Plexiform neurofibroma

Plexiform neurofibroma also is called PN or PNF. It is a type of noncancerous tumor called neurofibroma that forms in or around a nerve. Neurofibromas grow on the protective covering around the nerve, called the nerve sheath. When a neurofibroma grows on several nerve bundles, it’s called a plexiform neurofibroma.

The tumor grows along the nerve and can spread into nearby tissues such as skin, fat, bone and muscle. Plexiform neurofibroma is most often seen in people with a condition caused by a change in genes that affects how nerve cells grow and develop, called neurofibromatosis type 1 (NF1). Up to half of the people with NF1 develop plexiform neurofibromas.

Plexiform neurofibromas are different from other nerve tumors because they spread out in a networklike pattern. These tumors are known for their distinctive “bag of worms” texture, which means they feel like a bundle of tangled cords or threads. This is a classic sign of a plexiform neurofibroma.

Plexiform neurofibromas are most common in childhood and adolescence. Some people may notice swelling or a soft lump under the skin. These tumors often grow in the head, neck, trunk, arms or legs, but they can appear anywhere in the body.

Treatment depends on the size, location and symptoms of the plexiform neurofibroma. Most plexiform neurofibromas grow slowly and are not life-threatening. But some can cause serious symptoms depending on the size or location or if they become cancerous.

Plexiform neurofibromas can cause different symptoms based on where they grow, how big they are, and how they press on nearby nerves and tissues. Some people have no symptoms at first. Others may notice changes in how their bodies look, feel or move.

Common signs and symptoms of plexiform neurofibroma include:

• Pain. Ongoing pain, which may be moderate to severe, is common in people with plexiform neurofibroma. Pain from plexiform neurofibroma can make it difficult to do daily activities and affect movement.
• Swelling or soft lumps. Tumors can cause growths that can be seen or felt under the skin. These may grow over time and may be soft, spongy or thickened.
• Changes in appearance. Tumors in visible areas such as the face or limbs can cause disfigurement, leading to emotional or social concerns.
• Movement changes. Tumors pressing on nerves or muscles can make it harder to walk, grasp objects or perform everyday tasks.
• Vision changes. Tumors near the eyes or the optic nerve can cause blurred vision, drooping eyelids or other changes in how the eyes look or work.
• Numbness or tingling. These symptoms may occur when the tumor interferes with how a nerve works — either by pressing on it or growing into it.
• Bladder or bowel changes. Plexiform neurofibromas near the pelvis or lower spine can affect the nerves that control the bladder and bowel. This can lead to symptoms such as urgency, frequent urination, leakage or trouble emptying, as well as constipation or stool leakage.
• High blood pressure. Some tumors may affect nearby structures or organs in a way that leads to high blood pressure, especially if they press on blood vessels or involve the kidneys or adrenal glands.
• Emotional changes. Children may feel anxious, sad or lonely due to their symptoms, appearance or ongoing pain.

Most plexiform neurofibromas occur in people with a condition called neurofibromatosis type 1 (NF1). NF1 is caused by a change in the NF1 gene, which is located on chromosome 17. This gene typically helps control how cells grow. When it isn’t working properly, cells that support nerves may grow too much and form tumors like plexiform neurofibromas.

Plexiform neurofibromas are linked to a genetic condition called neurofibromatosis type 1 (NF1). Anyone with NF1 has a risk of developing these tumors. The number, size and location of tumors can vary from person to person.

Having NF1 is the main risk factor for plexiform neurofibroma. Up to 50% of people with NF1 will develop one or more plexiform neurofibromas during their lives.

There is no known way to prevent plexiform neurofibromas. The tumors develop because of a genetic change that is present from birth and cannot be reversed.

Plexiform neurofibromas are usually diagnosed based on a combination of medical history, physical exam and imaging tests. Most people who develop these tumors have a condition called neurofibromatosis type 1 (NF1). NF1 often is diagnosed in early childhood.

Healthcare professionals may begin by examining the body for visible signs of tumors or skin changes. When a plexiform neurofibroma is close to the surface, it may feel soft and irregular under the skin. Some tumors have a “bag of worms” texture, which means they feel like a bundle of tangled cords or threads. This is a classic sign of a plexiform neurofibroma.

Imaging for plexiform neurofibroma

Because many plexiform neurofibromas grow deep inside the body, imaging is important for understanding the size, location and impact of the tumor. Tests such as MRI or CT scans can help find tumors — even very small ones — and show whether nearby tissues are affected.

