Tapioca melanoma of the iris is a rare form of diffuse iris melanoma. To date, there have been a total of 20 cases of tapioca melanoma of the iris reported.1–13 It usually presents unilaterally with hyperchromic heterochromia and the patient may have glaucomatous changes secondary to obstruction of the aqueous outflow. The neoplasm is generally described as lightly pigmented or amelanotic. It has a nodular surface similar to the appearance of tapioca that is diffuse and circumferential and involving the iris, anterior chamber angle, and possibly the ciliary body.14,15 In contrast, the most common presentation of an iris melanoma usually involves a deeply pigmented, solitary mass, with distinct borders.
An iris nevus can be distinguished clinically in most cases and is a benign lesion. Iris melanoma is typically confirmed immunohistologically with histologic staining showing that the tumor is melanotic and cancerous. Furthermore, melanomas of the iris are known for their local invasion, and when they become metastatic, it is usually to the liver.15 Identification of tapioca melanomas of the iris is important because its presentation and surgical management may differ from that of other malignant iris melanomas.
A 14-year-old white female patient was referred to our clinic for evaluation of a mass on the iris of her right eye. The patient had no ocular pain, photophobia, or visual changes. Additionally, she had no significant medical or surgical history and her family history was non-contributory. The lesion was originally noted approximately 3 years before this examination; however, over the last 4 months a progressive increase in size of the lesion had been observed. The patient was being treated elsewhere with topical prednisolone acetate 1% drop four times per day on her right eye over the last week. On examination, best-corrected visual acuities were 20/20 in her right eye (OD) and her left eye (OS), and her intraocular pressures were 8 mm Hg and 11 mm Hg, respectively. She had no relative afferent pupil defect, but a distorted pupil OD; her confrontation visual fields and extraocular motility were intact, and Amsler grids were unremarkable.
The patient’s corneas had no erosions or abrasions, the stroma was clear, the endothelial surface was smooth, and there was no fluorescein staining. The anterior segment examination of the right eye revealed an elevated, markedly vascular, amelanotic, multifocal mass situated at the 5:30 clock hour of the iris, along with multiple multifocal smaller satellite lesions (Fig. 1A). The patient’s anterior segment OS was clear, without cell and flare, deep, well formed, and did not display iris heterochromia when compared to the fellow eye (Fig. 1B). On gonioscopic evaluation of the right eye, the lesion appeared to extend along the angle from the 4:30 to 7:00 clock hours (Fig. 2). High-resolution echography (Ellex Eye Cubed unit; Ellex Medical Pty. Ltd., Adelaide, Australia) measured the tumor to be approximately 8 × 7 × 2.2 mm, without posterior extension (Fig. 3). Dilated fundus examination was unremarkable OU.
The patient underwent an incisional biopsy of the lesion, which was sent to the pathology department at Bascom Palmer Eye Institute for analysis (Fig. 4). The stroma of the specimen was largely replaced by sheets and nests of cellular tumor. The tumor was composed of amelanotic or lightly pigmented spindle cells with bland nucleoplasm. Rare nucleoli were identified. The cells formed interweaving fascicles. The melan-A and S-100 stains were positive and the Ki-67 stain showed moderate positivity. The leukocyte common antigen (LCA) stain was negative. It was determined to be a low grade spindle melanoma, consistent with clinical findings.
On November 22, 2010, the patient underwent an uneventful enucleation of the right eye. She is presently free of metastatic disease.
Tapioca melanoma of the iris is a rare occurrence. It is also unique in that it presents in a much younger patient population than other melanomas of the iris.16 The average age at surgery for tapioca melanoma of the iris is 30 with the average age at surgery for other iris melanomas being 46.14 With our patient being 14 years old, she is not the youngest patient to have tapioca melanoma of the iris, but she is towards the lower end of the age range.
Iris tumors can be divided and subdivided into multiple categories. The first differentiation is cystic versus solid. Solid tumors are then divided into melanocytic or nonmelanocytic, amelanotic. The melanocytic tumors are divided into nevi, melanocytoma, melanoma, and melanocytosis. The amelanotic tumors are divided into choriostomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous, metastasis, lymphoid, leukemic, secondary, and nonneoplastic simulators. Iris melanomas are rare tumors and generally behave less aggressively than other uveal melanomas. Metastases have been found in 3% to 5% of cases.16 Important differential diagnoses to consider include neurofibromatosis, Cogan Reese syndrome, and uveitic conditions such as sarcoidosis. Patients with neurofibromatosis may have Lisch nodules on their iris. These will look yellow-brown on slit-lamp examination and look like dome-shaped papules. Cogan Reese syndrome will have an irregular corneal endothelium and pedunculated or diffuse pigmented nodules. In sarcoidosis, the patient may have systemic signs and symptoms as well as papillitis, direct invasion of the optic disc, or papilledema as well as granulomas anywhere in the eye.
