History
The initial presentation of cutaneous squamous cell carcinoma (cSCC) typically includes a history of a nonhealing ulcer or abnormal growth in a sun-exposed area (see the image below).
Large, sun-induced squamous cell carcinoma (SCC) on the forehead/temple. Image courtesy of Glenn Goldman, MD.
The clinical assessment should begin with a thorough review of the risk factors for cSCC development. An assessment of the rate of tumor growth is also important, as this often reflects the aggressiveness of the lesion. The clinician should ask about features that suggest peripheral nerve involvement by the tumor, such as local pain, numbness, twitching or muscle weakness, and, with cSCCs of the face, visual changes.
Physical Examination
Approximately 70% of all cSCCs occur on the head and neck, most frequently involving the lower lip, external ear and periauricular region, or forehead and scalp. Consequently, the head and neck should be of particular interest in a comprehensive examination of a patient with suspected cSCC. The following features of the lesion should be noted (see also the images below):
-
Location (eg, eyelid SCC is more common on the lower eyelid)
-
Size
-
Character (eg, smooth/nodular, vascularity, color): SCC may appear as plaques or nodules with variable degrees of scale, crust, or ulceration
-
Presence of ulceration
A 35-year-old man with human immunodeficiency virus (HIV) infection presented with a 2-year history of a slowly enlarging, left lower eyelid lesion; incisional biopsy revealed squamous cell carcinoma.
A large, ulcerated, invasive squamous cell carcinoma of the left lower eyelid. This patient also had perineural invasion of the infraorbital nerve extending into the cranial base.
Frequently, the presentation of cSCC is preceded by the presence of actinic keratoses. [36] These precancerous lesions appear as scaly plaques or papules, often with an erythematous base. An actinic keratosis is usually only several millimeters in size and ranges from normal skin color to pink or brown. Patients with multiple actinic keratoses have an estimated 6-10% lifetime risk of developing skin cancer.
The overall appearance of any skin lesion must be detailed. The classic presentation of a cSCC is that of a shallow ulcer with heaped-up edges, often covered by a plaque. Of course, the presenting appearance of each cSCC varies according to the site and extent of disease.
Tumor size and location
In addition to general appearance, the size and location of the lesion should be recorded, as both have prognostic and therapeutic importance. For instance, lesions larger than 2 cm and those located on the external ear or lip have been shown to have a higher rate of metastatic spread.
Additionally, tumor size and location affect the cosmetic and functional outcome of surgical excision. Therefore, reconstructive options should be carefully considered in the assessment of every head and neck cSCC. Lesions located near critical areas, such as around the eyes, may require additional evaluation by a dedicated reconstructive surgeon before excision.
Tumor characteristics
Surface changes on a typical SCC may include scaling, ulceration, crusting, or the presence of a cutaneous horn. Less commonly, the lesion may manifest as a pink cutaneous nodule without overlying surface changes.
The absence of surface changes should raise suspicion of a metastatic focus from another skin or nonskin primary site or of a different and potentially more lethal tumor, such as a Merkel cell carcinoma. A background of severely sun-damaged skin, including solar elastosis, mottled dyspigmentation, telangiectasia, and multiple actinic keratoses, is often noted.
Clinically, lesions of SCC in situ (SCCIS) range from a scaly, pink patch to a thin keratotic papule or plaque similar to an actinic keratosis. Bowen disease is a subtype of SCCIS characterized by a sharply demarcated, pink plaque arising on non–sun-exposed skin (see the image below).
SCC of the lip usually arises on the vermillion border of the lower lip. It is sometimes predated by a precursor lesion, actinic cheilitis, which manifests as xerosis, fissuring, atrophy, and dyspigmentation. Actinic cheilitis is analogous to actinic keratosis of the skin.
Perineural invasion
Up to 14% of cSCCs exhibit perineural invasion. Evidence of cranial nerve dysfunction on examination should raise concern of significant perineural invasion. The most frequently involved cranial nerves are the facial and trigeminal nerves, [37] underscoring the importance of assessment of facial movement and sensation. Therefore, every patient with head and neck cSCC should undergo systematic evaluation of cranial nerve function.
Tumor metastasis
Investigate regional spread of head and neck cSCC by palpating for enlarged preauricular, submandibular, and cervical lymph nodes. Regional metastasis occurs in 2-6% of cases of cSCC. The risk of metastasis correlates roughly with tumor size and differentiation. In general, metastasis from cSCC of the forehead, temples, eyelids, cheeks, and ears is to the parotid nodes; metastasis from cSCC of the lips and perioral region is primarily to the submental and submaxillary (upper cervical) nodes.
In head and neck cSCC, soft tissue metastasis, defined as metastatic spread to non-lymphatic soft tissue, suggests a poorer prognosis than extranodal extension. [38]
Rarely, cSCC presents as a parotid or neck mass because of lymphatic spread from an occult cutaneous lesion or remotely treated skin cancer (see the image below). [39] The median time from initial treatment to presentation with a parotid or neck mass ranges from 10 to 13 months. Fine-needle aspiration biopsy can be of assistance in the evaluation of any mass suspected to represent occult metastasis.
