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Chromatographic analysis of sera or urine is important in medicine for the evaluation of patients whose clinical status is associated with the presence of specific biochemical markers. Malignant melanoma has been a model for such studies due to the elaboration of melanin precursors and pigment as the tumor metastasizes. Computer-assisted methods for categorizing chromatographic data and clinical status are imperative due to the large number of detectable compounds and possible correlations. In addition, computer-based analysis of the data can readily extract patterns that are not obvious by visual inspection. In this paper, we present a neural network analysis of melanoma chromatographic and clinical data that categorizes subjects into normals, NED patients (No Evidence of Disease), and metastatic patients. The set of marker compounds for metastatic disease represents a significant advance over the correlations derived by visual inspection.

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The sequence of events leading ultimately to the diagnosis and treatment of malignant melanoma was investigated. We conducted interviews with 275 patients and the physicians whom they had consulted regarding their suspicious lesions before their eventual referral to a melanoma center. An average of 1 year elapsed from the time that patients first noticed a new or changed lesion and the date of diagnosis. Major components of delay were attributable to both patients and physicians. An average of 6 months elapsed between patients' recognition of a new or changed lesion and their realization that the lesion was suspicious. For 21% of cases, at least 2 months elapsed between physicians' observation of lesions and a definitive diagnosis of malignant melanoma, and 13% were diagnosed a minimum of 4 months following a visit to the physician. Patients routinely cannot distinguish between melanomas and moles. Physicians do not always diagnose melanoma accurately or act promptly in response to suspicious lesions. We have yet to take adequate advantage of the unique opportunity for early detection and cure in this readily visible, rapidly increasing malignancy.

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RECONSIDER, a computer program designed to perform as a diagnostic prompting aid, was evaluated for its ability to include the correct diagnosis in an ordered computed list of candidate diseases. The study was performed using 100 consecutive first admissions to the medical service of a university hospital, where the individuals entering the data into the program were blind to all but a limited set of findings known at time of admission. Each person entering the data created one or more lists of diagnostic possibilities (versions) using the program. The program suggested the correct diagnosis within the first 40 on its list 61% (498/797) of the time; the correct diagnosis was present with the first 40 in at least one version 93% (98/105) of the time. Performance was found to be best with cases having a single diagnosis and when more terms were entered into the program.

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To develop guidelines for the follow-up of patients with primary cutaneous melanoma (clinical Stage I), we studied 295 patients who had presented with a primary melanoma and who subsequently developed evidence of metastatic disease in the course of follow-up. Cox multivariate analysis was used to assess the influence of five variables in predicting the interval of time from the diagnosis of melanoma to the first clinical or laboratory evidence of metastatic disease (disease-free interval). The variables studied were tumor thickness, patient sex, patient age, elective lymph node dissection, and primary tumor location. Tumor thickness was found to be the major predictor of disease-free interval, which shortened progressively with increasing tumor thickness. Men had a shorter mean disease-free interval than women, although this effect did not reach statistical significance at the 0.05 level. Patient age, tumor location, and elective lymph node dissection were found not to be predictors of disease-free interval. The risk of recurrence of melanoma was tabulated, by year, for four intervals of tumor thickness. The increase in risk of recurrence associated with increases in tumor thickness above 1.5 mm was shown to occur predominantly in the early years following diagnosis-particularly in the first year. On the basis of our findings, we have suggested regimens of follow-up for melanoma.

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A total of 844 cutaneous malignant melanomas were examined prospectively for the presence or absence of histologic regression within the primary tumor. Cases were then stratified into three groups according to tumor thickness and survival was compared between substrata with and without regression in each group. The distribution of other major prognostic variables within these substrata was assessed and their influence as potential confounding variables considered. No statistically significant effect of regression on survival was found in any of the three thickness strata. These results do not confirm the finding of an earlier study, which suggested that regression may be a poor prognostic sign when found in association with thin malignant melanomas. Regression was almost invariably associated with the radial growth phase of melanomas. Regression was more common in male than in female patients, and was more frequent in association with truncal than extremity or head and neck melanomas.

