What to Look Out for in a Newborn with Multiple Papulonodular Skin Lesions at Birth

Round 1

Reviewer 1 Report

The authors present a very interesting, well written and educational article about papulonodular lesions appearing in the neonatal period. The text is accompanied by clinical and histopathological pictures that enrich the article, some of them of quite rare entities.

I suggest some minor improvements and corrections:

- Table 1 should be reformatted: it is somewhat confusing as it is; headings, subheadings, etc., should be clearer.

- The same as above is true for the organization of the whole text contained in the manuscript: it should become clearer which entities fall within each category.

- In malignant rhabdoid tumour, it would be better to say “exceedingly rare” instead of “excessively rare”.

Author Response

Dear reviewer

thank you so much for your compliments and support

Indeed tabIe 1 was unclear due to the layout of the publisher

I made it clearer as well as the organization of the whole text

I have changed "excessively" into "exceedingly"

Reviewer 2 Report

Some of these disorders are very rare, and never seen in a dermatology routine. However, to perform a biopsy in a newborn may be crucial but also hazardous as well. 

Author Response

Dear reviewer

thank you for your comment

I do understand your reluctance to biopsy a newborn. However most pediatric dermatologists are now used to it and this dosen't pose a problem to them. In addition it is worth it

Reviewer 3 Report

1. Semantic issue: there are no "papulonodular" (more beginning) or "maculopapular" (at end of manuscript) lesions, and thus these terms are irritating. "Macules (visable not touchable), papules (touchable up to 5mm, and nodules (5mm to 2cm of size)" have well been defined and should be used accordingly. This issue regards text as well as title of manuscript.
2. As "typical" has never been defined, "atypical" so too is nihilistic. What you can describe are cytologic as well as histological features such as hyperchromasia, pleomorphism, bizarre mitoses, cytoplasmic to nuclear ratio or cellular density.
3. "Hyaline" is a nihilistic term either. Depending on circumstances this may be erythrocytes (globules in Morbus Kaposi), basement membrane (cylindroma) or collagen (in fibrosclerosis), a.o.m. Please use adequate terminology for this term in metastatic rhabdoid tumor or "fibrosclerosis" in IM in figure legend 10, line 304.
4. "Histiocytes" and "histiocytic" have never been reliably been defined. What is meant are epithelioid cells which can occur in every cell line of differentiation, e.g. to give one example "histiocytic" metastasis of mammary carcinomas. In your instance "histiocytes are either "Langerhans cells or at least closely related cells" or "macrophages". Please, adapt accordingly.
5. Macrophages in JXG (as in other so called "histiocytoses") may appear in 5 variants, the earliest being mononuclear-vacuolated (Shapiro type) which is shown in your figures and well established in literature - see Zelger et al Am J Dermatopathol in mid-90-ies of last millenium, I think.
6. "clearly" (page 15, line 276) is not very scientific, better is "best or already". Moreover, the pattern in IM may be vice versa also, namely leiomyoma-like in center and hemangiopericytoma-like at periphery. Please, add. On same page in line 281 I think verb "is" is missing.
7. "extremely" is no academic or scientific expression rather than a political one. Please, better use "extraordinarily".
8. "Morbus Kaposi" is better than "Kaposi sarcoma" as in reality it is no sarcoma but an inflammatory HHV8-associated disease. Please, exchange.
9. In Figure 16 lesion in my perception is not "pink", but "bluish to violet".
10. Page 26, I miss heading of "cutaneous mastocytosis". Moreover, I don´t understand the figure legend to Figure 17b: "containing thrombieous mastocytosis" - please, explain and/or clarify.

Author Response

Dear reviewer

thanks a lot for your pertinent comments. I will do my best to answer

1 regarding the terms maculopapular and papulonodular I agree that , at a semantic point of view, they don't have a real existence. However at a clinical level they really have a meaning. Our clinical experience shows us that these babies present together with either papules and nodules, or macules and papules. So it is easier to call the lesions maculopapular or papulonodular lesions 

2 For a pathologist "atypical cells" makes sense. If I detail the exact significance  (pleomorphisms, high nuclear-cytoplasmic ratio...) I will make the manuscript longer and it is already long. If it is necessary I will make the change

3 I have changed the legend as requested

4 Thank you for this comment. I agree that histiocytes are either Langerhans cells or macrophages and that nor all authors agree withi the meaning of this word. However for many authors the term "histiocyte" is used for histiocyte-looking cells when they are located in the tissues and not circulating. I thing useful to keep this term as it is well understood by dermatopathologists

5 I agree. Zelger very well described these variants but, again, here, I wouldn't make this article too long. I added the "mononuclear-vacuolated " to my legend. Thank you

6 I have changed "clearly" into "best". In small children tha vascular component is almost always located at the center of the lesion. The vice versa is rather seen in adult myofibromas (in my experience)

7 I have changed "extremely" into "extraordinarily" in the manuscript

8 we know that Kaposi disease is not a true sarcoma but an infectious disease. Personally I prefer use the term "disease" rather than that of "sarcoma". However "Kaposi sarcoma" is widely used in all Anglophone litterature and the description of kaposiform hemangioendothelioma is the same in all articles and text-books. It is not the aim of this present article to make fundamental changes

 9 totally agree! I made the modification

10 Thank you for your comment. Issue with the layout. Tha end of the legend is "thrombi" then there is the title if the following paragraph; " cutaneous mastocytosis". I made the change in the manuscript