Cutaneous squamous cell carcinoma presents with a wide variety of clinical manifestations, including papules, plaques, or nodules, and smooth, hyperkeratotic, or ulcerative lesions. Skin biopsies are required to confirm the diagnosis. Biopsies also provide information that is useful for staging.
squamous cell carcinomas can develop on any cutaneous surface, including the head, neck, trunk, extremities, oral mucosa, periungual skin, and anogenital areas. In fair-skinned individuals, squamous cell carcinomas most commonly arise in sites frequently exposed to the sun. In a cohort of 145 patients with squamous cell carcinoma in Australia, the following distribution of squamous cell carcinoma was observed.
- Head and neck (55 percent)
- Dorsum of the hands and forearms (18 percent)
- Legs (13 percent)
- Arms (3 percent)
- Shoulder or back (4 percent)
- Chest or abdomen (4 percent)
The development of squamous cell carcinoma on non-sun-exposed skin is less common overall, but represents the most common distribution in individuals with dark skin. This finding is likely related to the protective effect of epidermal melanin against the carcinogenic effects of ultraviolet light. In African and Caribbean individuals, common sites for squamous cell carcinoma include the legs, anus, and areas of chronic inflammation or scarring. Lesions that develop in relation to chronic scarring processes account for 20 to 40 percent of squamous cell carcinoma in African and Caribbean patients.
The clinical appearance of cutaneous squamous cell carcinoma is influenced by the lesion type and site.
- Squamous cell carcinoma in situ (Bowen’s disease) — Cutaneous squamous cell carcinoma in situ typically presents as a well-demarcated, scaly patch or plaque. Lesions are often erythematous but can also be skin colored or pigmented. Squamous cell carcinoma in situ lesions tend to grow slowly, enlarging over the course of years. Unlike the inflammatory disorders that may resemble squamous cell carcinoma in situ, lesions are usually asymptomatic.
- Invasive squamous cell carcinoma— The clinical appearance of invasive squamous cell carcinoma often correlates with the level of tumor differentiation. Well-differentiated lesions usually appear as indurated or firm, hyperkeratotic papules, plaques, or nodules. Lesions are usually 0.5 to 1.5 cm in diameter, although some are much larger. Ulceration may or may not be present.
- In contrast, poorly differentiated lesions are usually fleshy, soft, granulomatous papules or nodules that lack the hyperkeratosis that is often seen in well-differentiated lesions. Poorly differentiated tumors may have ulceration, hemorrhage, or areas of necrosis.
Lesions of invasive squamous cell carcinoma are often asymptomatic but may be painful or pruritic. Local neurologic symptoms (eg, numbness, stinging, burning, paresthesias, paralysis, or visual changes) occur in approximately one-third of patients with histologic perineural invasion by the tumour. Perineural invasion is a poor prognostic factor.
Oral squamous cell carcinoma— Oral squamous cell carcinoma usually presents as an ulcer, nodule, or indurated plaque involving the oral cavity. The floor of the mouth and lateral or ventral tongue are the most common sites for these tumors. Lesions may arise in sites of erythroplakia (premalignant, persistent, red patches in the oral cavity) or leukoplakia (oral, persistent, white plaques). Oral squamous cell carcinoma is often associated with a history of tobacco or heavy alcohol use.
Keratoacanthoma — Keratoacanthomas are keratocytic epithelial tumors that clinically and histologically resemble squamous cell carcinoma. It is controversial whether keratoacanthomas represent a subtype of well-differentiated squamous cell carcinoma or a separate entity.
Keratoacanthomas are usually found on actinically damaged skin. Lesions typically exhibit rapid initial growth, manifesting as dome-shaped or crateriform nodules with a central keratotic core that develop within a few weeks.
Verrucous carcinoma — Verrucous carcinoma is a subtype of squamous cell carcinoma that presents with well-defined, exophytic, cauliflower-like growths that resemble large warts.
Squamous cell carcinoma of the lip — squamous cell carcinoma of the lip primarily occurs on the lower lip. Lesions may present as nodules, ulcers, or indurated or white plaques.
Marjolin’s ulcer — Marjolin’s ulcer is a term used to describe a rare type of SCC arising in sites of chronic wounds or scars. The malignant transformation is usually slow, with an average latency time of approximately 30 years.
The tumor may initially present as an ulceration that fails to heal; nodules may develop as the lesion progresses. Other clinical signs include rolled or everted wound margins, excessive granulation tissue, rapid increase in size, and bleeding on touch.
Squamous cell carcinomas arising in the setting of chronic wounds or scar are typically aggressive and are associated with a poor prognosis. The risk of local recurrence after treatment or metastasis is approximately 20 to 30 percent.
Cutaneous metastases — The most frequent site of metastasis for cutaneous squamous cell carcinoma is the regional lymph nodes; other potential sites for metastasis include the lungs, liver, brain, skin, or bone. Metastases to the skin can present with erythematous papules or nodules that resemble primary lesions of cutaneous squamous cell carcinoma.
