Summary: Noninvasive imaging of skin diseases is highly valued in both dermatological research and practice. Reflectance confocal microscopy (RCM) is primarily applied to assess melanocytic lesions because of its high resolution, whereas optical coherence tomography (OCT) is particularly used for non‐melanocytic skin tumors owing to its greater penetration depth. Line‐field confocal optical coherence tomography (LC‐OCT) combines the techniques of reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), enabling visualization of the skin down to the superficial dermis while simultaneously providing cellular resolution. The visualization of the skin changes can be done horizontally, vertically, in 3D mode or as a video in real time. The evaluation of the measurement can be supported by artificial intelligence if required. The field of application of LC‐OCT includes both melanocytic and non‐melanocytic lesions. In addition, preliminary studies show great potential in the diagnosis and therapy control of inflammatory and infectious skin diseases. Nevertheless, RCM and OCT still have their place in special cases such as tumors requiring a particularly high resolution or penetration depth > 500 µm.

Summary: Non‐invasive imaging techniques allow a quick and easy in vivo examination of the skin with different penetration depths and resolution depending on the applied technology. Established methods such as dermoscopy and high‐resolution sonography of the skin have been an integral part of everyday life for decades. Additionally, new emerging techniques such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM), and line‐field confocal OCT (LC‐OCT) have entered clinical practice. Multiphoton tomography and optoacoustic imaging are also considered promising new methods. RCM and LC‐OCT can also be used ex vivo on freshly excised tissue, for example in Moh's surgery margin assessment. The data generated by all imaging methods is ideal for the application of AI‐based algorithms to increase diagnostic accuracy and support experienced users. All mentioned methods have preferred indications depending on their strengths and limitations, both in skin tumor diagnostics and in inflammatory, infectious and parasitic dermatoses. The following guideline provides an overview of the various devices and techniques, explains how each method works and provides the current study situation with indications and limitations of each procedure.

Background/Objectives: Topical imiquimod is an established non-invasive treatment for superficial basal cell carcinoma (sBCC). However, data on treatment-associated changes in tumor microvascularization remain limited. This study investigated vascular changes before and after imiquimod therapy using multimodal non-invasive imaging. Methods: In this single-center, prospective observational study, 31 basal cell carcinomas in 20 patients were examined before and 12–16 weeks after topical imiquimod therapy (5%, five times weekly for six weeks) using dermoscopy, dynamic optical coherence tomography (D-OCT), and line-field confocal optical coherence tomography (LC-OCT). Analyses were performed as paired before-and-after comparisons. While approved for sBCC, a small number of thin nodular and infiltrative BCCs were included exploratorily; subgroup analyses were not powered. Results: Dermoscopy showed a nominally significant shift toward smaller vessel diameter categories after therapy (ATS = 8.183, df = 1, p = 0.004). D-OCT-derived parameters (vessel density, vessel diameter, and depth of the vascular plexus) did not show nominally significant changes. LC-OCT showed nominally lower apparent intratumoral flow scores (ATS = 13.285, df = 1, p < 0.001), reduced occurrence of vessel-wall-associated intraluminal structures showing a rolling-like motion pattern (86.7% before treatment versus 33.3% after treatment; ATS = 13.357; df = 1, p < 0.001), and a reduction in maximum vessel diameter (ATS = 6.110, df = 1, p = 0.013). The primary LC-OCT inferential analyses were performed at the lesion level without adjustment for within-patient clustering and should therefore be interpreted as exploratory. An additional patient-cluster-adjusted paired change-score sensitivity analysis for LC-OCT maximum vessel diameter yielded a directionally consistent estimate (−17.81 µm; 95% CI: −34.40 to −1.23; p = 0.037). The primary exploratory endpoints were LC-OCT–based apparent intratumoral flow and maximum vessel diameter; secondary endpoints included dermoscopic and D-OCT–based vascular parameters. In the exploratory response-stratified analysis, the change in LC-OCT-based maximum vessel diameter did not differ significantly among the assigned response groups (Kruskal–Wallis H = 3.870, df = 2, raw p = 0.144; BH-adjusted p = 0.753). Conclusions: LC-OCT detected several exploratory vascular changes between the pre-treatment examination and follow-up and may provide complementary information for the non-invasive assessment of BCC after imiquimod therapy. Given the exploratory design, limited sample size, and lack of systematic histological confirmation, these findings are hypothesis-generating and require validation in larger prospective studies.

