MR Imaging of Adenomas of the Nonpigmented Ciliary Epithelium of the Eye

Discussion

ANPCEs are rare slow-growing benign tumors arising from the inner surface of the ciliary body of the eye. Tumors of the NPCE can be divided into congenital and acquired tumors. The best known congenital tumor, medulloepithelioma, arises in the embryonic or early postnatal period.^1,16 Acquired adenoma and adenocarcinoma of the NPCE are less common and arise primarily in middle age (mean age, 45 years) in patients of both sexes.^2,3,6 The pathogenesis of ANPCE remains unknown. Although some authors speculate that these tumors might represent a nodular reactive proliferation initiated by trauma or inflammation,⁶ most published cases report no history of trauma or severe prior intraocular inflammation,^2–10 and none was elicited in our patients. Although ANPCEs are benign, they can exhibit locally aggressive behavior, resulting in cataract ipsilateral to the tumor.¹ For this reason, patients with ANPCE may present with painless vision loss due to secondary focal cataracts developing at an early stage or total cataracts or subluxed lens developing later.^2–4,6 Similarly, although generally taken to be signs of intraocular malignancy found in malignant melanoma or metastases, both intraocular neovascularization and development of episcleral sentinel vessels overlying the tumor may arise in patients with ANPCE, sometimes leading to cystoid macular edema.^2,6,10

The 2 tumors in our study that appeared melanotic under slit-lamp observation proved to be amelanotic by gross pathologic examination, consistent with the prior pathology literature.^2,3,6 In retrospect, it seems likely that in these 2 cases, pigmented epithelium adjacent to the tumor was misinterpreted as a melanotic surface of the tumor by slit-lamp observation. These 2 patients were referred for and underwent enucleation of the eyes that might have been spared had ANPCE been suspected preoperatively. This experience emphasizes both the present need to better define the appearance of and increase physician awareness of ANPCE within the differential diagnosis of intraocular masses. It also suggests a clear need for continuing investigation of complementary noninvasive imaging techniques, including MR imaging methods that could differentiate ANPCE from the more common malignant intraocular melanoma and metastases.

Because the literature to date neither describes ANPCE MR imaging findings in detail nor presents any indication of how MR imaging could contribute to the differential diagnosis of ANPCE from melanoma or other malignant lesions,^6,15 we set out primarily to define in detail the conventional MR imaging of ANPCE with a view to identifying features distinct enough to merit investigation in future diagnostic controlled trials. Because the prior literature reporting the T1 of ANPCE, uveal melanoma, and metastasis in comparison with the vitreous has demonstrated a broad overlap between these lesions,¹⁷ we evaluated the T1, T2, and degree of enhancement of the ANPCE with reference to the lacrimal gland as well as the vitreous.

On pregadolinium imaging, all 8 ANPCEs were found to have a T1 similar to that of the lacrimal gland, including the 2 cases clinically misdiagnosed as melanotic on slit-lamp examination. Although we did not design the current study to include formal assessment of uveal melanoma and we have not found any literature directly reporting the T1 of melanoma with respect to lacrimal gland, in our experience, the T1 of malignant melanoma is generally shorter than that in the lacrimal gland, suggesting that this feature may deserve further study as a potential differentiator of ANPCE in a future controlled trial. As expected from the fact that the T1 of the vitreous is longer than that of the normal lacrimal gland, in 7 of the 8 cases, the ANPCE T1 was also shorter (higher signal intensity on T1WI) than that in the vitreous. In the remaining case, the ANPCE T1 was essentially identical to that of the vitreous. Because nearly all intraocular melanoma and metastases have a T1 shorter than that in the vitreous, comparison of tumor with vitreous on T1WI is unlikely to contribute to the differential diagnosis of these lesions.

