Reviewer ’s report  
 
Title: A case of multicentric pancreatic mixed acinar -ductal carcinoma diagnosed by a yogurt -
like cell clump flowing from the papilla of Vater  
 
Version: 0 Date: 12 Jul 2016 
 
Reviewer:  Takashi  Muraki  
 
Reviewer’s report:  
 
This is a teaching case report of pancreatic poorly differentiated carcinoma with intra -ductal  
growth appearance. It is important to accumulate the cases showing not typical findings, 
especially in rare neoplasms. In this case, there were three uncommon features, which were 
presence of intra -ductal growth appearance, unusual pathological features, and multi -centric 
neoplasm. Although the authors focused on diagnosis by a yogurt -like cell clump flowing from 
the papilla of Vater, I believe more discussion about these features makes this report developing 
more.  
 
 
 There are some critiques as indicated wi th more detail in the following comments:  
 
Major Comments:  
 
I. Unusual pathological features  
 
1) Pathologically this lesions consisted of ductal formation. It seems to be ductal formation 
in Fig 2D. I feel like something is not quite right to diagnose as p oorly differentiated carcinoma. 
The diagnosis of "poorly differentiated" carcinoma is uncomfortable. It could be better to assess 
pathological findings, including immunohistochemistry again. This seems to be either acinar cell 
carcinomas (ACC) or neuroendo crine neoplasms (NET) pathologically. Because the rosettes are 
not around vascular cores but rather they seem to be true rosette formation (creating their own 
lumen -like structure), which speaks for ACC or NET. It could be better that the authors repeat 
immunohistochemistry for ACC and NET. Ki67 may also be helpful to ensure a low grade 
tumor.  
 
2) In "Case Presentation", it could be helpful to describe histopathological findings in more 
detail, such as those of background pancreatic parenchyma, pushing -border/infiltrated and so on.  
 
3) There were several difference features on the images between the body and tail lesions. 
Pathological difference was only presence of NET component?  
 
4) The authors mentioned that immunostaining of cytokeratin 19 was positive wit hin the 
neoplastic cells and progressed through the excretory ducts. Were there any ductal 
adenocarcinoma components in their neoplasms?  
 
II. Intra -ductal growth appearance  
 
1) In the literature, acinar cell carcinomas with prominent intraductal growth have  been 
shown to have more protracted clinical course, some surviving beyond 10 years. (Basturk O, 
Zamboni G, Klimstra DS, et al. Intraductal and papillary variants of acinar cell carcinomas: a 
new addition to the challenging differential diagnosis of intrad uctal neoplasms. Am J Surg 
Pathol. 2007;31:363 -370. Ban D, Shimada K, Sekine S, et al. Pancreatic ducts as an important 
route of tumor extension for acinar cell carcinoma of the pancreas. Am J Surg Pathol. 
2010;34:1025 -1036.)  
 
It could be helpful to descri be how prognosis of this case is at the present?  
 
 
III. Multicentric neoplasms  
 
1) Preoperative diagnosis for tail lesion was cystic lesion. How was on MRCP? MRCP 
shows high intensity signal on cystic lesions.  
 
2) It could be better to mention social historie s, including smoking and alcohol.  
 
 
Minor Comments:  
 
I. Unusual pathological features  
 
1) It could be helpful to show information about immunohistochemistry in more detail, 
including antibody source, clone and dilution.  
 
2) The authors described immunohistochemistry of CEA, CA19 -9 and MUC -1 in 
discussion. Were they all negative in this case? It could be better to describe them in "Case 
Presentation", also.  
 
3) Immunohistochemistry is very important for this case. It could b e better to show figures 
for the main immunohistochemistry for this case.  
 