Positron emission tomography (PET) scans are not used to diagnose plexiform neurofibromas, but they can be helpful if a healthcare professional is concerned that a tumor might be becoming cancerous. PET imaging can show how active the tumor cells are, which helps distinguish a noncancerous plexiform neurofibroma from a cancerous tumor, called malignant peripheral nerve sheath tumor (MPNST). However, it can still be difficult to tell a plexiform neurofibroma from an MPNST on a PET scan. At times, surgery or biopsy is needed.

Genetic testing for plexiform neurofibroma

If a child has signs of NF1 but no family history, your healthcare professional may order a genetic test to check for changes in the NF1 gene. A diagnosis of NF1 increases the likelihood of developing plexiform neurofibromas. Genetic testing can help confirm NF1, which is diagnosed when a person has at least two of seven clinical features — one of which is a plexiform neurofibroma.

Treatment for plexiform neurofibromas depends on the size, location and symptoms of the tumor. Some tumors don’t need treatment right away. Others may require surgery or medicine to manage pain, improve function or reduce tumor size.

• Surgery. This is the most common treatment for plexiform neurofibroma. Surgeons may try to remove a tumor that causes problems. But many plexiform neurofibromas are hard to remove completely because they grow into nearby nerves and tissues. This can make surgery risky and may lead to complications such as nerve damage, bleeding or slow healing.
• Medicine. Selumetinib (Koselugo), a pill taken by mouth, is an MEK inhibitor approved by the U.S. Food and Drug Administration (FDA) for children age 2 and older with plexiform neurofibroma tumors. This medicine helps shrink tumors by blocking a signal in cells that causes unhealthy growth. Mirdametinib (GOMEKLI), another MEK inhibitor, also is an FDA-approved medicine taken by mouth for use in adults and children age 2 and older with NF1 who have plexiform neurofibromas that cause symptoms and cannot be completely removed.
• Monitoring. Because these tumors often grow slowly, healthcare professionals usually monitor them with regular checkups. Sometimes this monitoring is all that’s needed. Imaging may be repeated if the tumor grows or new symptoms appear, such as pain, numbness or weakness. A sudden change in symptoms may be a warning sign that the tumor is growing or becoming cancerous.
• Supportive care. Some children with plexiform neurofibromas benefit from therapies that help them stay active and independent. Physical therapy can improve strength, balance and coordination. Occupational therapy may help with fine motor skills such as writing, getting dressed or using utensils. At times, pain or discomfort related to plexiform neurofibromas may be treated with medicines targeting nerve pain.

Accommodations for living with plexiform neurofibroma

People living with plexiform neurofibromas (PNFs) may need certain accommodations depending on tumor size, location and symptoms such as pain, fatigue or physical limitations.

Depending on your symptoms and how they impact your daily life, accommodations may include:

• Mobility support, including wheelchair access, accessible seating or limits on physical activity.
• Flexible scheduling or rest breaks to manage fatigue or pain.
• Excused absences for medical appointments or therapy.
• Learning supports, such as extra time or assistive technology, if thinking skills are affected.
• Adaptive furniture or layout changes to reduce pressure or discomfort caused by tumors.
• Therapy or counseling, such as counseling for body image, stigma or adjustment issues.

Prognosis

There is no cure for plexiform neurofibromas, but many people live well with them for years. Some tumors stay the same size and don’t cause symptoms, while others may grow and lead to pain, changes in appearance, or pressure on nearby nerves or tissues.

Regular checkups and imaging tests are important to watch for any changes in plexiform neurofibromas. In some cases, a plexiform neurofibroma can turn into an aggressive type of cancer called malignant peripheral nerve sheath tumor (MPNST).

Most plexiform neurofibromas do not become cancerous. With routine monitoring, and treatment when symptoms appear, many people are able to manage the tumors and maintain a good quality of life.

Potential future treatments

Researchers continue to study MEK inhibitors beyond selumetinib as treatments for plexiform neurofibromas. These medicines work by blocking signals that tell tumors to grow. This may help shrink the tumors or slow their growth.

Researchers are now studying whether other MEK inhibitors — such as trametinib (Mekinist) and binimetinib (Mektovi) — can provide similar or better tumor reduction with fewer or more manageable side effects compared with selumetinib. Cabozantinib (CABOMETYX) — a multityrosine kinase inhibitor — is under investigation.

