Neuroendocrine tumor of the sinonasal tract and paranasal sinuses

by Jason Wasserman MD PhD FRCPC
April 2, 2025

A neuroendocrine tumor (NET) is a rare type of cancer that arises from neuroendocrine cells in the nasal cavity or sinuses. Neuroendocrine cells normally produce hormones in response to nerve signals. Tumors formed by these cells can vary widely in their behavior, from slow-growing to highly aggressive.

What are the symptoms of a neuroendocrine tumor of the sinonasal tract and paranasal sinuses?

Symptoms of these tumors often resemble other, more common conditions affecting the nasal cavity and sinuses.

Common symptoms include:

• Nasal blockage or congestion.
• Nosebleeds.
• Facial pain or pressure.
• Reduced sense of smell.
• Swelling or mass in the nasal area.
• Vision changes if the tumor grows large enough to affect the eyes.

It’s important to see a healthcare provider if you experience these symptoms persistently.

What causes a neuroendocrine tumor of the sinonasal tract and paranasal sinuses?

The exact cause of neuroendocrine tumors in the sinonasal tract and sinuses is not clearly understood. There is no strong link to common risk factors like smoking or alcohol use, and no specific environmental or genetic cause has been identified. Ongoing research continues to look for potential factors that might contribute to their development.

How is this diagnosis made?

A diagnosis of a neuroendocrine tumor is typically made through the examination of a biopsy (tissue sample) taken from the tumor. A pathologist examines this sample under a microscope to identify the characteristic features of neuroendocrine tumors. Additional specialized tests called immunohistochemistry are often used to confirm the diagnosis.

What does this tumor look like under the microscope?

Microscopically, these tumors are composed of uniform (similar-looking) neuroendocrine cells arranged in small groups or nests, cords, or strands. The cells have a pale, grainy appearance, abundant cytoplasm, and round, uniform nuclei displaying a typical “salt-and-pepper” pattern. The tumor cells generally lie beneath the lining of the nasal cavity or sinus. The supporting tissue around the tumor often contains many blood vessels and can appear dense or scarred. The tumor cells usually do not show significant variation in shape or size.

What other tests may be ordered to confirm the diagnosis?

Pathologists often perform additional tests known as immunohistochemistry to confirm the diagnosis. Neuroendocrine tumors typically test positive for specific proteins, including INSM1 (a nuclear protein), synaptophysin, chromogranin A, and keratins such as CK8/18 and CAM5.2. Occasionally, these tumors produce substances like serotonin, calcitonin, or other hormones. Another test, Ki-67, helps determine how rapidly the tumor cells divide to create new tumor cells.

Histologic grade

Histologic grade describes how aggressive the tumor cells appear under a microscope, which helps guide treatment decisions and predict outcomes. Neuroendocrine tumors of the sinonasal tract and sinuses are divided into three grades: grade 1 (G1), grade 2 (G2), and grade 3 (G3).

Neuroendocrine tumour, grade 1 (G1)

G1 tumors are the least aggressive, slow-growing tumors. Under the microscope, they typically have fewer than two mitotic figures (dividing cells) per 2 mm² and no necrosis (cell death). The Ki-67 labeling index shows a low proliferation rate.

Neuroendocrine tumour, grade 2 (G2)

G2 tumors grow more rapidly and have between 2 and 10 mitotic figures (dividing cells) per 2 mm², sometimes with areas of necrosis. They usually show a higher Ki-67 labeling index than G1 tumors but typically less than 20%.

Neuroendocrine tumour, grade 3 (G3)

G3 tumors are the most aggressive and rapidly growing, displaying higher rates of cell division and extensive necrosis. The precise characteristics of G3 tumors in the sinonasal area are still being studied, and their classification continues to evolve.

What is the prognosis for someone diagnosed with a neuroendocrine tumor of the sinonasal tract and paranasal sinuses?

The prognosis for these tumors varies based on the tumor grade. Low grade (G1) tumors have a relatively good prognosis, especially when completely removed surgically. However, higher grade tumors (G2 and G3) are more aggressive, frequently presenting with advanced disease, and have a higher likelihood of recurrence after treatment. These cases often require extensive surgery and additional therapy, such as radiation or chemotherapy. Regular monitoring is important because of the potential for recurrence and distant metastasis (spread), especially to areas like the liver. Due to the rarity and variability of these tumors, individual outcomes can vary significantly.