Squamous Cell Carcinoma of the Skin

Aka: Squamous Cell Carcinoma of the Skin, Squamous Cell Skin Cancer, Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Epidermoid Carcinoma of the Skin, Squamous Cell Epithelioma, Malignant Squamous Cell Neoplasm, Planocellular Carcinoma, Bowen Disease, Bowen's Disease, Squamous Cell Carcinoma In Situ, CSCC

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II. Epidemiology

  1. Age-adjusted Incidence: 100-150 per 100,000 persons/year
    1. Affects 400,000 in U.S. per year
    2. Results in 3000 U.S. Deaths per year
  2. Gender: Twice as common in males
  3. Incidence in Skin of Color
    1. Ethnicities with CSCC as most common Skin Cancer
      1. Native Americans
      2. Black patients (Peak Incidence at ages 40-49)
    2. Ethnicities with CSCC as second most common Skin Cancer
      1. Chinese and Japanese (peaks after age 60 years old)
      2. Hispanic patients

III. Risk Factors

  1. See Nonmelanoma Skin Cancer
  2. Exposure to UVB
  3. Actinic Keratoses (precursor to CSCC)
    1. Malignant transformation rate varies from <10% in 10 years to as high as 20% per year
    2. Malignant transformation of Actinic Keratoses are responsible for 60% of CSCC cases
  4. Immunosuppression
    1. HIV Infection
    2. Organ transplant recipients (65 fold increased risk related to Immunosuppression)
      1. Lesion onset at 2-4 years after Transplantation and risk increases with time
  5. Advanced age
  6. Closer distance to the equator
  7. Chronically diseased or injured skin (e.g. Skin Ulcerations, sinus tracts)
  8. Xeroderma Pigmentosum

IV. Pathophysiology

  1. Arises from superficial layers of Keratinocytes
    1. Neoplastic transformation is triggered by UV radiation exposure
    2. CSCC is on the same spectrum as Actinic Keratoses
      1. Actinic Keratoses proliferate and extend into the Dermis at which point they are defined as SCC
    3. CSCC spreads by local infiltration
      1. Spreads along tissue planes and structures such as nerves, arteries and veins
  2. Precursor lesions
    1. Actinic Keratoses (60% of CSCC arises from actinics)
    2. Radiation and burn scars

V. Symptoms

  1. Nonhealing lesion that frequently bleeds without significant Trauma

VI. Signs

  1. Location
    1. Sun exposed areas
  2. Characteristics
    1. Firm, smooth hyperkeratotic Papule, Nodule, patch or Plaque on indurated base
    2. Central ulceration and crusting is common
    3. Thick white scale may be present
    4. Fleshy heaped-up edges of lesion
  3. Variants
    1. Verrucous carcinoma
      1. Wart-like CSCC lesion with higher malignant potential
    2. Bowen's Disease (Cutaneous Squamous Cell Carcinoma In Situ)
      1. Slow-growing, scaly red Plaque on sun-exposed skin
    3. Cutaneous horn (keratin horn, cornu cutaneum)
      1. Hyperkeratotic growth with similar appearance to a horn
      2. Starts as Actinic Keratosis and progresses to Squamous Cell Carcinoma

VII. Diagnosis: Skin Biopsy

  1. Raised lesion: Shave Biopsy if not pigmented
    1. Any suspicion of Melanoma needs full-thickness sample
  2. Flat lesions: Punch Biopsy or full excision
    1. Complete excision of small lesions with Punch Biopsy
    2. Punch Biopsy of the most abnormal appearing aspects of larger lesions

VIII. Differential Diagnosis

  1. See Nonmelanoma Skin Cancer
  2. Keratocanthoma

IX. Grading

  1. Sample inadequate for micro-staging
    1. Consider obtaining narrow-margin Excisional Biopsy
  2. Low Risk
    1. Well differentiated or moderately differentiated
    2. No High risk histologic subtypes (see high risk subtypes below)
    3. Superficial depth <2 mm (or Clark Level 1, 2 or 3)
    4. No perineural, lymphatic or vascular involvement
  3. High Risk
    1. Poorly differentiated
    2. Depth >= 2mm or Clark 3-4
      1. Depth should not include scale, crust or parakeratosis
      2. Measured from base of ulcer (if present)
    3. High risk histologic subtypes
      1. Adenoid or Acantholytic
      2. Adenosquamous (with mucin production)
      3. Desmoplastic
      4. Metaplastic (Carcinosarcomatous)

