Squamous cell carcinoma (SCC) is the second most common form of skin cancer, originating from the flat, scale-like squamous cells found in the outermost layer of the skin. Most cases of cutaneous SCC, which arises from sun-exposed skin, are caught early and cured with localized treatment. SCC can spread from its original site, though this is relatively infrequent for low-risk primary tumors. The estimated rate of metastasis for cutaneous SCC is generally low, ranging from 1% to 5% of all cases. However, SCC that develops on mucous membranes, such as in the mouth or throat, tends to be biologically more aggressive and carries a significantly higher potential for spread.
Factors Influencing Metastatic Risk
The likelihood of a primary squamous cell carcinoma spreading is determined by specific tumor and patient characteristics. These features help clinicians classify a tumor as high-risk, guiding the intensity of initial treatment and follow-up monitoring. A significant tumor feature is the size and depth of the lesion. Larger tumors, especially those greater than two centimeters in diameter, are associated with greater metastatic risk. Tumors that invade deeply beyond the subcutaneous fat layer or have a high Clark level of invasion are more likely to have accessed pathways for spread.
The appearance of cancer cells under a microscope also influences the risk assessment. Poorly differentiated tumors, where cells look highly abnormal and unlike healthy squamous cells, carry an elevated risk of metastasis. Conversely, well-differentiated tumors, where the cells still resemble normal tissue, have a much lower potential for spread. Perineural invasion is another microscopic feature where cancer cells follow the path of a nerve, allowing a direct route to deeper tissues and distant sites.
The anatomical location of the primary tumor is a well-established factor influencing metastatic potential. Lesions found on the lip or the ear are considered high-risk due to the complex lymphatic drainage networks in those areas. SCCs that arise in areas of chronic inflammation, such as old burn scars or chronic ulcers, are also more aggressive. A patient’s immune status is a major factor, as immunosuppressed individuals, such as organ transplant recipients, face a substantially higher risk of developing aggressive SCC.
Common Sites of Spread
When squamous cell carcinoma metastasizes, it typically utilizes the body’s lymphatic system. The first and most common destination is the regional lymph nodes, the filtering stations closest to the original tumor site. For a cutaneous SCC on the head or neck, cancer cells often travel to the parotid or cervical lymph nodes.
Spread to these nearby lymph nodes is categorized as locoregional metastasis and is the most frequent type of spread. If the tumor progresses beyond this stage, it can travel through the bloodstream to reach distant organs. Although distant metastasis is rare, its occurrence carries a poorer prognosis.
The most frequent sites for distant spread are the lungs, followed by the liver and the bone. The specific location of the primary tumor often determines which regional nodes are first affected. Detecting cancer at these distant sites signifies the most advanced stage of the disease.
Diagnostic Approaches for Detecting Metastasis
Detecting squamous cell carcinoma metastasis begins with a thorough physical examination. Clinicians carefully palpate regional lymph nodes to check for enlargement, firmness, or tenderness, as a suspicious node often indicates local spread. If the physical exam suggests potential metastasis, diagnostic imaging confirms the spread and determines the disease extent.
Imaging techniques include computed tomography (CT) scans and magnetic resonance imaging (MRI). CT scans are useful for evaluating lymph nodes and looking for bone or soft tissue invasion. MRI is often preferred when cancer is suspected of tracking along a nerve pathway (perineural invasion) or for assessing spread into the skull base or orbit.
Positron emission tomography (PET) scans are often used with CT scans (PET-CT) to detect cancer cells throughout the body, especially when searching for distant metastasis. To definitively confirm cancer in a suspicious lymph node, a fine-needle aspiration (FNA) or an excisional biopsy is performed. This procedure collects a tissue sample for pathological examination to confirm malignant cells.
Treatment Strategies for Advanced Disease
The management of confirmed metastatic squamous cell carcinoma requires a multidisciplinary approach, often combining localized and systemic treatments. Treatment strategies are tailored based on the extent of the spread, whether confined to regional lymph nodes or spread to distant organs. For locoregional metastasis, surgery is a primary treatment, often involving a lymph node dissection.
Radiation therapy is frequently used with surgery, either before or after the procedure, to target remaining cancer cells. For advanced disease too extensive for surgery or radiation, or for distant metastasis, systemic therapy is necessary. Systemic treatments destroy cancer cells wherever they have spread in the body.
Immunotherapy has significantly changed the landscape for treating advanced SCC. Specific PD-1 inhibitors, such as cemiplimab and pembrolizumab, are approved to treat metastatic or locally advanced SCC not curable with surgery or radiation. These agents harness the patient’s immune system to recognize and attack cancer cells, offering a new option for managing this advanced stage of the disease.