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.

No abstract

Testosterone analogs have been used as performance enhancers by athletes for more than 40 yr. We asked whether the anabolic steroid 17 alpha-methyl-4-androstene-17-ol-3-one (17 alpha-MT) would affect intrinsic contractile function of the heart. Male Sprague-Dawley rats, 125-150 g, were treated with 17 alpha-MT either parenterally or orally for up to 8 wk. Intrinsic contractile function of the hearts was assessed utilizing both the isolated working heart and isovolumic perfused heart preparations. Isolated working hearts from 17 alpha-MT-treated rats had a 45% decrease in heart work attributable largely to a similarly decreased stroke volume. Isovolumic perfused hearts from treated animals had elevated left ventricular systolic and diastolic pressures at similar interventricular volumes compared to controls. Rates of ventricular pressure development (+dP/dT) or relaxation (-dP/dT) were unchanged as a result of the treatment. However, static elastance was reduced in potassium-arrested hearts from the 17 alpha-MT treatment (63% increase in interventricular pressure), consistent with a limitation being imposed on stroke volume by a decreased myocardial compliance. Hydroxyproline content of the hearts was not altered by 17 alpha-MT treatment suggesting that increased stiffness was not a consequence of collagen proliferation. Treatment of the steroid rats with beta-aminopropionitrile, a compound that inhibits lysyl oxidase, restored the left ventricular volume-pressure relationship (elastance curve) to that of control hearts. Thus, chronic treatment with anabolic steroids appears to reduce left ventricular compliance, possibly related to an enhanced activity of lysyl oxidase, and results in increased crosslink formation between collagen strands in the extracellular matrix.

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.