Squamous Cell Carcinoma of the Larynx: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Zuzanna Gorski MD FRCPC
April 10, 2026

Squamous cell carcinoma is the most common type of cancer of the larynx, also known as the voice box. The larynx sits in the neck and plays an essential role in breathing, swallowing, and producing speech. It is divided into three regions, called subsites:

• Supraglottis — The upper part of the larynx above the vocal cords, including the epiglottis (the flap that prevents food from entering the airway) and the false vocal cords.
• Glottis — The middle part containing the true vocal cords, which vibrate to produce sound.
• Subglottis — The lower part, extending from below the vocal cords to the top of the trachea (windpipe).

Squamous cell carcinoma starts from the squamous cells that line the inner surface of these regions. The subsite where the cancer begins significantly affects symptoms, staging, treatment approach, and prognosis — glottic cancers (those involving the vocal cords) are often detected early because hoarseness develops even with small tumors, while supraglottic cancers may grow larger before causing symptoms.

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 larynx?

Squamous cell carcinoma of the larynx develops when the squamous cells lining the larynx accumulate genetic damage that allows them to grow uncontrollably. The major risk factors are tobacco use of any kind and heavy alcohol consumption, which work together — the combination of both multiplies risk substantially beyond either factor alone. These same exposures are also linked to keratinizing squamous dysplasia of the larynx, a precancerous condition that can progress to invasive squamous cell carcinoma if untreated.

Other contributing factors include occupational exposure to chemicals or dusts (such as asbestos, wood dust, or paint fumes), previous radiation to the head and neck region, and long-standing voice strain or chronic laryngeal irritation. Most squamous cell carcinomas of the larynx are not caused by human papillomavirus (HPV), unlike oropharyngeal cancers (tonsil and base of tongue cancers), where HPV plays a major role.

What are the symptoms?

Symptoms vary depending on which part of the larynx is affected and how large the tumor has grown. Common symptoms include:

• Hoarseness or a change in voice lasting more than two weeks — often the earliest symptom of glottic cancer
• A lump or sensation of fullness in the throat.
• Difficulty swallowing or pain when swallowing.
• Ear pain on one side that is not from an ear infection.
• Shortness of breath or noisy breathing if the tumor partially blocks the airway.
• Persistent cough or coughing up blood.
• Unexplained weight loss or fatigue.
• A lump in the neck from spread to a lymph node.

Any persistent change in voice or swallowing should be assessed by an ear, nose, and throat (ENT) specialist.

How is the diagnosis made?

The diagnosis is made after a tissue sample is examined under the microscope by a pathologist. The sample is obtained by biopsy during microlaryngoscopy — a procedure in which a thin scope is passed through the mouth under general anesthesia to allow direct visualization of the vocal cords and surrounding larynx, and tissue samples are taken from any suspicious areas.

Under the microscope, the pathologist identifies invasive squamous cell carcinoma — abnormal squamous cells that have broken through the epithelium (surface lining) and invaded the tissue beneath. The biopsy confirms the diagnosis and provides initial information about grade, but features such as cartilage invasion, exact tumor size, and margin status can only be fully assessed after the entire tumor is surgically removed. Once cancer is confirmed, imaging — typically CT and/or MRI of the neck, and PET-CT for more advanced disease — determines the extent of the tumor and lymph node involvement.

Histologic grade

Histologic grade describes how closely the cancer cells resemble normal squamous cells and how much keratin (the structural protein that squamous cells normally produce) is present in the tumor.

• Well differentiated — The cells closely resemble normal squamous cells and usually produce keratin, sometimes forming rounded structures called keratin pearls. These tumors tend to grow more slowly.
• Moderately differentiated — The cells show greater variation in size and shape and produce less keratin. More likely to invade surrounding tissue than well-differentiated tumors.
• Poorly differentiated — The cells look markedly abnormal and produce little or no keratin. These tumors tend to be more aggressive and more likely to spread.

Grade is included in your pathology report because it helps predict how the tumor may behave and contributes to treatment planning. Most laryngeal squamous cell carcinomas are moderately or well differentiated.

Tumor extension

Tumor extension describes how far the cancer has spread from its starting point in the larynx into surrounding structures. Squamous cell carcinoma of the larynx begins in the epithelium (inner lining). As it grows, it can invade progressively deeper structures: first the submucosal soft tissue, then the thyroid cartilage (the main cartilage forming the front of the voice box), the cricoid cartilage (the ring-shaped cartilage just below the thyroid cartilage), and beyond the larynx into adjacent structures such as the thyroid gland, esophagus, or soft tissues of the neck.

Tumor extension into cartilage or adjacent organs defines a higher stage (pT4) and has major treatment implications — more extensive disease may require total laryngectomy (complete removal of the voice box) and combined therapy with radiation or chemotherapy. Vocal cord mobility is also assessed and reported, because fixation of the vocal cord — caused by tumor invasion of the muscles that move the cord — raises the stage even without cartilage invasion.

