Mitotic Activity Within Dermal Melanocytes of Benign Melanocytic Nevi: A Study of 100 Cases With Clinical Follow-up

Abstract

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.

Wnt signaling potentiates nevogenesis

“…In humans, this may contribute to the recognized risk of nevi for progression to melanoma and reports that ∼25% of melanomas arise from a preexisting nevus (14,15). Underscoring the possible link between Wnt and neoplastic progression of nevi, we find that Wnt signaling is preferentially active in the least mature, more proliferative component of the nevus that appears to be of greater malignant potential (43)(44)(45). Recently, we also reported that nevus maturation is associated with marked changes in nuclear chromatin structure (55).…”

“…3B) (43,44). Maturation is associated with enhanced proliferation arrest because nevi can contain some mitotic cells, typically in the least mature upper portion of the nevus (45). Most important, maturation is an indicator of reduced malignant potential (43,44).…”

Nevic Mitoses

“…[5][6][7] Multiple mitotic figures within a single nevus were always distributed far from one another and were most often found in CMN in superficial locations. A further 19.5% of mitotically active cases, or 1.5% of all nevi, contained more than one mitotic figure, highlighting the potential for multiple mitotic figures in otherwise banal lesions.…”

“…[1][2][3][4][5][6][7] Reported rates in these studies have varied from 0% to 19.5%, reflecting a wide variation in methodology and inclusion criteria. [1][2][3][4][5][6][7] Reported rates in these studies have varied from 0% to 19.5%, reflecting a wide variation in methodology and inclusion criteria.…”

Cell Proliferation in Cutaneous Malignant Melanoma: Relationship with Neoplastic Progression

“…Quantitative assessments were used to derive a prognostic factor (PF) following PF = M* tumor thickness where M represented the number of mitosis per mm 2 [53]. More recently, a revival of mitosis interest emerged in CMM [54–56] and in melanocytic nevi as well [57]. Currently, it is possible to highlight mitoses using immunohistochemistry directed to specific M -associated histones.…”