Squamous Cell Carcinoma of the Lung: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 28, 2026

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Squamous cell carcinoma (SCC) is the second most common type of lung cancer after adenocarcinoma and belongs to the group of cancers known as non-small cell lung cancer (NSCLC). It develops from squamous cells — flat, scale-like cells that normally line the inner walls of the larger airways in the lungs. Unlike adenocarcinoma, which usually arises near the outer edges of the lung, squamous cell carcinoma most often starts in the central airways, close to where the main bronchi (breathing tubes) enter the lung. This central location makes it more likely to cause airway-related symptoms and may be detected by bronchoscopy and imaging. This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.

What causes squamous cell carcinoma of the lung?

Tobacco smoking is the dominant cause of squamous cell carcinoma of the lung, more strongly so than for any other lung cancer type. The vast majority of people diagnosed with lung SCC have a history of smoking, and the risk increases with the number of cigarettes smoked per day and the number of years of smoking. However, SCC can occasionally occur in people who have never smoked.

Other risk factors include:

• Occupational exposures — Prolonged contact with substances such as asbestos, silica dust, chromium compounds, nickel, or arsenic in certain workplaces is associated with an increased risk of lung SCC.
• Radon gas exposure — Radon is a naturally occurring radioactive gas that can accumulate in homes and buildings and is a recognized cause of lung cancer.
• Air pollution — Long-term exposure to outdoor air pollution contributes to lung cancer risk.
• Prior radiation therapy — People who have received radiation to the chest for a previous cancer have a modestly increased risk of developing a second lung cancer, including SCC.

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

Because squamous cell carcinoma most often arises in the central airways, it tends to cause airway-related symptoms earlier than adenocarcinoma, which usually grows silently near the outer lung until it becomes large.

Symptoms may include:

• A persistent or worsening cough.
• Coughing up blood (hemoptysis) — more common in centrally located SCC than in other lung cancer types.
• Shortness of breath, particularly if the tumor is narrowing or blocking an airway.
• Chest pain or discomfort.
• Recurrent or slow-to-resolve pneumonia in the same area of the lung is a warning sign that an airway may be partially blocked by a tumor.
• Wheezing or noisy breathing caused by partial airway obstruction.
• Fatigue or unintentional weight loss, particularly with more advanced disease.

If the cancer has spread to other parts of the body, additional symptoms may occur depending on the site involved. Spread to the bones can cause bone pain, and spread to the brain can cause headaches or neurological changes.

How is the diagnosis made?

The diagnosis is most often made from a tissue sample obtained by biopsy. Because squamous cell carcinoma commonly arises in the central airways, it is frequently accessible by bronchoscopy — a procedure in which a thin flexible tube is passed through the mouth into the airways to visualize the tumor and collect a tissue sample. For tumors in less accessible locations, a CT-guided needle biopsy through the chest wall, endobronchial ultrasound (EBUS), or fine needle aspiration may be used instead. In some cases, the diagnosis is made only after the entire tumor has been removed surgically.

Under the microscope, a pathologist identifies squamous cell carcinoma by recognizing the characteristic features of squamous differentiation. The cancer cells typically grow in dense groups called nests or sheets, and many show signs of squamous differentiation — including the formation of structures called keratin pearls (compact whorls of pink material produced by the tumor cells) and intercellular bridges (fine connections between adjacent cells visible under high magnification). The tumor cells are larger than normal airway cells, with dark-staining nuclei and irregular, variable shapes — features pathologists describe as pleomorphic. Numerous dividing cells (mitotic figures) are also typically present.

To confirm the diagnosis and distinguish SCC from other types of lung cancer — such as adenocarcinoma or neuroendocrine tumors that can look similar under the microscope — the pathologist performs immunohistochemistry (IHC), a laboratory technique that uses antibodies linked to colored dyes to detect specific proteins within the cells. Squamous cell carcinoma of the lung typically shows positive staining for p40 and CK5 (proteins specific to squamous cells) and negative staining for TTF-1 (a marker of lung adenocarcinoma and thyroid origin), chromogranin, and synaptophysin (markers of neuroendocrine tumors). This staining pattern confirms the squamous cell type and helps guide further testing and treatment planning.

Once the diagnosis is confirmed, imaging — typically CT of the chest and a PET scan — is used to assess the full extent of disease throughout the body.

