by Jason Wasserman MD PhD FRCPC
December 19, 2025
Olfactory neuroblastoma is a rare type of cancer that starts in cells normally found high in the nasal cavity. These cells play a role in detecting odors and sending smell-related signals to the brain. This tumour 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.
Where is olfactory neuroblastoma found?
Olfactory neuroblastoma arises in a particular region at the top of the nasal cavity, including the area near the cribriform plate, the superior turbinate, and the upper part of the nasal septum. Tumours that appear to arise entirely outside this region are very uncommon, and in those situations, doctors usually consider other diagnoses before concluding it is olfactory neuroblastoma.
As the tumour grows, it can extend into nearby structures such as the paranasal sinuses, the orbit (eye socket), and, in some cases, the cranial cavity.
What are the symptoms of olfactory neuroblastoma?
The most common symptom is nasal obstruction, meaning one side of the nose feels blocked. Many patients also experience nosebleeds, nasal discharge, or facial pressure or pain.
Symptoms can also occur if the tumour grows into nearby areas. Extension into the cribriform plate can cause loss of smell (anosmia). Growth toward the eye can cause eye pain, bulging of the eye (proptosis), double vision, or excessive tearing. If the tumour blocks the Eustachian tube, some people develop ear pressure, pain, or recurrent middle-ear infections. Tumour extension into the frontal sinus can cause headaches.
Rarely, olfactory neuroblastoma produces hormone-like substances that lead to paraneoplastic syndromes such as abnormal cortisol production or low sodium levels.
How is the diagnosis made?
Doctors use a combination of imaging studies and tissue examination to diagnose olfactory neuroblastoma. Imaging helps define the tumour’s location and extent of spread, while pathology confirms the diagnosis.
Imaging
Computed tomography and magnetic resonance imaging are commonly used. Magnetic resonance imaging is especially helpful for showing tumour extension into the orbit or intracranial space. Computed tomography is better for evaluating bone erosion, including whether the tumour involves the cribriform plate or nearby bony structures. Imaging may show characteristic findings such as small peripheral cysts and speckled calcifications.
Many olfactory neuroblastomas express somatostatin receptors, which are proteins on the tumour cells. For this reason, functional imaging such as Ga-68 DOTATATE positron emission tomography can help detect disease, recurrence, or spread, and may also help guide therapy in selected cases.
Biopsy and microscopic features
The diagnosis is confirmed by examining a biopsy under the microscope. Olfactory neuroblastoma typically forms nests, lobules, or sheets of small, round tumour cells beneath the surface lining of the nose. The tumour cells often have “salt and pepper” chromatin, which is a common appearance in neuroendocrine tumours.
A key feature is the presence of a delicate, fibrillary background called neuropil, which represents interconnecting processes from tumour cells. Some tumours show structures called rosettes. Homer Wright pseudorosettes with neuropil are especially supportive of the diagnosis when seen in the nasal cavity.
High-grade tumours tend to grow in more solid sheets and show more abnormal-looking nuclei, more cell division, and areas of tumour necrosis (cell death). Sustentacular cells, which are supportive cells around the tumour nests, may be reduced or absent in higher-grade tumours.
Immunohistochemistry
Immunohistochemistry uses special stains to look for proteins in tumour cells. Olfactory neuroblastoma typically shows positive staining for neuroendocrine markers such as synaptophysin and chromogranin. A helpful feature is a peripheral pattern of S100 staining in sustentacular cells.
Some tumours show focal pancytokeratin staining, which can make diagnosis more challenging because other sinonasal tumours can also exhibit overlapping staining patterns. Another marker, Ki-67, helps estimate how quickly tumour cells divide and often correlates with tumour grade. Olfactory neuroblastoma also commonly expresses somatostatin receptor 2.
Because many other tumours in the sinonasal area can look similar under the microscope, pathologists use the microscopic pattern, together with immunohistochemical analysis, to exclude other diagnoses, such as neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, lymphoma, rhabdomyosarcoma, and others.
Tumor grade
Olfactory neuroblastoma is commonly graded using the Hyams grading system. Grading describes how the tumour cells look under the microscope and provides essential information about how aggressive the tumour is likely to be.
The Hyams system divides tumours into four grades (I to IV). Grades I and II are considered low-grade, while grades III and IV are considered high-grade. The grade is based on several microscopic features, including how the tumour is arranged, how abnormal the cells look, how quickly they are dividing, and whether there is tumour cell death.
Low-grade tumours (Hyams grades I and II)
Low-grade olfactory neuroblastomas tend to grow in an orderly, lobular pattern, meaning the tumour is divided into rounded nests or groups of cells. The tumour cells look relatively uniform, with little to moderate variation in size and shape.
In these tumours, cell division is absent or limited, and areas of tumour necrosis (cell death) are not seen. A supportive background called a fibrillary matrix, which reflects normal nerve-like connections between cells, is prominent or clearly present.
Special microscopic structures called Homer-Wright pseudorosettes are often seen. These features indicate a more mature, better-differentiated tumour and are associated with a more favorable prognosis.
High-grade tumours (Hyams grades III and IV)
High-grade olfactory neuroblastomas also grow in a lobular pattern, but the cells appear much more abnormal. The nuclei show prominent to marked pleomorphism, meaning there is significant variation in size, shape, and appearance.
Cell division is more frequent, ranging from clearly increased to marked. The fibrillary background seen in low-grade tumours becomes minimal or completely absent, reflecting loss of normal maturation.
These tumours more commonly show Flexner–Wintersteiner rosettes rather than Homer-Wright pseudorosettes. Areas of tumour cell death may be present in grade III tumours and are common in grade IV tumours.
Overall, high-grade tumours look less organized, grow more aggressively, and are more likely to spread to lymph nodes or distant sites.
Because tumour grade strongly influences prognosis and treatment planning, the Hyams grade is an essential part of the pathology report.
How do doctors stage olfactory neuroblastoma?
Several staging systems are used, and no single system is accepted everywhere. The most commonly used system is the Kadish staging system.
Kadish A describes tumours confined to the nasal cavity. Kadish B includes tumours that extend into the paranasal sinuses. Kadish C includes tumours that extend beyond the sinuses into nearby structures such as the orbit or cranial cavity. A modified version adds Kadish D for tumours with lymph node or distant spread.
Other staging systems separate tumours based on whether the sphenoid sinus is involved, whether the tumour extends into the brain, and whether lymph node or distant metastases are present.
What is the prognosis for a person with olfactory neuroblastoma?
Prognosis depends most strongly on the stage and the microscopic grade. Higher-grade tumours are more likely to spread to lymph nodes or distant sites and have lower overall survival rates than lower-grade tumours.
In published studies, spread to lymph nodes in the neck occurs more often in high-grade tumours than in low-grade tumours. Distant metastases are also more common in high-grade tumours. Long-term survival is better for patients with low-grade tumours compared with those with high-grade tumours.
Questions to ask your doctor
- Where in my nasal cavity did the tumour start, and does it involve the cribriform plate?
- Has the tumour grown into my sinuses, orbit, or brain region?
- What is the Hyams grade of my tumour?
- What stage is my tumour using the Kadish system or another staging system?
- Do I need imaging of my neck or body to look for spread?
- How will I be monitored after treatment to check for recurrence?
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