Squamous-cell carcinoma of the skin
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.
Contents
- 1 Fixation
- 2 Gross processing
- 3 Microscopic evaluation
- 4 Re-excisions
- 5 Notes
- 6 Main page
- 7 References
Fixation
Generally 10% neutral buffered formalin.
- See also: General notes on fixation
Gross processing
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
<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 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

- 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:
- Atypia spanning the full thickness of the epidermis, being the main finding.[1]
- Hyperkeratosis and parakeratosis.[1]
- 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.
- Typical squamous-cell carcinoma cells are large with abundant eosinophilic cytoplasm and large, often vesicular, nuclei.[3]
- Two types of multinucleated cells may be seen:[1]
- Multinucleated giant cells
- Dyskeratotic cells engulfed in the cytoplasm of keratinocytes.
- Occasionally, cells of the upper epidermis will undergo vacuolization.[1]
There may be a mild to moderate lymphohistiocytic infiltrate detected in the upper dermis.[1]
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
Main differential diagnoses and their characteristics:[4]
Invasive squamous-cell carcinoma of the skin: Atypical and pleomorphic keratinocytes, involving the dermis and the sub-cutis with a potential metastatic spread.
Squamous-cell carcinoma in situ (Bowen’s disease): Atypical keratinocytes at every layer of epidermis.
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).
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.
Inverted follicular keratosis:[notes 5]: Sharply circumscribed endophytic verrucous proliferation with prominent squamous features.
Seborrheic keratosis: Acanthosis, absence of atypia, pseudo-horn cysts, in inflamed lesions, mitoses may be present.
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]
Overlap of squamous-cell and basal-cell carcinoma
Basal-cell carcinoma is generally distinguishable by for example relatively less cytoplasm, palisading, cleft formations and absence of horn cyst formation.
Yet, a high prevalence means a relatively high incidence of borderline cases, with main forms being:
Basaloid squamous-cell carcinoma, in this case showing a biphasic pattern with conventional dysplastic squamous surface component associated with basaloid elements (arrow heads) and conventional squamous cell carcinoma intimately associated with basaloid component (arrow).[5]
In unclear cases, the most useful immunohistochemistry marker appears to be MOC-31, which essentially always stains metatypical basal-cell carcinomas but not basaloid squamous-cell carcinomas.[6] UEA-1 appears to be the second most useful marker, staining almost all basaloid squamous-cell carcinomas but only a few metatypical basal-cell carcinomas.[6]
Clinical clues
In situ versus invasive
- In situ (Bowen's disease[notes 2])
- Intact basement membrane.
High magnification, demonstrating an intact basement membrane.[1]
- Invasive
- Dermal infiltration
Superficially invasive squamous cell carcinoma (SCCSI). These lesions often do not show the marked pleomorphism and atypical nuclei of SCC in situ, but demonstrate early keratinocyte invasion of the dermis.[1]
High magnification demonstrates the pleomorphism of the invading keratinocytes.[1]
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.[7]
Degree of differentiation
Applicable to invasive SCC.
Well-differentiated (and yet invasive) SCC, showing prominent keratinization and may form “pearllike” structures where dermal nests of keratinocytes attempt to mature in a layered fashion. Well-differentiated SCC has slightly enlarged, hyperchromatic nuclei with abundant amounts of cytoplasm. Intercellular bridges will frequently be visible.[1]
Moderately differentiated lesions of invasive SCC show much less organization and maturation with significantly less keratin formation.[1]
Poorly differentiated, where attempts at keratinization are often no longer evident. This is a clear-cell squamous cell carcinoma. The dysplastic cells here infiltrate in cords through the dermis. Poorly differentiated SCC has greatly enlarged, pleomorphic nuclei demonstrating a high degree of atypia and frequent mitoses.[1]
Perineural or vascular invasion
In SCC, at least a quick glance for any perineural or vascular invasion is warranted.
Perineural invasion: the arrow indicates a large peripheral nerve that has been surrounded by tumor cells.[1]
Vascular invasion: the arrow indicates a small cluster of atypical squamous cells in a small vessel.[1]
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] |
---|---|
|
|
Microscopy report
On this resource, the following formatting is 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:
- >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]."[7] 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:
((Skin excision with squamous epithelium with))(central 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.)) |
Invasive squamous cell carcinoma:
((Skin excision with ))( with 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.)) |
- See also: General notes on reporting
Re-excisions
Gross processing
Depending on radicality of previous excision:
- Previously radical (including thin margins): Submit at least one central section across the surgical scar.[8]
- Previously non-radical:
Notes
- ↑ 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.
- ↑ 2.0 2.1 2.2 Squamous-cell carcinoma in situ is essentially equivalent to and used interchangeably with the term Bowen’s disease.(Yanofsky, 2011)
- ↑ 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. - ↑ 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: . ISSN 2229-5178. - ↑ Main sun-exposed areas: body, including the face, neck, dorsal hands, and forearms, upper chest, back, and scalp. (Yanofsky, 2011)
- ↑ A more comprehensive report may state "Clear margins at over __ mm" or the value thereof if it has been measured more exactly.
- ↑ 8.0 8.1 Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.
Main page
References
- ↑ 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 1.21 1.22 1.23 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: . 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." - ↑ There are many variants for the processing of skin excisions. These examples use aspects from the following sources:
- . Handläggning av hudprover – provtagningsanvisningar, utskärningsprinciper och snittning (Handling of skin samples - sampling instructions, cutting principles and incision. Swedish Society of Pathology.
- For number of slices and coverage of lesions, depending on size. - Monica Dahlgren, Janne Malina, Anna Måsbäck, Otto Ljungberg. Stora utskärningen. KVAST (Swedish Society of Pathology). Retrieved on 2019-09-26.
- For slices towards the pointy ends to determine radicality, which can be parallel to the slices through the lesions (shown), or as longitudinal slices that go through each pointy end. - . Dermatopathology Grossing Guidelines. University of California, Los Angeles. Retrieved on 2019-10-23.
- For microtomy of the most central side at the lesion - "The principles of mohs micrographic surgery for cutaneous neoplasia
- 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. - . Handläggning av hudprover – provtagningsanvisningar, utskärningsprinciper och snittning (Handling of skin samples - sampling instructions, cutting principles and incision. Swedish Society of Pathology.
- ↑ Dr Nicholas Turnbull, A/Prof Patrick Emanual (2014-05-03). Squamous cell carcinoma pathology. DermNetz.
- ↑ 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: . 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/)."
- ↑ El-Mofty, SK. (2014). "Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas
". Medicina Oral Patología Oral y Cirugia Bucal: e377–e385. doi: . ISSN 16986946.
License: CC BY 2.5 - ↑ 6.0 6.1 Webb, David V.; Mentrikoski, Mark J.; Verduin, Lindsey; Brill, Louis B.; Wick, Mark R. (2015). "Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal ". Annals of Diagnostic Pathology 19 (2): 70–75. doi: . ISSN 10929134.
- ↑ 7.0 7.1 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.
- ↑ 8.0 8.1 Katarzyna Lundmark. Handläggning av hudprover – provtagningsanvisningar, utskärningsprinciper och snittning (Handling of skin samples - sampling instructions, cutting principles and incision. Swedish Society of Pathology.
- ↑ Pathology Department at NU Hospital Group, Sweden, 2019-2020.