Histologic subtypes of squamous cell carcinoma

Squamous cell carcinoma of the lung is divided into three subtypes based on microscopic features. All three subtypes behave similarly and carry a similar prognosis, but the subtype is included in the pathology report and influences which additional stains or tests may be needed to confirm the diagnosis.

• Keratinizing squamous cell carcinoma — The tumor cells produce keratin, a tough structural protein. Under the microscope, this is visible as keratin pearls — compact pink whorls — and prominent intercellular bridges between cells. This is the classic, most readily recognizable subtype of lung SCC.
• Non-keratinizing squamous cell carcinoma — The tumor cells show squamous features under the microscope but do not produce visible keratin. This subtype requires immunohistochemistry (p40 and CK5 positive staining) for confident classification, as it can resemble other poorly differentiated carcinomas without additional testing.
• Basaloid squamous cell carcinoma — The tumor cells resemble the basal cells normally found at the base of the airway lining. This subtype often appears poorly differentiated and may be associated with a somewhat more aggressive clinical course.

Histologic grade

The histologic grade of squamous cell carcinoma describes how closely the cancer cells resemble normal squamous cells under the microscope. Grade reflects how differentiated — or specialized — the tumor cells are, which in turn relates to how aggressively the tumor is likely to behave.

• Well differentiated (Grade 1) — The tumor cells closely resemble normal squamous cells and show prominent keratinization, including easily identifiable keratin pearls and intercellular bridges. These tumors tend to grow more slowly and are associated with a relatively better prognosis.
• Moderately differentiated (Grade 2) — The tumor cells retain some squamous features but show greater cellular irregularity and less keratinization than well-differentiated tumors. Behavior is intermediate.
• Poorly differentiated (Grade 3) — The tumor cells show minimal or no keratinization and bear little resemblance to normal squamous cells. These tumors tend to grow more aggressively and carry a higher risk of spread and recurrence. Immunohistochemistry is usually required to confirm the squamous origin of poorly differentiated tumors.

Histologic grade is one factor considered when planning treatment, particularly in early-stage disease.

Multiple tumors

In some cases, more than one tumor is found when the lung tissue is examined. Determining the relationship between multiple tumors is important because it affects staging, treatment, and prognosis.

When multiple tumors look identical under the microscope and share the same histologic subtype, they are more likely to represent spread from a single primary tumor. When the tumors differ in appearance or molecular profile — for example, one is squamous cell carcinoma, and another is adenocarcinoma — they are more likely to represent two separate, independent primary cancers. Molecular testing comparing tumor profiles can help make this distinction when microscopic features are ambiguous.

Separate tumor nodules in the same lobe as the primary tumor increase the T stage. Separate tumor nodules in a different lobe of the same lung are staged as pT4. Tumor deposits found in the opposite lung are considered distant metastasis and are classified as M1a disease.

Pleural invasion

The pleura is a thin membrane with two layers: the visceral pleura, which covers the outer surface of the lungs, and the parietal pleura, which lines the inside of the chest cavity. Pleural invasion means cancer cells have grown into one or both of these layers.

• Visceral pleural invasion — Cancer cells have grown through the elastic layer of the visceral pleura. This finding increases the T stage and is associated with a higher risk of recurrence.
• Parietal pleural invasion — Cancer cells have grown into the outer pleural layer, meaning the tumor has extended beyond the lung and reached the chest cavity lining. This represents more advanced local disease and further increases the T stage.

Pleural invasion is assessed using specialized elastic stains that highlight the fibrous layers of the pleura, making it easier to determine how deeply the tumor has penetrated.

Tumor extension into nearby structures

Large squamous cell carcinomas can grow beyond the lung and into adjacent structures. The lung is surrounded by the chest wall, diaphragm, phrenic nerve (which controls breathing), pericardium (the outer lining of the heart), esophagus, major blood vessels, and trachea. Invasion of any of these structures increases the T stage and influences treatment.

Your pathology report will describe whether the tumor has grown into any of these structures and, if so, which ones. Extension into the chest wall or pericardium places the tumor at pT3; extension into major vessels, the heart, trachea, esophagus, or spine places it at pT4. Involvement of these structures is relevant to both staging and determining whether surgery is technically feasible.

Treatment effect

If you received chemotherapy or radiation therapy before surgery — a strategy called neoadjuvant treatment — your pathology report will describe the treatment effect: an assessment of how much of the original tumor has been destroyed by treatment. The pathologist estimates the proportion of the tumor that still contains living (viable) cancer cells after treatment.

