Reviewer ’s report  
 
Title: Clinicopathologic and endoscopic features of early -stage colorectal serrated 
adenocarcinoma  
 
Version: 0 Date: 28 Jul 2017  
 
Reviewer: Oscar W. Cummings  
 
Reviewer's report:  
 
The authors reviewed their experience with early stage serrated adenocarcinomas of the 
colorectum.  This is a relatively recently recognized, poorly characterized su bcategory of colon 
cancer that is associated with a non -APC primary pathway of molecular carcinogenesis. They 
had 15 cases of putative T1 carcinomas. They correlated histomorphology with clinical 
parameters and suggest that these tumors are more aggressive  than conventional colorectal 
adenocarcinoma.  The paper is very well written and would be of interest to surgical pathologists 
and gastroenterologists.  
 
Comments  
1. Materials and methods section needs to be expanded.  Please add the initials of the review ing 
pathologists.  The paragraph states that the criteria of the WHO fascicle were employed for 
the diagnosis of serrated adenocarcinoma. However, the WHO fascicle does not provide any 
diagnostic criteria; it only describes some features that have been att ributed to this condition. 
It should be clear how these cancers were distinguished from other similar carcinomas 
including mucinous carcinoma and medullary carcinoma. Some of the histologic features 
associated with serrated adenocarcinoma are elaborated in  the following sentence and a 
reference should be added to support these statements.  Table 7 also elaborates a number of 
histologic criteria that are not spelled out in the materials and methods including: SM 
invasion depth measurements, tumor budding, an d scoring for vascular invasion. At a 
minimum, references should be given for each of these assessments.  
2. The terminology in the paper is somewhat confusing. Table 6 lists "serrated morphology" as 
a category that was not present in all cases. Table 7 lis ts "serrated morphology" and "serrated 
component". I think one category refers to the presence or absence of a classic serrated polyp 
(TSA, SSA/P or HP) associated with the carcinoma and the other category refers to serrated 
carcinoma features such trabecu lar growth or lack of tumor necrosis, but I'm not entirely 
sure. Obviously each lesion must have one or both of these features to be included in the 
study. It would help to clarify these points in the legend or the results sections.  
3. I am aware there are  differences in histologic interpretation between pathologists from 
different countries. I can only use my frame of reference for interpreting the images 
submitted in the manuscript. I mean no offense by the following comments. Figure 1 shows a 
serrated ad enoma/polyp. The quality of the image available to me is not optimal but at most 
it appears to show low grade cytologic dysplasia in an SSA/P, not in situ adenocarcinoma. 
Figure 2 is likewise less than optimal. I cannot see cytologic details of the mucosal  lesion. 
The mucosal lesion appears to push into the submucosa recapitulating an inverted growth 
pattern. There is no stromal reaction in the submucosa and therefore no submucosal invasion. 
See your reference 18 for examples of lesions I would consider T1 adenocarcinomas. That 
being said, it is difficult to interpret the significance of the information put forth in this 
report.  
Are the methods  appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclu sions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical rev iew is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain  or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the fut ure? 
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of  the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that i have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is acce pted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons .org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Clinicopathologic and endoscopic features of early -stage colorectal serrated 
adenocarcinoma  
 
Version: 0 Date: 28 Jul 2017  
 
Reviewer: Oscar W. Cummings  
 
Reviewer's report:  
 
The authors reviewed their experience with early stage serrated adenocarcinomas of the 
colorectum.  This is a relatively recently recognized, poorly characterized su bcategory of colon 
cancer that is associated with a non -APC primary pathway of molecular carcinogenesis. They 
had 15 cases of putative T1 carcinomas. They correlated histomorphology with clinical 
parameters and suggest that these tumors are more aggressive  than conventional colorectal 
adenocarcinoma.  The paper is very well written and would be of interest to surgical pathologists 
and gastroenterologists.  
 
