Folliculosebaceous Cystic Hamartoma with Spindle Cell Lipomatous and Neural Components

Round 1

Reviewer 1 Report

The manuscript could possibly benefit from an appended paragraph pointing out the shared/overlapping morphological features between the stroma of FSCH and the stroma of CD34+ spindle cell predominant trichodiscoma (SCTD) – another cutaneous adnexal hamartoma/malformation. In fact, the stroma – composed of mesenchymal mucin, CD34+ fibroblasts, lipomatous metaplasia, neural elements - appears to be the most fascinating and conceptually challenging part of these lesions.

In this discussion “Spindle cell predominant trichodiscoma” (SCTD) might be viewed as a “twin lesion” due to multiple overlapping features.

Just for comparison – and in short – the chronological and conceptual evolution of the cutaneous hamartomatous adnexal lesion aka “spindle cell predominant trichodiscoma” (SCTD) which started its dermatopathological CV in (1994) under the descriptive name of “Neurofollicular hamartoma” [PMID: 8030767] - definitely a misnomer that was induced by the neural component of the predominant stroma. The close association between adnexal-epithelial and stromal elements became obvious in (2006) when the lesion was re-christened as “Spindle cell predominant trichodiscoma: a fibrofolliculoma / trichodiscoma variant considered formerly to be a neurofollicular hamartoma: a clinicopathological and immunohistochemical analysis of 17 cases.” [PMID: 16456317]. Remarkably these lesions were completely devoid of any lipomatous metaplasia, and the neural components were negligible. As soon as soft tissue pathologists took a fresher look at these lesions, the stroma gained massively in importance – as in (2011) “Symplastic trichodiscoma: a spindle-cell predominant variant of trichodiscoma with pseudosarcomatous/ancient features.” [PMID: 21915028]. Admittedly, “for someone with a hammer everything looks like a nail” – consequently, soft tissue pathologists may have overinterpreted the CD34+ fibroblastic stroma with lipomatous metaplasia as “spindle cell lipoma in the skin”. It is now widely shared that this was definitely an overinterpretation; at least in the eyes of most cutaneous adnexal tumor specialists. Genuine spindle cell lipoma and the fibroblast-rich stroma with lipomatous metaplasia may share morphological and immunohistochemical features – but etiopathologically they are different. In fact, these are two completely different biological environments: tumor vs adnexal stroma.

However (sic!) - this may not be the entire truth, as a paper in (2019) clearly showed: “Spindle Cell Predominant Trichodiscoma or Spindle Cell Lipoma With Adnexal Induction? A Study of 25 Cases, Revealing a Subset of Cases With RB1 Heterozygous Deletion in the Spindle Cell Stroma.” [PMID: 30908293].

A most remarkable situation! In short, the stroma of these cutaneous adnexal malformations/hamartomas is still replete with riddles: lipomatous metaplasia vs “pre-adipocytes” (as you called them), stromal CD34+ fibroblasts vs rb1-deleted tumor cells (?), and others.

We know the so-called “dual nature of ……” from physics - as in the “dual nature of light”: light as a corpuscle vs light as a wave. But could something like this also be possible in biology? Hardly not! But the reader might benefit from these hypothetical musings anyhow: it is the stroma that makes these adnexal lesions so interesting!

Author Response

Response to Reviewer 1 comments

Please see the attachment.

 

Author Response File: Author Response.pdf

Reviewer 2 Report

The reviewer wishes to thank the editor and the authors for the opportunity to review this well written manuscript.  This article describes the case of a 55- year-old female who presented with a nasal lesion histologically diagnosed as a folliculosebaceous cystic hamartoma. Of interest, the mesenchymal components of said folliculosebaceous cystic hamartoma resembled a spindle cell lipoma and demonstrated “neural components.”  The authors present the case well and the discussion regarding the histopathologic differential diagnosis is robust.

 

There is some personal concern that the follicular unit does not demonstrate enough features to be the “folliculosebaceous cystic” component of this hamartoma.  Instead the follicle appears to be slightly dilated with perhaps an increase in sebaceous glands as can happen in this anatomic location.  One wonders if this is an incidental site specific change overlying a mesenchymal lesion.  Perhaps a lower power image of the lesion demonstrating the delineation of the stroma, or perhaps a deeper section showing increased “cystic” dilation may be of help.

 

Additionally, while I agree there appears to be small nerves, as identified in Figure 2, contained within the lesion, I am unsure if these are related to the tumor or merely entrapped. Does the surrounding dermis demonstrate similar numbers of similar caliber nerves?

 

Likewise, as the authors note that clinical features are lacking for this entity, a clinical photo of this lesion may make the manuscript more attractive to our readers for their future examination of patients.

Some grammatical changes needed. 

Towards the bottom of page two hematoxylin needs to be corrected. "In ematoxylin-eosin stained sections, short nerve bundles, embedded in the lesional stroma, were seen"

Page 5 and 6: "pilar sheat acanthoma" needs to be corrected to pilar sheath acanthoma.

Author Response

Response to Reviewer 2 comments

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Author Response File: Author Response.pdf