 
II. Intra -ductal growth appearance  
 
1) The authors described that ERP demonstrated the crab -claw -like obstruction in the MPD. 
What features were on MRI, CT and EUS at this component?   
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Unable to assess  
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please expl ain 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 review is recommended, please specify what aspects require furthe r 
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:  
 
Acceptabl e 
 
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 a n 
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 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 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 accepted 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: A case of multicentric pancreatic mixed acinar -ductal carcinoma diagnosed by a yogurt -
like cell clump flowing from the papilla of Vater  
 
Version: 0 Date: 12 Jul 2016 
 
Reviewer:  Takashi  Muraki  
 
Reviewer’s report:  
 
This is a teaching case report of pancreatic poorly differentiated carcinoma with intra -ductal  
growth appearance. It is important to accumulate the cases showing not typical findings, 
especially in rare neoplasms. In this case, there were three uncommon features, which were 
presence of intra -ductal growth appearance, unusual pathological features, and multi -centric 
neoplasm. Although the authors focused on diagnosis by a yogurt -like cell clump flowing from 
the papilla of Vater, I believe more discussion about these features makes this report developing 
more.  
 
 
 There are some critiques as indicated wi th more detail in the following comments:  
 
Major Comments:  
 
I. Unusual pathological features  
 
1) Pathologically this lesions consisted of ductal formation. It seems to be ductal formation 
in Fig 2D. I feel like something is not quite right to diagnose as p oorly differentiated carcinoma. 
The diagnosis of "poorly differentiated" carcinoma is uncomfortable. It could be better to assess 
pathological findings, including immunohistochemistry again. This seems to be either acinar cell 
carcinomas (ACC) or neuroendo crine neoplasms (NET) pathologically. Because the rosettes are 
not around vascular cores but rather they seem to be true rosette formation (creating their own 
lumen -like structure), which speaks for ACC or NET. It could be better that the authors repeat 
immunohistochemistry for ACC and NET. Ki67 may also be helpful to ensure a low grade 
tumor.  
 
2) In "Case Presentation", it could be helpful to describe histopathological findings in more 
detail, such as those of background pancreatic parenchyma, pushing -border/infiltrated and so on.  
 
3) There were several difference features on the images between the body and tail lesions. 
Pathological difference was only presence of NET component?  
 
4) The authors mentioned that immunostaining of cytokeratin 19 was positive wit hin the 
neoplastic cells and progressed through the excretory ducts. Were there any ductal 
adenocarcinoma components in their neoplasms?  
 
II. Intra -ductal growth appearance  
 
1) In the literature, acinar cell carcinomas with prominent intraductal growth have  been 
shown to have more protracted clinical course, some surviving beyond 10 years. (Basturk O, 
Zamboni G, Klimstra DS, et al. Intraductal and papillary variants of acinar cell carcinomas: a 
new addition to the challenging differential diagnosis of intrad uctal neoplasms. Am J Surg 
Pathol. 2007;31:363 -370. Ban D, Shimada K, Sekine S, et al. Pancreatic ducts as an important 
route of tumor extension for acinar cell carcinoma of the pancreas. Am J Surg Pathol. 
2010;34:1025 -1036.)  
 
It could be helpful to descri be how prognosis of this case is at the present?  
 
 
III. Multicentric neoplasms  
 
1) Preoperative diagnosis for tail lesion was cystic lesion. How was on MRCP? MRCP 
shows high intensity signal on cystic lesions.  
 
2) It could be better to mention social historie s, including smoking and alcohol.  
 
 
Minor Comments:  
 
I. Unusual pathological features  
 
1) It could be helpful to show information about immunohistochemistry in more detail, 
including antibody source, clone and dilution.  
 
2) The authors described immunohistochemistry of CEA, CA19 -9 and MUC -1 in 
discussion. Were they all negative in this case? It could be better to describe them in "Case 
Presentation", also.  
 
3) Immunohistochemistry is very important for this case. It could b e better to show figures 
for the main immunohistochemistry for this case.  
 
