New insights from non-invasive imaging: from prospection of skin photodamages to training with mobile application

Abstract

The incidence of non-melanoma skin cancer is on the rise and melanoma is among the most common cancers in the United States. Establishing an early diagnosis is essential for improving the prognosis of patients with skin cancer. High-resolution non-invasive imaging techniques may represent key tools for helping to identify and monitor early signs of skin cancer in seemingly healthy skin. Cumulative lifetime sun exposure leads to photoaging and photocarcinogenenis and the reaction of the skin to this solar-induced damage is balanced between the DNA repair and photoprotection defence mechanisms of melanocytes and keratinocytes. In the first part of this article we provide an overview of these defence mechanisms and of the photoaging process, and discuss how non-invasive imaging can be used to evaluate these changes. We then propose a model in which skin aging manifestations can be classified according to subject-specific sun-damage reaction profiles observed by reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). These photoaging profiles include an atrophic phenotype characterized by actinic keratosis, and a hypertrophic phenotype characterized by hyperplastic pigmented skin. According to our model, these phenotypes may be predictive of predispositions to different types of skin cancer: squamous cell carcinoma for the atrophic phenotype and lentigo maligna and freckles for the hypertrophic phenotype. In addition to RCM and OCT, dermoscopy is another non-invasive technique that has improved the diagnosis of skin cancer. In the second part of this article, we describe how the YouDermoscopy™ application can improve skills and thus enhance the dermoscopic recognition of sun-induced skin tumours, and then show how this training tool enables its users to collaborate with dermatologists worldwide to obtain second opinions for the diagnosis of ambiguous lesions. Altogether, RCM, OCT and dermoscopy are valuable tools that can contribute significantly to improving the early diagnosis of precancerous and cancerous lesions.

Keywords: actinic keratosis; confocal microscopy; dermoscopy; diagnosis; melanoma.

Figure 1

Chronoaging and photoaging induce different types of changes in keratinocytes and melanocytes. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Signs of photoaging of the skin (in lowercase) range from benign (black) to intermediate (blue) and to premalignant or malignant (red), and result from keratinocyte and melanocyte reactions to UV exposure (in the grey box): damage mechanisms (uppercase red) and protection mechanisms (uppercase blue) can have an additive effect. For instance, solar lentigo results from a combination of keratinocyte hyperplasia and pigmentation, whereas pigmented actinic keratosis (PAK) results from a combination of dyskeratosis and melanocyte hyperplasia.

Figure 3

A subject with photoaging characterized by actinic keratosis and field cancerization (a). Reflectance confocal microscopy (b) reveals that irregularly shaped keratinocytes (dyskeratosis) are present in the epidermis (dashed circle). Optical coherence tomography (c) reveals the presence of a thin epidermis (arrows) upon altered collagen fibres. The overall picture is characteristic of an atrophic photoaging phenotype. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 4

A subject with photoaging characterized by pigmentation and solar lentigines (a). Reflectance confocal microscopy (b) reveals that elongated epidermal cords forming polycyclic papillary contours (arrows), corresponding to the elongation and anastomosis of the rete ridge, are present at the dermal‐epithelial junction. Optical coherence tomography (c) reveals a thickened epidermis (arrows) upon dense and compact (elastotic) collagen fibres. The overall picture is characteristic of a hypertrophic/hyperplastic photoaging phenotype. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 5

Hypothesis 1: Skin aging manifestations (actinic keratosis [AK] or solar lentigo freckles) correspond to subject‐specific sun‐damage reaction profiles (dyskeratosis or keratinocyte [KC] hyperplasia, respectively).

Figure 6

The atrophic phenotype: a subject with clinically visible actinic keratosis lesions suggesting a low level of ‘protective reaction capability’ and a high level of ‘DNA damage susceptibility’ (a). Dynamic optical coherence tomography imaging on apparently healthy skin shows an atrophic epidermis with altered collagen and an expanded vascular plexus (b and c, respectively). The corresponding reflectance confocal microscopy (RCM) images reveal dyskeratotic keratinocytes in the epidermis (dashed circles) and fragmented collagen fibres in the upper dermis (arrows) (representative RCM images of the epidermis (d), junction (e) and upper dermis (f)). [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 7

The hypertrophic phenotype: a subject with clinically visible solar lentigines and freckles suggesting a high level of ‘protective reaction capability’ and a low level of ‘DNA damage susceptibility’ (a). Dynamic optical coherence tomography imaging on apparently healthy skin shows a thickened epidermis with dense collagen in clods and a diminished vascular plexus (b and c, respectively). The corresponding reflectance confocal microscopy (RCM) images reveal polycyclic papillary contours and epidermal cords (dashed circles), corresponding to an elongated rete ridge, as well as amorphous collagen and curled fibres (arrows), corresponding to elastosis in the upper dermis (representative RCM images of the epidermis (d), junction (e) and upper dermis (f)). [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 8

The mixed phenotype: a subject with clinically visible actinic keratosis, solar lentigines and freckles suggesting both ‘protective reaction capability’ and ‘DNA damage susceptibility’ (a). Dynamic optical coherence tomography imaging on apparently healthy skin shows an irregular epidermis with altered collagen and an irregular vascular plexus (b and c, respectively). The corresponding reflectance confocal microscopy images reveal dyskeratotic keratinocytes (dashed circles), as well as mottled pigmentation and epidermal cords (arrows), corresponding to elongation of rete ridge, with amorphous elastotic collagen in the upper dermis (d), junction (e) and upper dermis (f). [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 9

Hypothesis 2. (a) If background photodamage is related to skin cancer development, patients with squamous cell carcinoma (SCC) would also present a cancerization field, characterized by subclinical irregular keratinocytes, as well as clinically visible AK lesions, susceptible to undergoing neoplastic changes. (b) If background photodamage is related to skin cancer development, patients with lentigo maligna (LM) also present a ‘melaninization field’, characterized by subclinical epidermal hyperplasia (elongation of cristae on RCM images), as well as diffuse visible solar lentigo and freckles susceptible to undergoing neoplastic changes in an area with LM. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 10

The Youdermoscopy™ game format: users are shown a dermoscopic image of a pigmented skin lesion, and provided with a choice of eight possible diagnoses: the correct answer (MELANOMA) is highlighted in green, whereas the user's incorrect answer (NEVUS) is highlighted in red. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 11

Youdermoscopy™ ‘Play Live’: players who have completed the first three levels of the game format can submit a dermoscopic image of a pigmented skin lesion, together with data on the lesion location, and the sex, age and country of the patient (a), allowing them to ask the community for a second opinion. The community then votes for the most likely diagnosis, shown as a distribution of percentages (b). A group of experts also provides their opinion, with their vote being indicated by the icon of a scholar. The histopathological diagnosis is also provided – whenever it is available – and is indicated by the icon of a microscope and highlighted in green. In the example provided here: Case submitted on the 29/01/2019, 169 Answers: Melanoma 30.0%, Nevus 2.0%, Basal Cell Carcinoma 37.0%, Squamous Cell Carcinoma in situ or invasive 1%, Solar lentigo/seborrheic keratitis 1.0%, Vascular lesion 24.0%, Dermatofibroma None, and Other 1%. [Colour figure can be viewed at wileyonlinelibrary.com]