Local treatment failure after globe-conserving therapy for choroidal melanoma.

Local treatment failure after globe-conserving therapy for choroidal melanoma is a surgical complication with significant morbidity to the vision and eye. Few reports in the literature have addressed this complication exclusively. A review of the published literature with reference to local treatment failure in the management of choroidal melanoma was performed to make known the potential differences in failure rates between treatment modalities and methods. A search of the literature regarding local treatment failure was performed to identify relevant studies using combinations of the following keywords on PubMed: uveal melanoma, choroidal melanoma, local recurrence, local failure, endoresection, gamma knife, radiotherapy, helium, iodine, proton, palladium, ruthenium, trans-scleral resection, transpupillary thermotherapy. Further studies were found by searching the text and references of previously identified studies for articles reporting local treatment failure rates in choroidal melanoma. Among the 49 studies identified, the local treatment failure rate ranged from 0% to 55.6%, with follow-up ranging from 10 to 150 months. The two most widely used forms of radiation therapy, iodine-125 and ruthenium-106 brachytherapy, were both associated with a local recurrence rate of 9.6%. The weighted-average of treatment failure in all radiation therapies was 6.15% compared with 18.6% in surgical and 20.8% in laser therapies. Rates of local treatment failure for globe-conserving therapy of choroidal melanoma varied widely between modalities and between centres using similar modalities. Radiation therapy overall resulted in lower local treatment failures compared with surgical or transpupillary thermotherapy

Heterogeneity of monosomy 3 in fine needle aspiration biopsy of choroidal melanoma.

PurposeTo report on the heterogeneity of monosomy 3 in a fine needle aspiration biopsy obtained transsclerally from choroidal melanoma for prognosis.MethodsAll clinical records for patients who had been diagnosed with choroidal melanoma and underwent iodine-125 plaque brachytherapy with intraoperative transscleral fine needle aspiration biopsy from January 2005 to August 20, 2011, and who had a positive result for monosomy 3 according to fluorescence in situ hybridization as reported by clinical cytogenetics testing were collected. Patient age and sex, total number of cells evaluated and number of cells positive for monosomy 3, tumor size, and metastatic outcome were recorded for each patient.ResultsA positive result for monosomy 3 was reported in 93 patients who underwent transscleral fine needle aspiration biopsy. Two patients were lost to follow-up immediately post-operatively, and the remaining 91 patients were included in this study. The mean number of cells evaluated in the biopsy was 273 (range 28 to 520). The mean percentage of cells positive for monosomy 3 was 62.9% (range 4.7%-100%). The mean tumor height was 5.91 mm (range 1.99 to 10.85 mm). Larger tumors were associated with a higher percentage of cells positive for monosomy 3. During the average follow-up interval of 28.9 months (range 3-76 months), choroidal melanoma metastasis developed in 18 (20%) patients. Patients whose tumors had 1%-33% of cells positive for monosomy 3 had a significantly lower risk of metastasis-related death compared to patients whose tumors harbored a higher percentage of monosomy 3 (p = 0.04).ConclusionsCytogenetic heterogeneity of fluorescent in situ hybridization for monosomy 3 exists in a biopsy sample. Larger tumors were more likely to have a higher percentage of monosomy 3 positive cells in the sample. Furthermore, patients whose tumors had more than 33% of cells positive for monosomy 3 had a poorer prognosis than patients whose tumors had lower percentages of monosomy 3

Clinical and cytogenetic characteristics of choroidal melanoma in Vietnamese Asians

PURPOSE: To report the clinical and cytogenetic characteristics of choroidal melanoma in Vietnamese Asians. METHODS: In three Vietnamese Asians with choroidal melanoma, transscleral fine needle aspiration biopsy (FNAB) was performed immediately before Iodine-125 brachytherapy. Biopsy was examined for cytopathology, fluorescence in situ hybridization (FISH) for the centromere of chromosome 3, and analyzed by 250K whole genome Mapping Array and U133 plus 2.0 Expression Array. RESULTS: Three Vietnamese Asian men (50, 59, and 30 years of age) with clinical diagnosis of choroidal melanoma and no evidence of metastasis had FNAB immediately before Iodine-125 brachytherapy. Cytopathology showed heavily pigmented cells suggestive of or consistent with melanoma. Mapping Array and Expression Array revealed cytogenetic aberrations and gene expression profiles characteristic of choroidal melanoma. One patient (Case 2) with chromosome 3 loss and chromosome 8q gain developed biopsy-proven liver metastasis three years after brachytherapy. One patient (Case 1) with chromosome 6p, 9q and 17q gain and a second patient (Case 3) with 6p, 8q and 9q gains and losses in 6q and 8p have had no evidence of metastasis three years after brachytherapy. CONCLUSIONS: In this series of Vietnamese Asians with heavily pigmented choroidal melanoma, the clinical characteristics, cytogenetic aberrations and gene expression profiles were similar to characteristics in other ethnic/racial groups and the cytogenetic aberration of chromosome 3 loss was associated with the development of liver metastasis

