Rare TERT Promoter Mutations Present in Benign and Malignant Cutaneous Vascular Tumors
, Georg Christian Lodde 1, Anne Zaremba 1, Carl Maximilian Thielmann 1, Johanna Matull 1, Hansgeorg Müller 2, Inga Möller 1, Antje Sucker 1, Stefan Esser 1, Jörg Schaller 3, Dirk Schadendorf 1, Thomas Mentzel 4, Eva Hadaschik 1 and Klaus Georg Griewank 1,5,*Round 1
Reviewer 1 Report
This article try to describe the incidence of TERT in benign and malignant vascular tumors ( according with its title ).
Unfortunately the cohort is represented by 19 angiosarcomas , 21 kaposi sarcomas and 64 vascular malformations. The term hemangioma has been wrongly used . In fact up to 18 so-called " hemangiomas " are carrying mutations in GNA14 , GNA11 and GNAQ. Those mutations are commonly found in capillary malformations and congenital hemangiomas .
As all patients are adults with a mean age of 53 years , none of the studied vascular tumors could eventually be a congenital hemangioma.
As JB Mulliken stated on his book Vascular Anomalies , “cherry” or “senile” hemangioma is a clinically unimportant lesion in adults that does not fit the definition of a tumor, and therefore he classified it in the group of telangiectasias. ISSVA continues to avoid consideration of cherry hemangiomas as tumors.
It is difficult to understand why infantile hemangiomas, tufted angiomas , kaposiform hemangioendotheliomas or congenital hemangiomas among other very common vascular tumors have not been used for this study. Specimens are easy to be obtained.
This reported research deserves a better pathological and clinical delineation of the tissues involved in the study .
Author Response
Please see the attachment
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Dear Editor, this is a well written manuscript, I enjoyed the reading! Authors analysed mutations in the promotor of the telomerase reverse transcriptase gene in cutaneous vascular tumors. This mutations are rare (<10%) and do not differ between benign and malign vascular lesions. Other mutations were also analysed: GNA14 and 11 as GNAQ mutations were only found in hemangiomas, but not in vascular malformations, angiosarcomas or Kaposi sarcoma. This is the first work analysing TERT mutaions in benign and maligne vascular tumors and merits publication.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Reviewer 3 Report
Dear Authors,
thank you for uploading this manuscript. The manuscript is well written, however presents only negative results. You're clarly showing no correlation between analyzed neoplasms and TERT promoter mutations. There is no information wheter all the tumors are primary one or metastatic (in case of malignant ones). The additional histopathological and clinical data regarding tumor size, the metastasis status (in case of malignant tumors), introduced therapy etc would improve your manuscript. Were there any differences in histopathological or clinical aspects of wild types and "mutated" tumors? Additional figure with HE stained tumors would be a good addition to this manuscript.
Also in the Conclusion paragraph in extremely short, please elaborate.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
We suggest the cohort of patients being redefined with the most commonly diagnosed vascular tumors and malformations in order to be of increasing interest for vascular anomalies experts and patients community.
Reviewer 3 Report
Dear Authors,
thank you for uploading the revised version of manuscript and explaining all the inaccuracies. I have no further comments.
