br a Histopathology Royal Surrey County Hospital Guildford U
a Histopathology, Royal Surrey County Hospital, Guildford, UK
b Section of Anatomic Pathology, Department of Health Sciences, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
c Department of Pathology and Laboratory Medicine, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Warsaw, Poland
d Translational Cell and Tissue Research, Department of Imaging and Pathology, University of Leuven (KU Leuven), Leuven, Belgium
e Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
f Department of Pathology and Medical Biology, University Medical Center Groningen, the Netherlands
g Department of Pathology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
h Department of Surgical Oncology, Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, the Netherlands
Sentinel AMG-176 node;
Abstract The sentinel lymph node (SLN) biopsy is a highly accurate staging procedure and the most important prognostic factor in melanoma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group aimed to design an updated evolved SLN protocol for the histopathological workup and reporting. We herein recommend extending the distance between steps according to the short axis dimension of the lymph node and optimise both conventional sectioning and staining procedures including immunohisto-chemistry. We also provide guidance on the description of the spatial localisation of mela-noma deposits in a SLN. The histopathological features to be reported include the following: presence or absence of the metastasis, the intranodal location of the metastasis
* Corresponding author: Histopathology, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK.
E-mail address: [email protected] (M.G. Cook). 1 Martin G. Cook and Daniela Massi equally contributed to the study.
Immunohis-tochemistry; Nodal naevus cells; Recommendations M.G. Cook et al. / European Journal of Cancer 114 (2019) 1e7
(subcapsular, parenchymal, combined, extensive confluent and extensive multifocal), the num-ber of the metastatic deposits (1, 2e5, 6e10, 11e20 and >20), the maximum dimension of the largest metastasis (indicating its site) and the presence of extracapsular extension and of nae-vus cells. This updated EORTC protocol is expected to clarify and simplify the existing pro-cedures, ensuring a reasonable workload for the laboratory and for the pathologists resulting in cost saving with no loss, and possible increase, in accuracy.
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Sentinel lymph node (SLN) biopsy for melanoma introduced in the early 90s  has become an established procedure and is likely to remain so even after the Multicenter Selective Lymphadenectomy Trial-2 (MSLT-2)  suggested a lack of impact on melanoma-specific survival for completion lymphade-nectomy. In light of the evolving landscape of adjuvant therapy, its value is now mainly as a key staging pro-cedure to accurately define prognosis, provide more consistent grouping in clinical trials  and enable on-cologists to assess whether a patient is eligible for sys-temic therapy.
A wide divergence of protocols for the histopatho-logical handling of SLNs has developed, and this has not been resolved [3e20]. Furthermore, pathological reporting protocols are not harmonised, extensive pro-tocols have a significant impact on laboratory workload and in addition to this, there are problems of interpretation resulting in an apparently high number of errors detected in a pathological review of clinical trials. The quality of the report depends on having an excellent quality of dissection, sectioning and staining and immunohistochemistry. The technical variability is the main culprit in interpretation errors.
The European Organisation for Research and Treatment of Cancer (EORTC) protocol established in 2003  is a widely used method for the assessment of melanoma burden in SLN. The EORTC Melanoma Pathology Group is now proposing an improvement thereof by the assessment of a larger proportion of the SLN with the greatest efficiency. We noted that twice as many metastases were found by increasing the number of steps; however, this still leaves a considerable pro-portion of most lymph nodes unexamined, especially in those SLNs that have a more rounded shape. Because roundness correlates with a relative increase in length of the shortest axis, a larger volume of a nodal tissue parallel to the bisection plane remains unexamined compared with ellipsoid SLN using the current procedure.