A high treatment effect — meaning very little viable tumor remains — is a favorable finding and suggests the cancer responded well to pre-surgical treatment. A low treatment effect — meaning most of the tumor is still viable — suggests the cancer was less responsive. Treatment effect is expressed as the percentage of viable tumor remaining and may also be described using a standardized grading system. This information helps your oncology team assess the effectiveness of the treatment you received and plan any additional therapy.

Lymphovascular invasion

Lymphovascular invasion (LVI) means that cancer cells have been found within blood or lymphatic vessels — the small channels that carry lymph — in or near the tumor. These vessels can act as pathways for cancer cells to travel to distant parts of the body, including lymph nodes, liver, brain, or bones.

• Lymphovascular invasion not identified — No cancer cells are seen within blood or lymphatic vessels near the tumor. This is a favorable finding.
• Lymphovascular invasion present — Cancer cells are identified within vessels. This finding is associated with a higher risk of lymph node involvement and distant metastasis and may influence decisions about additional treatment after surgery.

Surgical margins

Surgical margins are the cut edges of the tissue removed during an operation. The pathologist examines all margins to determine whether the tumor was completely removed.

• Negative margin — No cancer cells are seen at the cut edge. This suggests the tumor was fully removed and is the most favorable outcome.
• Close margin — Cancer cells are present very near the cut edge but do not reach it. Depending on the distance and the margin involved, further treatment may be recommended.
• Positive margin — Cancer cells are present at the cut edge. This raises concern that some tumor remains and often leads to discussion of further surgery or radiation therapy.

Margins assessed in a lung resection specimen typically include the bronchial margin (where the airway was divided), the vascular margins (where blood vessels were cut), and the staple-line margin of the lung tissue. Your report will specify which margins were examined and their status.

Lymph nodes

Lymph nodes are small structures that are part of the immune system and are distributed throughout the chest. During surgery, the surgeon removes lymph nodes from specific locations within the lung and central chest — called lymph node stations — and sends them separately to the pathologist for examination under the microscope.

The pathology report will describe the total number of lymph nodes examined, their station locations, whether any contain cancer cells, and the size of any deposits found. The number and location of involved nodes determine the nodal stage (N stage) and strongly influence decisions about adjuvant treatment. In some cases, cancer cells may have broken through the outer wall of a lymph node and grown into the surrounding tissue — a finding called extranodal extension, which indicates more aggressive disease.

Biomarker and molecular testing

Biomarker testing is a standard part of the workup for squamous cell carcinoma of the lung, particularly in patients with advanced or metastatic disease. Although squamous cell carcinoma less frequently harbors the targetable driver mutations (such as EGFR, ALK, or ROS1) that are common in adenocarcinoma, several biomarkers are clinically important in SCC and directly guide treatment decisions.

PD-L1

PD-L1 (programmed death-ligand 1) is a protein found on the surface of some cancer cells that helps the tumor hide from the immune system by sending a “don’t attack” signal to immune cells. Drugs called checkpoint inhibitors block this interaction, restoring the immune system’s ability to recognize and destroy the cancer. PD-L1 testing is performed on all newly diagnosed advanced squamous cell carcinomas and is among the most important biomarkers for guiding first-line treatment decisions.

PD-L1 is measured by immunohistochemistry and reported as the Tumor Proportion Score (TPS) — the percentage of tumor cells showing PD-L1 staining on their surface.

• TPS <1% — PD-L1 negative. Chemotherapy combined with immunotherapy is generally preferred over immunotherapy alone.
• TPS 1–49% — Low to intermediate PD-L1 expression. Pembrolizumab combined with chemotherapy is a standard first-line option.
• TPS ≥50% — High PD-L1 expression. Pembrolizumab (Keytruda) alone — without chemotherapy — is a standard first-line option, with response rates of approximately 45–50% in patients with TPS ≥50%.

PD-L1 expression is the primary biomarker guiding immunotherapy selection in lung SCC, where targetable driver mutations are uncommon.