Comments  
1. Materials and methods section needs to be expanded.  Please add the initials of the review ing 
pathologists.  The paragraph states that the criteria of the WHO fascicle were employed for 
the diagnosis of serrated adenocarcinoma. However, the WHO fascicle does not provide any 
diagnostic criteria; it only describes some features that have been att ributed to this condition. 
It should be clear how these cancers were distinguished from other similar carcinomas 
including mucinous carcinoma and medullary carcinoma. Some of the histologic features 
associated with serrated adenocarcinoma are elaborated in  the following sentence and a 
reference should be added to support these statements.  Table 7 also elaborates a number of 
histologic criteria that are not spelled out in the materials and methods including: SM 
invasion depth measurements, tumor budding, an d scoring for vascular invasion. At a 
minimum, references should be given for each of these assessments.  
2. The terminology in the paper is somewhat confusing. Table 6 lists "serrated morphology" as 
a category that was not present in all cases. Table 7 lis ts "serrated morphology" and "serrated 
component". I think one category refers to the presence or absence of a classic serrated polyp 
(TSA, SSA/P or HP) associated with the carcinoma and the other category refers to serrated 
carcinoma features such trabecu lar growth or lack of tumor necrosis, but I'm not entirely 
sure. Obviously each lesion must have one or both of these features to be included in the 
study. It would help to clarify these points in the legend or the results sections.  
3. I am aware there are  differences in histologic interpretation between pathologists from 
different countries. I can only use my frame of reference for interpreting the images 
submitted in the manuscript. I mean no offense by the following comments. Figure 1 shows a 
serrated ad enoma/polyp. The quality of the image available to me is not optimal but at most 
it appears to show low grade cytologic dysplasia in an SSA/P, not in situ adenocarcinoma. 
Figure 2 is likewise less than optimal. I cannot see cytologic details of the mucosal  lesion. 
The mucosal lesion appears to push into the submucosa recapitulating an inverted growth 
pattern. There is no stromal reaction in the submucosa and therefore no submucosal invasion. 
See your reference 18 for examples of lesions I would consider T1 adenocarcinomas. That 
being said, it is difficult to interpret the significance of the information put forth in this 
report.  
Are the methods  appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclu sions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical rev iew is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain  or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the fut ure? 
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of  the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that i have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is acce pted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons .org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Clinicopathologic and endoscopic features of early -stage colorectal serrated 
adenocarcinoma  
 
Version: 0 Date: 28 Jul 2017  
 
Reviewer: Oscar W. Cummings  
 
Reviewer's report:  
 
The authors reviewed their experience with early stage serrated adenocarcinomas of the 
colorectum.  This is a relatively recently recognized, poorly characterized su bcategory of colon 
cancer that is associated with a non -APC primary pathway of molecular carcinogenesis. They 
had 15 cases of putative T1 carcinomas. They correlated histomorphology with clinical 
parameters and suggest that these tumors are more aggressive  than conventional colorectal 
adenocarcinoma.  The paper is very well written and would be of interest to surgical pathologists 
and gastroenterologists.  
 
Comments  
1. Materials and methods section needs to be expanded.  Please add the initials of the review ing 
pathologists.  The paragraph states that the criteria of the WHO fascicle were employed for 
the diagnosis of serrated adenocarcinoma. However, the WHO fascicle does not provide any 
diagnostic criteria; it only describes some features that have been att ributed to this condition. 
It should be clear how these cancers were distinguished from other similar carcinomas 
including mucinous carcinoma and medullary carcinoma. Some of the histologic features 
associated with serrated adenocarcinoma are elaborated in  the following sentence and a 
reference should be added to support these statements.  Table 7 also elaborates a number of 
histologic criteria that are not spelled out in the materials and methods including: SM 
invasion depth measurements, tumor budding, an d scoring for vascular invasion. At a 
minimum, references should be given for each of these assessments.  
2. The terminology in the paper is somewhat confusing. Table 6 lists "serrated morphology" as 
a category that was not present in all cases. Table 7 lis ts "serrated morphology" and "serrated 
component". I think one category refers to the presence or absence of a classic serrated polyp 
(TSA, SSA/P or HP) associated with the carcinoma and the other category refers to serrated 
carcinoma features such trabecu lar growth or lack of tumor necrosis, but I'm not entirely 
sure. Obviously each lesion must have one or both of these features to be included in the 
study. It would help to clarify these points in the legend or the results sections.  
3. I am aware there are  differences in histologic interpretation between pathologists from 
different countries. I can only use my frame of reference for interpreting the images 
submitted in the manuscript. I mean no offense by the following comments. Figure 1 shows a 
serrated ad enoma/polyp. The quality of the image available to me is not optimal but at most 
it appears to show low grade cytologic dysplasia in an SSA/P, not in situ adenocarcinoma. 
Figure 2 is likewise less than optimal. I cannot see cytologic details of the mucosal  lesion. 
The mucosal lesion appears to push into the submucosa recapitulating an inverted growth 
pattern. There is no stromal reaction in the submucosa and therefore no submucosal invasion. 
See your reference 18 for examples of lesions I would consider T1 adenocarcinomas. That 
being said, it is difficult to interpret the significance of the information put forth in this 
report.  
Are the methods  appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclu sions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical rev iew is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain  or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the fut ure? 
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of  the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that i have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is acce pted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons .org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant