Neuroendocrine Tumor of the Larynx: Understanding Your Pathology Report

Section Editor: Jason Wasserman MD PhD FRCPC
July 24, 2026

A neuroendocrine tumor (NET) of the larynx is an uncommon type of cancer that develops from neuroendocrine cells. These specialized cells are found throughout the body, receive signals from the nervous system, and respond by releasing hormones into the bloodstream. Small numbers of them are normally present in the lining of the larynx, the voice box in your neck that produces sound and protects your airway when you swallow.

You may also see this tumor called a well differentiated neuroendocrine tumor. “Well differentiated” means the tumor cells still look and behave much like normal neuroendocrine cells. This is an important distinction, because it separates this tumor from a different and more serious cancer called neuroendocrine carcinoma (which includes small cell and large cell types), where the cells look very different from normal, and the disease behaves quite differently. If your report says neuroendocrine tumor rather than neuroendocrine carcinoma, this article is the one that applies to you.

Although uncommon overall, neuroendocrine tumors are the second most frequent type of tumor found in the larynx, after squamous cell carcinoma. Most arise in the supraglottis, the part of the larynx above the vocal cords.

This article explains the findings you are likely to see on a pathology report for a neuroendocrine tumor of the larynx, what each one means, and why it matters for your care.

What causes a neuroendocrine tumor of the larynx?

The cause of a neuroendocrine tumor of the larynx is not well understood. Unlike squamous cell carcinoma, which is the most common cancer of the larynx and is strongly linked to tobacco and alcohol, no clear cause has been established for this tumor. Researchers continue to look at genetic and environmental factors, but at present there is no known exposure or behavior that explains why it develops.

This tumor is not known to be inherited, and having it does not mean your relatives are at increased risk.

What are the symptoms of a neuroendocrine tumor of the larynx?

The symptoms of a neuroendocrine tumor of the larynx come from the tumor growing within the voice box and, in some cases, spreading to lymph nodes in the neck. Common symptoms include:

Hoarseness or another lasting change in the voice
Difficulty or discomfort with swallowing
A sensation of something in the throat, or throat pain
Shortness of breath or noisy breathing
A lump in the neck, which may mean the tumor has spread to a lymph node

Because many far more common conditions cause these same symptoms, they usually lead to an examination of the larynx rather than immediately suggesting a tumor. Any hoarseness or swallowing difficulty lasting more than a few weeks should be assessed by a doctor.

How is the diagnosis made?

The diagnosis is made when a pathologist examines a sample of the tumor under the microscope. The sample is obtained by biopsy, usually taken during a short procedure in which a scope is passed into the throat to see the larynx directly.

Under the microscope, the tumor is made up of uniform, similar-looking cells arranged in small nests and cords beneath the surface lining of the larynx. Because these cells can resemble other tumors that occur in the same area, the pathologist confirms the diagnosis with a group of additional tests called immunohistochemistry, described in the next section. Once the diagnosis is confirmed, imaging such as a CT scan or MRI is used to show how far the tumor extends and whether lymph nodes in the neck are involved.

Immunohistochemistry

Immunohistochemistry uses antibodies to detect specific proteins in the tumor cells. For a neuroendocrine tumor, these tests confirm that the cells really are neuroendocrine and separate this tumor from other cancers of the larynx. The results appear on your pathology report as a list of markers, each reported as positive (the protein is present) or negative (it is absent). The markers most often reported are:

INSM1: positive. A protein found in the nucleus of neuroendocrine cells. It has become one of the most reliable markers for confirming that a tumor is neuroendocrine.
Synaptophysin: positive. A protein involved in releasing hormones from neuroendocrine cells. It is one of the standard markers used to confirm the diagnosis.
Chromogranin A: positive. Another protein found in the hormone-containing granules inside neuroendocrine cells, used alongside synaptophysin.
Keratins: positive. Your report may name specific keratins such as CK8/18, CAM5.2, or pancytokeratin. A positive keratin result confirms the tumor arises from epithelial cells (the cells that form linings), which helps separate a neuroendocrine tumor from other tumor types.
Ki-67: reported as a percentage. Unlike the markers above, Ki-67 is not simply positive or negative. It measures the proportion of tumor cells that are actively dividing, and the resulting number, called the Ki-67 labeling index, is used together with the mitotic count to determine the grade of the tumor. Grade is explained in the next section.

