Spinal Manifestation of Malignant Primary (PLB) and Secondary Bone Lymphoma (SLB)

Round 1

Reviewer 1 Report

Barz et al. provide a review of a series of lymphoma cases involving the spine. It provides a useful source of data on this subject for future reference, as there is not much in the existing literature. It is my understanding that the presented work is one of the larger ones, if not the largest. Therefore, it should be considered for possible publication; however, there are quite a few points to improve this manuscript in an attempt to make it more valuable to the readership, as follows and in no particular order:

• I am not clear on what is meant by "indolent lymphoma". Does it mean incidentally-identified? Low-grade? If so, what type?, etc... Please clarify.
• More of an editorial point on the part of typesetting, but there appears to be some inconsistencies in the way the references have been cited; e.g., some names with commas, some not, etc.
• It appears that the incidence of primary bone lymphoma is higher in the spine relative to the secondary bone lymphoma than that cited in general. Is this because the secondary cases do not always come to attention or diagnosed definitively in this location? Or, because not every spinal lesion in a case of systemic lymphoma is biopsied? Or, is there another explanation?
• I understand that there are a few papers on this subject; however, could the authors comment on this specifically to explain whether this type of investigation has been published before, the number of cases included in the previous papers, their findings and how this particular study differs from the existing ones? What were the types of lymphomas identified in them? In other words, what does this study add to the current literature?
• Even though 2013 WHO Classification has been mentioned (line 54), no reference citation was associated with it. In addition, the most recent (and current) WHO classification is the 2017 Revised 4th edition. Please make the appropriate corrections. 
• In such retrospective studies, it is important to review the pathologic diagnoses to ensure their uniformity and accuracy, as well as update any diagnoses that may have been made according to previously-published guidelines. I take it that this has not been done, as I do not see a pathologist's name in in the author line-up.
• Likewise, it may enrich the manuscript, expand the interest and readership, and make this work more informative if some images for representative of the major pathological findings and radiologic images are included.
• "SINS" should be spelled out at its first use in the text.
• Could the authors also comment on any effect that spine involvement may have on the general prognosis of these patients, whether primary or secondary? In other words, is it important to investigate for spine involvement in lymphoma patients besides the neurological disfunction or the discomfort this involvement cases?

 

Author Response

Dear Reviewer, Dear Editor,

Thank you very much for the stimulating criticisms. They have been answered as best as possible in the following and have been incorporated into the manuscript accordingly. We hope that we have done this to your satisfaction.

 

Reviewer 1

Barz et al. provide a review of a series of lymphoma cases involving the spine. It provides a useful source of data on this subject for future reference, as there is not much in the existing literature. It is my understanding that the presented work is one of the larger ones, if not the largest. Therefore, it should be considered for possible publication; however, there are quite a few points to improve this manuscript in an attempt to make it more valuable to the readership, as follows and in no particular order:

• I am not clear on what is meant by "indolent lymphoma". Does it mean incidentally-identified? Low-grade? If so, what type?, etc... Please clarify.

Thank you very much for your comment. We have designated low-grade lymphomas as such. It includes the following groups in our study: follicular lymphoma, mantle cell lymphoma and marginal zone lymphoma. We corrected table 5.

• More of an editorial point on the part of typesetting, but there appears to be some inconsistencies in the way the references have been cited; e.g., some names with commas, some not, etc.

Thank you for pointing that out, you are right. We have had the manuscript and references checked and corrected again by a professional proofreader.

• It appears that the incidence of primary bone lymphoma is higher in the spine relative to the secondary bone lymphoma than that cited in general. Is this because the secondary cases do not always come to attention or diagnosed definitively in this location? Or, because not every spinal lesion in a case of systemic lymphoma is biopsied? Or, is there another explanation?

Thank you for the comment. We of course mainly treat patients complaining of severe back pain and/or neurological deficits. This might be the reason for this distribution of primary and secondary lymphomas. We have added this in the discussion section.

• I understand that there are a few papers on this subject; however, could the authors comment on this specifically to explain whether this type of investigation has been published before, the number of cases included in the previous papers, their findings and how this particular study differs from the existing ones? What were the types of lymphomas identified in them? In other words, what does this study add to the current literature?

Thank you for the comment. There are a few publications however more common on conservative treatment of spinal lymphoma. On the one hand, we have a larger group of different lymphomas and can show that patients with neurological deficits do benefit from surgical treatment when followed by adjuvant therapy. We have added this in the discussion section.

• Even though 2013 WHO Classification has been mentioned (line 54), no reference citation was associated with it. In addition, the most recent (and current) WHO classification is the 2017 Revised 4th edition. Please make the appropriate corrections. 

Thank you for the comment. We have corrected it.

• In such retrospective studies, it is important to review the pathologic diagnoses to ensure their uniformity and accuracy, as well as update any diagnoses that may have been made according to previously-published guidelines. I take it that this has not been done, as I do not see a pathologist's name in in the author line-up.

Thank you for the comment. You are absolutely right, of course, the diagnoses are also made by neuropathologists. We have changed this accordingly and added our neuropathologist in charge.

• Likewise, it may enrich the manuscript, expand the interest and readership, and make this work more informative if some images for representative of the major pathological findings and radiologic images are included.

Thank you very much for your advice. We have added this and hope to be able to further enhance the manuscript.

 

 

• "SINS" should be spelled out at its first use in the text.

Thank you for the comment. We have corrected it accordingly.

• Could the authors also comment on any effect that spine involvement may have on the general prognosis of these patients, whether primary or secondary? In other words, is it important to investigate for spine involvement in lymphoma patients besides the neurological disfunction or the discomfort this involvement cases?

Thank you for the comment. Since lymphoma is radiosensitive and chemosensitive, no recommendation for an extension of the guidelines according to your comment can be made at the current time or based on this study. However, based on our study we can say that in case of neurological deficits surgical treatment followed by adjuvant therapy seems to be reasonable. Nevertheless, to address your question, we have searched the current literature for possible prognostic factors and added this to the discussion section.

 

Author Response File: Author Response.docx

Reviewer 2 Report

This is an interpreting but retrospective analysis on a very rare extra nodal lymphoma. Results are interesting and really useful for clinical practice.

The only point to modify is the inappropriate use of 'metastatic' (line 173) term in the last sentence of the paper. The concept of metastasis is inappropriate in lymphoma disease or any other haematological disease.

Author Response

Dear Reviewer, Dear Editor,

Thank you very much for the stimulating criticisms. They have been answered as best as possible in the following and have been incorporated into the manuscript accordingly. We hope that we have done this to your satisfaction.

 

 

Reviewer 2

 

This is an interpreting but retrospective analysis on a very rare extra nodal lymphoma. Results are interesting and really useful for clinical practice.

The only point to modify is the inappropriate use of 'metastatic' (line 173) term in the last sentence of the paper. The concept of metastasis is inappropriate in lymphoma disease or any other haematological disease.

Thank you very much for this nice comment. We have of course implemented your correction request directly.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Thank you very much for the additional effort to address the raised questions.