Primary orbital melanoma arising in an atypical diffuse (plaque-like) blue naevus/melanocytosis: a case report and review of literature.

BACKGROUND: Primary orbital melanoma is a rare disease and can occasionally develop from a pre-existing neoplasm of the blue naevus family of melanocytic lesions. CASE PRESENTATION: Herein we report a rare case of primary orbital melanoma arising from an unusual atypical diffuse (plaque-like) blue naevus/melanocytosis. A 27 year old man presented with mild pain and swelling of the left eye. Magnetic Resonance Imaging revealed a left lateral episcleral orbital mass and an incisional biopsy confirmed the diagnosis of malignant melanoma. Skin-sparing total left orbital exenteration was performed. Histopathological examination of the exenteration specimen revealed a primary orbital melanoma arising in a pre-existing blue naevus like melanocytosis. We demonstrate the evidence for histological progression, characterise the molecular profile of this tumour and discuss the related literature. CONCLUSIONS: This case emphasises the importance of a meticulous clinicopathological correlation in recognising such a tumour as a primary orbital melanoma rather than a metastasis, which is managed differently.

Progressive orbital granular cell tumour associated with medial rectus.

Granular cell tumour is a rare soft tissue tumour that can occur in any part of the body, but seldom in ocular adnexa. It usually behaves in a benign fashion. We report a case of a 54-year-old man with a well-demarcated, solitary, slow-growing orbital tumour which lead to significant ocular symptoms. The case was a diagnostic and therapeutic challenge due to its location and difficulty in obtaining tissue for a histological diagnosis. Surgical biopsy attempts were made but they all failed to uncover the true identity of the lesion. A definitive diagnosis was revealed with complete surgical excision of the tumour, which was challenging due to its size and close association with rectus muscle. This case has highlighted that orbital granular cell tumour may result in significant ocular symptoms. Adequate exposure to the anatomical site is the key to obtaining diagnosis and complete excision of a lesion.

Pooled genome wide association detects association upstream of FCRL3 with Graves' disease.

BACKGROUND: Graves' disease is an autoimmune thyroid disease of complex inheritance. Multiple genetic susceptibility loci are thought to be involved in Graves' disease and it is therefore likely that these can be identified by genome wide association studies. This study aimed to determine if a genome wide association study, using a pooling methodology, could detect genomic loci associated with Graves' disease. RESULTS: Nineteen of the top ranking single nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056 reaching genome wide significance (p = 5 × 10-8). Technical validation of top ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with individual genotyping in the discovery cohort revealed four single nucleotide polymorphisms with p ≤ 10-4. Rs17676303 on chromosome 1q23.1, located upstream of FCRL3, showed evidence of association with Graves' disease across the discovery, replication and combined cohorts. A second single nucleotide polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association supported by finding in the replication cohort that warrants further study. CONCLUSIONS: Pooled genome wide association study identified a genetic variant upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to those identified in the Major Histo-compatibility Complex. A second locus downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease that requires further confirmation.

Association of Polymorphisms in MACRO Domain Containing 2 With Thyroid-Associated Orbitopathy.

PURPOSE: Thyroid-associated orbitopathy (TO) is an autoimmune-mediated orbital inflammation that can lead to disfigurement and blindness. Multiple genetic loci have been associated with Graves' disease, but the genetic basis for TO is largely unknown. This study aimed to identify loci associated with TO in individuals with Graves' disease, using a genome-wide association scan (GWAS) for the first time to our knowledge in TO. METHODS: Genome-wide association scan was performed on pooled DNA from an Australian Caucasian discovery cohort of 265 participants with Graves' disease and TO (cases) and 147 patients with Graves' disease without TO (controls). Top-ranked single nucleotide polymorphisms (SNPs) then were genotyped in individual DNA samples from the discovery cohort, and two replication cohorts totaling 584 cases and 367 controls. RESULTS: In the GWAS of pooled DNA samples, several SNPs showed suggestive association with TO at genome-wide P ≤ 10-6; rs953128 located on chr10q21.1, rs2867161 on chr7q11.22, rs13360861 on chr5q12.3, rs7636326 on chr3q26.2, rs10266576 on chr 7q11.22, rs60457622 on chr3q23, and rs6110809 on chr20p12.1. However, the only SNP consistently associated with TO on individual genotyping in the discovery and replication cohorts was rs6110809, located within MACROD2 on chromosome 20p12.1. On combined analysis of discovery and replication cohorts, the minor A allele of rs6110809 was more frequent in TO than in Graves' disease controls without TO (P = 4.35 × 10-5; odds ratio [OR] = 1.77; 95% confidence interval [CI], 1.35-2.32) after adjusting for age, sex, duration of Graves' disease, and smoking. CONCLUSIONS: In patients with Graves' disease, a common genetic variant in MACROD2 may increase susceptibility for thyroid-associated orbitopathy. This association now requires confirmation in additional independent cohorts.

