The pathologic evaluation of lymph nodes (LNs) for metastatic disease plays an important role in the surgical staging of nearly all solid-organ malignancies. Nodal tissue is evaluated by pathology either as part of an en bloc resection or as separate, anatomically distinct specimens. In either case, the specimen is grossly examined and LNs are dissected and submitted for histologic examination via a variety of nonstandardized methods. The surgical pathology report typically includes both the total LN count (LNC), as well as the number of positive LNs, and has developed into a critical aspect of planning cancer treatment protocols. According to the 8th edition of the AJCC Cancer Staging Manual, the pathologic node staging (pN) of 29 of the approximately 70 solid-organ staging systems use LNCs in some form and, of these, 13 are staged solely on the number of positive LNs.1 LNC has been proposed as a metric to assess adequacy of surgical resection and/or pathologic examination, and thresholds of a minimum LNC have been required for inclusion in a number of clinical trials (ClinicalTrials.gov identifiers: NCT00002706 and NCT00340808).2,3
Interest regarding LNC and clinical outcomes is abundant. The literature is replete with large studies investigating the role of LNC and outcomes, many of which demonstrate improved outcomes with higher LNCs.4–7 However, these studies provide very little information regarding methods of nodal quantitation. Nearly all of the published literature simply cites the “pathology report” as the source of LNC data. In the studies that do give additional information on LNC methods, it is typically limited to a brief description of the tissue-processing technique and a nominal statement that tissue was evaluated by standard microscopy.
The lack of formally described LNC methods in these studies may come as a surprise to most non-pathologists. To the uninitiated, LNs in a specimen could be easily compared with jelly beans in a jar: dump them out and count. However, the actual process involves many factors, each with their own challenges. Multiple studies have attempted to assess LNC variability and have demonstrated a variety of factors, including the patient's anatomy, tumor biology, experience of the gross examiner, and use of fat-clearing solutions.6,8–12 Although many of these studies also identify the pathologist as a significant source of variation, this has not been uniformly true.13 By far, the least investigated aspect of LNC is the actual enumeration process of the pathologist during microscopic review; however, this is the time at which the LNC is determined. To date, a single study has evaluated this aspect and demonstrated significant interpathologist variability.14 However, the study was somewhat limited in the number of pathologists (N=10), and the heterogeneity of their practice setting (2 departments). In order to further assess whether LNC represents a scientifically meaningful number, we conducted the largest and most diverse study of LNC by pathologists.
We would like to thank the International Society of Gynecological Pathologists and the British Association of Gynaecological Pathologists for the distribution of the survey to their members. We are indebted to the gynecologic oncology and radiation oncology faculty at the University of Michigan for their thoughtful input into the manuscript.
The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
Results of the pilot study were previously presented as an abstract at the United States & Canadian Academy of Pathology 2017 Annual Meeting; March 4–10, 2017; San Antonio, Texas.
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