X. Management

  1. Mohs' Microographic Surgery
    1. Preferred as first-line therapy in most cases of Cutaneous Squamous Cell Carcinoma
    2. Indications
      1. Large lesions
        1. Central face, periorbital, periauricular: >6 mm
        2. Cheeks, forehead, neck, scalp: >10 mm
        3. Trunk, extremities: >20 mm
      2. Indistinct margins
      3. Recurrent lesions
      4. Lesion in close proximity to eyes, nose, mouth
      5. Preserve cosmetic appearance
    3. References
      1. Martinez (2001) Mayo Clin Proc 76:1253 [PubMed]
  2. Surgical excision
    1. Low-risk primary CSCC should be excised with 4-6 mm margin of uninvolved skin
    2. Complete excision recommended over ED&C
      1. Due to risk of metastases
    3. Imperative to confirm negative margins
    4. Indications
      1. Small lesions less than size criteria for Moh's
      2. Slow growing, well differentiated lesions
      3. Negative for neural or vascular invasion
  3. Radiation Therapy
    1. Indicated in age over 55 years with CSCC in high risk, surgically difficult areas

XI. Course

  1. More rapid growth than Basal Cell Carcinoma
  2. Locally destructive Skin Cancer
  3. Metastases
    1. Ocurs in 3-5% of cases to distant sites via hematogenous spread
    2. Risk factors (may confer up to 40% metastases risk)
      1. Large tumors >2 cm in diameter (3 fold increased risk of metastasis)
      2. Involvement of ear, lip or chronically diseased or injured skin
      3. Immunosuppression

XII. Prevention

  1. See Sun Exposure (lists general preventive measures)
  2. See Sunscreen

XIII. References

  1. Habif (2004) Dermatology p. 744-7
  2. Firnhaber (2020) Am Fam Physician 102(6): 339-46 [PubMed]
  3. Firnhaber (2012) Am Fam Physician 86(2): 161-8 [PubMed]
  4. Kim (2018) J Am Acad Dermatol 78(3): 560-78 [PubMed]
  5. Stulberg (2004) Am Fam Physician 70:1481-8 [PubMed]

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Related Studies

Ontology: Bowen's Disease (C0006079)

