A new vision of actinic keratosis beyond visible clinical lesions

In actinic keratosis (AK), clinical and subclinical lesions coexist across large areas of sun‐exposed skin resulting in field cancerization. The lesions are part of a disease continuum which can progress into invasive squamous cell carcinoma (SCC). Conventional biopsy sampling together with histopathological analysis of the excised tissue is still the gold standard for differentially diagnosing AK from invasive SCC and identifying the characteristic pathophysiological features of these lesions. Given that biopsy sampling is invasive and not suited to the investigation of disease across large fields of skin, several imaging technologies have been applied to non‐invasively investigate AK. Widely available imaging technologies such as cross‐polarized light, fluorescence and dermoscopy can assist the dermatologist in diagnosing AK and in identifying different types of AK lesions. Modern imaging technologies such as reflectance confocal microscopy (RCM) and high‐definition optical coherence tomography (HD‐OCT) provide high‐resolution images of the skin. These techniques can be used to image the histological changes that characterize AK and so can be used to diagnose the disease and its severity. They can also identify the presence of subclinical lesions and non‐invasively monitor the effects of AK treatments on both subclinical and clinical lesions over time. Both RCM and HD‐OCT have revealed a new vision of AK by visualizing in detail the cellular and histological changes that characterize both clinical and subclinical lesions, and confirming that the disease affects the entire sun‐exposed field. As a consequence of these findings, the target for the treatment of AK now needs to be the detection and clearance of all clinical and subclinical lesions across the entire sun‐exposed field.

[1]  S. Emre Actinic keratosis and field cancerization , 2016 .

[2]  R. Hofmann-Wellenhof,et al.  Dermoscopy of facial nonpigmented actinic keratosis , 2006, The British journal of dermatology.

[3]  T. Ehrig,et al.  Actinic Keratoses and the Incidence of Occult Squamous Cell Carcinoma: A Clinical–Histopathologic Correlation , 2006, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[4]  S. Baer,et al.  High rate of malignant transformation in hyperkeratotic actinic keratoses. , 1997, Journal of the American Academy of Dermatology.

[5]  C. Berking,et al.  High-Definition Optical Coherence Tomography for the in vivo Detection of Demodex Mites , 2012, Dermatology.

[6]  Salvador González,et al.  Clinical Applicability of in vivo Reflectance Confocal Microscopy for the Diagnosis of Actinic Keratoses , 2008, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[7]  W Sterry,et al.  Non‐invasive diagnosis and monitoring of actinic cheilitis with reflectance confocal microscopy , 2011, Journal of the European Academy of Dermatology and Venereology : JEADV.

[8]  Harald Kittler,et al.  Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model. , 2012, Journal of the American Academy of Dermatology.

[9]  V. del Marmol,et al.  High‐definition optical coherence tomography enables visualization of individual cells in healthy skin: comparison to reflectance confocal microscopy , 2012, Experimental dermatology.

[10]  C. Cockerell,et al.  Pathology and pathobiology of the actinic (solar) keratosis , 2003, The British journal of dermatology.

[11]  J. Ortonne,et al.  Effectiveness of cross polarized light and fluorescence diagnosis for detection of sub‐clinical and clinical actinic keratosis during imiquimod treatment , 2010, Experimental dermatology.

[12]  Marcelle N. Guirguis,et al.  Analysis of p53 and bcl‐2 protein expression in the non‐tumorigenic, pretumorigenic, and tumorigenic keratinocytic hyperproliferative lesions , 2004, Journal of cutaneous pathology.

[13]  B. Bošnjak,et al.  Expression of p53, bcl-2 and growth hormone receptor in actinic keratosis, hypertrophic type , 2003, Archives of Dermatological Research.

[14]  Sarah Norrenberg,et al.  Imaging actinic keratosis by high‐definition optical coherence tomography. Histomorphologic correlation: a pilot study , 2013, Experimental dermatology.

[15]  María Huerta-Brogeras,et al.  Validation of dermoscopy as a real-time noninvasive diagnostic imaging technique for actinic keratosis. , 2012, Archives of dermatology.

[16]  D. Slaughter,et al.  “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin , 1953, Cancer.

[17]  S. González,et al.  Clinical applicability of in vivo reflectance confocal microscopy in dermatology. , 2012, Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia.

[18]  J. Nicolas,et al.  EJD 20 th Anniversary , 2011 .

[19]  Christi Alessi Fox,et al.  Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses. , 2009, Archives of dermatology.

[20]  C. Berking,et al.  Actinic keratosis in the en‐face and slice imaging mode of high‐definition optical coherence tomography and comparison with histology , 2013, The British journal of dermatology.

[21]  T. Gambichler,et al.  Optical coherence tomography in dermatology: technical and clinical aspects , 2011, Archives of Dermatological Research.

[22]  S. González,et al.  Confocal microscopy patterns in nonmelanoma skin cancer and clinical applications. , 2014 .

[23]  R. Hofmann-Wellenhof,et al.  Discrimination of Actinic Keratoses from Normal Skin with Reflectance Mode Confocal Microscopy , 2008, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[24]  Leonard H Goldberg,et al.  Review ofactinic keratosis. Part I: etiology, epidemiology and clinical presentation. , 2010, Journal of drugs in dermatology : JDD.

[25]  W. Sterry,et al.  Reflectance Confocal Microscopy for Noninvasive Monitoring of Therapy and Detection of Subclinical Actinic Keratoses , 2009, Dermatology.

[26]  C. R. Leemans,et al.  A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. , 2003, Cancer research.

[27]  J. Malvehy,et al.  Monitoring treatment of field cancerisation with 3% diclofenac sodium 2.5% hyaluronic acid by reflectance confocal microscopy: a histologic correlation. , 2015, Acta dermato-venereologica.