Nodal distribution, stage migration due to diameter measurement and the prognostic significance of metastasis volume in melanoma sentinel lymph nodes: a validation study.

To validate metastasis location, maximum metastasis diameter (MMD) measurement induced stage migration and the prognostic significance of total metastatic volume (TMV) in melanoma sentinel lymph nodes (SLNs). A new 227 patient SLN cohort examined by complete step sectioning (250 μm) was tested for TMV and MMD prognostic significance; metastasis location by three different three-level protocols (Central vs Peripheral vs Global); and potential treatment changing down-staging by two restricted five-level protocols [Reduced Central (250 μm) vs Reduced Even (500 μm) sections]. Both TMV and MMD independently predicted recurrence (TMV, hazard ratio (HR): 1.21; 95% confidence interval (CI) 1.07-1.37; p = 0.003; and MMD, HR: 1.46; 95% CI 1.08-1.98, p = 0.02) and melanoma-specific death (TMV, HR: 1.30; 95% CI 1.11-1.51; p = 0.001; and MMD, HR: 1.82; 95% CI 1.25-2.66, p = 0.002). The Central, Peripheral and Global protocols detected 72%, 76% and 83% of metastases found by complete step sectioning. Based on MMD, using the Reduced Central or Reduced Even protocols, potential treatment changing down-staging occurred in 20 (20%) or 13 (13%) of SLN-positive patients. This validation study establishes that: (i) metastases are globally located in melanoma SLNs; (ii) MMD but not TMV leads to uni-directional stage migration; and (iii) TMV analysis is of prognostic significance.