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Biomedical subjects

J W Gamel

Publications and source records attributed to J W Gamel.

At least 73 records · Page 4Linked to original sources

Objective assessment of the malignant potential of intraocular melanomas with standard microslides stained with hematoxylin-eosin.

A method for extracting prognostic information from the cytologic details of intraocular melanomas was developed. With computer assistance, a technician measures the nucleolar area of 200 tumor cells randomly selected from a standard paraffin-embedded microsection stained with hematoxylin-eosin, a procedure that requires approximately 40 minutes with an apparatus that costs less than +30,000. Standard deviation of nucleolar area (SDNA), computed from these measurements, provides an objective assessment of nucleolar pleomorphism. Previous studies showed that second measurements of the same microsection or of the same tumor at different levels yield SDNA values that closely approximate the original measurements. The application of this method to 540 cases from three independent laboratories yielded a correlation of SDNA with death from tumor that was high (P much less than 0.001) and consistent among cases from all three sources. Thus, SDNA provides a clinically useful cytologic measure of the malignancy of intraocular melanomas and may ultimately prove valuable in the assessment of other types of tumors.

Cell Nucleolus↗

Malignant melanoma of the eye: treatment of posterior uveal lesions by Co-60 plaque radiotherapy versus enucleation.

Survival rates and visual acuity of 100 patients treated for posterior uveal malignant melanoma by cobalt-60 plaque radiotherapy were compared with 150 patients treated by enucleation for the same disease. Life-table comparisons of the entire group showed significant differences in survival rates, with plaque radiotherapy patients appearing to fare better. However, when patients with small or medium tumors were compared, only slight differences were seen, implying that criteria used to select patients for treatment may affect interpretation. The two groups were also compared using the Cox proportional hazards model, which predicts survival based on the impact of clinical variables. In this analysis, the survival rates of the plaque radiotherapy group were no worse than those of the enucleation group. The advantage of conservative therapy lies in the potential to preserve useful vision over a considerable time. Because patients were specifically selected for treatment modality and because the study size used to calibrate the Cox model was small, the results of this study must be interpreted with caution.

Cobalt Radioisotopes↗

Reproducibility of nucleolar measurements in human intraocular melanoma cells on standard histologic microslides.

The standard deviation of nucleolar area (SDNA), as determined by semiautomated measurement of routinely prepared histologic sections, has been shown to be an effective predictor of mortality for human intraocular melanoma. One hundred cases of this tumor underwent two independent determinations of SDNA by each of two technicians using the same device. One technician performed the two measurements within two months, the other within three weeks. Analysis of these 400 values revealed the following: the more experienced of the two technicians achieved an acceptable level of reproducibility in determining SDNA; the less-experienced technician achieved a lower level of reproducibility; a systematic bias was found upon comparing SDNA values of the two technicians; and this bias can be partially corrected by applying a linear transform. These findings support the value of SDNA as a practical clinical measure of malignant potential for intraocular melanoma but also suggest that experience can enhance the reproducibility of a technician's measurements.

Cell Nucleolus↗

Comparison of direct and microslide pathology measurements of uveal melanomas.

Many investigators have shown that large cilio-choroidal melanomas are more likely to be associated with an unfavorable outcome than small tumors by using data retrieved and measured from pathology files. In the past, the measurement of largest tumor dimension (LTD) may not have been recorded at the time of the gross examination, because the significance of this observation was not appreciated. If this information is not available, authors can eliminate cases from their studies, take all their measurements directly from glass microslides, or combine clinical estimates of tumor size for some cases with gross measurements for others. To date, there has been no formal study to compare the measurement of tumor dimensions from glass microslides with measurements made at the time of gross examination by the pathologist. This study of 112 cilio-choroidal melanomas reveals that measurements of the LTD made from the glass microslide correlate with direct measurements taken from the cut surface of the globe at the time of sectioning. Additionally, measurements of the LTD from the glass microslide are at least as effective in predicting patient outcome as direct measurements. These findings suggest that measurements of the LTD from the glass microslide provide as much prognostic information as direct measurements if it is known that the eye was cut to obtain representative sections of the tumor.

Humans↗

Mucoepidermoid carcinoma of the conjunctiva.

