What is Biphenotypic Sinonasal Sarcoma?
Sinonasal malignancies, which are forms of cancer that occur in the nasal cavity and sinuses, are relatively rare, making up 1-5% of all head and neck cancers. However, they can be of various types and their symptoms are often vague and non-specific, making them difficult to diagnose early. The most frequently diagnosed type of sinonasal malignancy is squamous cell carcinoma, which makes up about 36 to 58% of cases, followed by adenocarcinoma, mucosal melanoma, adenoid cystic carcinoma, and esthesioneuroblastoma.
There’s another lesser-known and recently categorized type of cancer called biphenotypic sinonasal carcinoma (BSNS), which was first described in 2012 and recognized by the World Health Organization in 2017. Although it is a slow-growing and less severe (or low-grade) form of cancer, BSNS tends to spread aggressively within the upper airway and digestive tract. About 20% of patients with BSNS already have bone involvement at the time of diagnosis, especially in areas like the orbit (or eye socket) and the cribriform plate (a thin bone between the brain and nasal cavity).
It is rare for this type of cancer to metastasize, meaning to spread to other parts of the body including the lymph nodes in the neck. Interestingly, BSNS tumors can grow up to 4 cm and are most commonly found in the nasal cavity or the ethmoid sinus, followed by the sphenoid sinus. The maxillary sinus is the most common site for any type of sinonasal cancer, but the ethmoid sinus also contains the primary tumor in 5 to 15% of patients. In case of BSNS, the ethmoid sinus is even more commonly involved, but the exact numbers are unclear.
Interestingly, compared to squamous cell carcinoma which has a 5-year survival rate of only 25 to 50%, no patients with BSNS had their cancer spread, and only one death has been recorded so far. It’s unclear how many sinonasal cancers are eventually diagnosed as BSNS, because it had previously been classified under various other names. So far, just over 100 cases have been described in medical literature, based on both examination of past specimens and new case reports.
What Causes Biphenotypic Sinonasal Sarcoma?
There aren’t any specific things that make you more likely to develop BSNS. Generally though, certain hazardous chemicals used in industries like textiles, furniture, and leather production can increase the risk for all kinds of tumors in the area near your nasal and cheek sinuses.
On a genetic level, a unique combination of genes, known as a PAX3-MAML fusion protein, can be identified using a technique called fluorescence-in-situ hybridization (FISH). This special combination of genes can lead to the development of BSNS.
Risk Factors and Frequency for Biphenotypic Sinonasal Sarcoma
Research shows that BSNS is more common in women than men, with the ratio ranging from 1.8:1 to 2.27:1. The average age of individuals affected by BSNS is around 50 to 52 years old. However, the age range can vary widely, affecting people from their mid-20s up to their mid-80s.
Signs and Symptoms of Biphenotypic Sinonasal Sarcoma
It’s common for individuals experiencing certain symptoms to have a nasal tumor. These symptoms tend to progress and usually include:
- Nasal obstruction
- Occasional nasal congestion
- Loss of sense of smell (anosmia)
- Swelling and pain in the face
- Nosebleeds (epistaxis)
- Numbness around the eyes
- Occasional blurred vision
- Nasal discharge (rhinorrhea)
Patients with advanced tumors may also develop other symptoms like:
- Watery eyes (epiphora)
- Double vision (diplopia)
- Bulging eyes (proptosis)
- Leaking brain fluid from the nose (CSF rhinorrhea)
In some cases, these symptoms can be mistaken for sinusitis due to the presence of pus-filled nasal drainage. Because these symptoms are quite general, they often lead to late diagnosis when the tumor is already in the advanced stage, similar to other tumors in the nose and sinus region. In severe cases, patients might have trismus (jaw muscle spasms) due to invasion into the pterygoids, cranial nerve palsies, and hearing loss due to invasion into the eustachian tube. These advanced symptoms are often linked to a worse prognosis.
Testing for Biphenotypic Sinonasal Sarcoma
If you have a type of tumor called BSNS, or sinonasal tumors, doctors may use scans to understand what’s going on in your nasal region. Two common types of scans are computed tomography (CT) scans and magnetic resonance imaging (MRI).
CT scans help doctors see the size and shape of the tumor and can show if it’s causing other changes in the area, like bone growth (hyperostosis), damage to adjacent bones (erosion), and blockage of the sinuses (post-obstructive sinus opacification).
MRI scans tell doctors more about the type of tissue in the tumor. For example, in BSNS, the tumor appears the same intensity as grey matter (normal brain tissue) on both T1 and T2 type images. The scans also show that BSNS may have a mixed appearance after contrast is given, likely due to the presence of glandular components (tissue that produces secretions like saliva or mucus). The tumor also shows restriction on diffusion-weighted imaging, which can provide further details about the nature of the tumor tissues.
Another type of scan is the positron emission tomography (PET) scan, which is often used to see if a cancer has spread to other parts of the body. But generally, PET scans aren’t as useful for BSNS tumors. That’s because BSNS tumors don’t typically show up well on PET scans and they rarely, if ever, spread either to nearby or distant parts of the body.
Treatment Options for Biphenotypic Sinonasal Sarcoma
The primary way to treat this condition is usually through surgery, which we will discuss more about below. The benefits of using radiation therapy aren’t clear, and adding chemotherapy seems to not improve the treatment’s effectiveness.
What else can Biphenotypic Sinonasal Sarcoma be?
Diagnosing BSNS, a kind of tumor in the nasal passages, can be tricky. This is because there are several other rare types of tumors in these areas that can look similar to BSNS. Some people have even been wrongly diagnosed before because there’s not a lot of information out there, which can make it hard to study these tumors under the microscope.
