The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

Additional primary malignancies in a Polish cohort of uveal melanoma patients: a review of 644 patients with long-term follow-up.

AIM: To investigate the frequency and location of additional primary malignancies in a Polish cohort of uveal melanoma (UM) patients registered in a single centre database. MATERIAL AND METHOD: Retrospective data analysis of patients treated for uveal melanoma at the Department of Ophthalmology, Poznan University of Medical Sciences, Poland between 1991 and 2017. Data on the diagnosis of the additional malignancies were obtained during the follow-up visits in our Department and/or from the Greater Poland Cancer Registry. The exclusion criteria comprised no confirmed follow-up or incomplete clinical entry data. RESULTS: Among 644 UM patients registered in the database up to 2017, the additional malignancy was diagnosed in 126 (20%) patients: 71 men, 55 women at the median age of 67 years (range: 34-94). In 48 patients (38%), the additional malignancy occurred prior to the diagnosis of UM, in 73 (58%) patients - after it. The most common locations of second cancer were skin (20 cases / 15%), breast (17 cases / 13%) and lungs (15 cases / 12%). The median follow-up was 36 months (range: 3-242). 87 patients (69%) died by the study close, 32 (37%) of them due to metastatic disease from uveal melanoma, 41 (47%) due to another cancer. CONCLUSIONS: The frequency of additional primary malignancies was higher in our cohort than reported by most of other groups. If there is a certain predisposition to a specific type of additional primary carcinoma in UM patients, the analysis of larger database is required.

Ruthenium brachytherapy for iris melanoma.

Purpose: The study aimed to review the long-term outcomes of ruthenium brachytherapy for iris and iridociliary melanoma. Material And Methods: Medical records of patients who underwent ruthenium plaque treatment for iris and iridociliary melanoma at the Department of Ophthalmology, Poznan University of Medical Sciences, between 1999 and 2021 were retrospectively reviewed. Results: We identified 24 patients, including 17 women and 7 men, with a median age of 61.5 years (range, 35-84 years). Median observation time before treatment was 3 months (range, 0-68 months). Nineteen (79%) patients received a treatment with 20 mm CCB plaque, 5 (21%) with 15 mm CCA plaque and 2 (8%) patients received total irradiation to the entire iridocorneal angle. Median follow-up was 67.5 months (range, 24-265 months). We noted one (4%) recurrence managed by irradiating the anterior segment. Twelve (50%) patients developed post-operative cataracts in a median time of 38 months following treatment, 5 (21%) required topical medications to control intraocular pressure, and one (4%) developed chronic macular edema (CME) that was managed with anti-VEGF therapy. Final visual acuity between 1.0 and 0.5 was observed for 16 (67%) patients, between 0.49-0.1 for 5 (21%) patients, and below 0.09 for 3 (12%) patients. Nine (37%) patients maintained final visual acuity stable; in 4 (17%) patients, it dropped more than 3 lines, and improved in 6 (25%) patients. Conclusions: Ruthenium brachytherapy with standard applicators is an effective and safe way of treatment for iris and iridociliary melanoma. We observed no significant post-operative complications in a long-term observation.

Radiation retinopathy following episcleral brachytherapy for intraocular tumors: Current treatment options.

Radiation retinopathy (RR) and radiation maculopathy (RM) can occur as a result of uveal melanoma radiation treatment and after irradiation of other head and neck extraocular tumors, even with precise targeting techniques, such as stereotactic or proton beam radiotherapy. This review provides an overview of the current understanding of potential radiation damage to ocular tissues, and how recent developments in ophthalmic multimodal imaging techniques and treatment modalities have improved managing options. Several treatment strategies have been employed so far for the management of RR, including laser photocoagulation, intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents or glucocorticosteroids and surgery. The use of intravitreal anti-VEGFs or dexamethasone implants have significantly altered the final visual outcome for uveal melanoma patients. As a prophylaxis, a few different strategies were proposed, but still there is a lack of large randomized clinical trials supporting these approaches and clear clinical guidelines for daily practice. Early detection and proper treatment are crucial in preventing or reducing vision loss, and improving patients' quality of life. Close monitoring and timely intervention are essential for successful management.

