Sentinel node metastasis mitotic rate (SN‐MMR) as a prognostic indicator of rapidly progressing disease in patients with sentinel node‐positive melanomas

Abstract

Risk stratification of sentinel lymph node biopsy (SNB)-positive patients with malignant melanoma differs among current classification systems. To improve classification of patients with rapidly progressive disease who may profit from adjuvant therapy with novel immune or targeted treatment modalities, a single-center retrospective analysis was performed including all melanoma patients diagnosed with a positive SN at a university-based skin cancer center over a 10-year period (2002-2012) (96 of 419 patients). Sentinel node metastasis mitotic rate (SN-MMR) and further histologic parameters were determined by blinded histological re-evaluation and correlated with clinical follow-up (overall [OS], melanoma-specific [MSS], and disease-free survival [DFS]). Median follow-up was 53 months. In univariate analyses, SN tumor penetrative depth (TPD), maximum tumor diameter (MTD), number of positive SN, SN-MMR and the S-, Rotterdam, RDC, Hannover I and II classification systems correlated with OS, MSS and DFS. Multivariate Cox regression analyses showed that a binary classification system based only on the SN-MMR (<1 vs. ≥1 mitoses/mm ) was the strongest independent prognostic indicator for all endpoints analyzed. Kaplan-Meier analyses confirmed binary SN-MMR to be superior to stratify patients into high- and low-risk groups (45.45% vs. 87.92% 5-yr MSS). The general prognostic validity of the published SN classification systems was confirmed. The novel SN-MMR classification system may improve discrimination of patients with slowly and rapidly progressive disease. We therefore propose its implementation into clinical practice as the SN-MMR can be easily and reliably determined in routine pathology reports. Its prognostic value for the selection of patients amenable to adjuvant therapies should be studied in clinical trials.

The sentinel node invasion level (SNIL) as a prognostic parameter in melanoma

“…However, similar to Meier’s observation [ 17 ], no significant differentiation from the adjacent intermediate-risk groups (R2, s2) was achieved by multivariate analyses (Table 4 ). We could only confirm the significance of the 1-mm cutoffs in the Rotterdam classification and the S-classification [ 12 , 39 ].…”

“…As a result, the use of CLND has decreased significantly, which reduces the importance of the number of lymph node metastases as a prognostic parameter for patients with clinical occult disease. Some SN tumor burden-based prognostic models offer feasible alternatives, for example the Rotterdam classification [ 10 ], the S-classification [ 11 ], the number of mitoses within SN metastasis [ 12 ], the microanatomic metastasis location according to Dewar [ 13 ], the number of SN metastatic foci [ 14 ], the SN cross-sectional area involved by melanoma [ 14 – 16 ], and the presence of extranodal involvement [ 14 , 17 ] (for review see [ 18 ]).…”

Protocolo de diagnóstico histológico para muestras de pacientes con melanoma cutáneo. Documento de consenso de la SEAP y la AEDV para el Registro Nacional de Melanoma

“…Otras variables propuestas se han rechazado por no conseguir consenso suficiente bien porque esa información ya está recogida en otras variables como la clasificación S de la metástasis del GC 12 o bien por la dificultad y la falta de evidencia atribuible a la presencia de mitosis en la metástasis linfática regional 13 .…”

P53 expression, Genome-wide transcriptome profiling and LGS test (a blood test to detect cancer): comparison of UVA exposed lymphocytes from malignant melanoma patients and healthy controls.

“…Once melanoma metastasises, it becomes life-threatening, and its incidence rate and mortality depend upon the early detection criteria. In cancer patients, a positive sentinel node indicates metastasis and is believed to be an important prognostic factor (Baum et al, 2017). Screening sentinel nodes have proved promising results in distinguishing slow-progressing cancers from metastasised tumours.…”