DEK::AFF2 Squamous Cell Carcinoma: Understanding Your Pathology Report

Section Editor: Jason Wasserman MD PhD FRCPC
November 2, 2026

DEK::AFF2 squamous cell carcinoma is a rare type of squamous cell carcinoma that starts most often in the nasal cavity or the sinuses. It is defined by a change in which two genes, called DEK and AFF2, are joined together inside the tumor cells. Your report may call this tumor DEK::AFF2 carcinoma or nonkeratinizing squamous cell carcinoma, DEK::AFF2 translocated.

Under the microscope, the cancer cells often look surprisingly bland, meaning they look only a little different from normal cells. Despite this, DEK::AFF2 squamous cell carcinoma frequently grows back after treatment and can spread to lymph nodes and other organs. Some older reports used the name low-grade papillary Schneiderian carcinoma for the same tumor.

This article explains how DEK::AFF2 squamous cell carcinoma is diagnosed and which tests confirm it. It also describes what the margins, lymph nodes, and stage in your pathology report mean for your care.

Who gets DEK::AFF2 squamous cell carcinoma?

DEK::AFF2 squamous cell carcinoma is found in adults. Because it was first described only in 2020, information about the typical age and sex of patients is still limited. It is one of the more common types of nonkeratinizing squamous cell carcinoma of the nose that is not caused by human papillomavirus (HPV).

About 4 in 10 of these tumors start in the nasal cavity. Others start in the sinuses, the base of the skull, the eye socket, or the middle ear and the surrounding temporal bone. Very few have been reported in the lung.

What causes DEK::AFF2 squamous cell carcinoma?

DEK::AFF2 squamous cell carcinoma is caused by a change in the tumor cells called a gene fusion. In this change, a piece of the DEK gene breaks off and joins to part of the AFF2 gene. The joined gene makes an abnormal protein that changes which genes the cell switches on, allowing the cell to grow out of control.

This fusion develops in the tumor cells during a person’s life and is not inherited. Unlike some other squamous cell carcinomas of the head and neck, DEK::AFF2 squamous cell carcinoma is not caused by human papillomavirus or Epstein-Barr virus.

What are the symptoms of DEK::AFF2 squamous cell carcinoma?

The symptoms of DEK::AFF2 squamous cell carcinoma depend on where the tumor starts. When it grows in the nose or sinuses, common symptoms include:

A blocked or stuffy nose.
Nosebleeds.
Pressure or pain in the face.
A growth that can be seen inside the nose.

When the tumor starts in the middle ear, it can cause hearing loss, ear pain, or ear discharge. Because these symptoms are common in much less serious conditions, doctors sometimes find the tumor only after removing and examining the growth.

How is the diagnosis of DEK::AFF2 squamous cell carcinoma made?

A pathologist diagnoses DEK::AFF2 squamous cell carcinoma after examining tumor tissue under a microscope. An ear, nose, and throat surgeon usually takes a biopsy during nasal endoscopy, using a thin camera passed through the nostril. Sometimes the diagnosis is made only after the whole tumor has been removed.

Under the microscope, the tumor is made of sheets, ribbons, and finger-like projections of squamous cells that grow both outward and down into the tissue below. The cells do not make keratin, a feature described as nonkeratinizing. Their nuclei are uniform and usually show few dividing cells. Many small inflammatory cells called neutrophils are often mixed in with the tumor cells.

Because the cells look so bland, a small biopsy of DEK::AFF2 squamous cell carcinoma can look like a noncancerous growth called a sinonasal papilloma. For this reason, the diagnosis is confirmed with special tests. Immunohistochemistry for a protein called AFF2 is often used first, as described in the next section.

The fusion itself can be confirmed with fluorescence in situ hybridization (FISH) or with RNA sequencing, a type of next-generation sequencing. Once the diagnosis is confirmed, CT and MRI scans show how far the tumor has spread into nearby bone, the eye socket, or the skull base.

Immunohistochemistry

Immunohistochemistry is used in DEK::AFF2 squamous cell carcinoma to confirm the tumor is squamous cell carcinoma and to look for the fusion protein. Immunohistochemistry uses antibodies to show which proteins are present in the tumor cells. Results that may appear in your report include:

AFF2. Positive in the nucleus of the tumor cells. This result strongly supports the diagnosis because normal squamous cells and most other nasal tumors do not show this pattern. A negative result makes DEK::AFF2 squamous cell carcinoma unlikely.
p40 and p63. Positive. These proteins are found in squamous cells, and a positive result confirms that the tumor is a squamous cell carcinoma.
Cytokeratins, including CK5. Positive. These proteins are made by epithelial cells, including squamous cells.
p16. May be positive or negative. In the nose, p16 can be positive in tumors not caused by HPV, so a positive p16 result alone does not mean the tumor is HPV-associated.
HPV testing. Negative. When HPV testing is performed, tests that look directly for the virus, such as in situ hybridization, are preferred over p16.

