Patients presenting with metastases: stage IV uveal melanoma, an international study

Objective To analyse ocular and systemic findings of patients presenting with systemic metastasis. Methods and analysis It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. Results Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. Conclusions Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.Ophthalmic researc

Estrogen and progesterone receptors expression in uveal melanoma tumor cells

Purpose: study of uveal melanoma (UM) cells receptor status to estrogen (ER) and progesterone (PR). Material and methods. 22 patients (8 men and 14 women) with UM aged 22 to 76 (mean 54.3 ± 2.2 years) were subjected enucleation (n = 20) or fine-needle aspiration biopsy, depending on clinical indications. The material for cytological examination (n =22) was obtained from enucleated eyes by imprinting. A routine cytological study was performed to confirm the diagnosis, while at the second stage the method of immunocytochemistry (ICC) was used to differentiate the melanocytic nature of the tumor. Results. The cytological diagnosis of melanoma was established in all patients, including two urgent cytological tests on the operating table. In 80 % of melanomas, a positive expression of HMB 45 (melanocytic differentiation marker) and cocktail Melan (a melanoma-associated marker) were observed, which confirmed the melanocytic nature of the tumor. A weak reaction to S100 (neuronal differentiation marker) was noted. In all cases, a pronounced reaction to vimentin was observed, which manifested itself as a brown coloration of the cytoplasm. When studying the expression of ER and PR, a negative result was obtained; none of the studied samples displayed a quantitatively positive reaction. Conclusions. In our investigation, based on UM samples study, 22 patients had no positive expression of estrogen and progesterone receptors in the tumor tissue, which correlates with literary data. For citation: Saakyan S.V., Zhiltsova M.G., Valskiy V.V., Tsygankov A.Yu. Estrogen and progesterone receptors expression in uveal melanoma tumor cells. Russian ophthalmological journal. 2018; 11 (1): 17-23. doi: 10.21516/2072-0076-2018-11-1-17-23 (In Russian)

Indications for enucleation after uveal melanoma brachytherapy

Purpose: to analyze indications for enucleation in uveal melanoma (UM) patients after brachytherapy (BT). Material and methods. 52 patients with UM (31 females and 21 males) aged 25 to 74 years (mean age 53.2 ± 12.3) underwent an enucleation after a previously administered BT. Tumor sizes before BT were 6.1 ± 2.1 (1.2-11) mm in thickness and 13.0 ±2.9 (6-19) mm in diameter. Immediately before enucleation, they were 5.3 ± 3.4 (1-17) mm and 12.4 ± 3.6 (5-20) mm respectively. The time span between BT and enucleation varied from 2 to 103 months (median, 25 months). 40 patients (77 %) had choroidal localization of UM (of these,16 had juxtapapillary localization), 10 patients (19.2 %) had ciliochoroidal localization, and 2 patients (3.8 %) had UM in the anterior areas of the eye (iris and ciliary body). Results. In more than a half of the patients (30 patients, or 58 %) tumor regrowth was detected 5-96 months after BT. The second frequent cause for enucleation was neovascular glaucoma found in 21 patients (40 %). Extraocular extension of UM, identified in 12 patients (23 %), took place 3-82 months after BT and turned out to be the third complication as far as frequency of occurrence is concerned. Conclusion. Tumor regrowth remained to be the main cause for secondary enucleation in UM patients after BT. As a matter of fact, complications that can require immediate enucleationmay develop at any time after BT (although the peak falls upon the first 2 years after BT. This fact confirms the need of lifelong follow-up of such patients. Hence, unfounded extension of indications for BT may result in ineffective prolongation of local treatment, a number of radiation complications requiring immediate secondary surgical treatment // Russian Ophthalmological Journal, 2016; 4: 46-51. doi: 10.21516/2072-0076-2016-9-4-46-51

Scleral necrosis after brachytherapy of uveal melanoma and methods of its elimination

Purpose: To analyze the results of scleroplastic operations aimed at eliminating radiation necrosis of the sclera in patients who underwent brachytherapy (BT) of uveal melanoma (UM) using a variety of plastic materials. Material and methods. The paper presents the results of treatment of 19 patients aged 32 to 67 years with radiation necrosis of the sclera after BT of UM. Scleroplasty was carried out 3 to 33 months (the median being 15 months) after brachytherapy using cadaveric sclera (13 patients), alloplant from the dura mater (3 patients) and synthetic ophthalmic material (4 patients). Results. On the whole, the materials and methods used for scleroplasty are effective and most cases save the patient’s eye (17 of 19 eyes have been saved)., However, they are imperfect, which requires that new materials and new methods of eliminating post-radiation defects of the sclera be elaborated and introduced into clinical practice. Conclusion. When planning and performing sclero plasty, strict individual approachs required. The operations have to be performed only in specialized ophthalmic hospitals in cases, of clear indications to uveal melanoma radiotherapy. Preventive measures should always be taken with regard to patients with a risk of necrosis, which will help reduce the frequency and severity of radiation sclera necrosis // Russian Ophthalmological Journal, 2017; 1: 43-8. doi: 10.21516/2072-0076-2017-10-1-43-48