Dr.Pukhraj Rishi, R08659, Dr. Ashutosh Agarwal, Dr.Jyotirmay Biswas
Abstract
Aim: To study the clinico-pathological features of anterior uveal tumors.
Methods: Eleven eyes of 11 patients were included in this retrospective case series. Cases included eight ciliary body (CB) tumors (choroidal melanoma, n=2; medulloepithelioma, n=2; leiomyoma, n=1; hematoma, n=1; Epitheloid neoplasm of uncertain origin, n=1; and IgG4 disease, n=1) and 3 iris tumors (Non-specific granuloma, n=1; foreign body granuloma, n=1; and Iris-CB fungal granuloma, n=1). Excisional biopsy was done by Partial Lamellar Sclero-Uvectomy (PLSU) for CB tumours, and via anterior limbal route for iris tumours. Primary enucleation was done for 3 cases. Histo-pathology reports were obtained for each case. Immunological markers were obtained as and when required.
Results: Mean age of the subjects was 45.3±20.5 years (range: 13-70 years), with a mean follow up period of 11.9 months (Range: 2 to 37 months). Mean BCVA was 0.51 logMAR which changed to 1.05 post-operatively. Mean IOP decreased from 16.4(±15.3) mm Hg to 13(±9.0) post-operatively. Adjuvant vitrectomy was performed for 6 cases. Three eyes were enucleated and 1 eye developed phthisis. Complications included vitreous hemorrhage (n=4), retinal detachment (n=4), hypotony (n=3), secondary NVG (n=2), hyphema (n=2), retro-lental cyclitic membrane (n=2), supra-choroidal effusion (n=1), scleritis(n=1), choroidal detachment(n=1) with no recurrence of the tumor in any case.
Conclusion: Excision of anterior uveal tumors can provide diagnosis of a myriad etiology.
Introduction
The diagnosis of a disease can be established on etiological, histopathological, or molecular basis. Tissue biopsy involves the surgical removal and histopathological/cytopathological evaluation of a tissue specimen to provide a diagnosis and estimate the prognosis.[1] Hirschberg in 1868 performed the first intraocular biopsy.[2] The techniques for intraocular biopsy have evolved over the years and serve to be imperative in the diagnosis and verification of malignant tumors before initiating any form of therapy.[3]
Anterior uveal tumors comprise of mass-lesions originating from the iris and ciliary body. Tumors in the anterior segment typically originate from uveal tissue and only rarely from the cornea or lens. Iris tumors can be broadly categorized into cystic or solid. Primary iris cysts including stromal cystsand pigment epithelial (IPE) cysts. Solid tumors can either be melanocytic or non-melanocytic in origin. Iris melanocytic tumors include freckle, nevus, melanocytoma, Lisch nodule, and melanoma. Shields et al reported the first comprehensive clinic-based series of iris tumors in 3680 cases.[4] The non-melanocytic tumors included categories of choristomatous, vascular, fibrous, neural, myogenic, epithelial, xanthomatous/xanthogranulomatous, metastasis, lymphoid, leukemic, secondary, and non-neoplastic simulators. Of the non-neoplastic lesions simulating iris tumors, the most common diagnoses were iridocorneal endothelial syndrome, iris atrophy, foreign body, coloboma, and heterochromia.
CB tumors include primary and secondary stromal tumors, neuro-epithelial tumors and non-neoplastic simulators of tumors. Primary stromal tumors comprise of nevus, melanocytoma, malignant melanoma, leiomyoma and mesectodermal leiomyomas, and peripheral nerve sheath tumors. Neuro-epithelial tumors consist of Fuchs adenoma, embryonal medulloepithelioma, and adenoma and carcinoma of the ciliary epithelium. Secondary stromal tumors include metastasis, lymphoma, and leukemia. Clinical characteristics of anterior uveal tumors are aided by ancillary tests, which include ultrasound biomicroscopy, AS-OCT (Anterior segment optical coherence tomography), fluorescein angiography, CT (Computed tomography), MRI (Magnetic resonance imaging), and FNAB (Fine needle aspiration biopsy) to reach a provisional diagnosis. Excision biopsy and histopathology along with immunohistochemistry (IHC) confirms the diagnosis and helps to differentiate between benign and malignant tumors, and non-neoplastic simulators of tumors. Accessibility of anterior segment tumors through the cornea and limbus provides an easier approach for excision biopsy, and fine needle aspiration (FNAB).
The aim of this retrospective case series was to correlate the clinical and histopathological diagnosis for various iris and ciliary body tumors. To the best of our knowledge, there is no case series from India which reports the clinico-pathological co-relation of anterior uveal tumors.
