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Squamous-cell carcinoma

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Main histopathology features of squamous-cell carcinoma

The term squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells.[1] These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts.[1]

Despite sharing the name "squamous-cell carcinoma", the SCCs of different body sites can show differences in their presented symptoms, natural history, prognosis, and response to treatment.

By body location


Human papillomavirus infection has been associated with SCCs of the oropharynx, lung,[2] fingers,[3] and anogenital region.

Head and neck cancer

A large head and neck squamous-cell carcinoma of the tongue as seen on CT imaging

About 90%[4] of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to SCC.



Cutaneous squamous-cell carcinoma is the second most common skin cancer, accounting for over 1 million cases in the United States each year.[5]



Primary squamous-cell carcinoma of the thyroid shows an aggressive biological phenotype resulting in poor prognosis for patients.[6]



Esophageal cancer may be due to either esophageal squamous-cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.[7]


Photograph of a squamous-cell carcinoma. The tumour is on the left, obstructing the bronchus (lung); beyond the tumour, the bronchus is inflamed and contains mucus.

When associated with the lung, it is typically a centrally located large-cell cancer (non-small-cell lung cancer). It often has a paraneoplastic syndrome causing ectopic production of parathyroid hormone-related protein, resulting in hypercalcemia, but paraneoplastic syndrome is more commonly associated with small-cell lung cancer. It is primarily due to smoking.[8]



Human papillomavirus (HPV), primarily HPV 16 and 18, are strongly implicated in the development of SCC of the penis. Three carcinomas in situ are associated with SCCs of the penis:[citation needed]

  1. Bowen's disease presents as leukoplakia on the shaft. Around a third of cases progress to SCC.
  2. Erythroplasia of Queyrat, a variation of Bowen's disease, presents as erythroplakia on the glans.
  3. Bowenoid papulosis, which histologically resembles Bowen disease, presents as reddish papules.[9]



When associated with the prostate, squamous-cell carcinoma is very aggressive in nature. It is difficult to detect as no increase in prostate-specific antigen levels is seen, meaning that the cancer is often diagnosed at an advanced stage.[citation needed]

Vagina and cervix


Squamous cell carcinoma of the vagina spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer.[10]



Ovarian squamous cell carcinoma (oSCC) or squamous ovarian carcinoma (SOC) is a rare tumor that accounts for 1% of ovarian cancers.[11]



Most bladder cancer is transitional cell, but bladder cancer associated with schistosomiasis is often SCC.[citation needed]



Conjunctival squamous cell carcinoma and corneal intraepithelial neoplasia comprise ocular surface squamous neoplasia (OSSN).


Biopsy of a highly differentiated squamous-cell carcinoma of the mouth. Typical squamous-cell carcinoma cells are large with abundant eosinophilic cytoplasm and large, often vesicular, nuclei.[12] Haematoxylin & eosin stain
Cytopathology of squamous-cell carcinoma, keratinizing variant, with typical features.[13] Pap stain.
Cytopathology of squamous-cell carcinoma, nonkeratinizing variant, with typical features.[14] Pap stain. Yet, these findings are overall less specific than for keratinizing squamous-cell carcinoma, and most can be seen in other cancers such as adenocarcinoma as well (which, however, tends to have fine chromatin).[15]

Medical history, physical examination and medical imaging may suggest a squamous-cell carcinoma, but a biopsy for histopathology generally establishes the diagnosis. TP63 staining is the main histological marker for squamous-cell carcinoma. In addition, TP63 is an essential transcription factor to establish identity of the squamous cells.[16]



Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous-cell carcinomas comprising one of the largest subsets.[17][18][19] All SCC lesions are thought to begin via the repeated, uncontrolled division of cancer stem cells of epithelial lineage or characteristics.[citation needed] SCCs arise from squamous cells, which are flat cells that line many areas of the body. Some of which are keratinocytes. Accumulation of these cancer cells causes a microscopic focus of abnormal cells that are, at least initially, locally confined within the specific tissue in which the progenitor cell resided. This condition is called squamous-cell carcinoma in situ, and it is diagnosed when the tumor has not yet penetrated the basement membrane or other delimiting structure to invade adjacent tissues. Once the lesion has grown and progressed to the point where it has breached, penetrated, and infiltrated adjacent structures, it is referred to as "invasive" squamous-cell carcinoma. Once a carcinoma becomes invasive, it is able to spread to other organs and cause the formation of a metastasis, or "secondary tumor".[citation needed]

