n ⫽ 28; 65%), “benign melanoma” (nevus, melanocytoma; n ⫽ 13; 30%), leiomyoma (n ⫽ 1; 2%), and uncertain pathogenesis (n ⫽ 1; 2%). They provided histopathologic descriptions of the tumors, and, when recorded, commented on the clinical findings and “the ultimate fate of the patients.” In 1963, Ashton published a series of 145 primary tumors of the iris evaluated in the Department of Pathology at the Institute of Ophthalmology in London.2 At that time, this was the largest and most comprehensive series on this topic. The tumors included iris melanoma (n ⫽ 105; 72%), leiomyoma (n ⫽ 21; 14%), nevus (n ⫽ 10; 7%), freckle (n ⫽ 4; 3%), angioma (n ⫽ 3; 2%), and pigment epithelial tumors (n ⫽ 2; 1%). In that report, extensive detail on histopathologic differentiation of various tumors was provided, with emphasis on melanoma therapy and prognosis. The high incidence of leiomyoma in that series raises the possibility that they were actually low grade spindle cell melanoma that was misdiagnosed before the advent of immunohistochemistry. In our extensive series, we only encountered 1 case of iris leiomyoma. Furthermore, most intraocular leiomyoma occurs in the ciliary body rather than the iris. In 1964, Heath3 presented at the American Ophthalmological Society a report on the histopathologic features of 232 iris tumors on record in the pathology laboratory at the Massachusetts Eye and Ear Infirmary. The specific diagnoses included melanoma (n ⫽ 113; 49%), acquired iris cysts (n ⫽ not listed), secondary invasion into iris (n ⫽ 70; 31%), leiomyoma (n ⫽ 5; 2%), metastatic tumors (n ⫽ 6; 3%), vascular tumors (n ⫽ 6; 1%), and rare conditions like teratoma, congenital cyst, “pearl cyst,” nevoxanthoendothelioma, myxoid leiomyoblastoma, medulloepithelioma, and congenital racemose artery (n ⫽ 1 each; ⬍1%). He constructed a “working outline of tumors, growths, and cysts of the iris,” which proved to be an early classification for these rare tumors. Part I of the outline included proliferations and hyperplasias of iris tissue (nevus and pigment epithelial tumors and cysts). Part II comprised tumors with origin from mesoderm, neural, reticuloendothelium, and congenital ectopic tissue. Part III included secondary benign iris tumors and part IV included primary malignant tumors of the iris (melanoma). In the discussion of his report, Sanders commented this large series of iris tumors allowed for an “idea of the broad spectrum of [iris] tumors,” “considering [their] relative rarity.”25 Since these 3 pathology-based reports were published, there has been little information on the broad clinical spectrum of iris tumors. Occasional publications on specific
diagnoses,6 –24 such as iris melanoma, nevus, metastasis, vascular tumors, and IPE tumors have been performed and textbook descriptions4,5 of iris tumors are available. However, there has been no large cohort analysis to define the clinical frequency of each type. In our clinic-based series, we specifically evaluated tumor classification and diagnosis in 3680 iris tumors managed over a 36-year period in a tertiary referral center. The diagnoses were most often established based on clinical features and diagnostic testing,26,27 and occasionally with needle biopsy or tissue biopsy. This clinical perspective has revealed iris tumors of either cystic (21%) or solid (79%) composition. The cystic tumors proved to be IPE cyst (86%), stromal cyst (11%), and epithelial downgrowth (2%). Pupillary margin cysts were more common in children (18/49 cases; 37%), whereas mid zonal cysts were more common in mid and older adults (129/188 cases; 69%; Table 2). The solid tumors proved to be melanocytic (87%) or nonmelanocytic (13%). A breakdown of the melanocytic lesions included nevus (60%), melanoma (26%), freckle (4%), melanocytoma (3%), Lisch nodules (3%), melanocytosis (3%), and others. Across all age groups, iris nevus was most common representing 51% to 62% of the melanocytic tumors (Table 3). Because of our interest in iris melanoma, the number of melanomas could be overrepresented in this series. Nonmelanocytic iris tumors included many different diagnoses such as choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid/ leukemic, secondary, and nonneoplastic simulating lesions. The simulating lesions most often included iris atrophy and iridocorneal endothelial syndrome, exposing underlying IPE and simulating a pigmented mass. Other simulating lesions included foreign body, coloboma, heterochromia, granuloma, and others (Table 1). In this analysis, we specifically looked at age at presentation for trends in tumor diagnoses. We found that the median age (years) at diagnosis included cystic (39), melanocytic (52), choristomatous (0.7), vascular (56), fibrous (53), neural (8), myogenic (42), epithelial (63), xanthomatous (1.9), metastasis (60), lymphoid (57), leukemic (25.5), secondary (59), and nonneoplastic simulators (49; Table 10; available online at http://aaojournal.org). Overall, the 3 most common specific diagnoses (children, young adult, mid adult, senior adult) were nevus (25%, 36%, 47%, and 47%, respectively), IPE cyst (28%, 30%, 15%, and 14%, respectively), and melanoma (8%, 16%, 20%, and 19%, respectively). In addition, we evaluated each tumor classification based on quadrant location and noted that melanocytic tumors occurred in the inferior quadrant in 51% cases, implying sun exposure as potential cause (Table 12; available online at http://aaojournal.org). Bilaterality of iris lesions was uncommon, except for some IPE cysts and iris nevi (Table 13; available online at http://aaojournal.org). This large cohort attempts to represent the entire clinical spectrum of iris tumors, but there are limitations. The most obvious limitation relates to our long-time interest in intraocular malignancies, thus possibly overrepresenting malignant iris tumors, particularly melanoma. An-
