Faculty Bibliography

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

In an attempt to determine whether exposure to fluorescent lights may cause an increased risk for developing melanoma, 114 patients with melanoma were compared to 228 age-matched controls. Fluorescent-light exposure, along with 10 other risk factors, was analyzed for its possible relationship to malignant melanoma. No association was found between fluorescent-light exposure and increased risk for acquiring malignant melanoma

In a clinicohistopathologic study of 557 patients with primary cutaneous malignant melanoma, there were fewer metastases and/or deaths from melanoma when histologic evidence of a coexisting acquired melanocytic nevus was found. A total of 130 patients with melanocytic nevus and 427 cases of melanoma without histologic evidence of a nevus (denovo) were studied. Clinical follow-up evaluation for evidence of metastases and/or death was obtained. Only ten of the patients (7.7%) with nevus-associated melanoma had metastases and/or death v 78 (18.3%) with de novo melanoma. When stratified by lesion thickness, the logrank test for survival revealed a statistically significant difference between the two groups. An overall favorable outcome seen in patients with malignant melanomas associated with acquired melanocytic nevi was found, therefore, to be independent of lesion thickness as well as six other variables reported to be related to the biologic behavior of malignant melanoma. Thus, the presence of nevus cells in a specimen of malignant melanoma portends a better prognosis and may have important implications in the biology of this neoplasm

Although thin malignant melanomas, i.e., those less than 0.76 mm in thickness, of the skin generally do not metastasize, it has been recently reported that when histologic regression is present, such lesions may then have a greater propensity for dissemination. However, this was not apparent in this study in which only one melanoma metastasized in a consecutive series of 41 thin lesions which were step-sectioned and had evidence of regression histologically. Possible explanations for this discrepancy are the failure of other authors to include only step-sectioned specimens of the primary melanomas in their material and/or geographic differences in the biologic behavior of this malignant neoplasm

A total of 672 consecutive patients with clinical stage I and stage II primary cutaneous malignant melanoma were treated by excision of 3.0 to 5.0 cm of surrounding skin down to and including the underlying fascia when the lesion exceeded 0.5 mm thickness (Breslow measurement). More conservative margins were taken in locations where such excisions would result in significant cosmetic or functional morbidity and for thinner lesions (less than 0.5 mm). Seven of 658 patients with clinical stage I disease (1.1%) and three of 14 patients with clinical stage II disease (21.4%) developed histologically verified local metastases within 5 cm of the primary excision scar or skin graft. Fifteen patients with stage I disease developed in-transit metastases (2.3%) at a site more than 5.0 cm proximal to the surgical scar or skin graft but not beyond the regional nodal group. Two patients with stage II disease who had developed local metastases also developed in-transit metastases (14.3%). No patient with a lesion less than 1.0 mm thick has had a local recurrence. Nine of the ten patients (90%) who developed local metastases and 12 of the 17 patients (70.6%) who developed in-transit metastases have also developed systemic metastases to date. Local and in-transit metastases following such definitive excision is a significant indicator of disseminated systemic metastatic melanoma

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

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%)

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

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