A 73-year-old man had a limbal nodule that, on histopathologic examination, proved to be mucoepidermoid carcinoma of the conjunctiva. Despite radiation therapy and extensive corneoscleral lamellar resection, widespread invasion of the lids and orbit ultimately led to exenteration. Although mucoepidermoid carcinoma of the conjunctiva resembles squamous cell carcinoma clinically and histopathologically, it pursues a more rapid and destructive clinical course. Intraepithelial invasion often leads to tumor involvement of conjunctiva and skin that seem normal on clinical examination. Special stains and a high level of suspicion are required for diagnosis of mucoepidermoid carcinoma of the conjunctiva, and proper initial management demands more aggressive surgical resection than is usually indicated for squamous cell carcinoma.

Aged↗

Modern developments in histopathologic assessment of uveal melanomas.

Uveal melanoma is the most common primary intraocular neoplasm in adults. Those histopathologic features that distinguish uveal nevi from small melanomas, and those that distinguish highly malignant from less malignant lesions, have been the subject of controversy over the past decades. This controversy arises primarily from the subjective methods by which such histopathologic distinctions are made, and the resulting ambiguities may have misguided the clinician in his management of certain uveal lesions. With methods made possible by modern technology, pathologists can now assess the malignant potential of uveal melanomas by objective measurement of cytologic structures within the tumor.

Cell Nucleolus↗

Computerized histopathologic assessment of malignant potential. III. Refinements of measurement and data analysis.

The nucleolar area of uveal melanomas, measured from standard hematoxylin-and-eosin-stained microslides , has been shown in previous work to correlate well with survival following enucleation of the tumor-bearing eye. Despite this correlation, the accuracy of the original system for measuring nucleolar area was affected by several sources of error: (1) the algorithm by which area was computed underestimated true area, (2) geometric and optical factors caused overestimation of nucleolar area unless measured in the center of the microscopic field of view and (3) the area of small nucleoli, as the result of several possible mechanisms, contains less useful information than the area of large nucleoli. This paper presents methods introduced to reduce error from these sources and demonstrates that the predictive value of nucleolar measurements is relatively insensitive to high levels of random variation.

Cell Nucleolus↗

Computerized histopathologic assessment of malignant potential. II. A practical method for predicting survival following enucleation for uveal melanoma.

To assess the malignant potential of uveal melanomas from standard histopathologic material, a single microslide from each of 100 cases underwent computer-assisted measurement of nucleolar cross-sectional area. The standard deviation of 200 measurements per slide correlated well with survival of patients following enucleation for their ocular tumor. Furthermore, a statistical model calculated from these measurements effectively predicted survival for 50 additional cases. Additional investigation demonstrated the following features of this method: (1) a high level of reproducibility; (2) acceptable constancy among different levels of the same tumor; (3) a practical expenditure of resources (assessment of each case required less than 40 minutes of a technician's time and an apparatus costing approximately $20,00). This method--computerized histopathologic assessment of malignant potential (CHAMP)--thus provides the pathologist with a practical method for extracting prognostic information from standard H & E-stained microslides of uveal melanomas. Previous studies by other researchers suggests that a similar method might be effective in assessing the malignant potential of more common neoplasms.

Autopsy↗

Modifications of Callender's classification of uveal melanoma at the Armed Forces Institute of Pathology.

One hundred well-documented cases of uveal melanoma accessioned at the Armed Forces Institute of Pathology before 1970 were reviewed and reclassified to identify changes made in the Callender classification. We compared the new classification with the original classification to determine the effect of the changes on the prediction of outcome for the patient after enucleation. Staff pathologists had originally classified 52 of the 100 cases as spindle-cell type melanoma. Only 31 of the 100 cases were reclassified as spindle-cell types (two spindle-cell nevi and 29 spindle-cell melanomas). Tumors classified as mixed-cell type were further subdivided into groups based on the percentage and size of the epithelioid cells. Tumors formerly classified as spindle-cell type that contained small or rare epithelioid cells were reclassified as mixed-cell type. This improved the prediction of outcome for the patient. We found that nucleolar size and pleomorphism are important variables that should be considered in the classification of uveal melanomas.

Humans↗

Computerized histologic assessment of malignant potential: a method for determining the prognosis of uveal melanomas.

