Actinic keratosis

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

Fixation

Generally 10% neutral buffered formalin.

  See also: General notes on fixation

Gross processing

Multiple lesions of actinic keratosis on the scalp.

Gross examination

Note:

• 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.

Tissue selection

Tissue selection from suspected malignant skin lesions, by lesion size:

<4 mm	4 - 8 mm	9 - 15 mm

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:

• Establishing a diagnosis of actinic keratosis rather than differential diagnoses:
• Excluding any presence of cutaneous squamous cell carcinoma in the lesion.

Characteristics

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).

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

• 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.

• 

  1(b). Early actinic keratosis with keratinocyte dysplasia confined to the lower third of the epidermis.

• 

  Civatte body (in a case in lichen planus).

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  1(d). A more established lesion of actinic keratosis demonstrating nearly full thickness keratinocyte dysplasia and prominent budding of the basal layer into the superficial dermis.

Squamous cell-like skin proliferations: Differential diagnosis

Main differential diagnoses and their characteristics:

• 

  Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread.

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  Squamous-cell carcinoma in situ (Bowen’s disease): Atypical keratinocytes at every layer of epidermis.

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  Actinic keratosis: Atypical keratinocytes that do not span the full thickness of the epidermis (or, in Bowenoid variant, are less disordered with less nuclear atypia and crowding).

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  Keratoacanthoma: Symmetrical and circumscribed proliferation of keratinocytes, with central horn plug, with epidermis that extends over the tumor. It can be regarded as a highly differentiated SCC.

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  Crush artifacts: Needles used to orient the skin sample may create crush artifacts (black arrow) mimicking cellular atypia with mainly hypereosinophilia and nuclear pleomorphism. Image also shows folding artifacts (white arrows).

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  Adnexal carcinomas: Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features.

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  Adenosquamous carcinoma: Mixed glandular and squamous differentiation.

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  Verruca vulgaris: Marked hyperkeratosis and papillomatosis. Rete ridges slope inward at the borders of the lesion.

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  Verrucous squamous cell carcinoma: Exophytic squamous proliferation with marked papillomatosis and low atypia and the presence of koilocyte-like changes. Found in head and neck locations, as well as in the genitalia and sole of the foot.

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  Inverted follicular keratosis:: Sharply circumscribed endophytic verrucous proliferation with prominent squamous features.

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  Seborrheic keratosis: Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present.

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  Bowenoid papulosis: Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease.

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  A melanoma may have relatively plentiful eosinophilic cytoplasm, and be seemingly continuous with the squamous epithelium (at left in image), thus resembling a squamous cell carcinoma. However, the nesting of cells at right in the image is more characteristic of a melanoma.

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  Metastasis: Personal medical history of the patient, nodular proliferation without connection to epidermis, immunohistochemical evaluation. Squamous-cell carcinoma metastasis from lungs to the skin is pictured.

Clinical clues

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

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":

(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

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