Nonkeratinizing Squamous Cell Carcinoma of the Nasal Cavity and Sinuses: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
July 7, 2026

Nonkeratinizing squamous cell carcinoma (NKSCC) is a type of cancer that begins in squamous cells, the flat cells lining the inner surfaces of the nasal cavity and paranasal sinuses. The nasal cavity is the hollow space inside the nose that warms, moistens, and filters the air we breathe. The paranasal sinuses, which include the maxillary, frontal, sphenoid, and ethmoid sinuses, are air-filled spaces within the bones around the nose that help lighten the skull and produce mucus to keep the nasal passages moist. Unlike keratinizing squamous cell carcinoma, this type does not produce keratin, a tough protein found in skin and hair. 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 nonkeratinizing squamous cell carcinoma?

Nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses can develop for several reasons, and in some cases more than one factor is involved.

Human papillomavirus (HPV) — High-risk HPV is linked to a meaningful share of cases, especially in North America and Europe, where roughly 36 to 58 percent of nonkeratinizing squamous cell carcinomas are HPV-associated. HPV16, a common high-risk type, accounts for 41 to 82 percent of these cases. The virus interferes with the normal controls that keep squamous cells from growing out of control.
Epstein-Barr virus (EBV) — Rarely, tumors in the nasal cavity and sinuses have been linked to EBV, a virus associated with certain cancers.
Genetic changes — In tumors not related to HPV or EBV, genetic changes may drive the cancer. Nearly half of HPV-negative cases show a fusion between two genes, DEK and AFF2, which is thought to promote tumor growth. A gene fusion occurs when two genes that are normally separate become joined, creating an abnormal combined gene that changes how the cell behaves.

What are the symptoms?

The symptoms of nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses depend on the size and location of the tumor. Common symptoms include nasal congestion or a blocked nose, nosebleeds, pain or pressure in the face or around the sinuses, difficulty breathing through the nose, a lump or swelling in the nasal area, and a decreased sense of smell. Some tumors do not cause noticeable symptoms until they grow larger or spread into nearby structures, which is one reason this cancer is sometimes found at a later stage.

How is the diagnosis made?

The diagnosis of nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses is made after a tissue sample is examined under the microscope by a pathologist. The sample is usually obtained through a biopsy, in which a small piece of tissue is removed from the tumor, often via an endoscope through the nose. In some cases, the diagnosis is made after the tumor has been surgically removed.

Under the microscope, nonkeratinizing squamous cell carcinoma consists of nests, lobules, or ribbon-like groups of tumor cells. Unlike many squamous cell carcinomas in other parts of the body, this tumor often grows with a smooth, pushing border rather than breaking irregularly through the surrounding tissue, even when it invades deeply. Some tumors form finger-like projections called papillae that extend along the surface. The tumor cells typically have large nuclei and relatively little cytoplasm, and cells at the edges of the nests are often aligned in an orderly row. By definition, these tumors do not produce keratin. The degree of abnormality can vary from one case to the next, and areas of cell death (necrosis) may be present.

Two subtypes are recognized. The HPV-associated squamous cell carcinoma subtype is linked to high-risk HPV and typically presents with a classic nonkeratinizing appearance, although some cases may show keratinizing, basaloid (small, dark cells), or adenosquamous (a mix of squamous and gland-forming cells) features. The DEK::AFF2 subtype is caused by the DEK::AFF2 gene fusion and often shows a distinctive growth pattern with both outward and inward projections; it overlaps with a tumor previously called low-grade papillary sinonasal carcinoma.

Several additional tests help confirm the diagnosis and identify the subtype. Immunohistochemistry, a test that uses specifically labeled antibodies to detect proteins in tumor cells, is used to detect p16. Strong, widespread p16 staining suggests that HPV is involved. To confirm HPV directly, in situ hybridization may be used to detect high-risk HPV within the tumor cells. When the DEK::AFF2 subtype is suspected, next-generation sequencing or fluorescence in situ hybridization (FISH) can identify the DEK::AFF2 gene fusion. Once the diagnosis is confirmed, imaging studies such as CT and MRI are used to determine the size of the tumor and whether it has spread to nearby structures.

Histologic grade

Unlike keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses is generally not assigned a histologic grade based on cell-to-cell abnormality. The diagnosis is defined by the tumor’s growth pattern and its lack of keratin, rather than by a grade, so your pathology report will usually not include a grade number for this tumor, which is expected. The pathologist’s assessment focuses instead on the tumor’s extent, the presence of features such as perineural or lymphovascular invasion, and the results of HPV and molecular testing.

Perineural invasion

In nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses, the pathologist looks for perineural invasion, which means cancer cells were seen attached to or growing along the outside of a nerve. Nerves run throughout the head and neck, carrying signals such as temperature, pressure, and pain between the body and the brain. Perineural invasion matters because cancer cells can use nerves as a pathway to invade nearby tissues, which increases the risk of the tumor returning after treatment. If perineural invasion is present, it will be described in your pathology report.