 
II. Intra -ductal growth appearance  
 
1) The authors described that ERP demonstrated the crab -claw -like obstruction in the MPD. 
What features were on MRI, CT and EUS at this component?   
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Unable to assess  
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please expl ain 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 review is recommended, please specify what aspects require furthe r 
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:  
 
Acceptabl e 
 
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 a n 
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 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 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 accepted 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: A case of multicentric pancreatic mixed acinar -ductal carcinoma diagnosed by a yogurt -
like cell clump flowing from the papilla of Vater  
 
Version: 0 Date: 12 Jul 2016 
 
Reviewer:  Takashi  Muraki  
 
Reviewer’s report:  
 
This is a teaching case report of pancreatic poorly differentiated carcinoma with intra -ductal  
growth appearance. It is important to accumulate the cases showing not typical findings, 
especially in rare neoplasms. In this case, there were three uncommon features, which were 
presence of intra -ductal growth appearance, unusual pathological features, and multi -centric 
neoplasm. Although the authors focused on diagnosis by a yogurt -like cell clump flowing from 
the papilla of Vater, I believe more discussion about these features makes this report developing 
more.  
 
 
 There are some critiques as indicated wi th more detail in the following comments:  
 
Major Comments:  
 
I. Unusual pathological features  
 
1) Pathologically this lesions consisted of ductal formation. It seems to be ductal formation 
in Fig 2D. I feel like something is not quite right to diagnose as p oorly differentiated carcinoma. 
The diagnosis of "poorly differentiated" carcinoma is uncomfortable. It could be better to assess 
pathological findings, including immunohistochemistry again. This seems to be either acinar cell 
carcinomas (ACC) or neuroendo crine neoplasms (NET) pathologically. Because the rosettes are 
not around vascular cores but rather they seem to be true rosette formation (creating their own 
lumen -like structure), which speaks for ACC or NET. It could be better that the authors repeat 
immunohistochemistry for ACC and NET. Ki67 may also be helpful to ensure a low grade 
tumor.  
 
2) In "Case Presentation", it could be helpful to describe histopathological findings in more 
detail, such as those of background pancreatic parenchyma, pushing -border/infiltrated and so on.  
 
3) There were several difference features on the images between the body and tail lesions. 
Pathological difference was only presence of NET component?  
 
4) The authors mentioned that immunostaining of cytokeratin 19 was positive wit hin the 
neoplastic cells and progressed through the excretory ducts. Were there any ductal 
adenocarcinoma components in their neoplasms?  
 
II. Intra -ductal growth appearance  
 
1) In the literature, acinar cell carcinomas with prominent intraductal growth have  been 
shown to have more protracted clinical course, some surviving beyond 10 years. (Basturk O, 
Zamboni G, Klimstra DS, et al. Intraductal and papillary variants of acinar cell carcinomas: a 
new addition to the challenging differential diagnosis of intrad uctal neoplasms. Am J Surg 
Pathol. 2007;31:363 -370. Ban D, Shimada K, Sekine S, et al. Pancreatic ducts as an important 
route of tumor extension for acinar cell carcinoma of the pancreas. Am J Surg Pathol. 
2010;34:1025 -1036.)  
 
It could be helpful to descri be how prognosis of this case is at the present?  
 
 
III. Multicentric neoplasms  
 
1) Preoperative diagnosis for tail lesion was cystic lesion. How was on MRCP? MRCP 
shows high intensity signal on cystic lesions.  
 
2) It could be better to mention social historie s, including smoking and alcohol.  
 
 
Minor Comments:  
 
I. Unusual pathological features  
 
1) It could be helpful to show information about immunohistochemistry in more detail, 
including antibody source, clone and dilution.  
 
2) The authors described immunohistochemistry of CEA, CA19 -9 and MUC -1 in 
discussion. Were they all negative in this case? It could be better to describe them in "Case 
Presentation", also.  
 
3) Immunohistochemistry is very important for this case. It could b e better to show figures 
for the main immunohistochemistry for this case.  
 
 
II. Intra -ductal growth appearance  
 
1) The authors described that ERP demonstrated the crab -claw -like obstruction in the MPD. 
What features were on MRI, CT and EUS at this component?   
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Unable to assess  
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please expl ain 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 review is recommended, please specify what aspects require furthe r 
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:  
 
Acceptabl e 
 
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 a n 
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 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 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 accepted 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