SMARCA4-deficient sinonasal carcinoma is a rare, fast-growing type of cancer that starts in the nasal cavity or the sinuses. The tumor cells have lost a protein called SMARCA4, also known as BRG1. Pathologists confirm the diagnosis by showing that this protein is missing from the tumor cells.
SMARCA4-deficient sinonasal carcinoma is one of two types of SWI/SNF complex-deficient sinonasal carcinoma. The other, more common type is SMARCB1-deficient sinonasal carcinoma. Before testing for SMARCA4 became available, many of these tumors were diagnosed as neuroendocrine carcinoma, sinonasal undifferentiated carcinoma, or teratocarcinosarcoma.
This article explains what SMARCA4-deficient sinonasal carcinoma is, how the diagnosis is confirmed, and what the findings in your pathology report mean for your care.
SMARCA4-deficient sinonasal carcinoma is found in adults, usually in their early 40s, although it has been reported from the age of 20 to the late 60s. People with this tumor tend to be younger than people with other carcinomas of the nose. About 2 in 3 people with SMARCA4-deficient sinonasal carcinoma are men.
The tumor most often starts in the nasal cavity. By the time it is found, it often extends into the nearby sinuses.
SMARCA4-deficient sinonasal carcinoma is caused by changes in the gene that makes the SMARCA4 protein. SMARCA4 is part of a group of proteins called the SWI/SNF complex. This complex controls which genes in a cell are switched on or off by loosening or tightening the way DNA is packed.
SMARCA4 normally acts as a tumor suppressor, meaning it helps stop cells from growing out of control. In this tumor, both copies of the gene are damaged, so the cell can no longer make the protein. These changes develop in the tumor cells during a person’s life, and no clear risk factors have been identified.
The symptoms of SMARCA4-deficient sinonasal carcinoma are caused by a mass growing inside the nose and sinuses. Because the tumor grows quickly, symptoms can appear and worsen over a short time. Common symptoms include:
The diagnosis of SMARCA4-deficient sinonasal carcinoma is made after tissue from the tumor is examined under the microscope by a pathologist. An ear, nose, and throat surgeon usually takes a biopsy during nasal endoscopy, using a thin camera passed through the nostril.
Under the microscope, SMARCA4-deficient sinonasal carcinoma is made of solid sheets and nests of cancer cells that do not look like any normal tissue in the nose. In most tumors the cells are large, but in some they are small and dark. Large areas of dead tumor, called necrosis, are common. The cells do not form glands or other structures that would show what kind of tissue they came from, a feature described as undifferentiated.
Because these features overlap with several other cancers of the nose, the diagnosis is confirmed with immunohistochemistry. The key result is the loss of SMARCA4 from the tumor cells, as described in the next section. Some laboratories also confirm the gene change with next-generation sequencing (NGS).
Once the diagnosis is confirmed, CT and MRI scans of the head and neck show how far the tumor has spread. Scans of the chest or a PET scan may also be used to look for spread to other parts of the body.
Immunohistochemistry is the main test used to diagnose SMARCA4-deficient sinonasal carcinoma. Immunohistochemistry uses antibodies to show which proteins are present in the tumor cells. The pathologist confirms that SMARCA4 is missing and uses other stains to rule out cancers that can look similar. Results that may appear in your report include:
Laboratories use different panels, and not every report will include every stain.
Teratocarcinosarcoma is another rare cancer of the nose and sinuses. It contains a mixture of tissues, including immature cells that look like developing nerve tissue, glands, and cartilage or bone. Most teratocarcinosarcomas have also lost SMARCA4.
Because of this shared change, pathologists think SMARCA4-deficient sinonasal carcinoma and teratocarcinosarcoma may be closely related. A SMARCA4-deficient sinonasal carcinoma shows only cancer cells without these mixed tissues. If your report mentions teratocarcinosarcoma, your pathologist can explain how it relates to your diagnosis.
SMARCA4-deficient sinonasal carcinoma is also different from SMARCA4-deficient undifferentiated tumor of the lung. That tumor has lost the same protein but starts in the chest.
SMARCA4-deficient sinonasal carcinoma is not given a histologic grade. Many carcinomas are graded as well, moderately, or poorly differentiated, depending on how much they resemble normal tissue. This tumor is defined by its missing protein rather than by how it looks, and it behaves as a high-grade cancer.
