False-Negative Interpretation of Breast Sentinel Lymph Node Touch Preps: Analysis of the Causes with Suggestions to Improve Diagnostic Accuracy

Frank Chen, D. Hicks, M. Nava, R. Cheney
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Abstract

Sentinel lymph node (SLN) biopsy has become widely accepted as an important procedure in staging breast cancer. False-negative results of touch prep (TP) examination at time of SLN biopsy requires additional surgery, delaying treatment and increasing cost. Therefore, we have analyzed our experience with false-negative interpretation on SLN TP’s. Eight-hundred and three consecutive SLN biopsies from 2003 to 2005 were obtained from the pathology archive of Roswell Park Cancer Institute. The intraoperative consultation results were correlated with the final diagnoses.  Twenty-five SLN intraoperative consultations had false-negative TP’s [false-negative rate = 3.1% (25/803), including 9 metastatic lobular carcinomas and 16 metastatic ductal carcinomas]. These cases were re-evaluated by 3 pathologists independently, and the metastases in the SLN sections were confirmed by positive cytokeratin staining.  Size of the metastatic focus, nuclear grade and the adequacy of TP’s were analyzed with regard to the cause of false-negative results. On re-screening of TP’s, we found that rare tumor cells of low nuclear grade were identified on 28% (7/25) of the TP’s (3 metastatic lobular carcinomas and 4 metastatic ductal carcinomas). In the remaining 72% (18/25) of TP’s, re-screening revealed no evidence of tumor.  Evaluation of these TP’s demonstrated that 50% (9/18) were unsatisfactory for evaluation or limited by scant cellularity. While cases that remained negative on re-screening tended to have smaller measured foci of tumor in the SLN (Average 0.65 mm vs. 0.94 mm from cases that were positive on re-screening), there was considerable overlap between these two groups. In conclusion, TP’s with scant cellularity, unsatisfactory TP’s and failure to identify tumor cells with low nuclear grade were found to significantly contribute to false-negative interpretations. We suggest that an additional TP or frozen section may be necessary if the cellularity of the initial TP is limited.  Correlation with the original core biopsy may be of value to help in identifying cancer cells of low nuclear grade.
乳房前哨淋巴结触诊假阴性解释:原因分析及提高诊断准确率的建议
前哨淋巴结(SLN)活检已被广泛接受为乳腺癌分期的重要程序。SLN活检时接触准备(TP)检查的假阴性结果需要额外的手术,延迟治疗并增加费用。因此,我们分析了我们在SLN TP上的假阴性解释的经验。从2003年到2005年,从Roswell Park癌症研究所的病理档案中获得了883例连续的SLN活检。术中会诊结果与最终诊断结果相关。术中SLN会诊有25例TP假阴性[假阴性率3.1%(25/803),其中转移性小叶癌9例,转移性导管癌16例]。这些病例由3名病理学家独立重新评估,细胞角蛋白染色阳性证实了SLN切片的转移。分析了转移灶的大小、核分级和TP的充分性对假阴性结果的影响。在TP的重新筛查中,我们发现28%(7/25)的TP中发现了罕见的低核级肿瘤细胞(3例转移性小叶癌和4例转移性导管癌)。其余72%(18/25)的TP患者,重新筛查未发现肿瘤。对这些TP的评价表明,50%(9/18)的评价不满意或受到细胞缺乏的限制。虽然重新筛查呈阴性的病例往往在SLN中有较小的肿瘤灶(平均0.65 mm对0.94 mm),但这两组之间存在相当大的重叠。总之,缺乏细胞性的TP,不满意的TP和不能识别低核分级的肿瘤细胞是导致假阴性解释的重要原因。我们建议,如果初始TP的细胞数量有限,可能需要额外的TP或冷冻切片。与原始核心活检的相关性可能有助于识别低核级别的癌细胞。
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