Mismatch repair (MMR) and microsatellite instability (MSI)

Mismatch repair (MMR) is a system of proteins — MLH1, PMS2, MSH2, and MSH6 — that correct errors in DNA copying. When this system is not working properly, the cancer is described as mismatch repair deficient (dMMR), and a related condition called microsatellite instability-high (MSI-H) develops. MMR deficiency is uncommon in lung SCC (approximately 1–2% of cases) but is important because dMMR and MSI-H tumors respond well to checkpoint immunotherapy. Pembrolizumab is approved for any solid tumor that is dMMR or MSI-H, regardless of where the cancer started, and this approval extends to lung SCC. If your tumor is found to be dMMR, your care team will likely discuss immunotherapy options. Testing is performed by immunohistochemistry for the four MMR proteins or by MSI testing using PCR or next-generation sequencing. Your report will describe the result as MMR intact (pMMR) or MMR deficient (dMMR).

Tumor mutational burden (TMB)

Tumor mutational burden (TMB) is a measure of the number of mutations in a cancer cell’s DNA. Tumors with a high number of mutations (TMB-high, defined as ≥10 mutations per megabase of DNA) tend to produce more surface proteins, making them more visible to the immune system and more likely to respond to checkpoint immunotherapy. Because lung SCC is so strongly associated with tobacco smoking — and smoking is one of the most powerful causes of DNA mutation — lung SCC tumors often carry high TMB. Pembrolizumab is approved for any solid tumor with TMB ≥10 mut/Mb that has progressed after prior treatment. TMB is measured by next-generation sequencing (NGS) and reported as mutations per megabase (mut/Mb).

Driver mutation and broad molecular profiling

Targetable driver mutations such as EGFR mutations, ALK rearrangements, ROS1 rearrangements, and KRAS mutations — which are common and clinically central in lung adenocarcinoma — are uncommon in squamous cell carcinoma. Nevertheless, current guidelines recommend performing broad molecular profiling (NGS) on all patients with advanced NSCLC, including SCC, for two reasons. First, rare but actionable alterations do occasionally occur in SCC, particularly in patients who are never-smokers or who have atypical clinical presentations. Second, comprehensive molecular profiling may identify eligibility for clinical trials targeting alterations such as FGFR1 amplifications or FGFR2/3 rearrangements, which are found in approximately 10–20% of lung SCCs and are being studied as potential therapeutic targets. Your report or a separate molecular testing report will describe the results of any NGS panel performed.

For more information about biomarker testing in cancer, visit the Biomarkers and Molecular Testing section of MyPathologyReport.

Pathologic stage (pTNM)

Squamous cell carcinoma of the lung is staged using the TNM system based on AJCC 8th edition criteria. The T category describes the size of the tumor and whether it has grown into nearby structures. The N category indicates whether cancer has spread to nearby lymph nodes. The M category — which describes spread to distant organs such as the brain, bones, or liver — is determined by imaging rather than the pathology specimen and is typically not reported in the surgical pathology report. Together, T, N, and M are combined to determine an overall stage, ranging from I (earliest) to IV (most advanced).

Tumor stage (pT)

• pT1a — Tumor is 1 cm or smaller, surrounded by lung or visceral pleura, with no involvement of the main bronchus.
• pT1b — Tumor is larger than 1 cm but no larger than 2 cm, otherwise meeting T1a criteria.
• pT1c — Tumor is larger than 2 cm but no larger than 3 cm, otherwise meeting T1a criteria.
• pT2a — Tumor is larger than 3 cm but no larger than 4 cm; or the tumor — regardless of size — has grown into the visceral pleura, involves the main bronchus without reaching the main airway junction (carina), or is associated with partial lung collapse.
• pT2b — Tumor is larger than 4 cm but no larger than 5 cm, otherwise meeting T2a criteria.
• pT3 — Tumor is larger than 5 cm but no larger than 7 cm; or the tumor has grown into the chest wall, phrenic nerve, or parietal pericardium; or a separate tumor nodule is present in the same lobe as the primary tumor.
• pT4 — Tumor is larger than 7 cm; or the tumor has grown into major structures such as the heart, large blood vessels, trachea, esophagus, or spine; or a separate tumor nodule is present in a different lobe of the same lung.

Nodal stage (pN)

• pNX — Lymph nodes were not examined.
• pN0 — No cancer cells found in any lymph nodes examined.
• pN1 — Cancer cells found in lymph nodes within the lung or near the main airway on the same side of the chest (intrapulmonary, hilar, or peribronchial nodes; stations 10–14).
• pN2 — Cancer cells found in lymph nodes in the central chest on the same side (ipsilateral mediastinal or subcarinal nodes; stations 4–9).
• pN3 — Cancer cells found in lymph nodes on the opposite side of the chest or in the lower neck (contralateral mediastinal, contralateral hilar, scalene, or supraclavicular nodes). This indicates advanced nodal disease.

