|Year : 2013 | Volume
| Issue : 3 | Page : 159-164
Review of cystic and solid tumors of the iris
Carol L Shields, Patrick W Shields, Janet Manalac, Chaisiri Jumroendararasame, Jerry A Shields
Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA., USA
|Date of Web Publication||30-Nov-2013|
Carol L Shields
Ocular Oncology Service, Suite 1440, Wills Eye Institute, 840 Walnut Street, Philadelphia, PA 19107
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Iris tumors are broadly classified into cystic or solid lesions. The cystic lesions arise from iris pigment epithelium (IPE) or iris stroma. IPE cysts classically remain stable without need for intervention. Iris stromal cyst, especially those in newborns, usually requires therapy of aspiration, possibly with alcohol-induced sclerosis, or surgical resection. The solid tumors included melanocytic and nonmelanocytic lesions. The melanocytic iris tumors include freckle, nevus (including melanocytoma), Lisch nodule, and melanoma. Information from a tertiary referral center revealed that transformation of suspicious iris nevus to melanoma occurred in 4% by 10 years and 11% by 20 years. Risk factors for transformation of iris nevus to melanoma can be remembered using the ABCDEF guide as follows: A=age young (<40 years), B=blood (hyphema) in anterior chamber, C=clock hour of mass inferiorly, D=diffuse configuration, E=ectropion, F=feathery margins. The most powerful factors are diffuse growth pattern and hyphema. Tumor seeding into the anterior chamber angle and onto the iris stroma are also important. The nonmelanocytic iris tumors are relatively uncommon and included categories of choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastatic, lymphoid, leukemic, secondary, and non-neoplastic simulators. Overall, the most common diagnoses in a clinical series include nevus, IPE cyst, and melanoma. In summary, iris tumors comprise a wide spectrum including mostly iris nevus, IPE cyst, and iris melanoma. Risk factors estimating transformation of iris nevus to melanoma can be remembered by the ABCDEF guide.
Keywords: Cyst, eye, iris, melanoma, metastasis, nevus, tumor
|How to cite this article:|
Shields CL, Shields PW, Manalac J, Jumroendararasame C, Shields JA. Review of cystic and solid tumors of the iris. Oman J Ophthalmol 2013;6:159-64
|How to cite this URL:|
Shields CL, Shields PW, Manalac J, Jumroendararasame C, Shields JA. Review of cystic and solid tumors of the iris. Oman J Ophthalmol [serial online] 2013 [cited 2017 May 27];6:159-64. Available from: http://www.ojoonline.org/text.asp?2013/6/3/159/122269
| Introduction|| |
There is a wide spectrum of tumors of the iris. , These lesions range from nevus to melanoma to juvenile xanthogranuloma to metastasis. There have been only a few published comprehensive series on the full array of iris tumors and most series have emanated from pathology laboratories. In 1958, Duke and Dunn recorded 43 cases. In 1963, Ashton found 145 cases and, shortly thereafter, Heath published on 232 iris tumors. ,, In 2012, Shields et al. reviewed a clinical series of 3680 iris tumors from a tertiary referral center, collected over a 40-year period. 
Iris tumors can be found in all races, but predominates in Caucasians. In the analysis of 3680 cases from the United States,  patient race was Caucasian (96%), African American (2%), Hispanic (1%), Asian (<1%), and others (<1%). The mean patient age at presentation was 48 years with range from 2 weeks to 95 years. The iris tumors occurred in children (≤20 years) in 12%, young adults (21-40 years) in 21%, mid-adults (41-60 years) in 36% and senior adults (>60 years) in 31%.
Iris tumors can be broadly categorized into cystic (21%) or solid (79%) [Table 1]. The differentiation is evident on slit lamp examination and confirmed on ocular imaging with ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS OCT).
