Comment on “Correlation of basal cell carcinoma subtype with histologically confirmed subclinical extension during Mohs micrographic surgery: A prospective multicenter study”

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To the Editor: We would like to thank the authors for their very interesting work. The subclinical extension (SE) of basal cell carcinomas (BCC) is crucial to predict before Mohs micrographic surgery because aggressive subtypes, nonaggressive subtypes (superficial BCC), or those with a histologic subtype drift can present SE. Noninvasive methods such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) may be useful in detecting a BCC’s SE and its histologic subtype drift pre-Mohs micrographic surgery and can also reduce the number of stages required for tumor clearance. These 2 in vivo methods combined give us both in-depth and horizontal information concerning the tumor. Identifying occult tumor extension is a topic of interest, especially from the perspective of avoiding possible BCC recurrences. RCM is an innovative in vivo examination tool which, with the help of a low-power laser, aids in the study of BCC lesions, revealing thin-sectioned images of this skin neoplasm.1Ghita M.A. Caruntu C. Rosca A.E. et al.Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma.Oncol Lett. 2016; 11: 3019-3024https://doi.org/10.3892/ol.2016.4354Crossref PubMed Scopus (27) Google Scholar RCM examination indicates both the patient’s BCC subtype and reveals a rather peculiar trait that was considered in the past as a tumor processing artifact: the tumor-stroma cleft/separation. The latter is revealed as a low-refractility area located between the tumor nodule/mass and the neighboring stroma, thus calling into question the involvement of local mucin in the development of the cleft.2Ulrich M. Roewert-Huber J. González S. Rius-Diaz F. Stockfleth E. Kanitakis J. Peritumoral clefting in basal cell carcinoma: correlation of in vivo reflectance confocal microscopy and routine histology.J Cutan Pathol. 2011; 38: 190-195https://doi.org/10.1111/j.1600-0560.2010.01632.xCrossref PubMed Scopus (83) Google Scholar By OCT examination, BCCs look like oval structures surrounded by dark areas. A 2021 OCT international consensus regarding BCC states that the 3 most important OCT traits for nodular BCC are (1) dermal hyporeflective ovoid nodules, (2) hyporeflective cleft areas, and (3) hyporeflective borders.3Fernández-Figueras M.T. Malvehi J. Tschandl P. et al.Position paper on a simplified histopathological classification of basal cell carcinoma: results of the European consensus project.J Eur Acad Dermatol Venereol. 2022; 36: 351-359https://doi.org/10.1111/jdv.17849Crossref PubMed Scopus (1) Google Scholar Combined RCM-OCT examination reveals amyloid deposits as a shapeless, hyperreflective, uniform material located inside the tumor nodules or around them; mucin, on the other hand, either on the inside or at the periphery of the tumor islands, is hyporeflective. What is crucial regarding these clefts and deposits (mucin and/or amyloid) is that they have been found in low-risk BCC (with less aggressive behavior—such as the nodular subtype). Such findings should be searched for by RCM-OCT examination, and where the cleft is missing, SE should be considered.4Niculet E. Craescu M. Rebegea L. et al.Basal cell carcinoma: comprehensive clinical and histopathological aspects, novel imaging tools and therapeutic approaches (Review).Exp Ther Med. 2022; 23: 60https://doi.org/10.3892/etm.2021.10982Crossref PubMed Google Scholar,5Fuchs C.S.K. Ortner V.K. Mogensen M. et al.2021 International consensus statement on optical coherence tomography for basal cell carcinoma: image characteristics, terminology and educational needs.J Eur Acad Dermatol Venereol. 2021; (Published online February 9, 2022)https://doi.org/10.1111/jdv.17969PubMed Google Scholar BCC is the subject of another theory called “the angiogenic switch,” a crucial step for tumor initiation and advancement, involving a prevalence of proangiogenic factors, resulting in an increased number of (irregular and congestive) blood vessels (with elevated vascular endothelial growth factor levels) and stroma remodeling. Thus, BCC is characterized by low metastatic rates, raising the question of whether “the angiogenic switch” is involved in the tumor’s aggressive behavior. This subject remains to be studied with the help of new, in vivo examination tools such as RCM and OCT, which lack the artifactual compression of tumor microvessels. Before surgical intervention, RCM and OCT may be useful to explore the possible SE and the presence or absence of a cleft structure; the 2 techniques combined give information on both lateral and deep tumor margins. None disclosed. This work was academically supported by the Dunarea de Jos University of Galati, Romania, Faculty of Medicine and Pharmacy through the Multidisciplinary Integrative Center for Dermatologic Interface Research (MIC-DIR).