A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.

Ulceration of a cutaneous melanoma on microscopic sections is an adverse prognostic finding. The five-year survival rate is reduced from 80% for non-ulcerated melanomas to 55% in the presence of ulceration for Stage I melanoma patients and from 53 to 12% for Stage II melanoma patients (P less than 0.001). As a group, ulcerated lesions are thicker and more likely to have a nodular growth pattern. However, survival rates were still worse for ulcerated melanomas when matched with nonulcerated lesions for thickness and stage of disease. The width but not the depth of surface ulceration significantly correlated with survival. The median ulcer depth was 0.08 mm (range 0.01-1.2 mm). In those few lesions with ulcer craters more than 0.2 mm in depth, the melanomas were so thick they had the same poor prognosis regardless of whether thickness was measured to the base of the ulcer or to the top of the lesion. The Breslow microstaging method of measuring thickness is therefore a valid prognostic indicator, even for ulcerated lesions. The incidence of ulceration for the entire patient group ranged from 12.5% for melanomas less than 0.76 mm thickness to 72.5% for melanomas greater than 4.0 mm thick (P of correlation = 0.0001); from 12% for Level II invasion to 63% for Level V lesions (P = 0.005); from 23% for superficial spreading growth patterns to 49% for nodular and 74% for polypoid lesions (P = 0.0001); and from 27% for lesions with a heavy lymphocyte infiltration to 60% for minimal or absent host response (P = 0.005). There was no significant correlation with anatomic location, pigmentation of the melanomas, or with the patient's age and sex. Since ulceration appears to have such an important influence on survival rates, this parameter should be considered as a stratification criterion in clinical trials and accounted for when analyzing results of melanoma treatment.

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.

An analysis of failure to control locally recurrent or metastatic melanoma was used to substantiate the value of thickness as a guide to surgical management. There were no local recurrences in patients with melanomas less than 0.76 mm in thickness, regardless of the skin margins excised. The three year actuarial incidence of subsequent regional metastases in patients initially treated by wide local excision (WLE) of their melanoma was directly correlated with tumor thickness (p = <0.001); it was 0% for lesions <0.76 mm, 25% for 0.76 to 1.50 mm lesions, 51% for 1.50 to 3.99 mm lesions and 62% for lesions >4.0 mm in thickness. At five years, patients with melanomas of 1.50 to 3.99 mm thickness who had WLE plus elective regional node dissection (RND) had a calculated 15% incidence of distant metastases and an actuarial survival rate of 83%, while patients with melanomas of the same thickness who had WLE alone as their initial surgical treatment had a 78% incidence of distant metastases and a 37% survival rate (p = 0.001 and 0.01, respectively). In patients with melanomas exceeding 4.0 mm in thickness, the potential benefits of RND were less apparent because of a high risk (>70%) of distant metastases at the time of initial diagnosis. Based upon this analysis, our initial surgical management of melanomas <0.76 is a WLE using a 2.0 cm margin of skin, while thicker lesions are excised using a 3 to 5 cm skin margin. Elective RND is not indicated for lesion C0.76 mm in thickness, but it is considered for 0.76 to 1.50 mm lesions in selected patients and is employed for virtually all patients with lesions exceeding 1.5 mm in thickness. The rationale of elective RND is improved survival in patients with intermediate thickness lesions (0.76 to 3.99 mm) while it is justifiable as a staging procedure for lesions exceeding 4.0 mm thickness.

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Ten patients developed pulmonary fibrosis after bischloroethylnitrosourea (BCNU) therapy for malignancy. This was lethal in seven patients, four of whom had no evidence of tumor at autopsy. Presenting symptoms were either the insidious onset of cough and dyspnea or the sudden onset of respiratory failure. Physical findings were unremarkable. Chest roentgenogram usually showed interstitial infiltrates. Pulmonary function studies showed resting hypoxia with diffusion and restrictive defects. This complication of therapy does not appear to be dose related and may be made more likely by the concomitant administration of cyclophosphamide. Prednisone therapy did not benefit most patients. The literature and the implications of the use of BCNU alone or in combination are reviewed.

A comparative ultrastructural study of a case of hemangiopericytoma and one of glomus tumor is presented. The study revealed the hemangiopericytoma cells to be large with large irregular nuclei. The intercellular spaces are filled with light osmiophilic material resembling basement membrane. In the glomus tumor, two types of cells are identified. The more frequent cells are epithelioid smooth muscle cells with large ovoid nuclei and cytoplasm filled with fine filaments. The second type of cell is less frequent and is recognized as a mast cell. It is suggested that the release of mast cell granules plays an important role in the contraction of epithelioid smooth muscle and therefore controls the flow of blood in the glomus structure.

Abnormal nipple discharge is rare, constituting only 3-5% of mammary consultation. In the present paper 267 patients with primary nipple discharge operated on at Institut Gustave-Roussay (IGR) in Villejuif, France, between January 1, 1960 and December, 1974 were evaluated. In all cases, the nipple discharge was symptomatic, spontaneous, and represented the primary reason for the patient's consultation. During the same period 1,145 cases of nipple discharge were treated at IGR. Of the 1,145 cases with symptomatic nipple discharge, 267 patients (23%) required surgical intervention. Among these, fibrocystic disease and duct ectasia were the leading causes of nipple discharge occurring in 42% of surgical specimens. Twenty one per cent of the patients had carcinoma and 35% were found to have intraductal papilloma. The overall incidence of malignancy, however, was 4.8% among the 1,145 women with nipple discharge. On the average, patients with nipple discharge due to malignancy were ten years older than those with benign lesions (Table 2). Approximately 25% of patients with malignant discharge and 5% with benign discharge have associated tumor. Over 60% of the patients with both discharge and a mass had malignancy.