Squamous cell carcinoma of the esophagus: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
April 3, 2026

Squamous cell carcinoma of the esophagus is a type of cancer that begins in squamous cells — the flat, overlapping cells that line the inside surface of the esophagus. The esophagus is the muscular tube that carries food and liquids from the mouth to the stomach. These squamous cells form a thin protective layer called the epithelium, which shields the esophageal wall from irritation during swallowing. In squamous cell carcinoma, these cells grow in an uncontrolled and abnormal way, forming a malignant tumour that can invade nearby tissues and spread to other parts of the body.

Squamous cell carcinoma is one of the two main types of esophageal cancer worldwide, along with adenocarcinoma of the esophagus. It most often develops in the middle or upper portion of the esophagus, unlike adenocarcinoma, which typically arises in the lower esophagus. This article will help you understand the findings in your pathology report and what they mean for your care.

What causes squamous cell carcinoma of the esophagus?

Squamous cell carcinoma develops from long-term irritation or injury to the squamous cell lining of the esophagus. The most important risk factors are tobacco use and heavy alcohol consumption. When both are used together, the risk increases significantly more than either alone.

Other factors that may increase risk include drinking very hot liquids habitually over many years, a diet low in fruits and vegetables, certain viral infections such as human papillomavirus (HPV) in some regions, and previous radiation therapy to the chest or neck. In parts of Asia and Africa, esophageal squamous cell carcinoma is far more common than in Western countries, reflecting regional differences in diet and environmental exposures.

Squamous cell carcinoma can be preceded by a non-invasive precancerous change called squamous cell carcinoma in situ (also called high-grade squamous dysplasia), in which abnormal squamous cells replace the normal lining but have not yet grown into the deeper layers of the esophagus. If present near your tumour, it will be mentioned in your pathology report.

What are the symptoms?

Many people do not notice symptoms until the tumour has grown large enough to narrow the inside of the esophagus. The most common symptom is difficulty swallowing (dysphagia), which often starts with solid foods and may gradually worsen. Some people experience pain when swallowing or chest or upper back discomfort. Unexplained weight loss is common, particularly when eating becomes difficult or painful.

Tumors in the upper esophagus may affect nearby nerves that control the voice, leading to hoarseness. A persistent cough and worsening CP can also occur if the tumour is close to the airway. Any of these symptoms, especially when they develop together, should be evaluated by a doctor.

How is the diagnosis made?

The diagnosis is usually made after an upper endoscopy (gastroscopy), during which a doctor passes a thin flexible tube with a camera through the mouth to examine the esophageal lining and take a small tissue sample called a biopsy. This sample is examined under a microscope by a pathologist, who identifies the characteristic features of squamous cell carcinoma.

Under the microscope, squamous cell carcinoma is composed of abnormal squamous cells growing downward from the inner lining into the deeper layers of the esophageal wall. The cells often grow in clusters called nests or in broad sheets. In many tumors, the cells produce keratin — the tough protein normally found in skin and nails — which can form round structures called keratin pearls. Some tumour cells exhibit intercellular bridges, visible connections between adjacent squamous cells. Both keratin pearls and intercellular bridges are hallmarks of squamous cell carcinoma and help the pathologist confirm the diagnosis. In more aggressive tumors, the cells may look very abnormal, and these typical features may be less obvious.

When the tumour cells look very abnormal, or the diagnosis is uncertain, the pathologist may use a special test called immunohistochemistry, which uses antibodies to detect specific proteins inside the cancer cells. Squamous cell carcinoma typically shows positive staining for proteins such as p40, p63, and cytokeratin 5/6, which are found in squamous cells. The tumour is usually negative for markers of gland-forming cancers such as CK7 or CDX2. These results help confirm the diagnosis and distinguish squamous cell carcinoma from adenocarcinoma.