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Ophthalmology Volume 119, Number 2, February 2012 other limitation in this clinical series is the lack of histopathologic confirmation in each case because many were diagnosed based on clinical features alone. This is expected as most were benign and did not require surgical biopsy. Last, these data reflect a tertiary referral center, and might not truly represent the frequency of tumors in a primary care setting. This comprehensive series provides a clinical spectrum of iris lesions for the practicing clinician. There are slight variations in diagnoses based on age and laterality. Overall, our clinical perspective from an ocular oncology center has revealed that iris nevus, IPE cyst, and iris melanoma remain the most common iris tumors. Acknowledgment. The authors thank Hong Sun, Christina Kytasty, Vanessa Viloria, Jaeyoon Chung, Evan Stiegel, Paul Kitei, Andy Ngo, John Walton, Margaret V. Shields, Haley Pearlstein, Sahitya Reddy, and Dhanushka Gunasekara for their data collection and contribution to this research.
References 1. Duke JR, Dunn SN. Primary tumors of the iris. Arch Ophthalmol 1958;59:204 –14. 2. Ashton N. Primary tumours of the iris. Br J Ophthalmol 1964;48:650 – 68. 3. Heath P. Tumors of the iris. Classification and clinical followup. Trans Am Ophthalmol Soc 1964;62:51– 82. 4. Reese AB. Tumors of the Eye. 3rd ed. Hagerstown, MD: Harper and Row; 1976;424-31. 5. Shields JA, Shields CL. Intraocular Tumors: An Atlas and Textbook. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2008;3-58. 6. Geisse LJ, Robertson DM. Iris melanomas. Am J Ophthalmol 1985;99:638 – 48. 7. Territo C, Shields CL, Shields JA, et al. Natural course of melanocytic tumors of the iris. Ophthalmology 1988;95: 1251–5. 8. McGalliard JN, Johnston PB. A study of iris melanoma in Northern Ireland. Br J Ophthalmol 1989;73:591–5. 9. van Klink F, de Keizer RJ, Jager MJ, Kakebeeke-Kemme HM. Iris nevi and melanomas: a clinical follow-up study. Doc Ophthalmol 1992;82:49 –55. 10. Batiog˘lu F, Gunalp I. Malignant melanomas of the iris. Jpn J Ophthalmol 1998;42:281–5. 11. Shields CL, Shields JA, Materin M, et al. Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology 2001;108:172– 8.
12. Demirci H, Shields CL, Shields JA, et al. Diffuse iris melanoma: a report of 25 cases. Ophthalmology 2002;109: 1553– 60. 13. Henderson E, Margo CE. Iris melanoma. Arch Pathol Lab Med 2008;132:268 –72. 14. Demirci H, Mashayekhi A, Shields CL, et al. Iris melanocytoma: clinical features and natural course in 47 cases. Am J Ophthalmol 2005;139:468 –75. 15. Shields JA, Shields CL, Kiratli H, de Potter P. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol 1995;119: 422–30. 16. Shields JA, Streicher TF, Spirkova JH, et al. Arteriovenous malformation of the iris in 14 cases. Arch Ophthalmol 2006; 124:370 –5. 17. Broaddus E, Lystad LD, Schonfield L, Singh AD. Iris varix: report of a case and review of iris vascular anomalies. Surv Ophthalmol 2009;54:118 –27. 18. Shields JA, Bianciotto CG, Kligman B, Shields CL. Vascular tumors of the iris in 45 patients: the 2009 Helen Keller Lecture. Arch Ophthalmol 2010;128:1107–13. 19. Shields JA. Primary cysts of the iris. Trans Am Ophthalmol Soc 1981;79:771– 809. 20. Shields JA, Kline MW, Augsburger JJ. Primary iris cysts: a review of the literature and report of 62 cases. Br J Ophthalmol 1984;68:152– 66. 21. Lois N, Shields CL, Shields JA, Mercado G. Primary cysts of the iris pigment epithelium: clinical features and natural course in 234 patients. Ophthalmology 1998;105:1879 – 85. 22. Lois N, Shields CL, Shields JA, et al. Primary iris stromal cysts: a report of 17 cases. Ophthalmology 1998;105: 1317–22. 23. Shields JA, Shields CL, Lois N, Mercado G. Iris cysts in children: classification, incidence, and management. The 1998 Torrence A Makley Jr Lecture. Br J Ophthalmol 1999;83: 334 – 8. 24. Shields JA, Shields CL, Mercado G, et al. Adenoma of the iris pigment epithelium: a report of 20 cases: the 1998 PanAmerican Lecture. Arch Ophthalmol 1999;117:736 – 41. 25. Sanders TE. In discussion of: Heath P. Tumors of the iris: classification and clinical follow-up. Trans Am Ophthalmol Soc 1964;62:83–5. 26. Bianciotto C, Shields CL, Guzman JM, et al. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ophthalmology 2011;118:1297–302. 27. Shields CL, Shields MV, Viloria V, et al. Iridocorneal endothelial syndrome masquerading as iris melanoma in 71 cases. Arch Ophthalmol 2011;129:1023–9.
