Reviewer’s report
Title: 
First case of endometrial cancer after yolk sac tumor in a patient with Li-
Fraumeni Syndrome
Version: 
0 
Date: 
07 Jan 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
RELEVANCE - Does this case report make a contribution to medical
knowledge, have educational value, or highlight the need for a change in clinical
practice or diagnostic/prognostic approaches? 
Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to
understand the patient's symptoms and course of treatment? 
No - there are minor issues
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the
diagnosis, interpretation, and course of treatment medically sound?
Yes, the work described is medically sound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the
importance of the findings and their relevance to future understanding of disease
processes, diagnosis or treatment? Has an adequate literature review pertinent to
the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED
version of this work represent a technically sound contribution?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: This is an interesting unique case report of an
separate advance endometrial cancer after previous diagnosis of a yolk sac tumor
in a patient with Li-Fraumeni Syndrome a rare genetic condition. This
combination of cancers has not been previously reported in the literature to my
knowledge. The rapid evolution of endometrial cancer in this condition has not
been previously noted either attesting to the novelty of this report. The paper is
well written with adequate imaging and pathology slides included to support the
main text. 
A number of clarifications will still need to be made before the manuscript can
be considered for publication consideration as listed subsequently
REQUESTED REVISIONS: 
1. Please elaborate further on initial presentation of germ cell tumor in 2017: ?
Duration of symptoms, ?any previous gynecologic abnormalities, ?Any other
imaging abnormalities beside the large solid cystic mass in the right adnexa, 
?
Any abnormalities in blood markers besides the abnormality in AFP such as
CA125, LDH, BHCG
2. Line 65-6 : Please describe intraoperative findings. 
Any evidence of other
intra-abdominal abnormalities ? 
Any staging procedures such as washing,
omentectomy, or retroperitoneal nodal evaluation was performed
intraoperatively ?Was frozen section examination performed
3. Was there any imaging staging workup after surgery and the diagnosis of
germ cell tumour was made such as ?Chest CT ? PET
4. Line 66-67 : Please include AFP level at the time of diagnosis and during
chemotherapy to assess degree of response to treatment
5. Line 67-8 : Please outline follow-up protocol including frequency imaging
tests performed at the authors institution for ovarian germ cell tumors
6. Line 70-71 : Please clarify if patient had previous menstrual abnormalities
before this prolonged menstrual bleeding ?
7. Line 81 : Please clarify what is "Roman index" and how does this assist in the
diagnosis of this patient with endometrial cancer ?
8. Line 70-81 : It would be highly unusual for a 
moderately differentiated
endometrial cancer to present with extensive metastatic disease on imaging after
only 2 months of abnormal vaginal bleeding. 
Please clarify what was the exact
histology and grade of the tumor on hysteroscopic biopsy ? 
Was there any
attempt to biopsy nodal disease before patient was taken for extensive surgery to
rule out other potential primary tumors ?
9. What was the outcome of the open cytoreductive surgery ? 
What was the
amount/location of residual disease ? 
Please clarify exactly what surgical
procedures were performed intraoperatively ?
10. Line 93-94 : Patient receive adjuvant chemotherapy with bevacizumab,
carboplatin, and liposomal doxorubicin. 
Please confirm that this is a standard
chemo for advanced metastatic endometrial cancer at the authors institution or
was there a reason to choose this specific chemo combination ? 
The combination
of carboplatin and paclitaxel is a most commonly utilized chemotherapy regimen
for metastatic endometrial cancer.
11. Line 120-121 : Please describe the patient current follow-up protocol for
other cancers. 
What other screening tests are being offered ?
12. Can the authors comment on whether cascade genetic testing for other family
members of this patient is indicated with the strong family history ?
ADDITIONAL REQUESTS/SUGGESTIONS: 
no
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of appropriate controls), and are the conclusions supported by the evidence
presented?
No
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No
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Yes
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Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
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Yes
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