Clinical, Morphological, and Molecular Study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma

Round 1

Reviewer 1 Report

The manuscript “Clinicopathological, Morphological and Molecular study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma” by Zhang et al. evaluates the clinicopathological, morphological, and especially molecular characteristics of grade 2 and 3 PXA respectively. However, some results disagreed with the reference #30; therefore, I would suggest authors may take a least a major revision of this work. Here are the comments and suggestions:

1.     Please extent the length of the introduction.

2.     What would be novelty of this work?

3.     Results in Fig. 4 disagreed with that in the reference #30, can authors add some comments on this issue.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

This topic is current and interesting, look at these points to improve the manuscript:

- "To more fully understand the biological characteristics in grade 2 and grade 3 PXA, we detected and compared the expression of conventional..." Please state at this point what is the aim of this paper.

- Methods. Case selection. Is this a retrospective or prospective study? State here.

- It seems that "Loss -10 p value 0.19" has a trend. What do authors think about this data? Discuss this.

- "There was no statistical difference in the overall survival of the cases with TERT promoter mutations compared with those without mutations" This point should also discuss in the conclusion section.

- In the discussion section: "Eosinophilic ranular bodies, perivascular lymphocytes, xanthic cells, muti-nucleated cells were histological features of classic PXA... Our results showed that with the upgrade tumor, the morphologic pleomorphism of tumor is gradually reduced..." Look at these important refs and discuss them: --  doi: 10.3390/genes13061054 -- doi: 10.1016/j.clineuro.2019.03.017 -- doi: 10.1016.44ee44

- "Our results suggested that CNS WHO grade 3 PXA is more prone to TERT gene alteration than grade 2 PXA" Add refs.

- "MGMT promoter methylation occurs in 40% of primary glioblastoma and is associated with increased survival after... [28]" Correct, but also "The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ" ref. doi: 10.3389/fonc.2022.969812  - Suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker.

- "CNS WHO grade remains a strong predictor of patient survival." What do author mean with this sentence.

- Improve conclusion. What did this paper find out?

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

The manuscript “Clinicopathological, Morphological and Molecular study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma” reports an interesting study on deep location, peritumoral edema, heterogeneous group of neoplasms, clinicopathological, histological, and molecular features of Grade 2 and 3 Pleomorphic xanthoastrocytoma (PXA). Results are not novel however, interesting for oncologists. I have some critical questions to be addressed by authors before considering for publication.

 

1.     Abstract: “Compared with grade 2, the grade 3 PXA has a deeper location and no superiority of temporal lobe, which is more likely to be accompanied by peritumoral edema, but the epilepsy symptoms are reduced.” In result and discussion part of the main text there is no information. Authors must include data for reduction in seizures, epilepsy and chronic headaches which are primary symptom of PXA patients.

2.     BRAF V600E analysis: “Amoy Diagnostucs Co.Ltd” should be Amoy Diagnostics Co. Ltd”.

3.     Statistical Analysis: “8 cases of all were lost to follow-up (case 29-34, case 52-53).” Authors must confirm that these lost subjects are used or not used for survival data analysis.

4.     Table 1: what is the significance of characterizing subjects in < 18 and > 18 years old age group?

5.     Figure 1: “Some cases showed eosinophilic granular bodies (Figure 1D-F). Non-palisading (focal) necrosis was only found in four grade 3 PXA cases.” Authors should label this in the corresponding figures.

6.     Table 2: “epitheliol cells” should be “Epithelial cells

7.     Page 9: “Our results showed that with the upgrade tumor, the morphologic pleomorphism of tumor is gradually reduced and tends to be monomorphic, which may be a predictor of histological progression.” What do author mean?

8.     Page 9: “our CDKN2A deletion rate is far lower than other reports.” Compared reports must be cited.

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

It seems more acceptable now.

Reviewer 2 Report

Good

Reviewer 3 Report

This version of the manuscript “Clinical, Morphological, and Molecular study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma” responses reviewers’ comments satisfactorily. I recommend for publication in present form.