Materials and methods
This was a retrospective, observational case series. Medical records of 11 eyes of 11 patients who presented with iris and ciliary body tumors of varying etiology, between April 2014 and September 2016, were analyzed. Institutional review board approval was sought for the study. All patients consented with a written informed consent form. The study adhered to the tenets of declaration of Helsinki. The cases included eight ciliary body (CB) tumors (2 CB-choroidal melanomas, 2 medulloepitheliomas, 1 leiomyoma, 1 hematoma, 1 Epithelioid neoplasm of uncertain origin and 1 IgG4 disease) and 3 iris tumors (1 non-specific granuloma, 1 foreign body granuloma and 1 iris CB fungal granuloma). At presentation, a detailed case history was noted. Clinical examination included measurement of BCVA, slit lamp examination, undilated gonioscopy, IOP measurement by GAT, dilated fundus examination and transillumination of the mass. Tumor size was noted on clinical examination. Measurement of greatest basal dimension and apical height were made using Ultrasound Biomicroscopy. Ancillary tests included fundus fluorescein angiography (FFA), computerized tomography (CT), magnetic resonance imaging (MRI), and fine needle aspiration biopsy (FNAB), as and when required. Excision biopsy of the tumors was done via the anterior limbal route for iris tumors, and by partial lamellar sclera-uvectomy (PLSU) for ciliary body tumors. Primary enucleation was done for melanomas involving both the ciliary body and choroid. Additional procedures including adjuvant vitrectomy, scleral buckling, lensectomy, scleral patch graft, pupilloplasty, plaque brachytherapy, diode laser photocoagulation, conjunctivoplasty, phacoemulsification and silicon oil removal were done, when required. Histo-pathology reports were obtained for all cases to verify the clinical diagnosis. Post-operative outcomes were noted in terms of globe salvage, best corrected visual acuity (BCVA), complications, and tumor recurrence.
Results
Eleven eyes of 11 patients were included in this retrospective, interventional case series. The mean age of the subjects was 45.3(±20.5) years, ranging from 13 to 70 years. All patients, except one, presented with complaints of dimness of vision. Other presenting complaints included ocular pain (n=2), redness (n=2), floaters (n=1), lid swelling (n=1), and a visual field defect (n=1). Previous ocular history included history of cataract surgery (n=3), Nd:YAG capsulotomy (n=1), sectoral PRP (n=1) and intravitreal injections (n=2). Case no. 6 was on treatment for scleritis and case no. 9 was being treated for suspected post-operative endophthalmitis. Four subjects did not have any surgery of past ophthalmic intervention in the affected eye. Three patients were known cases of systemic hypertension and one of them also had type II diabetes mellitus. The mean presenting BCVA was 0.51(±0.42) logMAR, ranging from 0 to 1.30. Mean IOP at baseline was 16.4 (±15.3) mm Hg; ranging from 2 to 56 mm Hg. Mean greatest linear dimension (GLD) as measured on ultrasound (UBM or B-scan) was 7.5 mm (±5.9) mm, with a range of 1.6 to 21.7 mm. Baseline demographic and tumor characteristics of individual subjects is mentioned in Table 1.
Three of 11 patients had iris tumors, with one of them involving the ciliary body as well. Six patients had ciliary body involvement only, and the remaining 2 patients had both ciliary body and choroidal involvement. Tumor related ocular complications and their management are listed in Table 2. PLSU was done for 6 cases, enucleation for 3 cases, iris excision biopsy, and plaque brachytherapy, for 1 case each. Adjuvant vitrectomy was done for 6 cases. Procedure related complications and management are listed in Table 3. Mean post-operative BCVA (n=8) was 1.05 (±0.69) with a range of 0 to 1.78. Mean post-operative IOP was 13 (±8.9) mm Hg with a range of 4 to 32 mm Hg. There was no tumor recurrence or systemic metastasis in any case. Three of 11 eyes had enucleation, and globe salvage was achieved in 8 cases. Details of the treatment outcomes are listed in Table 4.
