Actinic keratosis

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Authors: Mikael Häggström; Authors of integrated Creative Commons article[1] [note 1]
Actinic keratosis may present as suspected malignant skin excisions.


Generally 10% neutral buffered formalin.

  See also: General notes on fixation

Gross processing

Multiple lesions of actinic keratosis on the scalp.

Gross examination


  • Color
  • Well-defined or diffuse border
  • Size
  • Any elevation

Lesions of actinic keratosis are typically ill-marginated, erythematous, scaling, and rough papules or patches. These will typically be found in areas displaying other signs of solar damage, such as atrophy, uneven pigmentation, and telangiectasias.[1]

Tissue selection

Tissue selection from suspected malignant skin lesions, by lesion size:[2][note 2]
<4 mm 4 - 8 mm 9 - 15 mm
Tissue selection from skin excision with less than 4 mm suspected malignant lesion.png Tissue selection from skin excision with 4-8 mm suspected malignant lesion.png Tissue selection from skin excision with 9-15 mm suspected malignant lesion.png

In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used. Further information: Gross processing of skin excisions

Microscopic evaluation

  • Evaluation mainly consists of:


Normal skin (left) and actinic keratosis (right) with the defining characteristic of atypical basal keratinocytes that does not involve the full thickness of the epidermis.
1(a). Actinic keratosis at low magnification, showing discontinuous parakeratosis (as the dysplastic process spares adnexal structures, including sebaceous glands. This specimen also demonstrates dense dermal elastosis).[1]

By definition, actinic keratosis is confined to foci within the epidermis.[1]
it also generally has:[1]

  • Aggregates of atypical, pleomorphic keratinocytes which show nuclear atypia, dyskeratosis, and loss of polarity.
  • Hyperkeratosis and parakeratosis, the latter overlying the abnormal cells in the epidermis. Due to the sparing of segments of the epithelium overlying adnexal structures, a characteristic pattern of alternating orthokeratosis and parakeratosis, referred to as the “flag-sign,” can often be seen (Figure 1(a)).
  • Atypical keratinocytes will not span the full thickness of the epidermis (Figure 1(b)), although those in the basal cell layer will frequently extend into the granular and cornified layers. The exception to this criterion is the Bowenoid variant of actinic keratosis, which resembles cutaneous squamous-cell carcinoma in situ (Bowen's disease) but is less disordered with less nuclear atypia and crowding.
  • A more basophilic basal layer than normal, which is generally thought to be a consequence of the close crowding of atypical keratinocytes (Figure 1(b)).
  • Some cases will also show basal layer degeneration and the formation of Civatte bodies (Figure 1(c)), the result of a lichenoid infiltrate with irregular acanthosis. This can be distinguished from lichenoid dermatitis by the presence of keratinocyte atypia.
  • Dermoepidermal junction irregularities, with small round buds at the basal cell layer that will protrude slightly into the upper papillary dermis (Figure 1(d)).
  • There is almost always an associated solar elastosis in the dermis, and a lack thereof can often be sufficient to prompt reconsideration of the diagnosis.

Squamous cell-like skin proliferations: Differential diagnosis

Main differential diagnoses and their characteristics:[3]

Clinical clues

  • Biopsy from sun exposed area (including the face, neck, dorsal hands, and forearms, upper chest, back, and scalp).[1]
  • Generally middle-aged or older individuals.[1]

Further workup

Once a diagnosis of actinic keratosis is established, optionally characterize the degree of atypia into either mild, moderate or severe.

Actinic keratosis with moderate atypia, spanning approximately half of stratum spinosum.

Histopathology report

  • Objective findings
  • A diagnosis of actinic keratosis
  • Optionally: The degree of atypia.
  • Even absence of evidence of malignancy.

Example for the case in "Further workup":

Histopathology of actinic keratosis with moderate atypia.jpg
(Skin excision with squamous stratified epithelium with moderate) atypia in the basal epidermis (, with enlarged and dark cell nuclei as well as slightly disrupted cell arrangements.) No evidence of malignancy.

  See also: General notes on reporting


  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
  2. The excision example shows a superficial basal cell carcinoma.
  3. - Buschke–Löwenstein tumor is an alternative name for verrucous squamous cell carcinoma in the ano-genital region.
    - Carcinoma cuniculatum is a characteristic form of verrucous squamous cell carcinoma on the sole.
  4. Inverted follicular keratosis is generally thought to be a rare variant of seborrheic keratosis, but this position is not universally accepted.
    - Karadag, AyseSerap; Ozlu, Emin; Uzuncakmak, TugbaKevser; Akdeniz, Necmettin; Cobanoglu, Bengu; Oman, Berkant (2016). "Inverted follicular keratosis successfully treated with imiquimod ". Indian Dermatology Online Journal 7 (3): 177. doi:10.4103/2229-5178.182354. ISSN 2229-5178. 

Main page


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Initially largely copied from: Yanofsky, Valerie R.; Mercer, Stephen E.; Phelps, Robert G. (2011). "Histopathological Variants of Cutaneous Squamous Cell Carcinoma: A Review ". Journal of Skin Cancer 2011: 1–13. doi:10.1155/2011/210813. ISSN 2090-2905. 
    -"This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited."
  2. There are many variants for the processing of skin excisions. These examples use aspects from the following sources: ". Ochsner J 5 (2): 22–33. 2003. PMID 22826680. PMC: 3399331. Archived from the original. . 
    - With a "standard histologic examination" that, in addition to the lesion, only includes one section from each side along the longest diameter of the specimen.
    - It also shows an example of circular coverage, with equal coverage distance in all four directions.
    - The entire specimen may be submitted if the risk of malignancy is high.
  3. Initially copied from: Paolino, Giovanni; Donati, Michele; Didona, Dario; Mercuri, Santo; Cantisani, Carmen (2017). "Histology of Non-Melanoma Skin Cancers: An Update ". Biomedicines 5 (4): 71. doi:10.3390/biomedicines5040071. ISSN 2227-9059. 
    "This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ("

Image sources