Noninvasive Screening of Basal Cell Carcinomas: A Comparison of the Structure and Physical Properties of Large and Small Nodular Lesions Using Vibrational OCT and Histopathology

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript presents a comparative analysis of small and large nodular basal cell carcinomas (BCCs) using histopathology, optical coherence tomography (OCT), and vibrational optical coherence tomography (VOCT). The study attempts to correlate structural and mechanical properties of lesions with imaging signatures to support non-invasive diagnostics, an area of increasing relevance in dermatology and teledermatology.

Non-invasive diagnostics are becoming central to skin cancer screening and management, especially in regions with limited access to dermatologists. While OCT is widely studied, the use of vibrational OCT (VOCT) to detect mechanical resonance peaks associated with cancer-associated changes adds a unique dimension.

However there is some major information missing:

1. Please clarify how many patients were included in this study? The study compares only two lesions (one small and one large BCC). While the depth of analysis is commendable, the conclusions—particularly about lesion maturity, fibrosis, and mechanical spectra—require caution. Expansion to a larger dataset would increase generalizability and statistical validity.
2. Where there any obstacles regarding imaging artefact with e.g. crusts, blood?
3. Does the localization of the BCC affect the vibration signal? How would you deal with difficult anatomical areas like the nostrils, the triangular fossa of the ear or the inner corner of the eye when there is not enough space for the acoustic speaker?
4. A few typos are present throughout (e.g., “paxelwere” in Figure 1 legend). These should be addressed during revision.

Author Response

see attached file

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript provides a side-by-side analysis of small and large nodular BCCs using vibrational OCT (VOCT), standard OCT imaging, and histopathology. The study’s intention—to explore the utility of VOCT as a non-invasive diagnostic and screening tool—is commendable. However, there are issues in the way certain sections are structured, explained, or interpreted. Below are five specific sections where revisions are recommended to improve clarity, internal consistency, and academic rigour.

The introduction merges background on BCC morphology with a heavy discussion of molecular biology and collagen signalling pathways. This creates a lack of focus and makes it difficult for readers to follow the main rationale for the study. I would recommend to refocus the introduction to more clearly articulate the clinical gap this study addresses: the need for better non-invasive tools to differentiate BCCs.

In the methods, the explanation of VOCT mechanics and how frequency data maps onto tissue components is dense and uses jargon that could obscure reproducibility. It’s unclear how the frequencies were assigned or validated for specific tissue components. Please rephrase this section for greater clarity. Use plain language to explain how the VOCT frequencies correspond to tissue types and Provide a table summarising the frequency-to-tissue assignments.

While there is good qualitative description, the results rely heavily on subjective interpretations of OCT and VOCT signals without consistent comparison across the two lesions. The narrative lacks parallelism, making it hard to draw clean contrasts between small and large nodules. Please fix.

The discussion asserts that increased fibrosis and reduced VOCT signals at lower frequencies in large BCCs imply mature lesions with tightly bound CAF-collagen networks. This is plausible but speculative and phrased with undue certainty.

The conclusion reiterates results without adequately reflecting on the limitations of the study, especially the very limited sample size and the single-institution context.

Author Response

see attached file

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Accept in present form

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your responses which I find satisfactory