A plexiform neurofibroma diagnosis can be overwhelming and confusing. It can make you feel like you have little control over your health. But you can take steps to cope with the shock and grief that may come after your diagnosis. Consider trying to:

• Learn enough about plexiform neurofibroma to make decisions about your care. Ask your healthcare team about your specific type of tumor, including your treatment options and, if you like, your prognosis. As you learn more about plexiform neurofibroma tumors, you may become more confident in making treatment decisions.
• Keep friends and family close. Keeping your close relationships strong can help you deal with your plexiform neurofibroma. Friends and family can provide the practical support you may need, such as helping care for your home if you’re in the hospital. And they can serve as emotional support when you feel overwhelmed.
• Find someone to talk with. Find a good listener who is willing to listen to you talk about your hopes and fears. This may be a friend or family member. The concern and understanding of a counselor, medical social worker, clergy member or cancer support group also may be helpful. Ask your healthcare team about support groups in your area.

See your usual healthcare professional if you have any signs or symptoms that worry you. If you’re diagnosed with a plexiform neurofibroma you may be referred to specialists, such as:

• Doctors who specialize in brain and nerve conditions, called neurologists.
• Doctors who treat cancer with medicine, called medical oncologists.
• Doctors who use radiation to treat cancer, called radiation oncologists.
• Doctors who specialize in nervous system cancers, called neuro-oncologists.
• Surgeons who operate on the brain and nervous system, called neurosurgeons.
• Doctors who specialize in genetics and inherited conditions, called medical geneticists.
• Rehabilitation specialists.

Plexiform neurofibroma tumor treatment can be complex. Few hospitals have the expertise to care for many people with these kinds of tumors. If you don’t feel comfortable with the care at your local facility, consider seeking a second opinion at a more experienced cancer center. Ask your healthcare professional for a referral.

Here’s some information to help you get ready for your appointment.

What you can do

• Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there’s anything you need to do in advance, such as restrict your diet.
• Write down any symptoms you’ve been experiencing and how long you’ve had them.
• List your key medical information, including all conditions you have and the names of any medicines you’re taking. Include prescription medicines and medicines you can buy without a prescription. Also list any vitamins or supplements that you take and the doses.
• Take a family member or friend along. Sometimes it can be difficult to remember all of the information provided to you during an appointment. Someone who goes with you may remember something that you missed or forgot.
• Write down questions to ask your healthcare professional.

Questions to ask at your first appointment include:

• What may be causing my symptoms?
• Are there any other possible causes?
• What kinds of tests do I need? Do these tests require any special preparation?
• What do you recommend for the next steps in learning about my diagnosis and treatment?
• Should I see a specialist?

Questions to ask an oncologist or a neurologist include:

• What type of tumor do I have?
• Where is my tumor located?
• How large is my plexiform neurofibroma?
• How aggressive is my tumor?
• Is my tumor cancerous?
• Will I need more tests?
• What are my treatment options?
• Can any treatments cure my plexiform neurofibroma?
• What are the benefits and risks of each treatment?
• Is there one treatment you feel is best for me?
• Is there a clinical trial available to treat my type of tumor? Is it appropriate for me?
• How will treatment affect my daily activities, such as walking, talking and speaking?
• Should I see a specialist? What will that cost, and will my insurance cover it?
• Are there brochures or other printed material that I can take with me? What websites do you recommend?
• How often should I have checkups?

Note the three questions that are most important to you so you can be sure to get those answered if the time is limited. In addition to the questions that you’ve prepared to ask, don’t hesitate to ask other questions that occur to you.

What to expect from your doctor

Be prepared to answer questions about your symptoms and your health history. Questions may include:

• What are your symptoms?
• When did you first notice these symptoms?
• Have your symptoms gotten worse over time?
• If you have pain, where does the pain seem to start?
• Does the pain spread to other parts of your body?
• Have you participated in any activities that might explain the pain, such as a new exercise or a long stretch of gardening?
• Have you experienced any weakness or numbness in your legs?
• Have you had any difficulty walking?
• Have you had any problems with your bladder or bowel function?
• Have you been diagnosed with any other medical conditions?
• Are you currently taking any medicines, including prescription medicines and medicines that you can get without a prescription?
• Do you have any family history of noncancerous or cancerous tumors?