Intraorbital corticosteroid injection for the treatment of IgG4-related ophthalmic disease.

AIM: To review the efficacy of intraorbital corticosteroid injection for the treatment of IgG4-related ophthalmic disease (IgG4-ROD). METHODS: This study was a retrospective twin-centre histopathology review and observational case series. A chart review was undertaken for 10 cases of biopsy-confirmed IgG4-ROD treated with intraorbital corticosteroid injection. The main outcome measures were the magnitude, onset and duration of the clinical response. RESULTS: All cases received intraorbital injection(s) of 20 or 40 mg doses of triamcinolone acetonide suspension (Kenacort-A 40, Bristol-Myers Squibb, Australia). Intraorbital corticosteroid injection was associated with a swift positive response in all cases. 50% of cases achieved complete and sustained clinical remission during mean follow-up of 41 months. This was achieved with a single injection in three cases and with repeat injections in two cases. Peak clinical improvement was reached in ≤7 days following 61% of injections. 60% of cases suffered relapse and 56% of relapses occurred during weeks 3 or 4 following injection. Sclerosing histology was associated with a clinical response that was gradual in onset (p=0.01) and that tended to be incomplete (p=0.4). There were no complications of injection other than brief discomfort. CONCLUSIONS: Intraorbital injection of corticosteroid may be a useful treatment option for IgG4-ROD. It may have a role as a first-line therapy in selected cases of IgG4-ROD centred in the anterior orbit. However, most cases require repeat injections due to incomplete response and relapse.

Prevalence of excessive tearing in women with early breast cancer receiving adjuvant docetaxel-based chemotherapy.

PURPOSE: To define the incidence and impact of tearing in patients receiving adjuvant docetaxel-based chemotherapy and assess for lacrimal duct obstruction (LDO) as a causative factor. PATIENTS AND METHODS: Consecutive patients with early breast cancer recommended for docetaxel-based chemotherapy with no prior ocular symptoms were included. Before and after completion of chemotherapy, patients underwent lacrimal drainage evaluation by computed tomographic dacrocystography (CT-DCG) and ophthalmic assessment. Eye symptoms were assessed at baseline, during, and after completion of chemotherapy. RESULTS: Over a 22-month period, 100 patients were recruited. Asymptomatic LDO was present at baseline in 17% and 18% of patients, as assessed by ophthalmic review and CT-DCG, respectively. Overall, 86% of patients developed tearing, with no significant difference between those who did and did not have LDO (94% v 84%; P = .45). Blepharitis occurred in 37% and minor corneal epitheliopathy in 22% of patients, with neither condition predicting for the development of tearing. Impairment of visual activities was greatest after cycle one (70% of patients) but had decreased to < 5% by 4 months after treatment. CONCLUSION: Tearing occurs in the majority of patients receiving adjuvant docetaxel-based chemotherapy regimens and occurred similarly in patients with and without LDO. There was poor concordance between CT-DCG and ophthalmic examination in the detection of LDO. Tearing and other eye symptoms impaired visual activities, but in nearly all patients, both symptoms and functional impairment were mild and had resolved by 4 months after chemotherapy. Our study demonstrates docetaxel-related tearing is not caused by LDO, and as such, evaluation or stenting of the duct is not considered necessary.

Severe, unstable migraine: a risk factor for postoperative ophthalmic artery spasm?

Acute ophthalmic artery occlusion (AOAO) is rare. We describe a patient with severe unstable migraine who developed AOAO with a giant retinal fold following the removal of a cavernous haemangioma. We discuss prophylatic measures that may be taken in such patients.