Laboratories use different panels, and not every report will include every test.

Histologic grade

DEK::AFF2 squamous cell carcinoma is not given a histologic grade. Many squamous cell carcinomas are graded as well, moderately, or poorly differentiated, depending on how much they resemble normal tissue. The College of American Pathologists (CAP) updated its protocol for the nasal cavity and sinuses in 2026. It notes that newer types defined by specific genetic changes do not currently need a grade.

This matters because DEK::AFF2 squamous cell carcinoma often looks low grade, but it can still grow back and spread. In the largest published study, the number of dividing cells and other microscopic features did not predict tumor behavior. Your report may say that grade is not applicable, or it may not mention grade at all.

Perineural invasion

Perineural invasion means cancer cells are seen along or inside a nerve. In DEK::AFF2 squamous cell 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

Lymphovascular invasion means cancer cells are seen inside a blood vessel or lymphatic channel. In DEK::AFF2 squamous cell 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.

Surgical margins

A margin is the edge of tissue the surgeon cuts to remove the tumor. Margins are described only when DEK::AFF2 squamous cell carcinoma has been removed by surgery, not on a biopsy. Your report will describe them as follows:

Negative margin. No cancer cells are seen at the cut edge. Your report will also give the distance in millimeters (mm) from the cancer to the closest margin.
Positive margin. Cancer cells are seen at the cut edge. This means some cancer may remain, and your care team may consider further surgery or radiation therapy.
Cannot be determined. The margins could not be assessed. This happens most often when the tumor is removed in several pieces during endoscopic surgery.

Lymph nodes

Lymph nodes are small immune organs that filter fluid from the tissues. DEK::AFF2 squamous cell carcinoma can spread to lymph nodes in the neck, either at diagnosis or later. 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.

Biomarker and molecular testing

The DEK::AFF2 fusion is used to make the diagnosis of DEK::AFF2 squamous cell carcinoma, as described in the sections above. It does not currently make a person eligible for a specific targeted drug. Biomarker testing for this tumor is most often considered when the cancer has come back or spread.

PD-L1

PD-L1 is a protein that some cancer cells use to hide from the immune system. Drugs called immune checkpoint inhibitors block this hiding signal and help the immune system attack the cancer. PD-L1 is tested by immunohistochemistry and reported as a Combined Positive Score (CPS), which counts how many tumor and immune cells show the protein.

The US Food and Drug Administration (FDA) has approved the checkpoint inhibitor pembrolizumab for head and neck squamous cell carcinoma. This includes cancer that has come back or spread, approved in 2019, and some cancers that can be removed by surgery, approved in 2025. For several of these uses, approval depends on a CPS of 1 or higher. The main study behind the 2019 approval did not include cancers of the nose and sinuses. Your oncologist can explain how these approvals apply to your situation.

Your report will describe PD-L1 in one of these ways:

CPS less than 1. Little or no PD-L1 was found. This result may limit some immunotherapy options.
CPS of 1 or higher. PD-L1 was found. This result may make immunotherapy an option, depending on the situation.
CPS of 20 or higher. A high level of PD-L1 was found. This result is sometimes reported separately because it can affect how strongly immunotherapy is considered.

One person with DEK::AFF2 carcinoma had an exceptional response to a checkpoint inhibitor. Researchers think the fusion protein may help the immune system recognize the tumor, but larger groups have not yet confirmed this. More information is available in our article on PD-L1 testing in cancer and in the Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

The pathologic stage for DEK::AFF2 squamous cell carcinoma uses the TNM system in the AJCC Cancer Staging Manual, 8th edition. The pTNM stage combines the tumor stage (pT) and the nodal stage (pN). The metastasis stage (M) is usually decided from scans rather than from the pathology report.

Tumor stage (pT)

The tumor stage for DEK::AFF2 squamous cell carcinoma depends on where the tumor started. The CAP protocol does not include pT categories for tumors that start in the middle ear. For those tumors, your care team describes the extent of the cancer differently.

Nasal cavity and ethmoid sinus:

pT1. The tumor is limited to one area of the nasal cavity or ethmoid sinus, with or without growth into bone.
pT2. The tumor involves two areas of the nasal cavity or ethmoid sinus, or extends into a neighboring area, with or without bone involvement.
pT3. The tumor has grown into the floor or inner wall of the eye socket, the maxillary sinus, or the roof of the mouth. It may instead involve the cribriform plate, the thin bone below the brain.
pT4a. The tumor has grown into the front of the eye socket, the skin of the nose or cheek, or slightly into the front of the skull. It may instead have reached the pterygoid plates or the sphenoid or frontal sinuses.
pT4b. The tumor has grown into the back of the eye socket, the dura covering the brain, the brain itself, or the middle of the skull base. It may instead involve certain cranial nerves, the nasopharynx, or the clivus.