The prevalence of various eyelid skin lesions in a single-centre observation study.

INTRODUCTION: The role of the eyelids is to protect and moisturise the eye. Despite its small relative surface area, 5-10% of skin cancers originate in the eyelids. AIM: To assess the prevalence of different types of skin lesions in the area of eyelids based on retrospective histopathology data from a tertiary centre. MATERIAL AND METHODS: Among 544 included eyelid lesions, 429 (79%) were benign and 115 (21%) were malignant. In the benign group, the most common finding was a chalazion (49.2%) followed by squamous papilloma (22.8%), seborrheic keratitis (10%), epidermal cyst (8.2%), and intradermal nevus (5.1%). Out of all malignant lesions, the most common diagnosis was basal cell carcinoma (BCC) in 110 (95.7%) patients. RESULTS: Squamous cell carcinoma (SCC) was diagnosed in 3 (2.6%) patients and sebaceous gland carcinoma (SGC) in 2 (1.7%). No malignant melanoma was identified in the studied group. CONCLUSIONS: Although benign lesions are the most common eyelid tumours, it is essential to differentiate between benign and malignant eyelid tumours because early detection and appropriate treatment may improve the cosmetic effect and reduce recurrences.

Iris melanoma with ciliary body infiltration presenting as a presumed chronic unilateral inflammatory glaucoma. The challenges of iris tumor biopsy assessment.

Uveal melanoma is the most common primary malignancy of the eye in adults. It may involve the choroid and ciliary body, and in only 2-3% of cases it involves the iris. We present a case of a 56-year-old patient with a 6-year history of unilateral, inflammatory, refractory glaucoma of the right eye. Due to acquired heterochromia and heterogeneous thickness of the iris, iris melanoma was suspected, but the incisional biopsy did not confirm the diagnosis. In the next months, the lesion enlarged and the eye globe was enucleated. Histopathological examination revealed an iridociliary melanoma with annular growth pattern.

The Small Fatal Choroidal Melanoma Study. A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To determine the size at which choroidal melanomas can metastasize and to report the characteristics of small fatal choroidal melanomas (SFCM). DESIGN: Retrospective case series. METHODS: Ten ocular oncology services submitted 45 patients with a choroidal melanoma 3 mm or less in thickness and 9 mm or less in largest basal diameter (LBD), when treated, who developed metastases. RESULTS: Median tumor thickness was 2.4 mm (range, 1.0-3.0 mm) and LBD 7.3 mm (range, 3.0-9.0 mm). Of 14 (31%) tumors that were first observed, 12 grew a median of 0.5 mm (range, 0.1-1.2 mm) in thickness and 1.0 mm (range, 0-3.0 mm) in LBD within a median of 7 months; 3 were initially smaller than 3 mm in LBD. Number of risk factors for growth and metastasis was 0 for 4% of the tumors; 60% were over 2 mm in thickness, 63% had subretinal fluid, 84% caused symptoms, 57% had orange pigment, and 92% were within 3 mm of the disc. Local recurrence occurred in 8 of 31 eyes (26%) treated conservatively. Median metastasis-free survival was 4.5 years (range, 0.8-15.7 years). Kaplan-Meier estimate of metastasis developing was 15% (95% confidence interval [CI], 7-26), 51% (95% CI, 36-64) and 85% (95% CI, 71-92) by 2, 5, and 10 years, respectively. By the time of analysis, 37 patients had died of metastasis after a median of 7 months. CONCLUSIONS: Choroidal melanomas less than 3.0 mm in LBD are highly unlikely to metastasize. Risk factors of an SFCM are similar to those for all choroidal melanomas of similar size.

Ruthenium brachytherapy for intraocular growth of a conjunctival squamous cell carcinoma: a case report.