Once cancer is confirmed, additional tests such as endoscopic ultrasound, CT scan, or PET scan are used to assess how deeply the tumour has grown and whether it has spread to lymph nodes or distant organs before treatment is planned.

Tumour grade

Grade describes how closely the cancer cells resemble normal squamous cells when viewed under the microscope. Higher-grade tumors look more abnormal and tend to behave more aggressively.

• Grade 1 (well differentiated) — The cancer cells still closely resemble normal squamous cells and often produce keratin. These tumors tend to grow more slowly and are less likely to spread.
• Grade 2 (moderately differentiated) — The cells look more abnormal and are less organized than normal squamous cells, but squamous features are still recognizable.
• Grade 3 (poorly differentiated) — The cells look very different from normal squamous cells and grow in a disorganized pattern. These tumors tend to behave more aggressively and are associated with a higher risk of spread and recurrence.

Level of invasion

Invasion refers to how deeply the cancer has grown into the wall of the esophagus. The esophageal wall is made up of several distinct layers:

• Mucosa — the innermost lining, where squamous cell carcinoma begins. The mucosa has two sublayers: the lamina propria (thin connective tissue just below the surface cells) and the muscularis mucosae (a thin inner muscle layer).
• Submucosa — a layer of connective tissue beneath the mucosa, containing blood vessels and lymphatic channels.
• Muscularis propria — the thick outer muscle layer that contracts to move food toward the stomach.
• Adventitia — the outermost connective tissue layer that anchors the esophagus to surrounding structures. Unlike most other parts of the digestive tract, the esophagus lacks a serosa (smooth outer covering).

In advanced cases, the tumour may grow beyond the esophageal wall into nearby structures such as the trachea (windpipe), aorta, or pericardium (the tissue surrounding the heart). The deepest layer the tumour has reached determines the pathologic tumour stage (pT).

Perineural invasion

Perineural invasion means that cancer cells are growing along or around a nerve. Nerves travel through the tissue surrounding the esophagus, and tumour cells that reach them can use them as a pathway to extend into adjacent structures beyond the main tumour mass. Perineural invasion is considered an aggressive feature associated with a higher risk of local recurrence and spread. Your pathology report will state whether perineural invasion is present or absent.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells have entered small blood vessels or lymphatic channels within or around the esophageal wall. Once inside these vessels, cancer cells can travel to nearby lymph nodes or, through the bloodstream, reach distant organs. Its presence increases the risk of spread and may influence decisions about treatment such as chemotherapy or radiation therapy. Your report will state whether lymphovascular invasion is present or absent.

Surgical margins

Margins are the cut edges of the tissue removed during surgery. The pathologist examines these surfaces to determine whether any cancer cells are present at the edge of the specimen.

• Negative margin (clear or uninvolved) — No cancer cells are found at the cut edge. This suggests the tumour was completely removed in that area.
• Positive margin (involved) — Cancer cells are present at the cut edge, raising concern that some cancer remains. Additional treatment is usually recommended.

Several different margins are typically assessed and reported separately depending on the type of surgery performed:

• Proximal margin — the upper cut end of the removed esophagus, closest to the mouth.
• Distal margin — the lower cut end, closest to the stomach.
• Radial (circumferential) margin — the outer soft-tissue surface of the esophagus, particularly important for tumors that have grown deeply through the wall. This margin is considered positive if tumour cells are within 1 mm of the edge.
• Deep margin — the tissue directly beneath the tumour.

Treatment effect

Many patients with esophageal squamous cell carcinoma receive chemotherapy and radiation therapy before surgery (called neoadjuvant chemoradiation) to shrink the tumour and improve the chances of complete surgical removal. After the operation, the pathologist evaluates how much viable tumour remains in the specimen and assigns a treatment response score using the modified Ryan scheme:

• Score 0 — No viable cancer cells remain (complete response). The most favorable result is associated with the best outcomes.
• Score 1 — Only single cancer cells or rare small groups remain (near-complete response). Very few tumour cells survived treatment.
• Score 2 — Residual cancer is present with evidence that the tumour shrank or was affected by treatment (partial response). Treatment helped but did not destroy the tumour completely.
• Score 3 — Extensive residual cancer with no clear evidence that the tumour responded (poor or no response). The tumour looks largely unchanged.

