Your pathology report for squamous cell carcinoma of the esophagus

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
February 19, 2026

Squamous cell carcinoma of the esophagus is a type of cancer that begins in squamous cells, which are flat cells that line the inside surface of the esophagus. The esophagus is the muscular tube that carries food and liquids from your mouth to your stomach.

These squamous cells normally form a thin protective layer called the epithelium. Their job is to protect the esophagus from irritation caused by swallowing food and liquids. In squamous cell carcinoma, these cells grow in an abnormal and uncontrolled way, forming a malignant tumor, which means a cancer that can invade nearby tissues and spread to other parts of the body.

Squamous cell carcinoma is the most common type of esophageal cancer worldwide. It most often develops in the middle portion of the esophagus, but can occur anywhere along its length.

What are the symptoms of squamous cell carcinoma?

Many people do not notice symptoms until the tumor has grown large enough to narrow the inside of the esophagus. The most common symptom is difficulty swallowing, which often starts with solid foods and may gradually worsen. Some people experience pain when swallowing or discomfort in the chest or upper back.

Unexplained weight loss is common, especially if eating becomes difficult. Tumors located higher in the esophagus may affect nearby nerves that control the voice, leading to hoarseness or changes in the voice. A doctor should always evaluate persistent difficulty swallowing or unexplained weight loss.

What causes squamous cell carcinoma of the esophagus?

Squamous cell carcinoma develops from long-term irritation or injury to the esophageal lining. The most important risk factors are tobacco use and heavy alcohol consumption. When tobacco and alcohol are used together, the risk increases significantly.

Other factors that may increase risk include drinking very hot liquids over many years, poor nutrition with low intake of fruits and vegetables, certain viral infections such as human papillomavirus in some regions, and previous radiation therapy to the chest or neck.

In parts of Asia and Africa, squamous cell carcinoma of the esophagus is more common due to environmental and dietary factors.

How is this diagnosis made?

The diagnostic process usually begins with an upper endoscopy, a procedure in which a thin flexible tube with a camera is passed through the mouth into the esophagus. This allows the doctor to directly examine the inner lining of the esophagus and identify any abnormal areas.

If a suspicious area is seen, a small tissue sample called a biopsy is taken. The biopsy is then sent to a pathologist. The diagnosis of squamous cell carcinoma is made after microscopic examination of this tissue sample. The pathologist studies the cells under the microscope to determine whether cancer is present and to identify the specific type of cancer.

Microscopic features

Under a microscope, squamous cell carcinoma is composed of abnormal squamous cells that grow downward from the inner lining into the deeper layers of the esophagus. These cancer cells often grow in clusters called nests or in broad sheets.

In many tumors, the cells produce keratin, the same tough protein found in skin. This keratin may form round structures called keratin pearls. The tumor cells may also show intercellular bridges, which are visible connections between squamous cells. These features help confirm that the tumor is a squamous cell carcinoma.

In more aggressive tumors, the cells may look very abnormal and disorganized, and the typical features of squamous cells may be less obvious.

Immunohistochemistry

Sometimes the tumor cells look very abnormal, and it may not be immediately clear what type of cancer is present. In these cases, pathologists use a special test called immunohistochemistry. This test uses antibodies to detect specific proteins inside the cancer cells.

Squamous cell carcinoma usually shows positive staining for proteins such as p40, p63, and cytokeratin 5/6. These proteins are normally found in squamous cells and help confirm the diagnosis. The tumor is usually negative for markers associated with gland-forming cancers, such as CK7 or CDX2. These additional tests help ensure that the diagnosis is accurate.

What does tumor grade mean?

Tumor grade describes how abnormal the cancer cells look compared with normal squamous cells. In the esophagus, squamous cell carcinoma is divided into three grades.

In well-differentiated (Grade 1) tumors, the cancer cells still resemble normal squamous cells and often produce keratin. These tumors tend to grow more slowly.

In moderately differentiated (Grade 2) tumors, the cells look more abnormal and are less organized.

In poorly differentiated (Grade 3) tumors, the cells look very different from normal squamous cells and grow in a disorganized pattern. These tumors tend to behave more aggressively.

Depth of invasion

Squamous cell carcinoma begins in the inner lining of the esophagus, called the mucosa. The mucosa contains thin supportive layers, the lamina propria, and the muscularis mucosae.