Although clinical findings may strongly suggest a diagnosis of squamous cell carcinoma, histopathologic examination is necessary to confirm the diagnosis. Histopathologic examination is also useful for assessment for perineural invasion, tumor differentiation, and tumor depth, factors that are important for tumor staging and prognosis.
Biopsy — Shave, punch, or excisional biopsies may be used for diagnosis. Regardless of the biopsy technique selected, for lesions that are papular, nodular, or otherwise suspicious for invasive squamous cell carcinoma, biopsies that extend at least into the mid-reticular dermis are preferred to allow for adequate evaluation of invasive disease. More superficial biopsies may be performed in patients with lesions that are suggestive of in situ squamous cell carcinoma.
Squamous cell carcinomain situ — squamous cell carcinomain situ (Bowen’s disease) is diagnosed when histopathologic examination reveals keratinocytic dysplasia involving the full thickness of the epidermis without infiltration of atypical cells into the dermis. The keratinocytes are pleomorphic with hyperchromatic nuclei, and numerous mitoses are present. Frequently, there is associated thickening of the epidermis (acanthosis), as well as hyperkeratosis and parakeratosis of the stratum corneum. In contrast to SCC in situ, actinic keratoses demonstrate only partial-thickness epidermal dysplasia.
Invasive squamous cell carcinoma— Invasive squamous cell carcinomas have dysplastic keratinocytes involving the full thickness of the epidermis that penetrate the epidermal basement membrane to involve the dermis or deeper tissues. Well-differentiated cutaneous squamous cell carcinomas contain atypical keratinocytes that are slightly enlarged with abundant amounts of cytoplasm. Keratinization is usually present.
In poorly differentiated squamous cell carcinoma, keratinocytes are anaplastic, with little evidence for differentiation or keratinization. Multiple mitoses are often seen. Occasionally, the keratinocytic origin of the cells can only be determined by immunohistochemical stains.
Several histopathologic variants of invasive squamous cell carcinoma exist, including spindle cell squamous cell carcinoma, acantholytic (adenoid) squamous cell carcinoma, clear cell squamous cell carcinoma, adenosquamous (mucin-producing) squamous cell carcinoma, desmoplastic squamous cell carcinoma, single-cell squamous cell carcinoma, and others.
Multiple other skin disorders can resemble cutaneous squamous cell carcinoma.
Actinic keratoses — The most common clinical diagnostic dilemma involves actinic keratoses. Actinic keratoses are rough, scaly, erythematous macules that develop on sun-damaged skin and demonstrate keratinocytic atypia on histopathologic examination. Although only a fraction of 1 percent of actinic keratoses progress to squamous cell carcinoma, approximately 60 percent of squamous cell carcinomas arise from actinic keratoses.
Actinic keratoses are often found in close proximity to squamous cell carcinomas and can resemble squamous cell carcinoma in situ or early squamous cell carcinoma. Tenderness, bleeding, and palpable underlying substance suggest the possibility of squamous cell carcinoma and indicate the need for biopsy.
Other disorders — The well-demarcated, scaling, pink plaques of squamous cell carcinoma in situ can resemble inflammatory skin disorders or other malignancies. The differential diagnosis often includes:
- Nummular eczema
- Inflamed seborrheic keratosis
- Viral warts
- Superficial basal cell carcinoma
- Amelanotic melanoma
- Paget disease
Well-defined papules or nodules of well-differentiated squamous cell carcinoma can resemble:
- Viral warts
- Prurigo nodules
- Merkel cell carcinoma
- Basal cell carcinoma
- Atypical fibroxanthoma
- Amelanotic melanoma
- Cutaneous metastases of internal malignancy
Granulomatous or verrucous lesions may mimic:
- Pyogenic granulom
- Mycobacterial or deep fungal infections
- The differential diagnosis for squamous cell carcinoma manifesting as nonhealing ulcers includes:
- Basal cell carcinoma
- Pyoderma gangrenosum
- Venous stasis ulcers
- Traumatic ulcers
Staging of head and neck squamous cell carcinomas is carried using the American Joint Committee on Cancer (AJCC) 8th Edition of staging guidelines.
●Squamous cell carcinoma is a common cutaneous malignancy that can occur on any surface of the skin. Sun-exposed sites are the most common locations for squamous cell carcinoma in fair-skinned individuals; involvement of other areas is more common in people with dark skin.
●The clinical findings of cutaneous squamous cell carcinoma depend on the type of lesion and location of involvement. Squamous cell carcinoma frequently manifests as erythematous papules, plaques, or nodules. Hyperkeratosis, ulceration, or hyperpigmentation also may be present.
●Squamous cell carcinoma can develop in sites of chronic wounds, chronic inflammation, or scarring. Nonhealing ulcers or nodules in these sites can be a manifestation of squamous cell carcinoma.
●Biopsy is necessary to confirm the diagnosis of squamous cell carcinoma . For lesions clinically suspected to be invasive, a shave, punch, or excisional biopsy that extends at least into the mid-reticular dermis is preferred.
●Actinic keratoses can resemble lesions of squamous cell carcinoma . Lesions that are tender, painful, or that have underlying substance should be biopsied to evaluate for squamous cell carcinoma.
Squamous cell carcinoma excised from the right cheek.