The Role of Cytology in the Diagnosis of Metastatic Hepatocellular Carcinoma

Round 1

Reviewer 1 Report

In this study, Wang et al. reported that the cytology diagnosis could be a pivotal diagnostic method when histopathology fails. The topic of this study is important, and results are quite interesting. However, many claims in the manuscript lack strong support, as well as uncertain. I identified several major weaknesses in this manuscript. 1. This manuscript lacks the IHC results that mentioned, such as CK 7, CK 20, TTF-1, etc. Therefore, showing these data will be very helpful for the readers. 2. It would be very helpful to show abdominal echography images for patient #1 and #2. 3. It is not clear in Figure 2 that what panels belong to patient #1 or #2.

Author Response

Thank you for your kind review and comments.

Case reports or case series with their limited number of patients usually indeed work to initiate a small conclusion or a viewpoint which needs verification by subsequent studies with a larger number of patient cohort. This is just like a pilot study in a pre-clinical experimental trial.

Diagnosis of a metastatic hepatocellular carcinoma (HCC), to rare sites as in our work, must be established by morphologic confirmation. Traditionally, this work has been done mainly by histopathology with additional evidence of HCC-specific immunohistochemistry (IHC). However, the results of IHCs are ancillary as stated in the Discussion of our manuscript. Furthermore, since the quality of the biopsied samples in these two patients were poor with coexisting necrosis, showing the IHC data in these two patients might be of little help or even misleading to the readers. Therefore we would rather simply state than show the result of IHCs (such as CK 7, CK 20, TTF-1, etc).

We follow your comment to show the abdominal tomographic images (Figure 3) in Patient 1 to demonstrate progressive increase in tumor number in the liver and a new small lung nodule in anterior aspect of left lower lobe. However, we found it is very hard to so for Patient 2.

Finally, we follow your comment and add some amendment in the legend of Figure 2 to let the readers much more understand in that Figure 2 (a) and (b) belong to Patient 1 for bronchial brushing cytology and Figure 2 (c) and (d) belong to Patient 2 for fine needle aspiration cytology of cervical lymphadenopathy.

 

We wish our explanation could answer your comment.

Thank you!

Author Response File: Author Response.docx

Reviewer 2 Report

The authors showed two case reports of patients with metastatic hepatocellular carcinoma. Figure 1 shows a bronchoscopy of patient 1 and Figure 2 a bronchial brushing cytology and a fine needle aspiration cytology of patient 2. Could the authors also provide cytology figures for patient 1 and echography figures for patient 2 to provide complete datasets (figures) for both patients? 

Author Response

Thank you for your kind review and comments.

We follow your comment to show the abdominal tomographic images (Figure 3) in Patient 1 to demonstrate progressive increase in tumor number in the liver and a new small lung nodule in the anterior aspect of left lower lobe. However, we found it is very hard to so for Patient 2.

Cytologic figures for Patient 1 (bronchial brushing cytology) have been presented in Figure 2. To make the readers much more understand, we follow your comment and add some amendment in the legend of Figure 2 in that Figure 2 (a) and (b) belong to Patient 1 (bronchial brushing cytology) and Figure 2 (c) and (d) belong to Patient 2 (fine needle aspiration cytology of cervical lymphadenopathy).

 

 

We wish our explanation could answer your comment.

Thank you!

 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The revised version perfectly answered two of my questions. However, I still believe having the IHC data is the must for the manuscript to make a scientific unbiased conclusions. 

Author Response

Thank you very much again for your kind review and comment.

All of us, the authors, are clinicians not pathologists. All the pathologic reports of these two patients were made by our pathology colleagues. We believe that showing the IHC data in these two patients might be of little help or even blur the focus of this article because of the following reasons.

First, the quality of the biopsied samples in these two patients were poor with coexisting necrosis as in their pathologic reports, which will inevitably be subject to interpretation difficulty.

Second, our pathology colleagues have meticulously tried their best in interpretation particularly of the IHC data. We believe they have done their best in this issue. We trust and respect our pathology colleagues.

Third, the focus of our article stresses on the role of cytology rather than pathology in the diagnosis of metastatic hepatocellular carcinoma (HCC); showing the IHC data of these two patients might blur the focus of the article or even distract the attention of the readers.

And last but not least, the data of IHC play a role to help to answer some questions [please see Reference 3 in our manuscript p. 267 right column] in the diagnosis because the results of IHCs are in fact ancillary as stated in the “Discussion” of our manuscript [ibid. p. 266 right column] and not to mention to be able to make a scientific unbiased conclusions. After all, a close clinicopathologic correlation is mandatory for the final diagnosis in this scenario [ibid. p. 267 right column].

We wish our explanation could answer your comment and your concern.

Thank you.

 

Author Response File: Author Response.pdf

Round 3

Reviewer 1 Report

Showing the IHC data will further strengthen the manuscript.

Author Response

Dear Reviewer:

Thank you very much for your kind review and comment.

After thorough discussion with all the authors, we made a minor revision, an add-on Table 1, in our revised manuscript for the following reasons.

First, the quality of the biopsied samples in these two patients was poor due to coexisting tumor necrosis, which can hardly make scientific unbiased conclusions. Therefore, we put the status of all these sample specimens on the first column of Table 1 so that the readers can clearly understand at first what the situation of the pathologic studies stand and we believe Table 1 provides complete information of the IHCs and is much more persuasive than pathologic illustrations to the readers at first sight.

Second, it is the focus of this article to stress on the role of cytology rather than pathology in the diagnosis of metastatic hepatocellular carcinoma (HCC). Table 1 shows all IHCs what we have done, which consisted of so many items. Showing these IHC figures will not only blur the focus of the article but distract the attention of the readers. A summarized table of the IHC results (Table 1) we believe is a simple and explicit way to express better than too many unfocused IHC figures to the readers.

Third, the data of IHC in fact are ancillary as stated in the “Discussion” of our manuscript [Reference 3. p. 266]. After all, a close clinicopathologic correlation is mandatory for the final diagnosis in this scenario [ibid. p. 267] and we did have done it in the way in our preceding version of the revised manuscript.

Finally, we believe Table 1 provides not only the whole results of the IHC studies but convey the information no less than IHC figures, the latter might be subject to interpretation difference and scientific biased conclusions.

In summary, we provide an add-on Table 1 to summarize and show the results of all IHCs instead of the figures in our revised manuscript.

We wish our explanation will answer your comment and concern.

Thank you.

 

Author Response File: Author Response.pdf

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

As commented before, we occasionally experience the cases that cytology is useful for the diagnosis when histopathology fails to show the typical features of the disease. In those cases, clinical information is of course very useful and the disease should be correctly diagnosed using both pathological and clinical information. The current case report is not novel and does not seem to reach the quality for the publication as a case report. 

Reviewer 2 Report

I initially revised this paper and suggested rejection on the basis of low originality and low number of cases.  The authors replied that case reports or case series  usually initiate a small conclusion or a viewpoint which of
course awaits verification by subsequent studies with a larger patient cohort. 

I think that the Authors' response deserves further comment. I totally agree that case series can initiate a discussion and promote further studies. However, cytology and histology are often obtained together in clinical practice in difficult cases. So, I fail to see which novelties this case series might bring, as it basically endorses a practice already used in the routine practice. Also, in how many patients this double determination add diagnostic value? The Authors reported two cases, but amongst how many patients with HCC?
Consequently, I appreciate the Authors' response but I can not still recommend this paper for acceptance in Diagnostics.