High-resolution three-dimensional imaging for precise staging in melanoma.
High-resolution three-dimensional imaging for precise staging in melanoma.
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DOI：
10.1016/j.ejca.2021.09.026
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发表时间：
2021-11
影响因子：
8.4
通讯作者：
Simon F. Merz;P. Jansen;Ricarda Ulankiewicz;L. Bornemann;T. Schimming;K. Griewank;Zülal Cibir;Andreas Kraus;I. Stoffels;T. Aspelmeier;S. Brandau;D. Schadendorf;E. Hadaschik;G. Ebel;M. Gunzer;J. Klode
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文献类型：
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作者：
Simon F. Merz;P. Jansen;Ricarda Ulankiewicz;L. Bornemann;T. Schimming;K. Griewank;Zülal Cibir;Andreas Kraus;I. Stoffels;T. Aspelmeier;S. Brandau;D. Schadendorf;E. Hadaschik;G. Ebel;M. Gunzer;J. Klode
前言许多癌症指南包括前哨淋巴结(SLN)分期以识别微小转移疾病。目前对黑色素瘤患者的SLN分析是有效的，但有很大的缺点，即只对结节的一小部分进行采样，而大多数组织被丢弃。这可能解释了目前黑色素瘤SLN诊断的高临床假阴性率。此外，转移负荷和显微解剖定位的定量评估可能会产生更高精度的预后。因此，除了繁琐的连续物理切片外，需要用细胞分辨率来分析整个SLN。患者和方法11名符合SLN活检条件的黑色素瘤患者被纳入这项前瞻性研究。SLN固定，光学透明，整体染色，光片荧光显微镜(LSFM)成像。随后，相容和公正的金标准组织病理学评估使患者能够定期进行分期。这使得LSFM与组织学结果的样本内比较成为可能。此外，算法RAYhance的开发使LSFM数据能够以可浏览的组织学幻灯片方式轻松显示。结果我们全面量化了总肿瘤体积，同时可视化了相关SLN结构的细胞和解剖学特征。在对21名黑色素瘤患者进行的人类首例SLN研究中，LSFM不仅确认了常规组织病理学评估确定的所有转移，而且还发现了仅通过常规组织学无法发现的转移。这已经为一名患者带来了额外的治疗选择。结论我们的三维数字病理学方法可以提高SLN转移检测的敏感性和准确性，并有可能减少未来对常规组织病理学评估的需求。
IntroductionMany cancer guidelines include sentinel lymph node (SLN) staging to identify microscopic metastatic disease. Current SLN analysis of melanoma patients is effective but has the substantial drawback that only a small representative portion of the node is sampled, whereas most of the tissue is discarded. This might explain the high clinical false-negative rate of current SLN diagnosis in melanoma. Furthermore, the quantitative assessment of metastatic load and microanatomical localisation might yield prognosis with higher precision. Thus, methods to analyse entire SLNs with cellular resolution apart from tedious sequential physical sectioning are required.Patients and methodsEleven melanoma patients eligible to undergo SLN biopsy were included in this prospective study. SLNs were fixed, optically cleared, whole-mount stained and imaged using light sheet fluorescence microscopy (LSFM). Subsequently, compatible and unbiased gold standard histopathological assessment allowed regular patient staging. This enabled intrasample comparison of LSFM and histological findings. In addition, the development of an algorithm, RAYhance, enabled easy-to-handle display of LSFM data in a browsable histologic slide-like fashion.ResultsWe comprehensively quantify total tumour volume while simultaneously visualising cellular and anatomical hallmarks of the associated SLN architecture. In a first-in-human study of 21 SLN of melanoma patients, LSFM not only confirmed all metastases identified by routine histopathological assessment but also additionally revealed metastases not detected by routine histology alone. This already led to additional therapeutic options for one patient.ConclusionOur three-dimensional digital pathology approach can increase sensitivity and accuracy of SLN metastasis detection and potentially alleviate the need for conventional histopathological assessment in the future.German clinical trials register(DRKS00015737).