In cortical adrenal gland tumours there are discrepancies between morphological criteria for malignancy and biological behaviour. This makes it difficult to select the appropriate treatment. We have studied morphometric and DNA densitometric features of 24 adrenal proliferative lesions (hyperplasia, adenoma, and carcinoma) by means of slide cytometry. All variables have been correlated with pathological diagnosis. The samples were selected from paraffin-embedded tissue, and representative lesions were Feulgen stained. Densitometric study showed aneuploid cell lines in every carcinoma, 5 of 8 adenomas, and 5 of 10 hyperplastic lesions. Both DNA nuclear content (mean ploidy of 2.11 c, 2.41 c, and 3.05 c) mean nuclear area (average of 31.26 microns 2, 35.92 microns 2, and 42.39 microns 2) showed progressive increase from hyperplasia to adenoma, and carcinoma. Mean shape factors were lowest in adenomas (1.69) and highest in carcinomas (1.82). Those karyometric variables which showed statistically significant differences (p < 0.05) among diagnostic groups were included in a stepwise three-way discriminant analysis. Only three parameters, shape factor (p = 0.0008), mean ploidy (p = 0.0012), and adrenal weight (p = 0.0055) persisted as independent predictive factors. Using the three variables selected by discriminant analysis on our cases, 100% of the adenomas were correctly classified, 83% of the carcinomas, and 80% of the hyperplasias. Tumour weight and nuclear shape factor differentiated adrenal cortex adenoma from carcinoma, while mean ploidy distinguished adrenal cortical hyperplasia from carcinoma. Nuclear pleomorphism (shape factor) and DNA-ploidy are the most important nuclear features in predicting the biological course of proliferative adrenal cortex lesions, although by themselves they are not bona-fide discriminators.
Background. The biologic behavior of most paragangliomas cannot be predicted from their histologic appearance. Recently, cytometric studies have found an association between an aggressive clinical behavior and the presence of a hyperdiploid or tetraploid range in the DNA nuclear content. Methods. The authors have studied morphometric (nuclear area and nuclear form factor) and DNA densitometric (integral optical density and DNA ploidy) features of 23 cases of paraganglioma by means of slide cytophotometry with the micro TICAS system (University of Chicago, Chicago, IL). The samples were selected from paraffin‐embedded tissue, and representative sections were stained with the Feulgen technique. The differences between groups (cervical versus extracervical paragangliomes) were investigated with the Mann‐Whitney test and Fisher discriminant linear function. Results. The densitometric study showed aneuploid cell lines in 15 of 16 noncervical paragangliomas (with a DNA index within the tetraploid range), whereas 3 of 7 cervical paragangliomas were aneuploid and only 1 case did not have not a diploid cell line (with a DNA index within the peridiploid range). Mean ploidy (4.33 arbitrary units [AU] and 2.72 AU, respectively), nuclear area (58.74 μm2 and 32.08 μm2, respectively), the minor and major DNA indices (1.09–1.24 and 1.83–1.96, respectively), and DNA content variability (2c deviation indices [2cDI] of 8.62 and 1.88 AU, respectively) were higher in noncervical paragangliomas. With Fisher linear discriminant function, mean nuclear area (P = 0.0008), 2cDI (P = 0.0030), and the minor DNA index of each cell proliferation were correlated with location. None of the variables established statistically significant differences in comparisons of malignant and benign paragangliomas. Conclusions. Karyometric and DNA densitometric parameters have limited value in determining the prognosis of paragangliomas, although they are correlated with tumoral location, which is still an indicator in establishing the prognosis of these neoplasms.
The prognostic significance of objectively measured karyometric variables (ploidy pattern, nuclear roundness, area, elongation, chromatin texture, and nearest nucleus distance) was investigated in relation to clinical (stage and type of disease) and morphologic (histologic patterns) variables in 27 patients with the diagnosis of medullary thyroid carcinoma (MTC). The DNA and karyometric measurements of Feulgen-stained nuclei were made with a video cytometry system. The five-year and ten-year adjusted survival rates were 74.4 +/- 10.1% and 59.5 +/- 15.6%, respectively. Cox's survival analysis for mortality showed that only stage, age, sex, and 5N exceeding rate had predictive value (overall P = 0.0012) in decreasing order. Patients with the best prognosis were young females with clinical Stage I disease and low 5N exceeding rate tumors. When karyometric and histometric variables were considered by themselves survival correlates with the standard deviation (SD) of the nearest nuclear distance and nuclear elongation; that is, patients with crowded, high cellularity tumors and elongated cells had the worst prognosis. In univariate analyses only clinical stage correlated with adjusted survival rate. Multivariate survival analysis for morbidity showed that patients in Stages greater than or equal to II and high SD of ploidy values were free of symptoms for short intervals. When morphometric data were considered alone, patients with high variance in the chromatin texture and highly variable nuclear areas had shorter asymptomatic intervals.
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