What is Neurofibroma?

Introduction

Neurofibroma is a type of nerve sheath tumour. The nerve sheath is made up of various types of cells that together form a protective layer of tissue that insulates the nerves.¹

 Most neurofibromas are benign (non-cancerous, WHO grade 1), but in some cases, they can develop into a malignant (cancerous) form.² Cancerous neurofibromas can develop anywhere in the body where there are nerves but usually occur in the peripheral nervous system nerves, which are found outside the brain and spinal cord.³  

Importance in health and well-being

Individuals with (or suspecting they have)  neurofibroma need to seek medical advice from healthcare professionals as soon as possible. Early detection, monitoring and management can help prevent potential complications and improve their quality of life. 

Causes and risk factors 

About 90% of neurofibromas occur sporadically (i.e. have a non-genetic cause), while the remaining neurofibroma cases are often linked with the genetic condition neurofibromatosis.^3,5

Genetic factors

Neurofibromatosis is a condition caused by genetic disorders, which can cause the development of multiple neurofibromas throughout the body - in both the peripheral nervous system and central nervous system (including the brain and spinal cord).^3,6 

There are two main types: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2): 

Neurofibromatosis type 1 (NF1) 

NF1 (also known as von Recklinghausen’s disease) is the most common type (affecting 1 in 3500 births) of neurofibromatosis.⁷ NF1 is caused by abnormal changes (or mutations) in the NF1 gene. The NF1 gene is vital for the production and normal functioning of a protein called neurofibromin, which prevents cells from growing abnormally. As such, mutations in NF1 can cause abnormal cell growth and neurofibroma development. NF1 can be passed on from the parent to the child if the parent has a genetic mutation. 

NF1 is noticeable at birth or during early childhood. About 25% of affected children develop tumours that grow to cause medical issues.⁸ Some of the key signs individuals with NF1 may present with include: 

• Multiple light brown (café-au-lait) spots, especially in the groin, underarms and under the skin 
• Scoliosis (curving of the spine) 
• Bone enlargement or deformation
• Possible tumours in the central nervous system (brain and spinal cord) 

 Neurofibromatosis type 2 (NF2) 

NF2, also known as vestibular schwannoma neurofibromatosis, is much less common than NF1 (affecting 1 in 40,000 births).⁷ NF2 is caused by abnormal changes in the NF2 gene. The NF2 gene is vital for the production and normal functioning of a protein called Merlin, which, like NF1, prevents cells from growing abnormally. NF2 can be passed on from the parent to the child if the parent has a genetic mutation.⁹

NF2 can become noticeable during childhood, adolescence, or early adulthood. NF2 is most associated with acoustic neuromas, which are tumours of the auditory nerve. The auditory nerve is responsible for our hearing abilities and maintaining balance. Therefore, some of the key signs individuals with NF2 may present with include: 

• Hearing loss, which gradually worsens over time
• Ringing in the ears (tinnitus)
• Problems maintaining balance 

Non-genetic factors 

The majority of neurofibroma cases have no known genetic cause. It is unclear why these cases occur, but the following may increase the likelihood of neurofibroma:^3,12,18

• Environmental factors, including exposure to radiation or certain chemicals 
• Age – risk of tumour development was reported more in both male and female adults aged 20-30 years old   
• Hormonal changes or imbalances - such as in puberty or pregnancy 
• Other medical conditions - such as autoimmune disease and nervous system disorders

Types of neurofibroma

Depending on the pattern of growth, the types of neurofibroma can be described into 2 main types: cutaneous and plexiform.¹¹ 

Cutaneous neurofibroma

Cutaneous neurofibroma is the most common type of neurofibroma. Cutaneous neurofibromas are benign tumours that grow under the skin or along a nerve. They can appear as small, raised, soft and rubbery lumps, bumps, or nodules, which may be skin-coloured or hyperpigmented and can leave a “buttonhole” sign when pushed. These well-defined nodules can appear on the trunk, head, neck, arms, and legs. Cutaneous neurofibromas may develop at any age but are more likely to develop during periods of hormonal change, such as during puberty or pregnancy. Although not all individuals with cutaneous neurofibroma have NF1, individuals with NF1 often manifest cutaneous neurofibroma. Usually, they do not cause any medical issues, but some individuals may have cosmetic concerns.^3,11,12

