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

Cook, Martin; Massi, Daniela; Szumera‐Ciećkiewicz, Anna; Oord, Joost van den; Blokx, Willeke A.M.; Kempen, Léon C van; Thirunavukkarasu, Balamurugan; Bosisio, Francesca Maria; Koljenović, Senada; Portelli, Francesca; Akkooi, Alexander C. J. van

doi:10.1016/j.ejca.2019.03.010

Cited by 39 publications

(47 citation statements)

References 40 publications

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“…), to review the diagnosis and to assess tumour burden (in mm) and localisation (subcapsular and nonsubcapsular). Tumour burden was defined as the single measurement of the maximum diameter of the largest lesion in any direction, as per the EORTC protocol [20]. SN-negative patients were included to compare survival, and their pathology reports were analysed to see if nodal nevi were present.…”

Section: Study Populationmentioning

confidence: 99%

High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment

Sharouni

Laeijendecker

Suijkerbuijk

et al. 2021

European Journal of Cancer

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Introduction: Identification of sentinel node (SN) metastases can set the adjuvant systemic therapy indication for patients with stage III melanoma. Studies re-evaluating the diagnosis of initially positive SN biopsies are scarce. Materials and methods: Dutch patients with melanoma who underwent SN biopsy between 2003 and 2014 were selected from PALGA, the Dutch Pathology Registry. Histopathological slides of SN-positive patients were retrieved for review. A random sample was reassessed by an expert melanoma pathologist. Recurrence-free survival (RFS) of patients who were misclassified (false-positive) was compared with those with a true positive SN status. For comparison, a group of SN-negative patients was included. Multivariable logistic analysis was performed to assess clinicopathological characteristics associated with misclassification of SN status. Results: Diagnosis was downgraded from melanoma metastasis to nodal nevus in 38 of the 322 reviewed patients (11.8%). Considering the inclusion criteria of phase III adjuvant trials, at least 4.3% of patients would have falsely qualified for adjuvant therapy. In multivariable analysis, patients with a low SN tumour burden and subcapsular SN tumour location had a significantly higher chance of being misclassified. The five-year RFS of the 38 downgraded

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Section: Study Populationmentioning

confidence: 99%

High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment

Sharouni

Laeijendecker

Suijkerbuijk

et al. 2021

European Journal of Cancer

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“…Pathologic assessment of SNs was performed according to the EORTC protocol. 28 Patients with positive SNs were offered completion lymph node dissection (CLND) as additional therapy.…”

Section: Clinicopathologic Features and Fish Analysismentioning

confidence: 99%

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors

Maurichi¹,

Miceli

Patuzzo³

et al. 2020

Journal of the National Comprehensive Cancer Network

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Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. Patients and Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. Results: Median follow-up was 126 months (interquartile range, 104–157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node–negative and 3 patients who were sentinel node–positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%–99.2%) and 82.2% (95% CI, 77.3%–87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. Conclusions: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.

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“…These novel treatments are currently approved for adjuvant treatment in stage III disease (Amaria et al, 2019;Grob et al, 2018 (Cochran et al, 2000;Mitteldorf et al, 2009;Riber-Hansen et al, 2012;Satzger et al, 2007;Starz et al, 2001), only a very small portion of the SLN is sampled for histology. Without prior knowledge of tumor cell localization, the SLN is sectioned according to a predetermined cutting scheme (Figure 2, (Cook et al, 2019)). This black-box approach is prone to error allowing micrometastases to be missed entirely.…”

Section: Discussionmentioning

confidence: 99%

“…Conventional histology of two-dimensional (2-D) tissue sections is the currently used gold standard for SLN staging (Cook et al, 2019). However, by design this approach assesses only a few representative slices of the node, while discarding the majority of the tissue (Riber-Hansen et al, 2012) thus potentially explaining the reported high false-negative rates of SLN diagnosis (up to 38%), (Nieweg, 2009) today.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, determining the exact size of metastatic deposits is critical as melanoma-specific survival is reduced with increasing SLN tumor burden (Gershenwald et al, 2017a) and microscopic SLN tumor load is a stratification factor for adjuvant treatment (Eggermont et al, 2016; Long et al, 2017). Collectively, the reliable detection of few melanoma cells within the three-dimensional (3-D) space of entire SLNs with simultaneous volume quantification and 3-D localization of tumor foci relative to anatomical landmark structures within the SLN remains a diagnostically relevant challenge not adequately addressed to date (Cook et al, 2019; van Akkooi et al, 2009). These considerations highlight the unmet need for a method capable of determining exact tumor volume and location within a SLN.…”

Section: Introductionmentioning

confidence: 99%

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High-resolution 3-D imaging for precise staging in malignant melanoma

Merz

Jansen

Ulankiewicz

et al. 2020

Preprint

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High-resolution imaging of sentinel lymph nodes (SLN) from melanoma patients is a crucial approach to specify staging and determine individuals requiring adjuvant treatment. Current histologic SLN analysis has the substantial drawback that only a small portion of the node is sampled while most of the tissue is discarded which might explain the high false-negative rate of SLN diagnosis. Therefore, we developed an algorithm-enhanced light sheet fluorescence microscopy (LSFM) approach to three-dimensionally reconstruct the entire SLN with the power to identify single tumor cells. We comprehensively quantified total tumor volume while simultaneously visualizing cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human prospective study (21 SLN from 11 melanoma patients), LSFM not only identified all metastases seen histologically, but additionally detected metastases not recognized by routine histology. Thus, our 3-D digital pathology approach can increase sensitivity and accuracy of SLN-metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future.

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

Cited by 39 publications

References 40 publications

High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment

High discordance rate in assessing sentinel node positivity in cutaneous melanoma: Expert review may reduce unjustified adjuvant treatment

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors

High-resolution 3-D imaging for precise staging in malignant melanoma

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