The College of American Pathologists (CAP) protocol for the nasal cavity and sinuses notes that some newer tumor types, defined by specific genetic changes, do not need a grade. Your report may therefore say that grade is not applicable, or it may not mention grade at all.
Perineural invasion means cancer cells are seen along or inside a nerve. In SMARCA4-deficient sinonasal carcinoma, nerves near the skull base can give the tumor a path to spread toward the brain. Your report will say whether perineural invasion was identified, not identified, or could not be determined.
Lymphovascular invasion means cancer cells are seen inside a blood vessel or lymphatic channel. In SMARCA4-deficient sinonasal carcinoma, this finding raises concern that tumor cells could travel to lymph nodes or other organs. Your report will say whether lymphovascular invasion was identified, not identified, or could not be determined.
A margin is the edge of tissue cut by the surgeon to remove the tumor. Margins are described only when SMARCA4-deficient sinonasal carcinoma has been removed by surgery, not on a biopsy. Your report will describe them as follows:
Lymph nodes are small immune organs that filter fluid from the tissues. In SMARCA4-deficient sinonasal carcinoma, spread to lymph nodes in the neck can occur, sometimes along with spread to distant organs. Lymph nodes are removed in an operation called a neck dissection when scans show they may contain cancer.
When lymph nodes are examined, your report will say how many were removed and how many contain cancer cells. It will also give the size of the largest group of cancer cells in a lymph node. The report will also say whether extranodal extension is present, meaning cancer cells have broken through the outer capsule of a lymph node into surrounding tissue. Extranodal extension increases the nodal stage and is one of the findings your care team considers when planning treatment after surgery.
For SMARCA4-deficient sinonasal carcinoma, there are currently no established biomarker tests that guide the choice of a specific targeted drug. The loss of SMARCA4 is used to make the diagnosis, as described in the immunohistochemistry section above.
Research into treatments that target cancers with SMARCA4 loss is ongoing. In some cases, broader molecular testing may be performed to look for changes that could make a person eligible for a clinical trial. Your oncologist can tell you whether this testing is appropriate in your situation. More information is available in our Biomarkers and Genetic Testing section.
The pathologic stage for SMARCA4-deficient sinonasal carcinoma uses the TNM system in the AJCC Cancer Staging Manual, 8th edition. The pTNM stage combines the tumor stage, called pT, and the nodal stage, called pN. The metastasis stage (M) is usually decided from scans rather than from the pathology report.
The tumor stage for SMARCA4-deficient sinonasal carcinoma depends on where the tumor started. Many of these tumors have already grown into nearby structures by the time they are found.
Nasal cavity and ethmoid sinus:
Maxillary sinus:
If the tumor stage cannot be assessed, for example because the tumor was removed in many small pieces, your report may say that the pT stage was not assigned.
Your care team combines the pT stage, the pN stage, and your scans to assign an overall stage group from stage I to stage IV. A tumor that is pT4a is at least stage IVA, and a tumor that is pT4b is stage IVB. Cancer that has spread to distant organs is stage IVC.
SMARCA4-deficient sinonasal carcinoma is a serious cancer, and the prognosis is guarded. Because it was described only recently and is rare, the information about outcomes comes from small groups of patients. Those reports do not all agree.
In some early reports, many people died within months of diagnosis, often after the cancer spread to the brain, lungs, liver, or bones. A larger combined analysis found that survival was similar to SMARCB1-deficient sinonasal carcinoma, in which about half of people are alive 3 years after diagnosis. About 1 in 3 people develop spread to distant organs, called metastasis, at some point.
The tumor stage is one of the most important findings for predicting outcome. A pT4b tumor has grown into the brain, the dura, or the back of the eye socket, and it is harder to treat completely. Your care team can explain what the findings in your own report mean for your outlook.
Once SMARCA4-deficient sinonasal carcinoma has been confirmed, the next steps depend on the tumor stage and how far the cancer has spread. Your care team usually includes a head and neck surgeon, often with a skull base surgeon or neurosurgeon. A radiation oncologist and a medical oncologist are also involved. Treatment usually combines more than one approach:
After treatment, regular examinations with a nasal endoscope and scans are used to look for any sign that the cancer has returned or spread.