by Jason Wasserman MD PhD FRCPC
November 14, 2022
Sinonasal non-keratinizing squamous cell carcinoma (NKSCC) is a type of cancer that starts in the nasal cavity or one of the paranasal sinuses. This area of the body is described as the sinonasal tract, and it includes the maxillary sinus, ethmoid sinus, frontal sinus, and sphenoid sinus. The tumour starts from cells that line the inside surface of the nasal cavity and paranasal sinuses.
Over half of all sinonasal NKSCCs are caused by human papillomavirus (HPV). The virus infects cells that cover the inside surface of the sinonasal tract which over time leads to genetic changes that causes cancer. Tumours not associated with HPV are frequently caused by a genetic change called a fusion, involving two genes – DEK and AFF2. At present, doctors do not know why this genetic alteration occurs. Finally, a small number of sinonasal NKSCCs may arise from a non-cancerous tumour called a sinonasal papilloma.
Symptoms of sinonasal NKSCC include difficulty breathing through the nose, pain over the middle of the face or around the eyes, and recurrent nose bleeds. Unfortunately, these symptoms can also be seen in a variety of other sinonasal tract conditions and so they are not specific to sinonasal NKSCC.
The diagnosis is usually made after a small sample of the tumour is removed in a procedure called a biopsy. The tissue is then sent to a pathologist for examination under the microscope. In some situations, the diagnosis is only made after the entire tumour is removed in a procedure called an excision or resection.
p16 is a protein that is produced by normal cells throughout the body. Compared to normal cells, precancerous and cancerous tumours caused by HPV produce extra p16 which builds up inside the tumour cells. In order to determine if a group of cells has been infected with HPV, pathologists perform a test called immunohistochemistry to see how much p16 protein the cells are making and where the protein is located inside the cell. Sinonasal NKSCCs that are caused by HPV are almost always positive or reactive for p16. Sinonasal NKSCCs caused by other factors are typically negative or non-reactive for p16.
Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphovascular invasion is seen, it will be included in your report.
Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery. If perineural invasion is seen, it will be included in your report.
Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. Lymph nodes are not always removed at the same time as the tumour. However, when lymph nodes are removed, they will be examined under a microscope and the results will be described in your report.
Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.
The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.
Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.
Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.
All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.
In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.
Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. Because sinonasal NKSCC is often removed in multiple pieces, your pathologist may not be able to determine the margin status.
Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.
A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved.
The pathologic stage for sinonasal NKSCC 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 a more advanced disease and a worse prognosis.
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.
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.
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.
Sinonasal NKSCC is given a metastatic 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 metastatic stage cannot be determined and is listed as MX.