Neuroendocrine Carcinoma of the Nasal Cavity and Paranasal Sinuses: Understanding Your Pathology Report

Section Editor: Jason Wasserman MD PhD FRCPC
November 2, 2026

Neuroendocrine carcinoma of the nasal cavity and paranasal sinuses is a rare, fast-growing cancer. It starts in cells with features of neuroendocrine cells, which can release hormones into the blood. Doctors often call it sinonasal neuroendocrine carcinoma. Two main types exist: small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma.

Sinonasal neuroendocrine carcinoma is a high-grade cancer, meaning the cells look very abnormal and divide quickly. It differs from a neuroendocrine tumor of the sinonasal tract, which has more orderly cells and usually grows more slowly. The two names sound alike, so it helps to check which one appears on your report.

This article explains how small cell and large cell neuroendocrine carcinoma of the nose and sinuses are diagnosed. It also describes what the tests, margins, lymph nodes, and stage in your pathology report mean for your care.

Who gets sinonasal neuroendocrine carcinoma?

Sinonasal neuroendocrine carcinoma is found mostly in adults, with a typical age at diagnosis in the 50s. In a study of 415 patients from a large US cancer database, the median age was 58 years, and about 6 in 10 patients were men.

About half of these tumors start in the nasal cavity, the space inside the nose. Most of the rest start in the paranasal sinuses, the air-filled spaces in the bones around the nose and eyes. Small cell neuroendocrine carcinoma is more common than large cell neuroendocrine carcinoma at this site.

What causes sinonasal neuroendocrine carcinoma?

For most people with sinonasal neuroendocrine carcinoma, the cause is unknown. The cancer develops from genetic changes that build up in the tumor cells during a person’s life. Sinonasal neuroendocrine carcinoma is not known to run in families.

A small group of these tumors is linked to high-risk human papillomavirus (HPV), the same virus that causes cervical cancer and many throat cancers. HPV-associated squamous cell carcinoma of the throat usually has a favorable outlook. HPV-associated neuroendocrine carcinoma does not share that advantage, and it behaves like other neuroendocrine carcinomas.

What are the symptoms of sinonasal neuroendocrine carcinoma?

The symptoms of sinonasal neuroendocrine carcinoma come from a growing mass inside the nose or sinuses. The most common are:

A blocked or stuffy nose, often on one side.
Nosebleeds.
Pain or pressure in the face.
Swelling of the face or a bulging eye.

Because sinus infections and nasal polyps also cause these symptoms, the cancer is often large by the time it is found. Very rarely, the tumor cells release hormones into the blood and cause symptoms elsewhere in the body.

How is the diagnosis of sinonasal neuroendocrine carcinoma made?

The diagnosis of sinonasal neuroendocrine carcinoma is made after a tissue sample is examined under the microscope by a pathologist. The sample is usually removed during nasal endoscopy, either in the clinic or in the operating room. In this procedure, a thin camera is passed into the nose to see the tumor and take a biopsy.

Under the microscope, the pathologist sees sheets of tightly packed, abnormal cells. Many cells are dividing, and these dividing cells are called mitotic figures. By definition, a neuroendocrine carcinoma has more than 10 mitotic figures per 2 square millimeters. There are often large areas of dead tumor cells, called necrosis. The size and shape of the cells tell the pathologist whether the tumor is small-cell or large-cell.

Small cell carcinoma is much more common in the lung than in the nose. For this reason, your doctors will review scans of the chest to make sure the tumor in the nose did not spread from the lung. CT and MRI scans of the face and skull show how far the tumor has grown. A PET scan is often used to look for spread to lymph nodes or distant organs.

Sinonasal neuroendocrine carcinoma looks similar to several other fast-growing cancers of the nose. A panel of special stains is therefore needed to confirm the diagnosis, as described in the next section.

Immunohistochemistry

Immunohistochemistry uses antibodies to detect specific proteins inside cells. For sinonasal neuroendocrine carcinoma, it confirms that the tumor cells are neuroendocrine and rules out other cancers that look alike. Your report may list some or all of these results:

