Occurrence of retinoblastoma and uveal melanoma in the same period.
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Biomedical subjects
Publications and source records attributed to J Gamel.
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The malignant potential of 100 intraocular melanomas was assessed by determining the mean of the ten largest nucleoli (MTLN) using a modification of previously described techniques. For each microslide, a five millimeter path through the central portion of the tumor was traversed on a manually controlled mechanical stage. Selected nucleoli in this area were measured at 2000x power using a digital filar micrometer. In their reproducibility and correlation with malignant potential, these measurements proved comparable to standard deviation of nucleolar area (SDNA), which has been well documented as an objective histologic predictor of mortality from intraocular melanoma. This new method for measuring MTLN requires less than 11 minutes per case, compared to an average of 28 minutes for the original method. The measurements of SDNA required approximately 40 minutes per case and a much more elaborate system than that needed for MTLN.
The malignant potential of 100 intraocular uveal melanomas was assessed by determining the mean of the ten largest nucleoli (MTLN). On a single standard microslide from each tumor, the maximum diameter of the ten largest nucleoli was measured using a manually operated micrometer. For comparison, three additional histopathologic parameters were determined for each case: Standard deviation of nucleolar area (SDNA), Callender cell type (CT), and largest tumor dimension (LTD). Of these four parameters, MTLN and SDNA were most highly correlated with death from ocular tumor. Furthermore, repeat measurement of all 100 cases revealed a level of reproducibility for MTLN similar to that for SDNA. Of greatest importance, the micrometer technique employed in this study has substantial cost and labor advantage over the computer-controlled system required to measure SDNA.
The optimum treatment of malignant choroidal melanoma remains controversial. Some authors have hypothesized that enucleation promotes metastatic disease. This hypothesis has been demonstrated in the B16F10 melanoma mouse model. The present study used this model to examine the effect of external beam irradiation as a means of reducing metastases induced by enucleation. The results show a dose-dependent reduction in the DNA synthesis of irradiated melanoma cells. Administration of 800 cGy (800 rad) of radiation produced a 90% reduction in DNA synthesis; however, higher levels of radiation failed to produce further depression of cell proliferation. Irradiation of melanoma cells before intravenous injection resulted in a significant dose-dependent reduction in the number of lung metastases. While there was no effect with 100 cGy (100 rad) of radiation, 1000 cGy (1000 rad) produced a 95% reduction in metastases. In the animal model of enucleation-induced metastasis, 2000 cGy (2000 rad) delivered to the orbit either before or after enucleation produced a significant reduction in the number of lung tumors, compared with animals that did not undergo irradiation; 1000 cGy (1000 rad) delivered before enucleation did not have such an effect. These studies provide evidence that periorbital external beam irradiation is useful in reducing metastases following enucleation of a malignant melanoma in this animal model.
By applying the Cox regression model to 226 cases of intraocular melanoma, the authors detected a statistical association between tumor-related measurements and 42 deaths that were recorded as due to causes other than melanoma within 10 years of follow-up. This association may reflect a number of events, including errors in assignment of cause of death and confounding from any one of several sources.
The length of survival time following enucleation was determined for 29 patients with primary malignant melanoma of the choroid and ciliary body who subsequently died of metastatic disease. Histologic sections of the 29 tumors were studied by standard light microscopic techniques and computerized morphometry. The largest diameter of each tumor was measured on the 37% formaldehyde-fixed, paraffin-embedded slides; a cell type was assigned to each tumor on the basis of histologic study, using the modified Callender cell-type classification system; and inverse standard deviation of the nucleolar area (ISDNA) was determined for each tumor by computerized morphometric analysis. The observed death-order of these patients was then compared with the death-order predicted by ranking cases in ascending order of age at treatment, size of tumor, cell type, and ISDNA. Using rank-order correlation coefficient tests, only the correlation between ISDNA rank-order and observed death-order was found to be statistically significant. We believe that the limitations of the modified Callender cell-type classification system in predicting length of survival time following enucleation are related to the relatively few categories (four) in which to classify tumors, whereas the ISDNA represents a continuous spectrum of unlimited categories. As such, ISDNA can be more discriminant in selecting tumors of high malignant potential.
Tumor cell kinetic parameters were determined for 36 uveal melanomas retained in fixed tissue sections using flow cytometric techniques and computerized morphometry. By flow cytometry the majority of cells comprising the 36 tumors were in the G0/G1 phase (55.7%). The DNA index was 1.40 +/- 0.57 units. Using Spearman's rank order correlation test, the correlation between DNA index and the inverse standard deviation of nucleolar area was found to be statistically significant. The potential usefulness of flow cytometry in predicting tumors of high malignant potential is discussed.
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