Successful Multimodal Treatment of Intracranial Growing Teratoma Syndrome with Malignant Features

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors present a nice case of a mature teratoma which was definitively treated after initial management for a suspected germ cell tumor. The authors describe the steps in management and the diagnostic process with a detailed explanation of the genetic mutations of the tumor. The authors present the case very nicely and their decision making was clearly described and seemed sound. The report will be of interest to the readership in the neurosurgical literature due the high rate of misdiagnosis with these lesions. I commend the authors for the thoroughness and clarity of their work. Revisions may include a more in depth look at the downstream mechanism of the mutated genes identified and a review of what they could have done differently for the management of their patient. These are minor given the quality of the work. Nicely done. 

Author Response

We thank the reviewer for very positive comments. We have made minor changes to the manuscript based on his/her suggestions.

The authors present a nice case of a mature teratoma which was definitively treated after initial management for a suspected germ cell tumor. The authors describe the steps in management and the diagnostic process with a detailed explanation of the genetic mutations of the tumor. The authors present the case very nicely and their decision making was clearly described and seemed sound. The report will be of interest to the readership in the neurosurgical literature due the high rate of misdiagnosis with these lesions. I commend the authors for the thoroughness and clarity of their work.

We thank the reviewer for constructive comments.

Revisions may include a more in depth look at the downstream mechanism of the mutated genes identified and a review of what they could have done differently for the management of their patient. These are minor given the quality of the work. Nicely done. 

We thank the reviewer for raising an important point. We have now added speculation as to how DMRT1 loss impacts teratoma formation (lines 263-269) and 12p gain in malignant transformation of germ cell tumors (lines 273-278) in the Discussion section. We have also added a discussion on the possibility of more aggressive initial surgery or more intensive chemotherapy in the present case (lines 296-304).

Reviewer 2 Report

Comments and Suggestions for Authors

The authors present an intriguing case report detailing the multimodal management of intracranial growing teratoma syndrome. Furthermore, they provide compelling data regarding the tumor's methylation profile, DMRT1 loss, and 12p gain, which potentially elucidate the mechanisms underlying the growth and malignant transformation of the teratoma. This data informed the authors' decision to pursue intensive chemoradiation treatment for this high-risk germ cell tumor.

The authors deserve commendation for their meticulous analysis. The paper is well-written, with data presented clearly. I would like to offer the following minor observations for consideration:

• Initially, the authors performed only a biopsy of the lesion during the first surgery, which is understandable. However, it's worth noting that a biopsy only captures a small portion of the tumor. If teratomatous tumor components were identified in the initial specimens, would this have prompted the authors to consider altering the multimodal approach?

  Some sentences could benefit from improvement in terms of English usage. For instance, in line 37-38, the sentence structure is awkward, and a verb appears to be missing

Author Response

The authors present an intriguing case report detailing the multimodal management of intracranial growing teratoma syndrome. Furthermore, they provide compelling data regarding the tumor's methylation profile, DMRT1 loss, and 12p gain, which potentially elucidate the mechanisms underlying the growth and malignant transformation of the teratoma. This data informed the authors' decision to pursue intensive chemoradiation treatment for this high-risk germ cell tumor.

The authors deserve commendation for their meticulous analysis. The paper is well-written, with data presented clearly. I would like to offer the following minor observations for consideration:

We thank the reviewer for the positive comments.

• Initially, the authors performed only a biopsy of the lesion during the first surgery, which is understandable. However, it's worth noting that a biopsy only captures a small portion of the tumor. If teratomatous tumor components were identified in the initial specimens, would this have prompted the authors to consider altering the multimodal approach?

We thank the reviewer for raising some important points. As the reviewer correctly points out, the initial biopsy only captured a small portion of the tumor. However, we were able to discover an AFP-positive, embryonal carcinoma-like component during the initial biopsy. However, serum AFP was initially negative, so it was difficult to determine that a more intensive chemotherapeutic regimen may be necessary to shrink the tumor. We have added this issue to the discussion section (lines 296-304).

Some sentences could benefit from improvement in terms of English usage. For instance, in line 37-38, the sentence structure is awkward, and a verb appears to be missing

We thank the author for pointing out the grammatical error. We have now changed the sentence to “Growing teratoma syndrome is a rare condition in which paradoxical growth of a mature teratoma occurs during treatment for mixed malignant germ cell tumor, despite normalization of tumor markers.” We have also carefully looked over the entire manuscript again, and have made some minor edits.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed all concerns and I would like to support publication of the revised manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript could be accepted in the present form