Dermatology · Non-Melanoma Skin Cancer
The facts most likely to be tested
Squamous cell carcinoma presents as a hyperkeratotic, erythematous papule or plaque with a scaly, ulcerated, or crusted surface.
Chronic ultraviolet (UV) light exposure is the primary risk factor, though immunosuppression, human papillomavirus (HPV), and chronic scarring (Marjolin ulcer) are significant contributors.
Actinic keratosis is the most common precancerous lesion that serves as a direct precursor to cutaneous squamous cell carcinoma.
Histopathology reveals keratin pearls and intercellular bridges within the tumor cell nests.
Marjolin ulcer refers to a squamous cell carcinoma that arises within a chronic wound, burn scar, or osteomyelitis sinus tract and is characterized by a more aggressive clinical course.
The definitive diagnostic procedure for a suspicious lesion is a full-thickness excisional biopsy or a deep shave biopsy to assess the depth of invasion.
Mohs micrographic surgery is the treatment of choice for high-risk lesions located on the face, ears, nose, or genitalia to ensure complete margin clearance while sparing healthy tissue.
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A 68-year-old male presents to the clinic for a persistent lesion on his left lower lip. He has a 40-year history of working as a commercial fisherman and reports frequent sun exposure. Physical examination reveals a 1.2 cm indurated, ulcerated plaque with raised, pearly borders and surface crusting. The lesion is tender to palpation and does not bleed easily. There is no palpable cervical lymphadenopathy.
What is the most likely diagnosis?
Squamous cell carcinoma
The patient's history of chronic UV exposure and the presence of an indurated, ulcerated, hyperkeratotic lesion on a sun-exposed site (lip) are classic for squamous cell carcinoma, which is tested by the clinical presentation described in Bet 1.
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Etiology / Epidemiology
Second most common skin cancer; UV radiation is the primary driver. High risk in fair-skinned individuals and those with chronic immunosuppression.
Clinical Manifestations
Presents as a hyperkeratotic, ulcerated papule or plaque. Often described as a non-healing ulcer with a firm, indurated border.
Diagnosis
The punch biopsy or excisional biopsy is the gold standard for definitive diagnosis.
Treatment
Surgical excision (Mohs micrographic surgery) is the first-line treatment for high-risk lesions.
Prognosis
Metastatic risk is low (<5%) but significantly higher in ear, lip, or temple locations.
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Epidemiology & Etiology
Incidence increases with age and cumulative UV exposure. Major risk factors include HPV infection (genital/oral), chronic scarring (Marjolin ulcer), and arsenic exposure. Immunosuppressed patients, particularly organ transplant recipients, face a significantly higher risk of aggressive disease.
Pertinent Anatomy
Arises from the keratinocytes of the epidermis. Lesions on the head and neck are considered high-risk due to increased lymphatic drainage and potential for deep tissue invasion.
Pathophysiology
Chronic DNA damage from UV light leads to mutations in the TP53 tumor suppressor gene. Uncontrolled proliferation of atypical keratinocytes results in the formation of keratin pearls on histology. Progression from actinic keratosis to invasive SCC is a common clinical pathway.
Clinical Manifestations
Lesions often appear as a scaly, erythematous patch that evolves into a flesh-colored, firm nodule. Look for cutaneous horn formation or a non-healing ulcer that bleeds easily. Red flags include rapid growth, perineural invasion symptoms (numbness/tingling), or fixation to underlying structures.
Diagnosis
A full-thickness skin biopsy is required to differentiate from actinic keratosis. Histopathology reveals keratin pearls and atypical squamous cells invading the dermis. Mohs micrographic surgery is the preferred diagnostic and therapeutic approach for high-risk facial lesions to ensure clear margins.
Treatment
Surgical excision with standard margins is sufficient for low-risk lesions. Mohs micrographic surgery is indicated for high-risk sites (H-zone of face, genitalia, hands). Radiation therapy is reserved for patients who are poor surgical candidates. Topical 5-fluorouracil is only for pre-malignant actinic keratosis, not for invasive SCC.
Prognosis
Most cases are cured with local excision. Perineural invasion and tumor thickness >2mm are associated with higher recurrence. Patients require lifelong skin surveillance due to the high risk of developing subsequent primary skin malignancies.
Differential Diagnosis
Basal Cell Carcinoma: pearly papule with telangiectasias
Actinic Keratosis: sandpaper-like texture, pre-malignant
Seborrheic Keratosis: stuck-on, waxy appearance
Amelanotic Melanoma: lacks pigment, often misdiagnosed
Keratoacanthoma: rapid growth with central keratin plug