Footnotes and Financial Disclosures Originally received: May 27, 2011. Final revision: July 29, 2011. Accepted: July 29, 2011. Available online: October 27, 2011.
Manuscript no.: 2011-798.
Support provided by the Eye Tumor Research Foundation, Philadelphia, PA (CLS, JAS). The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review or approval of the manuscript.
From the Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Presented in part at Association for Research and Vision in Ophthalmology (ARVO), May 4, 2011. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.
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Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107. E-mail: carol.shields@ shieldsoncology.com.
Tumors of the iris are relatively uncommon and there are few published data on this subject. According to Duke and Dunn, “the accumulation of a sizable number of cases requires considerable time.”1 There have been only few reported series of iris tumors since the 1958 report by Duke and Dunn on 43 cases. In 1963, Ashton from London described 145 iris tumors, and in 1964 Heath from Boston reported on 232 iris tumors.1–3 These 3 series emanated from pathology laboratories so they represented iris tumors managed with surgical resection or enucleation. There are no comprehensive clinical studies on the relative frequency of the various iris tumors, particularly based on age. Comparative clinical features have been described in textbooks.4,5 Several subset studies on specific diagnoses have been published such as iris melanoma, melanocytoma, me© 2012 by the American Academy of Ophthalmology Published by Elsevier Inc.
tastasis, vascular tumors, and cysts, as well as iris pigment epithelial tumors and cysts.6 –24 We herein have reported a single-center, 4-decade, comprehensive clinical experience on the overall spectrum of iris tumors, and provide perspective based on patient age at presentation.
Methods We reviewed the computer-coded clinical records of all patients with an iris mass or lesion (tumor), examined and managed by members of the Ocular Oncology Service at Wills Eye Institute between July 1974 and August 2010. Institutional review board approval was obtained. Clinical data were gathered retrospectively regarding features of the patient and tumor. The clinical data was ISSN 0161-6420/12/$–see front matter doi:10.1016/j.ophtha.2011.07.059
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Ophthalmology Volume 119, Number 2, February 2012 Table 1. Clinical Survey of 3680 Iris Tumors in 3451 Patients: Diagnostic Category Patients
Tumor
Diagnostic Category
No. of Patients (n ⫽ 3451)
% of All Patients
No. of Tumors (n ⫽ 3680)
% of All Iris Tumors
Cystic Solid Melanocytic Nonmelanocytic Choristomatous Vascular Fibrous Neural Myogenic Epithelial Xanthomatous Metastatic Lymphoid Leukemic Secondary Nonneoplastic simulating lesion
718 2733 2375 358 4 53 2 2 2 35 8 65 11 2 12 162
21 79 69 10 ⬍1 2 ⬍1 ⬍1 ⬍1 1 ⬍1 2 ⬍1 ⬍1 ⬍1 5
768 2912 2510 402 4 57 2 3 2 35 8 67 12 2 12 198
21 79 68 11 ⬍1 2 ⬍1 ⬍1 ⬍1 1 ⬍1 2 ⬍1 ⬍1 ⬍1 5
then analyzed with regard to tumor classification and tumor diagnosis, and then compared with patient demographics. The data included patient demographics such as age, race, and gender. The tumor data included laterality, eye involved, iris color, lesion color, number of lesions, and location by radial site, clockhour site, quadrant site, and anteroposterior site. The tumor size in basal dimension (millimeters) and thickness (millimeters) was recorded. The tumor was coded according to diagnostic category including cystic, melanocytic, choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid, leukemic, secondary tumor, and nonneoplastic lesion simulating tumor. The specific diagnoses were listed. The tumor was then classified according to benign versus malignant and categorized based on age at presentation, race, and gender.