Perineural invasion

Perineural invasion means cancer cells are growing along or around a nerve. When tumor cells travel along nerve pathways, the cancer can spread further from the primary site and there is a higher risk of local recurrence after treatment. Perineural invasion is an adverse feature that may influence the radiation field used and is considered in decisions about adjuvant treatment. Your report will state whether perineural invasion is present or absent.

Lymphovascular invasion

Lymphovascular invasion means cancer cells have entered lymphatic channels or blood vessels near the tumor. These provide a route for cancer to spread to lymph nodes or, through the bloodstream, to distant organs. Your report will state whether lymphovascular invasion is present or absent. When present, it is associated with a higher risk of nodal spread and distant recurrence.

Surgical margins

Margins are the edges of tissue removed during surgery. The pathologist inks the specimen and examines multiple sections under the microscope to determine how close the tumor comes to each edge.

• Negative margin — No cancer cells at the cut edge. Suggests the tumor was completely removed.
• Close margin — Cancer cells are within a few millimeters of the edge but do not reach it. May prompt additional radiation therapy.
• Positive margin — Cancer cells are present at the cut edge. Suggests some tumor may remain; additional surgery or radiation is usually recommended.

For laryngeal tumors, margins are described as mucosal (at the surface lining), deep soft tissue (at the deep aspect of the resection), and cartilage margins (when cartilage is removed with the specimen). Each is assessed independently.

Lymph nodes

Lymph nodes are small immune organs that filter lymphatic fluid and can trap cancer cells. The larynx drains into lymph nodes on both sides of the neck, grouped into levels I through VI. Because squamous cell carcinoma of the larynx can spread to these nodes, surgeons often perform a neck dissection as part of the surgery.

Your report will include the total number of lymph nodes examined, the number containing cancer, the size of the largest tumor deposit, and whether extranodal extension is present — meaning cancer cells have broken through the outer capsule of a lymph node into surrounding tissue. Extranodal extension is a high-risk feature that typically triggers a recommendation for adjuvant concurrent chemoradiation after surgery. Lymph node involvement is an important part of pathologic staging and strongly influences decisions about additional treatment.

PD-L1

PD-L1 is a protein that some cancer cells produce to shield themselves from immune attack. Immunotherapy drugs called checkpoint inhibitors — particularly pembrolizumab (Keytruda) and nivolumab (Opdivo) — block this mechanism, allowing the immune system to recognize and attack the cancer. PD-L1 testing is typically performed for patients with advanced, recurrent, or metastatic squamous cell carcinoma of the larynx who are being considered for immunotherapy. Results are reported as a Combined Positive Score (CPS). A CPS of 1 or higher indicates that immunotherapy may provide benefit, with higher scores generally associated with a greater likelihood of response.

Pathologic stage (pTNM)

The pathologic stage for squamous cell carcinoma of the larynx is determined using the AJCC TNM staging system. The T stage is determined separately based on the subsite of origin (supraglottis, glottis, or subglottis), because each region has different anatomic boundaries and spread patterns. The N stage uses the same size-and-extranodal-extension-based system as other non-HPV head and neck cancers.

Tumor stage (pT)

Supraglottic tumors:

• pT1 — Tumor limited to one subsite of the supraglottis; vocal cords move normally.
• pT2 — Tumor involves more than one supraglottic subsite, the glottis, or an adjacent region (e.g., base of tongue, vallecula, medial wall of piriform sinus); vocal cords move normally.
• pT3 — Tumor limited to the larynx with vocal cord fixation, and/or invades the postcricoid area, pre-epiglottic space, paraglottic space, or inner cortex of the thyroid cartilage.
• pT4a — Tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx (trachea, soft tissues of the neck, strap muscles, thyroid gland, esophagus).
• pT4b — Tumor invades the prevertebral space, encases the carotid artery, or invades mediastinal structures. (Very advanced, typically unresectable.)

Glottic tumors:

• pT1a — Tumor limited to one vocal cord; normal mobility.
• pT1b — Tumor involves both vocal cords; normal mobility.
• pT2 — Tumor extends to the supraglottis or subglottis, and/or vocal cord mobility is impaired.
• pT3 — Tumor limited to the larynx with vocal cord fixation, and/or invades the paraglottic space or inner cortex of the thyroid cartilage.
• pT4a — Tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx.
• pT4b — Tumor invades the prevertebral space, encases the carotid artery, or invades mediastinal structures.

Subglottic tumors:

• pT1 — Tumor limited to the subglottis.
• pT2 — Tumor extends to the vocal cords; normal or impaired mobility.
• pT3 — Tumor limited to the larynx with vocal cord fixation.
• pT4a — Tumor invades through the cricoid or thyroid cartilage and/or invades tissue beyond the larynx.
• pT4b — Tumor invades the prevertebral space, encases the carotid artery, or invades mediastinal structures.

