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Purpose: To find immunohistochemical markers that distinguish adenocarcinoma of the nonpigmented ciliary epithelium (NPCE) from metastatic carcinoma, especially metastatic renal cell carcinoma., Design: Retrospective case series., Methods: Three cases of adenocarcinoma of the NPCE were examined histologically with hematoxylin-eosin stain and immunohistochemical stains including vimentin, AE1/AE3, Cam 5.2, CK7, PAX2, PAX8, AMACR, and CAIX. We also reviewed previously reported cases of this tumor., Results: We found that the immunohistochemical profile of adenocarcinoma of the NPCE can overlap with renal cell carcinoma. Both tumors can express vimentin, cytokeratin AE1/AE3, Cam 5.2, PAX2, PAX8, and AMACR. One of the adenocarcinomas of the NPCE in our series also expressed CD10 and the renal cell carcinoma marker (RCC Ma). Carbonic anhydrase IX (CAIX) was not detected in any of the 3 tumors., Conclusions: Adenocarcinomas arising in phthisic eyes can be diagnostically challenging. We have found it particularly difficult to distinguish adenocarcinoma of the NPCE from metastatic carcinoma, especially metastatic clear cell renal cell carcinoma and papillary renal cell carcinoma. Because of the immunophenotypic overlap, most patients will require systemic workup including imaging of the kidneys to be certain of the diagnosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To compare immunohistochemical and genetic overlaps and differences between intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain., Design: Retrospective histopathologic, immunohistochemical, and genetic analysis of 20 intraocular medulloepitheliomas., Methods: (1) Review of clinical data and hematoxylin-eosin-stained sections with (2) immunohistochemical staining of paraffin sections using a polyclonal antibody against the protein LIN28A, and (3) fluorescence in situ hybridization (FISH) testing for the amplification of the genetic locus 19q13.42 involving the C19MC cluster of miRNA. Ten retinoblastomas served as controls and to determine the specificity of these biomarkers for intraocular medulloepitheliomas., Results: Nineteen of the 20 intraocular medulloepitheliomas were either diffusely or focally LIN28A positive (weak, moderate, or strong). The most intense positivity correlated with aggressive behavior such as intraocular tissue invasion or extraocular extension. None of the cases studied by FISH harbored an amplicon for C19MC. The 10 retinoblastomas were LIN28A and C19MC negative., Conclusion: LIN28A has a putative role in oncogenesis and is found only in embryonic cells and malignancies. Intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain both display LIN28A positivity. Only the latter, however, display amplification of the 19q13.42 locus involving C19MC, implying that other causative factors are at play in intraocular medulloepitheliomas. More aggressive tumor behavior within the eye can be partially predicted by LIN28A staining intensity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical features, histopathology, treatment, and outcomes of ciliary body medulloepithelioma., Design: Retrospective study., Participants: Forty-one patients with medulloepithelioma., Intervention: Cryotherapy, plaque radiotherapy, external beam radiotherapy, tumor removal by partial lamellar sclerouvectomy (PLSU), or enucleation., Main Outcome Measures: Metastasis and death., Results: Of 41 patients with ciliary body medulloepithelioma, the median age at diagnosis was 5 years. The mean tumor basal diameter was 11 mm, and the mean tumor thickness was 7 mm. Related features included secondary glaucoma (n = 18, 44%), iris neovascularization (n = 21, 51%), cataract (n = 19, 46%), lens subluxation (n = 11, 27%), lens coloboma (n = 8, 20%), retrolental neoplastic cyclitic membrane (n = 21, 51%), intratumoral cysts (n = 25, 61%), and extraocular extension (n = 4, 10%). There was systemic association with pleuropulmonary blastoma in 2 cases (5%). Primary tumor treatment included enucleation (n = 21, 60%), tumor removal by PLSU (n = 8, 23%), plaque radiotherapy (n = 3, 9%), external beam radiotherapy (n = 1, 3%), cryotherapy (n = 1, 3%), or palliative chemotherapy (n = 1, 3%). In 1 case, medulloepithelioma was diagnosed histopathologically after inadvertent evisceration for blind painful eye. Subsequent treatment for residual or recurrent tumor in cases treated conservatively/inappropriately (n = 15) was necessary in 7 cases (47%). Histopathology disclosed benign features in 6 cases (20%), malignant features in 24 cases (80%), teratoid features in 11 cases (37%), and nonteratoid features in 19 cases (63%). In the 26 enucleated eyes, other features included retrolental neoplastic cyclitic membrane (n = 18, 69%), neoplastic epiretinal membrane (n = 6, 23%), and persistent hyaloid artery (n = 6, 23%). Systemic metastasis occurred in 3 cases (8%) over a mean follow-up of 49 months, all of whom presented with extrascleral extension of tumor due to mean delay in diagnosis by 39 months., Conclusions: Medulloepithelioma most commonly occurs in children. Systemic association with pleuropulmonary blastoma rarely is found. Patients with extrascleral medulloepithelioma are at risk for metastasis., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Uveal metastases are rare in children and metastasis from sarcoma is rare at any age. We report a purportedly healthy 10-year-old girl who developed ciliochoroidal metastasis from an occult primary extraosseous sarcoma of the ankle region. The patient died from widespread metastases 6 months after enucleation despite intensive chemotherapy., (Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