Results Over a 36-year period, there were 3451 patients with 3680 iris tumors referred for evaluation and management by the Ocular Oncology Service at Wills Eye Institute. There were 3302 Caucasians (96%), 76 African Americans (2%), 35 Hispanics (1%), 28 Asians (⬍1%), and 10 others (⬍1%). There were 1423 males (41%) and 2028 females (59%). The mean age at presentation was 48 years (median, 50; range, 2 weeks to 95 years). There were 449
(12%) tumors in children (ⱕ20 years), 788 (21%) in young adults (21– 40 years), 1308 (36%) in mid adults (41– 60 years), and 1135 (31%) in senior adults (⬎60 years). The major diagnostic categories for the 3680 iris tumors are listed in Table 1. There were 768 (21%) cystic and 2912 (79%) solid tumors. The solid tumors (n ⫽ 2912) comprised melanocytic tumors in 2510 (68%) and nonmelanocytic tumors in 402 (11%). The diagnostic categories were then evaluated separately for specific clinical diagnoses by age (children, young adults, mid adults, and senior adults). They are detailed in tables by category as follows: Cystic (Table 2), melanocytic (Table 3), vascular (Table 4), epithelial (Table 5), metastatic (Table 6), lymphoid/leukemic (Table 7), choristomatous, fibrous, neural, myogenic, xanthomatous, secondary (Table 8), and nonneoplastic simulators (Table 9, available online at http://aaojournal.org). The 768 cystic iris lesions were grouped according to a published classification of iris cysts.19 –22 The most common were peripheral cyst of the iris pigment epithelium (IPE; 55%) and mid zonal IPE cyst (24%; Table 2; Fig 1). Of the 96 iris stromal cysts, congenital stromal cyst was most common in children (25/35 cases; 71%) and acquired stromal cyst was most common in senior adults (19/49 cases; 39%). Of 2510 melanocytic iris tumors, the most common were nevus (n ⫽ 1534; 61%) and melanoma (n ⫽ 645; 26%; Table 3; Fig 2). Throughout the 4 age categories, nevus and melanoma prevailed,
Table 2. Cystic Iris Tumors in 768 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 768 tumors), n (%)
Children, 0–20 Years (n ⴝ 159 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 241 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 196 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 172 tumors), n (%)
IPE cyst, pupillary IPE cyst, mid zonal IPE cyst, peripheral IPE cyst, dislodged Iris stromal cyst, congenital Iris stromal cyst, acquired Epithelial downgrowth
49 (6) 188 (24) 424 (55) 11 (1) 35 (5) 49 (6) 12 (2)
18 (11) 29 (18) 78 (49) 2 (1) 25 (16) 6 (4) 1 (⬍1)
16 (7) 30 (12) 181 (75) 2 (1) 2 (1) 10 (4) 0 (0)
11 (6) 50 (26) 112 (57) 3 (2) 4 (2) 14 (7) 2 (1)
4 (2) 79 (46) 53 (31) 4 (2) 4 (2) 19 (11) 9 (5)
IPE ⫽ iris pigment epithelium.
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Shields et al 䡠 Clinical Survey of Iris Tumors Table 3. Melanocytic Iris Tumors in 2510 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 2510 tumors), n (%)
Children, 0–20 Years (n ⴝ 212 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 487 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 981 tumors), n (%)
Senior Adults >60 Years (n ⴝ 830 tumors), n (%)
Nevus Tapioca nevus Melanocytoma Melanocytosis Lisch nodules Melanoma Other
111 (4) 1503 (60) 31 (1) 68 (3) 64 (3) 70 (3) 645 (26) 18 (⬍1)
8 (4) 108 (51) 4 (2) 14 (7) 22 (10) 12 (6) 36 (17) 8 (4)
20 (4) 271 (56) 6 (1) 25 (5) 14 (3) 17 (3) 131 (27) 3 (⬍1)
33 (3) 606 (62) 10 (1) 24 (2) 18 (2) 29 (3) 258 (26) 3 (⬍1)
50 (6) 518 (62) 11 (1) 5 (⬍1) 10 (1) 12 (1) 220 (27) 4 (⬍1)
Table 4. Vascular Iris Tumors in 57 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 57 tumors), n (%)
Children, 0–20 Years (n ⴝ 4 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 10 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 18 tumors), n (%)
Senior Adults >60 Years (n ⴝ 25 tumors), n (%)
Varix Racemose hemangioma Capillary hemangioma Cavernous hemangioma Microhemangiomatosis Arteriovenous malformation
5 (9) 37 (65) 2 (4) 7 (12) 3 (5) 3 (5)
0 (0) 3 (75) 0 (0) 1 (25) 0 (0) 0 (0)
2 (20) 7 (70) 1 (10) 0 (0) 0 (0) 0 (0)
1 (6) 13 (72) 1 (6) 2 (11) 0 (0) 1 (6)
2 (8) 14 (56) 0 (0) 4 (16) 3 (12) 2 (8)
Table 5. Epithelial Iris Tumors in 35 Cases Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 35 tumors), n (%)
Children, 0–20 Years (n ⴝ 4 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 5 tumors), n (%)
Mid Adults, 41– 60 Years (n ⴝ 10 tumors), n (%)
Senior Adults >60 Years (n ⴝ 16 tumors), n (%)
IPE adenoma Medulloepithelioma IPE adenocarcinoma
31 (89) 3 (9) 1 (3)
1 (25) 3 (75) 0 (0)
4 (80) 0 (0) 1 (20)
10 (100) 0 (0) 0 (0)
16 (100) 0 (0) 0 (0)
IPE ⫽ iris pigment epithelium.