The aim of this study is to report the use of ruthenium brachytherapy as an adjunctive treatment in the management of an intraocular extension of the conjunctival squamous cell carcinoma (SCC). In 2013, a 73-year-old man presented with a tumor blocking the angle and infiltrating corneal endothelium. The patient was treated with iridectomy, and after one month, ruthenium brachytherapy was applied. 4.5 years post-irradiation, the treated eye is painless, and no recurrence was noted. We advocate the use of ruthenium brachytherapy as an eye salvage treatment with an intraocular extension of conjunctival SCC.

Ruthenium brachytherapy for uveal melanoma - single institution experience.

PURPOSE: The aim of this study was to report on results of uveal melanoma treatment with ruthenium-106 (106Ru) brachytherapy with long-term follow-up, in terms of local tumor control, eye retention rate, radiation retinopathy, and patients' survival. MATERIAL AND METHODS: Medical records of patients treated with ruthenium plaque due to uveal melanoma at the Department of Ophthalmology, Poznan University of Medical Sciences, Poland, between 1994 and 2014 were retrospectively reviewed. RESULTS: We identified 126 patients: 53 men, 73 women, mean age 60.04 years (range, 21-89). The largest basal diameter ranged from 4.04 mm to 18.9 mm (median, 10.67 mm), tumor height was 1.9 mm to 7.42 mm (median, 4.8 mm). Median scleral radiation dose was 570 Gy (range, 235-1,500 Gy), median apical dose 100 Gy (range, 60-129 Gy). Median follow-up was 66.5 months (range, 2-261 months). We noted a total of 19 (15%) recurrences. The actuarial rate of recurrence was 9.5% at 3 years, and 13.5% at 5 years postoperatively. Nine (7%) eye globes were lost, median time to enucleation was 5 years. The eye retention rate at 5 years was 92.7% and 81% at 10 years. Forty-three (34%) patients died before the end of the study, 24 (19%) of them due to metastatic disease. Metastatic death was related to: tumor size and TNM stage at presentation (p = 0.002 vs. p = 0.0006, respectively) but not to age, gender, and plaque dosimetry. CONCLUSIONS: 106Ru brachytherapy is an effective, globe sparing treatment that provides good tumor control and a high rate of survival. However, some ocular complications tend to appear late post-treatment, and therefore long-term follow-up is advised.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Demodex spp. within the limbal dermoid ­ causal pathogen or an irrelevant finding? Case report. / Demodex w obrebie dermoidu rabka rogówki ­ patogen czy przypadkowe znalezisko? Opis przypadku.

The aim of the study is to report a case of limbal dermoid associated with infestation of Demodex species (Demodex spp.). A 27-year-old man presented with ocular discomfort and a pink conjunctival lesion in his left eye. The lesion had been present since birth and it occassionally grew eyelashes. The tumour was located in an inferior temporal quadrant, involving approximately 1/6 of the limbal surface area. High frequency ultrasound revealed deep corneoscleral inifiltration, so a subtotal resection was performed. Histological evaluation revealed the presence of Demodex spp. in an abnormal sebaceous gland located within the tumour. Limbal dermoid might be associated with Demodex spp. infestation, if abnormal sebaceous glands are formed inside the lesion.

Core Endoresection as Neoadjuvant Treatment of Uveal Melanoma.

AIM: To present a case of neoadjuvant treatment of uveal melanoma with a limited core endoresection, which enabled ruthenium plaque radiotherapy to be administered. MATERIAL AND METHODS: A 77-year-old woman presented in 2005 with a ciliochoroidal uveal melanoma measuring 7.2 by 6.5 mm basally with a thickness of 6.2 mm. The vision in the affected eye was 6/9. Because of diagnostic uncertainty, we performed a biopsy, which produced a copious sample. The biopsy serendipitously reduced the tumour thickness to 4.4 mm, making ruthenium plaque brachytherapy possible. RESULTS: Histopathological examination showed the tumour to be a melanoma predominantly of spindle cell type. Postoperative complications included a dense vitreous haemorrhage, which cleared spontaneously, and raised intraocular pressure, controlled with latanoprost. Seven years after brachytherapy, the vision was 6/5 and the thickness of the residual tumour was 2.5 mm. Nine years after treatment, there was no evidence of any intra- or extraocular seeding or distant metastases. CONCLUSIONS: Core endoresection of a ciliochoroidal melanoma may reduce tumour thickness enough to allow subsequent ruthenium plaque radiotherapy.

