Mitotic activity within dermal melanocytes of benign melanocytic nevi: a study of 100 cases with clinical follow-up.

It is generally accepted that otherwise benign intradermal or compound melanocytic nevi may show mitotic activity within dermal melanocytes. However, it is not known whether there is any clinical significance to this finding. Our objective is to analyze and describe the clinicopathologic features of benign nevi with mitotic activity (NMA). To do this, we collected 100 consecutive NMA during the usual course of business in our private dermatopathology practice. These cases were seen between the years 2000 and 2008. We then collected clinical and pathologic data on these cases and compared the findings with 100 control nevi without mitotic activity (CN). We compared these nevi with regard to demographic features, clinical history provided by clinician, and clinical follow-up, as well as anatomic site and season of biopsy, type of nevus, and selected histologic features (ie, trauma). We also estimate the incidence of NMA and describe the amount and location of mitotic figures within the NMA. Our results indicate that the incidence of NMA is 0.91%. Most (80) NMA revealed only one mitotic figure, whereas some (20) NMA revealed more than one mitotic figure. Most NMA (89) showed mitotic activity in the upper portion of the nevus, whereas some (11) showed mitotic activity in the lower portion of the nevus. NMA patients were of younger age than the CN patients (P = 0.0019). Compared with CN, the NMA were more likely to be from the extremities (P = 0.0113) or head and neck (P = 0.0237) and less likely to be from the trunk (P < 0.001). The NMA were also more likely to show histologic features suggesting a congenital onset (P < 0.001) and were more likely to be Spitz nevi (P = 0.0185). Compared with the CN, the NMA were more often reexcised (P = 0.0073) and more often, there was residual nevus in the reexcision specimen (P = 0.13), although the latter finding was not statistically significant. Anecdotally, 2 of our NMA were identified adjacent to invasive melanomas; however, on clinical follow-up, we were unable to detect any increased incidence of melanoma.

Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma.

PURPOSE: Tumor cell proliferation is a central feature of melanoma progression. In this study, we characterized three biomarkers of proliferation (Ki67 expression, dermal mitotic rate [MR], and tumorigenicity) in thin (< or = 1.00 mm) primary cutaneous melanomas and examined their association with prognosis. PATIENTS AND METHODS: We used immunohistochemistry to determine Ki67 expression using the monoclonal antibody MIB-1 in lesions from a prospective cohort that included 396 patients with thin invasive primary melanomas seen between 1972 and 1991. A multivariate Cox proportional hazards model was used to define independent prognostic factors, and recursive partitioning was used to develop a prognostic tree identifying risk groups. RESULTS: Dermal Ki67 expression was lower than epidermal Ki67 expression in radial growth phase (RGP) melanomas (n = 171), and dermal Ki67 expression and MR were higher in tumorigenic vertical growth phase (VGP) melanomas (n = 193) compared with RGP and nontumorigenic VGP melanomas (n = 42). Dermal Ki67 expression, MR greater than 0, growth phase, thickness, ulceration, tumor-infiltrating lymphocytes, and sex were associated with metastasis at 10 years, however, only dermal Ki67 expression, MR greater than 0, and sex were independent prognostic factors. Two high-risk groups were identified: men and women with dermal MR greater than 0 and dermal Ki67 expression > or = 20% in tumor cells and men with MR greater than 0 and Ki67 expression less than 20%, with 10-year metastasis rates of 39% and 20%, respectively. CONCLUSION: Proliferation slows as melanoma cells enter the dermis and then increases with the onset of tumorigenic VGP. Ki67 expression and dermal MR provide independent prognostic information that can potentially be used in risk-based management of patients.