Table 6. Metastatic Iris Tumors in 67 Cases Based on Age at Presentation
Primary Site of Cancer Breast Lung Skin (melanoma) Kidney Gastrointestinal tract Carcinoid Other
All Ages (n ⴝ 67 tumors), n (%)
Children, 0–20 Years (n ⴝ 2 tumors), n (%)
Young Adults, 21–40 years (n ⴝ 4 tumors), n (%)
Mid Adults, 41– 60 Years (n ⴝ 31 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 30 tumors), n (%)
21 (31) 19 (28) 9 (13) 3 (4) 1 (1) 2 (3) 12 (18)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 2 (100)
2 (50) 0 (0) 2 (50) 0 (0) 0 (0) 0 (0) 0 (0)
11 (35) 5 (17) 3 (10) 3 (10) 1 (3) 1 (3) 7 (23)
8 (27) 14 (47) 4 (13) 0 (0) 0 (0) 1 (3) 3 (10)
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Ophthalmology Volume 119, Number 2, February 2012 Table 7. Lymphoid/Leukemic Iris Tumors in 14 Cases Based on Age At Presentation
Diagnosis Benign reactive lymphoid hyperplasia Lymphoma Plasmacytoma Multiple myeloma Leukemia
All Ages (n ⴝ 14 tumors), n (%)
Children, 0–20 Years (n ⴝ 1 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 2 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 8 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 3 tumors), n (%)
1 (7)
0 (0)
1 (50)
0 (0)
0 (0)
8 (57) 2 (14) 1 (7) 2 (14)
0 (0) 0 (0) 0 (0) 1 (100)
1 (50) 0 (0) 0 (0) 0 (0)
5 (63) 2 (25) 0 (0) 1 (13)
2 (67) 0 (0) 1 (33) 0 (0)
but in children there was higher incidence of referral for melanocytosis and melanocytoma. Melanoma represented 17% (36/212 cases) of all iris tumors found in children, 27% (131/487) in young adults, 26% (258/981) in mid adults, and 27% (220/830) in senior adults. Of 57 vascular iris tumors,18 the most common were racemose hemangioma (n ⫽ 37; 65%) and cavernous hemangioma (n ⫽ 7; 12%; Table 4; Fig 3). Vascular iris tumors were more common in mid adults and senior adults (43/57 cases; 75%) compared with children and young adults (14/57 cases; 25%). Of the 35 epithelial iris tumors, the most common was IPE adenoma (n ⫽ 31; 89%; Table 5; Fig 3). Adenoma of the IPE was more common in mid and senior adults (26/31 cases; 84%) compared with children and young adults (5/31 cases; 16%). Medulloepithelioma comprised 9% (n ⫽ 3) of epithelial iris tumors and was found only in children (3/3 cases). Of the 67 metastatic iris tumors, the most common primary cancer site was in the breast (n ⫽ 21; 31%), lung (n ⫽ 19; 28%), skin (melanoma; n ⫽ 9; 13%), and kidney (n ⫽ 3; 4%; Table 6; Fig 3). Metastatic iris tumors were more common in mid adult and
senior adults (61/67 cases; 91%) compared with children and young adults (6/67 cases; 9%). Of the 14 lymphoid/leukemic iris tumors, the most common type was lymphoma (n ⫽ 8; 57%; Table 7; Fig 3). Iris lymphoma was more common in mid adult and senior adults (7/8 cases; 88%) compared with children and young adults (1/8 cases; 12%). Of the 4 choristomatous iris tumors, all occurred in children and included lacrimal gland choristoma (n ⫽ 3; 75%) and iris dermoid cyst (n ⫽ 1; 25%; Table 8). In this series, only 1 iris leiomyoma was found, occurring in a senior adult. There were 16 cases of xanthoma/xanthogranuloma, all in children. Of the 198 nonneoplastic lesions simulating iris tumors, the most common diagnoses included iris atrophy (n ⫽ 42; 21%), iridocorneal endothelial syndrome (n ⫽ 42; 21%), foreign body (n ⫽ 20; 10%), coloboma (n ⫽ 20; 10%), and heterochromia (n ⫽ 19; 10%; Table 9 [available online at http://aaojournal.org]; Fig 4). Of the 49 simulating lesions in children, the most frequent diagnoses were coloboma (17/49 cases; 35%) and congenital heterochromia (10/49 cases; 20%), compared with the 113 simulators in mid and senior adults that proved to be iris atrophy (33/113; 29%),
Table 8. Choristomatous, Fibrous, Neural, Myogenic, Xanthomatous, and Secondary Iris Tumors Based on Age at Presentation
Diagnosis
All Ages (n ⴝ 40 tumors), n (%)
Children, 0–20 Years (n ⴝ 26 tumors), n (%)
Young Adults, 21–40 Years (n ⴝ 3 tumors), n (%)
Mid Adults, 41–60 Years (n ⴝ 4 tumors), n (%)
Senior Adults, >60 Years (n ⴝ 7 tumors), n (%)
Lacrimal gland choristoma Dermoid Fibroma Neurofibroma Rhabdomyosarcoma Leiomyoma Xanthoma Xanthogranuloma Ciliary body melanoma Retinoblastoma NPCE adenoma
3 (8) 1 (3) 2 (5) 4 (10) 1 (3) 1 (3) 2 (5) 14 (35) 2 (5) 1 (3) 9 (23)
3 (12) 1 (4) 0 (0) 4 (15) 1 (4) 0 (0) 2 (8) 14 (54) 0 (0) 1 (4) 0 (0)
0 (0) 0 (0) 1 (33) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (33) 0 (0) 1 (33)
0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 4 (100)
0 (0) 0 (0) 1 (14) 0 (0) 0 (0) 1 (14) 0 (0) 0 (0) 1 (14) 0 (0) 4 (57)
NPCE ⫽ nonpigmented ciliary body epithelium.
