D Paridaens

Patient survival in uveal melanoma is not affected by oncogenic mutations in GNAQ and GNA11.

Background:Mutations in GNAQ and GNA11, encoding the oncogenic G-protein alpha subunit q and 11, respectively, occur frequently in the majority of uveal melanomas.Methods:Exons 4 and 5 from GNAQ and GNA11 were amplified and sequenced from 92 ciliary body and choroidal melanomas. The mutation status was correlated with disease-free survival (DFS) and other parameters.Results:None of the tumours harboured a GNAQ exon 4 mutation. A GNAQ mutation in exon 5 codon 209 was found in 46 out of 92 (50.0%) of the tumours. Only 1 out of 92 (1.1%) melanomas showed a mutation in GNA11 exon 4 codon 183, whereas 39 out of 92 (42.4%) harboured a mutation in exon 5 of GNA11 codon 209. Six tumours did not show any mutations in exons 4 and 5 of these genes. Univariate analyses showed no correlation between DFS and the mutation status.Conclusion:GNAQ and GNA11 mutations are, in equal matter, not associated with patient outcome.

The Prognostic Value of Extraocular Extension in Relation to Monosomy 3 and Gain of Chromosome 8q in Uveal Melanoma

PURPOSEnTo identify the prognostic value of extraocular extension in enucleated uveal melanoma (UM) patients and to correlate extraocular extension to chromosomal aberrations, metastasis-free survival (MFS), and clinico-histopathological risk factors.nnnMETHODSnRetrospective study of patients with UM treated with enucleation between 1987 and 2011. Melanoma-related metastasis and death were recorded. Statistical analysis (log-rank test or Cox regression analysis) was performed to correlate MFS with tumor characteristics, extraocular extension, episcleral diameter of the extraocular extension, cell type, extracellular matrix patterns, inflammation, loss of chromosome 3, and gain of chromosome 8q.nnnRESULTSnIn 43 (12%) of 357 patients, extraocular extension was observed. In this subset of patients, we noted a reduced survival of 70 months (105.5 months, P = 0.010) compared with patients without extraocular extension (175.8 months). Patients with gain of chromosomal region 8q in UM with extraocular extension had an increased risk of metastatic disease (P < 0.001). In multivariate Cox proportional hazard analysis, largest basal tumor diameter (P = 0.001), extracellular matrix patterns (P = 0.009), episcleral diameter of the extraocular extension (P = 0.016), loss of chromosome 3 (P < 0.001), and gain of 8q (P < 0.001) were independent predictors for MFS.nnnCONCLUSIONSnLarger episcleral diameter of the extraocular extension and additional gain of chromosome 8q in extraocular extension UM correlates to a worse prognosis. MFS is significantly reduced in UM with a large basal tumor diameter, extracellular matrix patterns, loss of chromosome 3, and gain of chromosome 8q.

Metastatic disease in polyploid uveal melanoma patients is associated with BAP1 mutations

PURPOSEnMost of the uvea melanoma (UM) display a near-diploid (normal, -2N) karyotype with only a few chromosomal changes. In contrast to these simple aberrations 18% of the UM samples show a polyploid character (>2N) and this was associated with an unfavorable prognosis. This study attempts to gain insight in the prognostic value of polyploidy in UM.nnnMETHODSnIn 202 patients the ploidy status of the UM was determined using cytogenetic analysis, fluorescence-in-situ-hybridization (FISH), multiplex ligation dependent probe amplification (MLPA), and/or single nucleotide polymorphism (SNP) array analysis. Immunohistochemistry was used to determine the BAP1 expression and mutation analyses of BAP1 (coding regions) and the mutation hotspots for the SF3B1, EIF1AX, GNAQ, and GNA11 genes was carried out using Sanger sequencing or whole-exome sequencing.nnnRESULTSnTwenty-three patients had a polyploid UM karyotype (11.4%). Patients with a polyploid tumor had larger tumors (15.61 vs. 13.13 mm, P = 0.004), and more often loss of heterozygosity of chromosome 3 (P = 0.003). No difference in occurrence of mutations between polyploid and diploid tumors was observed for BAP1, SF3B1, EIF1AX, GNAQ, and GNA11. Polyploidy did not affect survival (P = 0.143). BAP1 deficiency was the only significant independent prognostic predictor for patients with polyploid tumors, with a 16-fold increased hazard ratio (HR 15.90, P = 0.009).nnnCONCLUSIONSnThe prevalence of mutations in the UM related genes is not different in polyploid UM compared with diploid UM. Moreover, similar to patients with diploid UM, BAP1 mutation is the most significant prognostic predictor of metastasis in patients with polyploid UM.

Pure orbital blowout fractures reconstructed with autogenous bone grafts: functional and aesthetic outcomes

The purpose of this study was to investigate the ophthalmic clinical findings following surgical reconstruction with autogenous bone grafts of pure blowout fractures. A retrospective review of 211 patients who underwent surgical repair of an orbital fracture between October 1996 and December 2013 was performed. Following data analysis, 60 patients who were followed up over a period of 1 year were included. A solitary floor fracture was present in 38 patients and a floor and a medial wall fracture in 22 patients. Comparing preoperative findings between these two groups, preoperative diplopia and enophthalmos were almost twice as frequent in the group with additional medial wall fractures: diplopia 8% and 14% and enophthalmos 18% and 55%, respectively. One year following surgery there was no diplopia present in either group. In the solitary floor fracture group, 3% still had enophthalmos. It can be concluded that at 1 year following the repair of pure orbital floor fractures using autogenous bone, good functional and aesthetic results can be obtained. In the group with both floor and medial wall fractures, no enophthalmos was found when both walls were reconstructed. When the medial wall was left unoperated, 29% of patients still suffered from enophthalmos after 1 year.

Blowout fracture in a 3-year-old.

A 3-year-old patient was referred to the oral and maxillofacial department with a fracture of the orbital floor. Due to the lack of clinical symptoms, a conservative approach was chosen. After 3 weeks, an enophthalmos developed. The orbital floor reconstruction was successfully performed through a transconjunctival approach. This case highlights the rarity of pure blowout fractures in young children. The specific presentation and diagnostics of orbital floor fractures in children and the related surgical planning and intervention are discussed.