Definition (NCI) A form of squamous cell carcinoma in situ. It is a distinct clinicopathological entity and arises from the skin or the mucocutaneous junction. It affects predominantly white males in their 6-8th decades of life. Exposed and non-exposed skin sites are equally affected. UV damage and ingestion of inorganic arsenic may play a role in the development of the disease. On the skin surface, it presents as a single or multiple erythematous, scaly, keratotic patches or plaques. The clinical entity of erythroplasia of Queyrat is regarded as Bowen disease of the penis and it presents as an asymptomatic, red, circumscribed plaque. Morphologically, Bowen disease is characterized by the presence of hyperkeratosis, parakeratosis, dyskeratosis, and acanthosis. The keratotic squamous cells are atypical and display hyperchromatism and abnormal mitotic figures. The dermoepidermal basement membrane is intact. Complete surgical removal of the lesion may be curative.
Definition (NCI_NCI-GLOSS) A skin disease marked by scaly or thickened patches on the skin and often caused by prolonged exposure to arsenic. The patches often occur on sun-exposed areas of the skin and in older white men. These patches may become malignant (cancer).
Definition (MSH) A persistent progressive non-elevated red scaly or crusted plaque which is due to an intradermal carcinoma and is potentially malignant. Atypical squamous cells proliferate through the whole thickness of the epidermis. The lesions may occur anywhere on the skin surface or on mucosal surfaces. The cause most frequently found is trivalent arsenic compounds. Freezing, cauterization or diathermy coagulation is often effective. (From Rook et al., Textbook of Dermatology, 4th ed, pp2428-9)
Concepts Neoplastic Process (T191)
MSH D001913
ICD10 M8081/2 , D00-D09
SnomedCT 84999002, 269582000, 154507009, 240544007, 189208007, 189569001, 254656002
English Bowen Disease, Bowens Disease, Disease, Bowen, Disease, Bowen's, Intraepiderm SCC-Bowen's type, Intraepidermal SCC - Bowen's, Intraepidermal squamous cell carcinoma - Bowen's type, BOWEN'S DISEASE, BOWENS DIS, BOWEN DIS, [M]Bowen's disease, Bowen's Disease of the Skin, Intraepidermal Squamous Cell Carcinoma, Bowen Type, Bowen Disease of the Skin, Bowen's disease (diagnosis), Bowen disease, Bowen's Disease [Disease/Finding], Disease;Bowens, disease bowen's, bowen disease, bowen's disease, bowens disease, Intraepidermal squamous cell carcinoma - Bowen's type (disorder), [M]Bowen's disease (morphologic abnormality), Intraepidermal squamous cell carcinoma, Bowen's type, Bowen's disease, Bowen's disease of skin, SCC - Intraepidermal squamous cell carcinoma - Bowen's type, BD - Bowen's disease, Bowen's disease (morphologic abnormality), Bowen's Disease, Bowens disease
Portuguese DOENCA DE BOWEN, Doença de Bowen
Swedish Bowens sjukdom
Japanese ﾎﾞｰｴﾝﾋﾞｮｳ, Bowen病, ボーウエン病, ボーエン病
Czech Bowenova nemoc, Bowenova choroba, Bowenova dermatóza
Finnish Bowenin tauti
Russian BOUENA BOLEZN', БОУЭНА БОЛЕЗНЬ
French MALADIE DE BOWEN, Dyskératose lenticulaire en disque, Maladie de Bowen
Polish Choroba Bowena
Croatian BOWENOVA BOLEST
Hungarian Bowen-kór
Norwegian Bowens sykdom
Spanish [M]enfermedad de Bowen, [M]enfermedad de Bowen (anomalía morfológica), carcinoma escamoso intraepidérmico, tipo Bowen, enfermedad de Bowen (anomalía morfológica), enfermedad de Bowen, Enfermedad de Bowen
Dutch ziekte van Bowen, Ziekte van Bowen
German Bowen Krankheit, Bowen-Krankheit, Bowen-Syndrom, Dermatitis praecancerosa Bowen, Morbus Bowen
Italian Malattia di Bowen
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Squamous cell carcinoma (C0007137)

