Squamous Cell Carcinoma of the Skin: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD
April 23, 2026

Squamous cell carcinoma (SCC) is one of the most common types of skin cancer. It starts from squamous cells, the flat cells that normally form the outermost layer of the skin (the epidermis). In invasive SCC, the cancer cells have broken through the epidermis and grown into the deeper layers of the skin. Pathologists call this process invasion. Invasion increases the risk that the cancer can spread to lymph nodes or distant organs.

Most cutaneous SCCs develop from a precancerous condition such as actinic keratosis or from an earlier non-invasive form of skin cancer called squamous cell carcinoma in situ (also known as Bowen’s disease). These precursor conditions are confined to the epidermis and have not yet invaded the deeper tissue.

This article will help you understand the findings in your pathology report for invasive squamous cell carcinoma of the skin — what each term means and why it matters for your care.

What causes squamous cell carcinoma of the skin?

The main cause of cutaneous SCC is long-term damage to skin cells from ultraviolet (UV) radiation. Most of this damage comes from sunlight, but similar damage can be caused by artificial UV sources such as tanning beds. UV radiation damages DNA in squamous cells, and over time, these genetic changes allow the cells to grow out of control.

Other risk factors include:

• Fair skin — People with lighter skin, light-colored eyes, and red or blond hair are more susceptible because their skin contains less protective melanin.
• Older age — Most cutaneous SCCs occur after age 50 because UV damage accumulates over a lifetime.
• Weakened immune system — People taking anti-rejection medications after an organ transplant, living with HIV, or receiving other forms of immune suppression are at much higher risk. Organ transplant recipients, for example, have a risk of developing cutaneous SCC that is many times higher than that of the general population.
• Chronic inflammation or scarring — SCC can develop in long-standing wounds, burn scars, or areas of chronic skin disease.
• Previous radiation therapy — Skin treated with radiation in the past has an increased risk of developing SCC years later.
• Genetic conditions — Inherited conditions such as xeroderma pigmentosum and epidermolysis bullosa greatly increase the risk.
• Human papillomavirus (HPV) — Certain HPV types are associated with SCC in specific sites, including the genitals and the skin around the fingernails.
• Exposure to certain chemicals or substances — Long-term exposure to arsenic, tar, or industrial chemicals can contribute to SCC development.

Understanding the cause is important because it can influence follow-up care. For example, people with immune suppression are more likely to develop additional skin cancers and typically need more frequent skin checks.

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

The appearance and symptoms of cutaneous SCC can vary depending on where it occurs, how deep it has grown, and whether it is near nerves or blood vessels. Common signs and symptoms include:

• A firm lump or nodule that may feel rough or scaly on the surface.
• An open sore or ulcer that does not heal or that heals and returns.
• A wart-like growth with a raised, irregular surface.
• Crusting or bleeding, even after minor injury.
• Pain, tenderness, or numbness, especially if the cancer is growing around a nerve.

Because SCC most often occurs on sun-exposed skin — such as the face, ears, lips, neck, scalp, forearms, and backs of the hands — any new or changing lesion in these areas should be assessed promptly. However, SCC can also develop on skin that is not regularly exposed to the sun.

How is the diagnosis made?

The diagnosis of invasive squamous cell carcinoma of the skin is made after a tissue sample is examined under the microscope by a pathologist. The sample is obtained by a skin biopsy. Depending on the size and location of the lesion, the biopsy may be a shave biopsy (the surface of the lesion is shaved off), a punch biopsy (a small cylinder of skin is removed with a circular tool), or an excisional biopsy (the entire lesion is removed). Under the microscope, the pathologist identifies abnormal squamous cells that have broken through the epidermis and grown into the deeper layers of the skin. Features the pathologist looks for include cells that have lost their normal, organized arrangement, variation in cell size and shape, and the formation of keratin (a protein made by squamous cells). Once invasive SCC is confirmed, imaging — such as ultrasound, CT, or MRI — may be used to determine the full extent of the tumor and whether it has spread to nearby lymph nodes or other parts of the body. Imaging is typically reserved for larger tumors or tumors with high-risk features.