Synaptophysin, chromogranin, and INSM1. These neuroendocrine markers show that the tumor cells make proteins typical of neuroendocrine cells. Synaptophysin, chromogranin, and INSM1 are usually positive, which supports the diagnosis. Some reports also include CD56.
Keratin. Keratins are proteins found in carcinomas and in the normal lining of the nose. They are usually positive, often as a small dot in each cell. A positive keratin helps separate this cancer from olfactory neuroblastoma, which is usually keratin negative.
Ki-67. Ki-67 marks cells preparing to divide. In neuroendocrine carcinoma, the Ki-67 result is above 20 percent by definition and is often much higher. This helps separate it from a neuroendocrine tumor, which usually has a lower result.
TTF-1. TTF-1 is often positive in small cell carcinoma of the lung. It can also be positive in small cell carcinoma that starts in the nose, so a positive result does not prove the tumor came from the lung.
p16 and HPV testing. p16 is often positive in neuroendocrine carcinoma, whether or not HPV is present. A separate test that detects the virus itself is therefore needed to show that a tumor is HPV-associated.
SMARCB1 (INI1) and SMARCA4. These proteins are normally present, or retained, in neuroendocrine carcinoma. Loss of either one points instead to SWI/SNF complex-deficient sinonasal carcinoma.
NUT. This stain is negative in neuroendocrine carcinoma. A positive result means the tumor is a NUT carcinoma.
p40 and p63. p40 and p63 are markers of squamous cells. They are used to look for squamous cell carcinoma mixed with neuroendocrine carcinoma.

Not every sinonasal neuroendocrine carcinoma needs every stain. The pathologist chooses the panel based on what the tumor looks like and which other cancers need to be ruled out.

What are the different types of sinonasal neuroendocrine carcinoma?

The World Health Organization (WHO) Classification of Head and Neck Tumors, 5th edition, published in 2022, divides sinonasal neuroendocrine carcinoma into two types. The College of American Pathologists (CAP) protocol for the nasal cavity and sinuses also lists a combined form. Your report will name one of the following:

Small cell neuroendocrine carcinoma. The tumor cells are small, with very little cytoplasm and finely speckled nuclei. The nuclei are often squeezed together so tightly that they change each other’s shape. Your report may call it neuroendocrine carcinoma, small cell type, or small cell carcinoma. This is the more common type in the nose and sinuses.
Large cell neuroendocrine carcinoma. The tumor cells are larger, with more cytoplasm and prominent nucleoli. Your report may call it neuroendocrine carcinoma, large cell type. It is less common than the small cell type, so less is known about its behavior at this site.
Combined neuroendocrine carcinoma. Part of the tumor is neuroendocrine carcinoma and part is a different kind of carcinoma, most often squamous cell carcinoma. Your report may call this combined or composite small cell carcinoma. The report will usually name both parts.

Small cell and large cell neuroendocrine carcinoma are both high grade and are usually treated similarly. A related diagnosis, called neuroendocrine tumor grade 3, has orderly cells that divide quickly. It is a separate diagnosis and is described in our article on neuroendocrine tumors of the sinonasal tract.

Histologic grade

Sinonasal neuroendocrine carcinoma is not divided into well, moderately, or poorly differentiated grades. Both the small cell and the large cell types are high-grade cancers by definition. Older reports sometimes used the term poorly differentiated neuroendocrine carcinoma for the same diagnosis.

Your report may describe the tumor as high-grade, or the grade line may say that grade is not applicable. Either way, the diagnosis itself tells your care team that the tumor grows quickly and is likely to spread. The grade does not need to be assigned separately to guide treatment decisions.

Perineural invasion

Perineural invasion means cancer cells are seen along or inside a nerve. In sinonasal neuroendocrine carcinoma, nerves near the skull base can give the tumor a path to spread toward the brain. Your report will say whether perineural invasion was identified, not identified, or could not be determined.

Lymphovascular invasion

Lymphovascular invasion means cancer cells are seen inside a blood vessel or lymphatic channel. In sinonasal neuroendocrine carcinoma, this finding raises concern that tumor cells could travel to lymph nodes or other organs. Your report will say whether lymphovascular invasion was identified, not identified, or could not be determined.

Surgical margins

A margin is the edge of tissue the surgeon cuts to remove the tumor. Margins are described only when sinonasal neuroendocrine carcinoma has been removed by surgery, not on a biopsy. Your report will describe them as follows:

Negative margin. No cancer cells are seen at the cut edge. Your report will also give the distance in millimeters (mm) from the cancer to the closest margin.
Positive margin. Cancer cells are seen at the cut edge. This means some cancer may remain, and your care team may consider further surgery or radiation therapy.
Cannot be determined. The margins could not be assessed. This happens most often when the tumor is removed in several pieces during endoscopic surgery.

Lymph nodes

Lymph nodes are small immune organs that filter fluid from the tissues. Sinonasal neuroendocrine carcinoma can spread to lymph nodes in the neck. Lymph nodes are removed in an operation called a neck dissection when scans show they may contain cancer.

