Invasive Squamous Cell Carcinoma (SCC) SCC of the skin is a malignant tumor of keratinocytes, arising in the epidermis. SCC usually arises in epidermal precancerous lesions and, depending on etiology and level of differentiation, varies in its aggressiveness. The lesion is a plaque or a nodule with varying degrees of keratinization in the nodule and/or on the surface. Thumb rule: Undifferentiated SCC: is soft and has no hyperkeratosis; Differentiated SCC: is hard on palpation and has hyperkeratosis. Exposure: Sunlight. Phototherapy, PUVA (oral psoralen + UVA). Excessive photochemotherapy can lead to promotion of SCC, particularly in patients with skin phototypes I and II or in patients with history of previous exposure to ionizing radiation or methotrexate treatment for psoriasis. Lesions : Indurated papule, plaque, or nodule ; adherent thick keratotic scale or hyperkeratosis ; when eroded or ulcerated, the lesion may have a crust in the center and a firm, hyperkeratotic, elevated margin Clark levels level I, intra-epidermal; level II, invades papillary dermis; level III fills papillary dermis; level IV, invades reticular dermis; level V, invades subcutaneous fat.

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Invasive Squamous
Cell Carcinoma (SCC)

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Invasive Squamous Cell Carcinoma
(SCC)
• SCC of the skin is a malignant tumor of
keratinocytes, arising in the epidermis.
• SCC usually arises in epidermal
precancerous lesions and, depending on
etiology and level of differentiation, varies
in its aggressiveness.

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• The lesion is a plaque or a nodule with
varying degrees of keratinization in the
nodule and/or on the surface.
Thumb rule:
• Undifferentiated SCC: is soft and has no
hyperkeratosis;
• Differentiated SCC: is hard on palpation
and has hyperkeratosis.

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Epidemiology and Etiology
• Age of Onset :
Older than 55 years of age in the United States;
• Sex :
Males > females.

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• Exposure:
Sunlight. Phototherapy, PUVA (oral psoralen +
UVA). Excessive photochemotherapy can lead to
promotion of SCC, particularly in patients with skin
phototypes I and II or in patients with history of
previous exposure to ionizing radiation or
methotrexate treatment for psoriasis.

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• Race:
Persons with white skin and poor tanning
capacity (skin phototypes I and II). Brown- or
black-skinned persons can develop SCC
from numerous etiologic agents other than
UVR.
• Geography:
Most common in areas that have many days
of sunshine annually, i.e., in Australia and
southwestern United States.

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• Occupation:
Persons working outdoors—farmers, sailors,
lifeguards, telephone line installers,
construction workers, dock workers.

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1- Ultraviolet Radiation
2- Human Papillomavirus:
• Oncogenic HPV type -16, -18, -31 most
commonly, -33, -35, -39, -40, and -51 to -
60 are associated with epithelial dysplasia,
SCCIS, and invasive SCC. HPV-5, -8, -9
have also been isolated from SCCs.
Etiology

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3- Other Etiologic Factors:
Immunosuppression
Chronic Inflammation
Industrial Carcinogens
Inorganic Arsenic: used in the past in
medications such as Asiatic pills, Donovan pills, Fowler
solution (used as a treatment for psoriasis). Historically
trivalent arsenic was used for treatment of psoriasis.
Arsenic is still present in drinking water in some
geographic regions (West Bengal and Bangladesh).

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Clinical Manifestation
• Slowly evolving —any isolated keratotic
or eroded papule or plaque in a suspect
patient that persists for over a month is
considered a carcinoma until proved
otherwise. Also, a nodule evolving
Rapidly evolving —invasive SCC can
erupt within a few weeks and is often
painful and/or tender.

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For didactic reasons, two types can be
distinguished:
1. Highly differentiated SCCs:
which practically always show signs of keratinization either
within or on the surface (hyperkeratosis) of the tumor.
These are firm or hard upon palpation .
2. Poorly differentiated SCCs:
which do not show signs of keratinization and clinically
appear fleshy, granulomatous, amd consequently are soft
upon palpation .

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Squamous cell carcinoma: invasive on
the lip

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Differentiated SCC
• Lesions :
• Indurated papule, plaque, or nodule ;
adherent thick keratotic scale or
hyperkeratosis ; when eroded or ulcerated,
the lesion may have a crust in the center and
a firm, hyperkeratotic, elevated margin

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Distribution
• Usually isolated but may be multiple. Usually
exposed areas. Sun-induced keratotic and/or
ulcerated lesions especially on the bald scalp ,
cheeks, nose, lower lips , ears , pre-auricular
area, dorsa of the hands, forearms, trunk, and
shins (females) .
• Other Physical Findings : Regional
lymphadenopathy due to metastases

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• Special Features: In UV-related SCC
evidence of dermatoheliosis and solar
keratoses.
• Special form : carcinoma cuniculatum,
usually on the soles, highly differentiated,
HPV-related but can also occur in other
settings

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SCC (carcinoma
cuniculatum)
in a patient with
peripheral
neuropathy due
to leprosy

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Undifferentiated SCC
• Lesions:
Fleshy, granulating, easily vulnerable,
erosive papules and nodules and
papillomatous vegetations . Ulceration with a
necrotic base and soft, fleshy margin.
Bleeds easily, crusting. Red. Soft.
Polygonal, irregular, often cauliflower-like.

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• Distribution:
• Isolated but also multiple, particularly on
the genitalia, where they arise from
erythroplasia and on the trunk lower
extremities, or face, where they arise from
Bowen disease.
• Miscellaneous Other Skin Changes:
Lymphadenopathy as evidence of regional
metastases is far more common than with
differentiated, hyperkeratotic SCCs

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Management
Surgery Depending on localization and
extent of lesion, excision with primary
closure, skin flaps, or grafting.
Microscopically controlled surgery in difficult
sites. Radiotherapy should be performed
only if surgery is not feasible.

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Squamous cell carcinoma, well differentiated
• A. A nodule on the lower arm covered with a dome-shaped dark
hyperkeratosis.
• B. A large, round, hard nodule on the nose with central
hyperkeratosis. Neither lesion can be distinguished from
keratoacanthoma
A B

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Squamous cell carcinoma, undifferentiated
There is a circular, dome-shaped reddish
nodule

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• Squamous cell carcinoma, advanced, well
differentiated, on the hand of a 65-yearold
farmer The big nodule is smooth, very hard
upon palpation,

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• Squamous cell carcinoma, highly differentiated, on
the ear There is a relatively large plaque covered by
adherent hard hyperkeratoses.

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Course And Prognosis
• Recurrence and Metastases SCC
causes local tissue destruction but it has a
significant potential for metastases.
Metastases are directed to regional lymph
nodes and appear 1 to 3 years after initial
diagnosis.

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High-risk SCCs: are defined as:
1) having a diameter >2 cm,
2) a level of invasion > 4 mm,
3) and Clark levels IV or V ∗ ;
4) tumor involvement of bone, muscle, and
nerve (so-called neurotropic SCC, occurs
frequently on the forehead and scalp);
5) location on ear, lip, and genitalia;
6) tumors arising in a scar or following
ionizing radiation are usually highly
dedifferentiated tumors.

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∗ Clark levels
1) level I, intra-epidermal;
2) level II, invades papillary dermis;
3) level III fills papillary dermis;
4) level IV, invades reticular dermis;
5) level V, invades subcutaneous fat.

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• SOURCE: From FITZPATRICK’S COLOR ATLAS
AND SYNOPSIS OF CLINICAL DERMATOLOGY
SIXTH EDITION

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