2025/03/20 by Robert Stephens, Antony Johnston, Rolf B. Saager +1 · 1 voice
Dentistry · Engineering · Medicine · #Nanoplatforms for cancer theranostics #Oral and Maxillofacial Pathology #Vascular Malformations and Hemangiomas
paper · pdf · doi:10.1111/ajd.14458
openalex created_date 2025/03/20 · openalex publication_date 2025/03/20 · openalex updated_date 2026/07/28
Pigment is considered a contraindication to photodynamic treatment (PDT) of BCC as melanin acts as a competing chromophore and interferes with the passage of light. This interference can be overcome with high irradiance scattered light that can be achieved using intense pulsed light (IPL) delivered in a second phase immediately following first-phase red light. The method is that IPL is delivered with enough mechanical pressure in the handpiece to blanch the skin to remove blood [1]. Removing blood will augment the passage of green-yellow wavelengths that have higher protoporphyrin IX (PpIX) activation potential and can be included in the IPL emission using select cut-off filters. Despite the removal of blood, free oxygen generated in tissue from red light activation remains available. A 59-year-old woman presented with an 18-month history of a growing pink plaque just above her right eyebrow (Figure 1a). Dermatoscopy showed a tumour with an arborising vessel pattern and flecks of pigment supporting a diagnosis of pigmented BCC. Optical coherence tomography (OCT) showed granular hypo-reflective ovoid nests within the papillary dermis and epidermal atrophy. These are highly convincing features of nodular BCC. Maximum tumour depth on OCT was 1.06 mm. A 2 mm punch biopsy was also performed, and the histology showed a nodular BCC reaching a depth of 1 mm. The patient consented to PDT, which was undertaken using the two-phased activation protocol described in our 2020 study [1]. A curette was used gently to remove scale; methylaminolevulinate cream was then applied under an occlusive dressing for 3 h. Photoactivation consisted of 37 J cm−2 red light (Aktilite) immediately followed by 30 J cm−2 IPL (2 × 15 J cm−2 passes) using a 560 nm cut-off filter (Treatment 1). A second treatment was given 2 weeks later following the same procedure but with 45 J cm−2 IPL (3 × 15 J cm−2 passes). The IPL was delivered with enough mechanical pressure so the skin was blanched. The pulse duration was set at 200 ms. We have found that durations ≥ 100 ms have little or no damaging photothermal effects on Types 1–3 skin using the above settings. We refer to this two-phased protocol as ‘biphasic PDT’. Both treatments were well tolerated. Upon review 4 months later, there was no clinical or dermatoscopic evidence of residual tumour (Figure 1b). A follow-up OCT scan was also performed, which showed no evidence of residual tumour. OCT-imaging is highly sensitive in detecting residual tumour following topical treatment such as PDT. Our positive experience is confirmed by two recent studies [2, 3]. Our case illustrates a second point concerning the passage of light in bloodless skin. BCC tumour nests are themselves translucent. When blood is removed during lesion compression, more photons can reach the underlying collagen to thereafter scatter in all directions, overcoming shadows created by melanin. This applies particularly to green and yellow light in the IPL-emission. The green-yellow spectrum has a higher PpIX activation potential than conventional red light. When blood is removed from tissue, this may deplete oxygen, which is essential for photoactivation. We postulate, though, that during first-phase (red-light) activation, increased supply of oxy-haemoglobin occurs (via hyperaemia) and that heat generated from first-phase activation will promote dissociation to free oxygen in tissue [4, 5]. We have used the biphasic protocol since 2018. Reactions are often strong and targeted, unlike our experience using the conventional PDT protocol. The nodular tumours that respond best are pink-red tumours up to 1.1 mm in depth, having an endophytic growth pattern of the type indicated in the OCT image (Figure 2). This may be due to a light-trapping effect from thicker collagen that surrounds the tumour–stroma complex, and the pink-red colour may indicate that sufficient free oxygen will be met. The OCT appearance is likened to a bird's nest. We posit that first-phase red-light starts activation and generates a free-oxygen surplus, and that second-phase IPL under pressure optimises tissue optical characteristics for improved photodynamic effect. Further research into biophysical aspects of biphasic PDT, along with clinical studies, are needed to confirm our hypotheses. The authors have nothing to report. The authors declare no conflicts of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.