Spindle Cell Squamous Cell Carcinoma of the Larynx: Understanding Your Pathology Report

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

Spindle cell squamous cell carcinoma — also called sarcomatoid squamous cell carcinoma — is a rare and aggressive subtype of squamous cell carcinoma of the larynx. It is called “spindle cell” because the cancer cells have an elongated, spindle-like shape quite different from the rounded cells of typical squamous cell carcinoma. This unusual shape makes spindle cell squamous cell carcinoma look similar to a type of cancer called sarcoma under the microscope — but despite its appearance, this tumor arises from squamous cells lining the larynx, not from connective tissue. Special laboratory tests called immunohistochemistry are used to confirm the correct diagnosis.

Spindle cell squamous cell carcinoma most commonly arises in the glottis (the vocal cord region) of the larynx, though it can involve any laryngeal subsite. 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 spindle cell squamous cell carcinoma of the larynx?

Like conventional squamous cell carcinoma of the larynx, spindle cell squamous cell carcinoma is strongly associated with tobacco smoking and heavy alcohol consumption. These are the most important modifiable risk factors. Many tumors arise from or alongside a precancerous condition called keratinizing squamous dysplasia (also called high grade dysplasia of the larynx), in which abnormal squamous cells accumulate in the surface lining of the larynx before becoming invasive cancer.

Prior radiation therapy to the head and neck is a particularly important risk factor for spindle cell squamous cell carcinoma, specifically, a higher proportion of these tumors arise in previously irradiated fields compared to conventional laryngeal squamous cell carcinoma. Occupational exposures to certain chemicals, dust, or fumes may also contribute.

What are the symptoms?

Spindle cell squamous cell carcinoma most commonly arises on or near the vocal cords, so the most frequent presenting symptom is hoarseness — a change in the quality of the voice that may sound scratchy, strained, or rough. Other symptoms may include:

• A sensation of fullness or a lump in the throat.
• Difficulty or pain swallowing.
• Shortness of breath or noisy breathing if the tumor obstructs the airway.
• Ear pain on one side.
• A lump in the neck from spread to a lymph node.

Any persistent change in voice lasting more than two weeks 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 visualize the vocal cords and larynx and collect tissue from any abnormal area.

Under the microscope, spindle cell squamous cell carcinoma is made up of large, very abnormal-looking spindle cells — elongated cells with tapered ends and irregular, enlarged nuclei. The cells are often described as pleomorphic, meaning there is marked variation in their size, shape, and appearance throughout the tumor. Some tumors also contain areas of more recognizable squamous cell carcinoma alongside the spindle cell component; finding these areas of conventional squamous differentiation helps confirm the diagnosis. Special tests, such as immunohistochemistry (described below), are routinely performed to confirm the squamous origin of the spindle cells and to exclude the possibility of a true sarcoma. Once cancer is confirmed, imaging — CT and/or MRI of the neck, and PET-CT for more advanced disease — determines the tumor’s full extent and lymph node involvement.

Immunohistochemistry

Immunohistochemistry (IHC) is a laboratory test that uses antibodies to detect specific proteins inside tumor cells, making them visible under the microscope. It plays a critical role in diagnosing spindle cell squamous cell carcinoma because the elongated, sarcomatoid appearance of the tumor cells closely resembles true sarcoma — a cancer of connective tissue — which requires completely different treatment. IHC allows the pathologist to determine whether the spindle cells are actually of squamous (epithelial) origin.

In spindle cell squamous cell carcinoma, the tumor cells are typically positive for markers of squamous differentiation, including:

• Pan-cytokeratin (AE1/AE3) — Confirms the cells are derived from epithelium rather than connective tissue. However, staining can be weak or focal in spindle cell tumors, so its absence does not exclude the diagnosis.
• p63 and p40 — Nuclear markers of squamous differentiation that are often more reliably positive in the spindle cell component than cytokeratins.
• CAM5.2 — An additional cytokeratin marker that may be positive when AE1/AE3 staining is weak.

True sarcomas — such as fibrosarcoma or undifferentiated pleomorphic sarcoma — are negative for these epithelial markers. When the IHC pattern is positive for squamous markers (even focally) in the right clinical context, the diagnosis of spindle cell squamous cell carcinoma is confirmed over sarcoma. Your report will list which IHC markers were tested and whether each was positive or negative.

Histologic grade

Spindle cell squamous cell carcinoma is not routinely assigned a formal histologic grade in the same way as conventional squamous cell carcinoma. By its nature, this tumor is considered high grade — the spindle cell and pleomorphic features indicate a high degree of cellular abnormality, corresponding to poorly differentiated behavior. Most pathology reports will either note this directly or will describe the tumor as high grade based on the degree of pleomorphism and mitotic activity (the number of cells actively dividing). Your report may include a mitotic count or comment on the degree of pleomorphism as a reflection of tumor aggressiveness.

