Joan Mullaney

Prognostic factors following enucleation of 111 uveal melanomas.

Follow up information was retrieved on 111 patients who underwent enucleation for uveal melanoma between 1964 and 1987, allowing a minimum postoperative period of 5 years. Univariate survival analysis was carried out using Kaplan-Meier curves and the differences between the curves were analysed with the Mantel-Cox test. Multivariate analysis used the Cox proportional hazards model. Univariate analysis isolated each of the following as significant prognosticators: largest tumour diameter (LTD) (p < 0.002), presence of epithelioid cells (p < 0.03), and glaucoma (p < 0.001). A combination of cell type, glaucoma, and LTD (p < 0.0001) had strong and independent prognostic significance in multivariate analysis. The results of this series are compared with previous studies and the value of cell type information and new quantitative parameters is discussed.

Prognostic Value of Morphometric Features and the Callender Classification in Uveal Melanomas

PURPOSE Cytomorphometric analysis of uveal melanoma has focused on nucleolar characteristics, although nuclear measurements are easier and more reproducible. In this study, we examine a restricted set of nuclear and nucleolar cytomorphometric variables in the search for the most quantifiable and reproducible prognostic parameter among these and discover a means of assessing the malignancy of tumors within the different Callender subgroups. METHODS Uveal melanomas from 94 patients with a minimum follow-up of 5 years underwent nuclear and nucleolar morphometric analysis using a digitized interactive video overlay system. Statistical analysis included univariate and multivariate survival analysis on morphometric variables and classic prognostic parameters (such as Callender cell type, size, etc.). RESULTS Univariate analysis of cytomorphometric parameters showed the standard deviation of nuclear area (NASD) to be the most significant variable (P < 0.0001: Mantel-Cox, 15.2). This was followed by the difference between nuclear and nucleolar areas (P < 0.002; Mantel-Cox, 9.5), the standard deviation of nucleolar area (SDNA) (P < 0.01; Mantel-Cox, 6.4), and the standard deviation of the shortest nuclear axis (P < 0.02; Mantel-Cox, 6.4). There was a trend for significance with the mean of the ten largest nucleoli (P < 0.07). Multivariate analysis of clinical and cytomorphometric variables showed improvement of prognostic prediction with a combination of the NASD, largest tumor dimension, and glaucoma (P < 0.0001; Mantel-Cox, 26.3). Callender cell type was strongly correlated with the NASD (P < 0.0002), the mean axis ratio of the nuclear area (P < 0.0007), and the mean of the ten largest nucleoli (P < 0.0007). CONCLUSION Cytomorphometric analysis of uveal melanoma should include nuclear area and may identify tumors of differing malignancy within the same Callender class.

Ocular vasculitis in Behçet's disease

The clinical and pathological presentation of Behçets disease are discussed. Necrotising arteriolitis and phlebitis with thromboses are demonstrated when a rare enucleation specimen became available for examination in this condition. Immunohistochemical studies show mural IgG, IgA, and C3 deposits in episcleral and some choroidal veins. The value of the clinical use of fibrinolytic agents is discussed.

Deoxyribonucleic Acid Ploidy Studies in Choroidal Melanomas

In several tumors of different organ sites, the amount of DNA in a cell (ploidy) is associated with malignancy. We performed DNA quantitation in 21 choroidal melanomas and compared flow cytometry with image analysis in 11 of these melanomas. We modified our preparation technique to overcome problems with pigment and control cell populations in the image analysis group. Fifteen tumors were diploid and two tumors were tetraploid. Four tumors were unprocessable by flow cytometry, but two of these tumors were diploid by image analysis. Image analysis also detected tetraploidy in two tumors that were diploid by flow cytometry. During image analysis, cells were classified according to the Callendar classification and histograms were plotted for each cell type. All spindle A cells were diploid and most tetraploid peaks were formed by epithelioid cells. The use of image analysis on small samples of choroidal melanomas may be of value both in confirmation of diagnosis and prognosis of these lesions, and perhaps therapeutically, for example, in the monitoring of radiation treatment.

SYNTACTIC STRUCTURE ANALYSIS IN UVEAL MELANOMAS

Syntactic structure analysis was carried out successfully on 92 paraffin embedded uveal melanomas, taken from patients with a minimum follow up of 5 years. This simple, fast, and reproducible method of describing the tumour architecture has been significantly correlated with malignancy in tumours from several sites. Paraffin sections 5 microns thick, were cut and stained with haematoxylin and eosin. Tumours were classified according to a modification of the Callender classification. A minimum spanning tree (MST), using the centre points of tumour nuclei, was constructed in five randomly chosen fields with an interactive digitising video overlay system. Ten syntactic structure features were derived from each MST; subsequently, the mean and standard deviation of the five fields analysed were calculated for further statistical analysis. Reproducibility was acceptable with a mean correlation coefficient of 0.70. In univariate survival analysis, the percentage of points with three neighbours yielded prognostic significance (p < 0.05). Minimum spanning tree variables were compared (chi 2 test) with classic tumour prognosticators and there was a significant correlation between Callender cell type and the following MST parameters: mean number of points (p < 0.003); MST length (p < 0.003); mean line length (p < 0.01); number of nuclei with one neighbour (p < 0.004); number of nuclei with two neighbours (p < 0.02), and number of nuclei with three neighbours (p < 0.005). Syntactic structure analysis is an evolving technique, but may be able to mathematically (and reproducibly) describe melanoma architecture across the spectrum of the Callender classes. This would also allow architectural grading of tumours within the specific Callender groups, providing more precise prognostic information. Further modifications of this technique are necessary to optimise prognostic potential when applied to uveal melanomas.

Retinoblastoma, a review and some new aspects

SummaryThe incidence, genetic and pathological aspects of retinoblastoma are reviewed and reference is made to the recent observation of D.N.A. precipitation in these tumours. Possible new areas of immunological, biochemical and morphological research are discussed with reference to the controversial problem of the histogenesis of retinoblastoma.

A comparative analysis over a decade of the changing indications for penetrating keratoplasty in Ireland

SummaryA retrospective analysis of the indications for, and the management of, both penetrating and lamellar keratoplasty was carried out. The two groups chosen were the 49 keratoplasties performed during the period from January 1975 to June 1977 and the 84 keratoplasties performed between January 1985 and September 1986. Significant changes, in both indications and management, were noted.

Epidermolysis bullosa acquisita with pulmonary tuberculosis: a case report

Our case is that of a 67‐year‐old man who presented with a blistering, scarring eruption at sites of trauma. Histologically the blistering was subepidermal. IgG and C3 were present at the basement membrane zone. Electronmicroscopy demonstrated bulla formation to be beneath the basal lamina and that it contained amorphous electron‐dense material. These clinical and investigational findings are consistent with a diagnosis of epidermolysis bullosa acquisita (EBA). The patient also had pulmonary tuberculosis which again highlights the association between EBA and diseases in which the immune system is compromised.