Predictive accuracy of elevated mitotic rate on lymph node positivity and recurrence in thin melanomas

Abstract

BackgroundMitotic rate (MR) is considered an important prognostic factor for melanoma but is not currently used for staging because its nuanced effect is not yet well-delineated. We sought to determine if T category-specific MR is predictive of sentinel lymph node (SLN) positivity, recurrence, and melanoma-specific mortality (MSM).MethodsA retrospective review of patients with primary cutaneous melanoma from 1994 to 2020 at a single academic center was performed. Patient demographics and tumor characteristics were recorded. MR was considered elevated for each AJCC8-defined T category if it was ≥2 mitoses/mm2 for T1, ≥4 mitoses/mm2 for T2, ≥6 mitoses/mm2 for T3, or ≥7 mitoses/mm2 for T4. Statistical analysis was performed to assess the predictive accuracy of MR on selected outcomes while controlling for ulceration.ResultsData from 2,984 patients with complete records were analyzed. Along with Breslow thickness and ulceration, elevated MR was associated with higher risk of MSM (HR 1.816, P=0.0001). There was no difference among patients with ulcerated T1 or T2 tumors regardless of MR, but those with non-ulcerated T1 or T2 tumors and elevated MR were more likely to have positive SLNs (P<0.0001 and P=0.0043, respectively) and recurrence (P=0.0007 and P=0.0004, respectively) compared to counterparts with low MR. There were no notable differences for T3 or T4 tumors based on MR.ConclusionsElevated MR is associated with SLN positivity and recurrence in thin melanomas, independent of ulceration. SLN biopsy should therefore be strongly considered for patients with non-ulcerated lesions <0.8 mm thick if the MR is ≥2 mitoses/mm2.

The Prognostic Value of Proliferative Activity in Cutaneous Melanoma: A Pilot Study Evaluating the Mitotic Rate and Ki67 Index to Predict Patient Outcomes

“…Despite these results, there is still no consensus regarding the prognostic cut-off value for the number of mitoses as different studies have used various thresholds, such as absent vs. present, ≥1/mm 2 , ≥2/mm 2 , or 5 mitoses/mm 2 [ 1 , 42 , 43 , 44 , 45 ]. Moreover, the significant cut-off values may vary based on the tumor stage, and further studies are required to fully establish how the mitotic index should be reported in cutaneous melanomas [ 7 , 40 , 46 ]. Another possible limitation of assessing the mitotic index is the interobserver variability.…”

Immunotherapy utilization in stage IIIA melanoma: less may be more

“…Age was categorized into three groups for ease of interpretation and because these split points have been previously shown to be associated with timely access to melanoma treatment ( 25 ). Patients were categorized into mitotic rate groups of 0-1, 2-3, and ≥4 mitoses/mm 2 , as these split points have been previously demonstrated to hold the highest prognostic value for T1 and T2 melanomas ( 26 ).…”