Nancy L. Robinson

Histopathologic characteristics of uveal melanomas in eyes enucleated from the collaborative ocular melanoma study COMS report no. 6

PURPOSE To describe the principal histopathologic findings in a series of 1,527 globes with uveal melanoma and the relationship of these findings to each other. METHODS All eyes enucleated in the Collaborative Ocular Melanoma Study (COMS) were examined independently by three ophthalmic pathologists and the findings recorded on a data form. A composite of findings was obtained after adjudication. RESULTS The diagnosis was choroidal melanoma in 1,527 (99.7%) of 1,532 cases examined. Misdiagnoses were metastatic adenocarcinoma (four) and hemangioma (one). Spindle cell (9.0%), mixed cell (86.0%), and epithelioid cell (5.0%) types were observed. Medium tumors were located more posteriorly than large tumors. Considerable local invasion was seen: rupture of Bruchs membrane (87.7%), invasion of the retina (49.1%), tumor cells in the vitreous (25.2%), vortex vein invasion (8.9%), invasion of tumor vessels by tumor cells (13.8%), and invasion into emissary canals (55.0%). Overall, 81.1% demonstrated local invasion, excluding rupture of Bruchs membrane. Scleral invasion was present in 55.7% of eyes, and extrascleral extension was present in 8.2%. Mitotic activity was significantly reduced in eyes that had received preenucleation radiation treatment (P < .001). The number of macrophages in the tumor increased with increased pigmentation (P < .001) and increased necrosis (P < .01). CONCLUSION The accuracy of diagnosis in the COMS is high, with histopathologic confirmation of the diagnosis at 99.7%. Extensive local invasion of the tumor was seen. Preenucleation irradiation significantly reduced the number of mitotic figures. An association was found regarding the presence of macrophages, the level of pigmentation, and degree of necrosis.

Increased Incidence of Choroidal Malignant Melanoma Occurring in a Single Population of Chemical Workers

In five patients with choroidal melanoma occurring among present or former workers of the duPont Belle, West Virginia, plant the involved eye was enucleated and histopathologic confirmation of the diagnosis was made. This represents a statistically significantly greater than expected occurrence of choroidal melanomas in the white male study population.

Glial cell component in retinoblastoma

The right eye of a 4-month-old girl with a large, unilateral, sporadic retinoblastoma was enucleated. The tumor was unusual because it contained Flexner-Wintersteiner rosettes with extremely large lumina. Smaller rosettes and undifferentiated tumor cells were observed within the lumina. Also of importance were cells resembling glial cells which were intermixed with more typical cuboidal retinoblastoma cells. These cells had electron microscopic features typical of glial cells and stained positively for glial fibrillary acidic protein in immunohistochemical studies. Rosettes and glial cells continued to be observed in the tumor carried in tissue culture through two passages over a 7-month period. This tumor is presented because of its unusual rosette structures and because it confirms recent reports describing a glial cell component in retinoblastoma.

Retinoblastoma and angiogenesis activity.

Aqueous hum or from 30 enucleated retinoblastomabearing eyes and 9 cell cultures of retinoblastoma were tested for angiogenesls activity using capillary endothelial cell migration assays. Aqueous from 90% of retinoblastoma eyes stimulated endothelial cell migration, compared with 25% of control eyes. Five of nine retinoblastoma cultures stimulated endothelial cell migration and five showed chorioallantoic membrane (CAM) neovascularization when compared with positive controls for angiogenesis activity. These results suggest an inverse relation between the length of time in culture and the ability of these cells to stimulate angiogenesis using these assays. Cells in culture for short periods of time gave positive test results, whereas continuous cell lines of retinoblastoma were consistently negative. While aqueous humor from retinoblastoma-bearing eyes demonstrated significant angiogenesis activity, cultured retinoblastoma cells show this only in early passages. Several possible explanations for this are considered. RETINA 4:189-194, 1984

Serologic and immunopathologic findings in temporal arteritis.

In 104 patients undergoing biopsies for temporal arteritis, lymphocyte characterization identified both T4 helper/inducer and T8 cytotoxic/suppressor lymphocytes in approximately equal numbers. B lymphocytes were absent. Deposition of IgM and IgG was observed in three of 16 positive biopsy specimens. Antinuclear antibodies were present in ten of 16 biopsy-proven cases of temporal arteritis compared with 19 of 55 in the control group with negative biopsy specimens. Anti-smooth-muscle, anti-DNA, and antimitochondrial antibodies were not useful in distinguishing between the two groups.

The herpes simplex virus type 1 ribonucleotide reductaseis required for acute retinal disease

SummaryWe have used a herpes simplex virus type 1 (HSV-1) ribonucleotide reductase (RR) null mutant (ICP6Δ) to determine if the HSV-1 RR is required for acute retinal disease. Injection of the ICP6Δ mutant into the vitreous induced mild transient signs of infection (vitreal infiltrate, retinal inflammation, and changes in retinal cytology). In contrast, the parental KOS and a revertant virus (ICP6Δ + 3.1) in which the RR gene had been restored, caused severe retinitis. Injection of media alone also induced mild transient signs of disease. Two months after infection, ICP6Δ injected eyes could not be distinguished from normal eyes. Repeated injection of ICP6Δ (3 times, 2 weeks apart) resulted in vitreal infiltrate near the site of injection but the retina did not appear damaged. The mutant, ICP6Δ, grew to peak titers 1 × 103 to 1 × 105-fold lower and cleared faster than KOS or ICP6Δ + 3.1 in the injected eyes suggesting that the reduced virulence was due to reduced ability of the virus to grow. These results show that the viral RR is required for acute retinal disease.

Scanning electron microscopy of retinoblastoma

Abstract The surface morphology of two continuous cell lines of human retinoblastoma (Y79 and WERI-Rbl) and freshly removed retinoblastoma were studied by scanning electron microscopy (SEM). Commonly observed surface features included microvilli, lamellipodia, filopodia, and zeiotic blebs. A close similarity was seen between the surface morphology of established cell lines of retinoblastoma and that of fresh tumor. Smooth, sphere-like cells were present in both cultured and fresh retinoblastoma. Samples of cultured retinoblastoma cells showed rosettes on light and transmission electron microscopy and the scanning electron microscopic counterparts were observed. The surface characteristics of retinoblastoma were compared to human neuroblastoma and human medulloblastoma grown in tissue culture. Some distinctions in the characteristics were found. No rosettes were seen and the smooth, sphere-like cells were absent. Scanning electron microscopy can be a useful adjunct to light microscopy and transmission electron microscopy (TEM) in the differential diagnosis of small undifferentiated round cell tumors.

Therapy of experimental herpes simplex keratitis in rabbits with 5-lodo-5'-amino-2',5'-dideoxyuridine (39882).

Summary AIU (5-iodo-5′-amino-2′,5′-dideoxyuridine, AIdUrd) has been shown to be as effective as IdUrd in the treatment of experimental herpes simplex keratitis in rabbits. AIUs striking lack of cellular or systemic toxicity or teratogenicity and its specific inhibition of viral metabolism are discussed. The authors acknowledge the valuable technical assistance of Mr. Alfred S. Fiore and Mr. Ronald Callahan (Departments of Pharmacy and Nuclear Medicine, Massachusetts General Hospital). Mrs. Brigitte A. Prusoff performed the statistical analysis.