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Background: Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma., Methods: Twenty-five patients with stage IV uveal melanoma who had received 0-1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m(2)) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS)., Results: No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0-14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1-6 months] and the 6-month PFS was 29% [95% CI: 13%-48%]. The median OS was 11 months [95% CI: 7-14 months]., Conclusion: In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients., Trial Registration: ClinicalTrials.govNCT00329641.

An 11-year-old, neutered male domestic short-hair cat was presented with buphthalmos of the right eye and diagnosed with advanced glaucoma. Sonographic examination revealed an iridial thickening. Neoplasia was suspected and an enucleation was performed. Histopathology of the enucleated eye revealed abundant amyloid deposition predominantly in the anterior uveal tract accompanied by few to moderate numbers of well-differentiated plasma cells. The amyloid deposits were identified by staining with Congo red and showing green birefringence under polarized light. Immunohistochemically, amyloid and plasma cells stained intensely only with anti-ALλ antibody, supporting the amyloid tumor being an immunoglobulin-λ-light chain origin. Additional abnormalities included narrowing of the filtration angle and collapse of the ciliary cleft, and trabecular meshwork. One year post-enucleation, the cat was still healthy without signs of systemic amyloidosis or apparent metastatic disease. This is the first report of a cat with noncutaneous extramedullary plasmacytoma originating in the anterior uveal tract with resulting local amyloid., (© 2011 American College of Veterinary Ophthalmologists.)

Objective: To determine whether cyclooxygenase-2 (COX-2) is expressed in benign or malignant canine uveal melanocytic neoplasms and whether expression correlates with malignancy., Sample Population: Tissue sections from 71 globes; 57 with benign (n = 15), malignant (34), or mixed (8) uveal melanocytic neoplasms; 10 with nonneoplastic disease; and 4 with no abnormalities., Procedures: Bleached sections from all globes and canine kidney were incubated with mouse monoclonal antibody directed against rat COX-2 protein or mouse antibody isotype control. Location, intensity, and percentage of immunolabeled cells were scored., Results: Expression of COX-2 was detected in all but 5 globes, all of which contained neoplasms. Expression of COX-2 was detected in regions infiltrated by neoplasia in 21 globes; however, definitive labeling of tumor cells was detected in only 2 of those. In the remaining 19 globes, COX-2 expression was detected in areas also labeled in globes without disease and globes with nonneoplastic disease, especially the aqueous outflow tract and ciliary body. However, only globes with uveal malignant melanomas had detectable COX-2 expression in the iris. Expression of COX-2 was detected in the ciliary body of more globes with uveal malignant melanoma (20/34) than in those without disease (1/4), with nonneoplastic disease (4/10), or with melanocytoma (3/15) or mixed neoplasms (3/8)., Conclusions and Clinical Relevance: Canine globes with uveal melanocytic neoplasia appeared to express COX-2 in similar sites and with similar intensity as globes without neoplasia. Differentiation of benign from malignant canine uveal melanocytic neoplasms was not possible.

Background: Fine-needle aspiration biopsy recently has been used as a diagnostic modality for selected intraocular tumors and simulating conditions. However, the value of fine-needle aspiration biopsy for intraocular tumors previously has not been clarified., Methods: Transocular fine-needle aspiration biopsy was performed on selected patients who had intraocular lesions that were suspected clinically to be neoplasms but in which there was diagnostic uncertainty based on noninvasive clinical evaluation. These cases were analyzed to determine accuracy, complications, and limitations of the technique., Results: Of 6500 patients referred to the Oncology Service for evaluation of possible intraocular tumor, transocular fine-needle aspiration biopsy was used clinically in 159 cases (2.4%). It proved to be a reliable diagnostic method for intraocular malignancies such as uveal melanoma, uveal metastasis, retinoblastoma, lymphoma, and leukemia. In the 140 cases (88%) in which adequate cytologic material was obtained, the sensitivity rate was 100% and the specificity rate was 98%. In 19 cases where the cytologic material was too scant to render a diagnosis, the sensitivity rate was 84% and the specificity rate was 98%. The problem of insufficient material for cytologic diagnosis has been greatly minimized with the recent use of a 22-gauge needle. The main complication was localized intraocular hemorrhage. Retinal detachment and tumor recurrence have not been observed., Conclusions: Transocular fine-needle aspiration biopsy is a safe and reliable diagnostic method for suspected intraocular tumors and inflammatory conditions in which noninvasive diagnostic modalities have failed to establish the diagnosis and in which cytologic verification of the diagnosis is necessary to institute appropriate treatment. Although the authors have had few complications with fine-needle aspiration biopsy, the technique should be reserved for selected cases where the diagnosis has not been established by less-invasive diagnostic measures.