Histologic grade

Histologic grade describes how abnormal the cancer cells look compared with normal squamous cells under the microscope. The grade is important because it helps predict how the tumor is likely to behave and guides treatment planning. Most cutaneous SCCs are divided into three grades:

• Well differentiated (grade 1) — The cancer cells look very similar to normal squamous cells. These tumors tend to grow slowly and have a lower risk of spreading.
• Moderately differentiated (grade 2) — The cells look different from normal but still show recognizable features of squamous cells. These tumors have an intermediate growth rate and an intermediate risk of recurrence or spread.
• Poorly differentiated (grade 3) — The cells look very abnormal and may barely resemble squamous cells. These tumors grow more quickly, are more likely to spread, and often require additional treatment after surgery, such as radiation therapy.

Higher-grade tumors are considered one of several high-risk features that may influence decisions about margins, follow-up, and additional treatment.

Histologic subtypes and variants

Pathologists recognize several variants of cutaneous SCC. Most behave similarly to conventional SCC, but some are associated with more aggressive behavior and may require closer follow-up.

• Keratoacanthoma-like SCC — Some invasive SCCs resemble keratoacanthomas — dome-shaped growths that can sometimes shrink on their own. Because there is no reliable way to predict behavior, these tumors are treated as SCC and are usually removed surgically.
• Acantholytic (pseudoglandular) SCC — The cancer cells lose their connections to one another, creating spaces that can mimic glands. This variant may behave slightly more aggressively than conventional SCC.
• Spindle cell (sarcomatoid) SCC — The cancer cells become elongated and resemble the cells of a soft tissue cancer. This variant tends to grow more aggressively.
• Desmoplastic SCC — The cancer cells are embedded in dense scar-like tissue. This variant is associated with a higher risk of perineural invasion and local recurrence.
• Adenosquamous carcinoma — A rare variant that combines features of SCC with features of a gland-forming cancer (adenocarcinoma). It is more aggressive than conventional SCC.

Tumor thickness and depth of invasion

Tumor thickness measures how far the cancer has grown from the skin surface into deeper tissue. It is one of the most important features in predicting how the cancer will behave. A tumor thicker than 2 mm is more likely to come back after surgery, and a tumor thicker than 6 mm is considered high risk because it is more likely to spread to lymph nodes or distant organs.

The pathologist also reports how deep the tumor has grown in relation to the normal layers of the skin. In general, tumors that remain in the dermis (the layer just beneath the epidermis) are at a lower risk of spreading, while tumors that invade beyond the subcutaneous fat (the layer beneath the dermis) are considered deep invasion and are a high-risk feature.

Some older pathology reports may describe the depth of invasion using Clark’s levels, a five-level system that describes how far the tumor has grown through the layers of the skin. Clark’s level is no longer used for cancer staging in current guidelines, but you may still see it mentioned in some reports.

Perineural invasion

Perineural invasion (PNI) means cancer cells are growing along or into a nerve. This is an important finding because nerves can act as highways that allow cancer to spread further into surrounding tissue — sometimes well beyond the visible edge of the tumor. Perineural invasion makes the cancer harder to remove completely with surgery and is associated with a higher risk of local recurrence and spread. When perineural invasion involves a large, named nerve, it is considered a high-risk feature and may lead to recommendations for additional surgery or radiation therapy, especially when the tumor is on the head or neck.

Lymphovascular invasion

Lymphovascular invasion (LVI) means cancer cells have entered a small blood vessel or lymphatic channel. This is significant because blood vessels and lymphatic channels provide a direct route for cancer cells to spread to lymph nodes or distant organs. When lymphovascular invasion is present, there is a higher risk of the cancer spreading, and closer monitoring or additional treatment may be recommended.

Margins

A margin is the edge of the tissue removed during surgery. Pathologists examine margins under the microscope to see whether any cancer cells are present at the cut edge. For cutaneous SCC, both the peripheral margin (the side edges of the removed skin) and the deep margin (the bottom of the removed tissue) are evaluated.

• Negative margin — No cancer cells are seen at the cut edge. This suggests the tumor was completely removed and lowers the risk of recurrence.
• Close margin — Cancer cells are within a few millimeters of the cut edge but not reaching it. A close margin may still be associated with a higher risk of recurrence and may lead to recommendations for additional treatment.
• Positive margin — Cancer cells are present at the cut edge. This means some tumor may have been left behind, and additional surgery or radiation therapy is usually recommended.