Tissue of origin


The International Classification of Diseases for Oncology (ICD-O) system lists a number of morphological subtypes and variants of malignant squamous-cell neoplasms, including:[20]

  • papillary thyroid carcinoma (code 8050/3)
  • verrucous squamous-cell carcinoma (code 8051/3)
  • papillary squamous-cell carcinoma (code 8052/3)
  • squamous-cell carcinoma (code 8070/3)
  • large-cell keratinizing squamous-cell carcinoma (code 8071/3)
  • large-cell nonkeratinizing squamous-cell carcinoma (code 8072/3)
  • small-cell keratinizing squamous-cell carcinoma (code 8073/3)
  • spindle-cell squamous-cell carcinoma (code 8074/3) It is also known as spindle-cell carcinoma,[21] and is a subtype characterized by spindle-shaped atypical cells.[22]
  • adenoid/pseudoglandular squamous-cell carcinoma (code 8075/3)
  • intraepidermal squamous-cell carcinoma (code 8081/3)
  • lymphoepithelial carcinoma (code 8082/3).

Other variants of SCCs are recognized under other systems, such as keratoacanthoma.

Other histopathologic subtypes


One method of classifying squamous-cell carcinomas is by their appearance under microscope. Subtypes may include:

  • adenoid squamous-cell carcinoma (also known as pseudoglandular squamous-cell carcinoma) is characterized by a tubular microscopic pattern and keratinocyte acantholysis.[22]
  • basaloid squamous-cell carcinoma is mostly found in or near the tongue, tonsils, or larynx, but may also occur in the lung or elsewhere.[24]
  • clear-cell squamous-cell carcinoma (also known as clear-cell carcinoma of the skin) is characterized by keratinocytes that appear clear as a result of hydropic swelling.[22]
  • signet ring-cell squamous-cell carcinoma (occasionally rendered as signet ring-cell squamous-cell carcinoma) is a histological variant characterized by concentric rings composed of keratin and large vacuoles corresponding to markedly dilated endoplasmic reticulum.[22] These vacuoles grow to such an extent that they radically displace the cell nucleus toward the cell membrane, giving the cell a distinctive superficial resemblance to a "signet ring" when viewed under a microscope.



Studies have found evidences for an association between diet and skin cancers, including SCC. The consumption of high-fat dairy foods increases SCC tumor risk in people with previous skin cancer. Green leafy vegetables may help prevent development of subsequent SCC and multiple studies found that raw vegetables and fruits are significantly protective against SCC risk.[25][26] On the other hand, consumption of whole milk, yogurt, and cheese may increase SCC risk in susceptible people.[27] In addition, meat and fat dietary pattern can increase the risk of SCC in people without a history of SCC, but the association is again more prominent in people with a history of skin cancer.[28] Tobacco smoking and a dietary pattern characterized by high beer and liquor intake also increase the risk of SCC significantly.[29][25]


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  11. ^ [non-primary source needed] Srivastava, Himsweta; Shree, Sneha; Guleria, Kiran; Singh, Usha R (May 2017). "Pure Primary Squamous Cell Carcinoma of Ovary – A Rare Case Report". Journal of Clinical and Diagnostic Research (Case report). 11 (5): QD01–QD02. doi:10.7860/JCDR/2017/16899.9771. ISSN 2249-782X. PMC 5483757. PMID 28658855.
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  13. ^ - Image annotated by Mikael Häggström
    - Reference for entries: Gulisa Turashvili, M.D., Ph.D. "Cervix - Squamous cell carcinoma and variants". Pathology Outlines.{{cite web}}: CS1 maint: multiple names: authors list (link) Last author update: 24 September 2020. Last staff update: 4 April 2022.
    - Source image from National Cancer Institute (Public Domain)
  14. ^ - Image annotated by Mikael Häggström
    - Reference for entries: Gulisa Turashvili, M.D., Ph.D. "Cervix - Squamous cell carcinoma and variants". Pathology Outlines.{{cite web}}: CS1 maint: multiple names: authors list (link) Last author update: 24 September 2020. Last staff update: 4 April 2022.
    - Source image by Ravi Mehrotra, Anurag Gupta, Mamta Singh and Rahela Ibrahim (Creative Commons Attribution 2.0 Generic license.)
  15. ^ Authors: Caroline I.M. Underwood, M.D., Alexis Musick, B.S., Carolyn Glass, M.D., Ph.D. "Adenocarcinoma overview". Pathology Outlines.{{cite web}}: CS1 maint: multiple names: authors list (link) Last staff update: 19 July 2022
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