Olfactory Neuroblastoma: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
July 13, 2026

Olfactory neuroblastoma is a rare type of cancer that starts from the specialized cells high in the nasal cavity that detect odors and send smell-related signals to the brain. It usually begins near the roof of the nasal cavity, close to a thin bone called the cribriform plate, which separates the nose from the brain, and it may also involve the superior turbinate and the upper part of the nasal septum. As the tumor grows, it can extend into nearby structures such as the paranasal sinuses, the orbit (eye socket), and, in some cases, the cranial cavity. Olfactory neuroblastoma is also known as esthesioneuroblastoma. Its behavior varies from slow-growing to fast-growing depending mainly on its microscopic grade.

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 olfactory neuroblastoma?

Olfactory neuroblastoma develops from the olfactory neuroepithelium, the specialized nerve tissue high in the nasal cavity responsible for the sense of smell. What causes these cells to become cancerous is not known, and there are no established environmental or inherited risk factors. The tumor can occur at almost any age, but it is most often diagnosed in adults.

What are the symptoms?

The most common symptom of olfactory neuroblastoma is nasal obstruction, meaning one side of the nose feels blocked. Many people also have nosebleeds, nasal discharge, or facial pressure or pain. Because the tumor starts in the area responsible for smell, growth into the cribriform plate can cause loss of smell (anosmia). If the tumor grows toward the eye, it can cause eye pain, bulging of the eye (proptosis), double vision, or excessive tearing, and growth into the frontal sinus can cause headaches. If the tumor blocks the Eustachian tube, some people develop ear pressure, pain, or recurrent middle ear infections. Rarely, olfactory neuroblastoma produces hormone-like substances that cause paraneoplastic syndromes, such as abnormal cortisol production or low sodium levels.

How is the diagnosis made?

The diagnosis of olfactory neuroblastoma is made using a combination of imaging and tissue examination. Imaging defines the tumor’s location and how far it has spread, while examining a tissue sample under the microscope confirms the diagnosis. Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used; MRI is especially helpful for showing whether the tumor has extended into the orbit or the space around the brain, while CT is better for showing bone erosion, including involvement of the cribriform plate. Because many olfactory neuroblastomas carry a protein called somatostatin receptor 2 on their surface, a functional imaging scan called Ga-68 DOTATATE PET can also be used to detect the tumor, find recurrence, or assess spread (this is described further in the biomarker section below).

The diagnosis is confirmed by examining a biopsy under the microscope by a pathologist. Olfactory neuroblastoma typically forms nests, lobules, or sheets of small, round tumor cells beneath the surface lining of the nose. The cells often have a fine, speckled pattern in the nucleus that pathologists describe as “salt and pepper,” a common appearance in neuroendocrine tumors. A helpful feature is a delicate, fibrillary background called the neuropil, composed of interconnecting extensions of the tumor cells. Some tumors contain circular arrangements of cells called rosettes; a specific type known as a Homer Wright pseudorosette, formed around a center of neuropil, strongly supports the diagnosis when seen in the nasal cavity.

Additional tests help confirm the diagnosis and rule out other tumors. Immunohistochemistry, a test that uses specially labeled antibodies to detect proteins in the tumor cells, typically shows that olfactory neuroblastoma is positive for neuroendocrine markers such as synaptophysin and chromogranin. A characteristic finding is a rim of S100-positive supportive cells, called sustentacular cells, around the edges of the tumor nests. Some tumors show focal staining for cytokeratins, which can make the diagnosis more challenging, as other sinonasal tumors can also show this feature. A marker called Ki-67 estimates how quickly the tumor cells are dividing and often reflects the tumor’s grade. Because several other sinonasal tumors can look similar, the pathologist uses the microscopic appearance together with these stains to exclude other diagnoses, such as neuroendocrine tumors, sinonasal undifferentiated carcinoma, lymphoma, and rhabdomyosarcoma.

Histologic grade

Olfactory neuroblastoma is graded using the Hyams grading system, which describes how the tumor cells look under the microscope and provides important information about how the tumor is likely to behave. The Hyams system divides tumors into four grades (I to IV) based on how the tumor is arranged, how abnormal the cells look, how quickly they divide, and whether tumor cell death is present. Grades I and II are considered low grade, while grades III and IV are considered high grade. Because the grade strongly influences prognosis and treatment planning, the Hyams grade is an essential part of the pathology report.

Low grade (Hyams grades I and II) — The tumor grows in an orderly, lobular pattern (divided into rounded nests of cells), and the cells look relatively uniform. Cell division is absent or limited, and there is no tumor necrosis (cell death). The fibrillary background (neuropil) is prominent, and Homer Wright pseudorosettes are often seen. These features indicate a more mature, better-differentiated tumor and are associated with a more favorable outlook.
High grade (Hyams grades III and IV) — The tumor still grows in a lobular pattern, but the cells look much more abnormal, with prominent to marked pleomorphism (variation in size and shape). Cell division is more frequent, and the fibrillary background becomes minimal or absent. A different type of rosette, called a Flexner–Wintersteiner rosette, is more common, and areas of necrosis may be present in grade III and are common in grade IV. High-grade tumors are less organized and are more likely to spread to lymph nodes or distant sites.