™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3 Figure 1. Clinical spectrum of iris cysts. A, Pupillary margin iris pigment epithelium (IPE) cyst. B, midzonal IPE cyst. C, peripheral IPE cyst. D, congenital iris stromal cyst. E, acquired iris stromal cyst. F, acquired iris stromal cyst.
™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™™3 Figure 2. Clinical spectrum of melanocytic iris tumors. A, Iris melanocytosis, sector involvement sparing inferior iris. B, Iris Lisch nodules, multifocal. C, Iris freckles. D, Iris sector nevus, with corectopia and mild ectropion uveae. E, Iris nevus, with trace corectopia. F, Iris melanocytoma. G, Iris nodular melanoma. H, Iris large melanoma. I, Iris diffuse melanoma. IPE ⫽ iris pigment epithelium.
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Figure 3. Clinical spectrum of non-melanocytic iris tumors. A, Iris metastasis from lung cancer. B, Iris racemose hemangioma. C, Iris lymphoma. D, Iris pigment epithelial adenocarcinoma.
iridocorneal endothelial syndrome (n ⫽ 32; 28%), and foreign body (n ⫽ 15; 13%). Among all races, melanocytic and nonneoplastic simulators prevailed as the most common iris tumors, representing 70% of iris tumors in Caucasians (2307/3302 patients), 41% in African Americans (31/76 patients), and 51% in combined Asian, Hispanic, and other races (37/73 patients; Table 10, available online at http:// aaojournal.org). Cystic lesions were found slightly more often in females (433/718 patients; 60%), as were melanocytic lesions (1382/2375 patients; 58%).
The tumor location was listed according to anteroposterior site (Table 11, available online at http://aaojournal.org), quadrant (Table 12, available online at http://aaojournal.org), and laterality (Table 13, available online at http://aaojournal.org). Melanocytic tumors were most often located inferiorly (1275/2510 cases; 51%; Table 12; available online at http://aaojournal.org). Bilaterality of tumors was found with cystic (62/718 cases; 9%), vascular (4/53 cases; 8%), and melanocytic (155/2375 cases; 7%). The bilateral melanocytic tumors were nevi in all cases and there was no case of bilateral iris melanoma.
Figure 4. Clinical spectrum of lesions that simulate iris tumors. A, Iris atrophy (along 8:00 meridian) simulating melanoma. B, Iris juvenile xanthogranuloma simulating melanoma. C, Iris foreign body granuloma simulating metastasis.
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Shields et al 䡠 Clinical Survey of Iris Tumors In the entire cohort of 3680 tumors, the most common specific diagnoses included iris nevus (n ⫽ 1503; 41%), melanoma (n ⫽ 645; 17%), IPE cyst peripheral (n ⫽ 424; 12%), IPE cyst midzonal (n ⫽ 188; 5%), ⫽ 111; 3%), Lisch nodules (n ⫽ 70; 2%), melanocytoma (n ⫽ 68; 2%), and melanocytosis (n ⫽ 64; 2%). The remaining diagnoses each represented ⱕ1% of all cases.
