Effect of anatomical location on prognosis in patients with clinical stage I melanoma.

A study of the influence of the anatomical location of malignant melanoma on the prognosis of 971 patients with stage I disease disclosed specific high-, intermediate-, and low-risk sites. High-risk sites included scalp, mandibular area, midline of trunk (anterior and posterior), upper medial thighs, hands, feet (except the arches), popliteal fossae, and genitalia. The life-table-adjusted five-year disease-free survival was 54% in the high-risk locations, 79% in intermediate-risk locations, and 93% in low-risk sites. A Cox proportional hazards analysis demonstrated that the grouping of lesions by their anatomical risk location had prognostic value that was significant in a model of eight other known predictive variables (thickness, sex, age, type, level, mitotic index, ulceration, and presence of preexistent nevus). The results indicate that anatomical location of the primary melanoma is significantly associated with five-year disease-free survival.

Regression in malignant melanoma.

A multiple stepwise logistic regression analysis shows that histologic regression is more likely to be found in a malignant melanoma that is level III or less, more than 10 mm in diameter, associated with solar elastosis, located on an anatomic area other than the head or neck, and when there are areas of whiteness clinically. Although patients with malignant melanomas displaying signs of regression histologically have a slightly better 5-year disease-free survival, this may be attributed to a difference in tumor thickness.

"Small" melanomas: relation of prognostic variables to diameter of primary superficial spreading melanomas.

In a consecutive series of 648 superficial spreading melanomas a significantly better 5-year disease-free survival rate was observed for patients whose primary tumors were 14 mm or less in diameter when compared with those 15 mm or larger in diameter. Other distinguishing features of the group of "smaller" superficial spreading melanomas were that they occurred in younger patients; were of shorter durations; were more common in women; occurred disproportionately on the lower limbs; were less elevated; tended to be round in shape; were thinner (Breslow); penetrated less deeply (Clark levels); showed less histologic regression; and developed fewer metastases. Based on these findings it is recommended that educational programs be undertaken for the medical profession and for the public to promote early diagnosis and prompt treatment of superficial spreading melanomas when they are small in diameter and more often curable. A color atlas of "small" melanomas is presented.

Prognostic factors for melanoma patients with lesions 0.76 - 1.69 mm in thickness. An appraisal of "thin" level IV lesions.

Fourteen variables were tested for their prognostic usefulness in 203 patients with clinical Stage I melanoma and primary tumor 0.76-169 mm thick. Only two variables, primary tumor location and level of invasion, were useful in predicting death from melanoma for these patients. Of the 12 deaths from melanoma, 11 occurred in patients with primary tumors located on the upper back, posterior arm, posterior neck, and posterior scalp (=BANS). There has been only one death from melanoma in 136 patients with melanoma located at other sites (11/67 vs 1/136, p less than 0.0001 Fisher's Exact Test). Of the 67 BANS patients, 51 had level II or level III lesions and five (10%0 died of melanoma. This compared with six deaths from melanoma in 16 patients (37.5%) with level IV BANS lesions (5/51 vs 6/16, p = 0.01 Fisher's Exact Test). The relatively high incidence of both melanoma deaths and regional node metastases for the BANS group merits consideration for testing the efficacy of elective regional node dissection for these patients.

A multivariate analysis of prognostic factors for melanoma patients with lesions greater than or equal to 3.65 mm in thickness. The importance of revealing alternative Cox models.

Fourteen prognostic factors were examined in 79 patients with clinical Stage I melanoma greater than or equal to 3.65 mm in thickness. All nine patients with melanoma of the hands or feet died of melanoma. A Cox proportional hazards (multivariate) analysis of the remaining 70 patients showed that a combination of the following four variables best predicted bony or visceral metastases: 1) a nearly absent or minimal lymphocyte response at the base of the tumor, 2) histologic type other than superficial spreading melanoma, 3) location on the trunk, and 4) positive nodes or no initial node dissection. Ulceration and/or ulceration width were not useful in predicting outcome either singly or in combination with other variables. Patients with negative lymph nodes and primary tumors of the trunk, hands, and feet did not do better than patients with positive nodes at those sites. Conversely, non of 16 patients with negative lymph nodes and extremity melanomas (excluding the hands and feet) or head and neck melanomas developed visceral or bony metastases (i.e., five-year disease-free survival rate 100%).

Prognostic factors for patients with clinical stage I melanoma of intermediate thickness (1.51 - 3.39 mm). A conceptual model for tumor growth and metastasis.