A complete or near-complete response (scores 0–1) is associated with a significantly better prognosis. The treatment response score is always interpreted in conjunction with pathologic stage and other findings.

Lymph nodes

Lymph nodes are small immune organs that can trap cancer cells as they spread through the lymphatic system. During surgery for esophageal squamous cell carcinoma, nearby lymph nodes are removed and examined by the pathologist. Your report will state how many lymph nodes were examined and how many, if any, contain cancer cells.

Lymph nodes are described as positive if they contain cancer and negative if they do not. If cancer is present, the report may also note whether the cancer has broken through the outer wall of the node — a finding called extranodal extension, which is associated with a worse prognosis. The number of involved lymph nodes is used to determine the nodal stage (pN) and is one of the strongest predictors of outcome after surgery.

Biomarker and molecular testing

Biomarker testing is increasingly important in esophageal squamous cell carcinoma, particularly for advanced disease, to determine which systemic treatments are most likely to be effective.

PD-L1

PD-L1 is a protein that some cancer cells produce to shield themselves from immune attack. Immunotherapy drugs called checkpoint inhibitors (such as pembrolizumab and nivolumab) work by blocking this shielding mechanism, allowing the immune system to recognize and attack the cancer.

PD-L1 testing uses the Combined Positive Score (CPS), which measures PD-L1 expression across both tumour cells and nearby immune cells. A CPS of 1 or higher is considered positive and indicates that immunotherapy — particularly when combined with chemotherapy — may be beneficial. A CPS below 1 suggests little or no PD-L1 expression, though immunotherapy may still be considered in some clinical settings. PD-L1 CPS testing is now routinely performed for esophageal squamous cell carcinoma, as the result influences treatment decisions in advanced disease.

Mismatch repair (MMR) protein testing

Mismatch repair proteins — MLH1, PMS2, MSH2, and MSH6 — are part of the cell’s system for repairing errors in DNA. When one or more of the tumour cells are absent, the result is called mismatch repair-deficient (MMR-deficient or dMMR), also described as microsatellite instability-high (MSI-high). When all proteins are present, the result is MMR-proficient (pMMR).

MMR deficiency is uncommon in esophageal squamous cell carcinoma. Still, when present, it has two important implications: the tumour may respond particularly well to checkpoint inhibitor immunotherapy, and the finding may indicate Lynch syndrome. This hereditary condition significantly increases the lifetime risk of several cancers. Referral for genetic counseling is usually recommended when MMR deficiency is identified, as this may have implications for family members.

For detailed explanations of PD-L1 and MMR testing in esophageal and upper gastrointestinal cancers, visit our Biomarkers and Molecular Testing section.

Tumour subtypes

Most esophageal squamous cell carcinomas are classified as conventional squamous cell carcinoma. A small number are recognized as distinct subtypes based on their microscopic appearance. These subtypes are uncommon, and most patients reading this article will have conventional squamous cell carcinoma. However, if your report mentions one of the following, here is what it means:

• Verrucous squamous cell carcinoma — A rare, slow-growing form. The word “verrucous” means warty, and these tumors often form thick, raised growths. Under the microscope, the cells look very similar to normal squamous cells with minimal abnormality. This subtype tends to grow locally and is much less likely to spread to distant organs than conventional squamous cell carcinoma, though it can become large if left untreated.
• Spindle cell (sarcomatoid) squamous cell carcinoma — This subtype contains both typical squamous cancer cells and elongated spindle-shaped cells that can resemble cells seen in connective tissue cancers. Because of this unusual appearance, additional immunohistochemistry testing is often needed to confirm the diagnosis. These tumors sometimes grow as polyp-like masses projecting into the esophagus.
• Basaloid squamous cell carcinoma — A more aggressive subtype in which the cancer cells are small and dark, resembling basal cells normally found in the deepest layer of the epithelium. These tumors often grow in solid sheets and may contain areas of dead tissue called necrosis. Special testing is often required to confirm the diagnosis and distinguish this subtype from other high-grade cancers.