Lymphovascular invasion

Lymphovascular invasion means that cancer cells from the nonkeratinizing squamous cell carcinoma were seen within a blood or lymphatic vessel. Blood vessels carry blood throughout the body, and lymphatic vessels carry a fluid called lymph. Both types of vessels connect to other parts of the body, so cancer cells that enter them can travel to distant sites such as lymph nodes or the lungs. If lymphovascular invasion is present, it will be included in your pathology report.

Surgical margins

A surgical margin is the edge of the tissue that the surgeon cuts through when removing the tumor. Margins are assessed after a procedure that removes the entire tumor, such as an excision or resection, and are usually not evaluated after a biopsy, which removes only part of the tumor. Because tumors in the nasal cavity and sinuses are often removed in more than one piece, the pathologist may not be able to assess every margin, and the report may describe the margins as indeterminate.

Negative margin — No cancer cells are present at the cut edge of the tissue. This suggests the tumor was completely removed.
Close margin — Cancer cells are near the cut edge but do not reach it. The distance from the nearest cancer cells to the edge may be measured and reported, because a very close margin can be relevant to decisions about additional treatment.
Positive margin — Cancer cells are present at the cut edge. This means some tumor may remain in the body, and the treatment team will use this finding when considering whether additional surgery or radiation therapy is appropriate.

Lymph nodes

Lymph nodes are small immune organs found throughout the head and neck. Cancer cells from a nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses can travel through lymphatic vessels to reach these nodes. When lymph nodes are removed during surgery, they are examined under the microscope, and the results are described in your pathology report.

Your report will include the total number of lymph nodes examined, the number that contain cancer cells, and the size of the largest deposit of cancer cells (often called a “focus” or “deposit”). A node that contains cancer cells is described as “positive,” and a node with no cancer cells is described as “negative.” The pathologist also checks for extranodal extension, which means cancer cells have broken through the outer capsule of a lymph node and spread into the surrounding tissue. Lymph node findings are used to determine the pathologic nodal stage (pN) and, along with evidence of cancer cells spreading beyond the tumor (metastasis), may influence decisions about additional treatment, such as radiation therapy, chemotherapy, or immunotherapy.

Biomarker and molecular testing

For nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses, the molecular tests used to confirm the diagnosis and its subtype (HPV testing and DEK::AFF2 testing) are described above under “How is the diagnosis made?” The biomarker below becomes relevant when the cancer is advanced, has come back after treatment, or has spread to distant sites.

PD-L1

PD-L1 (programmed death ligand 1) is a protein that some cancer cells express on their surface to evade immune recognition. Drugs called immune checkpoint inhibitors block this protein, allowing the immune system to recognize and attack the cancer. In squamous cell carcinomas of the head and neck, PD-L1 testing helps identify patients who may benefit from these drugs when the cancer is recurrent or metastatic.

PD-L1 is measured by immunohistochemistry and, for head and neck cancers, is usually reported as a Combined Positive Score (CPS), which reflects PD-L1 staining on both the cancer cells and nearby immune cells. A higher score indicates a greater chance that immunotherapy will be effective. Your report will state the score and whether it is above or below the threshold used for treatment decisions. A CPS of 1 or higher is generally used to identify patients who may be eligible for the immune checkpoint inhibitor pembrolizumab (Keytruda) in recurrent or metastatic disease. A result below the threshold does not rule out immunotherapy in every situation, but it makes eligibility less likely. Evidence on PD-L1 specifically in nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses is still developing, and your medical oncology team will explain how the result applies to your situation. You can read more in the PD-L1 testing overview and in the full Biomarkers and Molecular Testing section.

Pathologic stage (pTNM)

The pathologic stage for nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses is based on the TNM staging system, as defined in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. This system describes the tumor using three categories: the primary tumor (pT), the regional lymph nodes (pN), and distant spread (pM). In general, a higher stage reflects more advanced disease. The metastatic stage (pM) is determined by imaging and clinical evaluation, not by the pathologist examining the surgical specimen. Because the tumor stage depends on where the cancer began, the criteria differ for tumors that start in the maxillary sinus versus those that start in the nasal cavity or ethmoid sinus.

Tumor stage (pT) — maxillary sinus

Tis — The cancer is “in situ,” confined to the surface layer and has not invaded deeper tissue.
pT1 — The tumor is limited to the lining (mucosa) of the maxillary sinus and has not damaged the surrounding bone.
pT2 — The tumor has eroded or destroyed bone, possibly including the hard palate or the middle nasal passage, but has not reached the back wall of the maxillary sinus or the pterygoid plates (wing-shaped bones at the base of the skull).
pT3 — The tumor has invaded the back wall of the maxillary sinus, the tissue beneath the skin, the floor or inner wall of the orbit (the socket that holds the eye), the pterygoid fossa (a depression at the side of the skull), or the ethmoid sinuses.
pT4a — The tumor has grown into the front part of the eye socket, the skin of the cheek, the pterygoid plates, the infratemporal fossa (a space at the side of the skull), the cribriform plate (a bony shelf at the top of the nasal cavity), or the sphenoid or frontal sinuses.
pT4b — The tumor has grown into the deepest part of the eye socket, the coverings of the brain, the brain itself, the middle cranial fossa, specific cranial nerves, the upper throat behind the nose (nasopharynx), or a bony area at the base of the skull (clivus).