Spectral-domain optical coherence tomography of conjunctival mucosa-associated lymphoid tissue lymphoma with presumed choroidal involvement

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma has been well-described, but rarely do these lesions demonstrate intraocular involvement. We report a case of conjunctival MALT lymphoma with intraocular involvement and novel spectral-domain ocular coherence tomography (SD-OCT) findings. A 75-year-old woman with biopsy-proven MALT lymphoma of the conjunctiva presented with ipsilateral yellowish diffuse choroidal infiltrates on fundoscopic examination. Choroidal involvement was documented clinically, on ultrasonography, on fluorescein angiography, and by SD-OCT. Treatment consisted of 3 weeks of oral doxycycline and six cycles of systemic chemotherapy with cyclophosphamide, vincristine, prednisone, and rituximab. There was no evidence of progression or recurrence of MALT lymphoma after 9 months of follow-up. Despite complete resolution of clinical findings, ultrasound, and fluorescein angiography, the choroidal lesions remained unchanged on SD-OCT. Choroidal involvement of conjunctival MALT is rare, and can be successfully treated. Persistence of irregularities on SD-OCT did not influence management in the presence of clinical improvement and resolution on ultrasonography and fluorescein angiography

Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene

Local treatment failure after globe-conserving therapy for choroidal melanoma.

Local treatment failure after globe-conserving therapy for choroidal melanoma is a surgical complication with significant morbidity to the vision and eye. Few reports in the literature have addressed this complication exclusively. A review of the published literature with reference to local treatment failure in the management of choroidal melanoma was performed to make known the potential differences in failure rates between treatment modalities and methods. A search of the literature regarding local treatment failure was performed to identify relevant studies using combinations of the following keywords on PubMed: uveal melanoma, choroidal melanoma, local recurrence, local failure, endoresection, gamma knife, radiotherapy, helium, iodine, proton, palladium, ruthenium, trans-scleral resection, transpupillary thermotherapy. Further studies were found by searching the text and references of previously identified studies for articles reporting local treatment failure rates in choroidal melanoma. Among the 49 studies identified, the local treatment failure rate ranged from 0% to 55.6%, with follow-up ranging from 10 to 150 months. The two most widely used forms of radiation therapy, iodine-125 and ruthenium-106 brachytherapy, were both associated with a local recurrence rate of 9.6%. The weighted-average of treatment failure in all radiation therapies was 6.15% compared with 18.6% in surgical and 20.8% in laser therapies. Rates of local treatment failure for globe-conserving therapy of choroidal melanoma varied widely between modalities and between centres using similar modalities. Radiation therapy overall resulted in lower local treatment failures compared with surgical or transpupillary thermotherapy

Correlation of Immunocytochemistry of BRCA1-associated Protein-1 (BAP1) With Other Prognostic Markers in Uveal Melanoma

PURPOSE:Prior studies have shown that nuclear reactivity for BRCA1-associated protein-1 (BAP1) yields prognostic information for paraffin-embedded uveal melanomas. Lacking are immunocytochemical studies of BAP1 on fine needle aspiration biopsies of uveal melanoma that correlate with prognosis or other markers of prognosis. Our purpose was to fill this gap. DESIGN:Experimental laboratory study. METHODS:Fine needle aspiration biopsies were performed prospectively on 113 patients with uveal melanomas, garnering limited subsets of cases for comparison. Agreement between immunocytochemistry for BAP1 nuclear staining vs chromosome 3 ploidy analysis and gene expression profiling was assessed by 2 × 2 contingency table analysis. RESULTS:The presence or absence of suppression of nuclear expression of BAP1 was strongly associated (73%, P = .000002) with monosomy and disomy chromosome 3, respectively. BAP1 nuclear expression was also correlated with gene expression profiling. Chromosome 3 ploidy analysis correlated with gene expression profiles. CONCLUSION:When adequate material is obtained, immunocytology using BAP1 is a potentially informative tool for prognostication of uveal melanoma