We report a ciliary body melanoma that apparently arose from a melanocytoma in a 15-year-old black teenager. The eye was enucleated, and metastatic evaluation remained negative at 5 years' follow-up. This unusual case, confirmed histopathologically, reveals that young patients with melanocytoma can have malignant transformation at an early age., (Copyright 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Purpose: To describe progressive enlargement of intralesional cavities within a mass that masqueraded clinically as an iris pigment epithelial cyst for 2 years but later proved to be a melanoma., Methods: An 81-year-old woman developed asymptomatic focal elevation of the iris, and ultrasound biomicroscopy showed a fluid-filled mass that was interpreted as an iris pigment epithelial cyst. Over a 2-year period of observation, the cavity enlarged from 0.7 to 10 mm, and the solid component enlarged from approximately 6 to 16 mm basal dimension., Results: On referral, visual acuity was 20/400 in the right eye and 20/25 in the left eye. The affected right eye displayed a pigmented mushroom-shaped ciliary body mass with anterior chamber invasion, distorting the pupil and occupying 40% of the anterior chamber. Ultrasound biomicroscopy and B-scan ultrasonography revealed many cavities within the 14-mm-thick mass, suggestive of ciliary body melanoma. After enucleation, histopathology disclosed multiple cavities, some with granular eosinophilic material, within a mushroom-shaped mixed-cell melanoma., Conclusion: Cavitation can occur in ciliary body melanoma and can lead to misinterpretation as a cyst. Cavitary melanoma should be considered in the differential diagnosis of cystic lesions of the anterior segment.

Background: Ring melanoma of the ciliary body is a rare variant of uveal melanoma that has a poor prognosis. Only isolated cases have been reported in the literature., Methods: A retrospective review of the clinical features, management, histopathology, and prognosis of 23 consecutive patients with ring melanoma of the ciliary body was performed., Results: Of 8,800 patients with uveal melanoma treated on the Oncology Service at Wills Eye Hospital over a 25-year period, only 23 patients (0.3%) were found to have ring melanoma of the ciliary body. The mean patient age was 59 years (median, 63 years; range, 8-81 years). The only visual symptom was blurred vision in 17 patients (74%), and the other six patients (26%) were asymptomatic. At the initial presentation elsewhere, melanoma was recognized in 13 cases (57%). In the remaining 10 cases (43%), the initial clinical diagnosis was glaucoma in three (13%), iris nevus in three (13%), cataract in two (9%), ciliary body detachment in one (4%), and iridocyclitis in one (4%). The patients were observed elsewhere for a mean of 3 months before the diagnosis of melanoma was suspected and referral to Oncology Service was made. On examination, the tumor involved a mean of eight clock hours of the ciliary body. Seven patients (30%) had complete circumferential (360 degrees) involvement of the ciliary body, and 16 (70%) had incomplete (180-360 degrees) ring involvement. The mean tumor thickness was 8 mm. Associated findings included neovascularization of the iris in one case (4%), shallow anterior chamber in 11 (48%), anterior chamber inflammation in five (22%), cataract in nine (39%), lens indentation in eight (35%), and lens subluxation in three (13%). A prominent episcleral (sentinel) vessel (17 cases, 74%), multilobulation of the mass (19 cases, 83%), blockage of light on transillumination (23 cases, 100%), and ultrasonographic hollowness with intrinsic pulsations (23 cases, 100%) were important features differentiating this tumor from simulating conditions. The tumor was managed with enucleation in all 23 patients. Histopathologic studies revealed epithelioid cell-type melanoma in two patients (9%), mixed cell-type in 17 (74%), and spindle cell-type in four (17%). Extraocular extension was present in eight patients (35%). Metastasis developed in 12 of 23 patients (52%) after a mean follow-up of 55 months., Conclusions: Ring melanoma of the ciliary body is a rare tumor that can remain hidden from ophthalmoscopic examination. Certain features, such as prominent episcleral sentinel vessels, multilobulation of the mass, light blockage on transillumination, and ultrasonographic hollowness with intrinsic vascular pulsations, suggest the diagnosis. The life prognosis is poor.

