Riber-Hansen Rikke, Nyengaard Jens R, Hamilton-Dutoit Stephen J, Steiniche Torben
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Cancer. 2009 May 15;115(10):2177-87. doi: 10.1002/cncr.24268.
Melanoma metastasis size estimates are of prognostic significance for groups of patients, but to the authors' knowledge, measurement consensus does not exist.
Maximum metastasis diameter, maximum centripetal tumor depth, microanatomic location of metastases, and complete metastasis volume were measured in 156 positive sentinel lymph nodes (SLNs) from 99 melanoma patients.
The number of SLN-positive patients was increased by up to 41% using complete step-sectioning compared with less extensive protocols. Assessing maximum metastasis diameters, up to 27% of patients positive by the less extensive protocols went from 1 metastasis diameter group to a larger one when complete step-sectioning was performed. No patients were down-staged. Apparently minor protocol changes (eg, adding an extra step) led to substantial changes in maximum metastasis diameter. Similar protocol-dependent results were noted measuring the maximum centripetal tumor depth and the microanatomical location of metastases. By using semiquantitative tumor burden estimates, stage migration was always unidirectional (ie, moving from a lower to higher stage). Stereologic tumor burden estimates in step-sectioned SLNs also varied according to the number of step sections assessed, but could increase, decrease, or remain constant, so that stage migration was multidirectional.
Adding extra steps to pathology protocols when assessing semiquantitative parameters leads to unidirectional stage migration ("the protocol trap"). This systematical bias makes it difficult to base treatment decisions on semiquantitative metastasis size estimates. Although based on metastatic melanoma, the principles described herein will apply when measuring nodal tumor burden in other metastasizing cancers, including breast carcinoma.
黑色素瘤转移灶大小估计对患者群体具有预后意义，但据作者所知，目前尚无测量共识。
对99例黑色素瘤患者的156枚阳性前哨淋巴结（SLN）测量转移灶最大直径、最大向心性肿瘤深度、转移灶的微观解剖位置以及转移灶总体积。
与范围较小的方案相比，采用完整连续切片时，SLN阳性患者数量增加了41%。在评估最大转移灶直径时，采用范围较小的方案为阳性的患者中，多达27%在进行完整连续切片时从一个转移灶直径组变为更大的组。没有患者分期降低。明显较小的方案改变（如增加一个步骤）会导致最大转移灶直径发生显著变化。在测量最大向心性肿瘤深度和转移灶的微观解剖位置时也发现了类似的方案依赖性结果。通过使用半定量肿瘤负荷估计，分期迁移总是单向的（即从较低分期变为较高分期）。连续切片的SLN中的体视学肿瘤负荷估计也因评估的连续切片数量而异，但可能增加、减少或保持不变，因此分期迁移是多向的。
在评估半定量参数时，在病理方案中增加额外步骤会导致单向分期迁移（“方案陷阱”）。这种系统偏差使得难以基于半定量转移灶大小估计做出治疗决策。尽管本文所述原则基于转移性黑色素瘤，但在测量其他转移性癌症（包括乳腺癌）的淋巴结肿瘤负荷时也将适用。