Definition (CHV) a cancer arises from a cell called squamous epithelium. this is the most common type of skin cancer
Definition (CHV) a cancer arises from a cell called squamous epithelium. this is the most common type of skin cancer
Definition (CHV) a cancer arises from a cell called squamous epithelium. this is the most common type of skin cancer
Definition (CHV) a cancer arises from a cell called squamous epithelium. this is the most common type of skin cancer
Definition (CHV) a cancer arises from a cell called squamous epithelium. this is the most common type of skin cancer
Definition (CHV) a cancer arises from a cell called squamous epithelium. this is the most common type of skin cancer
Definition (NCI) A carcinoma arising from squamous epithelial cells. Morphologically, it is characterized by the proliferation of atypical, often pleomorphic squamous cells. Squamous cell carcinomas are graded by the degree of cellular differentiation as well, moderately, or poorly differentiated. Well differentiated carcinomas are usually associated with keratin production and the presence of intercellular bridges between adjacent cells. Representative examples are lung squamous cell carcinoma, skin squamous cell carcinoma, and cervical squamous cell carcinoma.
Definition (NCI_CDISC) A malignant neoplasm arising from squamous epithelial cells.
Definition (NCI_NCI-GLOSS) Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts.
Definition (MSH) A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
Definition (CSP) carcinoma developed from squamous epithelium.
Concepts Neoplastic Process (T191)
MSH D002294
ICD10 M8070/3
SnomedCT 28899001, 189566008, 154605007, 402815007
LNC LP17968-6
English Carcinoma, Epidermoid, Carcinoma, Planocellular, Carcinoma, Squamous Cell, Carcinomas, Epidermoid, Carcinomas, Planocellular, Carcinomas, Squamous Cell, Epidermoid Carcinomas, Planocellular Carcinoma, Planocellular Carcinomas, Squamous Cell Carcinomas, Carcinoma, Squamous, Carcinomas, Squamous, Squamous Carcinomas, Squamous Cell Cancer, Epidermoid Cell Cancer, Malignant Epidermoid Cell Neoplasm, Malignant Epidermoid Cell Tumor, Malignant Squamous Cell Neoplasm, Malignant Squamous Cell Tumor, CARCINOMA SQUAMOUS, [M]Squamous cell carcinoma NOS, Squamous cell carcinoma NOS, Squamous Cell Epithelioma, squamous cell carcinoma (diagnosis), squamous cell carcinoma, Squamous cell carcinoma, no ICD-O subtype, Squamous Cell Carcinoma, Carcinoma epidermoid, Carcinoma squamous, Carcinoma, Squamous Cell [Disease/Finding], squamous cell carcinomas, squamous cell epithelioma, squamous carcinomas, squamous carcinoma, [M]Squamous cell carcinoma NOS (morphologic abnormality), Squamous cell carcinoma, no ICD-O subtype (morphologic abnormality), Squamous cell carcinoma, no International Classification of Diseases for Oncology subtype (morphologic abnormality), Squamous cell carcinoma, no International Classification of Diseases for Oncology subtype, MALIGNANT SQUAMOUS CELL NEOPLASM, MALIGNANT SQUAMOUS CELL TUMOR, EPIDERMOID CELL CANCER, SQUAMOUS CELL CANCER, epidermoid carcinoma, SQUAMOUS CELL EPITHELIOMA, CARCINOMA, SQUAMOUS CELL, MALIGNANT, EPIDERMOID CARCINOMA, MALIGNANT EPIDERMOID CELL TUMOR, MALIGNANT EPIDERMOID CELL NEOPLASM, SQUAMOUS CARCINOMA, Epidermoid carcinoma, Squamous carcinoma, Squamous cell epithelioma, SCC - Squamous cell carcinoma, Squamous cell carcinoma (disorder), Epidermoid carcinoma, NOS, Squamous cell carcinoma, NOS, Squamous cell carcinoma (morphologic abnormality), Squamous cell carcinoma, Epidermoid Carcinoma, Squamous Carcinoma
Italian Carcinoma spinocellulare, Carcinoma planocellulare, Carcinoma epidermoide, Carcinoma squamoso, Carcinoma a cellule squamose
Dutch epidermoïdcarcinoom, carcinoom squameus, carcinoom epidermoïd, squameuscelcarcinoom, Carcinoom, planocellulair, Carcinoom, squameus, Carcinoom, squameuze-cel-, Squameuze-celcarcinoom, Carcinoom, epidermoïd-
German Karzinom epidermoid, Karzinom squamoes, epidermoides Karzinom, Plattenepithelkarzinom, Karzinom, Epidermoid-, Karzinom, Plattenepithel-, Karzinom, flachzelliges, Karzinom, plattenepitheliales
Portuguese Carcinoma epidermóide, CARCINOMA ESPINOCELULAR, Carcinoma Epidermoide, Carcinoma Espinocelular, Carcinoma de Células Planas, Carcinoma pavimentocelular, Carcinoma de Células Escamosas, Carcinoma Escamoso, Carcinoma Planocelular
Spanish Carcinoma epidermoide, Carcinoma escamoso, carcinoma de células escamosas, no clasificado como subtipo en CIE-O, carcinoma de células escamosas, sin subtipo en la CIE O (anomalía morfológica), carcinoma de células escamosas, sin subtipo en la CIE O, carcinoma de células escamosas, no clasificado como subtipo en CIE-O (anomalía morfológica), [M]carcinoma de células escamosas, SAI (anomalía morfológica), [M]carcinoma de células escamosas, SAI, [M]carcinoma epidermoide, SAI, carcinoma de células escamosas (anomalía morfológica), carcinoma de células escamosas (trastorno), carcinoma de células escamosas, carcinoma epidermoide, carcinoma escamoso, carcinoma espinocelular, epitelioma de células escamosas, epitelioma espinocelular, Carcinoma de células escamosas, Carcinoma de Células Escamosas, Carcinoma Epidermoide, Carcinoma Escamoso, Carcinoma Planocelular
Japanese ﾙｲﾋｮｳﾋｶﾞﾝ, ﾍﾝﾍﾟｲｼﾞｮｳﾋｶﾞﾝ, 扁平上皮癌, 癌-扁平細胞, 扁平上皮がん, 扁平細胞癌, 有棘細胞癌, 類表皮癌, 有きょく細胞癌, 癌-扁平上皮, 癌-類表皮
Finnish Levyepiteelikarsinooma
Russian KARTSINOMA SKVAMOZNAIA, KARTSINOMA EPIDERMOIDNAIA, KARTSINOMA PLOSKOKLETOCHNAIA, КАРЦИНОМА ПЛОСКОКЛЕТОЧНАЯ, КАРЦИНОМА СКВАМОЗНАЯ, КАРЦИНОМА ЭПИДЕРМОИДНАЯ
French CARCINOME SQUAMEUX, Cancer épidermoïde, Épithélioma épidermoïde, Épithélioma spinocellulaire, Carcinome épidermoïde, Carcinome spino-cellulaire, Carcinome spinocellulaire, Épithelioma malpighien spino-cellulaire
Czech Karcinom dlaždicobuněčný, Epidermoidní karcinom, Dlaždicobuněčný karcinom, Karcinom epidermoidní, epidermoidní karcinom, spinocelulární karcinom, dlaždicový karcinom, karcinom dlaždicobuněčný, skvamozní karcinom, dlaždicobuněčný karcinom, skvamocelulární karcinom
Croatian KARCINOM, PLANOCELULARNI
Swedish Skivepitelkarcinom
Polish Rak naskórkowy, Rak płaskonabłonkowy, Rak płaskokomórkowy
Hungarian Epidermoid carcinoma, Pikkelysejtes carcinoma, Squamosus sejtes carcinoma
Norwegian Plateepitelkarsinom
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Squamous cell carcinoma of skin (C0553723)