When lymph nodes are examined, your report will say how many were removed and how many contain cancer cells. It will also give the size of the largest group of cancer cells in a lymph node. The report will also say whether extranodal extension is present, meaning cancer cells have broken through the outer capsule of a lymph node into surrounding tissue. Extranodal extension increases the nodal stage and is one of the findings your care team considers when planning treatment after surgery.

In a large US database study of sinonasal neuroendocrine carcinoma, cancer in several lymph nodes, or in one large node, was linked to shorter survival.

Biomarker and molecular testing

For sinonasal neuroendocrine carcinoma, there is currently no biomarker test that selects a targeted drug made specifically for this cancer. When the cancer has returned or spread, your care team may order broader tests on the tumor. These tests look for rare features that make a patient eligible for drugs approved for any solid tumor, no matter where it started. These approvals are called tumor-agnostic.

Mismatch repair (MMR) and microsatellite instability (MSI)

Mismatch repair proteins fix mistakes made when a cell copies its DNA. Testing is usually done by immunohistochemistry for four proteins, called MLH1, PMS2, MSH2, and MSH6. Your report will describe the result in one of these ways:

Intact, retained, or MMR proficient. All four proteins are present. This is the expected result in sinonasal neuroendocrine carcinoma.
Loss of expression, or MMR deficient (dMMR). One or more proteins are missing. The same finding may be reported as microsatellite instability-high (MSI-high).

A deficient result can make a patient eligible for immunotherapy. The US Food and Drug Administration (FDA) approved pembrolizumab in 2017 for dMMR or MSI-high solid tumors. The FDA approved dostarlimab in 2021 for dMMR solid tumors. A deficient result can also indicate an inherited condition called Lynch syndrome, so genetic counseling may be offered.

Tumor mutational burden (TMB)

Tumor mutational burden is the number of genetic changes found in the tumor cells. Next-generation sequencing (NGS) measures it. Results are reported as mutations per megabase, or mut/Mb. A result of 10 mut/Mb or more is called TMB-high, and a lower result is called TMB-low. In 2020, the FDA approved pembrolizumab for TMB-high solid tumors that have grown after earlier treatment when no good alternative exists.

Other tumor-agnostic changes

NGS can also find rare changes such as an NTRK or RET gene fusion or a BRAF V600E mutation. The FDA has approved targeted drugs for solid tumors carrying each of these changes, regardless of where the cancer started. These changes are uncommon in sinonasal neuroendocrine carcinoma, so a negative result is expected. More information is available in our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for sinonasal neuroendocrine carcinoma uses the TNM system in the AJCC Cancer Staging Manual, 8th edition. The pTNM stage combines the tumor stage (pT) and the nodal stage (pN). The metastasis stage (M) is usually decided from scans rather than from the pathology report.

Tumor stage (pT)

The tumor stage for sinonasal neuroendocrine carcinoma depends on where the tumor started. In a large US database study, about two in three of these tumors had already grown into nearby structures and were classified as T4.

Nasal cavity and ethmoid sinus:

pT1. The tumor is limited to one area of the nasal cavity or ethmoid sinus, with or without bone involvement.
pT2. The tumor involves two areas of the nasal cavity or ethmoid sinus, or extends into a neighboring area, with or without bone involvement.
pT3. The tumor has grown into the floor or inner wall of the eye socket, the maxillary sinus, or the roof of the mouth. It may instead involve the cribriform plate, the thin bone below the brain.
pT4a. The tumor has grown into the front of the eye socket, the skin of the nose or cheek, or slightly into the front of the skull. It may instead have reached the pterygoid plates or the sphenoid or frontal sinuses.
pT4b. The tumor has grown into the back of the eye socket, the dura covering the brain, the brain itself, or the middle of the skull base. It may instead involve certain cranial nerves, the nasopharynx, or the clivus.

Maxillary sinus:

pT1. The tumor is limited to the lining of the maxillary sinus, with no damage to the bone.
pT2. The tumor has damaged the sinus bone or grown into the roof of the mouth or the middle part of the nasal cavity.
pT3. The tumor has grown into the back wall of the sinus, the tissue under the skin, or the floor or inner wall of the eye socket. It may instead involve the pterygoid fossa or the ethmoid sinuses.
pT4a. The tumor has grown into the front of the eye socket, the cheek skin, or the pterygoid plates. It may instead involve the infratemporal fossa, the cribriform plate, or the sphenoid or frontal sinuses.
pT4b. The tumor has grown into the back of the eye socket, the dura, the brain, or the middle of the skull base. It may instead involve certain cranial nerves, the nasopharynx, or the clivus.

