Reviewer ’s report  
 
Title: Microscopic features of small bowel mucosa of patients with Crohn ’s disease  
 
Version: 1 Date: 29 Oct 2019  
 
Reviewer: HJ Van Kruiningen  
 
Reviewer's report:  
 
In their response to me the authors say that detailed morphologic description of granulomatous 
lymphangitis "have not been well illustrated yet". This statement is simply false, as the papers by 
Sura and me well illustrate the granulomatous  lymphangitis. Furthermore the idea that 
"histologic characteristics of Crohn's disease are non -specific characteristics", expressed in the 
paper, is also false. Pathologists all over the world recognize that non -tb granulomas plus 
obstructed lymphatics eq uals Crohn's disease. Analyzing 19 other microscopic findings doesn't 
make better diagnosis. Counting all these fine points and then subjecting them to statistical 
analysis doesn't improve our understanding. It represents trivial pursuits, i.e., not import ant for 
any pathologist to know or care about. I presume the authors aim is to have pathologists check 
each of 21 boxes, and then achieve a meaningful score, for example 7 or 8 rather than 3 or 4; 
some cut -off point. That's absurd; a pathologist will have to interpret granulomas and lymphatic 
obstruction, plus edema and fibrosis. These are qualitative decisions, not quantitative.I appreciate 
that the authors agree with our works showing that granulomatous obstruction of lymphatics, 
elephantiasis, is the bas ic lesion in Crohn's disease, but all these other counted elements detract 
from the message. I suggest that the authors select 4 or 5 morphologic features that have real 
meaning and rewrite the paper; less is more!  
 
 
Throughout the paper the authors speak of  "on" the mucosa, when they mean "in" the mucosa. 
And they have not given adequate recognition that CD is not a mucosal disease, but rather 
submucosal and muscular. 68% of granulomas are not in the mucosa. Perhaps they can take 
some of their findings here and compare them to findings in resection specimens. To say that "A 
dense network of lymphocytes, histiocytes, and macrophages" causes obstruction is incorrect. 
The granuloma arises from damaged endothelium and fills or partly fills the lymphatic lumen. 
Lymphocytes there and in other lymphatics are passive, being caught upstream of the granuloma. 
Rather than speak of compacted macrophages, simply call them granulomas. It appears there 
were two forms of granulomatous lymphangitis, not many as inferred in the  paper:obstructed and 
partially obstructed.  
 
 
The photos are too numerous, made from sections that were too thick and most are out of focus. 
The white backgrounds are not white. Some if the images are too dark and all are not clear.   
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions 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 th e manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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, f ees, funding, or salary from an 
organisati on that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscrip t, either now or in the future?  
 
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 co mpeting 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 Acc ess Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understa nd that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
Reviewer ’s report  
 
Title: Microscopic features of small bowel mucosa of patients with Crohn ’s disease  
 
Version: 1 Date: 29 Oct 2019  
 
Reviewer: HJ Van Kruiningen  
 
Reviewer's report:  
 
In their response to me the authors say that detailed morphologic description of granulomatous 
lymphangitis "have not been well illustrated yet". This statement is simply false, as the papers by 
Sura and me well illustrate the granulomatous  lymphangitis. Furthermore the idea that 
"histologic characteristics of Crohn's disease are non -specific characteristics", expressed in the 
paper, is also false. Pathologists all over the world recognize that non -tb granulomas plus 
obstructed lymphatics eq uals Crohn's disease. Analyzing 19 other microscopic findings doesn't 
make better diagnosis. Counting all these fine points and then subjecting them to statistical 
analysis doesn't improve our understanding. It represents trivial pursuits, i.e., not import ant for 
any pathologist to know or care about. I presume the authors aim is to have pathologists check 
each of 21 boxes, and then achieve a meaningful score, for example 7 or 8 rather than 3 or 4; 
some cut -off point. That's absurd; a pathologist will have to interpret granulomas and lymphatic 
obstruction, plus edema and fibrosis. These are qualitative decisions, not quantitative.I appreciate 
that the authors agree with our works showing that granulomatous obstruction of lymphatics, 
elephantiasis, is the bas ic lesion in Crohn's disease, but all these other counted elements detract 
from the message. I suggest that the authors select 4 or 5 morphologic features that have real 
meaning and rewrite the paper; less is more!  
 
