Analysis of the histological findings on an objective basis, using a cluster analysis programme, provided an encouraging degree of separation into the diagnostic groups. When a number of known carcinoma cases were included in the cluster analysis as " markers ", a small number of leukoplakia and keratosis cases were placed by the computer into the same cluster as these " markers ". Of the original 187 cases originally diagnosed as leukoplakia or keratosis, 4.8% are known to have developed a carcinoma, but of the 11 cases the computer placed in the same cluster as the " marker " cases of carcinoma, 36% have subsequently developed carcinoma. Thus, in the cluster analyses, the computer is tending to " recognize " those cases that later developed carcinoma, and to separate them from the bulk of the cases in which malignant change has not occurred.
SUMMARY.-In a retrospective survey of 235 cases in which the diagnosis on biopsy was lichen planus, keratosis or leukoplakia, the histological features were re-assessed as objectively as possible and without reference to the original diagnosis.The tissue changes were recorded under39 headings, and many were assessed on a roughly quantitative basis. In addition, two clinical features were included; whether the biopsy was from the buccal mucosa (as opposed to some other intraoral site) and whether the lesions involved multiple intraoral sites. For each possible pair of diagnostic categories (keratosis and leukoplakia, lichen planus and keratosis, lichen planus and leukoplakia) the recorded findings were subjected to discriminant analysis in order to provide a quantitative assessment of the value of each individual feature for discriminating between the two diagnostic groups. The computer programme also provided for the application of these calculated values to yield a " score " for each case, and for an assessment of the significance of the separation of the diagnostic groups thus achieved. In general, the values calculated by the computer for the discriminatory value of each tissue change accorded with our subjective impressions, but a number of features that were given a relatively high value had not previously been recognized as important in differential diagnosis.A discriminant analysis was also performed on those cases of leukoplakia known to have later developed a carcinoma, in comparison with the leukoplakia cases that did not develop carcinoma. High values were accorded mainly to the well-known features of epithelial atypia, but a similar high value was indicated for the presence of Russell bodies. We had not previously realized that the presence of Russell bodies was of prognostic significance in this context. When the total scores for the groups of cases were analysed, it was found that the separation of each pair of diagnostic groups was significant at the 1% level. The separation of leukoplakia cases that subsequently developed carcinoma, from those that did not develop carcinoma, was significant at the 5% level. In this latter analysis, a better separation might be achieved with larger numbers of cases, but there will always be the complicating factor that an unknown number of leukoplakia cases would develop carcinoma if the patient had received no treatment.IN previous papers (Kramer et al., , 1970Kramer, 1969) we have shown that cluster analysis, applied to the process of histopathological diagnosis, enabled us to examine the validity of certain aspects of our diagnostic criteria. Dis-
(22,23). A few studies of the qualitative nature of the urinary steroids in patients with this type of tumor seem to confirm such a conclusion (13,24). Accordingly, when the opportunity arose to study a patient bearing a testicular -tumor thought to be of this type, it seemed worthwhile to attempt to establish the exact nature of the steroids produced. The study presented here was therefore undertaken.This paper presents a description of the patient, histological observations on the tumor, the results of urinary steroid assays and the results of experiments in which slices of the tumor were incubated with C14-labeled steroid precursors.
EXPERIMENTAL AND RESULTS
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