Some of these similar types of tumors that might be wrongly identified as BSNS are:
- Solitary fibrous tumors
- Fibromatosis
- Myofibrosarcoma
- Schwannoma
- Leiomyosarcoma
- Synovial sarcoma
- Malignant peripheral nerve sheath tumor (Triton tumor)
- Glomangiopericytoma
- Inverted papilloma
Even though they seem alike visually, studying them under the microscope can help tell them apart. Here are some key features of BSNS that can help distinguish it from other similar types of tumors:
- It contains a large number of cells that are shaped like spindles, but it doesn’t have too many cells that split or die.
- It has uneven or widespread staining for S100 and SMA, but doesn’t have staining for SOX10.
- It has a genetic marker known as PAX3-MAML fusion.
In contrast, solitary fibrous tumors show cytokeratin presence unlike BSNS. Fibrosarcomas are less cellular and do not exhibit S-100 positivity. Schwannomas and nerve-related tumors stain positive for SOX1, and leiomyosarcoma doesn’t show S-100 positivity and features cigar-shaped cell nuclei with halos around them. Synovial sarcoma might look like BSNS due to the presence of false gland-related structures. However, it shows cytokeratin expression and extra thick collagen bundles that are not seen in BSNS.
The nerve disease known as neurofibromatosis type 1 is strongly linked with Triton tumor, which has some common features but also shows faster growth and other features not seen in BSNS. Glomangiopericytoma is more similar to epidermal cells, doesn’t stain positive for S100, and its small cell-like pattern differs from BSNS. Inverted papilloma might look similar to BSNS because of its respiratory lining component, but it has a significantly more noticeable gland-like structure and lacks spindle cell proliferation that is seen in BSNS.
Remember, none of these conditions show PAX3-MAML fusion on a specific genetic test (FISH), which is a key marker for BSNS. It’s worth noting that synovial sarcoma, fibrosarcoma, and low-grade malignant peripheral nerve sheath tumors are the ones most often incorrectly diagnosed as BSNS.
Surgical Treatment of Biphenotypic Sinonasal Sarcoma
Surgery is typically the main treatment for BSNS. However, in order to avoid damaging crucial structures like your eye socket or base of your skull, the surgeon may sometimes need to leave some parts of the tumor behind.
There are various ways this surgery can be done, both through endoscopy, a non-invasive surgery that uses a tube-like instrument with a light, or through open-surgery – both methods depending on where the tumor is located and how far it has spread. The type of surgery also depends on what the surgeon prefers. Open-surgery options can include bifrontal craniotomy, which is opening the skull, and lateral rhinotomy, which is surgical incision into the nose.
If there’s any damage to the base of your skull from the tumor, it can be repaired using tissue from your own body, such as a flap of skin from the top of the head, or using synthetic materials.
Just to note, since the rate of these sinonasal cancers spreading to the lymph nodes (small glands that remove bacteria and particles in the body) is low, preventive surgery to remove them is usually not needed.
What to expect with Biphenotypic Sinonasal Sarcoma
Studies on the behavior of BSNS (basosquamous cell carcinoma) are limited, so the likelihood of it recurring or resulting in death isn’t completely clear. However, research suggests that the survival rate within five years of treatment might potentially be higher than the 25% to 50% survival rate reported for SCC (Squamous Cell Carcinoma), a form of skin cancer, in the nose and sinus regions.
Out of approximately 100 cases reported in medical literature, between 32% to 40% of patients experienced the illness returning. Only one death has been recorded, which was due to the illness returning for a second time and spreading to the brain.
The time between treatments without the illness returning (or recurrence-free range) varies, recorded over the range of 1 year to 9 years. In a documented series of five patients, two patients experienced a return of the illness and received repeat surgery. One of these two patients also had additional proton beam therapy, which is a type of radiation treatment that uses energy to kill cancer cells.
The potential for BSNS to spread or worsen is unknown, as scientists are still studying the effects of gene fusion. This refers to combining parts of two different genes, a process that results in the characteristic traits of BSNS.
Possible Complications When Diagnosed with Biphenotypic Sinonasal Sarcoma
: BSNS, or brain surgery, by its nature grows slowly and thus doesn’t often have immediate complications. However, the most common issue that patients face after the surgery is the return of their previous condition. In addition, some patients may encounter problems such as blurry or loss of vision, leakage of cerebrospinal fluid (a clear fluid found in the brain and spinal cord), presence of air within the skull, post-surgery infection, death of the tissue used to repair the base of the skull, recurring nasal congestion, and blockage of the frontal sinus.
If the original repair of a skull base defect doesn’t work, doctors can use alternate flaps of tissue or grafts from different parts of the body to carry out a revision surgery. These can come from sources such as the lining covering the brain, the nasal septum, or the tensor fascia lata muscle which is located on the side of the thigh.
Common Side Effects:
- Return of previous condition
- Blurry or loss of vision
- Leakage of cerebrospinal fluid
- Presence of air within the skull
- Post-surgery infection
- Death of the tissue used to repair the base of the skull
- Recurring nasal congestion
- Blockage of the frontal sinus
Recovery from Biphenotypic Sinonasal Sarcoma
The recovery process after endoscopic surgery for BSNS (a type of nose and skull base surgery) is similar to the normal recovery process after other endoscopic sinus and skull base procedures. This includes precautions to protect the sinuses and cleaning the operated area using a specific type of small surgical tool known as an endoscope. Depending on the level of disability after surgery, and if the patient experienced complications due to radiation therapy, suitable recovery services should be provided.