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Actinic keratoses

Actinic keratoses (AKs), are precancerous lesions of the epidermis. They usually result from chronic exposure to ultraviolet light (UV light).1 Therefore, they typically occur on areas of the body that are highly exposed to UV light1,2, such as the face, ears, hairless scalp, neck/décolleté, back of the hands, forearms and shoulders.
Actinic keratosis (AK) is an early form (carcinoma in situ, CIS) of squamous cell carcinoma (SCC): It has been shown that at least 65% of SCCs form within or near pre-existing AK lesions.1,3
AKs may sometimes appear as isolated lesions but can often also present across an entire area. In this case the affected skin area is known as field cancerisation or field change.1

Higher life expectancy and AK – a skin disease on the rise

Apart from chronic UV exposure, there are certain risk factors associated with AK.1 In general, more men than women seem to develop AKs.1 Although epidemiological data is sparse, several publications on this topic particularly mention the increasing risk of developing AKs with advanced age. It can be estimated, using data from prevalence studies conducted in the UK as well as the National Institute of Health and Care Excellence (NICE), that at least one AK was present in 19-24% of individuals older than 60.1, 4,5
Geographic location may also play an important role in the development of AK:1 For example, the relationship of AK incidence to sun exposure is suggested, as reported prevalence rates range from 11 to 25% in various northern hemisphere populations, but from 40 to 60% amongst Australian adults.6
Other risk factors include: 7,8

  • severe sunburns
  • chronic immunosuppression
  • occupations with prolonged UV exposure
  • fair skin type

Diagnosis and classification

Clinical diagnosis of AK lesions is usually made by visual inspection and palpation.
AKs are clinically classified into four grades according to the Olsen classification9:

If the clinical diagnosis is unclear, dermoscopy, confocal laser microscopy, optical coherence tomography or any other suitable non-invasive diagnostic method can be used for confirmatory purposes.
In case of therapy resistance or atypical clinical findings, histological examination of a tissue sample is recommended.1
Based on a histological examination, AK can be divided into three grades depending on the extent of atypical keratinocytes within the epidermis according to Röwert-Huber10:

The Olsen classification correlates only to a limited extent with the histological classification according to Röwert-Huber. Due to the lack of correlation between the two classification systems, no valid conclusions about the histological grade of AKs can be drawn from the clinical appearance.11
In addition, a recent study has focused on the differences in basal growth of AKs. Depending on the depth extension of the atypical keratinocytes towards the dermis, the lesions were classified into three categories (PRO I – PRO III), of which the PRO III category is characterized by the most pronounced basal growth.12 Again there is no correlation between basal growth and the established histologic AK I-III classification system.

Development into squamous cell carcinoma (SCC)

The current incomplete understanding of the aetiology and development of actinic keratoses means that it is difficult to make conclusive assumptions about prognosis and the transition probabilities from AK to SCC.13

In the past, AKs were usually considered to first undergo a progressive evolution from mild to severe clinical grades before finally progressing to SCC. However, more recent data could refute this assumption. On the contrary, it was shown that invasive SCC can most frequently be associated with AK I lesions according to Röwert-Huber.14 It must be assumed that even subclinical AKs can develop into SCC without first becoming clinically conspicuous.

In addition, a study of basal growth of AK showed that AKs with a distinct basal growth pattern (PRO III) were most common in close proximity to invasive SCC.15 This leads to the assumption that basal atypical keratinocytes play an important role in the progression of AK to SCC.

In summary, the results of these studies suggest that the clinically and/or histologically diagnosed grade does not predict the risk of progression from individual AK lesions to SCC.

Therefore, all patients with AK should be treated early and effectively to prevent progression to invasive squamous cell carcinoma.13

Therapy

The primary treatment goal is complete clearance of all visible and subclinical AK lesions in the patient.16 Various field-directed therapy options are available for this purpose:13

In the case of topical drug therapies and PDT, there are drugs approved for lesion-directed, as well as those approved for field-directed therapy of AK. When selecting the form of therapy, the respective approval should be taken into account. The choice of therapy also depends on the previous course of the disease, the age of the patient, the medications to be taken, and the extent of the skin damage (solitary AK lesions or field cancerisation).8 Other available but exclusively lesion-directed therapeutic options, such as cryotherapy and other surgical procedures, are rather unsuitable for the treatment of field cancerization. The advantage of field-directed therapy options is that they are used to treat subclinical lesions in addition to those that have been clinically diagnosed.13
According to a 2014 network meta-analysis, PDT with narrow-spectrum red light is currently considered the most effective treatment modality for mild to moderate AKs on the face and scalp.17 In another meta-analysis of treatment interventions for AK, ALA-PDT showed the highest probability of complete clearance.18

References

  1. De Berker et al. British Journal of Dermatology 2017;176: 20–43
  2. Emre S. World J Dermatol 2016;5:115-124.
  3. Criscione VD, et al. Cancer 2009;115:2523–30.
  4. Harvey I et al. Br J Cancer 1996;74:1302–7.
  5. Memon AA et al. Br J Dermatol 2000;142:1154–9.
  6. Frost CA and Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994 Oct;131(4):455-64.
  7. Schwartz RA et al. J Eur Acad Dermatol Venereol 2008;22:606-615.
  8. Dirschka T et al. J Dermatolog Treat 2017;28:431-442.
  9. Olsen EA et al. J Am Acad Dermatol 1991;24:738-743.
  10. Röwert-Huber J et al. Br J Dermatol 2007;156(Suppl 3):8-12.
  11. Schmitz L et al. J Eur Acad Dermatol Venereol 2016;30:1303-1307.
  12. Schmitz L et al. J Eur Acad Dermatol Venereol 2018;32:745-751.
  13. Werner RN et al. J Eur Acad Dermatol Venereol 2015;29:2069-2079.
  14. Fernández-Figueras MT et al. J Eur Acad Dermatol Venereol 2015;29:991-997.
  15. Schmitz L et al. Br J Dermatol 2019;180:916-921.
  16. Reinhold U. Future Oncol 2017;13:2413-2428.

UKBF-2022-006j-V01, Date of preparation December 2022