Imaging of the iris generally involves high-resolution anterior segment photography using the slit lamp biomicroscope. In addition, imaging can be performed with cross-sectional analysis using UBM or AS OCT.  UBM is a high frequency ultrasonographic unit that provides acoustic imaging in the range 20-50 megahertz (MHz). Image resolution is approximately 25 microns and to a penetration of 5-6 mm depth. This technique requires the patient to be in a reclined position so that a water bath can be placed on the ocular surface for immersion of the probe. AS OCT, on the other hand, is a noncontact device that employs a superluminescent diode at 1310 nanometer wavelength for optical imaging with image resolution of 18 microns and penetration depth of 3-4 mm. AS OCT is a more comfortable and convenient imaging modality compared to UBM.
In an analysis of 200 consecutive eyes with anterior segment tumors, mostly in the iris, Bianciotto et al. showed that UBM provided better overall tumor visualization and better resolution of the posterior margin whereas AS OCT provided better resolution of the anterior margin.  In particular, UBM provides better imaging of pigmented iris tumors as they are optically shadowed on AS OCT.
Cystic lesions of the iris
There are two major categories of primary iris cysts including stromal cysts and pigment epithelial (IPE) cysts  [Table 2] and [Figure 1]. The iris stromal cyst can be congenital or acquired. The stromal cyst has a characteristic clinical appearance with a smooth surface, lucent mass on or within the iris stroma, occasionally with fluid-debris level. , This tumor can enlarge and rupture, leading to secondary iritis, photophobia, pain and glaucoma. This is especially important in newborn infants as the congenital cyst can manifest within the first few weeks of life and cause photophobia and buphthalmos.
|Figure 1: Iris cysts (a,b) Iris pigment epithelial (IPE) cyst pupillary margin seen clinically (a) and by optical coherence tomography (b), (c) IPE cyst mid-zonal, (d) IPE cyst dislodged and in the anterior chamber angle, (e) Iris stromal cyst in an infant, (f) Iris stromal cyst with hemorrhage in an infant|
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Lois et al. studied 17 congenital iris stromal cysts and noted that those discovered in children under 10 years of age tended to have a more aggressive course, requiring multiple surgeries and ultimately with poor visual outcome.  Those congenital cysts in teenagers and adults were more benign in behavior, requiring intervention in about 25% of cases. Shields et al. reviewed a relatively new technique for iris stromal cysts that involves cyst aspiration and wash with absolute alcohol under viscoelastic protection of the anterior chamber structures.  This approach avoids open surgical resection. They were successful in inducing cyst collapse with sclerosis and protection of visual acuity in 15 of 16 patients, including children.
The IPE cyst is probably more common than previously realized now that UBM is commonly detecting this asymptomatic mass. , Primary IPE cysts arise on the posterior surface of the iris and were misdiagnosed as ciliary body melanoma in the past due to their similar color and configuration. These cysts can be categorized into pupillary margin (3%), mid-zonal (21%), peripheral (73%), dislodged (3%), and free floating (<1%).  Pupillary margin cysts can be seen without dilation as dark black elongated or collapsed mass at the edge of the pupil. Mid-zonal IPE cysts appear brown to black and fusiform with dome-shaped appearance and emanating on the back of the iris. With dilation, the cyst often everts over the pupillary margin edge onto the anterior iris. This type closely resembles ciliary body melanoma. Peripheral IPE cysts remain hidden in the iridociliary junction and can rarely be visualized even with wide dilation. They cause an asymptomatic iris stromal bulge and are best detected with UBM or AS OCT as a cystic lesion. Dislodged IPE cyst is one that has been presumably free floating and stuck into the anterior chamber angle. Free floating IPE cyst can be found in anterior chamber or in the vitreous and generally require no treatment. It is important to rule out melanoma and IPE adenoma with each of these types of IPE cysts.
