This article will help you read and understand your pathology report for sinonasal undifferentiated carcinoma (SNUC).
by Jason Wasserman, MD PhD FRCPC, updated January 5, 2021
When we breathe, air enters our body through our nose and mouth and travels down a long tube called the trachea into our lungs. The inside of the nose is called the nasal cavity and it helps to warm and clean the air before it reaches our lungs. The nasal cavity is surrounded by small paired (there is on each side of the face) air-filled spaces called paranasal sinuses that connect to the nasal cavity by small openings. Because the nasal cavity and sinuses are connected to each other, pathologists describe this area of the body as the sinonasal tract.
The inside of the nasal cavity and the sinuses are lined by specialized epithelial cells that form a barrier called the epithelium. The tissue underneath the epithelium is called stroma and it is made up of blood vessels and small round structures called glands that make a substance called mucin. Pathologists use the word mucosa to describe tissue that includes both the epithelium and the stroma.
Sinonasal undifferentiated carcinoma (SNUC) is a type of cancer that starts from the cells in the epithelium of the sinonasal tract. When examined under the microscope, the cells in sinonasal undifferentiated carcinoma do not look like any of the cells normally found in the epithelium. Pathologists use the word undifferentiated to describe cancer cells that do not look anything like normal, healthy cells.
Sinonasal undifferentiated carcinoma can start in the nasal cavity or any of the surrounding paranasal sinuses. The tumour is often large at the time of diagnosis and symptoms include nose bleeds, pain, congestion, or visual changes.
Sinonasal undifferentiated carcinoma is an aggressive disease with a poor prognosis. The cancer cells in sinonasal undifferentiated carcinoma commonly spread outside of the sinonasal tract into the bones of the jaw, the orbit, and the base of the skull. The cancer cells also commonly travel to lymph nodes and other more distant parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.
Compared to other cancers of the head and neck, very little is known about what causes sinonasal undifferentiated carcinoma although some patients may have received radiation therapy in the past for a different cancer in the same area of the body.
The diagnosis of sinonasal undifferentiated carcinoma is usually made after a small sample of tissue is removed from your body in a procedure called a biopsy. The tissue is then sent to a pathologist who examines it under a microscope. A test called immunohistochemistry is often performed to confirm the diagnosis.
Most patients with sinonasal undifferentiated carcinoma will be treated with radiation although you may be offered surgery first to remove the tumour. If the tumour is removed, it will be sent to a pathologist who will prepare another pathology report. This report will confirm or revise the original diagnosis and provide additional important information such tumour size and spread of tumour cells to lymph nodes. This information is used to determine the cancer stage and to decide if additional treatment is required.
Your pathologist may perform a test called immunohistochemistry on tissue from the tumour before they make the diagnosis of sinonasal undifferentiated carcinoma.
The cancer cells in sinonasal undifferentiated carcinoma are usually positive (reactive) for proteins called keratins including pan-cytokeratin, low molecular weight keratin, and cytokeratin 8/18 (CK8/18).
The cancer cells are usually negative (non-reactive) for cytokeratin 5 (CK5), p40, synaptophysin, and chromogranin although any of these may be described as ‘focally’ positive. Your report may also describe the cancer cells as being negative for p16, EBER, S100, and CD45.
This is the largest dimension of the tumour measured in centimetres. However, tumours from the sinonasal tract are often removed in multiple pieces. As a result, your pathologist may not be able to accurately measure the tumour size. In this case, an approximate tumour size may be described.
Nerves are like long wires made up of groups of cells called neurons. Nerves transmit information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve.
Perineural invasion is important because cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. For this reason, perineural invasion is associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.
Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.
Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.
Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Seeing lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.
A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.
A margin is considered positive when there are cancer cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment. A negative margin means there were no cancer cells at the very edge of the cut tissue.
Because these tumours are often removed in multiple pieces, your pathologist may not be able to reliably assess the margins of the tumour. For that reason, most pathology reports for sinonasal undifferentiated carcinoma do not information about margins.
Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called a metastasis.
Lymph nodes from the neck are sometimes removed at the same time as the main tumour in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination.
Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.
Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.
The number of lymph nodes that contain cancer cells and their location in the body is used to determine the nodal stage (see Pathologic stage below).
A group of cancer cells inside of a lymph node is called a tumour deposit. If a tumour deposit is found, your pathologist will measure the deposit and the largest tumour deposit found will be described in your report.
Larger tumour deposits are associated with worse prognosis. The size of the largest tumour deposit is also used to determine the nodal stage (see Pathologic stage below).
The pathologic stage for sinonasal undifferentiated carcinoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer.
This system uses information about the primary tumour (pT), lymph nodes (pN), and distant metastatic disease (pM) to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and worse prognosis.
Tumour stage (pT) for tumours that start in the nasal cavity or ethmoid sinus
These tumours are given a tumour stage between 1 and 4. The tumour stage is based on how far the tumour has spread outside of the nasal cavity or ethmoid sinus.
Tumour stage (pT) for tumours that start in the maxillary sinus
These tumours are given a tumour stage between 1 and 4. The tumour stage is based on how far the tumour has spread outside of the maxillary sinus.
Nodal stage (pN) for tumours that start in the nasal cavity or paranasal sinuses
These tumours are given a nodal stage between 0 and 3 based on the following three features:
The nodal stage will be higher if any of the tumour deposits are larger than 3 cm, more than one lymph node contains cancer cells, cancer cells are found in lymph nodes on both sides of the neck, and if any of the lymph nodes show extranodal extension.
If no cancer cells are found in any of the lymph nodes examined, the nodal stage is N0.
If no lymph nodes are submitted for pathological examination, the nodal cannot be determined and the stage is listed as NX.
Metastatic stage (pM) for sinonasal undifferentiated carcinoma
Sinonasal undifferentiated carcinoma is given an metastasis stage (pM) of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastasis stage cannot be determined and is listed as MX.