On T2WI, 6 of our ANPCEs had T2s longer than those in the lacrimal gland (producing higher signal intensity on T2WI), and 2 had T2 similar to that of the lacrimal gland. Again, because we recognize that the design of our current study does not include formal assessment of uveal melanoma, in our experience, the T2 of malignant melanoma is generally shorter than that of the lacrimal gland, suggesting that T2 longer than or equal to that of the lacrimal gland could contribute to the differentiation of ANPCE from melanoma and that this feature deserves to be included in further differential diagnostic MR imaging studies.

The T2 of ANPCE in our study was also shorter than that of the vitreous in most cases. Unfortunately, the literature documents that melanoma characteristically also has a T2 shorter than that of the vitreous, suggesting that lacrimal gland tissue may offer a superior reference to the vitreous or orbital fat for assessing the signal intensity of ciliary body tumors on T2WI and T1WI.

Our results indicate that ANPCE most commonly presents as an oval or round mass. While roughly one-third of melanomas have a characteristic mushroom-shape not observed in our series, up to two-thirds of melanomas and nearly half of metastases may appear as oval or round masses.^{11,12,14,17,18} Thus, while a mushroom shape may be used to favor melanoma over ANPCE, an oval or round shape cannot reliably differentiate ANPCE from melanoma or metastasis. In addition, MR imaging evidence of extraocular growth was not seen in our series and would be very unusual for a benign lesion such as ANPCE but has frequently been reported in malignant melanoma.^11,12,14 Thus, although the round or oval shape and the absence of extraocular extension characteristically observed in ANPCE cannot be used to favor ANPCE over melanoma to any significant degree, the observation of a mushroom shape, or more conclusively extraocular extension, may help to exclude ANPCE from the differential diagnosis.

The most important consideration in the differential diagnosis of tumors of the ANPCE is ciliary body melanoma because melanoma is more common and, unlike ANPCE, requires enucleation. Other main considerations in the differential diagnosis are medulloepithelioma, adenoma, or adenocarcinoma of the ciliary pigment epithelium, leiomyoma, schwannoma, metastatic carcinoma, and granuloma.^{2–6,12–14,16,19,20}

Unlike ANPCE, many of these lesions require enucleation. Medulloepithelioma, a congenital tumor with its onset in the first decade of life and often associated with lens coloboma, iris neovascularization, and signs of persistent primary vitreous,¹⁶ can be differentiated readily by clinical findings. Metastatic carcinoma is more likely to occur in patients with a history of carcinoma and concurrent metastases elsewhere.^12,13 Ciliary body granuloma is always associated with more severe uveal inflammation, and the patient tends to have systemic manifestations of a granulomatous condition.^12,13

Two relatively less common lesions in the differential diagnosis that may present difficulty clinically include adenomas or adenocarcinomas of the ciliary pigment epithelium. The distinction between these 2 entities is based on the degree of histologic invasion, but because these may be distinguished from unpigmented lesions such as ANPCE on slit-lamp examination due to their pigmented appearance, they could be confused with melanoma. Our limited experience suggests that the 2 adenomas of the ciliary pigment epithelium we have encountered were hyperintense on T1WIs and hypointense on T2WIs relative to lacrimal gland tissue and presented a potential clinical and MR imaging mimic of melanoma. Similarly, leiomyoma and schwannoma of ciliary body may be indistinguishable from ANPCE by clinical or imaging findings but may also be treated with local resection, like ANPCE.^12,20 The most appropriate management for ANPCE is generally local tumor resection only, rather than enucleation, if ANPCE is detected clinically at a relatively early stage.

Although ANPCE can behave aggressively locally, it appears less likely to recur after removal of the tumor locally. The life expectancy for patients with ANPCE is excellent. Although ANPCE may evolve into adenocarcinomas of the NPCE, adenocarcinomas of the NPCE have no tendency to metastasize, so differentiation of these 2 pathologically distinct but clinically similar entities is of little practical importance.⁶ Thus while a method to suspect ANPCE rather than melanoma preoperatively in appropriate cases would not completely resolve the problem of diagnosing ocular masses, this differentiation could prevent the unnecessary enucleation of a number of benign lesions and seems an important goal for orbital MR imaging.