This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

No abstract

Apart from the rare malignant melanomas occurring in blue nevi, primary cutaneous malignant melanoma arises in 1 of 3 ways, regardless of the presence or absence of a pre‐existing nevus. These three types have been designated: 1. Malignant melanoma, invasive, with adjacent intra‐epidermal component of Hutchinson's melanotic freckle type; 2. Malignant melanoma, invasive, with adjacent intra‐epidermal component of superficial spreading type; and 3. Malignant melanoma, invasive, without adjacent intra‐epidermal component. Occasionally, both clinically and histologically, there may be difficulty in deciding whether a malignant melanoma belongs to category 1 or 2, but, in the majority of cases, these 2 types can be quite readily distinguished. In addition to recording the histogenetic mode of development of a malignant melanoma, a histologic system of reporting is recommended which includes mitotic activity, levels of invasion, and vascular involvement. There are other parameters such as the cell type, pigmentation, lymphocytic infiltrates, evidence of spontaneous regression, associated nevi, and solar changes in the dermis, all of which are of unknown significance. The recording of these features, which are clearly of interest for research purposes, is left to individual discretion. It is emphasized that all the usual macroscopic descriptions and measurements should continue to be recorded.

Previous studies have shown that smoking i s associated with a high incidence of certain malignancies and a high incidence of metastatic spread of melanoma. The purpose of the present study was t o examine whether this high incidence of malignancy could be associated with certain aspects of immune function believed to be important in restricting tumour growth. Age-and sex-matched smoking and non-smoking normal subjects and male, smoking and non-smoking melanoma patients, were studied for the natural killing (NK) activity of their blood leukocytes against cultured melanoma and Chang cells. The levels of the various immunoglobulin classes in their sera and the E rosette levels of the normal subjects were also assessed. The results indicate that the N K activity of blood leukocytes from both normal subjects and melanoma patients who smoked was significantly lower against cultured melanoma cells than that of non-smokers. Smokers were also shown t o have lower IgG and IgA immunoglobulin levels i n their sera compared t o nonsmokers but no differences i n the percentage of E-rosetting (T) cells was detected. Recent studies provide some basis for the belief that the low N K activity and immunoglobulin levels i n smokers may be related. These results further suggest that a closer examination of the effects of this environmental hazard on the immune system and i t s relation t o malignancy i s needed.It is well known that smoking is associated with a raised incidence of a variety of malignant diseases such as carcinoma of the lung, oesophagus and bladder (Doll and Peto, 1976). It has also been shown that there is a higher incidence of metastatic disease, after 5 years, in male patients with malignant melanomas who smoke, than in those who are nonsmokers (Shaw et al., 1979). The underlying cause for this association between smoking and the increased incidence of malignancy is unknown and it is probable that multiple factors may be involved, including direct carcinogenic effects of products formed from tobacco during smoking.One of the possible associations, however, that has received little attention, is that related to the effects of smoking on the immune system. There is much experimental evidence from studies on both man and animals to show that smoking causes changes in the immune system (Holt and Keast, 1977) and surveillance by the immune system is considered important in control of tumour emergence and growth.In particular, recent studies have suggested that natural killer (NK) activity may play an important role in tumour surveillance (Kiessling and Haller, 1978; Baldwin, 1977; Hersey, 1979). Research originating in this laboratory has provided additional support for a surveillance role for NK cells in that melanoma patients with low post-operative NK activity against melanoma target cells had a significantly higher incidence of recurrence of melanoma than did patients with higher post-operative NK activity (Hersey et al., 1978).The present study was undertaken to determine whether an association between smoking a...

TMR was confirmed to be an important independent predictor of survival of patients with primary cutaneous melanoma. However, its predictive value was less than it was when assessed according to the 1982 revisions of the 1972 TMR recommendations.

Risk factors associated with local recurrences were analyzed from a series of 3445 clinical Stage I melanoma patients. In single‐factor analysis, tumor thickness, ulceration, and increasing age were highly significantly predictive of recurrence (p < 0.00001). After 5 years of follow‐up, local recurrence rates were 0.2% for tumors less than 0.76 mm thick, 2.1% for tumors 0.76 to 1.49 mm thick, 6.4% for tumors 1.5 to 3.99 mm thick, and 13.2% for tumors 4.0 mm or greater in thickness. Ulcerated melanomas recurred more often than nonulcerated lesions (11.5% versus 1.9%). When analyzed as a continuous variable, increasing age increased the risk of local failure. In multifactorial analysis, all of these three factors remained independently predictive of local recurrence. Recurrences were more common with nodular melanomas (5.6%) compared to superficial spreading (2.5%) or lentigo maligna melanoma (2.5%), but this difference did not reach statistical significance (P = 0.115). Lower extremity (4.7%) and head and neck lesions (4.4%) recurred more frequently than upper extremity (1.6%) or trunk (1.2%) melanomas (P = 0.0217). The highest recurrence rates were observed in patients with melanomas located on the foot (11.6%) and hand (11.1%). The safety of conservative margins for the excision of low‐risk melanomas was demonstrated in a review of 1151 consecutive patients with melanomas less than 1 mm thick where only one local recurrence was observed. Sixty‐two percent of these patients had resection margins of 2 cm or less. In 95 patients local recurrence developed as the first site of relapse and were treated with surgical excision. The median survival for this group was 3 years, whereas 20% of this group survived 10 years. These data demonstrate that: (1) the risk of local recurrence rises with increasing tumor thickness, presence of ulceration, and age; (2) melanomas less than 1 mm thick have a very low local recurrence rate, even when excised with margins of 2 cm or less; and (3) local recurrence is a poor prognostic sign because regional and systemic metastases subsequently develop in many patients. Cancer 55:1398‐1402, 1985.

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (less than 0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging). 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Cox's regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p less than 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision +/- node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm.) For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variable. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.

In a case-control study, 287 women with malignant melanoma were compared with 574 age-matched controls. Red hair colour at age 5 years was associated with a tripling of risk [relative risk (RR) = 3.0], blonde hair with a 60% increase (RR = 1.6) and fair skin with a doubling (RR = 2.1). Women with melanoma also reported that they tended to burn (RR = 1.4) and to freckle (RR = 1.9) after exposure to sunlight. Since fair skin, red hair, and the tendency to burn or freckle after exposure to sunlight all cluster in the same individuals, the extent to which each of these factors had an independent influence on susceptibility to melanoma was investigated. Hair colour, especially red hair, proved to be the major determinant, followed by skin colour. The reporting of above average numbers of naevi on the body was as strong a predictor of melanoma as was red hair colour (RR = 3.4). A history of psoriasis was also more common in cases than controls (RR = 3.0) as was a history of vitiligo (RR = 1.8). A history of acne appeared to be protective (RR = 0.4) as did a history suggestive of chloasma (RR = 0.6) and premature greying of the hair (RR = 0.6). These relationships were irrespective of hair and skin colour.