A Review on Splenic Diffuse Red Pulp Small B-Cell Lymphoma

Round 1

Reviewer 1 Report

The 2017 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues places "splenic diffuse red pulp small B-cell lymphoma" (the topic of this review article) and "hairy cell leukemia variant" under the umbrella term, "Splenic B-cell lymphoma/leukemia, unclassifiable," by noting "the precise diagnostic criteria and most appropriate terminology for these provisional entities have not yet been fully established." 

Do authors believe that the precise diagnostic criteria have been established since? If so, they should spell of the diagnostic criteria of splenic diffuse red pulp small B-cell lymphoma. Is it only cyclin D3 expression? Which, by the way, is not available in most hematopathology services. Should we introduce this marker into our immuhistochemistry panel? Do authors have experience with this antibody? If yes, what about the cyclin D3-negative cases? Is the cyclin D3 stain reliable in tissue core biopsies?

Author Response

There are still no established diagnostic criteria for splenic diffuse red pulp small B-cell lymphoma (SDRPL), and it remains a diagnosis of exclusion. 2016 WHO classification describes major features that help differentiate SDRPL from SMZL, HCL and HCL-v. These features include diffuse splenic red pulp involvement, absence of follicular replacement, low level lymphocytosis, and absence of CD11c, CD25, CD103 and CD123 staining. Cyclin D3 expression is reported in majority of the SDRPL cases and could support the diagnosis of SDRPL cannot a be part of diagnostic criteria as its positivity is not universal.

Reviewer 2 Report

Dear authors,

this narrative review is very interesting and well-written.

The idea to unify a classical literature review and a case report is very cute and may help the reader very much. Moreover, the topic chosen is rare and so any comments/resumen/.... are desirable.

I have only some minor points/suggestions:

• I suggest to add some figures with CT, PET images of your patient. This could help the reader
• something more about the potential role of PET in evaluatin spelnic lymphoma could be add. is this rare disease FDG avid? SMZL?
• also in the table 1 something aboult imaging role needs to be write
• I don't understand very much the position in the text of the clinical vignette. I suggest to put this interesting case in the final part of the manuscript, immediately before the conclusion

Author Response

We have added two figures from another patient with SDRPL showing mild-moderate splenomegaly with increased FGD uptake in the spleen. (the patient in the case report unfortunately had PET/CT imaging done elsewhere and we do not have access to original PET/CT images).

We have moved the part 1 of the clinical vignette to the end, just before the part 2.

Reviewer 3 Report

Yilmaz Elif and colleagues' manuscript entitled "a review on splenic diffuse red pulp small B cell lymphoma." summarizes the epidemiological, clinical, morphological, immunophenotypic and molecular aspects that characterize this uncommon lymphoma recognized as a provisional entity in the 2008 update of the WHO Classification.

Comments
-The author should extend the introduction, better describing the main histotypes of primitive lymphomas of the spleen, according to the revised 2017 WHO classification.
-The authors could modify Figure 1 by adding some of the most useful immunohistochemical stains for the diagnosis, such as CD20, DBA.44, Bcl2, Ki67 etc.
-They could also add a panel with the most characteristic patterns (interstitial and sinusoidal pattern) of bone marrow infiltration.
-The table is non-flowing and challenging to read.

Author Response

We have added a few more sentences to the introduction and added a legend under the table 1 to explain the grading system.