Squamous-cell carcinoma of the skin

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


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


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

Squamous cell carcinoma in situ (essentially synonymous with Bowen’s disease) often presents as an erythematous, well-demarcated, scaly patch or plaque, with a fairly irregular border. They occasionally present as dark skin focalities, 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][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 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.


Squamous cell carcinoma in situ, showing prominent dyskeratosis and aberrant mitoses at all levels of the epidermis, along with marked parakeratosis.[1]
Main characteristics of squamous-cell carcinoma regardless of location.
  • 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) 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]

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

Main differential diagnoses and their characteristics:[4]

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. In such cases, look particularly at the surface and attempt to classify as either of the following:

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

  • 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]

In situ versus invasive

In situ (Bowen's disease)
Intact basement membrane.
Invasive SCC

Invasive SCC is defined by 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]


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

This is applicable to invasive SCC. edit

Perineural or vascular invasion

In SCC, look for any perineural invasion,[note 5] and at least a quick glance for any vascular invasion.

Perineural invasion is defined as tumor in close proximity to nerve and involving at least 33% of its circumference or tumor cells within any of the three layers of the nerve sheath (epineurium, perineurium and endoneurium).[8] First look along the border of the tumor, followed by surrounding tissue, and if still not found, look through the rest of the tumor area as well.[1]


The AJCC, 8th Ed., does not include any staging system for skin SCC, except for tumors of the vulva.[9]

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

Further work-up

In vulvar squamous cell carcinoma, generally perform p16 immunohistochemistry, which is considered a surrogate marker for oncogenic HPV infection.[10]

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 invasion[note 5]
  • ((Even absence of or vascular invasion.))
  • Radicality, mainly into either of the following: edit
  • >1 mm (as per Radicality above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
  • <1 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]."[7] Numbers are generally given at an exactness of 0.1 mm.
  • Continuous with margin: "Not radically excised at (location)."
  • Staging is only applicable for the head and neck (lip, ear, face, scalp and neck - see staging at Medscape) and vulva (see staging at cancer.net).

((You may also add a synoptic report (see examples):))


Squamous cell carcinoma in situ:

Micrograph of squamous cell carcinoma in situ - 100x.jpg
((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, right breast, excision:)
Invasive keratinizing squamous cell carcinoma, well differentiated, measuring 1.7 cm in greatest dimension.
Surgical margins are negative for carcinoma.
(Negative for lymphovascular and perineural invasion.)
((Solar elastosis.))

((Example synoptic report:))

  • Procedure: Skin excision.
  • Tumor site: Scalp
  • Tumor laterality: Right
  • Tumor focality: Unifocal
  • Tumor size: 1.6 x 1.4 cm
  • Tumor depth of invasion: 0.3 cm
  • Histologic type: Squamous cell carcinoma
  • Histologic grade: Moderately differentiated
  • Specimen margins: Uninvolved by invasive tumor.
  • Lymphovascular invasion: Not identified
  • Perineural invasion: Not identified
  • Regional lymph nodes: No lymph nodes submitted or found.
  • Pathologic Stage Classification (pTNM, AJCC 8th Edition):
  • Primary Tumor: pT1
  • Regional Lymph Nodes: pNX: Regional lymph nodes cannot be assessed
  • Additional pathologic findings: Actinic keratosis

Example microscopic description of invasive squamous cell carcinoma:

  • Squamous epithelium, with central ulceration, surrounded by hyperkeratosis. In this area in the dermis there are infiltrative nests of epithelioid cells with nuclear pleomorphism and <sparse / moderate / abundant> keratin formation.

  See also: General notes on reporting


Gross processing

Tissue selection from skin re-excisions.png

((Submit the entire specimen, or)) depending on radicality of previous excision:

  • Previously radical (including thin margins): Submit at least one central section across the surgical scar.[11]
  • Previously non-radical:
  • Visible lesion: Submit the entire scar.[11]
  • Lesion not visible: At least one additional radicality slice towards the tips, up to the entire specimen.[12]


  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. 
  5. 5.0 5.1 Presence or absence of perineural invasion in squamous-cell carcinoma affects whether adjuvant radiotherapy will be used.

Main page


  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 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: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. Dr Nicholas Turnbull, A/Prof Patrick Emanual (2014-05-03). Squamous cell carcinoma pathology. DermNetz.
  4. 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/)."
  5. 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:10.4317/medoral.20184. ISSN 16986946. 
    License: CC BY 2.5
  6. 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:10.1016/j.anndiagpath.2015.01.004. ISSN 10929134. 
  7. 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. Strowd, Roy (2021). Neuro-oncology for the clinical neurologist . Philadelphia, PA: Elsevier. ISBN 978-0-323-69494-0. OCLC 1220993756. 
  9. Amin, Mahul (2017). AJCC cancer staging manual (8 ed.). Switzerland: Springer. ISBN 978-3-319-40617-6. OCLC 961218414. 
    - For access, see the Secrets chapter of Patholines.
    - Copyright note: The AJCC, 8th Ed. is published by a company in Switzerland, and the tables presented therein are Public Domain because they consist of tabular information without literary or artistic innovation, and therefore do not fulfil the inclusion criterion of the Swiss Copyright Act (CopA) which applies to "literary and artistic intellectual creations with individual character" (see Federal Act on Copyright and Related Rights (Copyright Act, CopA) of 9 October 1992 (Status as of 1 January 2022)). edit
  10. Anjelica Hodgson, M.D., Carlos Parra-Herran, M.D.. p16. Pathology Outlines. Last author update: 1 July 2017. Last staff update: 20 July 2022
  11. 11.0 11.1 Katarzyna Lundmark. Handläggning av hudprover – provtagningsanvisningar, utskärningsprinciper och snittning (Handling of skin samples - sampling instructions, cutting principles and incision. Swedish Society of Pathology.
  12. Pathology Department at NU Hospital Group, Sweden, 2019-2020.

Image sources