Key points

Introduction

Invasive squamous cell carcinoma (SCC) represents the second most common skin cancer in humans, but their earliest form, namely actinic keratoses (AK), affects up to 60% of the elderly population. AKs typically arise in the context of field cancerization, representing one step in the continuum from chronic photo damage with subclinical dysplasia to invasive SCC. In this regard, AKs have been referred to as early in situ SCC with different grades describing the level of epidermal involvement ( Table 1 ).

Despite this classic pathway that describes the stepwise progression from AK to invasive SCC, recent data suggest an alternative pathway of AK grade 1 directly progressing to invasive SCC.

The clinical grading of AKs is mainly based on the grade of hyperkeratosis, which has not yet been shown to correlate with histologic grading of AK. In fact, although the clinical grade III refers to hyperkeratotic AKs, grade III in histopathology refers to fully developed intraepithelial carcinoma affecting the whole epidermis.

In most cases, the diagnosis of AK has been made clinically. However, the distinction between AK and other forms of nonmelanoma skin cancer, such as superficial basal cell carcinoma or benign lesions, may pose a diagnostic challenge. Furthermore, the distinction from different grades of AK, in situ SCC/Bowen disease, or even invasive SCC may be difficult, but is of major importance for treatment selection. Dermoscopy seems to aid the differentiation between the different stages in the continuum of keratinocyte skin cancer, because AK, in situ SCC/Bowen disease, and invasive SCC have been related to different patterns.

The criteria of AK have already been described in the beginning of the era of reflectance confocal microscopy (RCM) by Aghassi and colleagues, and further studies have analyzed the sensitivity and specificity of the AK criteria as well as the differentiation of AK from Bowen disease/SCC in situ and invasive SCC.

Herein, the morphologic criteria of the complete spectrum of squamous neoplasia on RCM evaluation are described. Furthermore, the use of RCM for the monitoring of AK is discussed.

Introduction

Invasive squamous cell carcinoma (SCC) represents the second most common skin cancer in humans, but their earliest form, namely actinic keratoses (AK), affects up to 60% of the elderly population. AKs typically arise in the context of field cancerization, representing one step in the continuum from chronic photo damage with subclinical dysplasia to invasive SCC. In this regard, AKs have been referred to as early in situ SCC with different grades describing the level of epidermal involvement ( Table 1 ).

Despite this classic pathway that describes the stepwise progression from AK to invasive SCC, recent data suggest an alternative pathway of AK grade 1 directly progressing to invasive SCC.

The clinical grading of AKs is mainly based on the grade of hyperkeratosis, which has not yet been shown to correlate with histologic grading of AK. In fact, although the clinical grade III refers to hyperkeratotic AKs, grade III in histopathology refers to fully developed intraepithelial carcinoma affecting the whole epidermis.

In most cases, the diagnosis of AK has been made clinically. However, the distinction between AK and other forms of nonmelanoma skin cancer, such as superficial basal cell carcinoma or benign lesions, may pose a diagnostic challenge. Furthermore, the distinction from different grades of AK, in situ SCC/Bowen disease, or even invasive SCC may be difficult, but is of major importance for treatment selection. Dermoscopy seems to aid the differentiation between the different stages in the continuum of keratinocyte skin cancer, because AK, in situ SCC/Bowen disease, and invasive SCC have been related to different patterns.

The criteria of AK have already been described in the beginning of the era of reflectance confocal microscopy (RCM) by Aghassi and colleagues, and further studies have analyzed the sensitivity and specificity of the AK criteria as well as the differentiation of AK from Bowen disease/SCC in situ and invasive SCC.

Herein, the morphologic criteria of the complete spectrum of squamous neoplasia on RCM evaluation are described. Furthermore, the use of RCM for the monitoring of AK is discussed.

Reflectance confocal microscopy criteria of squamous neoplasia

Actinic Keratosis and Actinic Cheilitis

On RCM, mosaics AK are characterized by central or multilocal disruption of the stratum corneum by overlying hyperkeratotic or parakeratotic scale ( Fig. 1 A). On higher magnification, RCM single images (0.5 mm × 0.5 mm) allow the identification of single detached keratinocytes and small bright round structures corresponding to parakeratosis. In hyperkeratotic lesions, the scale may be compact, and if covering the complete or majority of a lesion, it may significantly impair the evaluation. Rarely, inflammatory cells may be observed within the stratum corneum as a sign of impetiginization. At the level of the stratum granulosum and spinosum, an atypical honeycomb pattern may be observed. Atypical keratinocytes show pleomorphism by variations in their size and shape, thus resulting in an architectural disarray of the epidermis. In the papillary dermis, discrete increase in vasculature may be observed showing small, elongated vessels. Curled fibers may commonly be observed in the upper dermis, corresponding to solar elastosis. Furthermore, other changes of the collagen such as huddles may often be seen as a sign of photoaging. Recently, it has been shown that according to the grading, a histopathology of different grades of AK may also be differentiated by RCM, thus allowing an improved severity assessment and better selection of treatment. Actinic cheilitis shows similar criteria with atypical keratinocytes at the epidermal layers (see Fig. 1 ).

( A ) RCM mosaic of AK illustrating disruption of the stratum corneum with several areas of overlying scale and parakeratosis. ( B ) RCM single image showing small bright structures within the stratum corneum corresponding to parakeratosis. ( C ) RCM single image of the stratum granulosum. ( D ) RCM single image of the stratum spinosum. Please note the atypical honeycombed pattern. ( E ) RCM single image of the upper dermis illustrating solar elastosis with curled and clumped fibers and small dilated vessels ( arrow ).

Reflectance confocal microscopy features of actinic keratoses

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  Bright cells in the stratum corneum (parakeratosis)

  
  
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  Atypical honeycombed pattern

  
  
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  Upper dermis with curled fibers and slightly elongated vessels