Histopathology and/or immunohistochemistry confirmed the diagnosis in each case. Case 1 demonstrated spindle cells arranged in a fascicular pattern arising from the ciliary epithelium on histo-pathology. A diagnosis of mesectodermal leiomyoma was made on immunohistochemistry. In Case 2, histopathology showed the presence of a hematoma along with pigmented macrophages, thus refuting the diagnosis of a malignancy. Case 3 was suspected to have a PEComa (perivascular epithelioid cell tumor) of the ciliary body on histo-pathology. Immunohistochemistry was positive for vimentin, cytokeratin and S-100 but negative for SMA, HMB 45, CD 34 and Melan A; ruling out the diagnosis of PEComa. The tumor was diagnosed as epithelioid neoplasm of uncertain origin. Cases 4 and 5 were diagnosed to have ciliary body medulloepithelioma. The tumor cells were arranged in a tubular and cord like pattern with the formation of pseudo-rosettes. Classic intra-tumoral cystic spaces were also present. There was focal invasion into the vitreous and sclera in one case. There was no extension into the choroid or optic nerve. No teratoid features were seen. Case 6 had ciliary body IgG4 disease. Cytological smear showed the presence of clumps of oval cells with high nuclear to cytoplasmic ratio along with the presence of mixed inflammatory cells. Immunohistochemistry showed the presence of 50 to 60 IgG4 plasma cells per high power field (plasma cells were positive for CD138, kappa and lambda), although the serum IgG4 level was normal at 1.02 g/L. All three iris tumors were confirmed to be granulomas on histopathology. Case 7 had a tuberculoid granuloma, Case 8 was a non- specific granuloma and, Case 9 was fungal granuloma. Cases 10 and 11 had ciliary body-choroidal melanoma. Primary enucleation was done for both these cases. Histo-pathological section of the enucleated eyes demonstrated a mixed cell tumor in one case, with the other showing predominantly spindle B-cells.
Discussion
Shields et al reported a diagnostic yield of 88% with intraocular biopsy.,[5, 6, 7] Schneider and Augsburger obtained enough specimen for cytopathologic diagnosis in 76.5% cases.[8] Bechrakis et al obtained sufficient tissue in all casesin their study with vitreous cutter, allowing a histopathologic diagnosis in 97% of cases and being also adequate for immunohistochemical studies, producing an even higher diagnostic accuracy.[9]
It is important for a close cooperation between Ophthalmic oncologist and ophthalmic pathologist because the tumor samples are usually very small and could easily be lost during processing. Patholologist must interpret the histopathological and cellular features within the clinical context. In conclusion, complete excision of anterior uveal tumors is often possible with histopathological and immunohistochemistry studies unravelling a myriad of etiological diagnosis. This study provides unique inputs on the histopathological features of anterior uveal tumors in Indian subjects.
References
- Rishi P, Dhami A, Biswas J. Biopsy techniques for intraocular tumors. Indian J Ophthalmol. 2016 Jun;64(6):415-21.
- Long JC, Black WC, Danielson RW. Aspiration biopsy in intraocular tumors. AMA Arch Ophthalmol 1953; 50:303–10.
- Sanders TE. Intraocular biopsy: An evaluation. Trans Am Ophthalmol Soc 1952; 50:375-405.
- Shields CL, Kancherla S, Patel J, et al. Clinical survey of 3680 iris tumors based on patient age at presentation. Ophthalmology. 2012 Feb;119(2):407-14.
- Jensen OA, Andersen SR. Late complications of biopsy in intraocular tumors. Acta Ophthalmol (Copenh)1959;37:568 – 75.
- Sanders TE, Smith ME. Biopsy of intraocular tumors: a re-evaluation. Int Ophthalmol Clin1972;12:163–76.
- Shields JA, Shields CL, Ehya H, Eagle RC, Potter PD. Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology 1993;100:1677– 84.
