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%).

Black and white box: Take good gross pathology photographs.

Macroscopic study of surgical samples sent to the histopathology lab provides the first diagnostic approach. Obtaining quality photographs of these pieces facilitates proper case documentation for publication, sharing, teaching and research.This device has been originally designed for enucleated eyes but it could be used for a wide diversity of human or animal samples including thyroids, pituitary glands, prostates… It can be coupled to any smartphone camera.The Black and White Box is an affordable and easy option for taking gross pathology photographs of high quality. In this work we provide full instructions on how to make it.

Pattern of Local Recurrence After I-125 Episcleral Brachytherapy for Uveal Melanoma in a Spanish Referral Ocular Oncology Unit.

PURPOSE: To describe the time, frequency, and clinical characteristics of treatment failure after I-125 brachytherapy in patients with uveal melanoma treated and followed in a Spanish referral ocular oncology unit. DESIGN: Prospective, consecutive, interventional case series. METHODS: Patients diagnosed with uveal melanoma from 1995 to 2016 and treated with episcleral brachytherapy were included. Demographic data collection, ophthalmic evaluation, ultrasound scan, and systemic studies were performed at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Recurrence was defined as presence of tumor growth after treatment. Baseline analysis was performed by descriptive methods and survival by Kaplan-Meier curves. RESULTS: From 732 patients diagnosed with uveal melanoma, 311 were treated with brachytherapy. In the follow-up (mean 79 months, standard deviation = 55), 16 local tumor recurrences (5.1%) were detected. All relapsing patients had choroidal tumors and 15 presented with visual symptoms. All patients were treated with I-125 brachytherapy, and 2 received associated transpupillary thermotherapy. All the eyes were enucleated after recurrence. Kaplan-Meier analysis showed a mean time of recurrence of 3.7 years (standard deviation = 2.94 years, ranging from 1 to 12 years). Three patients had metastasis in the follow-up. Kaplan-Meier analysis showed worse survival for patients with recurrence. CONCLUSION: Local treatment failure was a relatively infrequent event after I-125 brachytherapy in our series. Recurrences appear not only early but also late in the follow-up. They do not have a distinctive clinical pattern and are associated with poorer survival.

Iris color: validation of a new classification and distribution in a Spanish population-based sample.

PURPOSE: To design and validate a standard, simple, and reliable iris color classification and to study its distribution in a Spanish population. Iris color has a geographic distribution and has been correlated with different ocular diseases. However, there is no standard and validated iris color classification allowing comparison among different studies. METHODS: Classification was made in three grades (blue-gray, hazel-green, brown) and was validated by 3 independent readers. Initially, a preliminary study was made in 50 iris photographs to detect technical hitches. Afterwards, based on this procedure, 221 iris photographs were graded. RESULTS: Measures of interobserver reliability were 0.786 by kappa index with an agreement of 89.6%.Iris color distribution in the Spanish cohort was blue-grey 16.29%, hazel-green 55.2%, and brown 28.5%. CONCLUSIONS: This classification is simple, reliable, and easy to use in clinical research and by ophthalmologists or generalists in practice. The Spanish cohort from this study shows a different iris color distribution from those previously published in other countries.

Conjunctival pigmentation in Stevens-Johnson syndrome.

We report a 29-year-old white female with conjunctival pigmentation after a Stevens-Johnson syndrome (SJS) episode triggered by sulfasalazine. The patient developed bilateral tarsal and forniceal conjunctiva and black pigmentation. Diagnostic biopsy showed stromal monocyte infiltration consistent with chronic phase SJS and conjunctival pigment of melanic origin and not due to drug deposition. Treatment with topical steroids and unpreserved artificial tears resulted in improvement of clinical symptoms; however, pigmentation was unchanged after 2 years.

Conjunctival pigmentation in Stevens-Johnson syndrome.