Each subtype is still considered a form of squamous cell carcinoma. Identifying the subtype provides additional information about how the tumour may behave and, in some cases, may influence treatment decisions.

Pathologic stage (pTNM)

The pathologic stage is determined after surgery and describes how far the cancer has spread. It uses the internationally recognized TNM staging system, which considers the primary tumour (T), lymph node involvement (N), and distant metastasis (M). The pathologist from the surgical specimen determines the pT and pN stages; the M stage is typically determined by imaging.

Tumour stage (pT)

• pT1a — Cancer is confined to the lamina propria or muscularis mucosae — the thin inner layers of the mucosa.
• pT1b — Cancer has grown into the submucosa, the connective tissue layer beneath the mucosa.
• pT2 — Cancer has grown into the muscularis propria (the main muscle layer of the esophageal wall).
• pT3 — Cancer has grown through the muscle layer and into the adventitia (the outermost connective tissue of the esophagus).
• pT4a — Cancer has grown into adjacent resectable structures such as the pleura, pericardium, azygos vein, diaphragm, or peritoneum. Surgery may still be possible.
• pT4b — Cancer has invaded critical structures such as the aorta, vertebral body, or airways. Surgery is usually not possible.

Nodal stage (pN)

• pN0 — No cancer found in any lymph nodes examined.
• 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 — Lymph nodes were not assessed.

What is the prognosis for squamous cell carcinoma of the esophagus?

The prognosis for esophageal squamous cell carcinoma depends on several factors. The most important is the pathologic stage at the time of surgery, particularly how deeply the tumour has grown into the esophageal wall and how many lymph nodes are involved. Tumors confined to the inner layers (pT1a or pT1b) with no lymph node involvement have a significantly better prognosis than those that have penetrated the full thickness of the wall or spread to multiple nodes.

Additional factors that influence prognosis include tumour grade (higher-grade tutumorsehave more aggressive behavior), the presence of lymphovascular or perineural invasion, margin status (whether the tumour was fully removed), and — when neoadjuvant chemoradiation was given before surgery — the degree of treatment response. A complete or near-complete pathologic response (score 0 or 1) is associated with a meaningfully better long-term outcome.

Biomarker results are also relevant: PD-L1-positive tumors and, less commonly, MMR-deficient tumors may benefit substantially from immunotherapy, which has improved outcomes for patients with advanced esophageal squamous cell carcinoma. Clinical trials continue to evaluate new immunotherapy combinations that may further improve results.

Your treatment team will consider all of these factors together when discussing your individual prognosis and planning your care.

Questions to ask your doctor

Your pathology report contains important information that will guide your care. The following questions may help you prepare for your next appointment.

• What is the pathologic stage of my cancer (pT and pN), and what does that mean for my prognosis?
• How deeply did the cancer grow into the esophageal wall?
• Were any lymph nodes involved, and if so, how many?
• Were the surgical margins clear? Was the tumour completely removed?
• Was lymphovascular or perineural invasion present, and how does that affect my treatment plan?
• What was the tumour grade, and does my tumour belong to a specific subtype?
• If I received treatment before surgery, what was the tumour regression score, and what does it mean for my outlook?
• What was the PD-L1 CPS score, and does immunotherapy play a role in my treatment?
• Was the cancer tested for mismatch repair deficiency, and should I be referred for genetic counseling?
• What additional treatment is recommended based on these pathology findings?
• Are there clinical trials available for my stage and tumour profile?
• What follow-up tests and imaging will I need, and how often?