A neuroendocrine tumor (NET) of the sinonasal tract and paranasal sinuses 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 behave in different ways, from slow-growing to fast-growing, depending mainly on the tumor’s grade. This article describes a well-differentiated neuroendocrine tumor composed of relatively organized, mature-looking cells. It is a different tumor from sinonasal neuroendocrine carcinoma (NEC), which is made up of more poorly organized cells and behaves differently. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.
The exact cause of a neuroendocrine tumor of the sinonasal tract and paranasal sinuses is not clearly understood. Unlike some other cancers of the nasal cavity and sinuses, there is no strong link to common risk factors such as smoking or alcohol use, and no specific environmental or inherited cause has been identified. Because these tumors are rare, research is ongoing to understand the factors that lead to their development.
The symptoms of a neuroendocrine tumor of the sinonasal tract and paranasal sinuses often resemble those of more common conditions affecting the nasal cavity and sinuses. Common symptoms include nasal blockage or congestion, nosebleeds, facial pain or pressure, a reduced sense of smell, and swelling or a mass in the nasal area. If the tumor grows large enough to affect the eye, it can cause vision changes. Because these symptoms overlap with everyday conditions such as sinus infections, it is important to see a healthcare provider if they persist.
The diagnosis of a neuroendocrine tumor of the sinonasal tract and paranasal sinuses is made after a tissue sample is examined under the microscope by a pathologist. The sample is usually obtained through a biopsy taken from the tumor. Under the microscope, the tumor consists of uniform (similar-looking) neuroendocrine cells arranged in small groups, nests, cords, or strands, usually lying beneath the lining of the nasal cavity or sinus. The cells have a pale, grainy cytoplasm and round, uniform nuclei with a fine, speckled pattern that pathologists describe as “salt and pepper.” The supporting tissue around the tumor often contains many blood vessels.
Additional tests help confirm the diagnosis. Immunohistochemistry, a test that uses specially labeled antibodies to detect proteins in the tumor cells, typically shows that the tumor is positive for neuroendocrine markers such as INSM1 (a protein found in the nucleus), synaptophysin, and chromogranin, as well as cytokeratins such as CK8/18 and CAM5.2. Some tumors also produce hormone-like substances such as serotonin or calcitonin. A test called Ki-67 is used to estimate how quickly the tumor cells are dividing, which helps determine the tumor’s grade. 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.
The grade of a neuroendocrine tumor of the sinonasal tract and paranasal sinuses describes how quickly the tumor cells are dividing, which helps predict how the tumor is likely to behave and guides treatment decisions. The grade is based mainly on the number of dividing cells (mitotic figures) seen in a set area of tumor, the Ki-67 labeling index (the percentage of dividing cells), and whether tumor necrosis (cell death) is present. Well-differentiated neuroendocrine tumors are divided into three grades.
A biomarker is a feature of the tumor, often a protein, that provides information beyond the diagnosis itself, such as how the tumor may respond to a particular treatment. For a well-differentiated neuroendocrine tumor of the sinonasal tract and paranasal sinuses, the most useful biomarker is a protein called somatostatin receptor 2.
Somatostatin receptor 2 (SSTR2) is a protein found on the surface of most well-differentiated neuroendocrine tumor cells. It is important because it can be targeted for both imaging and treatment. For imaging, a scan called Ga-68 DOTATATE PET uses a tracer that binds to SSTR2, which helps doctors locate the tumor, assess spread, and detect recurrence after treatment. For treatment, drugs called somatostatin analogs (such as octreotide and lanreotide) attach to SSTR2 and can help control symptoms caused by hormone production and slow tumor growth. In selected patients with advanced or spreading disease, a therapy called peptide receptor radionuclide therapy (PRRT), using a drug such as Lu-177 DOTATATE, attaches to SSTR2 and delivers radiation directly to the tumor cells. These approaches are well established for well-differentiated neuroendocrine tumors that start in other parts of the body and may be considered for sinonasal tumors as well.
SSTR2 can be assessed in tumor tissue using immunohistochemistry, and its activity can also be demonstrated on DOTATATE PET imaging. Your report or imaging results will describe whether the tumor expresses SSTR2, which helps guide whether somatostatin-receptor-based imaging or therapy may be useful. You can read more in the Biomarkers and Molecular Testing section.
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.
Lymph nodes are small immune organs found throughout the head and neck. A neuroendocrine tumor of the sinonasal tract and paranasal sinuses can spread through lymphatic vessels to reach these nodes, although this is uncommon for low-grade (G1) tumors and more likely with higher-grade tumors. When lymph nodes are removed, sometimes in a procedure called a neck dissection, 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 tumor cells, and the size of the largest deposit. A node that contains tumor cells is described as “positive,” and a node with no tumor cells is described as “negative.” The pathologist may also check for extranodal extension, which means tumor cells have broken through the outer capsule of a lymph node into the surrounding tissue. Lymph node involvement, along with the finding of tumor cells spreading to other parts of the body (metastasis), influences decisions about additional treatment.
Because a neuroendocrine tumor of the sinonasal tract and paranasal sinuses is rare, there is no single staging system for it that is accepted everywhere. Instead, the stage is based on how far the tumor has spread: whether it is confined to where it started, has grown into nearby structures such as the sinuses, orbit, or base of the skull, or has spread to lymph nodes or distant organs (most often the liver). Staging combines the pathology findings with imaging studies, which may include CT, MRI, and DOTATATE PET. Your treatment team will explain how the extent of your tumor affects your treatment plan.
Prognosis refers to the likely long-term outcome after a diagnosis. For a neuroendocrine tumor of the sinonasal tract and paranasal sinuses, the outlook depends most strongly on the tumor’s grade and how far it has spread.
Because these tumors are rare and vary widely in behavior, individual outcomes can differ significantly, and long-term follow-up is important.
Treatment for a neuroendocrine tumor of the sinonasal tract and paranasal sinuses is planned by a multidisciplinary team that may include ear, nose, and throat (ENT) surgeons, neurosurgeons for tumors near the base of the skull, radiation oncologists, and medical oncologists. The approach is guided by the grade, stage, and location of the tumor, along with the specific findings in the pathology report.
Surgery is the main treatment for tumors that can be removed, and complete removal with clear margins offers the best chance of controlling low-grade tumors. Radiation therapy may be added, particularly for higher-grade tumors or when margins are positive or close, and these specific findings directly inform that decision. For tumors that express somatostatin receptor 2, somatostatin analogs (such as octreotide and lanreotide) may help control symptoms and slow tumor growth, and in advanced or spreading disease, somatostatin-receptor-targeted therapy (PRRT) may be considered. Chemotherapy may be used for higher-grade or advanced tumors. After treatment, long-term follow-up with imaging and physical examination is important, because these tumors can return or spread years later.