Some of these tumors also produce hormones such as serotonin or calcitonin, and your report may mention testing for these. This does not change the diagnosis, but in rare cases hormone production can cause symptoms elsewhere in the body.

Histologic grade

The grade of a neuroendocrine tumor describes how quickly the tumor cells are dividing. It is one of the most important findings on your report, because it helps predict how the tumor is likely to behave. Grade is determined by combining two measurements: the number of dividing cells (called mitotic figures) counted in a set area of tumor, and the Ki-67 labeling index described above. The pathologist also notes whether there is any necrosis, an area of dead tumor tissue.

Neuroendocrine tumors are divided into three grades:

Grade 1 (G1). Fewer than 2 mitotic figures per 2 square millimeters of tumor, a low Ki-67 index, and no necrosis. These are the slowest growing of the three.
Grade 2 (G2). Between 2 and 10 mitotic figures per 2 square millimeters, a Ki-67 index usually below 20%, and sometimes areas of necrosis. These grow more quickly than grade 1 tumors.
Grade 3 (G3). More than 10 mitotic figures per 2 square millimeters or a Ki-67 index above 20%, often with necrosis. These are the fastest growing. Grade 3 neuroendocrine tumors of the larynx are rare, and how they are best classified and treated is still being studied.

It is worth repeating one point here. Even a grade 3 neuroendocrine tumor is a different diagnosis from a neuroendocrine carcinoma, because the cells still look well differentiated under the microscope. If you are uncertain which one your report describes, this is a good question for your doctor.

Perineural invasion

Perineural invasion means that tumor cells are growing along or around a nerve. Nerves run throughout the larynx and neck, and they provide a path that tumor cells can follow, sometimes reaching beyond the visible edge of the tumor. Your report will state whether perineural invasion is present or absent. When present, it is associated with a higher chance of the tumor returning at the original site, and it is one of the findings the treatment team weighs when deciding whether treatment after surgery is needed.

Lymphovascular invasion

Lymphovascular invasion means tumor cells have entered a small blood vessel or lymphatic channel near the tumor. These vessels can carry tumor cells away from where the cancer started. Your report will state whether it is present or absent. When present, it points to a higher chance that tumor cells have reached the lymph nodes in the neck or, less often, traveled elsewhere in the body.

Surgical margins

Margins are the cut edges of the tissue removed during surgery. The goal of surgery is to remove the tumor along with a rim of normal tissue around it, so that no tumor is left behind. The pathologist coats the edges of the removed tissue with ink and examines how close the tumor comes to each edge.

Negative (clear) margin. No tumor cells at the inked edge, with normal tissue separating the tumor from the edge. This suggests the tumor was removed completely.
Close margin. Tumor cells come near the edge without reaching it. This raises the chance of the tumor returning at the same site.
Positive (involved) margin. Tumor reaches the inked edge, meaning some may remain. This is one of the main reasons a treatment team considers further surgery or radiation.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Neuroendocrine tumors of the larynx spread to the lymph nodes in the neck more often than many other laryngeal tumors, so the surgeon frequently removes a group of these nodes at the same time as the tumor, in an operation called a neck dissection. The pathologist examines each node and reports:

How many lymph nodes were examined and how many contained tumor. Usually written as a ratio, such as 2 of 28.
Extranodal extension. This means tumor cells have broken through the outer wall of a lymph node into the surrounding tissue. It is an important finding that raises the nodal stage and often influences whether additional treatment is recommended.

If no tumor is found in any lymph node, your report will say so. This is a favorable finding.