Margin status is one of the most important findings in your report because it helps determine whether surgery was successful and whether more treatment is needed.

Lymph nodes

Lymph nodes are small immune organs that help filter harmful substances. Cancer cells can travel to lymph nodes via lymphatic channels, making lymph nodes one of the first sites where cutaneous SCC can spread.

If lymph nodes are removed, the pathology report will usually include:

• The total number of lymph nodes examined and the number that contain cancer cells.
• The size of the largest group of cancer cells within a lymph node.
• Whether extranodal extension is present. Extranodal extension means cancer cells have broken through the outer capsule of a lymph node into surrounding tissue. This is an important finding because it is associated with a higher risk of the cancer coming back and often leads to recommendations for additional treatment such as radiation therapy.

Finding cancer in a lymph node means the cancer has started to spread and will change the pathologic stage. Spread to lymph nodes is uncommon in typical cutaneous SCC (occurring in roughly 2–5% of cases overall) but is more likely when the tumor has high-risk features such as large size, deep invasion, poor differentiation, perineural invasion, or when the patient is immunosuppressed.

Biomarker and molecular testing

Routine biomarker testing is not typically performed for cutaneous SCC that can be managed with surgery alone. However, for locally advanced or metastatic disease — cancer that cannot be completely removed by surgery or radiation — biomarker information becomes more relevant because of the availability of immunotherapy.

PD-L1

PD-L1 is a protein on the surface of some cancer cells and immune cells. When PD-L1 binds to a receptor called PD-1 on immune cells, it puts the brakes on the immune response, allowing cancer cells to evade the immune system. Drugs called immune checkpoint inhibitors block this interaction, allowing the immune system to attack the cancer. For advanced cutaneous SCC, the PD-1 inhibitors cemiplimab (Libtayo) and pembrolizumab (Keytruda) are approved regardless of PD-L1 status. For this reason, PD-L1 testing is not routinely required before starting immunotherapy for cutaneous SCC, although some centers still perform it.

Tumor mutational burden

Tumor mutational burden (TMB) is a measure of the number of mutations (genetic changes) present in cancer cells. Cutaneous SCC has among the highest TMB of any cancer type because UV radiation causes a large number of DNA mutations. A high TMB helps explain why cutaneous SCC tends to respond well to immunotherapy — more mutations create more abnormal proteins that the immune system can recognize and attack. TMB testing is not routinely performed for most cutaneous SCC but may be reported when comprehensive molecular testing is done for advanced disease.

For more information about biomarkers and molecular testing in cancer, visit the Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for cutaneous SCC is based on the TNM system created by the American Joint Committee on Cancer (AJCC). This system uses information about the primary tumor (T), regional lymph nodes (N), and distant metastatic disease (M) to determine the overall stage. The M category is usually determined by imaging rather than by pathology. The AJCC 8th edition TNM system applies specifically to cutaneous SCC of the head and neck; cutaneous SCCs on the trunk and extremities are staged using similar criteria but are not covered by the same formal AJCC chapter.

Tumor stage (pT)

• pT1 — Tumor measures 2 cm or less in greatest dimension.
• pT2 — Tumor measures more than 2 cm but no more than 4 cm in greatest dimension.
• pT3 — Tumor measures more than 4 cm, OR there is minor erosion of underlying bone, OR the tumor shows perineural invasion of a named nerve, OR there is deep invasion (tumor thickness greater than 6 mm or invasion beyond the subcutaneous fat).
• pT4a — Tumor shows invasion of the cortex of a bone or bone marrow visible to the naked eye.
• pT4b — Tumor invades the base of the skull, a skull base foramen, or a vertebra.

Nodal stage (pN)

• pN0 — No cancer cells in any examined lymph nodes.
• pN1 — Cancer is found in a single lymph node on the same side as the tumor, measures 3 cm or less, and does not show extranodal extension.
• pN2 — Cancer is found in a single lymph node on the same side as the tumor that is larger than 3 cm but no more than 6 cm, OR in more than one lymph node on the same side none larger than 6 cm, OR in lymph nodes on both sides of the body or on the opposite side from the tumor none larger than 6 cm.
• pN3 — Cancer is found in a lymph node larger than 6 cm, OR any lymph node shows extranodal extension (except in the smallest ipsilateral nodes, where extranodal extension is classified as pN2).

