Olfactory neuroblastoma

by Jason Wasserman MD PhD FRCPC
March 7, 2022

What is olfactory neuroblastoma?

Olfactory neuroblastoma is a type of cancer that starts from cells normally found in a part of the nasal cavity called the cribriform plate (an area at the top of the nasal cavity and near the base of the skull). As the tumour grows it can extend into the paranasal sinuses, orbit (the space around the eye), and the bones near the base of the skull. Olfactory neuroblastoma is considered a type of neural tumour because the cells in the cribriform plate are part of the nervous system.

How do pathologists make the diagnosis of olfactory neuroblastoma?

The diagnosis of olfactory neuroblastoma is typically made after a small tissue sample is removed in a procedure called a biopsy. The diagnosis can also be made after most of the tumour is removed in a procedure called a resection. Because of the complex anatomy of the nasal cavity and paranasal sinuses, this procedure usually involves removing the tumour in multiple pieces or specimens. The tissue is then sent to a pathologist who examines it under the microscope.

What does olfactory neuroblastoma look like under the microscope?

Most olfactory neuroblastomas are made up of medium-sized cells, arranged in round groups that pathologists describe as nests or lobules. Larger groups of cells are called sheets. A specialized type of cell called a sustentacular cell may be seen surrounding the groups of tumour cells.

The nucleus of the tumour cell (the part that holds the genetic material) is usually round and the chromatin (genetic material) inside the nucleus is often described as granular or having a ‘salt and pepper appearance. Occasionally, the tumour cells may be arranged in rings with thin cellular processes pointing towards the centre of the ring. These rings are called Homer Wright rosettes (or pseudorosettes) and the thin cellular processes are a type of neural tissue called neuropil.

More aggressive tumours may show additional features such as mitoses (tumour cells that are dividing to create new tumour cells), necrosis (dead tumour cells), and pleomorphism (tumour cells that vary in shape and size). The tumour cells may also be arranged in round gland-like structures called Flexner–Wintersteiner rosettes. These rosettes are different from Homer Wright rosettes in that the centre of the round structure is open and there is no neuropil.

Pathologists often perform a test called immunohistochemistry to confirm the diagnosis. This test uses a probe that allows pathologists to see chemicals called proteins inside cells. When immunohistochemistry is performed, the tumour cells in olfactory neuroblastoma are usually positive (reactive) for proteins such as chromogranin, synaptophysin, and neuron-specific enolase (NSE) while the sustentacular cells are positive for S100. Some tumours may produce a small amount of protein called cytokeratin which is normally found in epithelial cells. Because the production of this protein is only seen in small areas of the tumour, it is usually described as being focal.

What is Hyams grade?

The Hyams grade is a system that divides olfactory neuroblastomas into four levels or grades in order to help predict how the tumour will behave over time. Hyams grade 1 and 2 tumours are called low-grade while Hyams grade 3 and 4 tumours are called high-grade. The Hyams grade is important because higher grade (grade 3 and 4) tumours are more likely to grow into areas of the head outside of the nasal cavity and to spread to other parts of the body.

In order to determine the Hyams grade, pathologists look for the following six microscopic features: pattern of growth, mitoses (tumour cells dividing to create new tumour cells), necrosis (dead or dying tumour cells), pleomorphism (tumour cells that vary in size and shape), neuropil, and rosettes. Low-grade olfactory neuroblastomas will typically be growing in round nests or lobules but will have very few mitoses, no necrosis, and very little pleomorphism. Low-grade tumours will also contain some neuropil and may have Homer Wright rosettes. High-grade olfactory neuroblastomas often grow in large sheets and with mitoses, necrosis, and pleomorphism. High-grade tumours also contain less neuropil and Flexner–Wintersteiner rosettes may be seen.