br The maximum dimension of the largest metastasis has
The maximum dimension of the largest metastasis has prognostic significance, but care must be taken to measure only those metastases with confluent neoplastic cells. The maximum dimension of the largest deposit may be a sufficiently accurate estimate of tumour burden except when the pattern of metastasis is in the form of numerous scattered small metastases. For this reason, we recommend that in addition to measuring the maximum dimension of the largest metastatic deposit (and indicating its site) and the pattern of distribution of metastases, all deposits should be counted in the most representative slides as 1, 2e5, 6e10, 11e20 or over 20. If single cells or paucicellular clusters of melanoma cells are identified, they are referred to according to their size and site as for larger metastasis.
Starz measured the depth of metastases from the Concanamycin A as another way of assessing prognosis. We feel that the assessment of metastatic pattern using the subcapsular or parenchymal site is a simpler and quicker way to achieve the same objective, but Starz method is a reasonable alternative [10,14].
The extracapsular extension is often quoted as an important predictor of poor clinical outcome and has been classified as focal ( 2 mm) or extensive (>2 mm) . Rao et al.  have found that nodal extracapsular extension has a significant adverse effect on relapse-free survival but not on overall survival. Crookes et al.  have confirmed the significant independent adverse prognostic impact of extranodal spread on patterns of recurrence and survival in advanced stage melanoma patients. However, in our experience, extracapsular extension in SLNs is a rare event because it is almost al-ways associated with extensive involvement of a large lymph node which would usually be palpable clinically and therefore not usually excised as a sentinel lymph node. Extracapsular extension, meaning invasion extending through the fibrous tissue of the capsule and into surrounding adipose tissue with or without lymphatic involvement, if present, is clearly a bad prog-nostic sign but is so uncommon in this context, it is not often useful. What may be confused with extracapsular extension is melanoma in afferent lymphatics or those lymphatics traversing the capsule. Tumour in afferent lymphatics without node involvement is reported as a positive SLN. This is uncommon and is usually associated with minimal or subcapsular or combined pattern of
metastases in the adjacent lymph node. When intra-lymphatic tumour cells are present but tumour is not seen infiltrating through the fibrous tissue of the capsule, we classify this pattern according to the intranodal pattern and have found that extracapsular lymphatic permeation in this context is not a worse predictive sign.
Regarding the non-SLNs, we recommend that each lymph node is bivalved, and from each cut-surface, two sections are stained, one stained with H&E and one with S100 protein. We recommend to stain with S100 protein since recognition of single or small clusters of melanoma cells in H&E stained sections can be difficult and, therefore, result in missed metastases.
6. Recommended reporting
It is recommended that the following histopathological features are included in the pathology report:
1. Metastases: present or absent
2. Intranodal location: subcapsular, parenchymal, combined (subcapsular and parenchymal), extensive confluent and extensive multifocal
4. Maximum dimension of the largest metastatic deposit (measured in millimeters to the nearest 0.1 mm) and indi-cating its site
5. Extracapsular extension: present or absent
6. Presence of naevus cells (capsular and/or trabecular)
7. Future studies
With the establishment of SLN biopsy or melanoma as a standard procedure in melanoma management, the protocol for pathological handling and reporting needs to be made as succinct and simple as is compatible with optimum management of the patients. Whether the current procedure is sufficient or excessive needs to be confirmed. Our suggestions are therefore an interim recommendation. One of the benefits foreseen in this updated EORTC protocol is the reduction in technical workload resulting in cost saving with no loss, and possible increase, in accuracy.
Future studies will be designed to clarify which pa-tients may benefit from the SLN procedure, validate the accuracy of the current protocol and to establish which of the numerous assessments that can be performed on the primary melanoma are the most useful.
In addition, it is not clear whether multiple metasta-ses with the same tumour burden as a single or the small number of larger metastases have the same, worse or better prognosis and requires an in-depth analysis.