Expert opinion in melanoma: The sentinel node; EORTC Melanoma Group recommendations on practical methodology of the measurement of the microanatomic location of metastases and metastatic tumour burden

Abstract

The sentinel node (SN) status has been recognised to be the most important prognostic factor in melanoma. Many studies have investigated additional factors to further predict survival/lymph node involvement. The EORTC Melanoma Group (MG) has formulated the following question: How should we report the microanatomic location and SN tumour burden?

The EORTC MG recommends the following: the EORTC MG SN pathology protocol or a similarly extensive protocol, which has also been proven to be accurate, should be used. Only measure what you can see not what you presume. Cumulative measurements decrease the accuracy and reproducibility of measuring. The most reproducible measure is a single measurement of the maximum diameter of the largest lesion in any direction (1-D). If there is any infiltration into the parenchyma, this lesion can no longer be considered solely subcapsular. Reporting of the microanatomic location of metastases should be an assessment of the entire sentinel node, not only of the largest lesion. Multifocality reflects a scattered metastatic pattern, not to be confused with multiple cohesive foci, which fall under the regular location system. A subcapsular metastasis should have a smooth usually curved outline, not ragged or irregular.

We recommend all pathologists to report the following items per positive SN for melanoma patients: the microanatomic location of the metastases according to Dewar et al. for the entire node, the SN Tumour Burden according to the Rotterdam Criteria for the maximum diameter of the largest metastasis expressed as an absolute number, and the SN Tumour Burden stratified per category; <0.1 mm or 0.1–1.0 mm or >1.0 mm.

Introduction

The sentinel node (SN) biopsy has become a routine staging procedure for primary melanoma patients without any clinical evidence of regional or distant metastases. Depending on the extent of the pathology protocol used and the Breslow thickness of the population, SN positivity rates range from 15% to 33%.1, 2, 3, 4, 5, 6 It has been demonstrated that SN positive patients (approximately 50–70% survival at 5 years) have a significantly worse prognosis compared to SN negative patients (approximately 90% survival at 5 years).3, 4, 6, 7

Since its introduction in the 1990s increasingly more centres worldwide have been performing, and more patients have been undergoing, SN procedures for melanoma, each year. Together with this increase in the number of performed procedures, came an increase in scientific projects to research and evaluate the efficacy and results of the SN procedure to a deeper extent. Although these studies have answered some questions, they have perhaps raised more new questions at the same time.

One of these issues is the importance of SN tumour burden and possible clinical implications. Many studies have assessed this issue, but agreement has not been achieved.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 One conclusion can be drawn: the prognosis of patients decreases with increasing SN tumour burden, no matter how you measure this, even if only by approximate measurements.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22

Since all these studies have used different methods and most often have not elaborated on how they practically measured SN tumour burden or established the microanatomic location of a metastasis, the following questions present themselves in the everyday clinical practice of pathologists in the reporting of SN tumour burden:

How should we report the microanatomic location of metastases within the SN and how should we measure the amount of tumour burden within the SN?

The following comments are based on the experience of the authors following reporting of several thousands of sentinel node biopsies. They are practical responses to frequently arising questions. They are still subject to further evaluation and may be shown to be suboptimal in the light of further studies, but seem the most appropriate in the current state of understanding of sentinel lymph nodes and melanoma.