Iris melanocytic tumors
Iris melanocytic tumors include freckle, nevus, melanocytoma, Lisch nodule, and melanoma , [Figure 2]. A freckle can be single or multifocal and rests on the iris stromal surface as a pigmented or nonpigmented lesion, usually about 1-2 mm in diameter. A nevus shows deeper penetration into the iris stroma, with distortion of the stroma and often associated with ectropion and corectopia. A melanocytoma is a dark brown to black dome-shaped mass with little to no ectropion and often with a granular "mound of black sand" appearance. Occasionally there is minor seeding into the anterior chamber angle or onto the iris stroma. A Lisch nodule can be unifocal or multifocal, appears after age 5 years in most cases, has a round, slightly pigmented appearance and is most often about 1 mm in diameter. Lisch nodule can be a melanocytic marker for neurofibromatosis. These melanocytic tumors are all benign.
|Figure 2: Iris melanocytic tumors (a) Iris nevus (pigmented), (b) Iris nevus (nonpigmented) causing minor corectopia inferiorly, (c) Iris melanocytoma, (d) Iris Lisch nodules scattered on the entire iris surface, (e) Iris melanoma involving the anterior chamber angle, (f) Iris melanoma causing corectopia|
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In an analysis of 1611 eyes with iris nevus from a clinical tertiary referral center, Shields et al. found that the mean age at referral was 51 years and the mean tumor basal diameter was 3 millimeters (mm).  Keep in mind, most of these iris nevi were considered to have suspicious features for melanoma and hence were referred for evaluation to an ocular oncology center. The nevus was found in male (39%) or female (61%) patients. The patient race was Caucasian (97%), African American (2%), Hispanic (<1%), Asian(<1%), or other (each < 1%). The iris color was blue (51%), green (21%), or brown (27%). In this analysis, growth into melanoma was detected in 2% of cases. However, by Kaplan-Meier analysis, growth was detected in 4% by 10 years and 11% by 20 years. Regarding demographics, patient gender and race were not predictive of growth. However, age was important and the mean patient age at referral in those that showed growth was 39 years compared to 52 years in those without growth. The authors created a lettering ABCDEF guide to remember the risk factors predictive of iris nevus growth to melanoma where A = Age young, B = Blood, C = Clock hour inferior, D = Diffuse configuration, E = Ectropion and F = Feathery margin  [Table 3]. These key clinical features help to identify iris melanoma at a time when therapy could be life-saving.
|Table 3: The ABCDEF guide for factors predictive of transformation of iris nevus to iris melanoma|
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Iris melanocytoma is a subset of iris nevus with distinct clinical and histopathologic features. Clinically, this tumor presents as a deeply pigmented, dark brown domed lesion with a slightly granular surface. , The natural course is variable. Most cases remain stable and require no intervention. Spontaneous necrosis with resultant pigment dispersion and secondary glaucoma can occur and transformation to melanoma is rarely encountered. In an analysis of 47 eyes with iris melanocytoma, the mean patient age at presentation was 37 years. The mass appeared nodular (85%) or diffuse (15%) and was heavily pigmented in nearly every case.  The melanocytoma was located in the inferior (45%) or lateral (38%) quadrants most often. The tumor was a mean size of 3 mm diameter and thickness of 2 mm. Other features included heterochromia (13%), satellite tumors (26%), ectropion (6%). The tumor had shed seeds into the anterior chamber angle in 26% for a mean extent of 8 clock hours. By Kaplan-Meier analysis at 10 years follow-up, new tumor seeds developed in 63%, secondary glaucoma in 11%, and mild growth in 48%.  The growth was attributed slow benign enlargement in all cases and there was no instance of transformation to melanoma in that series.