Tumor stage (pT) — nasal cavity and ethmoid sinus

Tis — The cancer is “in situ,” confined to the surface layer.
pT1 — The tumor is limited to one area (subsite) of the nasal cavity or ethmoid sinus, with or without involvement of the surrounding bone.
pT2 — The tumor involves two subsites within the nasal cavity or ethmoid sinus, or extends into an adjacent area within this region, with or without involvement of the surrounding bone.
pT3 — The tumor has invaded the floor or inner wall of the orbit, the maxillary sinus, the palate (the roof of the mouth), or the cribriform plate.
pT4a — The tumor has grown into the front part of the eye socket, the skin of the nose or cheek, a limited area at the base of the skull, or nearby bones.
pT4b — The tumor has grown into the deepest part of the eye socket, the coverings of the brain, the brain itself, the middle cranial fossa, specific cranial nerves, or deep areas of the skull.

Nodal stage (pN)

pNX — The lymph nodes could not be assessed.
pN0 — No cancer cells were found in any of the lymph nodes examined.
pN1 — Cancer cells were found in a single lymph node on the same side of the neck as the tumor. The node is 3 cm or smaller and shows no extranodal extension.
pN2a — Cancer cells were found in a single lymph node on the same side of the neck that is either 3 cm or smaller with extranodal extension, or larger than 3 cm but no larger than 6 cm without extranodal extension.
pN2b — Cancer cells were found in more than one lymph node on the same side of the neck. None is larger than 6 cm, and none shows extranodal extension.
pN2c — Cancer cells were found in lymph nodes on both sides of the neck, or on the opposite side from the tumor. None is larger than 6 cm, and none shows extranodal extension.
pN3a — A lymph node containing cancer cells is larger than 6 cm and shows no extranodal extension.
pN3b — A lymph node with extranodal extension is present, or multiple involved nodes show extranodal extension.

What is the prognosis?

Prognosis refers to the likely long-term outcome after a diagnosis. For nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses, the outlook depends mainly on the size and location of the tumor, whether it has spread to nearby tissues or to lymph nodes, and the person’s overall health. The five-year survival rate for sinonasal squamous cell carcinoma overall is approximately 60 percent. Several findings on the pathology report are associated with a higher risk of the cancer returning after treatment.

Tumor stage — Tumors that have grown into the orbit, skull base, or brain are harder to remove completely and carry a higher risk of recurrence.
Lymph node involvement — Cancer found in the lymph nodes, and especially extranodal extension, is associated with a higher risk of spread.
Perineural and lymphovascular invasion — Either finding is associated with a higher chance that the tumor will return.
Margin status — Positive or close margins are associated with a higher risk of cancer returning in the same area.
HPV status — Some studies suggest HPV-associated tumors may have a better outlook than tumors not linked to HPV, though this benefit is not seen consistently in the nasal cavity and sinuses the way it is in the oropharynx.

What happens after the diagnosis?

Treatment for nonkeratinizing squamous cell carcinoma of the nasal cavity and sinuses is planned by a multidisciplinary team that may include ear, nose, and throat (ENT) surgeons, neurosurgeons for tumors near the skull base, radiation oncologists, and medical oncologists. The approach is guided by the location, size, and stage of the tumor, along with the specific findings in the pathology report.

Surgery is the main treatment for tumors that can be removed, and may be performed endoscopically through the nose or through a larger open approach for more extensive tumors. The goal is complete removal of the tumor with clear margins. When the report shows positive or close margins, perineural invasion, lymphovascular invasion, or cancer in the lymph nodes, radiation therapy after surgery may be considered, and these specific findings directly inform that decision. For advanced disease, chemotherapy may be added, and for recurrent or metastatic tumors, immunotherapy may be an option depending on the PD-L1 result. After treatment, regular follow-up with imaging and physical examination is used to watch for any sign of the cancer returning.

Questions to ask your doctor

Where exactly did my cancer start — the nasal cavity, maxillary sinus, or ethmoid sinus?
Was my tumor found to be HPV-associated, DEK::AFF2, or neither, and what does that mean for me?
What is my pathologic stage (pT and pN), and what does that mean for my treatment?
Were the surgical margins negative, or were they indeterminate because the tumor was removed in pieces?
Was perineural invasion present in my tumor?
Was lymphovascular invasion present in my tumor?
Were lymph nodes examined, and did any contain cancer cells? Was extranodal extension present?
Was PD-L1 testing performed, and if so, what was the result?
Will I need radiation therapy after surgery, and which findings in my report influenced that recommendation?
What signs of recurrence should I watch for, and how will I be monitored after treatment?
Are there any clinical trials available for my type of cancer?