Definition (NCI) A carcinoma arising from the squamous cells of the epidermis. Skin squamous cell carcinoma is most commonly found on sun-exposed areas. The majority of the tumors are well-differentiated.
Concepts Neoplastic Process (T191)
SnomedCT 254651007
English Cutaneous SCC, SCC-Squam cell carcin of skin, Squamous cell carcinom of skin, Squamous cell carcinoma of the skin, squamous cell carcinoma of skin, squamous cell carcinoma of skin (diagnosis), skin squamous cell cancer, squamous cell carcinoma skin, cancers cell skin squamous, squamous cell skin cancer, cancer cell skin squamous, carcinoma cell skin squamous, Squamous cell carcinoma - skin, Spinous cell carcinoma, Cutaneous squamous cell carcinoma, SCC - Cutaneous squamous cell carcinoma, SCC - Squamous cell carcinoma of skin, Squamous cell carcinoma of skin (disorder), squamous cell carcinoma of the skin, cancer of the skin, squamous cell, carcinoma of the skin, squamous cell, carcinoma, epidermoid, skin, carcinoma, squamous cell, skin, epidermoid carcinoma of the skin, skin cancer, epidermoid carcinoma, skin cancer, squamous cell, Cutaneous Squamous Cell Carcinoma, Epidermoid Carcinoma of Skin, Epidermoid Carcinoma of the Skin, Epidermoid Skin Carcinoma, Skin Squamous Cell Carcinoma, Squamous Cell Carcinoma of Skin, Squamous Cell Carcinoma of the Skin, Squamous Cell Skin Carcinoma, Squamous cell carcinoma of skin
Italian Carcinoma a cellule squamose della cute
Japanese 皮膚有棘細胞癌, ﾋﾌﾕｳｷｮｸｻｲﾎﾞｳｶﾞﾝ
Czech Dlaždicobuněčný karcinom kůže
Hungarian Bőr squamosus sejtes carcinoma
Spanish carcinoma de células escamosas de la piel (trastorno), carcinoma de células escamosas de la piel, carcinoma escamoso de la piel, Carcinoma de células escamosas de la piel
Portuguese Carcinoma espinhocelular da pele
Dutch squameuscelcarcinoom van de huid
French Carcinome épidermoïde cutané
German Plattenepithelkarzinom der Haut
Derived from the NIH UMLS (Unified Medical Language System)

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