Iris melanoma is a malignant iris tumor with risk for metastasis and death. ,,,,,, In a large analysis of 8033 eyes with melanoma, Shields et al. found 4% of iris origin and 96% of choroidal or ciliary body origin.  A subsequent series of 317 patients with iris melanoma revealed this tumor to occur in children (8%), mid-adults (59%), and older adults (33%).  Iris melanoma showed features of location in the inferior quadrant (45%) most often, mean basal diameter of 6.2 mm and mean thickness of 2.3 mm, partially or completely pigmented in 90%, and features of corectopia (45%), ectropion uveae (24%), hyphema (3%), glaucoma (35%), angle seeding (28%) for mean 2 clock hours, and extraocular extension (3%).  The mean intraocular pressure was 20 mm Hg, but it ranged from 17 to 80 mm Hg. There was no age-related differences in race, sex, tumor location, or tumor thickness. There was an age-related difference in tumor basal diameter, intraocular pressure and tumor seeding based on age, with increasing features with age in years. By Kaplan-Meier analysis, iris melanoma lead to metastasis in 5% at 5 years, 9% at 10 years, and 11% at 20 years.  By multivariate analysis, the main factors predictive of metastasis included extraocular extension and elevated intraocular pressure.  Treatment of iris melanoma includes surgical resection if the tumor is confined to 3-4 clock hours and without seeding. Plaque radiotherapy can be employed if the tumor is large and with seeding, keeping the eye intact without entering the anterior chamber.  Enucleation is advised if there is uncontrollable secondary glaucoma.
The American Joint Committee on Cancer (AJCC) staging manual, 7 th edition, provides a detailed classification for anterior (iris) and posterior (ciliary body and choroid) uveal melanoma for prognostication. In this classification, iris melanoma is classified as T1 with tumor limited to the iris, T2, with tumor extending posteriorly into ciliary body or choroid, T3 with additional scleral extension, and T4 with additional extrascleral extension.  In a collaborative report on 131 eyes with iris melanoma, Khan and coworkers found 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3 and 1% of tumors as T4.  Survival without metastasis was 100% for T1, 90% for T2 and 50% for T3 and T4.
Iris non-melanocytic tumors
In a large analysis of 3680 iris tumors, non-melanocytic lesions were found in 402 (11%) cases.  The non-melanocytic tumors included categories of choristomatous (<1%), vascular (2%), fibrous (<1%), neural (<1%), myogenic (<1%), epithelial (1%), xanthomatous/xanthogranulomatous (<1%), metastasis (2%), lymphoid (<1%), leukemic (<1%), secondary (<1%), and non-neoplastic simulators (5%) [Table 1] and [Figure 3].
|Figure 3: Iris non-melanocytic tumors (a,b) Iris vascular tumor diagnosed as racemose hemangioma, barely seen clinically (a) as ectatic vessel, but more obvious on fluorescein angiography (b) as tortuous dilated vessel (c) Iris juvenile xanthogranuloma in a one-year-old child, (d) Iris lymphoid tumor, (e) Iris metastasis from breast cancer, (f) Iris metastasis from remote cancer|
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Of 57 vascular iris tumors, the most common included racemose hemangioma (n = 37) and cavernous hemangioma (n = 7).  Vascular iris tumors were more common in mid-adult and senior adults (n = 43) compared to children and young adults (n = 14). Other studies have described various iris vascular tumors. ,, Shields et al. reviewed iris vascular tumors in an analysis of 45 cases and found several iris vascular tumors including racemose hemangioma, cavernous hemangioma, capillary hemangioma, varix and microhemangiomatosis.  Most vascular tumors occurred in adults at a mean age of 55 years. They noted that transient hyphema was the main complication, present in 30% of eyes. 
Of the 67 metastatic iris tumors, the malignancy arose from carcinoma of the breast (n = 21), lung (n = 19), kidney (n = 3), and skin [melanoma] (n = 9).  Metastatic iris tumors were more common in mid-adult and senior adults (n = 61) compared to children and young adults (n = 6). In a publication on 40 patients with metastatic tumors to the iris, the authors noted that all metastases were unilateral and secondary glaucoma was present in 38%. In 32% of cases there was no history of previous cancer and systemic evaluation disclosed the primary site in the lung, colon, breast, kidney and skin.
