Kidney Failure and Abdominal Discomfort as Initial Signs of Extramedullary Acute Myelogenous Leukemia
Round 1
Reviewer 1 Report
The case report concerns a young woman who developed renal failure and abdominal discomfort. The symptoms turned out to be a consequence of AML. The patient was correctly diagnosed only after developing full blown leukemia.
I have no comments as to the presentation and description of the case report, it is well prepared.
Throughout the article, I miss a comment on the prognosis - is it worse in the case of such manifestation of symptoms? Are patients with such syndrome particularly at higher risk of relapse/death.
The language is good, article is easy to read. Minor spell check is needed.
The appearance of the publication citation should be changed, though. If a given paragraph is described on the basis of one article, there is no need to cite it after each sentence, e.g. page 1, lines 34-36, page 2, lines 42-43, page 7, and lines 152-157.
I recommend your manuscript for publication in Journal of Clinical Medicine after minor spell check and aforementioned changes.
Author Response
We are grateful for the mainly positive comments from reviewer 1 regarding our present manuscript. The alterations suggested have helped us to improve our manuscript.
Regarding the prognosis of extramedullary manifestations in AML, this is a topic of considerable discussion, and given the rarity of the manifestations, this it not straightforward. A detail discussion regarding prognosis with of extramedullary manifestations falls without the scope of this paper. However, we have in short discussed the possible role of extramedullary disease, and potential therapeutic cand prognostic implications.
We agree in the comments regarding citation and references, and accordingly we have change this.
Again, the manuscript is thoroughly proofread, and minor alterations are performed.
Reviewer 2 Report
The manuscript by Steinfeld et al. nicely summarises an interesting case report on an extramedullary manifestation of AML leading to acute kidney injury. The delay in diagnosing the AML is critical and such a report can sharpen everyone’s awareness for rare causes of postrenal obstruction.
Is the headline “Material and Methods” adequate for a case report? The manuscript is currently divided into introduction, material and methods and discussion. Is this specified by the journal?
In line 157 the authors state that “diagnosis was delayed because tumor obstruction was not initially a suspected cause” but do not comment on whether the tumor masses were already present on the initial CT or even ultrasonography but merely overlooked.
The diagnosis of AML in bone marrow is described cytogenetically (inversion 16) and the diagnosis in the myeloid sarcoma describes the FAB subtype. Were there differences between the AML cells in bone marrow compared to those in the solid tumor? Especially concerning differentiation of the blasts and immunophenotype?
Figure 5 shows post-treatment PET-CT in A and then pre-treatment PET-CT in B. Please change the order or delete the pretreatment figure (pre-treatment PET-CT images are already shown in Figure 2).
In Line 193 authors state that “Metabolic imaging utilizing FDG-PET/CT substantially contributes to the diagnosis and treatment of different types of leukemia” while only citing a single reference. While it is true, that PET-CT/PET-MRI imaging has become standard of care in diseases such as Hodgkin’s lymphoma, it is not a routine method in leukemia. The benefit in extramedullary manifestations of acute leukemia seems obvious, but systematic data is still lacking.
To improve the discussion part on extramedullary manifestation in AML I recommend a recently released review by R.M. Shallis: “Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved”.
Author Response
We are grateful for the comments regarding our manuscript for the present paper, and special thanks for the highly relevant and constructive criticism raised by reviewer 2. They have indeed helped us improved the manuscript.
We agree that the subheading “Material and Methods” not seem appropriate, and accordingly we have changed this subheading to “Case presentation» and keep the “Introduction” and “Discussion” part as also stated by the journal.
We agree that formulation “diagnosis was delayed because tumor obstruction was not initially a suspected cause diagnosis was delayed because tumor obstruction was not initially a suspected cause” was unprincely. Accordingly, we have changed this statement.
We are grateful for the comment regarding morphology and immunophenotype of the malignant blasts. The morphologic could be somehow different in blood, bone marrow and sarcoma. Howler in this setting the blasts seem to be of quit same morphological and immunophenotypic features, as they were compatible with acute myeloblastic leukemia (FAB M4). To furtherer state this important features we have in our revised version also include pictures from blood same and bone marrow smear to demonstrate the morphological features of the leukemic blasts. We also strengthen this position in or discussion part.
We agree that the order of the PET-CT pictures was somehow misleading, and accordingly we have changed it.
We agree in the comment regarding PET-CT, as this has currently not been routinely used in leukemia diagnostic and prognostic work up, and accordingly we have changed this statement.
We are glad for the recommendation of the update review from Shallis and coworkers, which as some interesting aspects, and we have used this as a central reference in our revised version of the manuscript.
Round 2
Reviewer 1 Report
Thank you for your response to suggested issues. I found your reply sufficient and I recommend your revised manuscript for publication in Clinics and Practice in the present form.
Author Response
We are very glad for the positive feedback from reviewer 1.
Reviewer 2 Report
The authors have addressed most of the issues/questions raised in my first review. Unfortunately they did not answer my question whether the tumor could have been spotted on the first CT-scan (shown in figure 1) or in the initial ultrasonography. All of us have experienced cases in which we retrospectively see things on MRIs or CT scans only after knowing them to be there.
Author Response
We apologize for this ambiguity which peer reviewer 2 correctly points to. The initial CT examination was performed for urinary tract examinations, and therefore has little sensitivity to detect parenchymal organ changes or changes outside the urinary tract. For the ultrasound examination of the abdomen, it is also difficult to gain insight into potential tumors on the posterior abdominal wall, and tumor changes were therefore probably not detected. We have specified this in our revised version of this manuscript, both in the case presentation and in the discussion part.