Pathologic stage (pTNM)

The pathologic stage describes how far the tumor has spread, based on the tissue examined under the microscope. It uses the TNM system, which has three parts: T for the size and extent of the primary tumor, N for spread to the lymph nodes in the neck, and M for spread (metastasis) to more distant parts of the body. The letter “p” in front, as in pT and pN, means the stage was determined by examining tissue rather than by imaging alone.

Neuroendocrine tumors of the larynx are staged using the same system as other cancers of the larynx, and the T categories depend on which part of the larynx the tumor started in and how far it has grown.

Tumor stage (pT)

pT1. Tumor is limited to one area of the larynx, and the vocal cords still move normally.
pT2. Tumor has grown into a neighboring area of the larynx or the tissue just beyond it, without fixing the larynx in place.
pT3. Tumor is confined to the larynx but has caused a vocal cord to stop moving, or has grown into certain adjacent tissues.
pT4a. Tumor has grown through the thyroid cartilage or into tissues beyond the larynx, such as the neck muscles, thyroid gland, or esophagus.
pT4b. Tumor has grown into deeper structures and usually cannot be removed completely by surgery.

Nodal stage (pN)

pN0. No tumor found in any lymph node.
pN1. Tumor in a single lymph node on the same side as the tumor, 3 cm or smaller, without extranodal extension.
pN2. Tumor in a larger node, in more than one node, or in nodes on both sides of the neck, in ways set out by the staging system.
pN3. Tumor in a node larger than 6 cm, or a node with extranodal extension.

Your report may not include the M category, because spread to distant parts of the body is usually determined by imaging rather than by the pathologist. Your treatment team combines the pathology findings with your scans to arrive at the overall stage. You can read more in the article on TNM staging.

What is the prognosis for a neuroendocrine tumor of the larynx?

Prognosis means the likely course and outcome of a disease. For a neuroendocrine tumor of the larynx, prognosis depends most on the grade of the tumor, the stage, and whether lymph nodes contain tumor.

Grade 1 tumors generally have the most favorable outlook, with reported five-year survival around 80%. Grade 2 tumors are more often found at a later stage and return after treatment more frequently, with roughly 60% recurring in published series. Because these tumors are rare, the available figures come from small groups of patients followed over many years, so they describe general patterns rather than predicting what will happen for any one person.

Two further points are worth knowing. Neuroendocrine tumors of the larynx spread to lymph nodes in the neck relatively often, and they can also spread to more distant sites, including the liver, skin, and bone, sometimes years after the original treatment. This is the main reason follow-up continues over the long term rather than stopping after a few years.

What happens after the diagnosis?

After the diagnosis is confirmed, your pathology report is reviewed together with your imaging and overall health, usually by a team that includes head and neck surgeons, radiation oncologists, medical oncologists, and pathologists. The report does not decide treatment on its own, but the grade, stage, margins, and lymph node findings all shape the options the team will discuss with you.

Surgery to remove the tumor, often with removal of lymph nodes in the neck, is the main treatment for tumors that can be completely removed. Well differentiated neuroendocrine tumors tend to respond less well to radiation and chemotherapy than neuroendocrine carcinomas do, which is why complete surgical removal is usually the focus. Radiation may still be considered after surgery when the margins are positive or close, when lymph nodes are involved, or when the tumor cannot be fully removed.

Follow-up involves regular examination of the larynx and neck along with imaging. Because these tumors can return or spread many years later, follow-up generally continues long term rather than for a fixed period.

Questions to ask your doctor

Does my report describe a neuroendocrine tumor or a neuroendocrine carcinoma?
What grade is my tumor, and what were the mitotic count and Ki-67 result?
Where in the larynx did the tumor start, and how far had it grown?
Were the surgical margins clear?
Was perineural or lymphovascular invasion found?
How many lymph nodes were removed, and how many contained tumor?
Was extranodal extension present?
What are my pT and pN categories, and what is my overall stage?
Is radiation or any other treatment being considered after surgery?
How will my voice, swallowing, and breathing be affected and supported?
How often will I be followed, and for how long?