Squamous-cell carcinoma of the skin

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Authors: Mikael Häggström; Authors of integrated Creative Commons article[1] [notes 1]
Squamous-cell carcinoma (SCC) of the skin may present as suspected malignant skin excisions.

Fixation

Generally 10% neutral buffered formalin.

See also: General notes on fixation

Gross processing

Squamous cell carcinoma in situ.
SCC with scaling and ulceration.

If re-excision, see separate section at bottom.

Gross examination

Note:

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

Squamous cell carcinoma in situ (Bowen’s disease[notes 2]) often presents as an asymptomatic, erythematous, well-demarcated, scaly patch or plaque. It usually has a fairly irregular border. Lesions may become hyperkeratotic, crusted, fissured or ulcerated, and can occasionally be pigmented, especially when found in the genital region and the nails.[1]

Invasive SCC typically has ill-marginated, erythematous, scaling, and rough papules or patches.[1]

Tissue selection

Tissue selection from suspected malignant skin lesions, by lesion size:[2][notes 3]
<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 consists of:

  • Determining whether it is a SCC rather than a differential diagnosis.
  • Distinguishing a SCC in situ from an invasive SCC
  • Radicality, and if radical, determine the least distance to a margin.

Characteristics

Squamous cell carcinoma in situ, showing prominent dyskeratosis and aberrant mitoses at all levels of the epidermis, along with marked parakeratosis.[1]
  • Malignant keratinocytes demonstrating intense mitotic activity, pleomorphism, and greatly enlarged nuclei. They will also show a loss of maturity and polarity, giving the epidermis a disordered or “windblown” appearance.

In situ

In SCC in situ (Bowen’s disease[notes 2]) the epidermis will show:[1]

  • Atypia spanning the full thickness of the epidermis, being the main finding.
  • Hyperkeratosis and parakeratosis
  • Marked acanthosis with elongation and thickening of the rete ridges. These changes will overly keratinocytic cells which are often highly atypical and may in fact have a more unusual appearance than invasive SCC.
  • Two types of multinucleated cells may be seen:
  • Multinucleated giant cell
  • Dyskeratotic cell engulfed in the cytoplasm of a keratinocyte.
  • Occasionally, cells of the upper epidermis will undergo vacuolization, demonstrating an abundant and strongly eosinophilic cytoplasm.

There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis.[1]

Histopathology of squamous cell carcinoma in situ.jpg
Atypia spanning the full thickness of the epidermis is enough in this case for the diagnosis of SCC in situ. There is also a lymphohistiocytic infiltrate.

Squamous cell-like skin proliferations: Differential diagnosis

Condition[3] Characteristics[3] Image
Invasive squamous-cell carcinoma of the skin Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread. Micrograph of invasive squamous cell carcinoma - 150x.jpg
Squamous-cell carcinoma in situ (Bowen’s disease) Atypical keratinocytes at every layer of epidermis. Micrograph of squamous cell carcinoma in situ - 100x.jpg
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). Micrograph of actinic keratosis - low magnification.jpg
Keratoacanthoma Symmetrical and circumscribed proliferation of keratinocytes, with central horn plug, with epidermis that extends over the tumor. Highly differentiated SCC. Keratoacanthoma (2197016163).jpg
Adnexal carcinomas Squamous differentiation, but does not show connection with the epidermis and highlights adnexal features. Micrograph of microcystic adnexal carcinoma - superficial follicular keratin-filled cysts.jpg
Adenosquamous carcinoma Mixed glandular and squamous differentiation. Micrograph of cutaneous adenosquamous carcinoma - 40x.jpg
Verrucous squamous cell carcinoma[notes 4] 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. Micrograph of penile verrucous carcinoma - 20x.jpg Micrograph of penile verrucous carcinoma - 200x.jpg
Inverted follicular keratosis[notes 5] Sharply circumscribed endophytic verrucous proliferation with prominent squamous features. Inverted follicular keratosis 1 (3059309003).jpg Inverted follicular keratosis 3 (3060145758).jpg
Seborrheic keratosis Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present. Histopathology of seborrheic keratosis.jpg
Bowenoid papulosis Atypical keratinocytes and mitoses. Histology similar to Bowen’s disease. Low-magnification micrograph of oral bowenoid papulosis.jpg High-magnification micrograph of oral bowenoid papulosis.jpg
Metastasis Personal medical history of the patient, nodular proliferation without connection to epidermis, immunohistochemical evaluation.
Squamous-cell carcinoma metastasis from lungs to the skin

In contrast to actinic keratosis, the basal epidermal layer in SCC in situ is frequently spared, and will show little to no visible atypia. Additionally, SCC in situ will almost always involve both the interfollicular and adjacent follicular epithelium and adnexal structures.[1]

Clinical clues

  • Biopsy from sun exposed area.[notes 6][1]
  • Generally middle-aged or older individuals.[1]

In situ versus invasive

In situ (Bowen's disease[notes 2])
Intact basement membrane.
Invasive
Dermal infiltration

This infiltrate can be somewhat difficult to detect in the early stages of invasion: however, additional indicators such as full thickness epidermal atypia and the involvement of hair follicles can be used to facilitate the diagnosis. Later stages of invasion are characterized by the formation of nests of atypical tumor cells in the dermis, often with a corresponding inflammatory infiltrate.[1]

Radicality

Determine whether the distances between atypical cells are more or less than 1 mm from the deep and radial edges. If less than 1 mm, quantify the distance.[4]

Degree of differentiation

Applicable to invasive SCC.