Nodal stage (pN)

• pNX — No lymph nodes submitted for pathologic examination.
• pN0 — No cancer in any lymph nodes examined.
• pN1 — Cancer in a single ipsilateral (same side) lymph node, 30 mm or smaller, no extranodal extension.
• pN2a — Cancer in a single ipsilateral node: either ≤30 mm with extranodal extension, or >30 mm but ≤60 mm without extranodal extension.
• pN2b — Cancer in multiple ipsilateral lymph nodes, all ≤60 mm, no extranodal extension.
• pN2c — Cancer in bilateral or contralateral lymph nodes, all ≤60 mm, no extranodal extension.
• pN3a — Cancer in any lymph node larger than 60 mm, no extranodal extension.
• pN3b — Extranodal extension present in any involved lymph node, regardless of size or number.

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

The prognosis depends on several factors — the subsite of origin, the stage at diagnosis, the presence of adverse pathologic features, and whether the patient continues to smoke and drink after treatment.

Glottic (vocal cord) cancers are generally diagnosed at an earlier stage because hoarseness develops with even small tumors. Early-stage glottic cancer (pT1–T2, pN0) is highly curable with either radiation therapy or surgery, and five-year survival rates exceed 85–90%. Because early glottic cancer is so amenable to voice-preserving treatment, many patients retain normal or near-normal voice function.

Supraglottic cancers are typically diagnosed at a more advanced stage — they do not cause hoarseness early, and the supraglottis has a rich lymphatic supply that facilitates early spread to lymph nodes. Even when lymph nodes are involved, outcomes can still be favorable with comprehensive treatment, but five-year survival for advanced disease is lower than for early glottic cancer.

Subglottic cancers are the rarest and generally carry the worst prognosis among the three subsites, partly because they are often diagnosed at an advanced stage.

Across all subsites, the following pathologic features are associated with a higher risk of recurrence and worse survival:

• Positive or close margins — Substantially increase local recurrence risk.
• Extranodal extension — One of the strongest adverse prognostic factors; typically triggers recommendation for adjuvant concurrent chemoradiation.
• Perineural invasion — Associated with higher local failure rates.
• Cartilage invasion (pT4a) — Reflects deep local extension; often requires total laryngectomy.
• Multiple positive lymph nodes — Associated with higher rates of distant recurrence.

Smoking cessation after diagnosis and treatment significantly improves outcomes — continued tobacco use is associated with substantially higher rates of recurrence and reduced survival. It also increases the risk of developing a second primary cancer in the head and neck or lungs.

What happens after the diagnosis?

After diagnosis, your healthcare team reviews your pathology report, imaging results, and overall health to plan treatment. The team typically includes an ENT surgeon, a radiation oncologist, a medical oncologist, and a pathologist.

For most patients, surgery is the primary treatment. Depending on the tumor’s size, location, and extent, surgery may remove part of the larynx (partial laryngectomy, including transoral laser microsurgery for early-stage glottic cancers) or the entire larynx (total laryngectomy). Lymph nodes in the neck are also removed and examined. When the tumor has high-risk features — positive or close margins, perineural invasion, extranodal extension, cartilage invasion, or multiple positive lymph nodes — adjuvant radiation or combined chemoradiation is usually recommended after surgery to reduce the risk of recurrence.

For recurrent, metastatic, or unresectable cancer, systemic therapies including chemotherapy, targeted therapy (cetuximab), or immunotherapy (pembrolizumab or nivolumab, guided by PD-L1 results) may be offered. Clinical trial participation is also an important option for advanced disease.

After treatment, patients are followed closely with regular laryngoscopy and periodic imaging. Speech therapy, swallowing rehabilitation, and nutrition support are essential parts of recovery — especially after total laryngectomy. Smoking cessation, alcohol reduction, and consistent dental and medical care help lower the risk of recurrence and improve long-term quality of life.

Questions to ask your doctor

• In which part of my larynx did the cancer start — supraglottis, glottis, or subglottis?
• What was the histologic grade — well, moderately, or poorly differentiated?
• What does my pathology report say about tumor extension — has the tumor grown into cartilage or beyond the larynx?
• Are the vocal cords still mobile, or has movement been affected?
• Was perineural invasion or lymphovascular invasion found?
• Were the surgical margins clear? Is additional surgery or radiation needed?
• How many lymph nodes were examined, and did any contain cancer? Was extranodal extension present?
• What is my pathologic stage (pT and pN)?
• Was PD-L1 testing performed, and what was the CPS score?
• What treatment is recommended — partial laryngectomy, total laryngectomy, radiation, chemoradiation, or a combination?
• Will I be able to preserve my voice after treatment?
• How will speech, swallowing, and breathing be supported during and after treatment?
• How often will I need follow-up examinations and imaging?