Radiological and Pathological Features of Cyst Formation in Idiopathic Multicentric Castleman Disease

Round 1

Reviewer 1 Report

This is a very interesting description of 8 cases of a rare form of Castelman disease presenting as interstitial lung disease, very nicely analyzed from a radiological and pathological point of view, and offering an interesting hypothesis regarding the mechanism of cyst formation.

As some of the cases were diagnosed in the early 2000, did the clinic have access at that time to HRCT? It is described that all CT scans were performed with thin slices. Was this after excluding some cases in which HRCT was not available, or was it possible to re-analyze the images with a more modern technology?

In Table 1, please add units for Rheumatoid factor.

Figure 5 is displaced and image D is not visible. You might re-place the 4 images, 2 in a row.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

This study provides valuable insights into the radiological and pathological features of cyst formation in idiopathic multicentric Castleman disease (MCD) patients. The authors performed a thorough analysis of eight cases, which were well-characterized and described in detail. The findings suggest that cysts in MCD may form due to the loss of elastic fibers resulting from marked plasma cell infiltration and are likely irreversible changes.

The strength of this study lies in its clear presentation of the data and findings, as well as the detailed descriptions of radiological and pathological features. The authors also provide a convincing explanation for the formation of cysts and their potential irreversibility.

However, there are some limitations to the study that should be addressed. The sample size is relatively small, which may limit the generalizability of the findings. Additionally, the retrospective nature of the study may introduce potential biases. Future research should aim to corroborate these findings in larger, prospective cohorts, and explore potential therapeutic interventions to mitigate or reverse cyst formation in MCD patients.

In conclusion, this study offers valuable information about the radiological and pathological features of cyst formation in idiopathic multicentric Castleman disease patients. The results may aid clinicians in understanding the underlying mechanisms of cyst formation and inform future research on potential therapeutic interventions.

The introduction provides a concise background on multicentric Castleman disease (MCD), a rare polyclonal lymphoproliferative disease of unknown etiology. The authors highlight the distinction between two subtypes of MCD: human herpesvirus-8-associated MCD and idiopathic MCD. They mention that the radiological features of diffuse lung disease in idiopathic MCD are not well-understood due to the rarity of the condition. Previous studies have reported interlobular septal thickening, multiple centrilobular nodules, and thin-walled cysts as characteristic findings in idiopathic MCD. However, the authors emphasize that the radiological and pathological features of cystic formation in MCD remain unclear.

The introduction effectively establishes the research gap by emphasizing the limited understanding of radiological and pathological features of cystic formation in MCD. The authors present a clear research question, which is to investigate these features in idiopathic MCD patients at their hospital.

Overall, the introduction is well-structured, concise, and effectively sets the stage for the study. The language is clear and technical terms are properly explained. The authors could potentially strengthen the introduction by briefly mentioning the clinical implications of understanding the radiological and pathological features of cystic formation in MCD patients. However, this is a minor point and does not detract from the overall quality of the introduction.

The Materials and Methods section of this study is well-structured and provides a clear description of the methods used to collect and analyze data. The authors detail their patient selection process, data collection from medical records, and the international diagnostic criteria used for diagnosing idiopathic MCD. The process for evaluating radiological and pathological findings is outlined, including the use of high-resolution computed tomography (HRCT) and the assessment of histological sections from surgical lung biopsy specimens. The authors also describe their method for the semiquantitative grading of pathological features. Lastly, the authors briefly mention the statistical analysis and presentation of the data.

Strengths of this section include the precise description of the patient selection process, diagnostic criteria, and the evaluation of radiological and pathological findings. The authors also provide a thorough explanation of the semiquantitative grading system for pathological features.

However, there are some areas where the authors could provide more information or clarification:

The study design could be more explicitly stated as a retrospective analysis at the beginning of the section.

The sample size should be mentioned in this section for clarity.

The statistical analysis section is quite brief and could benefit from more detail regarding the specific statistical tests used to analyze the data and the criteria for determining statistical significance.

Overall, the Materials and Methods section is well-written and provides a clear and detailed description of the study's methodology. With some minor improvements, this section will better support the study's findings and conclusions.

In the Discussion section, the authors summarize their study findings and highlight three key points: (1) the presence of ground-glass attenuation (GGA) around cysts in idiopathic MCD and the emergence of new cysts from the GGA area, (2) the pathological evaluation revealing a high degree of plasma cell infiltration and loss of elastic fibers of the alveolar wall around the cyst wall, and (3) the persistence of cysts despite treatment, suggesting that cystic lesions in MCD are irreversible changes. The authors propose that the loss of elastic fibers may be an important factor in cyst formation, and they emphasize the importance of early therapeutic intervention for MCD.

Strengths of this section include a clear presentation of the main findings and the proposal of a possible mechanism for cyst formation in idiopathic MCD. The authors also acknowledge the limitations of their study, including the small sample size, retrospective design, and single-institution setting, as well as the lack of pathological evaluation of cysts in all patients.

To improve the Discussion and Conclusion sections, the authors should consider the following:

Compare and contrast their findings with existing literature to provide context and support for their conclusions. Discussing how their study adds to or differs from previous research can strengthen their argument and highlight the study's contributions to the field.

Offer suggestions for future research, such as potential avenues for further investigation, targeted therapies, or preventive measures that could be explored based on their findings.

Consider providing a more detailed explanation of the clinical implications of their findings, including potential impacts on patient management, prognosis, and treatment strategies.

By addressing these points, the authors can provide a more comprehensive discussion of their study's implications and further support their conclusions. Overall, the Discussion and Conclusion sections are well-structured and effectively summarize the study's findings, but additional context and elaboration on the implications of their research will enhance the overall impact of the paper.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors answered all my comments and suggestions. 

I have nothing else to add.