ObjectiveTo analyze the genetic features of melanocytomas and melanomas of the anterior uvea and assess the value of molecular testing for diagnosis and prognostication.DesignRetrospective case-control study.SubjectsPatients with melanocytoma (n = 16) and melanoma (n = 19) of the anterior uvea.MethodsTargeted next-generation sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue from anterior uveal melanocytic tumors and correlated with clinicopathologic features.Main outcome measuresPresence or absence of accompanying oncogenic alterations beyond GNAQ/GNA11 and their association with histologic features and local recurrence.ResultsHotspot missense mutations in GNAQ/GNA11 were identified in 91% (32/35) of all cases. None of the melanocytomas with or without atypia demonstrated chromosomal imbalances or additional oncogenic variants beyond GNAQ mutation, and none recurred over a median follow-up of 36 months. Additional alterations identified in a subset of melanomas include mutations in BAP1 (n = 3), EIF1AX (n = 4), SRSF2 (n = 1), PTEN (n = 1), and EP300 (n = 1); monosomy 3p (n = 6); trisomy 6p (n = 3); trisomy 8q (n = 2); and an ultraviolet mutational signature (n = 5). Local recurrences were limited to melanomas, all of which demonstrated oncogenic alterations in addition to GNAQ/GNA11 (n = 5). A single melanoma harboring GNAQ and BAP1 mutations and monosomy 3 was the only tumor that metastasized.ConclusionsIn this study, anterior segment uveal melanocytomas did not display oncogenic alterations beyond GNAQ/GNA11. Therefore, they are genetically similar to uveal nevi rather than uveal melanoma based on their molecular features known from the literature. Molecular testing can be performed on borderline cases to aid risk stratification and clinical management decisions.

Purpose: This study investigated the ocular distribution of bimatoprost, latanoprost, and their acid hydrolysis products in the aqueous humor, cornea, sclera, iris, and ciliary body of patients treated with a single topical dose of 0.03% bimatoprost or 0.005% latanoprost for understanding concentration-activity relationships. Methods: Thirty-one patients undergoing enucleation for an intraocular tumor not affecting the anterior part of the globe were randomized to treatment with bimatoprost or latanoprost at 1, 3, 6 or 12 h prior to surgery. Concentrations of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid in the human aqueous and ocular tissues were measured using liquid chromatography tandem mass spectrometry. Results: Following topical administration, intact bimatoprost was distributed in human eyes with a rank order of cornea/sclera >iris/ciliary body >aqueous humor. Bimatoprost acid was also detected in these tissues, where its low levels in the cornea relative to that of latanoprost acid indicated that bimatoprost hydrolysis was limited. Latanoprost behaved as a prodrug that entered eyes predominantly via the corneal route. Levels of latanoprost acid were distributed as cornea >>aqueous humor>iris>sclera>ciliary body. Conclusions: Our study provided experimental evidence that levels of bimatoprost in relevant ocular tissues, and not only aqueous humor, are needed to understand the mechanisms by which bimatoprost lowers intraocular pressure (IOP) in human subjects. The data suggest that bimatoprost reached the target tissues favoring the conjunctival/scleral absorption route. Findings of intact bimatoprost in the target ciliary body indicated its direct involvement in reducing IOP. However, bimatoprost acid may have only a limited contribution on the basis that bimatoprost has greater/similar IOP-lowering efficacy than latanoprost, yet bimatoprost acid levels were a fraction of latanoprost acid levels in the aqueous humor and cornea and only sporadically detectable in the ciliary body. In this report, human ocular tissues were examined concurrently with aqueous humor for the in vivo distribution of bimatoprost, bimatoprost acid, latanoprost, and latanoprost acid. [ABSTRACT FROM AUTHOR]