What is the prognosis?

The prognosis for cutaneous squamous cell carcinoma is generally excellent. Most tumors are found early while they are small and superficial, and these are cured by surgery alone in more than 95% of cases. The outlook depends heavily on the features of the tumor and the overall health of the patient.

Pathologic features associated with a higher risk of recurrence, spread, or death from disease include:

• Large tumor size — Tumors larger than 2 cm across are at higher risk of spreading than smaller tumors.
• Deep invasion — Tumor thickness greater than 6 mm or invasion beyond the subcutaneous fat increases the risk of lymph node spread.
• Poor differentiation — Grade 3 (poorly differentiated) tumors behave more aggressively than well or moderately differentiated tumors.
• Perineural invasion — Particularly when a large, named nerve is involved.
• Lymphovascular invasion — Indicates the cancer has access to vessels that can carry cells to other parts of the body.
• High-risk location — Tumors of the lip, ear, temple, and scalp are associated with higher risk of recurrence and spread.
• Immunosuppression — Organ transplant recipients and others on long-term immunosuppressing medications have a substantially higher risk of aggressive behavior and recurrence.
• Recurrent tumor — A cancer that has come back after previous treatment is more difficult to cure.
• Positive or close surgical margins — Increase the risk of local recurrence.

Most cutaneous SCCs that spread first spread to nearby lymph nodes. Once it spreads to distant organs, a cure becomes much less likely, although newer immunotherapy drugs have substantially improved outcomes for advanced disease compared with the chemotherapy options that were available in the past.

What happens after the diagnosis?

Treatment of cutaneous squamous cell carcinoma is usually coordinated by a team that may include a dermatologist, a surgeon (often a Mohs surgeon for high-risk or cosmetically sensitive areas), a radiation oncologist, and, for advanced disease, a medical oncologist.

For most cutaneous SCCs, surgery is the primary treatment. Options include standard surgical excision with a margin of healthy tissue or Mohs micrographic surgery, a specialized technique in which the tumor is removed in thin layers that are examined under the microscope during the operation to ensure all cancer cells are removed. Mohs is often used for tumors on the face and other areas where preserving healthy tissue is important.

Radiation therapy may be recommended after surgery when there are high-risk features such as perineural invasion of a named nerve, positive margins that cannot be re-excised, or extensive lymph node involvement. Radiation can also be used as the primary treatment for patients who are not candidates for surgery.

For cancer that has spread to lymph nodes, surgery to remove the affected nodes (lymph node dissection) is often combined with radiation therapy. In selected high-risk tumors without clinically enlarged lymph nodes, a sentinel lymph node biopsy may be considered to check for microscopic spread.

For locally advanced or metastatic disease that cannot be controlled with surgery or radiation, systemic treatment with a PD-1 inhibitor such as cemiplimab (Libtayo) or pembrolizumab (Keytruda) is now the standard first-line approach. These drugs work by removing the brakes that cancer cells place on the immune system, allowing it to recognize and attack the cancer.

After treatment, regular skin examinations and follow-up are important. People who have had one cutaneous SCC are at higher risk of developing additional skin cancers, and ongoing sun protection is essential for prevention.

Questions to ask your doctor

• Where on my body did the cancer start, and what was the size of the tumor?
• What was the histologic grade of my tumor, and what does that mean for my outlook?
• Was a specific subtype or variant identified, and does it affect my treatment?
• How thick was the tumor, and did it invade beyond the subcutaneous fat?
• Was perineural invasion found? If so, was a large, named nerve involved?
• Was lymphovascular invasion found?
• Were the surgical margins negative, close, or positive? Do I need further surgery?
• Were any lymph nodes removed, and did any contain cancer? Was extranodal extension present?
• What is the pathologic stage of my cancer?
• Do I need additional treatment such as radiation therapy or immunotherapy?
• Am I at higher risk of developing additional skin cancers? How often should I have skin checks?
• What steps can I take to reduce my risk of future skin cancers?
• If I am immunosuppressed, should my medications be reviewed to lower my risk?