 
Throughout the paper the authors speak of  "on" the mucosa, when they mean "in" the mucosa. 
And they have not given adequate recognition that CD is not a mucosal disease, but rather 
submucosal and muscular. 68% of granulomas are not in the mucosa. Perhaps they can take 
some of their findings here and compare them to findings in resection specimens. To say that "A 
dense network of lymphocytes, histiocytes, and macrophages" causes obstruction is incorrect. 
The granuloma arises from damaged endothelium and fills or partly fills the lymphatic lumen. 
Lymphocytes there and in other lymphatics are passive, being caught upstream of the granuloma. 
Rather than speak of compacted macrophages, simply call them granulomas. It appears there 
were two forms of granulomatous lymphangitis, not many as inferred in the  paper:obstructed and 
partially obstructed.  
 
 
The photos are too numerous, made from sections that were too thick and most are out of focus. 
The white backgrounds are not white. Some if the images are too dark and all are not clear.   
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions 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 th e manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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, f ees, funding, or salary from an 
organisati on that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscrip t, either now or in the future?  
 
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 co mpeting 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 Acc ess Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understa nd that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, 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: Microscopic features of small bowel mucosa of patients with Crohn ’s disease  
 
Version: 1 Date: 29 Oct 2019  
 
Reviewer: HJ Van Kruiningen  
 
Reviewer's report:  
 
In their response to me the authors say that detailed morphologic description of granulomatous 
lymphangitis "have not been well illustrated yet". This statement is simply false, as the papers by 
Sura and me well illustrate the granulomatous  lymphangitis. Furthermore the idea that 
"histologic characteristics of Crohn's disease are non -specific characteristics", expressed in the 
paper, is also false. Pathologists all over the world recognize that non -tb granulomas plus 
obstructed lymphatics eq uals Crohn's disease. Analyzing 19 other microscopic findings doesn't 
make better diagnosis. Counting all these fine points and then subjecting them to statistical 
analysis doesn't improve our understanding. It represents trivial pursuits, i.e., not import ant for 
any pathologist to know or care about. I presume the authors aim is to have pathologists check 
each of 21 boxes, and then achieve a meaningful score, for example 7 or 8 rather than 3 or 4; 
some cut -off point. That's absurd; a pathologist will have to interpret granulomas and lymphatic 
obstruction, plus edema and fibrosis. These are qualitative decisions, not quantitative.I appreciate 
that the authors agree with our works showing that granulomatous obstruction of lymphatics, 
elephantiasis, is the bas ic lesion in Crohn's disease, but all these other counted elements detract 
from the message. I suggest that the authors select 4 or 5 morphologic features that have real 
meaning and rewrite the paper; less is more!  
 
 
Throughout the paper the authors speak of  "on" the mucosa, when they mean "in" the mucosa. 
And they have not given adequate recognition that CD is not a mucosal disease, but rather 
submucosal and muscular. 68% of granulomas are not in the mucosa. Perhaps they can take 
some of their findings here and compare them to findings in resection specimens. To say that "A 
dense network of lymphocytes, histiocytes, and macrophages" causes obstruction is incorrect. 
The granuloma arises from damaged endothelium and fills or partly fills the lymphatic lumen. 
Lymphocytes there and in other lymphatics are passive, being caught upstream of the granuloma. 
Rather than speak of compacted macrophages, simply call them granulomas. It appears there 
were two forms of granulomatous lymphangitis, not many as inferred in the  paper:obstructed and 
partially obstructed.  
 
 
The photos are too numerous, made from sections that were too thick and most are out of focus. 
The white backgrounds are not white. Some if the images are too dark and all are not clear.   
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions 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 th e manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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, f ees, funding, or salary from an 
organisati on that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscrip t, either now or in the future?  
 
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 co mpeting 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 Acc ess Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understa nd that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
 
assistant