The authors evaluated 50 cases of primary melanoma of the choroid and ciliary body. In each case, 100 cells were randomly selected from a single histologic slide, and on each cell computer-assisted measurements were made of 18 nuclear and nucleolar features. Means and standard deviations were calculated for each of these features in each tumor. Thirteen calculated variables (six means and seven standard deviations) were found to correlate significantly with patient mortality following enucleation. Standard deviations of statistically significant nuclear and nucleolar features demonstrated significantly greater correlation with mortality than the means of these features, thus confirming the great value of nuclear pleomorphism for predicting the malignant potential of uveal melanomas. Furthermore, when the standard deviation of the nucleolar circumference, a feature highly correlated with survival (P less than 0.00001), was combined with the measurement of the largest dimension of the tumor, linear discriminant analysis correctly predicted the clinical course of 88 per cent of cases.

Cell Nucleolus↗

Adenoid cystic carcinoma of the lacrimal gland: the clinical significance of a basaloid histologic pattern.

The authors reviewed 74 adenoid cystic carcinomas of the lacrimal gland, 54 of which had sufficient follow-up data for analysis of survival. Patients with a basaloid pattern in their tumor had a five-year survival rate of 21 per cent and a median survival of three years, whereas patients whose tumor contained no trace of a basaloid component had a five-year survival rate of 71 per cent and a median survival rate of eight years. Nonparametric statistical analysis revealed that this difference in survival was significant at the 0.0005 level. The authors propose that, in the future, pathologists label all adenoid cystic carcinomas as either "basaloid" or "nonbasaloid" and code each case accordingly.

Adult↗

Acute ischemic optic neuropathy in severe preeclampsia.

A 32-year-old woman developed bilateral blindness along with severe preeclampsia of pregnancy. Ophthalmoscopic examination disclosed chalky-white optic disks with only minimal changes in the retinal vasculature. After caesarean section, the preeclampsia improved, and complete return of visual acuity occurred during a three-day period. Blindness has rarely been reported as a complication of preeclampsia. In almost all cases it has been associated with severe compromise of the retinal vasculature. conversely, the ophthalmoscopic findings in our case strongly support acute ischemic optic neuropathy as the cause of blindness.

Adult↗

Uveal melanomas: correlation of cytologic features with prognosis.

Forty uveal melanomas were examined, half of which had proved fatal. Twenty cells were selected from each tumor, and six cytologic features were measured on each of these cells. It was found that the cells selected from fatal tumors had longer nuclei, more nucleoli, and greater nuclear pleomorphism than those selected from nonfatal tumors. Also, cells from melanomas classified as mixed cell type by the Callender classification had wider nuclei and longer nucleoli than those from tumors classified as spindle B cell type. Since the former cell type is associated with a worse prognosis, these features would probably assist in assigning prognosis to a large group of randomly selected malanomas. Thus, five nuclear characteristics (long nuclei, wide nuclei, long nucleoli, multiple nucleoli, and nuclear pleomorphism) should prove useful for predicting death from the dissemination of uveal melanoma.

Cell Nucleolus↗

Quantitative analysis of the Callender classification of uveal melanoma cells.

Six experienced ophthalmic pathologists independently classified 90 uveal melanoma cells according to the Callender classification. They frequently disagreed among themselves, but at least four of the six agreed on the classification of 77 cells. In an effort to delineate those cytologic features that are most useful in the application of Callender classification, 12 factors were evaluated for each of these cells. Multivariate analysis (MVA) proved that six factors (chromatin clumping, minimum nuclear diameter, nucleolar diameter, chromatin margination, maximum nuclear diameter, and abundant cytoplasm) were useful for determining the cell type selected by the majority of pathologists, although some cells could not be sharply classified. It was concluded that uveal melanoma cells occupy a continuous cytologic spectrum, from benign-appearing spindle A cells to very malignant-appearing epithelioid cells.

Cell Count↗

Correlation of in vitro 32P counts with histologic features of malignant melanoma of choroid and ciliary body.

The radioactive phosphorus uptake of 30 samples fron nine uveal melanomas was determined by liquid scintillation counting. These in vitro measurements correlated positively with clinical (in vivo) 32P values and with the number of mitotic figures and percentage of epithelioid cells (PEC) within the specimens. Three possible explanations were found for the failure of previous workers to demonstrate a correlation between cell type and clinical 32P. (1) Cell type, using Callender's classification, provides only a crude estimate of the PEC within a tumor; in particular, tumors of mixed cell type can vary widely in epithelioid cell content. (2) The rate of 32P absorption is not su-ficiently sensitive to distinguish spindle cell tumors from mixed cell tumors with a low PEC. (3) Clinical 32P measurements may be affected by extraneous factors that cause large deviations from the expected values.

Choroid Neoplasms↗