- Augsburger JJ, Schneider S, Ehya H. The role of transvitreal fine needle aspiration biopsy in small suspected choroidal melanomas. Invest Ophthalmol Vis Sci 1999;40:1287. 21-24
- Bechrakis NE, Forster MH, Bornfeld N. Biopsy in indeterminate intraocular tumors. Ophthalmology 2002;109:235-42. 17
| Table 1: Baseline Characteristics | |||||||
| Patient no. | Age(years) | Sex | Eye | BCVA
(logMAR) |
IOP
(mm Hg) |
Tumor location
(clock hours) |
Tumor size(mm) |
| 1 | 58 | F | OS | 0.3 | 33 | 10 to 2.30 | 8.1×6.8×6.6 |
| 2 | 63 | M | OS | 1 | 14 | 1 to 3.30 | 4.6 x 4.1 |
| 3 | 26 | F | OD | 0.6 | 12 | 2 to 7 | 5.2×8 |
| 4 | 15 | M | OD | 0.48 | 11 | 12 to 9 | 21.7×21.2×12.5 |
| 5 | 13 | F | OS | 0.3 | 56 | 4 to 10 | 5.9×6.7×5.9 |
| 6 | 37 | M | OS | 1.3 | 2 | 7 to 1 | 4.6×3.7 |
| 7 | 40 | M | OD | 0 | 14 | 7 to 7.30 | 1.2×1.6 |
| 8 | 69 | M | OD | 0.6 | 5 | 2.30 to 3.30 | 3.3×4.0 |
| 9 | 70 | F | OD | 0.88 | 9 | 5.30 to 7.30 | 2.3 x 5.4 |
| 10 | 54 | M | OD | 0.18 | 12 | 6 to 9 | 8x6x7, 6x8x2 |
| 11 | 53 | F | OS | 0 | 12 | 10 to 3 | 13.4×13.1 |
| Table 2: Tumor related complications | ||
| Pt no | Tumor related complications | Medical intervention for associated complications |
| 1 | Neovascular glaucoma, iridodialysis | AGM |
| 2 | None | NA |
| 3 | Grade 1 hyphema | None |
| 4 | Exudative RD, Vitreous cells, retrolental cyclitic menbrane, intratumoral cysts | None |
| 5 | NVG, NVD, NVE, VH, retrolental cyclitic membrane, Intratumoral cyst. | Oral diamox and 3 AGMs – IOP 32. DLPC done subesequently. |
| 6 | Scleritis, Raised IOP, Pars plana edema, peripheral CD | AGM, topical steroids, oral MTX |
| 7 | A/S inflammation | Antibiotic and steroid eye drops |
| 8 | A/S inflammation, Hypotony | None |
| 9 | Vitreous cells, CME | None |
| 10 | Localised RD, Retinal invasion of tumor | None |
| 11 | Localised RD, VH | None |
| Table 3: Procedure Related Complications | |||
| Pt no | Procedure | Complication | Management of complication |
| 1 | FNAB
PLSU |
Hyphema
Conjunctival hooding |
Observation
Conjunctivoplasty |
| 2 | FNAB
PLSU Vitrectomy SOR + lensectomy |
Dispersed VH
Dispersed VH, Inferior RD, CD, Sub retinal hemorrhage Sub silicon oil hemorrhage Hypotony |
Observation
Vitrectomy Observation Lost to follow up |
| 3 | PLSU | Hyphema | Observation |
| 4 | FNAB | Vitreous hemorrhage | Observation |
| 5 | Plaque brachytherapy | ? Disc pallor | Observation |
| 6 | PLSU | Scelral thinning, hypotony, localised suprachoroidal effusion | Scleral patch graft |
| 7 | Iris excision biopsy | No complications | NA |
| 8 | PLSU | Hypotony | None |
| 9 | PLSU | No complications | NA |
| 10 | Enucleation + BI | No complications | NA |
| 11 | Enucleation + BI | No complications | NA |
| Table 4: Treatment Outcomes | ||||||||
| Patient No. | H/P Diagnosis | Procedure | Adjuvant Vitrectomy | BCVA
(logmar) |
IOP
(mm Hg) |
Tumor Recurrence | Metastasis | Globe Salvage |
| 1 | CB mesectodermal leiomyoma | PLSU | Yes | 0.48 | 18 | No recurrence | No | Yes |
| 2 | CB hematoma | PLSU | Yes | 1.78 | 13 | No recurrence of hematoma | NA | Phthisis bulbi |
| 3 | CB epithelial cell tumor of unknown origin | PLSU | Yes | 0.3 | 13 | No recurrence | No | Yes |
| 4 | CB medulloepithelioma | Enucleation | NA | na | na | No recurrence | No | Enucleated |
| 5 | CB medulloepithelioma | Plaque Brachytherapy | NA | 1.3 | 32 | Regressed | No | Yes |
| 6 | IgG4 disease | PLSU | Yes | 1.48 | 4 | No recurrence | No | Yes |
| 7 | Iris granuloma | Iris excision biopsy | NA | 0 | 10 | No recurrence | NA | Yes |
| 8 | Iris foreign body granuloma | PLSU | Yes | 1.78 | 4 | No recurrence of granuloma | NA | Phthisis bulbi |
| 9 | Iris CB fungal granuloma | PLSU | Yes | 1.3 | 10 | No recurrence of granuloma , persistent CME. | NA | Yes |
| 10 | CB choroidal melanoma | Enucleation | NA | na | na | No recurrence of granuloma | No | Enucleated |
| 11 | CB choroidal melanoma | Enucleation | NA | na | na | No recurrence | No | Enucleated |
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