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

Abstract

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.

Reducing workload in malignant melanoma sentinel node examination: a national study of pathology reports from 507 melanoma patients

“…Although the high metastasis detection rates of extensive protocols are appealing, they may be a waste of resources. On the other hand, when streamlining an SN protocol to best possible cost benefit some metastases may be missed or changed to a smaller diameter if workload is reduced, which ultimately may affect the cancer treatment 3–5. However, the prognostic significance of micrometastases is unclear, with some studies suggesting that they may not have prognostic value,16–21 and other studies suggesting that even very small metastases may affect the prognosis negatively 22–24.…”

“…If true, it may not be necessary to extensively examine the peripheral parts of the SN. Meanwhile, other studies have found that metastases were located throughout the parenchyma and that they were equally sized 4–6 21 26–28. Thus, examining both the central and the peripheral parts of the SN would ensure higher metastasis detection rates compared with only examining the central parts of the node.…”

“…Generally, protocols with extensive step-sectioning combined with immunohistochemistry (IHC) correlate with increased metastasis detection rates as well as increased diameter of detected metastases. Nevertheless, extensive protocols imply a high workload 3–5…”

An updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for pathological evaluation of sentinel lymph nodes for melanoma

“…A range of procedures can be used to estimate quantitatively tumour burden in the SLN, such as the maximal number of metastatic foci within the node, the maximum size of the largest metastasis, the maximum depth from the capsule of the tumour deposit (tumour penetrative depth) and the percentage crosssectional area of the SLN involved by the tumour [3,14,16,30,33e39]. Some of these involve calculations at several levels [17,40].…”