Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects<sup>,</sup>

Reinehr, Clarissa Prieto Herman; Bakos, Renato Marchiori

doi:10.1016/j.abd.2019.10.004

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Continuing Medical Education • An. Bras. Dermatol. 94 (6) • 2019 • https://doi.org/10.1016/j.abd.2019.10.004 copy

Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects^☆ ☆ How to cite this article: Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol. 2019;94:637-57. ^,^☆☆ ☆☆ Study conducted at the Department of Dermatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

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Abstract

Actinic keratoses are dysplastic proliferations of keratinocytes with potential for malignant transformation. Clinically, actinic keratoses present as macules, papules, or hyperkeratotic plaques with an erythematous background that occur on photoexposed areas. At initial stages, they may be better identified by palpation rather than by visual inspection. They may also be pigmented and show variable degrees of infiltration; when multiple they then constitute the so-called field cancerization. Their prevalence ranges from 11% to 60% in Caucasian individuals above 40 years. Ultraviolet radiation is the main factor involved in pathogenesis, but individual factors also play a role in the predisposing to lesions appearance. Diagnosis of lesions is based on clinical and dermoscopic examination, but in some situations histopathological analysis may be necessary. The risk of transformation into squamous cell carcinoma is the major concern regarding actinic keratoses. Therapeutic modalities for actinic keratoses include topical medications, and ablative and surgical methods; the best treatment option should always be individualized according to the patient.

KEYWORDS
Dermoscopy; Keratosis, actinic; Neoplasms, squamous cell; Precancerous conditions; Skin neoplasms

Publications in chronological order	What the classification is based on
Olsen et al. (1991)⁷⁷77 Olsen EA, Abernethy ML, Kulp-Shorten C, Callen JP, Glazer SD, Huntley A, et al. A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol. 1991;24:738-43.	Clinical examination
	Grade I: easily palpable and barely visible
	Grade II: easily visible and palpable
	Grade III: visible and hyperkeratotic
Goldberg et al. (1994)⁸⁰80 Goldberg LH, Joseph AK, Tschen JA. Proliferative actinic keratosis. Int J Dermatol. 1994;33:341-5.	Clinical examination and evolutionary characteristics
	Proliferative lesions: resistant to therapy, tendency to growth and progression to SCC
	Non-proliferative
Cockerell (2000)³3 Cockerell CJ. Histopathology of incipient intraepidermal squamous cell carcinoma (“actinic keratosis”). J Am Acad Dermatol. 2000;42:11-7.	Clinical and histological examination
	Grade I: flat macula without hyperkeratosis, including subclinical, histopathology with atypia of keratinocytes in the lower third of the epidermis
	Grade II: hyperkeratotic lesion with variable induration, histopathology with atypia in the lower two-thirds of the epidermis
	Grade III: indurated plaques, may be pigmented, intense atypia throughout the epithelium
Röwert-Huber et al. (2007)⁶6 Röwert-Huber J, Patel MJ, Forschner T, Ulrich C, Eberle J, Kerl H, et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol. 2007;156:8-12.	Histological findings
	Grade I: atypical keratinocytes in the basal and suprabasal layers of the epidermis
	Grade II: atypical keratinocytes in the lower two-thirds of the epidermis
	Grade III: atypia superior to two-thirds of the epidermis and involvement of the adnexal epithelium
Zalaudek et al. (2014)⁷⁹79 Zalaudek I, Piana S, Moscarella E, Longo C, Zendri E, Castagnetti F, et al. Morphologic grading and treatment of facial actinic keratosis. Clin Dermatol. 2014;32:80-7.	Dermatoscopic findings
	Grade I: erythematous pseudonetwork, discrete scales
	Grade II: erythematous pseudonetwork, keratotic and enlarged follicular openings
	Grade III: hyperkeratosis with thick scales or enlarged keratotic follicular openings associated with scales

Clinical diagnosis	Dermatoscopic findings
Actinic keratosis	Red pseudonetwork
Actinic keratosis evolving to in situ SCC	Starburst pattern
In situ SCC	Yellowish opaque structures and dotted vessels
In situ SCC progressing to invasive SCC	White areas without structures, dotted and hairpin vessels
Minimally invasive SCC	Central keratin mass and vessels hairpin
Invasive SCC	Central keratin mass, ulceration, and irregular linear vessels

	Pigmented actinic keratosis	Lentigo maligna melanoma	Senile lentigo	Seborrheic keratosis	Lichenoid keratosis
Rhomboidal structures	+	+	-	-	+/-
Grayish-brown granulation	Uniform perifollicular distribution	Diffuse distribution	-	-	Diffuse distribution
Annular-granular pattern	+	+	-	-	+
Asymmetric follicular pigmentation	-	+	-	-	-
Homogeneous areas of pigment	-	+	-	-	-
Moth-eaten border	+/-	-	+	+	-
Jelly sign	-	-	+	+	-
Fingerprint-like structures	-	-	+	+	-

Modalities of surgical treatments	Topical and oral treatment modalities
Cryosurgery (recommendation grade A, level of evidence 1++)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.	5-Fluorouracil (recommendation grade A, level of evidence 1++)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.
	Imiquimod (recommendation grade A, level of evidence 1++)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.
CO₂ laser (recommendation grade B, level of evidence 1+)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.	Ingenol mebutate (recommendation grade A, level of evidence 1+)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.
	Photodynamic therapy (recommendation grade A, level of evidence 1+)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.
Curettage and electrodessication (recommendation grade D, level of evidence 4)	Diclofenac (recommendation grade A, level of evidence 1+)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.
	Topical retinoids (recommendation grade B, level of evidence 1+)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.
Surgical exeresis (recommendation grade D, level of evidence 4)	Systemic therapies (recommendation grade C, level of evidence 2+)¹³¹131 De Berker D, McGregor JM, Mohd Mustapa MF, Exton LS, Hughes BR. British Association of Dermatologists’ guidelines for the care of patients with actinic keratosis 2017. Br J Dermatol. 2017;176:20-43.

Answers: Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors. An Bras Dermatol. 2019;94(5):503-520.
1. c	3. a	5. d	7. a	9. a
2. b	4. c	6. c	8. b	10. d

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[1] * Corresponding author. E-mail:cla.reinehr@gmail.com (C.P.H. Reinehr).

Cutaneous horn	Conical projection, markedly hyperkeratotic, white to yellowish in color, erythematous papular base with varying degrees of infiltration⁷⁰70 Mantese SA, de O, Diogo PM, Rocha A, Berbert ALCV, Ferreira AKM, et al. Corno cutâneo: estudo histopatológico retrospectivo de 222 casos. An Bras Dermatol. 2010;85:157-63.
	Differential diagnosis with squamous cell carcinoma⁶⁸68 Moy RL. Clinical presentation of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000;42:8-10.
Actinic cheilitis	Reddish and/or leukoplastic plaque with desquamation, fissures, ulcerations, and/or areas of focal hyperkeratosis on the lips (95% of the cases in the lower lips)
	Differential diagnosis with squamous cell carcinoma⁷¹71 Vieira RA, Minicucci EM, Marques MEA, Marques SA. Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects. An Bras Dermatol. 2012;87:105-14.
Pigmented actinic keratosis	Scaly papules or plaques, rough with brown and black color⁶⁶66 Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Ger Soc Dermatol. 2007;5:970-6.
	Differential diagnosis with lentigo maligna
Lichenoid actinic keratosis	Pink plaque or papule
	Usually on the upper extremities or trunk
	Differential diagnosis mainly with basal cell carcinoma⁶⁶66 Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Ger Soc Dermatol. 2007;5:970-6.