Malignant eccrine differentiated sweat gland tumours, including porocarcinoma and eccrine spiradenocarcinoma, are rare and aggressive neoplasms that pose diagnostic and therapeutic challenges. This case report aims to describe the role of in‐vivo and ex‐vivo line‐field confocal optical coherence tomography (LC‐OCT), optical coherence tomography (OCT), and ex‐vivo fusion confocal microscopy (evFCM) in diagnosing and assessing the margins of a malignant eccrine differentiated sweat gland tumour with features of both porocarcinoma and eccrine spiradenocarcinoma. An 84‐year‐old man presented with a nodular scalp lesion. The lesion was evaluated using dermoscopy, OCT, in‐vivo and ex‐vivo LC‐OCT and evFCM. The findings were followed by Mohs micrographic surgery and histopathological examination to confirm the diagnosis. Dermoscopy revealed a vascular pattern with polymorphous vessels, while in vivo LC‐OCT and OCT demonstrated large nodules with necrotic areas and cuboidal cells. Ex‐vivo LC‐OCT and evFCM confirmed the complete tumour excision, corroborated by histology. Histopathologic evaluation identified a malignant epithelial tumour with two components: epithelioid clusters mimicking glandular lumina and polymorphic cells with pronounced pleomorphism. The diagnosis of a malignant eccrine differentiated sweat gland tumour with features of porocarcinoma and eccrine spiradenocarcinoma was made. This case highlights the utility of LC‐OCT, OCT, and evFCM in diagnosing and managing malignant eccrine differentiated sweat gland tumours. These noninvasive imaging techniques offer near‐histological resolution, enabling more precise diagnosis and margin assessment. Further studies are warranted to validate these findings and improve diagnostic protocols for such rare tumours.

Zusammenfassung: Nichtinvasive Bildgebungstechniken erlauben schnell und schmerzfrei diagnostische Blicke in die Haut, je nach angewandter Methode mit unterschiedlich hoher Auflösung und Eindringtiefe. Schon seit Jahrzehnten aus dem Alltag nicht wegzudenken sind die etablierten Untersuchungsmethoden wie die Dermatoskopie und die hochauflösende Sonographie der Haut und Subkutis. Weitere innovative Verfahren wie die optische Kohärenztomographie (OCT), die konfokale Lasermikroskopie (KLM) und die Line‐field konfokale OCT ( Line‐field confocal OCT ; LC‐OCT), die die Untersuchung der Haut mit sehr hoher Auflösung erlauben, haben Einzug in die klinische Routine gehalten. Die Multiphotonentomographie sowie die optoakustische Bildgebung gelten ebenfalls als vielversprechende neuere Verfahren. Neben den nichtinvasiven Verfahren, die in vivo direkt am Patienten zum Einsatz kommen, können die KLM und die LC‐OCT auch ex vivo an exzidiertem Gewebe zur Schnellschnittdiagnostik angewendet werden. Die bei allen Bildgebungsmethoden generierten Daten eignen sich hervorragend für die Anwendung KI‐basierter Algorithmen zur Erhöhung der diagnostischen Treffsicherheit und Unterstützung des erfahrenen Anwenders. Alle genannten Verfahren haben ihre Stärken, Limitationen und bevorzugte Indikationen. Im Folgenden wird ein Überblick über die verschiedenen Geräte und Techniken gegeben und für jede Methode die Funktionsweise und die aktuelle Studienlage zu Indikationen und Grenzen des jeweiligen Verfahrens dargelegt.