Perineural or vascular invasion

In SCC, at least a quick glance for any perineural or vascular invasion is warranted.

Vascular invasion most frequently involves a complete encircling of the nerve or vessel by tumor cells. An incomplete, crescent-like pattern of atypical cells is also commonly seen. Occasionally, tangential contact, permeation, and lamination can be observed. Invasion almost always occurs contiguous to the main body of the tumor; however, it has been known on occasion to affect more distant nerve and vascular sites. Usually, tumor cells arranged in solid or sheet-like patterns are less invasive, and will pass around the nerve or vessel. In contrast, individual tumor cells will generally penetrate and track along associated structures.[1]

Optionally: Grading

Multiple variables can be combined to classify a SCC as low or high grade:

Low-Grade SCC[1] High-Grade SCC[1]
  • Well to moderately differentiated: intercellular bridges and keratin pearls
  • Tumor cells arranged in solid or sheet-like patterns
  • Association with solar damage and precursor actinic keratosis
  • Diameter less than 2 cm
  • Depth less than 2 mm
  • Poorly differentiated: clear-cell, sarcomatoid, or single cell features
  • Presence of infiltrating individual tumor cells
  • Arising de novo or in site of prior injury (ulcer, burn scar, or osteomyleitis)
  • Perineural and/or perivascular invasion
  • Diameter greater than 2 cm
  • Depth greater than 2 mm

Microscopy report

In this page, the following signs and text coloring are used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))

Components of the report:

  • Diagnosis of squamous-cell carcinoma
  • Whether it is in situ or invasive. If invasive:
  • Degree of differentiation.
  • (High or low grade.)
  • ((Even absence of perineural or vascular invasion.))
  • Radicality, mainly into either of the following: edit
  • >1 mm (as per Radicality above): "Clear margins".[notes 7]
  • <1 mm but not continuous with edge: "Close margins at __ mm at (location)[notes 8]."[4] Numbers are generally given at an exactness of 0.1 mm.
  • Continuous with margin: "Not radically excised at (location)[notes 8]."

Examples

Squamous cell carcinoma in situ:

Micrograph of squamous cell carcinoma in situ - 100x.jpg
((Squamous epithelium with parakeratosis. ))(The epidermis is thickened and exhibits disturbed stratification. )All cell layers show atypical epithelial cells with polymorphic and partially hyperchromatic nuclei. The basement membrane is intact. Clear margins. ((There is elastosis and inflammatory cells in the dermis.))

Moderately differentiated invasive squamous cell carcinoma:

(Squamous epithelium with central ulceration, surrounded by hyperkeratosis. )In this area in the dermis there are inflitrative nests of epithelioid cells with nuclear pleomorphism and <sparse / moderate / abundant> keratin formation. Atypical cells are seen ___ mm from the deep/radial resection edge. / Clear margins. ((No perineural or vascular invasion is seen. There are inflammatory infiltrates adjacent to atypical cells. General elastosis is noted in the dermis.))
  • Moderately differentiated
See also: General notes on reporting

Re-excisions

Gross processing

Tissue selection from skin re-excisions.png

edit
Depending on radicality of previous excision:

  • Previously radical (including thin margins): Submit at least one central section across the surgical scar.[5]
  • Previously non-radical:
  • Visible lesion: Submit the entire scar.[5]
  • Lesion not visible: At least one additional radicality slice towards the tips, up to the entire specimen.[6]

Microscopic evaluation

Suspected squamous cell carcinoma in re-excision, with a band of epithelioid cells.

Focus on the scar area, and look for epithelioid cells.

Notes

  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. 2.0 2.1 2.2 Squamous-cell carcinoma in situ is essentially equivalent to and used interchangeably with the term Bowen’s disease.(Yanofsky, 2011)
  3. The excision example shows a superficial basal cell carcinoma.
    • 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. 
  5. Main sun-exposed areas: body, including the face, neck, dorsal hands, and forearms, upper chest, back, and scalp. (Yanofsky, 2011)
  6. A more comprehensive report may state "Clear margins at over __ mm" or the value thereof if it has been measured more exactly.
  7. 8.0 8.1 Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 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. 3.0 3.1 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 (http://creativecommons.org/licenses/by/4.0/)."
  4. 4.0 4.1 1 mm as cutoff for close margin: Brodie M Elliott, Benjamin R Douglass, Daniel McConnell, Blair Johnson, Christopher Harmston (2018-12-14). New Zealand Medical Journal.
  5. 5.0 5.1 Katarzyna Lundmark. Handläggning av hudprover – provtagningsanvisningar, utskärningsprinciper och snittning (Handling of skin samples - sampling instructions, cutting principles and incision. Swedish Society of Pathology.
  6. NU Hospital Group, Sweden