We report a 29-year-old white woman with conjunctival pigmentation after a Stevens-Johnson syndrome (SJS) episode triggered by sulfasalazine. The patient developed bilateral tarsal and forniceal conjunctiva and black pigmentation. Diagnostic biopsy showed stromal monocyte infiltration consistent with chronic phase SJS and conjunctival pigment of melanic origin that was not due to drug deposition. Treatment with topical steroids and unpreserved artificial tears resulted in improvement of clinical symptoms; however, pigmentation was unchanged after 2 years.

Hughes technique, amniotic membrane allograft, and topical chemotherapy in conjunctival melanoma with eyelid involvement.

A 59-year-old woman presented with a pigmented mass in the inferior tarsal conjunctiva of the left eye with an associated diffuse, multifocal pigmentation involving largely the inferior half of the bulbar conjunctiva, fornix, and eyelid skin. Histopathologic examination of map biopsies disclosed conjunctival melanoma from primary acquired melanosis. Surgical excision of the inferior bulbar conjunctiva, fornix, and lower eyelid with histopathologic free margins was performed. Adjuvant cryotherapy was applied. The bulbar conjunctiva and lower fornix were reconstructed with an amniotic membrane allograft. Lower eyelid reconstruction was accomplished by use of the Hughes technique. Topical mitomycin C (0.04%) was applied after surgery. After 2 years of follow-up, no tumor recurrence has been detected and the eyelid and conjunctival defect have been satisfactorily corrected. This combined surgical procedure using amniotic membrane allograft and a composite tarsoconjunctival flap is shown to be useful in the treatment of an advanced conjunctival neoplasia with extensive eyelid involvement.

Cavitary choroidal melanoma.

CASE REPORT: We report an unusual case of cavitary choroidal melanoma. The results of ultrasonography, magnetic resonance imaging, computed tomography, and immunohistochemical studies are presented for a 38-year-old woman who developed an amelanotic tumor in the posterior choroid. B-scan ultrasonography disclosed intratumoral cavitations. Systemic and extraocular extension studies were negative. Enucleation was performed and histopathologic examination showed a choroidal melanoma of spindle cell type, with intratumoral cavitations lined by flattened tumor cells. COMMENTS: The majority of previous reports of intraocular cavitary tumors describe cavitary ciliary body tumors. Uveal melanoma should be included in the differential diagnosis of choroidal cavitary lesions. As far as we know, this is the second documented clinicopathologic correlation of a cavitary choroidal melanoma.

Iris colour and uveal melanoma.

Iris pigmentation has several physiologic functions, including protection of the underlying tissues from ultraviolet radiation and a protective role in various diseases, such as age-related macular degeneration, cataract and uveal melanoma. Uveal melanoma has been reported to be more prevalent among white people with light irides. It has been suggested that the increased risk may be due to the lack of pigmentation, which allows greater light transmission to the uvea. In this article the author reviews the association between iris colour and ocular disease, particularly uveal melanoma.

Proliferative vitreoretinopathy: cytologic findings in vitreous samples.

PURPOSE: To compare the cellularity of vitreous samples obtained from patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy (PVR) and from patients with uncomplicated rhegmatogenous retinal detachment (RD) to detect possible variations in cellularity over time. METHODS: One hundred and twenty-five vitreous specimens collected from patients with RD (n = 41) and PVR (n = 84) were processed through direct paraffin embedding and cytospin. Different cell types were identified by light-microscopy (hematoxylin-eosin and Papanicolaou stain) according to their morphologic features, and a scale of cellular density was established for each cell type. Student's t test was used to analyze differences in the cellularity of RD versus PVR. A quadratic model was used to identify variations in the density of each cellular type in the PVR group, based on its evolution time. RESULTS: During the first months after surgery, more macrophages and fibroblast-like cells were observed in the PVR group, but at other times no differences were found. CONCLUSIONS: There are some differences in vitreous cellularity in PVR specimens when compared with RD. Especially relevant could be the large number of macrophages in earlier stages and their constant presence over time in PVR samples. The cytology of vitreous samples may shed light on the chronology of PVR cell pathobiology.