Gastrointestinal Granular Cell Tumor: The First Report of a Multifocal and Potentially Hereditary Case

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Sigon et al., described a case report of a patient with multifocal gastrointestinal granular cell tumors (GCTs) and suggested a potential hereditary component based on the detection of GCT in the patient’s 12-year-old daughter.

 

The case report is interesting and clinically relevant, but it is not well described and focused. The authors provided with a lot of information about the current knowledge about GCTs but only marginally focused on the clinical aspects of the patient and the patient’s daughter.

 

Major comments:

It would be very important for the authors to include information about patient's GCTs immunochemistry. For example, is the patient positive for S-100, CD56, CD68, SOX-10? More information is also warranted for the patient’s daughter.

 

Material and Methods and Ethical consent are missing.

 

Minor comments:

Please add the scale bar in the Figures and use proper annotation for each panel.

 

Author Response

Dear Reviewer,

thank You very much for Your precise evaluation.

In the revised version of the manuscript, we created a new paragraph with the description of matherials and methods, also underlying the Ethical consent provided by the patient.

We also included a more complete description about immunohistochemistry both in the patient and her daughter and added the scale bar in the figures, as requested.

Best regards

 

Reviewer 2 Report

Comments and Suggestions for Authors  

 

 

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

thank You very much for Your positive evaluation. 

In the revised version of the manuscript we provided a better description of our conclusions

Reviewer 3 Report

Comments and Suggestions for Authors

This report is basically a case study of an unusual and as authors state, novel presentation of Abrikossof granuloma cell tumor, first detected in the esophagus but later found elsewhere in the GI tract.  The study is simple, the data sufficient and interpreted correctly.  The finding of a tongue tumor in the daughter leads to a speculation of hereditary / genetic origin which could not be previously proposed. There is the possibility to determine this for the lack of mutations of the ATP6 genes which may be pivotal for the GCT development. This was not pursued in the daughter and is a minor deficit of the study. On line 165 the term ‘lonely driver’ is used but needs clarification.   A few notable typos are found, eg histopathologic line 38.  Also the formatting of the text needs to be altered as spacing is often incorrect.   

Comments on the Quality of English Language

few minor changes needed

Author Response

Dear Reviewer,

thank You very much for Your complete evaluation.

In the revised version of the manuscript we clarified the term "lonely driver" (line 165) simply refers to a driver mutation, which could be at the basis of a new GCT.

The evaluation of the daughter was unfortunately not possibile due to parents' will, so we do not have this data. 

We also corrected the typos you described and reformatted empty spaces. 

Best regards 

Reviewer 4 Report

Comments and Suggestions for Authors

The Title and Abstract summarize the main aspect of the work.

The Introduction contains literature data regarding gastrointestinal granular tumors.

The Methods described by this study are clear.

The Results are clearly presented but with some important observations.

                Main observation: no histological and/or immunohistochemical images were provided for the authors, for esophageal, and colonic subepithelial lesions, and also for the daughter of the patient. Although the authors presented a very interesting case of association of esophageal granular cell tumor with diffuse colonic granular tumors and pathology results were mentioned in the paper, the lack of the corresponding pathology image may affect the quality of the presentation of the current case report.

Observation 2: the details regarding the number and the technique of biopsies from esophageal and colonic lesions may help to increase the accuracy of the presentation.

 

In the Discussions section of the paper, the authors analyzed the current literature data regarding gastrointestinal granular tumors, mostly case reports. The prevalence, macroscopic and microscopic characteristics of GGT, the potential for malignancy, and current pathogenic data were discussed.

The Conclusions are clear.

Comments on the Quality of English Language

Minor adjustments of the language are needed: in Line 38 “histopathological” instead of “istopathological”, also in Conclusions “benign” instead of “bening” and “esophagus” instead of “esofagus”. Other minor adjustments were noted. 

Author Response

Dear Reviewer, 

thank You very much for Your complete evaluation.

In our revised version we better described the number and type of biopsies taken from esophageal and colonic lesions.

Regarding Your main observation "no histological and/or immunohistochemical images were provided for the authors, for esophageal, and colonic subepithelial lesions, and also for the daughter of the patient", we unfortunately do not have this data at the moment. We will ask help to our Pathological Anathomy Unit to provide this information, if they will be able. 

We also provided to correct the typos You mentioned.

Best regards

Reviewer 5 Report

Comments and Suggestions for Authors

In current manuscript, Campigotto and co-workers documented the case of one patient with panenteric gastrointestinal GCTs while also suggesting a potential hereditary component, due to the concomitant diagnosis of a tongue GCT affecting the patient’s daughter. As mentioned in the manuscript, there is no specific clinical or endoscopic guidelines exist to deal with these rare tumors so this kind of case report will be beneficial for researcher. The reviewer recommend this article for the publication after minor revision.

 

Comments:

1.       In current case report, author has documented for the one patient. However, if author could provide few more cases that can provide more insight of this rare tumors.

2.       Author believes that GCTs are a potential hereditary component. Did author has any preliminary data to support this?

3.       Can author provide the some information regarding what are the treatments has given to patient?

Author Response

Dear Reviewer,

thank You very much for Your complete evaluation.

Comment number 1 "In current case report, author has documented for the one patient. However, if author could provide few more cases that can provide more insight of this rare tumors."

Reply number 1: We further review scientific literature but we could not find more supportive elements. In particular, no other cases of multifocal or potentially inherited GCTs or case reports describind different genes involved were found.

Comment number 2 "Author believes that GCTs are a potential hereditary component. Did author has any preliminary data to support this?"

Reply number 2: in the revised version of the manuscript, we better described the potential hereditary component was hypothised according to the same istological and immunohistochemical data. We unfortunately still have no data about the genetic evaluation which was proposed to the patient and will take several months.

Comment 3: Can author provide the some information regarding what are the treatments has given to patient

Reply number 3: In the revised version of the manuscript, we underlined that our unfortunately there is no a specific therapy to be administered to our patient. We described our proposal was a deep, regular follow-up both in the patient and in her daughter, pending genetic evaluation.

Best regards

Reviewer 6 Report

Comments and Suggestions for Authors

Good choice of images for this very interesting case report. It is a long discussion, but it can be condensed.

Comments on the Quality of English Language

In an interesting case, the long discussion can be condensed.

 

Author Response

Dear Reviewer,

thank You very much for Your kind evaluation.

In our revised version, we tried to shorten the discussion. However, such a complicated and intriguing case deserves a thorugh description.

Best regards

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed the major concerns previously raised.

Comments on the Quality of English Language

English is fine.

Reviewer 4 Report

Comments and Suggestions for Authors

The authors stated that currently no histological and/or immunohistochemical images are available. Although histological images may be important in order to increase the quality of the presentation, in cases where multiple medical facilities are involved in patient care, it is sometimes very difficult to obtain full data for such rare cases.