Four patients with primary intraocular reticulum-cell sarcoma were presented. All of the patients were followed at the Wilmer Institute for periods of up to ten years. All had decreased visual acuity and a uveitis that was refractory to standard forms of therapy. In one case, the correct diagnosis was made clinically. At autopsy, two of the patients had systemic reticulum-cell sarcoma, a third had intracranial reticulum-cell sarcoma, and in a fourth case the disease process was confined to the eye. The literature is reviewed and the clinico-pathologic features of the total of 14 cases are analyzed. It is emphasized that a recalcitrant uveitis was present in almost all of the cases reported. Differential diagnosis and methods of diagnosis are discussed.

A 47-year-old man developed chronic unilateral iridocyclitis with secondary glaucoma, and elevated plasma CEA levels. The eye was enucleated seven months later, and histopathologic examination revealed a metastatic mucin producing CEA positive adenocarcinoma. The patient died one year after the initial onset of symptoms. The primary site of the tumor was not proven, but most likely was the gastrointestinal tract.

A male Chinese neonate had a melanocytic hamartoma that involved the entire orbit and the eye, but did not involve the orbital bones or eyelid skin. Although usually benign, these hamartomas may be locally invasive, and rare cases of malignant transformation have occurred.

A 65-year-old woman had been observed for more than four years with bilateral chronic nongranulomatous uveitis and vitreous clouding of unknown cause. Her death was from reticulum cell sarcoma of the brain (microglioma). Both eyes were obtained post mortem. Histopathologic examination revealed malignant cell in the vitreous of both eyes, but no other tumor was demonstrable in the ocular tissues. Reticulum cell sarcoma should be suspected in middle-aged or older persons with chronic unilateral or bilateral uveitis of unknown cause who develop cerebral manifestations during the course of the disease.

Twenty-nine patients who had undergone enucleation for ocular malignant melanoma were studied. The results of the radioactive phosphorus uptake (32P) tests were correlated with histopathologic observations. There was a positive correlation between the 32P test results and the histologic degree of malignancy. Mixed cell melanomas were more frequent in the patients ranked with higher 32P test results. Spindle cell melanomas occurred more frequently in patients with lower 32P test results. Mitoses per field and degree of malignancy correlated positively with 32P test results when ranked in a masked manner by two ocular pathologists. Tumor volume and clinical factors did not correlate with the 32P test results. While patients with mixed cell melanomas had higher mean 32P test results than those with spindle cell melanomas, a large variance was noted. Because of this the 32P test is unreliable in predicting the histopathology of a tumor in individual cases.

Lymphoma is a term which encompasses a diverse group of human lymphoid malignancies. Most lymphomas rarely affect the intraocular tissues, and those that do are generally of the diffuse large cell (histiocytic) type. The typical clinical patterns of presentation of intraocular lymphoma are (1) diffuse intravitreal cells, (2) geographic subretinal pigment epithelial infiltrates, and (3) uveal tumors. In this paper, the authors illustrate the most common presentations of this disorder, review the differential diagnosis of these different presentations, and suggest an approach to diagnosis and management of affected patients based on their experience and a review of the literature.

Sixteen uveal melanomas in celloidin sections and eight other fresh cases of melanoma were examined using different clinical and histological methods. A recession of the lateral border of the anterior chamber angle was found in most of them. The grade of this distortion varied from very deep to insignificant, but was apparent in most cases. Seven fresh cases were gonioscopically examined and some recession was seen in five of them.

Ultrastructural characteristics of four mixed-cell type human uveal melanomas cultivated in vitro were described. The authors stress the significance of melanosome microtubules in the process of melaninisation. They also stress the significance of smooth membraness for the formation of premelanosomes. The question of differentiation between melanocytes and lysosomes in ultrastructure is discussed.