Plexiform neurofibroma

Plexiform neurofibroma is the less common but more complex type of neurofibroma. Although plexiform neurofibromas can occur in the absence of genetic disorders, approximately 30-50% of individuals with NF1 develop plexiform neurofibroma.11,13 Plexiform neurofibroma can be present at birth and grow larger as the individual grows older. Unlike cutaneous neurofibroma, which grows superficially, this type of neurofibroma grows deeper within the body and involves large nerve bundles, such as the spinal cord. They often appear as swelling along the nerve, which tends to be less well-defined and affects a larger area, with a “bag of worms” appearance. Commonly affected locations include the abdomen, arms, legs, groin, head, and neck. Although neurofibromas are often benign tumours, about 10% of plexiform neurofibromas become malignant (cancerous). These plexiform neurofibromas, also known as malignant peripheral nerve sheath tumours (MPNSTs), can cause more significant (and sometimes life-threatening health issues.^11,12

Signs, symptoms and manifestations

About 1 in 3 people with neurofibromas have no symptoms or problems.⁷ It is important to know that the signs and symptoms may vary by type, cause, size, location, and pattern of growth of the neurofibroma.^3,14 Cosmetic concern is the most reported sign and symptom of neurofibroma. If you have any concerns, please speak to a healthcare professional. 

Although the cause is not fully understood, some signs, symptoms and complications may include:^3,6-9,17

• The skin is most commonly affected and causes symptoms such as:
  • Pea-sized bumps on or under the skin 
  • Large swollen area(s) on or under the skin 
  • Freckling under the arms, under the breast, or in the groin area
  • Six or more “café-au-lait” birthmarks (light or dark brown spots on the skin) that can be anywhere on the body
  • Itchiness and or bleeding - due to inflammation 
• Neurological:
  • Pain or discomfort, which can vary with duration and intensity
  • Numbness or weakness due to the tumour pressing against the nerves responsible for sensation or muscle movement
  • Changes in sensation, such as feeling very sensitive to touch and/or temperature (feeling too hot or cold)
  • Migraines 
  • Learning disabilities
  • Seizure
  • Hyperactivity
  • Problems maintaining balance
  • Problems walking
• Physical:
  • Bone abnormalities such as abnormal curvature of the spine (scoliosis), abnormally larger head (macrocephaly), bowing of the legs, short stature, etc.
  • Changes in vision - due to tumour, also known as optic pathway glioma (OPG)
  • Yellow-brown spots on the iris of the eye (Lisch nodules) 
  • Changes in hearing - gradual hearing loss or hearing ringing or buzzing (tinnitus)
• Others may include:
  • High blood pressure - may be caused by narrowing of the arteries 
  • Larger tumour 
  • Compression of internal organs, which may cause difficulties in breathing, speech or swallowing, abdominal pain, etc

Early diagnosis and treatment are recommended to minimise severe complications¹²

Diagnosis of neurofibroma 

Neurofibromas are diagnosed by healthcare specialists (such as dermatologists, neurologists, geneticists, and surgeons) through a combination of physical examination, imaging studies, and biopsies.^7-11

Clinical evaluation

The healthcare professional will review any relevant medical conditions, both of the individual and any family members. They will also perform a thorough physical examination, including checking any skin lumps to identify any development of neurofibroma in the body.  

Imaging studies 

Imaging studies, such as X-ray, magnetic resonance imaging (MRI) or computed tomography (CT), may be used to identify and better understand the size, location, and development of neurofibroma(s) in the body. PET scans may also be used if the doctor suspects you have malignant peripheral nerve sheath tumours. These will also help differentiate whether the tumour(s) is/are neurofibromas (s) or not. 