What is the prognosis?

The prognosis for squamous cell carcinoma of the lung depends on the stage at diagnosis, tumor grade, the presence of specific pathologic features, and response to treatment. Outcomes have improved meaningfully over the past decade with the introduction of immunotherapy. Five-year survival rates by stage provide a general sense of outcomes based on population-level data, but individual outcomes vary considerably:

• Stage I — Five-year survival is approximately 70–85% for stage IA and 55–65% for stage IB. Complete surgical resection offers the best chance of cure.
• Stage II — Five-year survival is approximately 45–55%. Adjuvant chemotherapy is recommended after surgery for most patients with stage II disease to reduce the risk of recurrence.
• Stage III — Five-year survival ranges from approximately 15–35% depending on the extent of nodal involvement. Concurrent chemotherapy and radiation, followed by consolidation with durvalumab immunotherapy, is the standard approach for unresectable stage III disease.
• Stage IV — Outcomes have improved substantially with immunotherapy. Patients with high PD-L1 expression (TPS ≥50%) treated with pembrolizumab monotherapy have median overall survivals of approximately 20–26 months in clinical trials — a significant improvement over historical outcomes with chemotherapy alone.

Pathologic features associated with a higher risk of recurrence and worse outcomes include:

• High histologic grade — Poorly differentiated tumors are associated with more aggressive behavior.
• Lymphovascular invasion — Indicates a higher risk of spread to lymph nodes and distant organs.
• Pleural invasion — Increases the T stage and is associated with worse outcomes.
• Positive or close surgical margins — Raises concern for residual disease.
• Lymph node involvement — The number and location of involved nodes is one of the strongest predictors of recurrence risk.

Smoking cessation improves survival even after a lung cancer diagnosis and reduces the risk of developing a second primary lung cancer. Your oncology team can connect you with cessation resources if needed.

What happens after the diagnosis?

After the pathology report is finalized, your doctor will review the findings along with your imaging results and overall health to develop a treatment plan. Squamous cell carcinoma of the lung is managed by a multidisciplinary team including a thoracic surgeon, medical oncologist, radiation oncologist, respirologist, and pathologist.

For early-stage disease (stages I and II), surgery to remove the tumor — along with surrounding lung tissue and sampled lymph nodes — is the primary treatment. The extent of surgery depends on the tumor’s size and location; options include wedge resection, segmentectomy, lobectomy, or rarely pneumonectomy. After surgery, adjuvant chemotherapy is recommended for most patients with stage II disease. Unlike adenocarcinoma, there is no currently approved adjuvant targeted therapy for resected lung SCC, so immunotherapy adjuvant trials are an active area of research.

For locally advanced disease (stage III), treatment typically combines chemotherapy and radiation. Durvalumab immunotherapy given after definitive chemoradiation has been shown to significantly improve survival and is now a standard approach for unresectable stage III NSCLC.

For advanced or metastatic disease (stage IV), treatment is guided by PD-L1 expression, TMB, and MMR status. Options include pembrolizumab monotherapy (for TPS ≥50%), pembrolizumab combined with chemotherapy, or other checkpoint inhibitor-based regimens. Molecular profiling by NGS is performed to identify any rare targetable alterations or clinical trial opportunities.

Follow-up after treatment includes regular chest CT imaging and physical examinations to monitor for recurrence. The frequency and duration of follow-up will be determined by your care team based on your stage and treatment.

Questions to ask your doctor

• What is the histologic subtype and grade of my squamous cell carcinoma, and what does this mean for my prognosis?
• What stage is my cancer, and how does that affect my treatment options?
• Was pleural invasion found, and how does it affect my stage?
• Did the cancer grow into any nearby structures outside the lung?
• Was lymphovascular invasion identified in my pathology report?
• Were the surgical margins clear? If not, what are the next steps?
• Did the cancer spread to any lymph nodes, and if so, how many and in which locations?
• What was my PD-L1 score, and does it affect my eligibility for immunotherapy?
• Was broad molecular profiling (NGS) performed on my tumor, and what were the results?
• Was my tumor found to be MMR-deficient or MSI-high?
• Is adjuvant therapy recommended for my stage?
• If I received treatment before surgery, what did the treatment effect show?
• Are there clinical trials I might be eligible for?
• What is my follow-up schedule, and what symptoms should prompt me to contact you sooner?