Dysembryogenetic Pathogenesis of Basal Cell Carcinoma: The Evidence to Date

Abstract

The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread. A potential correlation between the onset of BCC and a dysembryogenetic process has long been hypothesised. A selective investigation of PubMed-indexed publications supporting this theory retrieved 64 selected articles published between 1901 and 2024. From our analysis of the literature review, five main research domains on the dysembryogenetic pathogenesis of BCC were identified: (1) The correlation between the topographic distribution of BCC and the macroscopic embryology, (2) the correlation between BCC and the microscopic embryology, (3) the genetic BCC, (4) the correlation between BCC and the hair follicle and (5) the correlation between BCC and the molecular embryology with a specific focus on the Hedgehog signalling pathway. A large amount of data from microscopic and molecular research consistently supports the hypothesis of a dysembryogenetic pathogenesis of BCC. Such evidence is promoting advances in the clinical management of this disease, with innovative targeted molecular therapies on an immune modulating basis being developed.

Keywords: Hedgehog signalling pathway; basal cell carcinoma; embryogenesis; embryology; pathogenesis.

Figure 1

The original Tessier anatomical diagram of craniofacial clefts: localization on the soft tissues (a) and skeleton (b). Dotted lines are either uncertain localizations or uncertain clefts. Reprinted with permission from Ref. [15]. 1976, Elsevier.

Figure 2

The hairline indicators are the superior and lateral extensions of the Tessier original craniofacial cleft classification. Reprinted with permission from Ref. [16]. 1988, Wolters Kluwer Health.

Figure 3

Anatomical diagram of the typical sites of congenital clefts, fistulas, and cysts of the neck: the laterocervical line (L.L.) and the anterior neck midline (Tessier cleft number 30). Reprinted with permission from Ref. [14]. 2014, Wolters Kluwer Health.

Figure 4

Original full-size anatomical diagram showing the sites of the embryonic fusion planes of the auricle according to Streeter, Wood-Jones, Park, Porter, and Minoux. The hyoid–mandibular fusion plane (HM–FP) is featured in red and the free ear fold-hyoid fusion plane (FEFH–FP) in blue. Reprinted with permission from Ref. [17]. 2018, SAGE Publications.