Prognostic factors in young women with cutaneous melanoma.

BACKGROUND: Gender is an established prognostic factor in cutaneous melanoma; women as a group have a better overall prognosis than men. However, the investigators hypothesized that melanoma in young women may have distinct clinicopathologic features and biologic behavior compared with melanoma in older women, possibly related to tanning bed use and excessive acute episodes of sun exposure. METHODS: A retrospective analysis was performed of a large multicenter study that accrued patients between 1996 and 2003 and included patients aged 18 to 70 years with cutaneous melanoma ≥1 mm Breslow thickness and no evidence of regional or distant metastatic disease. All women with follow-up data were included. Univariate and multivariate analyses as well as Kaplan-Meier (KM) analysis were performed to test for differences in clinicopathologic variables, disease-free survival (DFS), and overall survival (OS) between female patients ≤40 and >40 years of age. RESULTS: A total of 1,056 female patients were divided into 2 groups: those >40 years of age (n = 757 [71.7%]) and those ≤40 years of age (n = 299 [28.3%]). Overall, there were no differences in Breslow thickness, ulceration, or sentinel lymph node status between groups. Compared with older women, younger women were more likely to have truncal melanomas (39.5% vs 29.5%, P = .0017) and less likely to have regression of the primary tumor (6.4% vs 11.5%, P = .0208). The mean number of sentinel lymph nodes removed was 2.82 for younger women and 2.29 for older women (P < .0001). Multivariate analysis revealed that Breslow thickness, ulceration, and tumor-positive sentinel lymph node were associated with worse DFS in both the younger and older groups; truncal location was associated with worse DFS in the younger group only. The same factors were predictive of OS in both groups, except that ulceration was not significant in the younger patient group. In the younger patient group, the 5-year KM DFS rates were 78.1% for truncal melanomas and 92.5% for nontruncal melanoma locations (P = .0009); the corresponding 5-year KM OS rates were 76.6% and 93.9% (P = .0003). In the older patient group, the 5-year KM DFS rates were 84.1% for truncal and 82.8% for nontruncal melanomas (P = NS), and the corresponding 5-year KM OS rates were 81.6% and 87.5% (P = .0049). CONCLUSIONS: Although women with cutaneous melanoma tend to have a better prognosis than men, women ≤40 years of age with primary melanoma of the trunk may represent a subgroup at higher risk for disease recurrence and metastasis.

Assessment of mitotic rate reporting in melanoma.

BACKGROUND: In patients with cutaneous melanoma, mitotic rate (MR) historically has been reported as the number of mitoses per high-power field (hpf) or per 10 hpf. The most recent revision of the American Joint Committee on Cancer melanoma staging system now incorporates MR and specifies that MR should be reported as mitoses per mm(2), with a conversion factor of 1 mm(2) equaling 4 hpf. However, because many pathologists continue to report MR in hpf units, we sought to compare the 2 conventions for reporting MR; this is important now that MR is used for staging and prognostic information. METHODS: A retrospective analysis was performed of a database that combined patients from a large multicenter study and our single-institution melanoma database. All patients with pathology reports that included MR were included. For patients with MR reported in hpf units, MR was converted to mitoses per 10 hpf. Statistical analysis was performed to test differences in Breslow thickness (BT), ulceration, sentinel lymph node (SLN) status, and overall survival (OS) (log-rank test) between the mitoses per mm(2) group versus the mitoses per 10-hpf group. RESULTS: A total of 1,148 patients were identified; of these, 759 were reported as per mm(2) and 389 were reported in hpf units. When patients were subdivided into categories of MR of 0, 1, or more than 1, there was no statistically significant difference in mean or median BT, ulceration, or SLN positivity within categories between patients with MR per mm(2) versus patients with MR reported per 10 hpf. There was also no difference in OS between groups. Subdividing into smaller categories of MR of 0, 1, 2, 3, 4, 5, or more than 5 did not yield different results. CONCLUSIONS: Although the American Joint Committee on Cancer staging system reports a conversion factor for MR of 1 mm(2) equals 4 hpf, no clinically meaningful differences in predictors of prognosis (BT, ulceration, SLN positivity) or OS were seen between groups when a conversion factor of 1 mm(2) equaling 10 hpf was used. Therefore, for practical purposes, MR reported per 10 hpf approximates MR per mm(2).