Fourteen variables were tested for their ability to predict visceral or bony metastases in 177 patients with clinical Stage I melanoma of intermediate thickness (1.51 - 3.39 mm). A Cox multivariate analysis yielded a combination of four variables that best predicted bony or visceral metastases for these patients: 1) mitoses greater than 6/min 2 (p = 0.0007), 2) location other than the forearm of leg) p = 0.009, 3) ulceration width greater than 3 mm (p = 0.04), 4) microscopic satellites (p = 0.05). The overall prognostic model chi square was 32.40 with 4 degrees of freedom (p less than 10 (-5). Combinations of the above variables were used to separate these patients into at least two risk groups. The high risk patients had at least a 35% or greater chance of developing visceral metastases within five years, while the low risk group had greater than an 85% chance of being disease free at five years. Criteria for the high risk group were as follows: 1) mitoses greater than 6/mm 2 in at least one area of the tumor, irrespective of primary tumor location, or 2) a melanoma located at some site other than the forearm or leg and histologic evidence in the primary tumor of either ulceration greater than 3 mm wide or microscopic satellites. The low risk group was defined as follows: 1) mitoses less than or equal to 6/mm 2 and a location on the leg or forearm, or 2) mitoses less than or equal to 6/mm 2 and the absence in histologic sections of the primary tumor of both microscopic satellites and ulceration greater then 3 mm wide. The number of patients in this series who did not undergo elective regional node dissection (N = 47) was probably too small to detect any benefit from this procedure. Based on survival rates from this and other studies, it is estimated that approximately 1500 patients with clinical Stage I melanoma of intermediate thickness in each arm of a randomized clinical trial would be needed to detect an increase in survival rates from elective regional node dissection.

Factors related to thickness of melanoma. Multifactorial analysis off variables correlated with thickness of superficial spreading malignant melanoma in man.

Computer analyses to identify correlations between thickness of primary superficial spreading malignant melanoma and eighteen variables previously reported to be related to prognosis were performed on a series of malignant melanomas. The variables that showed statistically significant (less than or equal to 0.05) direct relationships to thickness were level (Clark), elevation of lesion, age of patient, least and greatest diameters of lesion, history of bleeding, ulceration, clinical and histologic stage, anatomic location, pedunculation, and satellitosis. The variables that did not correlate with thickness were clinical diagnosis of regional lymphadenopathy, in-transit metastasis, duration of lesion, sex, history of a previous malignant melanoma, and history of a pre-existing lesion at the site of the development of melanoma. Multiple regression analysis of the factors that showed statistically significant correlation with thickness of the primary lesion revealed a subset of six dominant variables that were most predictive of thickness, namely, level, elevation, largest diameter of lesion, ulceration, histologic stage, and age of the patient.

Correlation of thicknesses of superficial spreading malignant melanomas and ages of patients.

In a prospective study of 455 consecutive patients with superficial spreading malignant melanomas entered into the data base of the Melanoma Cooperative Group of New York University Medical Center, it was found by linear-regression analysis that there is a statistically significant (p = 0.005) positive correlation between the ages of the patients and the thickness of their lesions. Although the reasons for the correlation between ages and thicknesses ae not certain, several possible explanations were considered, namely: (1) the greater prevalence of superficial spreading malignant melanomas in the aged on the lower limbs where thicker lesions were present in our patients, (2) the altered skin of the elderly, which may favor deeper penetration by these neoplasms, (3) impaired immunologic responses in the aged, (4) the delay in diagnosis of malignant melanomas in the elderly because of obsuration of them by numerous benign pigmented lesions that frequently develop with aging, and (5) lesser concern of the elderly with their physical appearances in particular and medical problems in general.

The significance of augmented radiocolloid uptake by the spleen in patients with malignant melanoma.

Increase in splenic uptake of Tc-99m sulfur colloid was noted in 47 of 147 (32%) patients with cutaneous malignant melanoma early in the coure of disease. Patients with disseminated disease and/or clinical or laboratory evidence of hapatic dysfunction were excluded from study. Recurrence rate of 2 yr was higher for those patients with splenic scans demonstrating augmented uptake compared with patients having normal scans, 36% against 16% (p less than 0.02). These differences resulted from a much more favorable prognosis in women with normal scans contrasted with women with increased uptake, 6% against 26% (p less than 0.05). Women with increased splenic uptake, and all men regardless of scan status, seemed to have a higher rate of recurrence than women with normal spleen scans. Scan status may be an adjunctive prognostic marker in women.

Ultrastructural study of superficial spreading melanoma and benign simulants.

Ultrastructural examination of the intraepidermal component of superficial spreading melanomas (SSM) and benign melanocytic lesions was undertaken to determine the diagnostic value of electron microscopy in clinically "borderline" melanoma problems. Seventeen SSMs and ten benign melanocytic nevi and lentigenes which clinically resembled melanoma were studied. Melanocytes of the intraepidermal component of the SSMs showed a greater tendency for abnormal melanosome formation than did melanocytes of the benign simulants. However, the abnormalities were variable and were not limited to the SSMs. Our observations suggest that qualitative ultrastructural evaluation cannot be reliably used differentiating SSMs from benign melanocytic lesions.

Distribution of technetium-99m sulfur colloid in mice bearing melanomas or mammary carcinomas.

Three groups of 24 C57BL/6J black mice were studied. One group was implanted with B16 malignant melanoma, another was implanted with mammary adenocarcinoma, and the third was not given tumor implants. After 14 to 17 days, the mice were given injections i.v. of technetium-99m sulfur colloid and killed 30 min later. Organs were weighed, and radioactivity was counted. The ratios of specific radioactivities of the spleens to those of the liver were higher only in the group of mice bearing malignant melanomas. This finding suggests that the "hot spleen" phenomenon observed in humans with malignant melanomas may be due to increased specific activity rather than increased splenic volume.