Discussion In 1958, Duke and Dunn reported on 43 cases of primary tumors of the iris examined at the pathology laboratory of the Wilmer Institute over a 31-year period.1 They identified malignant melanoma (n ⫽ 28; 65%), “benign melanoma” (nevus, melanocytoma; n ⫽ 13; 30%), leiomyoma (n ⫽ 1; 2%), and uncertain pathogenesis (n ⫽ 1; 2%). They provided histopathologic descriptions of the tumors, and, when recorded, commented on the clinical findings and “the ultimate fate of the patients.” In 1963, Ashton published a series of 145 primary tumors of the iris evaluated in the Department of Pathology at the Institute of Ophthalmology in London.2 At that time, this was the largest and most comprehensive series on this topic. The tumors included iris melanoma (n ⫽ 105; 72%), leiomyoma (n ⫽ 21; 14%), nevus (n ⫽ 10; 7%), freckle (n ⫽ 4; 3%), angioma (n ⫽ 3; 2%), and pigment epithelial tumors (n ⫽ 2; 1%). In that report, extensive detail on histopathologic differentiation of various tumors was provided, with emphasis on melanoma therapy and prognosis. The high incidence of leiomyoma in that series raises the possibility that they were actually low grade spindle cell melanoma that was misdiagnosed before the advent of immunohistochemistry. In our extensive series, we only encountered 1 case of iris leiomyoma. Furthermore, most intraocular leiomyoma occurs in the ciliary body rather than the iris. In 1964, Heath3 presented at the American Ophthalmological Society a report on the histopathologic features of 232 iris tumors on record in the pathology laboratory at the Massachusetts Eye and Ear Infirmary. The specific diagnoses included melanoma (n ⫽ 113; 49%), acquired iris cysts (n ⫽ not listed), secondary invasion into iris (n ⫽ 70; 31%), leiomyoma (n ⫽ 5; 2%), metastatic tumors (n ⫽ 6; 3%), vascular tumors (n ⫽ 6; 1%), and rare conditions like teratoma, congenital cyst, “pearl cyst,” nevoxanthoendothelioma, myxoid leiomyoblastoma, medulloepithelioma, and congenital racemose artery (n ⫽ 1 each; ⬍1%). He constructed a “working outline of tumors, growths, and cysts of the iris,” which proved to be an early classification for these rare tumors. Part I of the outline included proliferations and hyperplasias of iris tissue (nevus and pigment epithelial tumors and cysts). Part II comprised tumors with origin from mesoderm, neural, reticuloendothelium, and congenital ectopic tissue. Part III included secondary benign iris tumors and part IV included primary malignant tumors of the iris (melanoma). In the discussion of his report, Sanders commented this large series of iris tumors allowed for an “idea of the broad spectrum of [iris] tumors,” “considering [their] relative rarity.”25 Since these 3 pathology-based reports were published, there has been little information on the broad clinical spectrum of iris tumors. Occasional publications on specific
diagnoses,6 –24 such as iris melanoma, nevus, metastasis, vascular tumors, and IPE tumors have been performed and textbook descriptions4,5 of iris tumors are available. However, there has been no large cohort analysis to define the clinical frequency of each type. In our clinic-based series, we specifically evaluated tumor classification and diagnosis in 3680 iris tumors managed over a 36-year period in a tertiary referral center. The diagnoses were most often established based on clinical features and diagnostic testing,26,27 and occasionally with needle biopsy or tissue biopsy. This clinical perspective has revealed iris tumors of either cystic (21%) or solid (79%) composition. The cystic tumors proved to be IPE cyst (86%), stromal cyst (11%), and epithelial downgrowth (2%). Pupillary margin cysts were more common in children (18/49 cases; 37%), whereas mid zonal cysts were more common in mid and older adults (129/188 cases; 69%; Table 2). The solid tumors proved to be melanocytic (87%) or nonmelanocytic (13%). A breakdown of the melanocytic lesions included nevus (60%), melanoma (26%), freckle (4%), melanocytoma (3%), Lisch nodules (3%), melanocytosis (3%), and others. Across all age groups, iris nevus was most common representing 51% to 62% of the melanocytic tumors (Table 3). Because of our interest in iris melanoma, the number of melanomas could be overrepresented in this series. Nonmelanocytic iris tumors included many different diagnoses such as choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid/ leukemic, secondary, and nonneoplastic simulating lesions. The simulating lesions most often included iris atrophy and iridocorneal endothelial syndrome, exposing underlying IPE and simulating a pigmented mass. Other simulating lesions included foreign body, coloboma, heterochromia, granuloma, and others (Table 1). In this analysis, we specifically looked at age at presentation for trends in tumor diagnoses. We found that the median age (years) at diagnosis included cystic (39), melanocytic (52), choristomatous (0.7), vascular (56), fibrous (53), neural (8), myogenic (42), epithelial (63), xanthomatous (1.9), metastasis (60), lymphoid (57), leukemic (25.5), secondary (59), and nonneoplastic simulators (49; Table 10; available online at http://aaojournal.org). Overall, the 3 most common specific diagnoses (children, young adult, mid adult, senior adult) were nevus (25%, 36%, 47%, and 47%, respectively), IPE cyst (28%, 30%, 15%, and 14%, respectively), and melanoma (8%, 16%, 20%, and 19%, respectively). In addition, we evaluated each tumor classification based on quadrant location and noted that melanocytic tumors occurred in the inferior quadrant in 51% cases, implying sun exposure as potential cause (Table 12; available online at http://aaojournal.org). Bilaterality of iris lesions was uncommon, except for some IPE cysts and iris nevi (Table 13; available online at http://aaojournal.org). This large cohort attempts to represent the entire clinical spectrum of iris tumors, but there are limitations. The most obvious limitation relates to our long-time interest in intraocular malignancies, thus possibly overrepresenting malignant iris tumors, particularly melanoma. An-
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Ophthalmology Volume 119, Number 2, February 2012 other limitation in this clinical series is the lack of histopathologic confirmation in each case because many were diagnosed based on clinical features alone. This is expected as most were benign and did not require surgical biopsy. Last, these data reflect a tertiary referral center, and might not truly represent the frequency of tumors in a primary care setting. This comprehensive series provides a clinical spectrum of iris lesions for the practicing clinician. There are slight variations in diagnoses based on age and laterality. Overall, our clinical perspective from an ocular oncology center has revealed that iris nevus, IPE cyst, and iris melanoma remain the most common iris tumors. Acknowledgment. The authors thank Hong Sun, Christina Kytasty, Vanessa Viloria, Jaeyoon Chung, Evan Stiegel, Paul Kitei, Andy Ngo, John Walton, Margaret V. Shields, Haley Pearlstein, Sahitya Reddy, and Dhanushka Gunasekara for their data collection and contribution to this research.