Leiomyoma is a rare intraocular tumor that arises from uveal smooth muscle. Herein, we report a large leiomyoma that occupied nearly 50% of the globe, closely resembling melanoma. A 40-year-old female presented with a 17 × 15 × 11 mm amelanotic ciliochoroidal mass causing visual defect in her right eye (OD). Based on transillumination features of tumor shadow and ultrasonographic features of acoustically solid mass, there was low clinical suspicion for leiomyoma or schwannoma, and a preliminary diagnosis of ciliochoroidal melanoma was rendered. Following enucleation, histopathology revealed a paucicellular tumor comprised of spindle cells, with positive immunostaining for smooth muscle actin and negative stains for melanoma markers (S-100 protein, HMB45, and MITF-2). These features were consistent with ciliochoroidal leiomyoma. Benign uveal leiomyoma can achieve an unusually large size and block light transmission on transillumination, features that simulate malignant melanoma. [ABSTRACT FROM AUTHOR]

Cyst-like cavities in uveal melanoma occur rarely and can simulate a benign intraocular cystic lesion resulting in delayed diagnosis and inappropriate management. Herein, we describe a 66-year-old Caucasian female who presented with a "cystic" ciliary body mass in the right eye oculus dexter (OD). Slit lamp examination OD showed anterior bulging of the iris temporally from an underlying pigmented ciliary body mass and transillumination disclosed slight shadow from the tumor. Ultrasound biomicroscopy (UBM) revealed multiple cyst-like cavities within a tumor, lined by "thick walls" of at least 200 μm and occupying 80% of the tumor volume. A clinical diagnosis of multicavitary ciliary body melanoma was suspected and partial lamellar sclero iridocyclectomy was performed. Histopathology confirmed the diagnosis of low-grade spindle melanoma of the ciliary body with multiple empty and fluid filled cyst-like cavities without epithelial lining. UBM is an important diagnostic tool in the differentiation of "thick walled" cavitary melanoma from "thin walled" benign pigment epithelial cyst. [ABSTRACT FROM AUTHOR]

To evaluate the distribution of the PAX8 transcription factor protein in ocular tissues and to investigate if immunohistochemical stains for this biomarker are useful in the diagnosis of intraocular tumors. Observational case series. Excision and cytologic analysis specimens of 6 ciliary body epithelial neoplasms, 2 iris epithelial neoplasms, 3 retinal pigment epithelial neoplasms, 3 intraocular medulloepitheliomas, 15 uveal melanomas, and 5 uveal melanocytomas. Hematoxylin–eosin and PAX8 immunohistochemical stains were performed on all specimens. In appropriate cases, bleached preparations and other immunohistochemical stains, including AE1/AE3 cytokeratin, Lin28A, and CD45, were performed. Distribution of PAX8 expression in normal and neoplastic tissue. Strong nuclear PAX8 expression was observed in the normal corneal epithelium, iris sphincter pupillae muscle, iris pigment epithelium and dilator muscle complex, nonpigmented and pigmented epithelia of the ciliary body, lens epithelium, and a subset of retinal neurons. The normal retinal pigment epithelium and uveal melanocytes did not stain for PAX8. The ciliary body epithelial and neuroepithelial tumors (adenoma, adenocarcinoma, and medulloepithelioma) showed uniform strong nuclear PAX8 immunoreactivity. All melanocytic tumors (iris melanoma, ciliary–choroidal melanoma, and melanocytoma) and retinal pigment epithelial neoplasms showed negative results for PAX8. A subset of tumor-associated lymphocytes, most prominent in uveal melanoma, showed positive results for PAX8. The uniformity of the PAX8 staining was superior to the variable cytokeratin staining in the ciliary epithelial neoplasms and the variable Lin28A staining in malignant medulloepithelioma. The veracity of PAX8 staining was equally as robust on cytologic analysis and open-flap biopsy specimens of ciliary epithelial and iris epithelial neoplasms, melanocytoma, and melanoma. PAX8 has proven to be a very useful diagnostic marker in a select group of adult intraocular tumors, and we highly recommend its inclusion in diagnostic antibody panels of morphologically challenging intraocular neoplasms. [ABSTRACT FROM AUTHOR]