Prognostic implications of anatomic location of primary cutaneous melanoma of 1 mm or thicker.

BACKGROUND: Breslow thickness, ulceration, and sentinel lymph node (SLN) status are well established as the most important prognostic factors for patients with cutaneous melanoma. Anatomic location of the primary tumor is generally considered to play a minor role in determining prognosis compared with these other factors. This analysis was performed to better define the influence of anatomic location of the primary melanoma on prognosis. METHODS: In this post hoc analysis of a prospective randomized trial that included patients ages 18 to 70 years with melanomas 1 mm or greater in Breslow thickness, all patients underwent SLN biopsy and completion lymphadenectomy if tumor-positive SLN were found. Kaplan-Meier survival analysis and univariate and multivariate analyses were performed to evaluate factors predictive of disease-free survival (DFS), local and in-transit recurrence-free survival (LITRFS), and overall survival (OS). RESULTS: A total of 2,500 patients were included in this analysis with a median follow-up period of 68 months. Anatomic locations included head, neck, trunk, upper extremity, and lower extremity. Age, Breslow thickness, and percentage of patients with a positive SLN were significantly different by anatomic location on univariate analysis, as were positive SLN status, presence of regression, sex, and histologic subtype (P < .0001). On multivariate analysis, anatomic location was an independent predictor of SLN status (P < .0001), DFS (P = .045), LITRFS (P = .023), and OS (P < .0001). By Kaplan-Meier analysis, anatomic location was associated significantly with DFS, LITRFS, and OS. CONCLUSIONS: Anatomic location of the primary melanoma is an important independent predictor of SLN status and prognosis. Patients with primary melanomas of the head/neck and trunk have a worse prognosis than primary melanomas of other anatomic locations.

Lymphovascular invasion as a prognostic factor in melanoma.

The prognostic significance of lymphovascular invasion (LVI) in melanoma remains controversial. Clinicopathologic data from a prospective trial of patients with melanoma were analyzed with respect to LVI. Disease-free survival and overall survival (OS) were evaluated by Kaplan-Meier (KM) analysis. Univariate and multivariate analyses were performed to evaluate factors predictive of tumor-positive sentinel nodes (SLN) and survival. A total of 2183 patients were included in this analysis; 171 (7.8%) had LVI. Median follow-up was 68 months. Factors associated with LVI included tumor thickness, ulceration, and histologic subtype (P < 0.05). LVI was associated with a greater risk of SLN metastasis (P < 0.05). By KM analysis, LVI was associated with worse OS (P = 0.0009). On multivariate analysis, age, gender, thickness, ulceration, anatomic location, and SLN status were predictors of OS; however, LVI was not an independent predictor of OS. Among patients with regression, the 5-year OS rate was 49.4 per cent for patients with LVI versus 81.1 per cent for those with no LVI (P < 0.0001). LVI is associated with a greater risk of SLN metastasis. Although LVI is not an independent predictor of OS in general, it is a powerful predictor of worse OS among patients who have evidence of regression of the primary tumor.

Regression does not predict nodal metastasis or survival in patients with cutaneous melanoma.

Controversy exists regarding the prognostic implications of regression in patients with cutaneous melanoma. Some consider regression to be an indication for sentinel lymph node (SLN) biopsy because regression may result in underestimation of the true Breslow thickness. Other data support regression as a favorable prognostic indicator, representing immune system recognition of the primary tumor. This analysis was performed to determine whether regression predicts nodal metastasis, disease-free survival (DFS), or overall survival (OS). Post hoc analysis was performed of a multicenter prospective randomized trial that included patients aged 18 to 70 years with cutaneous melanomas 1 mm or greater Breslow thickness. All patients underwent SLN biopsy; those with tumor-positive SLN underwent completion lymphadenectomy. Kaplan-Meier analysis of survival, univariate analysis, and multivariate analysis were performed. A total of 2220 patients (261 with regression; 1959 without regression) were included in this analysis with a median follow-up of 68 months. Patients with regression were more likely to be male, older than 50 years old, and have lower median Breslow thickness, superficial spreading histologic subtype, and a nonextremity anatomic location (P < 0.05 in all cases). Regression was not significantly associated with Clark level, ulceration, lymphovascular invasion, number of SLNs removed, or SLN metastasis. On multivariate analysis, factors independently predictive of DFS included Breslow thickness, ulceration, and SLN status (P < 0.05 in all cases); the same factors along with age, gender, and anatomic tumor location were significantly associated with OS (P < 0.05 in all cases). Regression was not significantly associated with DFS (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.67-1.27; P = 0.68) or OS (RR, 1.01; 95% CI, 0.76-1.32; P = 0.93). These data suggest that regression is not a significant prognostic factor for patients with cutaneous melanoma and should not be used to guide clinical decision-making for such patients.

