Squamous Cell Carcinoma (and Variants)

Squamous Cell Carcinoma (and Variants)

David Cassarino, MD, PhD

Clinical photograph shows an extensive SCC arising on the distal foot in a patient with a history of previous burn injury. (Courtesy S. Yashar, MD.)

Moderately differentiated invasive SCC shows prominent keratin pearls image and a sclerotic stroma with scattered inflammatory cells.



  • Squamous cell carcinoma (SCC)


  • Epidermoid carcinoma

  • Sarcomatoid carcinoma/spindle cell carcinoma/carcinosarcoma/metaplastic carcinoma

  • Acantholytic/adenoid/pseudoglandular SCC

  • Verrucous carcinoma (well-differentiated variant)

  • Keratoacanthoma (KA) (well-differentiated variant, regresses spontaneously)


  • Malignant tumor of squamous keratinocytes


Environmental Exposure

  • Most cases are related to UV radiation

  • Some cases are likely related to chronic inflammation (i.e., SCC arising in burns, lupus, lichen planus)

  • Previous radiation therapy is implicated in some cases, usually associated with more aggressive SCC

  • Chronic wounds and burn scars also can be associated with high-risk SCC

  • HPV is associated with some cases

    • Especially verrucous carcinoma (low grade) and SCC in immunosuppressed patients (high grade)



  • Age

    • Usually in the elderly, especially solar-related lesions

    • However, can present in a wide age range (34-95 years)

      • Rare cases in children (should prompt genetic studies)

  • Gender

    • Slightly more common in males, overall


  • Slow-growing papular, nodular, or plaque lesion

  • Often arises in sun-damaged skin (head and neck tumors)

    • Vast majority of cases associated with preexisting actinic keratosis (AK)

  • May be ulcerated or bleeding

  • Ear canal and middle ear tumors may present with pain, hearing loss, and discharge


  • Surgical approaches

    • Complete surgical excision is optimal and definitive therapy

      • Mohs surgery has been shown to be highly effective for most tumors

  • Drugs

    • If patients are not surgical candidates, topical chemotherapeutics or immunomodulators may be used

  • Radiation

    • May be used for very advanced cases where surgical therapy is not curative


  • Usually excellent in most cases

  • Worse prognosis with poorly differentiated, deeply invasive, or rare aggressive subtypes

  • Site of tumor important for prognosis

    • Lip and ear tumors more aggressive, regardless of degree of differentiation


General Features

  • Papular to nodular or plaque-like lesion; can be exophytic

    • May be ulcerated or hemorrhagic


  • Variable; can be small or large lesions


Histologic Features

  • Proliferation of invasive atypical keratinocytes

    • Cells are present in nests, sheets, and infiltrative cords

    • Often show areas of keratinization (keratin pearls) and squamous eddies

    • Attachments to overlying epidermis in most cases

    • Associated AK is very common; less likely, may be associated with SCC in situ (Bowen disease)

    • Cytologically, cells show abundant eosinophilic cytoplasm and large nucleus with vesicular chromatin and prominent nucleoli

    • Intercellular bridges (desmosomes) should be present on high-power examination

    • Presence of dyskeratotic cells (apoptotic keratinocytes) is reliable sign of squamous differentiation

    • If no definite squamous differentiation is present, immunohistochemistry should be used to confirm diagnosis

  • Degree of differentiation is variable, ranging from well- to moderately to poorly differentiated

    • Amount of keratinization typically decreases and cytologic atypia increases with higher grades

    • Mitotic figures are usually numerous, and atypical forms are found especially in moderately to poorly differentiated cases

  • Multiple variants of differing malignant potential described

    • Low-risk variants include well-differentiated SCC arising in AK, keratoacanthoma, verrucous carcinoma, and tricholemmal (variant of clear cell) carcinoma

    • Intermediate-risk variants include acantholytic (adenoid/pseudoglandular) and lymphoepithelioma-like carcinoma of the skin (LELCS)

    • High-risk variants include spindle cell/sarcomatoid, basaloid, adenosquamous, and desmoplastic

      • Also, radiation, burn scar, and immunosuppression-related SCCs

    • Rare variants of uncertain malignant potential include clear cell SCC, signet ring cell SCC, follicular SCC, papillary SCC, pigmented SCC, and SCC arising from adnexal ducts or cysts

Predominant Pattern/Injury Type

  • Epithelioid/squamoid

Predominant Cell/Compartment Type

  • Squamous cell

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Squamous Cell Carcinoma (and Variants)
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