Another subset of non-melanocytic iris tumors includes solid epithelial tumors. In the large analysis on 3680 cases, there were 35 cases of iris epithelial solid tumors including IPE adenoma (n = 31), medulloepithelioma of iris (n = 3), and IPE adenocarcinoma (n = 1).  The medulloepitheliomas generally had a component in the non-pigmented ciliary epithelium and arose in children whereas the adenoma arose in mid-adults or senior adults (84%). The single case of adenocarcinoma arose in young adult. Other series on iris pigment epithelial adenoma and adenocarcinoma have provided descriptive details of this tumor and its notably lack of metastatic disease, despite showing aggressive malignant cytology. 
All xanthoma/xanthogranuloma (n = 16, <1%) of the iris, in this large analysis, occurred in children.  From a different perspective, of the total 446 iris tumors in children, the most common diagnoses included iris nevus (24%), IPE cyst (28%), iris stromal cyst (7%), juvenile xanthogranuloma (4%) and melanoma (8%).
Of the 198 non-neoplastic lesions simulating iris tumors, the most common diagnoses were iridocorneal endothelial syndrome (n = 50), iris atrophy (n = 42), foreign body (n = 20), coloboma (n = 20) and heterochromia (n = 19)  [Table 4]. In children, there were 49 non-neoplastic lesions simulating iris tumor and these included most often iris coloboma (n = 17) and congenital heterochromia (n = 10), compared to the 113 simulators in mid- and senior adults that proved to be iris atrophy (n = 33), iridocorneal endothelial syndrome (n = 32) and foreign body (n = 15). In a separate analysis of 71 cases of iridocorneal endothelial syndrome simulating iris melanoma, features that differentiated this degenerative condition from iris melanoma included corneal guttatae, multidirectional corectopia, polycoria, broad peripheral anterior synechiae, iris pigment epithelial defects, and lack of elevated mass with iridocorneal endothelial syndrome  [Figure 4].
|Figure 4: Non-neoplastic tumors simulating iris tumors (a) Iridocorneal endothelial syndrome with temporally directed ectropion, corectopia contracted iris and broad peripheral anterior synechiae, (b) Iridocorneal endothelial syndrome with broad peripheral anterior synechiae inferotemporally and iris adherence to endothelium with iris stromal tear, allowing visualization of the underlying iris pigment epithelium|
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| Discussion|| |
In the past, most series on iris tumors have emanated from pathology laboratories. In 1958, Duke and Dunn reported on 43 cases of iris tumors in a pathology laboratory and found malignant melanoma (n = 28), "benign melanoma" [nevus, melanocytoma] (n = 13), leiomyoma (n = 1) and uncertain (n = 1).  In 1963, Ashton published 145 iris tumors from a pathology department and found iris melanoma (n = 105), leiomyoma (n = 21), nevus (n = 10), freckle (n = 4), angioma (n = 3) and IPE tumors (n = 2).  In 1964, Heath reported on 232 iris tumors from a pathology laboratory including melanoma (n = 113), secondary invasion into iris (n = 70), leiomyoma (n = 5), metastatic tumors (n = 6), vascular tumors (n = 6) and other rare conditions.  In 2012, Shields et al. reported the first comprehensive clinic-based series of iris tumors in 3680 cases.  Much of the information in this review was extracted from this report. They categorized iris tumors [Table 1] and provided organization and illustrations to recognize the various types of iris lesions. In addition, they specifically evaluated the age at diagnosis of the various iris tumors and 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 non-neoplastic simulators (49).  Overall, in this series from a tertiary referral ocular oncology center, the three most common specific diagnoses (children, young adult, mid-adult, senior adult) were nevus (25%, 36%, 47%, 47%), IPE cyst (28%, 30%, 15%, 14%) and melanoma (8%, 16%, 20%, 19%). 
In summary, in this report we provide an overview of the clinical features and frequency of iris tumors. Iris tumors are broadly classified into cystic or solid lesions. Cystic lesions are generally benign. Solid lesions are most often melanocytic. Iris nevus is the most common solid iris tumor in all age groups. Risk factors for transformation of nevus into melanoma can be recalled using the ABCDEF guide.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]