Prognostic significance of tumor infiltrating lymphocytes in melanoma.

The prognostic significance of tumor infiltrating lymphocyte (TIL) response in cutaneous melanoma is controversial. This analysis of data from a prospective, randomized trial included patients with cutaneous melanoma > or = 1.0 mm Breslow thickness who underwent wide local excision and sentinel lymph node (SLN) biopsy. Univariate and multivariate analyses were performed to determine factors associated with TIL response, disease-free survival (DFS), and overall survival (OS). A total of 515 patients were included; TIL response was classified as "brisk" (n = 100; 19.4%) or "non-brisk" (n = 415; 80.6%). Patients in the nonbrisk TIL group were more likely to have tumor-positive SLN (17.6% vs 7%; P = 0.0087). On multivariate analysis, nonbrisk TIL response, increased tumor thickness, and ulceration were significant independent predictors of tumor-positive SLN. By Kaplan-Meier analysis, 5-year DFS rate was 91 per cent for those with a brisk TIL response compared with 86 per cent in the nonbrisk group (P = 0.41). The 5-year OS rates were 95 per cent versus 84 per cent in the brisk versus nonbrisk TIL groups, respectively (P = 0.0083). However, on multivariate analysis, TIL response was not a significant independent factor predicting DFS or OS. TIL response is a significant predictor of SLN metastasis but is not a major predictor of DFS or OS.

Does mitotic rate predict sentinel lymph node metastasis or survival in patients with intermediate and thick melanoma?

BACKGROUND: The significance of mitotic rate (MR) in melanoma remains controversial. METHODS: In this retrospective analysis of a prospective randomized trial that included patients with melanoma of 1.0 mm or greater, all patients underwent wide excision and sentinel node (sentinel lymph node [SLN]) biopsy. Univariate and multivariate analyses were performed to evaluate factors predictive of disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 551 patients had MR reported. A cut-off point of 6 mitoses/mm(2) best discriminated DFS and OS: 455 patients (82.6%) had MR less than 6/mm(2). SLN were tumor-positive in 14.7% of low MR versus 31.3% of high MR patients (P = .0003). There were significant differences in DFS (P = .0014) and OS (P = .0002) between the 2 groups, however, MR failed to remain significant in the multivariate model. CONCLUSIONS: MR is weakly predictive of SLN status but it is not an independent predictor of survival for melanomas 1.0 mm or thicker.

Elastofibroma: diagnosis and treatment of six cases.

Elastofibroma is a rare, benign pseudotumor that arises from connective tissue, most commonly found at the right scapular tip. These tumors usually can be distinguished from malignant soft-tissue tumors by their anatomical location and also through imaging techniques. Although elastofibroma is rare, it is important for surgeons to be aware of this diagnosis to prevent unnecessary biopsies and unnecessary operations. We report a series of six patients, four of whom were female, with a median age of 62.5 years, diagnosed with and treated for elastofibroma. Five of the six patients had unilateral lesions, while one patient had bilateral elastofibromas. All unilateral lesions were found on the right side. The elastofibroma in five of six patients was located on the subscapular tip, the remaining patient's elastofibroma was found on the chest wall external to the pleural surface. The pathogenesis of this lesion is discussed, as recent evidence suggests a neoplastic origin to elastofibroma. Additionally, cellular changes occurring in elastofibroma may reflect the pathogenesis of other disorders of elastic fibers.