Peripancreatic Head Paraganglioma Versus Neuroendocrine Tumor: A Roller Coaster Diagnostic Dilemma in Fine Needle Aspiration Cytology Requiring a Note That “A Definite Diagnosis Cannot Be Concluded”

Comments 1: This paper describes the difficulty of differential diagnosis between NET and paraganglioma (PG). Both tumors consists of cells with synaptophysin positive, while S100 positive cells are included just in PG. If a clinician suspects of PG on radiolagical images and gives the information, the histopathological diagnosis of PG is not hard using S100 staining. Therefore, evaluating radiological images are very important for diagnosing PG. However, this report does not present any of radiological images, so readers learn nothing from this report. Moreover, the clinician dianosed the tumor as GIST. The authors should present radiological images in this study. 

Response 1:  Thank you for pointing this out. We agree with this comment. Therefore, we have added a radiology image. The changes made in the article as follows:

1.    “The peripancreatic lesion impose many differentials, these includes lymph node, leiomyoma, gastrointestinal stromal tumor, neuroendocrine tumor, paragangliomas and carcinomas. Fine needle aspiration of these lesions is always a diagnostic challenge for pathologist”. These lines are added in the introduction, Page 1, para1 and line #36 to 39

2.    The radiology images are added as figure 1. With a description as follows “Transaxial ⁶⁸Ga-DOTA PET/CT image show focal area of increased tracer uptake of SUV max 10.3 (black arrow) in the soft tissue nodule anterior to the pancreatic head measuring 2.1 cm (white arrow). Findings are consistent with somatostatin receptor avid soft tissue nodule in the upper abdomen adjacent to the pancreatic head”. These lines are added in page 2, line #77 to 80. Alos a radiology image is added.  

Kindly note that an updated manuscript has been uploaded with changes highlighted using red ink

Response to Reviewer 2 Comments

1. Summary

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in track changes in the re-submitted files.

Yes

Can be improved

Does the introduction provide sufficient background and include all relevant references?

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(x)

Is the research design appropriate?

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( )

Are the methods adequately described?

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( )

Are the results clearly presented?

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( )

Are the conclusions supported by the results?

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(x)

Yes

Can be improved

3. Point-by-point response to Comments and Suggestions for Authors

Comments 1: Dear Authors,

I have read your manuscript entitled <> with great interest.

I enjoyed reading the detailed report of the diagnostic decision making as evidences and data accumulated, thank you for sharing your experience.

I would like to invite you to expand a bit the discussion: as it stands it is a concise review of literature (of good value per se) but it misses the opportunity of reflecting on the presented clinical trial. I would like to read your thoughts on:
- would you have done anything different, had the needle cytology returned a more informative result?
- could you have requested (and would you recommend the reader does) any other test to reach the correct diagnosis before excision?

Response 1: Thank you for pointing this out.  We agree with this comment. Therefore, we have

Comments 2: since after all the excision recommendation appears to having been based on clinical criteria, would there have been value to knowing the correct diagnosis early on? Or what are the risks of misdiagnosing?

Response 2: Agree. We have, accordingly added and modified the artcle to inclued to emphasize this point.

1.    “The peripancreatic lesion impose many differentials, these includes lymph node, leiomyoma, gastrointestinal stromal tumor, neuroendocrine tumor, paragangliomas and carcinomas. Fine needle aspiration of these lesions is always a diagnostic challenge for pathologist”. These lines are added in the introduction, Page 1, para1 and line #36 to 39

2.       The radiology images are added as figure 1. With a description as follows “Transaxial ⁶⁸Ga-DOTA PET/CT image show focal area of increased tracer uptake of SUV max 10.3 (black arrow) in the soft tissue nodule anterior to the pancreatic head measuring 2.1 cm (white arrow). Findings are consistent with somatostatin receptor avid soft tissue nodule in the upper abdomen adjacent to the pancreatic head”. These lines are added in page 2, line #77 to 80. Alos a radiology image is added.  “[updated text in the manuscript if necessary]”

3.       “The loco-regional management in paragangliomas includes observation, surgical resection and radiation. Whereas management in NET is a multidisciplinary approach; with surgical resection is gold standard, followed by neoadjuvant therapy based on the resectabililty and stage. NET requires active patient surveillance.”

These lines are added in line #138 to 142,  for the management change and observation of the patient with paraganglioma and NETS

4.       “Palade et al[12] mentioned in their study that there is still a lot to debate on paragangliomas. They concluded that “the fact that they have a high rate of genetic inheritance has been proven, but clear correlations between gene mutation and the behavior of paragangliomas remain to be established. The lack of consensus among the practitioners regarding the necessity of surgery and the surgical approach is a result of the rarity of these tumors and the lack of experience in treating them. With the development of efficient conservative therapies, such as radiotherapy, proton therapy, and chemotherapy, studies should be carried on harmonizing all treatment methods and issue standardized guidelines”.”

These are thelines added regards the new clinical trials in line 148 to 156

4. Response to Comments on the Quality of English Language

Point 1: The manuscript presents several typos (e.g. line #34 "boarders" should be "borders"; line #74 "Authors" shouldn't be there) and a quick check would elevate the overall fruibility of the text

Response 1:  Have made necessary changes, Thank you so much

5. Additional clarifications

nil