Beneath the mucosa is the submucosa, which contains connective tissue, blood vessels, and lymphatic channels. Below that is the muscularis propria, a thick muscle layer that contracts to move food toward the stomach. The outermost layer is called the adventitia, which is a layer of connective tissue that anchors the esophagus to surrounding structures. Unlike other parts of the digestive tract, the esophagus lacks a protective outer covering called the serosa.

As the tumor grows, it may extend deeper through these layers. The pathologist reports the deepest layer that contains cancer and determines the pathologic tumor stage (pT). This stage is part of the TNM staging system and helps guide treatment decisions.

• pT1 means the tumor is limited to the mucosa or submucosa.

  • pT1a indicates invasion into the lamina propria or muscularis mucosae.

  • pT1b indicates invasion into the submucosa.

• pT2 means the tumor has invaded the muscularis propria.

• pT3 means the tumor has grown through the muscle layer into the adventitia.

• pT4 means the tumor has spread beyond the esophagus into nearby organs or structures.

In more advanced cases, the tumor may invade nearby structures such as the windpipe, major blood vessels, or tissue surrounding the heart. The depth of invasion is one of the most important factors in determining the extent of the cancer.

Lymph nodes and pathologic nodal stage (pN)

Lymph nodes are small immune organs that help filter harmful substances. Cancer cells can travel to lymph nodes through lymphatic vessels.

After surgery, the removed lymph nodes are examined under the microscope. The number of lymph nodes containing cancer determines the nodal stage:

• pN0: No cancer found in lymph nodes.

• pN1: Cancer found in 1 or 2 lymph nodes.

• pN2: Cancer found in 3 to 6 lymph nodes.

• pN3: Cancer found in 7 or more lymph nodes.

• pNX: No lymph nodes were examined.

Lymph node involvement increases the risk that the cancer has spread elsewhere in the body.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells are seen inside small blood vessels or lymphatic channels. This finding suggests that the tumor can spread to other parts of the body.

Perineural invasion

Perineural invasion means that cancer cells are growing along or around a nerve. Nerves carry signals between the brain and the body. When cancer is seen involving a nerve, it is considered a higher-risk feature because it suggests more aggressive local spread.

Margins

A margin is the edge of the tissue removed during surgery. If cancer cells are seen at the edge of the removed tissue, the margin is described as positive. If no cancer cells are seen at the edge, the margin is negative. Negative margins suggest that the tumor was completely removed.

Biomarkers

PD-L1

PD-L1 is a protein that some cancer cells use to evade immune detection. Tumors that express PD-L1 may respond to immunotherapy, a type of treatment that helps the immune system attack cancer cells.

PD-L1 is tested using immunohistochemistry. Results are reported as a Combined Positive Score (CPS). A CPS of 1 or higher is considered positive and may increase the likelihood that immunotherapy will be effective. Treatment decisions depend on multiple factors, not just PD-L1 status.

Subtypes of squamous cell carcinoma

Most tumors are classified as conventional squamous cell carcinoma. However, several less common subtypes exist.

Verrucous squamous cell carcinoma

Verrucous squamous cell carcinoma is a rare, slow-growing form. The word “verrucous” means warty, and these tumors often form thick, raised growths. Under the microscope, the cells appear very similar to normal squamous cells and usually show minimal abnormality. This subtype tends to grow locally and is less likely to spread to distant organs, though it can become large if left untreated.

Spindle cell (sarcomatoid) squamous cell carcinoma

This subtype contains both typical squamous cancer cells and spindle-shaped cells, which are long, narrow cells that can resemble cells seen in connective tissue cancers. Because of this unusual appearance, additional testing may be needed to confirm the diagnosis. These tumors sometimes grow as polyp-like masses that project into the inside space of the esophagus.

Basaloid squamous cell carcinoma

Basaloid squamous cell carcinoma is a more aggressive subtype. The cancer cells are small and dark, resembling basal cells, which are normally found in the lower part of the epithelium. These tumors often grow in solid sheets and may contain areas of cell death, called necrosis. Because they can resemble other high-grade cancers, special tests are often required to confirm the diagnosis.

Each subtype is still considered a form of squamous cell carcinoma. Identifying a subtype can provide additional information about how the tumor may behave.

Questions to ask your doctor

• What stage is my cancer?

• What was the tumor grade?

• How deeply did the tumor grow into the wall of the esophagus?

• Were any lymph nodes involved?

• Were the surgical margins clear?

• Did the tumor show lymphovascular or perineural invasion?

• Was PD-L1 testing performed, and what were the results?

• What treatment options are recommended next?