Squamous Cell Carcinoma of the Lip: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
March 2, 2026

Squamous cell carcinoma of the lip is a type of cancer that begins in squamous cells, the flat cells that form the surface layer of the lip. These cells normally create a protective barrier on the outside of the lip.

When squamous cells grow uncontrolled and invade deeper tissues, the condition is called squamous cell carcinoma. This is the most common type of cancer affecting the lip.

Squamous cell carcinoma most often develops on the lower lip, which receives more sun exposure than the upper lip.

What are the symptoms of squamous cell carcinoma of the lip?

The symptoms of squamous cell carcinoma of the lip vary. Early lesions may appear as a persistent scaly patch, crusted area, or sore that does not heal. As the tumor grows, it may form a firm lump or ulcer.

Common symptoms include:

  • A non-healing sore on the lip.

  • Bleeding or crusting.

  • Pain or tenderness.

  • Swelling or thickening of the lip.

  • Numbness in advanced cases.

If the cancer spreads to nearby lymph nodes, swelling in the neck may occur.

What causes squamous cell carcinoma of the lip?

The most important risk factor for developing squamous cell carcinoma of the lip is long-term sun exposure. Ultraviolet (UV) radiation damages the DNA inside squamous cells, which can lead to cancer over time.

Actinic cheilitis, a precancerous condition caused by sun damage, often develops before squamous cell carcinoma.

Other risk factors include:

  • Tobacco use.

  • Heavy alcohol use.

  • Immune suppression.

  • Older age.

  • Fair skin.

How is this diagnosis made?

The diagnosis of squamous cell carcinoma of the lip begins with a clinical examination. If a suspicious lesion is identified, a biopsy is performed. The tissue sample is examined under a microscope by a pathologist.

The diagnosis of squamous cell carcinoma is made when abnormal squamous cells invade the deeper connective tissue beneath the surface epithelium.

Microscopic features

Under the microscope, squamous cell carcinoma is composed of abnormal squamous cells growing beyond the surface layer into the underlying tissue.

The tumor cells may form nests or sheets. Many tumors produce keratin, the same protective protein found in normal skin. Keratin may form rounded structures called keratin pearls, which help confirm the diagnosis.

The cells often have enlarged, dark nuclei and may show frequent mitotic figures, which are cells actively dividing. In more aggressive tumors, the cells may appear highly disorganized and produce little keratin.

Immunohistochemistry

Immunohistochemistry is a laboratory test that detects specific proteins within tumor cells. It may be used if the tumor appears poorly differentiated and the diagnosis is uncertain.

Squamous cell carcinoma typically expresses markers such as p40, p63, and cytokeratin 5/6. These proteins help confirm squamous differentiation.

What does tumor grade mean?

Tumor grade describes how abnormal the cancer cells look compared to normal squamous cells.

Squamous cell carcinoma of the lip is usually divided into three grades:

  • Well differentiated (Grade 1): The tumor cells resemble normal squamous cells and often produce keratin.

  • Moderately differentiated (Grade 2): The cells are more abnormal and less organized.

  • Poorly differentiated (Grade 3): The cells look very different from normal and grow in a more disorganized pattern.

Higher-grade tumors tend to behave more aggressively.

Depth of invasion and pathologic tumor stage (pT)

Squamous cell carcinoma begins in the surface epithelium and grows downward into deeper tissues. The depth of invasion describes how far the tumor has extended beneath the surface.

Pathologists measure the depth of invasion from the base of the epithelium to the deepest point of tumor invasion. This measurement is important because deeper tumors have a higher risk of spreading to lymph nodes.

The pathologic tumor stage (pT) is determined based on tumor size and depth of invasion. Larger tumors and those that invade deeply into muscle or adjacent structures are assigned a higher stage.

Lymph nodes and nodal stage (pN)

Lymph nodes are small immune organs located in the neck that help filter lymph fluid. Cancer cells can spread from the lip to nearby lymph nodes.

During surgery, lymph nodes may be removed and examined under the microscope. The pathology report will describe them as:

  • Negative, if no cancer cells are found.

  • Positive, if cancer cells are present.

The number of involved lymph nodes determines the nodal stage. Lymph node involvement increases the risk of distant spread and affects treatment planning.

Lymphovascular invasion

Lymphovascular invasion (LVI) means that cancer cells are seen inside small blood vessels or lymphatic channels. This finding increases the risk that the tumor may spread beyond the original site.

Perineural invasion

Perineural invasion (PNI) means that cancer cells are growing around or along a nerve. This is considered a higher-risk feature because it may allow the tumor to spread locally and increase the chance of recurrence.

Margins

A margin refers to the edge of the tissue removed during surgery.

After the tumor is removed, the pathologist examines the margins to determine whether cancer cells are present at the cut edge.

  • A negative margin means no cancer cells are seen at the edge, suggesting the tumor was completely removed.

  • A positive margin indicates cancer cells are present at the edge, suggesting additional treatment may be needed.

The distance between the tumor and the margin may also be reported.

Biomarkers

Biomarkers are proteins or molecular features found in tumor cells that may help guide treatment decisions. In squamous cell carcinoma of the lip, biomarker testing is most often performed in advanced or recurrent disease when systemic therapy is being considered.

PD-L1

PD-L1 is a protein that helps cancer cells evade immune system detection. When PD-L1 binds to its receptor on immune cells, it sends a signal that reduces the immune response. Some squamous cell carcinomas produce PD-L1, which may make them more responsive to immunotherapy, a type of treatment that helps the immune system attack cancer cells.

How do pathologists test for PD-L1?

PD-L1 is tested using immunohistochemistry on tumor tissue. This test uses antibodies to detect PD-L1 protein within the cancer cells and surrounding immune cells.

How are PD-L1 results reported?

Results are usually reported using a scoring system, such as the Combined Positive Score (CPS). The CPS measures the number of PD-L1–positive tumor cells and immune cells compared to the total number of tumor cells.

A CPS of 1 or higher is generally considered positive and may increase the likelihood that immunotherapy will be effective. However, treatment decisions depend on multiple factors, including tumor stage, overall health, and prior treatments.

Prognosis

When detected early and treated appropriately, squamous cell carcinoma of the lip often has a good prognosis.

Prognosis depends on tumor size, depth of invasion, lymph node involvement, and high-risk features such as perineural or lymphovascular invasion. Early-stage tumors confined to the lip have a high cure rate.

Questions you may want to ask your doctor

  • What stage is my cancer?

  • How deep did the tumor invade?

  • Were any lymph nodes involved?

  • Were the surgical margins negative?

  • Did the tumor show perineural or lymphovascular invasion?

  • What follow-up or additional treatment is recommended?

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