Cytology and Histology of Thyroid Nodules: Exploring Novel Insights in the Molecular Era for Enhanced Patient Management

Round 1

Reviewer 1 Report

I enjoyed reading, very informative, no issues detected. The only minor mistake: on page 3 paragraph B) HTT is once misspelled as HHT.

The authors gave a thorough report on the novelties of WHO and TBSRTC classifications, explained the differences, problems and intentions of these classifications, they put in in a historical and regional context where appropriate. Especially the relevant newly classified entities are explained in detail. Furthermore the authors reviewed the concept of ROM The topic original or relevant in the field. Both above mentioned classifications are not so easy to understand especially for clinicians not familiar with histological/cytological and molecular testing issues. As the classifications have impact on the therapeutic strategies (conservative vs. surgical) it is of interest for all dealing with thyroid nodules/tumors. To the best of my knowledge there are no recent publications on this term so far. Very appropriate as the authors focussed to the most important publications and included even not-yet published material (3rd edition BSRTC) The authors choose very impressive images as for histology as for cytology, something I miss in the most publications to this theme. Tables are conclusive So in general I regard this paper as one of the best I reviewed so far, very straightforward and conclusive, therefore my comment/review was very short in order to warrant rapid publication.

 

Author Response

Thanks a lot for your very positive and comprehensive review

Typing error has been modified 

Best regards

Reviewer 2 Report

Outstanding paper widely but concisely picturing the recent evolutions of thyroid cancer histology and cytology classifications. It clearly emerges the high expertise of the authors in such fields, so I have no major concerns.

To further improve the paper, I would suggest authors to build an exhaustive figure highlighting the correspondence between cytology categories (as updated in the upcoming Bethesda) and the WHO 2022 schematized thyroid tumors. Something like a diagram flux.

Similarly, I suggest to introduce a specific Table dedicated to the WHO 2022 schematized thyroid tumors and the corresponding molecular alterations.

Finally, I suggest to expand the little paragraph dedicated to molecular analysis, better addressing the role of specific mutations for the diagnostic and prognostic setting. In this context, I would better focus the actual diagnostic value of BRAF, RAS, and TERT mutations in cytology specimens, with particular mention to the meaning of RAS mutations in the Bethesda III category and also in the Bethesa II  (Marotta V, Bifulco M, Vitale M. Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer. Cancers (Basel). 2021 Jul 27;13(15):3785. doi: 10.3390/cancers13153785. PMID: 34359686; PMCID: PMC8345070; Puzziello A, Guerra A, Murino A, Izzo G, Carrano M, Angrisani E, Zeppa P, Marotta V, Faggiano A, Vitale M. Benign thyroid nodules with RAS mutation grow faster. Clin Endocrinol (Oxf). 2015 Aug 11. doi: 10.1111/cen.12875. [Epub ahead of print] PubMed PMID: 26260959.).

 

 

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Author Response

Thanks a lot for all your comments I agree with all of them !  

You have asked for some more discussion about the molecular testings. These tests have recently offered a better knowledge of the thyroid tumors .....but I also agree with you that their results do not resolve all the diagnostic dilemna for the best management of the patients who very often would like to keep their thyroid gland .......with a zero ROM !!! Therefore we have included a short comment at the end of the paragraph concerning the molecular markers and mentionned the excellent manuscript of Marotta et al; we haven't added a diagram for the molecular tests combined with the indeterminate cytological results because we should include all the existing tests (very complex) or reproduce some existing published algorithms and we cannot because of  copyright; but as you have seen we have mentionned the manuscript of the very recent SFE consensus available on Pubmed ( ref 14); furthermore we are limited by the editor for the number of words and we already have exceeded the number ...

Again thanks a lot for your review