Tumor extension

Tumor extension describes how far the cancer has spread from its original site in the larynx. Spindle cell squamous cell carcinoma begins in the epithelium (inner lining) of the larynx but can grow into the deeper layers of the laryngeal wall, adjacent cartilage (the thyroid cartilage or cricoid cartilage), or beyond the larynx into surrounding structures such as the thyroid gland, trachea, esophagus, or soft tissues of the neck. When tumor spreads from one laryngeal subsite (for example, the glottis) into an adjacent subsite (such as the supraglottis or subglottis), this is called transglottic extension and raises the pathologic tumor stage.

Tumors confined to the larynx behave less aggressively than those that extend into adjacent structures or organs, which are more likely to spread to lymph nodes and to recur after surgery. Your report will describe which structures are involved and whether vocal cord mobility has been affected — fixation of the vocal cord, caused by tumor invasion of the underlying muscles, also raises the stage even without cartilage invasion.

Perineural invasion

Perineural invasion means cancer cells are growing along or around a nerve. When tumor cells spread along nerve pathways, there is a higher risk that the cancer will recur after treatment or spread beyond the primary site. Perineural invasion is an adverse feature that may influence the radiation field used and contribute to 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 examines the cut surfaces 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 assessed at the mucosal (surface), deep soft tissue, and cartilage edges. Each is reported independently.

Lymph nodes

Lymph nodes are small immune organs in the neck that can trap cancer cells. Squamous cell carcinoma of the larynx can spread to neck lymph nodes at levels I through VI, and a neck dissection is often performed as part of surgical treatment. 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 prompts a recommendation for adjuvant concurrent chemoradiation after surgery.

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. PD-L1 testing is typically performed for patients with advanced, recurrent, or metastatic disease. Results are reported as a Combined Positive Score (CPS); a CPS of 1 or higher indicates that immunotherapy may provide benefit.

Pathologic stage (pTNM)

Spindle cell squamous cell carcinoma of the larynx is staged using the same AJCC TNM staging system as conventional squamous cell carcinoma of the larynx. The T stage is determined by which laryngeal subsite the tumor arises in, because each subsite has different anatomic boundaries and spread patterns.

Tumor stage (pT)

Supraglottic tumors:

• pT1 — Tumor limited to one supraglottic subsite; vocal cords move normally.
• pT2 — Tumor involves more than one supraglottic subsite or extends to the glottis or an adjacent region; 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 extends beyond the larynx into surrounding structures.
• pT4b — Tumor invades the prevertebral space, encases the carotid artery, or involves mediastinal structures.

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 extends beyond the larynx.
• pT4b — Tumor invades the prevertebral space, encases the carotid artery, or involves 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 extends beyond the larynx.
• pT4b — Tumor invades the prevertebral space, encases the carotid artery, or involves 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 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 spindle cell squamous cell carcinoma of the larynx?

Spindle cell squamous cell carcinoma is considered more aggressive than conventional laryngeal squamous cell carcinoma. Overall prognosis is less favorable, with a higher tendency for local recurrence and, in some series, a higher rate of distant metastasis. However, outcomes depend significantly on stage at diagnosis and treatment, and early-stage tumors treated with complete surgical resection can have acceptable outcomes.

The following pathologic features are associated with a higher risk of recurrence and worse overall outcomes:

• Positive or close margins — Strongly associated with local recurrence; adjuvant radiation is typically recommended.
• Extranodal extension — High-risk feature prompting adjuvant chemoradiation.
• Perineural invasion — Associated with higher rates of local failure.
• Tumor extension beyond the larynx (pT4) — More advanced disease with greater recurrence risk.
• Lymph node involvement — Signals systemic spread; number of involved nodes and extranodal extension both affect outcome.
• Prior radiation history — Tumors arising in a previously irradiated field tend to behave particularly aggressively and may have limited treatment options.

Smoking cessation is strongly recommended — continued tobacco use after diagnosis and treatment worsens outcomes and 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 — typically an ENT surgeon, radiation oncologist, medical oncologist, and pathologist — reviews your pathology report, imaging, and overall health to plan treatment.

Surgery is the primary treatment for most patients. Depending on the tumor’s size and location, this may involve partial or total laryngectomy (removal of part or all of the voice box), with neck dissection to remove lymph nodes. Given the aggressive nature of this tumor type, adjuvant radiation therapy is often recommended even for early-stage disease to reduce the risk of local recurrence. When high-risk features are present — positive or close margins, extranodal extension, perineural invasion, or multiple positive lymph nodes — adjuvant concurrent chemoradiation is typically recommended.

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

After treatment, close follow-up with regular laryngoscopy and imaging is essential given the higher recurrence risk of this tumor type. Speech, swallowing, and nutritional rehabilitation are important parts of recovery, particularly after total laryngectomy.

Questions to ask your doctor

• Was the diagnosis of spindle cell squamous cell carcinoma confirmed by immunohistochemistry — which markers were tested, and what were the results?
• Was a sarcoma excluded as part of the diagnostic workup?
• In which part of my larynx did the cancer start — the glottis, supraglottis, or subglottis?
• Has the tumor spread beyond the larynx into adjacent structures or cartilage?
• Are the vocal cords still mobile, or has movement been affected?
• Was perineural invasion or lymphovascular invasion found?
• Were the surgical margins negative? Is additional treatment needed for a close or positive margin?
• 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 often will I need follow-up examinations and imaging?