The Value of Fine Needle Aspiration Biopsy in the Pre-Operative Assessment of the Axilla in Breast Cancer Patients
Round 1
Reviewer 1 Report
This is a comprehensive review by Raymond W and Kleinig P on the role of FNAC of axillary lymph nodes in the pre-operative approach of breast cancer patients. It is not the first review to be published on the issue after the Z0011 trial, but it is the first in several years to thoroughly revisit the subject and correctly surmises the most recent literature. The images, radiological and cytological, as well as illustrations are clear, practical and hold value for any practicing cytologist. The text is clear and concise, and conclusions are valid and derived from the reviewed literature. The topic is interesting, clinically important, and adds to the available management strategies to axillary lymph nodes in breast cancer patients. Furthermore, it highlights the capabilities of FNAC in this setting, which is of increasing importance in the age of minimally invasive medicine.
There are a few minor points which may be improved, however.
Overall, I would recommend a minor proof-read for small mistakes. Of note, in lines 40 and 41, I believe a verb may be missing. On line 90, "sited" should be replaced with "seated". On lines 106 through 108, it is not immediately clear why the cytopathologist brings the mentioned advantages to the procedure, until ROSE is mentioned in the following sentence. On line 200, there is a problem with the figure legend ("epiTable 200" - please correct).
On line 120, a reference appears to be missing.
On line 70, pathology readers might appreciate a brief explanation of "Tissue Harmonic", a term they might not be familiar with.
On line 257 and in other parts of the paper, the authors mention it is easier to perform IHC in CNBs, but also that this may be done in cellblocks. Although a thorough visit to this topic is clearly outside the scope of this paper, given that this is an important topic when discussing FNACs of breast carcinomas, perhaps the authors would like to elaborate a bit more.
The authors compare FNACs to core needle biopsies. Even though it is an invasive method and in a different branch of the algorithmic approach to the axilla, perhaps a very brief discussion of sentinel lymph node biopsy is warranted.
In the clinical utility section (line 285 onwards) and conclusions (line 324 onwards), the authors discuss the role of axillary lymph node FNAC in pre-operative staging of breast cancer patients and its possible impact on patient management. The literature is not consensual, however, and approaches vary between centers. Given the undeniable advantages of FNAC, and its known limitations, what should, in the authors' opinion, be the focus of future research? Should guidelines for FNAC use in this setting (with imaging correlation) be written up, and validated prospectively? Could this enable wider adoption of the technique? Please comment.
Author Response
Thank you for your review and suggestions to improve our paper. We have corrected the minor errors in the text on lines 40, 90 (deep seated), 106, and 200, rewriting a few sentences to clarify meaning. A whole line of the Fig 9 legend on line 200 was somehow lost in the transfer to the final proof as this was correct in my version. This has been corrected.
On line 120 there was no reference to the comment on experience of pathologists as this is essentially based on personal experience.
We have included an explanation of the "Tissue Harmonic setting" for US (line 71).
We have slightly elaborated on the use of IHC but do agree a detailed discussion is outside the scope of the paper as it is not generally performed in the setting of axillary FNAB to confirm metastatic disease (line 283).
We have defined sentinel lymph node biopsy (line 164) but as this is a complex and essentially surgical topic, with difference in technique in different centres and countries, we believe further discussion is beyond the scope of this paper.
Regarding the comment about future research we have included an extra paragraph at the end of the discussion incorporating an additional Figure (Fig 15, Flow Chart) to highlight the focus of future research.
Reviewer 2 Report
Excellent review of this topic.
Suggest that the authors might consider creating and presenting in this paper an algorithm as a diagram regarding the use of FNAB of axillary lymph nodes to embody the discussions section description of usage.
In the figure legends 'DQ' is used and is a brand name. IF DiffQuik was used, then need to state manufacturer and where based/manufactured. If not, then use 'Giemsa stain', not DQ.
The term 'FNAC' has been superseded internationally by 'FNAB' for fine needle aspiration biopsy. Suggest changing throughout. Similarly, 'clusters' and 'aggregates' when describing epithelial tissue fragments/metastases have been superseded internationally by 'tissue fragments'. Suggest changing throughout. 'Aggregates' are elements/cells that have come together rather than existed in the body as actual tissue eg. inflammatory cell aggregates. Lymphoid germinal centres are also 'germinal centre tissue fragments'.
The IAC Yokohama Reporting System for Breast FNAB Cytopathology, that has attracted considerable international research and publications, recommends and is supported by an article reviewing and recommending FNAB of axilla. The synergies with FNAB of clinically or US suspicious axillary lymph nodes in women with breast lesions undergoing FNAB (or CNB) are huge, and worth referencing in this updating and detailed article.
Figure 9(a) legend does not make sense. Please review.
Author Response
Thank you for your review and suggestions to improve our manuscript. We have included a flow chart (as Figure 15) for preoperative management of the Axilla to clarify usage of FNAB.
DiffQuik staining was used and the abbreviation and manufacturer details have been stated (in Fig 4).
We have replaced the term FNAC with FNAB (although this has not been tracked) and included the term "tissue fragments" where applicable for the cytology descriptions in the figures.
The reference article (Gibbons et al, 2019) in the IAC Yokohama Reporting System text, supporting the use of FNAB in the axilla has been included. I am not sure why this did not come up in my literature search, but I agree is a valuable reference. Additional references have been added (ref 25 and 26), cited in the text at lines 161 and 337.
A whole line of the Fig 9 legend on line 200 was somehow lost in the transfer to the final proof as this was correct in my version. This has been corrected.
Reviewer 3 Report
This is an excellent manuscript. The following paper should be added in the references: J Clin Oncol 2002 20(5):1304-10. Rouzier R et al. PMID: 11870173
Author Response
Thank you for your review and suggestion. We have included this interesting article in our references (ref 39).