Biomarker and molecular testing

A biomarker is a feature of the tumor, often a protein or gene change, that provides information beyond the diagnosis itself, such as how the tumor may respond to a particular treatment. For olfactory neuroblastoma, the most useful biomarker is the somatostatin receptor 2.

Somatostatin receptor 2 (SSTR2)

Somatostatin receptor 2 (SSTR2) is a protein found on the surface of many olfactory neuroblastoma cells, as well as on other neuroendocrine tumors. 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, in selected patients with advanced or recurrent disease, peptide receptor radionuclide therapy (PRRT) may be considered. PRRT uses a drug such as Lu-177 DOTATATE that attaches to SSTR2 and delivers radiation directly to the tumor cells. This approach is well established for other neuroendocrine tumors and is an emerging option in olfactory neuroblastoma.

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.

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 olfactory neuroblastoma arises close to the base of the skull, it is sometimes removed in more than one piece, and the pathologist may not always be able to fully assess the margins.

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. Olfactory neuroblastoma can spread through lymphatic vessels to reach the lymph nodes in the neck. This is more common with high-grade tumors than with low-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 cancer cells, and the size of the largest deposit of cancer cells. A node that contains cancer cells is described as “positive,” and a node with no cancer cells is described as “negative.” The pathologist may also check 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 involvement, along with evidence of cancer cells spreading to other parts of the body (metastasis), is an important factor in staging and decisions about additional treatment.

Staging

Because olfactory neuroblastoma is uncommon and arises in a specific location, it is not staged using the TNM system used for most other cancers, and no single staging system is accepted everywhere. The most commonly used system is the Kadish staging system, which is based on how far the tumor has spread. Staging combines the pathology findings with imaging results.

Kadish A — The tumor is confined to the nasal cavity.
Kadish B — The tumor extends into one or more of the paranasal sinuses.
Kadish C — The tumor extends beyond the sinuses into nearby structures such as the orbit or the cranial cavity.
Kadish D — Added in a modified version of the system, this describes tumors that have spread to lymph nodes or to distant parts of the body.

Other staging systems also exist. Some separate tumors based on whether the sphenoid sinus is involved, whether the tumor extends into the brain, and whether lymph node or distant spread is present. Your treatment team will explain which system applies to your situation.

What is the prognosis?

Prognosis refers to the likely long-term outcome after a diagnosis. For olfactory neuroblastoma, the outlook is generally favorable compared with many other cancers of the nasal cavity and sinuses, and it depends most strongly on the tumor’s grade and stage. Reported five-year survival rates vary but are often in the range of 60 to 80 percent overall, and are higher for low-grade, early-stage tumors.

Hyams grade — Low-grade tumors (Hyams I and II) are less likely to spread and have better long-term survival than high-grade tumors (Hyams III and IV).
Stage — Tumors confined to the nasal cavity (Kadish A) have a more favorable outlook than tumors that have spread to the sinuses, orbit, cranial cavity, lymph nodes, or distant sites.
Lymph node spread — Cancer found in the lymph nodes of the neck is associated with a higher risk and occurs more often with high-grade tumors.

Because olfactory neuroblastoma can return many years after treatment, long-term follow-up is important.

What happens after the diagnosis?

Treatment for olfactory neuroblastoma is planned by a multidisciplinary team that may include ear, nose, and throat (ENT) surgeons, neurosurgeons (because the tumor arises near the base of the skull), radiation oncologists, and medical oncologists. The approach is guided by the grade, stage, and location of the tumor, as well as the specific findings in the pathology report.

Surgery is the main treatment for most tumors that can be removed, often performed endoscopically through the nose or, for tumors that reach the skull base, through a combined approach with neurosurgery. The goal is complete removal with clear margins. Radiation therapy is frequently given after surgery, particularly for higher-grade or more advanced tumors or when margins are positive or close, and these specific findings directly inform that decision. Chemotherapy may be added for high-grade or advanced disease. In selected patients with advanced or recurrent tumors that express somatostatin receptor 2, somatostatin-receptor-targeted therapy (PRRT) may be considered. After treatment, long-term follow-up with imaging and physical examination is important, because this tumor can return years later.

Questions to ask your doctor

Where in my nasal cavity did the tumor start, and does it involve the cribriform plate?
Has the tumor grown into my sinuses, orbit, or the area around the brain?
What is the Hyams grade of my tumor, and is it low grade or high grade?
What stage is my tumor using the Kadish system or another staging system?
Were the surgical margins negative, and does the report suggest the tumor was completely removed?
Were lymph nodes examined, and did any contain cancer cells?
Does my tumor express somatostatin receptor 2, and could DOTATATE imaging or PRRT be useful for me?
Will I need radiation therapy or chemotherapy after surgery, and which findings influenced that recommendation?
Do I need imaging of my neck or body to look for spread?
How will I be monitored after treatment, and for how long, to check for recurrence?