Primary Co-Occurrence of Gonadal and Extragonadal Central Nervous System (CNS) Germ Cell Tumors (GCTs): Case Report and Review of the Literature

Round 1

Reviewer 1 Report

The manuscript by Francesco Tengattini and co-authors presents the case report and literature review of co-occurrence of gonadal and extra-gonadal central nervous system germ cell tumors. The manuscript provides excellent coverage of relatively rare co-occurrence of the two types of germ cell tumors and identifies a patient out of 29 patients with such presentation. In my opinion, the manuscript is well written and adds valuable information in this field.

A few minor points which need clarification are following:

1) The literature search dates indicated in lines 29--31 are different from those mentioned in lines 90–91.

2) Figures 1 and 2 are not annotated properly and it is not clear what area of the scan is being referred to in the text.

3) Line 74 indicates that patient consent was obtained, however, line 362 indicates that informed consent was not applicable.

Minor English editing is needed.

Author Response

Thank you for your suggestions. The corrrections have been done. Regarding the second point i also added red arrows to better explain the images.

Reviewer 2 Report

In this case report the authors described a case of metachronous co-occurrence of a primary CNS NGGCT in a 34-year-old patient with a known testicular NGGCT. Some concerns and suggestions are listed as below:

The authors should mention why this case is novel in the part of introduction since some similar cases have been reported previously.

The part of Materials and Methods can be removed. Just focus on the description of this case. More information can be discussed in the part of discussion.

His medical history was positive for a left testicular NGGCT. MRI scans at the very beginning should be provided.

In Figure 1, I can see the A, while B and C are lacking. MRI scans during follow-up should also be provided.

Apart from germ cell tumors, other potential diagnosis should also be considered and discussed. 

Any pathological picture results to support the diagnosis in this case?

Why genetic test was not performed in this case?

fine

Author Response

Thank for your suggestions. Please find below the replies to your comments:

1) The part about the importance of describing this case has been added to the manuscript in the introductive section

2) Thank you for your comment. However, we would like to keep the paragraph to provide a better understanding of the procedures and approach to study search and data collection and analysis. We believe this is very important to establish the study quality.

3) Unfortunately, the testicular MRI scan from diagnosis are not available. In fact, the patient was treated for testicular NGGCT 16 years before the brain NGGCT in another hospital and no images are available from that time.

4) The letters A,B,C have been added in the images. Two-year follow up images are shown in Figure 2.

5) Other potential diagnosis have been considered and discussed in the paper in the presentation of the institutional case 

6) Unfortunately histopathology images are not available.

7) The patient refused to undergo the genetic test despite medical advice. The following sentence has been added to the manuscript “Despite medical advice, the patient and his family did not undergo any genetic analysis to investigate cancer predisposition”.

Reviewer 3 Report

The article submitted by Tengattini et al. is related to an institutional case report of a primary testicular NGGCT and extragonadal CNS GCTs compared to 6 other cases found in the literature through a careful bibliographic investigation. Taking into account the limited number of existing cases, the review is very interesting.

I found a discrepancy (to be corrected) between the date reported in the abstract relating to the first literary search carried out (September 8, 2023) with update on December 10, 2023 compared to that indicated in chapter 2.2., page. 2 line 91, which instead indicates March 2, 2023 with update on July 8, 2023.

Furthermore, several abbreviations are missing (to be inserted if the Editor deems appropriate) regarding the molecular pathways involved in the pathogenesis of the rare pathological condition under study. Finally, some acronyms seem incorrect to me, such as KI67, which is generally referred to as Ki67, MTOR, which is reported as mTOR, as well as mdm2, which is generally written as MDM2.

Author Response

Thank you for the suggestions. The correction have been done. 

Round 2

Reviewer 2 Report

No further comments

fine