Skin nonmelanocytic tumors
Carcinoma (nonadnexal)
Squamous cell carcinoma (SCC)

Topic Completed: 1 December 2014

Revised: 13 December 2019

Copyright: 2003-2018,, Inc.

PubMed Search: Squamous cell carcinoma [title] skin

Ghassan A. Tranesh, M.D.
Hong Qu, M.D.
Page views in 2018: 41,339
Page views in 2019 to date: 49,053
Cite this page: Tranesh G. Squamous cell carcinoma (SCC). website. Accessed December 14th, 2019.
Definition / general
  • #2 most common invasive skin cancer, after basal cell carcinoma
  • Derived from keratinocytes in epidermal layer

Risk factors
  • Usually UV light / ionizing radiation
  • Actinic keratosis (precursor lesion), albinism (lack of pigmentation in skin), arsenic
  • Burn scars
  • Chronic ulcers
  • Epidermodysplasia verruciformis
  • Hidradenitis suppurativa
  • Immunosuppression (post-transplant or HIV)
  • Necrobiosis lipoidica
  • Osteomyelitis - draining sinuses
  • PUVA treatment for psoriasis
  • Tars/oils
  • Xeroderma pigmentosa: disorder with diminished capacity for DNA repair after UV light exposure, due to gene at 9q22.3; associated with squamous cell, basal cell carcinoma and melanoma

  • Often graded somewhat subjectively based on degree of differentiation and keratinization: well, moderate, poorly differentiated
  • Well differentiated: abundant pink cytoplasm, mild to moderate atypia, well developed keratinization
  • Moderately differentiated: focal keratinization; features between well and poorly differentiated
  • Poorly differentiated: no / minimal keratinization, high nuclear to cytoplasmic ratio, nuclei are markedly atypical or frankly anaplastic
  • Undifferentiated: tumors presumed to be SCC based on prior biopsy at same site, but no keratinization identified by light microscopy; immunohistochemistry is usually necessary to exclude melanoma or sarcoma

Histologic patterns
  • Commonly affects men > 60 years
  • Incidence: 1 per 1000 individuals (250,000 new case per year) in U.S.
  • Face, ears, scalp, dorsal hands
  • Often induced by ionizing radiation
  • Tends to affect sun damaged, fair skin of older individuals and skin of solid organ transplant recipients
  • HPV / human papillomavirus has major role in development of SCC of penis, vulva, perianal and periungual skin or mucosal sites, but can lead to SCC at any site, particularly in individuals with epidermodysplasia verruciformis
  • Also associated with chemical carcinogens or chronic wounds, such as nonhealing ulcers, burn scars, sinus tracts
  • Marjolin ulcer: SCC arising at site of chronic inflammation, presenting as persistent ulceration
  • When diagnosed in a child / young person, consider a genodermatosis such as xeroderma pigmentosum
Clinical features
  • May present as thin plaque or erythematous scaly papule
  • Thin SCC (superficially invasive) may clinically simulate in situ carcinoma or actinic keratosis
  • Thicker tumors typically present as erythematous plaque, nodule, ulcer
Prognostic factors
  • Excellent prognosis
  • < 1% die of disease (~2200 per year in US)
  • Metastases uncommon if tumor < 1.5 cm deep
  • 5% metastasize if 2 cm or more and definite dermal invasion; most common site is lung
  • Metastatic rate is 5 - 10% in transplant patients, who do poorly with metastatic disease
  • Metastases more likely in tumors that originate in scars or ulcers
  • Most superficial tumors are indolent

  • Favorable features:
    • Low stage
    • No / superficial dermal invasion
    • Small vertical tumor thickness (< 4 mm)
    • Well differentiated
    • Short duration
    • Location other than scalp, ear, lip, nose, eyelid or soft tissue (which readily invade subcutaneous tissue)

  • Unfavorable features:
    • High risk anatomic sites (scalp, ear, lip, nose, eyelid)
    • Immunosuppression
    • Size (width) greater than 2 cm; depth greater than 4 mm
    • Lymphovascular or perineural invasion
    • Poorly differentiated
Case reports
  • Surgical excision with adequate margins
  • Also curettage, electrodessication, cryotherapy, radiation therapy
Clinical images

Images hosted on other servers:

62 year old man with cutaneous horn on scalp

Tumor on volar aspect

Various images

Gross description
  • Often white plaque (leukoplakia)
  • May have induration, ulceration, hemorrhage
Microscopic (histologic) description
  • Carcinoma that infiltrates dermis
  • An associated precursor lesion (actinic keratosis / keratinocytic dysplasia / in situ squamous cell carcinoma) is often present, but may not be detectable due to ulceration
  • Spectrum of histologic features, which has led to descriptions of various "types" of SCC; all share downward growth below level of adjacent or overlying epidermis
Microscopic (histologic) images

Images hosted on PathOut server:

Case of the Week #290:


Images hosted on other servers:

Superficially invasive

Well differentiated

Clear cell type

"Pearl-like" structures

Arising in Marjolin ulcer

Perineural and vascular invasion

Contributed by Semir Vranić, M.D., Ph.D.

Acantholytic type

Positive stains
Negative stains
Differential diagnosis
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