Ocular tumours.

Ocular tumours may arise from various tissues and therefore present as a heterogeneous group of diseases with unspecific symptoms. Some of the tumours carry a high mortality with a life expectancy less than 50% after ten years. Early diagnosis and treatment are essential for a good outcome, and centralization has led to a decreased morbidity and increased survival in Denmark. Tumour-specific somatic mutations can be used for personalized follow-up programmes and may lead to new treatment modalities, as argued in this review.

Metachronous, non-pineal, trilateral retinoblastoma in a patient with a seemingly reduced-expressivity RB1 germline deletion.

The clinical course of trilateral retinoblastoma can be unpredictable, and expressivity of germline RB1 variants may vary during development. We describe an unexpected fatal case of trilateral retinoblastoma with an intracranial tumor in an unusual location and discuss genetic copy number analyses as a useful diagnostic tool with therapeutic potential.

A multidimensional cohort study of late toxicity after intensity modulated radiotherapy for sinonasal cancer.

PURPOSE: To evaluate the occurrence of late toxicity after curatively intended intensity modulated radiotherapy (IMRT) for sinonasal cancer and assess dose-response associations. METHODS: Patients treated with IMRT in 2008-2016 were included. Cross sectional examinations of toxicity from the optic pathway, the brain, the pituitary gland and the nose were performed along with quality of life - (QoL) and dose-response analyses. RESULTS: Twenty-seven patients were enrolled; median age was 67 years (range 47-83). Five patients (19%) had radiation-related ocular toxicity. The risk of visual acuity impairment increased with increasing dose (grade 2 odds ration (OR) 1.12, p = 0.01; grade 3 OR 1.14, p = 0.02) and dose constraint violations (grade 2, OR = 21, p < 0.01; grade 3, OR = 41, p < 0.01). Six patients (22%) exhibited evidence of radiation-related hypopituitarism, but no dose-response association was detected. Seventeen patients (63%) had impaired olfactory function. The risk of olfactory impairment increased with higher stage (OR = 3.32, p = 0.03). Three patients (11%) had structural abnormalities in irradiated areas of the brain, and impaired cognitive function was present in 17 patients (63%). Cognitive, physical, role functioning as well as fatigue and insomnia were affected the most in QOL analyses. Fifteen patients (56%) had grade 2 radiation-related impairment in at least one organ. Grade 3 toxicity was only present in patients with toxicities in >3 organs and in patients initially treated for T4 tumours. Three patients (11%) had radiation-related impaired function in all examined OARs. CONCLUSION: Late toxicity after radiotherapy was substantial in all examined organs, with dose-response associations between visual acuity impairment and the optic nerve. The results have led to changed praxis for follow-up examinations in Denmark.

Late onset retinoblastoma presenting with vitreous haemorrhage.

Our work describes the management of young patients who presents with vitreous haemorrhage. It is important to note that the causes differ significantly from adults with vitreous haemorrhage.A 16-year old patient presented with vitreous haemorrhage. B-scan ultrasonography showed hypodense elements in the retina. A vascularized gelatinous mass was revealed after vitrectomy. Later the patient developed white cysts in the anterior chamber and histological findings were indicative of a retinoblastoma. The patient was enucleated and the diagnosis of retinoblastoma was confirmed. Intraocular surgery in young people with unknown retinoblastoma enhances the risk of metastasis development, orbital recurrence and death. Unexplained vitreous haemorrhage can obscure the view of a tumour but ultrasonic findings of a retinal mass calls for further imaging e.g. through MRI. The case illustrates the importance of excluding intraocular malignancy and advises a limited use of surgery in the initial examination of vitreous haemorrhage in young people.

Proteomics of uveal melanomas suggests HSP-27 as a possible surrogate marker of chromosome 3 loss.

PURPOSE: To compare the proteomic profiles of primary uveal melanomas, with and without loss of chromosome 3. METHODS: Frozen specimens from three uveal melanomas with disomy 3 and from four tumors with monosomy 3, according to fluorescence in situ hybridization (FISH) analysis, were subjected to high-resolution, two-dimensional (2-D) gel electrophoresis. The protein expression profiles of the two uveal melanoma cytogenetic groups were compared: Proteins that differed significantly were excised and analyzed by tandem mass spectrometry. Differentially expressed proteins were further analyzed with Western blot analysis. An independent cohort of 41 formalin-fixed, paraffin-embedded (FFPE) uveal melanomas, whose chromosome 3 status had been determined by multiplex ligation-dependent probe amplification (MLPA), was examined for the appropriate antigens by immunohistochemistry. RESULTS: Four protein spots were 1.5-fold (Student's t-test, P < 0.05) differentially expressed in the two uveal melanoma types: two spots were overexpressed in the disomy 3 group compared with the monosomy 3 group, whereas two spots were underexpressed. Identification of the four spots yielded nine proteins. Western blot analysis confirmed the results for heat shock protein (HSP)-27, vimentin, and pyruvate dehydrogenase beta (PDHB), with a statistical significance for the first two proteins. HSP-27 was significantly downregulated, whereas vimentin was upregulated in the monosomy 3 tumors (Student's t-test, P = 0.003 and P = 0.005, respectively). Immunohistochemistry confirmed low-to-negative HSP-27 protein expression in monosomy 3 uveal melanomas (Student's t-test; P = 0.011). CONCLUSIONS: Low-to-negative HSP-27 protein expression in uveal melanoma correlates strongly with monosomy 3. Further validation is necessary to determine whether immunohistochemical assessment of HSP-27 expression correlates with metastatic mortality.