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Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCNARB1+/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCNARB1+/+ retinoblastoma and age-matched children with RB1-/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing (RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCNARB1+/+ retinoblastoma and 88 control children with RB1-/- retinoblastoma. Children in the MYCNARB1+/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1-/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCNARB1+/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCNARB1+/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCNARB1+/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

This report describes a case of cystic, extranodal, marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue of the orbital lobe of the lacrimal gland in a 70-year-old female. Case of cystic MALT lymphoma isolated to the orbital lobe of the lacrimal gland are rare, with six case reported in the literature. Initial clinical examination revealed bilateral dermatochalasis and a medial left upper lid contour deformity thought to be involutional ptosis. There was no suspicion for a mass lesion. Imaging and subsequent specialist clinical, pathologic, an immunochemical evaluation showed diagnostic features of cystic lacrimal gland orbital lobe MALT lymphoma. Clinical, radiographic, and immunohistopathologic and immunohistochemical findings are detailed. A review of literature was performed and discussed.

PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigates the clinical findings, treatment and outcome of patients with metastatic cutaneous melanoma to the vitreous. The majority of patients received checkpoint inhibition for the treatment of their systemic disease and the significance of this is explored. PARTICIPANTS: 14 eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. DESIGN: Multicenter, retrospective cohort study METHODS: Clinical records, including fundus photography and ultrasound, were retrospectively reviewed and relevant data was recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments and outcome RESULTS: The median age at presentation of ophthalmic disease was 66 years (range 23–88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of eleven patients were treated with immune checkpoint inhibition, at some point in their treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range 4.5 to 38 mos). Half the eyes had amelanotic vitreous debris. Five eyes developed elevated intraocular pressure and four eyes developed a retinal detachment. Six patients had metastatic disease in their central nervous system. Ophthalmic treatment included: external beam radiation (30–40Gy) in six eyes, intravitreous melphalan (10–20μg) in four eyes, enucleation in one eye, local observation while on systemic treatment in two eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception (NLP). CONCLUSION: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this appears to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and the majority of eyes have poor visual potential. Approximately one quarter of the patients had ocular disease that preceded central nervous system metastasis . Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.

To determine whether long-term cultured nondividing human retinal pigment epithelial (hRPE) cells are sensitive to oxidant-induced apoptosis and whether the Fas pathway is involved in the process.Confluent hRPE cells were maintained for 2 to 3 months in the basal medium (DMEM containing 2% fetal bovine serum) with one medium change per week. DNA synthesis was measured by incorporation of bromodeoxyuridine (BrdU) and the cell cycle was analyzed by flow cytometry. Intracellular glutathione (GSH) and glutathione disulfide (GSSG) were measured by HPLC. Apoptosis was triggered with the oxidant tert-butylhydroperoxide (tBH), recombinant soluble Fas ligand (sFasL), or agonistic anti-Fas antibody (CH-11). Cell viability was assessed by tetrazolium salt (WST-1) assay, and apoptosis was determined by measuring DNA cleavage or phosphatidylserine exposure. FasL and Fas proteins were detected by flow cytometry and Western blot. FasL and Fas transcripts were analyzed by RT-PCR.After incubation in basal medium for more than 2 months, hRPE cells were largely nondividing and accumulated autofluorescent granules identified by electron microscopy to be lysosomes. Compared with proliferating hRPE cells, the nondividing cells had lower intracellular GSH, GSSG, and GSH/GSSG and a more oxidized redox potential (E(h)). Downregulation of Fas but upregulation of FasL was observed in these cells. The nondividing hRPE cells appeared more susceptible to tBH-induced apoptosis. Similar to proliferating hRPE cells, the apoptosis induced by tBH was preceded by induction of FasL, and antioxidants inhibited both FasL increase and apoptosis. Apoptosis was also inhibited with the antagonistic anti-Fas antibody ZB4. However, the nondividing hRPE cells had decreased sensitivity to apoptosis triggered by sFasL or CH-11.Long-term hRPE culture created cells that were nondividing and accumulated autofluorescent granules. The increased sensitivity to tBH-induced apoptosis in these cells was associated with intracellular oxidation and upregulation of FasL. These results suggest that an increase in FasL may contribute to the vulnerability of nondividing hRPE cells to oxidant-induced apoptosis.