Maxillary sinus:

pT1. The tumor is limited to the lining of the maxillary sinus, with no damage to the bone.
pT2. The tumor has damaged the bone of the sinus, or grown into the roof of the mouth or the middle part of the nasal cavity.
pT3. The tumor has grown into the back wall of the sinus, the tissue under the skin, or the floor or inner wall of the eye socket. It may instead involve the pterygoid fossa or the ethmoid sinuses.
pT4a. The tumor has grown into the front of the eye socket, the skin of the cheek, or the pterygoid plates. It may instead involve the infratemporal fossa, the cribriform plate, or the sphenoid or frontal sinuses.
pT4b. The tumor has grown into the back of the eye socket, the dura, the brain, or the middle of the skull base. It may instead involve certain cranial nerves, the nasopharynx, or the clivus.

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.

Nodal stage (pN)

pN0. No cancer cells are found in the lymph nodes examined.
pN1. Cancer is found in one lymph node on the same side as the tumor. The node is 3 cm or smaller, with no extranodal extension.
pN2a. Cancer is found in one lymph node on the same side. Either it is 3 cm or smaller with extranodal extension, or it is larger than 3 cm but not larger than 6 cm without extranodal extension.
pN2b. Cancer is found in more than one lymph node on the same side, none larger than 6 cm and none with extranodal extension.
pN2c. Cancer is found in lymph nodes on the opposite side or on both sides, none larger than 6 cm and none with extranodal extension.
pN3a. Cancer is found in a lymph node larger than 6 cm, without extranodal extension.
pN3b. Cancer is found in a lymph node with extranodal extension, other than the single small node described under pN2a.
pNX. Lymph nodes were not examined.

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.

What is the prognosis for DEK::AFF2 squamous cell carcinoma?

The prognosis for DEK::AFF2 squamous cell carcinoma is still being studied because few people have been followed for long. The main concern is local recurrence, meaning the tumor grows back in the same place. In the largest study, people had an average of almost 2 recurrences, and some had many more.

The cancer can also spread to lymph nodes in the neck and, less often, to distant organs, called metastasis. In that same study, about 6 in 10 people had no sign of cancer at their last visit. About 3 in 10 were living with the disease. Overall survival was similar to other squamous cell carcinomas of the nose, but the time without disease was shorter.

Deaths from DEK::AFF2 squamous cell carcinoma have been reported. Because the cells look bland, the appearance of the tumor under the microscope does not predict how it will behave. Doctors do not yet know which pathology findings best predict the outcome.

What happens after the diagnosis of DEK::AFF2 squamous cell carcinoma?

Once DEK::AFF2 squamous cell carcinoma has been confirmed, the next steps depend on the tumor site, the stage, and the margins. Your care team usually includes a head and neck surgeon, a radiation oncologist, and a medical oncologist. A skull base surgeon or ear specialist may also be involved. Treatment options include:

Surgery. Surgery to remove the tumor with clear margins is usually part of treatment. It may be performed through the nostrils with an endoscope or through an open approach.
Radiation therapy. Radiation therapy may be given after surgery. The team considers findings such as positive margins, perineural invasion, or lymph node spread when planning it.
Chemotherapy. Chemotherapy may be combined with radiation therapy, or used when the cancer has spread.
Immunotherapy. When the cancer has come back or spread, the team may consider immunotherapy, guided in part by the PD-L1 result.
Clinical trials. Because this cancer was described only recently, your care team may discuss whether a clinical trial is right for you.

Because DEK::AFF2 squamous cell carcinoma often grows back, follow-up usually includes regular endoscopy and scans for a long time.

Questions to ask your doctor

How was the DEK::AFF2 fusion confirmed in my tumor?
Was AFF2 immunohistochemistry performed, and what did it show?
Was HPV testing done, and which test was used?
Was my tumor first thought to be a papilloma?
Where did the tumor start, and which structures has it grown into?
What is the pT stage, and what is my overall stage group?
Were the margins negative or positive, and how close was the cancer to the nearest margin?
Were perineural invasion or lymphovascular invasion identified?
Were any lymph nodes examined, and did any contain cancer?
Was PD-L1 tested, and what was the CPS?
Do I need radiation therapy or chemotherapy after surgery?
How often will I need endoscopy and scans, and for how many years?