Management of patients with uveal metastases at the Liverpool Ocular Oncology Centre.

BACKGROUND: Uveal metastasis is the most common intraocular malignancy. METHODS: This was a retrospective study of all patients with uveal metastases referred to the Liverpool Ocular Oncology Centre between January 2007 and December 2012. Biopsy was performed as a primary investigation if the clinical examination suggested metastasis with no evidence of any extraocular metastases. RESULTS: Ninety-six patients (109 eyes) were included. Breast and lung carcinomas were the most common primary malignancies, affecting 41 and 27 patients, respectively. The median time interval between detection of primary cancer and uveal metastasis was 24 months (range 1-288 months). Thirty-nine patients underwent ocular biopsy, confirming the diagnosis in all patients. The biopsy indicated the site of origin in 24 out of the 27 without a known primary tumour. In 7 of these 27 cases, previous systemic investigations had failed to identify the primary tumour. Seventy-three patients received external beam irradiation; two patients received photodynamic therapy; and two patients had Ru-106 plaque radiotherapy. The visual acuity was stable or improved in 75.5% of the cases. CONCLUSIONS: Immediate biopsy provides a quick diagnosis that may expedite treatment and improve any opportunities for conserving vision while facilitating the general oncologic management on these patients.

Primary uveal lymphoma effectively managed with oral chlorambucil: a case report.

INTRODUCTION: Ocular lymphomas account for five to 10 percent of all extra-nodal lymphomas. Primary uveal lymphoma is quite a rare entity and usually unilateral. We present a case of a primary uveal lymphoma with conjunctival and orbital extension, successfully managed with oral chlorambucil. CASE PRESENTATION: A 71-year-old Caucasian man presented to our facility with visual loss in his only functioning eye (left). On clinical examination, we found a conjunctival lesion with a choroidal infiltration and a secondary retinal detachment. Ultrasound and magnetic resonance imaging studies revealed a choroidal tumour mass and two other lesions around the optic nerve. Results from an incisional biopsy revealed a low-grade B-cell lymphoma (CD20+, CD43+, bcl2+, CD3-). A diagnosis of primary uveal lymphoma was made. Our patient was started on a chemotherapy regime with no effect, and then oral chlorambucil was administered, with a relatively good result. At 10 months after the start of chlorambucil treatment, a best-corrected visual acuity of 0.4 was recorded, the choroidal mass had practically disappeared and the extra-ocular lesions had shrunk. CONCLUSIONS: In all, 61 to 80 cases of primary uveal lymphoma have already been described in the literature. Generally, it is an indolent tumor with a good prognosis. However, there are some reports of aggressive tumor behavior a few years after initial diagnosis (about eight percent of cases). Other treatment options are orbital irradiation at low doses (20 to 40 Gy) or steroid administration. This is the first documented report of the efficacy of oral chlorambucil in the treatment of primary uveal lymphoma.

Poststreptococcal syndrome mimicking conjunctival lymphoma.

BACKGROUND: Poststreptococcal syndrome (PSS) can be a consequence of nonpurulent primary infection with group A streptococci (GAS). Postreptococcal uveitis is a well recognized entity with quite a few descriptions in the literature, but so far no conjunctival involvement has been reported.The aim of the study is to present a rare case of postreptococcal conjunctival lesions mimicking a lymphoma. CASE PRESENTATION: 19-years-old Caucasian female presented with pink, nodular infiltrates in the right conjunctiva that occurred a few months after upper respiratory tract infection and tonsillectomy. Histopathological examination of collected lesion samples revealed inflammatory reaction with lymphocytes proliferation and failed to rule out a myeloma. Complementary flow-cytometry did not show monoclonal proliferation of lymphocytes B. During follow-up we observed the complete regression of conjunctival lesions after the benzyl penicillin treatment prescribed by ENT specialist due to elevated plasma ASO levels. Therefore, we suppose that those lesions must have represented a part of poststreptococcal syndrome. CONCLUSIONS: To conclude, this is, to the best of our knowledge, the first report of conjunctival involvement in the course of PSS related to group A streptococci.

