Cutaneous Squamous Cell Carcinoma: An Up-to-Date Comprehensive Review with a Focus on Contemporary Optical Imaging Diagnostic Modalities

Cutaneous squamous cell carcinoma (cSCC) arises from the abnormal proliferation of keratinocytes of the epidermis, most commonly due to UV-light-induced DNA damage. Although histopathological assessment is the gold standard for diagnosing cSCC, nascent optical imaging diagnostic modalities enable clinicians to perform “optical or virtual biopsy” in real-time. We aim to report advances in optical imaging diagnostics for cSCC, along with an updated review of the literature. A comprehensive literature review was performed using PubMed, Embase, and Cochrane databases for manuscripts published from 2008 to 2022. The search yielded a total of 9581 articles, out of which 136 relevant articles were included in the literature review after fulfilling screening and eligibility criteria. This review highlights the current optical imaging devices used for diagnosing cSCC and their diagnostic features. These devices include in vivo and ex vivo reflectance confocal microscopy, optical coherence tomography, line-field confocal optical coherence tomography, multiphoton tomography, and high-frequency ultrasonography. Although surgical excision or Mohs micrographic surgery is considered the gold standard, the latest developments in nonsurgical management of cSCC are discussed. Based on he review of the literature, we conclude that contemporary optical imaging devices such as confocal microscopy, optical coherence tomography, line-field confocal optical coherence tomography and multiphoton tomography have revolutionized real-time diagnostic imaging in dermatology, particularly within the realm of skin cancer. These devices enable rapid diagnoses and allow for a faster initiation of therapy. The application of newer imaging devices to cSCC management may benefit high-risk patients (e.g., chronic UV radiation exposure or organ transplant recipients) or patients with multifocal cSCC, for whom multiple biopsies would be impractical, thus avoiding unnecessary biopsies. Together with dermoscopy, optical imaging technologies can help to improve the efficiency of diagnosis by reducing the turnaround time and the need for extensive laboratory processing resources.