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Skin - Nonmelanocytic tumors

Carcinoma (non-adnexal)

Squamous cell carcinoma

Reviewer: Christopher Hale, M.D. (see Reviewers page)
Revised: 7 April 2014, last major update June 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.


● Common, derived from keratinocytes in epidermal layer
● Often associated with sun exposure (UV light may induce p53 mutations and diminish surveillance function of Langerhans cells in epidermis)

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)

Clinical features

● Usually men
● Very rare in blacks
● 5% are node positive at diagnosis
● Slow growing, locally invasive but rarely metastasizes outside nodes

● Excellent
● 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

Good prognostic factors:
● Low stage, no/superficial dermal invasion, small vertical tumor thickness (< 4 mm), well differentiated, short duration, location other than scalp, ears, lips, nose, eyelids or soft tissue (which readily invade subcutaneous tissue)


● Surgical excision with adequate margins
● Also curettage, electrodessication, cryotherapy, radiation therapy

Case reports

● 82 year old woman (Dermatology Online Journal 6;1:11)
● 87 year old woman with forearm skin lesion (Case of the Week #290)

Clinical images

62 year old man with cutaneous horn on scalp

82 year old woman

Various images

Gross description

● Often white plaque (leukoplakia)
● May have induration, ulceration, hemorrhage

Micro description

● Atypia at all levels of epidermis
● 80% are well differentiated with keratin pearls, intercellular bridges and no/rare keratohyaline granules
● Invade dermis by definition
● May contain non-neoplastic melanocytes that transfer melanin to tumor cells
● Occasionally clear cells, rarely signet ring cells
Spindle, adenoid and verrucous variants are described separately
● Other variants are acantholytic (pseudoglandular, tumor clefts produced by acantholysis of tumor cells) and pseudoangiosarcomatous (clefts separate neoplastic lobules)

Low grade (well differentiated):
● Cell differentiation, uniform cell size, intact intercellular bridges, no/rare mitotic figures, no/mild pleomorphism

High grade (poorly differentiated):
● Little cell differentiation, pleomorphism with spindle cells, necrosis, marked mitotic activity, deep invasion

Micro images


Various images

Case of the Week #290

Contributed by: Dr. Semir Vranic

Positive stains

● High molecular weight keratin, EMA, involucrin, p53 (50%), variable CEA

Negative stains

● Ber-EP4, usually CK7 and CK20 (head and neck tumors, Mod Pathol 2004;17:407)

Differential diagnosis

● Keratoacanthoma (for well differentiated tumors)

Additional references

J Skin Cancer 2011;2011:210813

End of Skin - Nonmelanocytic tumors > Carcinoma (non-adnexal) > Squamous cell carcinoma

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