Squamous cell carcinoma

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Squamous cell carcinoma. H&E stain. (WC)

This article deal with squamous cell carcinoma, also squamous carcinoma, a very common epithelial derived malignant neoplasm that can arise from many sites. It is commonly abbreviated SCC.



Head and neck

Tumour extent

  • There is no agreed upon measure of tumour extent (tumour thickness/depth of invasion)[1] - proposed measures:[2]
    • "Tumour thickness" = perpendicular distance from mucosal surface to deepest point of invasion.
    • "Tumour depth" = perpendicular distance from epithelial basement membrane to deepest point of invasion.

Uterine cervix


Tumour extent

Thickness is measured:[3][4]

  • No kerinization present: mucosal surface to the deepest point of invasion.
  • Kerinization present: bottom of granular layer to the deepest point of invasion.



  • Upper and middle esophagus.


  • Most common form of anal cancer.

Other sites



SCC is subdivided by the WHO into:[5]

  • Keratinizing type (KT).
    • Worst prognosis.
    • More common than non-keratinizing type.[6]
  • Undifferentiated type (UT).
    • Intermediate prognosis.
    • EBV association.
  • Non-keratinizing type (NT).
    • Good prognosis.
    • EBV association.

Features based on classification:[5]

  • KT subtype:
    • Keratinization & intercellular bridges through-out most of the malignant lesion.
  • UT:
    • Non-distinct borders/syncytial pattern.
    • Nucleoli.
  • NT:
    • Well-defined cell borders.

Invasive squamous cell carcinoma


  • Eosinophilia.
  • Extra large nuclei/bizarre nuclei.
  • Inflammation (lymphocytes, plasma cells).
  • Long rete ridges.
  • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges.


  • Tangential cuts.
    • If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.

Notes on invasion:



There are several subtypes:[8]

  • Adenosquamous carcinoma.
  • Ancatholytic squamous cell carcinoma.
  • Basaloid squamous cell carcinoma - poor prognosis, usu. diagnosed by recognition of typical SCC.
  • Carcinoma cuniculatum.
  • Verrucous carcinoma - good prognosis, rare.
  • Papillary squamous cell carcinoma.
  • Lymphoepithelial carcinoma - rare.
  • Spindle cell squamous carcinoma - a common spindle cell lesion of the H&N.

Carcinoma cuniculatum


  • Rare.
  • Good prognosis.[9]


  • Usually lower extremities.
    • Classically plantar aspect of foot.[9]



  • Nests squamous epithelium with minimal atypia in the dermis - key feature.
  • Hyperkeratosis.
  • Parakeratosis.
  • Acanthosis.

Verrucous squamous cell carcinoma

  • AKA verrucous carcinoma.

Spindle cell squamous carcinoma

  • AKA sarcomatoid squamous cell carcinoma.[10]


  • Common spindle cell lesion of the head and neck.



  • Histomorphologic key to the diagnosis: finding a component of conventional squamous cell carcinoma.
  • Malignant spindle cell neoplasm.




  • Typically keratin -ve.
  • p63 +ve.
    • Soft tissue tumour uncommonly positive.[11]

Basaloid squamous cell carcinoma

Should not be confused with basosquamous carcinoma.




  • "Basaloid" cells - "blue" at low power.
    • Nests.
      • Basal pallisading.
  • +/-Keratinization - useful.
  • +/-Squamous dysplasia in overlying skin.
  • Conventional squamous cell carcinoma.


Clear cell squamous cell carcinoma




  • Clear cytoplasm.


Lymphoepithelial (squamous cell) carcinoma

This is discussed in detail in the lymphoepithelioma-like carcinoma (LELC) article.
In the head and neck this is a separate entity known as nasopharyngeal carcinoma.


  • Rare.
  • +/-EBV.
  • Some consider this a distinct entity - rather than a subtype of SCC.[14]



  • Malignant squamoid cells (eosinophilic cytoplasm, nuclear atypia).
  • Abundant mononuclear inflammatory cells (plasma cells, lymphocytes).

Images: see the LELC article.



  • CK5/6 +ve.
  • p63 +ve.
  • K903 +ve.
  • p16 +ve/-ve -- dependent on site, +ve favours non-lung SCC.[15]
  • p40 +ve.


  • Immunostains not particularly helpful for establishing primary site of squamous cell carcinoma. p16 may be helpful but is not definitive for non-lung SCC.[15]

See also


  1. Pentenero, M.; Gandolfo, S.; Carrozzo, M. (Dec 2005). "Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature.". Head Neck 27 (12): 1080-91. doi:10.1002/hed.20275. PMID 16240329.
  2. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/LipOralCav_11protocol.pdf. Accessed on: 3 April 2012.
  3. Yoder, BJ.; Rufforny, I.; Massoll, NA.; Wilkinson, EJ. (May 2008). "Stage IA vulvar squamous cell carcinoma: an analysis of tumor invasive characteristics and risk.". Am J Surg Pathol 32 (5): 765-72. doi:10.1097/PAS.0b013e318159a2cb. PMID 18379417.
  4. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Vulva_11protocol.pdf. Accessed on: 3 April 2012.
  5. 5.0 5.1 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 975. ISBN 978-0781740517.
  6. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/LipOralCav_11protocol.pdf. Accessed on: 3 April 2012.
  7. Wenig BM (March 2002). "Squamous cell carcinoma of the upper aerodigestive tract: precursors and problematic variants". Mod. Pathol. 15 (3): 229–54. doi:10.1038/modpathol.3880520. PMID 11904340. http://www.nature.com/modpathol/journal/v15/n3/pdf/3880520a.pdf.
  8. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/LipOralCav_11protocol.pdf. Accessed on: 3 April 2012.
  9. 9.0 9.1 Kruse, AL.; Graetz, KW. (Jul 2009). "Carcinoma cuniculatum: a rare entity in the oral cavity.". J Craniofac Surg 20 (4): 1270-2. doi:10.1097/SCS.0b013e3181ace06b. PMID 19625845.
  10. Hall, JM.; Saenger, JS.; Fadare, O. (Mar 2008). "Diagnostic utility of P63 and CD10 in distinguishing cutaneous spindle cell/sarcomatoid squamous cell carcinomas and atypical fibroxanthomas.". Int J Clin Exp Pathol 1 (6): 524-30. PMID 18787630.
  11. Jo, VY.; Fletcher, CD. (Nov 2011). "p63 immunohistochemical staining is limited in soft tissue tumors.". Am J Clin Pathol 136 (5): 762-6. doi:10.1309/AJCPXNUC7JZSKWEU. PMID 22031315.
  12. URL: http://www.biomedcentral.com/1471-2407/6/146. Accessed on: March 9, 2010.
  13. Lawal, AO.; Adisa, AO.; Olajide, MA.; Olusanya, AA. (Jan 2013). "Clear cell variant of squamous cell carcinoma of skin: A report of a case.". J Oral Maxillofac Pathol 17 (1): 110-2. doi:10.4103/0973-029X.110697. PMID 23798842.
  14. Skinner, NE.; Horowitz, RI.; Majmudar, B. (Oct 2000). "Lymphoepithelioma-like carcinoma of the uterine cervix.". South Med J 93 (10): 1024-7. PMID 11147469.
  15. 15.0 15.1 15.2 Pereira, TC.; Share, SM.; Magalhães, AV.; Silverman, JF. (Jan 2011). "Can we tell the site of origin of metastatic squamous cell carcinoma? An immunohistochemical tissue microarray study of 194 cases.". Appl Immunohistochem Mol Morphol 19 (1): 10-4. doi:10.1097/PAI.0b013e3181ecaf1c. PMID 20823766.