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A small proportion of "thin" malignant melanomas will metastasize and cause death. To assess the role of discordance between the major indicators of tumor depth (thickness and level) as a possible explanation for this phenomenon, prognosis by level has been examined in 255 cases, with tumors ranging in thickness from 0.6 to 1.1 mm. This is the range of thickness at which levels II, III, and IV overlap. The 5-year survival rate of patients with level IV tumors in this thickness range (59.35%) was poor (p less than 0.0001), relative to that of patients with level II (96.8%) and III (94.49%) lesions in the same range of tumor thickness. The distributions of other major prognostic indicators, among the groups of patients with tumors at each level, were examined to assess the possible contribution of factors other than level to the differences in survival between the three groups. These differences in survival could not be attributed to differing distributions of tumor thickness, tumor location, or patient sex. Of six prognostic variables, examined by Cox multivariate regression analysis, for tumors of thickness 0.6 to 1.1 mm, only level was found to have independent prognostic significance (p = 0.0025). The thin level IV melanoma appears to be an important exception to the rule that this melanomas are associated with an excellent prognosis. In this, as well as in other studies, after accounting for the effect on prognosis of tumor thickness, level has been shown to be a prognostic indicator with independent significance. The continued use of level as a prognostic indicator, in addition to thickness, is recommended.

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This study investigated the relationship between prognosis (estimated by histopathologic indicators) in cutaneous malignant melanoma and a comprehensive set of physical risk, demographic, psychosocial, and situational variables. These variables were derived from the medical examination, the pathology report, psychosocial self-report measures, and an hour-long videotaped interview with 59 patients from two melanoma clinics in San Francisco. Variables significantly correlated with tumor thickness were: darker skin/hair/eye coloring, longer patient delay in seeking medical attention, two correlated dimensions within an operationally defined 'Type C' constellation of characteristics, two character style measures, and less previous knowledge of melanoma and understanding of its treatment. Of these variables, delay was the most significant in a hierarchical multiple regression analysis in which tumor thickness was the dependent variable. Associations between tumor thickness and psychosocial measures of Type C were considerably stronger and more significant for subjects less than age 55, suggesting that the role of behavioral and psychosocial factors in the course of malignant melanoma is more potent for younger than for older subjects.

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This study investigated the relationship between patient delay in seeking medical attention and prognostic indicators, tumor characteristics, and demographic and behavioral factors in 106 patients with cutaneous malignant melanoma. Patients with less readily apparent lesions, particularly on the back, had longer delays in seeking treatment, as might be expected. The prognostically unfavorable nodular melanomas were detected more frequently by patients themselves than they were found during visits to physicians for unrelated problems. In terms of behavioral variables, patients with less knowledge of melanoma or its appropriate treatment had significantly longer delays. Patients who minimized the seriousness of their condition were more likely to seek treatment sooner, perhaps because this reduced fear and anxiety about the disease or its treatment. For superficial spreading melanoma, delay was significantly and positively correlated with Clark's level of invasion, and also with tumor thickness when only noncoincidentally diagnosed patients were included; whereas for the nodular type, delay was significantly and positively associated with tumor thickness, whether the patient was coincidentally diagnosed or not. The significance of these findings for early detection, and hence improved prognosis of malignant melanoma, is discussed.

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A retrospective study was undertaken of local, regional, and distant recurrences in 346 patients with primary melanomas of tumor thickness less than 1.0 mm that were excised with margins of normal skin varying between 0.1 cm and 5.0 cm or more. Prospective histopathologic examination of 284 melanomas for the presence of microsatellites was also performed and their effect upon the frequency of local recurrence was studied. Margins of excision did not influence the frequency of local, regional, or distant metastases. Four recurrences of in situ superficial spreading melanoma occurred, however, when very narrow margins of excision (0.5 cm or less) were employed. Microsatellites were uncommon with tumors less than 3.0 mm in thickness (2.8% of all tumors of less than 3.0 mm in thickness, taken together), but relatively frequent in association with thicker tumors (37%). Melanomas with microsatellites were associated with a greater frequency of local clinical metastasis than those without (14% vs. 3%). Removal of more than 1.0 cm of normal skin around a melanoma of less than 1.0 mm in thickness does not further reduce rates of recurrence of any type. The use of margins of 0.5 cm or less for melanomas with a radial growth phase does appear to result in an increased frequency of local recurrence of the primary melanoma with an epidermal in situ component. These recurrences can be prevented by the removal of 1.0 cm of normal skin around such a melanoma. Microsatellites constitute a risk factor for local recurrence, but are a relatively uncommon phenomenon at tumor thickness less than 3.0 mm.

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We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.

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