Small-cell lung carcinoma metastasis to the iris - case presentation.

INTRODUCTION: Metastatic tumors are the most common intraocular malignancies in adults. Anterior segment metastases account for about 7.2-14.1% of all intraocular metastatic tumors with those to the iris representing 3.6-7.8% of the cases. Breast and lung are the most frequent primary sites of metastasizing cancer. The aim of this study is to present the case of a 43-year-old patient with a rare small-cell lung carcinoma metastasis to the iris. CASE REPORT: A patient with small-cell lung carcinoma and metastases in the brain who had been treated with chemo- and radiotherapy attended an outpatient clinic because of redness of her left eye. Based on the ophthalmological examination, a diagnosis of numerous metastatic tumors to the iris was made and the patient was referred for re-chemotherapy. Complete regression of the iris lesions was observed after 5 months but unfortunately two months later the patient died, due to progression of her systemic disease. DISCUSSION: Among lung cancers, adenocarcinomas are much more likely to produce distant metastases to the iris than small-cell carcinomas [4]. More than 50% of patients with small-cell lung carcinoma have metastases in the brain. The survival rate in cases of lung cancer with eye involvement is poor and approximates to 7 months. However, since there is a strong probability of angle involvement and subsequent secondary glaucoma, the early onset of treatment can improve the patient's quality of life during the terminal phase of the disease.

[Isolated congenital hamartoma of retinal pigment epithelium in a long term follow-up--case report]. / Wrodzony nowotwór lagodny nablonka barwnikowego siatkówki typu hamartoma --dlugoterminowa obserwacja przypadku klinicznego.

Retinal pigment epithelium hamartomas are rare, benign tumors, usually with no growth potential. The case of hamartoma observed at the Ocular Oncology Service, Department of Ophthalmology, University of Medical Sciences in Poznan is presented. In 2008 a 30-year-old woman presented with an asymptomatic choroidal pigmented lesion. Fundus evaluation revealed a lesion typical of retinal pigment epithelium hamartoma. The optical coherence tomography, fluorescein angiography and indocyanine green angiography results confirmed the diagnosis of retinal pigment epithelium hamartoma. No lesion growth was documented throughout the follow-up period of 4 years. Differential diagnosis between congenital retinal pigment epithelium hypertrophy (congenital hypertrophy of the retinal pigment epithelium) or uveal melanoma was included in the report. retinal pigment epithelium hamartoma, fluorescein angiography, optical coherence tomography.

[Choroidal melanoma treatment by endoresection]. / Leczenie czerniaka naczyniówki metoda endoresekcji.

PURPOSE: To report choroidal melanoma treatment by endoresection. MATERIAL AND METHODS: A retrospective review of a series of 2 patients with choroidal melanoma that did not meet the criteria for brachytherapy. Both patients were treated by tumor endoresection supported by brachytherapy. Outcome measures included preoperative and postoperative visual acuity at 1, 3, 6 months. Preoperative evaluation included tumor measurements in ultrasound. Systemic evaluation (liver function test, chest x ray, abdominal ultrasound), was carried out to monitor possible metastases in the observation period. RESULTS: The two operated patients were followed-up for 6 months. Visual acuity deteriorated from 5/16 (0.51 logMAR) preoperatively to 5/25 (0.7 logMAR) postoperatively in patient 1, and improved from 3/50 (1.22 logMAR) do 5/25 (0.7 logMAR) in patient 2. This corresponded to deterioration by 0.19 logMAR and improvement by 0.52 logMAR respectively. Neither tumor recurrence nor metastases were detected in the follow-up period. CONCLUSIONS: Endoresection is a treatment option, alternative to enucleation, that can conserve the eye It sometimes can be performed in eyes that are not eligible for trans-scleral resection. Further larger studies are needed to establish the efficacy of this still controversial surgery.