The diagnosis of tapioca melanoma of the iris is based on biomicroscopy, with attention to gonioscopy, and histopathology. The tumor surface is nodular with significant vascularity that has been shown on fluorescein angiography to have distinct leakage within the tumor, but not outside of the tumor, which differentiates it from a granulomatous iritis.12 There is generally a large primary tumor that is present inferiorly with a nodular and often diffuse growth pattern over the iris. The tumor can be poorly adhesive, with multiple lesions, indicative of tumor seeding and malignancy.
Gonioscopic evaluation is important as extension of the tumor into the angle or seeding may be present, causing an increase in intraocular pressure. The elevated pressures in this specific type of iris melanoma are usually a result of the accumulation of epithelioid cells in the anterior chamber. Diffuse melanomas of the iris are known to have a higher incidence of epithelioid cells than other iris tumors.
The most unique presentation of the patient in this case was the lack of acquired iris heterochromia. It has been thought that tapioca melanoma of the iris occurs in patients with heterochromia,13,15 but, as can be clearly seen by Fig. 1, our patient did not present with heterochromia. This is likely a result of the fact that although small satellite lesions covered some of our patient’s iris, the majority of the tumor remained localized inferiorly, allowing excellent visualization of the iris stroma. Localization of the tumor may also explain why our patient’s IOP was not elevated because it spared the majority of the anterior chamber angle.
Immunohistologically, our patient tested positive for S-100, which is used to stain for neural tissue and melanomas, melan-A, which stains for melanocytes, and Ki-67, which is used to stain proliferating cells. The combination of S-100 and melan-A shows that the tumor is a melanoma, and the addition of Ki-67 shows us that this is a cancerous tumor. She tested negative for LCA which is used to differentiate hematopoietic cells from non-hematopoietic cells. Other stains that can be used are HMB-45, which also stains melanocytes, and p53, which stains cells that have had their tumor suppressor gene inactivated.11,13
Also of importance are the contributing factors that may cause a patient to acquire melanoma of the iris. In our patient, there is no family history of cutaneous melanoma or melanoma of the iris. Predisposing factors to uveal melanoma are ocular melanocytosis, neurofibromatosis type 1, dysplastic nevus syndrome with familial atypical mole and melanoma syndrome, and familial uveal melanoma.17 Once again, our patient had none of those predisposing factors.
Various management strategies have been utilized and proposed. Because tapioca melanoma of the iris generally has locally invasive growth, it may be observed with serial photography until growth is observed, at which time total surgical excision may be indicated. At this point, echography should be employed to determine extraocular extension, which is useful in determining management. There are additional reports that suggest the tumor should be excised when growth exceeds 3 mm diameter or 1 mm prominence, but there is no agreement in the literature on any particular tumor size criteria for surgical management. A sector iridectomy can only be recommended when the anterior chamber angle is uninvolved and no satellite lesions are evident. If the angle is involved, an en bloc excision of the tumor with adjacent structures is an option.18 However, because this variety of tumor has malignant potential, enucleation should be considered. The anterior chamber must also be monitored for free-floating tumor nodules. Iris tapioca melanoma has poor cellular adhesion within the tumor. It can break apart during surgery or during tumor growth, which allows for seeding as well as tumor recurrence. Although careful examination and aspiration of any free nodules during or following excision may control additional tumor formation, enucleation of the eye is preferred to definitively prevent additional seeding. Another management for melanomas of the iris is I-125 brachytherapy.19 This has been used successfully, and may be a future treatment for tapioca melanoma of the iris, but it has yet to be used for these lesions because of the likelihood of sparing satellite tumor cells. In this case, the patient underwent enucleation of her eye. This management was chosen because of the seeding that was apparent upon anterior chamber evaluation and to limit the chance of metastatic disease that may occur with a wait-and-watch approach. Our patient is currently free of known metastasis; however, metastatic disease cannot be ruled out definitively, as microscopic tumor cells may be too small to be detectable through conventional imaging. Because of this, our patient is still closely monitored by a medical oncologist in addition to our serial observation. Additionally, our patient declined professional psychological counseling; however, therapy should be considered with a potential life-altering management strategy for a young patient.
Clinical differentiation between benign and malignant lesions of the iris is extremely difficult. A rare yet devastating form of melanoma with an amelanotic nodular appearance known as tapioca melanoma of the iris should be included into this vast differential. In this case report, this extremely rare tumor presented in an even rarer patient. Our patient was towards the very young end of the age range and was not heterochromic. She did not have elevated intraocular pressures nor did she show any glaucomatous changes. These deviations from the norm of this rare disease may bring up the question of different genomic types of tapioca melanoma of the iris with different presentations in different patient populations. Furthermore, tapioca melanoma of the iris should be included in the list of differentials for patients presenting with amelanotic iris lesions, even when iris heterochromia is not evident.
Received October 18, 2013; accepted December 20, 2013.
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