If the tumor stage cannot be assessed, for example because the tumor was removed in many small pieces, your report may say that the pT stage was not assigned.

Nodal stage (pN)

pN0. No cancer cells are found in the lymph nodes examined.
pN1. Cancer is found in one lymph node on the same side as the tumor. The node is 3 cm or smaller, with no extranodal extension.
pN2a. Cancer is found in one lymph node on the same side. Either it is 3 cm or smaller with extranodal extension, or it is larger than 3 cm but not larger than 6 cm without extranodal extension.
pN2b. Cancer is found in more than one lymph node on the same side, none larger than 6 cm and none with extranodal extension.
pN2c. Cancer is found in lymph nodes on the opposite side or on both sides, none larger than 6 cm and none with extranodal extension.
pN3a. Cancer is found in a lymph node larger than 6 cm, without extranodal extension.
pN3b. Cancer is found in a lymph node with extranodal extension, other than the single small node described under pN2a.
pNX. Lymph nodes were not examined.

Your care team combines the pT stage, the pN stage, and your scans to assign an overall stage group from stage I to stage IV. A tumor that is pT4a is at least stage IVA, and a tumor that is pT4b is stage IVB. Cancer that has spread to distant organs is stage IVC.

What is the prognosis for sinonasal neuroendocrine carcinoma?

The prognosis for sinonasal neuroendocrine carcinoma is guarded, because the cancer tends to grow back and to spread to distant organs. Because the disease is rare, survival figures come from pooled case reports and database studies rather than clinical trials.

A 2016 review pooled 115 published cases of sinonasal small cell carcinoma. About 46 percent of these patients had not died of the cancer five years after diagnosis, which means more than half had. Some recent single-center reports describe better results, but they include only small numbers of patients. Survival figures for the large cell type at this site have not been published in large enough groups to give a reliable number.

Several findings are linked to a worse outcome:

Tumor stage. In a large US database study, tumors classified as T4 were linked to shorter survival.
Lymph node spread. Cancer in several lymph nodes or in a large node (N2 or N3) was also linked to shorter survival.
Spread to distant organs. Cancer that has already spread at diagnosis is the most difficult to control.
Older age. Older patients had shorter survival in both the pooled review and the database study.

Patients who received more than one kind of treatment did better in the same database study. Your care team can explain how these findings apply to you.

What happens after the diagnosis of sinonasal neuroendocrine carcinoma?

Once sinonasal neuroendocrine carcinoma has been confirmed by pathology, the next steps depend on the type of carcinoma, the stage, and whether the cancer has spread. Your care team will usually include a head and neck surgeon, a radiation oncologist, and a medical oncologist. No single standard treatment exists because the disease is rare.

When the cancer has not spread to distant organs, the team often combines treatments. Options include:

Chemotherapy first. Chemotherapy with a platinum drug and etoposide is often given first. How well the tumor shrinks helps the team choose the next treatment.
Chemoradiation. Radiation therapy is given together with chemotherapy, without surgery.
Surgery followed by radiation. The tumor is removed, then radiation therapy or chemoradiation is given. The margins and lymph nodes on the pathology report help guide this decision.

When the cancer has spread, chemotherapy with a platinum drug and etoposide is the usual starting point. For small cell carcinoma, some teams consider the approach used for small cell lung cancer. That approach adds an immunotherapy drug such as atezolizumab, which the FDA approved in 2019 for small cell lung cancer. It is not approved for cancer that starts in the nose, so its use here would be off-label.

No drug has been approved by the FDA specifically for neuroendocrine carcinoma of the nose and sinuses. Clinical trials are testing new drugs for neuroendocrine carcinomas that start outside the lung, and your oncologist can tell you whether any are open to you. After treatment, regular endoscopy and scans are used to watch for the cancer coming back.

Questions to ask your doctor

Is my tumor small cell, large cell, or a mixed type?
How do you know this is a neuroendocrine carcinoma and not a neuroendocrine tumor?
What was my Ki-67 result?
Which other cancers were ruled out by the immunohistochemistry stains?
Was HPV testing done, and what did it show?
Have my chest scans shown any sign of cancer in the lung?
Has the cancer spread to lymph nodes or other organs?
What is the pT stage, and what is my overall stage group?
If I had surgery, were the margins negative, and how far was the cancer from the closest margin?
Will I receive chemotherapy before other treatment, and how will you judge whether it worked?
Was mismatch repair, TMB, or other molecular testing done on my tumor?
Are there clinical trials for neuroendocrine carcinoma that I could join?
How often will I need endoscopy and scans after treatment?