How to Diagnose and Treat CD5-Positive Lymphomas Involving the Spleen

Round 1

Reviewer 1 Report

This is a well written interesting review paper.

The following are comments the authors:

Lines 104-106 and 403-406:

Percent prolymphocytes in CLL/SLL do not indicate a diagnosis of B-Prolymphocytic leukemia (B-PLL) in the new 2017 WHO; this is considered “prolymphocytoid transformation”. CLL/SLL excludes that diagnosis. B-PLL is now controversial and many hematopathologists do not believe B-PLL exists as an exclusive entity. I would modify or remove these sentences.

Lines 425-427:

LPL is not the only small B cell lymphoma to show both cytoplasmic and membrane light chains. We do not routinely look for cytoplasmic staining but will look if surface light chains are absent. There is no technical issue when looking for cytoplasmic light chains.

Figures 1-3 are indicated but not present.

Author Response

COMMENT 1

Lines 104-106 and 403-406. Percent prolymphocytes in CLL/SLL do not indicate a diagnosis of B prolymphocytic leukemia (B-PLL) in the new 2017 WHO; this is considered prolymphocytoid transformation”. CLL/SLL excludes that diagnosis. B-PLL is now controversial and many hematologists do not believe B-PLL exists as an exclusive entity. I would modify or remove these sentences.

REPLY We thank the reviewer to raise this important point. We agree that B-PLL is a now controversial entity and that an increase in the percentage of prolymphocytes should be called prolymphocytoid transformation in CLL/SLL. We corrected the sentence as suggested (lines 115-117, 418 and 430). We also reviewed section 4.1 on B-PLL accordingly.

COMMENT 2

Lines 425-427. LPL is not the only small B cell lymphoma to show both cytoplasmic and membrane light chains. We do not routinely look for cytoplasmic staining but will look if surface light chains are absent. There is no technical issue when looking for cytoplasmic light chains.

REPLY

Again we are grateful to the reviewer for this comment, with which we agree.  As such, we eliminated the comment on cytoplasmic light chains from section 4.2 on lymphoplasmacytic lymphoma (line 454)

COMMENT  3

Figures 1-3 are indicated but not present

REPLY

We regret that the three figures attached to the original submissoin, were not sent to the reviewer. They are now included in the paper, as well as a table summarizing the main differential diagnosis of CD5-positive lymphomas infiltrating the spleen (pages 4, 8 and 11).

Reviewer 2 Report

The paper by Cabecadas et al. is an interesting narrative review about CD5-positive lymphoma involving the spleen. The topic is surely of clinical interest and a challenge for the clinicians. The idea of the authors is brilliant and the structure of paper is nice. To start with a clinical vignette is fashonable and the subsequent path is logical and clear.

I have a problem with the figures because I didn't find them in the manuscript file. Is it normal?

I have only some comments:

• some parts are very long and I suggest to reduce to help the reader;
• nothing about the diangostic role of PET, CT, MRI in this field is described. Please add a short paragraph about this point. The spleen can be an interesting challenge nucelar medicine physician and radiologists.
• Is it possible to resume in a table/figure the main results of your review. This could help very much

Author Response

Comment 1

Some parts are very long  and I suggest to reduce to help the reader

REPLY

We are very grateful for this suggestion, that we adopted. We thoroughly reviewed and edited the text, eliminating redundancy to improve clarity. We also adopted section numbering and added bullet points in the conclusion, as suggested.

COMMENT 2

Nothing about the diagnostic role of PET, CT, MRI in this field is described. Please add a short paragraph about this point. The spleen can be an interesting challenge for nuclear medicine physicians and radiologists.

REPLY

We agree that this is a very relevant topic for the subject. We added a paragraph discussing the main issues concerning the interpretation of the spleen morphology by imaging methods in the Introduction section (page 2, lines 67-76)

COMMENT 3

Is it possible to resume in a table/figure the main results of your review? This could help very much.

REPLY

We again fully agree with the comment. The table summarizing the main differential diagnosis of CD5-positive lymphomas infiltrating the spleen, attached to the original submission, is now included in pages 11-12.