References 1. Duke JR, Dunn SN. Primary tumors of the iris. Arch Ophthalmol 1958;59:204 –14. 2. Ashton N. Primary tumours of the iris. Br J Ophthalmol 1964;48:650 – 68. 3. Heath P. Tumors of the iris. Classification and clinical followup. Trans Am Ophthalmol Soc 1964;62:51– 82. 4. Reese AB. Tumors of the Eye. 3rd ed. Hagerstown, MD: Harper and Row; 1976;424-31. 5. Shields JA, Shields CL. Intraocular Tumors: An Atlas and Textbook. 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2008;3-58. 6. Geisse LJ, Robertson DM. Iris melanomas. Am J Ophthalmol 1985;99:638 – 48. 7. Territo C, Shields CL, Shields JA, et al. Natural course of melanocytic tumors of the iris. Ophthalmology 1988;95: 1251–5. 8. McGalliard JN, Johnston PB. A study of iris melanoma in Northern Ireland. Br J Ophthalmol 1989;73:591–5. 9. van Klink F, de Keizer RJ, Jager MJ, Kakebeeke-Kemme HM. Iris nevi and melanomas: a clinical follow-up study. Doc Ophthalmol 1992;82:49 –55. 10. Batiog˘lu F, Gunalp I. Malignant melanomas of the iris. Jpn J Ophthalmol 1998;42:281–5. 11. Shields CL, Shields JA, Materin M, et al. Iris melanoma: risk factors for metastasis in 169 consecutive patients. Ophthalmology 2001;108:172– 8.
12. Demirci H, Shields CL, Shields JA, et al. Diffuse iris melanoma: a report of 25 cases. Ophthalmology 2002;109: 1553– 60. 13. Henderson E, Margo CE. Iris melanoma. Arch Pathol Lab Med 2008;132:268 –72. 14. Demirci H, Mashayekhi A, Shields CL, et al. Iris melanocytoma: clinical features and natural course in 47 cases. Am J Ophthalmol 2005;139:468 –75. 15. Shields JA, Shields CL, Kiratli H, de Potter P. Metastatic tumors to the iris in 40 patients. Am J Ophthalmol 1995;119: 422–30. 16. Shields JA, Streicher TF, Spirkova JH, et al. Arteriovenous malformation of the iris in 14 cases. Arch Ophthalmol 2006; 124:370 –5. 17. Broaddus E, Lystad LD, Schonfield L, Singh AD. Iris varix: report of a case and review of iris vascular anomalies. Surv Ophthalmol 2009;54:118 –27. 18. Shields JA, Bianciotto CG, Kligman B, Shields CL. Vascular tumors of the iris in 45 patients: the 2009 Helen Keller Lecture. Arch Ophthalmol 2010;128:1107–13. 19. Shields JA. Primary cysts of the iris. Trans Am Ophthalmol Soc 1981;79:771– 809. 20. Shields JA, Kline MW, Augsburger JJ. Primary iris cysts: a review of the literature and report of 62 cases. Br J Ophthalmol 1984;68:152– 66. 21. Lois N, Shields CL, Shields JA, Mercado G. Primary cysts of the iris pigment epithelium: clinical features and natural course in 234 patients. Ophthalmology 1998;105:1879 – 85. 22. Lois N, Shields CL, Shields JA, et al. Primary iris stromal cysts: a report of 17 cases. Ophthalmology 1998;105: 1317–22. 23. Shields JA, Shields CL, Lois N, Mercado G. Iris cysts in children: classification, incidence, and management. The 1998 Torrence A Makley Jr Lecture. Br J Ophthalmol 1999;83: 334 – 8. 24. Shields JA, Shields CL, Mercado G, et al. Adenoma of the iris pigment epithelium: a report of 20 cases: the 1998 PanAmerican Lecture. Arch Ophthalmol 1999;117:736 – 41. 25. Sanders TE. In discussion of: Heath P. Tumors of the iris: classification and clinical follow-up. Trans Am Ophthalmol Soc 1964;62:83–5. 26. Bianciotto C, Shields CL, Guzman JM, et al. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ophthalmology 2011;118:1297–302. 27. Shields CL, Shields MV, Viloria V, et al. Iridocorneal endothelial syndrome masquerading as iris melanoma in 71 cases. Arch Ophthalmol 2011;129:1023–9.
Footnotes and Financial Disclosures Originally received: May 27, 2011. Final revision: July 29, 2011. Accepted: July 29, 2011. Available online: October 27, 2011.
Manuscript no.: 2011-798.
Support provided by the Eye Tumor Research Foundation, Philadelphia, PA (CLS, JAS). The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review or approval of the manuscript.
From the Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Presented in part at Association for Research and Vision in Ophthalmology (ARVO), May 4, 2011. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.
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Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107. E-mail: carol.shields@ shieldsoncology.com.