Preauricular and helical scars (black arrows) from prior excisions are noted in a patient who presented with cervical metastases (white arrow) from an occult cutaneous squamous cell carcinoma.
Conjunctival squamous cell carcinoma
Most SCCs involving the conjunctiva manifest as chronic, unilateral, localized patches of redness or more diffuse conjunctivitis (see the image below). They can also present as a mass in the interpalpebral fissure at the nasal or temporal limbus with a gelatinous and velvety, papilliform, or leukoplakic appearance. Prominent feeder vessels may be seen. The corneoscleral limbus is the most common location, although the palpebral conjunctiva or cornea may be involved, particularly in the interpalpebral region.
Extensive conjunctival squamous cell carcinoma of the left eye. The patient had limbal and corneal involvement temporally, as well as scleral invasion with intraocular spread. A malignant cellular reaction in the anterior chamber was present. The patient was treated with a lid-sparing exenteration.
Individuals with HIV infection and those with xeroderma pigmentosa are more likely to develop conjunctival SCC, probably because of their diminished immune status. Often, small conjunctival masses are noted on routine eye examinations.
Distinguishing conjunctival SCC from conjunctival intraepithelial neoplasia is difficult on clinical examination alone. [40] Conjunctival SCC represents a type of conjunctival intraepithelial neoplasia that has either broken through the basement membrane to involve the subepithelial tissue or has metastasized. [41, 42, 43]
Given its variable appearance, conjunctival SCC may pose a diagnostic challenge as a masquerade syndrome. Patients with an atypical pterygium may have a conjunctival tumor and should be observed much more closely than patients with a classic pterygium. Unsuspected ocular surface neoplasia may be present within excised pterygia. For this reason, one study recommends the submission of all excised pterygia for histopathologic analysis. [44]
The examination of conjunctival SCC should determine the full extent of the lesion; rose Bengal dye is helpful for this evaluation. In addition, assess any suspicion of intraocular involvement via slit lamp examination, gonioscopy, and echography. Orbital involvement should be investigated with computed tomography (CT) scanning or magnetic resonance imaging (MRI).
-
Large, sun-induced squamous cell carcinoma (SCC) on the forehead/temple. Image courtesy of Glenn Goldman, MD.
-
Preauricular and helical scars (black arrows) from prior excisions are noted in a patient who presented with cervical metastases (white arrow) from an occult cutaneous squamous cell carcinoma.
-
Contrast-enhanced, axial computed tomography (CT) scan of a patient with soft tissue invasion of the right parotid gland (arrow) by an ulcerative cutaneous squamous cell carcinoma.
-
Large, neglected cutaneous squamous cell carcinoma of the right ear that requires wide local excision via auriculectomy and reconstruction. The risk of lymph node metastasis with this deeply ulcerative tumor is high enough to warrant elective neck dissection.
-
Squamous cell carcinoma in situ (Bowen disease). Courtesy of Hon Pak, MD.
-
Extensive conjunctival squamous cell carcinoma of the left eye. The patient had limbal and corneal involvement temporally, as well as scleral invasion with intraocular spread. A malignant cellular reaction in the anterior chamber was present. The patient was treated with a lid-sparing exenteration.
-
A 35-year-old man with human immunodeficiency virus (HIV) infection presented with a 2-year history of a slowly enlarging, left lower eyelid lesion; incisional biopsy revealed squamous cell carcinoma.
-
Axial magnetic resonance image (MRI) of a large squamous cell carcinoma of the left lower eyelid with invasion of the anterior orbit.
-
A large, ulcerated, invasive squamous cell carcinoma of the left lower eyelid. This patient also had perineural invasion of the infraorbital nerve extending into the cranial base.
-
Progressively severe atypia. The epithelium to the left is close to normal, but the epithelium to the right shows full-thickness atypia (ie, carcinoma in situ). This image illustrates carcinogenesis, the process whereby cells exposed to a carcinogen become cancerous over time.
-
Squamous cell carcinoma. The lesion closely approximates the specimen in the previous image. Field cancerization is illustrated; that is, if >1 cell is exposed to a carcinogen, >1 cell becomes cancerous. Note the marked inflammatory-cell response. Should limited biopsy reveal only severe atypia with a severe inflammatory response, the lesion should be investigated further, because a cancer is likely nearby.
Tables
Stage |
Primary Tumor |
Regional Lymph Nodes |
Distant Metastasis |
Stage 0 |
Tis |
N0 |
M0 |
Stage I |
T1 |
N0 |
M0 |
Stage II |
T2 |
N0 |
M0 |
Stage III |
T3 |
N0 |
M0 |
T1-3 |
N1 |
M0 |
|
Stage IV |
T4 |
N0 |
M0 |
Any T |
N2-3 |
M0 |
|
Any T |
Any N |
M1 |