Biopsy 

A biopsy may be necessary in some cases to confirm the diagnosis of neurofibroma, particularly for larger lesions.³ During a biopsy, a small sample of tissue from the suspected tumour will be extracted, and a pathologist will examine this further using a microscope.¹⁶ 

Genetic testing 

Genetic testing, although not done routinely, may be recommended to confirm where a genetic cause, such as neurofibromatosis, is suspected to cause the neurofibroma.¹⁵ 

Management and treatment 

There is currently no cure for neurofibroma. However, there are effective treatments available to help manage symptoms and improve your quality of life.^3,8,9 

Regular check-ups and imaging studies over time are important to monitor any further growth of the tumour. These check-ups can include:

• Detailed skin examinations
• Vision tests 
• Bone assessments 
• Blood pressure checks
• Physical development checks
• Behavioural and neurological assessments
• For children, school performance will also be considered - such as problem-solving, comprehension, reading and writing abilities. 

Healthcare professionals will provide an individualised treatment plan based on the individual’s comprehensive health and well-being check. Most often, regular monitoring is enough. Further treatments depend on the size and location of the neurofibroma and may include:^{8,9,12,17,18,20}

• Surgical removal - whilst usually successful, there may be some scarring, and complete removal may be challenging for neurofibromas like plexiform type.
• Pain management with medication or physical therapies 
• Targeted therapies, such as medications that target specific genetic mutations linked to neurofibromatosis 
• Radiation therapy - but this is not recommended for benign neurofibroma(s) due to the risk of them turning cancerous.  
• Clinical trials - there are many undergoing recent developments, and you may be eligible for clinical trial testing
• Physiotherapy
• Psychological support 
• Speech and language therapy
• Occupational therapy 
• Educational psychology
• Support groups and charities¹⁹

When discussing your treatment plan,  healthcare professionals should listen to and address your concerns and thoroughly discuss the justification for and pros and cons of having the treatment(s). 

FAQs

What is neurofibroma?

A neurofibroma is a benign (non-cancerous) tumour that arises from Schwann cells, which form the myelin sheath that covers and insulates the nerves. Neurofibromas can occur anywhere in the body where there are nerves. 

What are the symptoms of neurofibroma?

The symptoms depend on the types, causes, and location of the neurofibroma. The most common symptoms are lumps on the skin. Read more on the ‘signs, symptoms and manifestation’ section.

Are neurofibromas cancerous?

Neurofibromas are typically benign (non-cancerous). However,in rare cases, benign neurofibromas can turn into cancerous tumours called malignant peripheral nerve sheath tumours (MPNSTs). 

What causes neurofibromas? 

Most neurofibromas occur sporadically (non-genetic and unknown cause), but the primary cause is genetic mutations, particularly in the NF1 or NF2 genes.

Is neurofibroma hereditary?

It can be. Neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) are genetic disorders, which can be passed on from the parent to the child. 

How are neurofibromas diagnosed?

Diagnosis usually involves a thorough medical check-up and imaging studies like X-ray, MRI etc. Although not done routinely, genetic testing may be offered to confirm any diagnosis of neurofibromatosis. 

Can neurofibromas be prevented?

No, but early diagnosis, monitoring and treatment can effectively minimise further complications. 

What are the treatment options for neurofibroma?

Treatment options may include surgical removal, radiation therapy, medications, and active monitoring. 

Do all neurofibromas need treatment?

Not all neurofibromas require treatment. If the patient is asymptomatic (no symptoms) and the individual is coping well, monitoring will likely be sufficient. 

Can neurofibromas grow back after surgery?

Depending on the type of neurofibroma, some neurofibromas, particularly the plexiform type, have a slight chance of recurring. 

How common are neurofibromas?

Neurofibromas are relatively common and can affect both adults and children, with varying ranges of severity. 

What is the difference between a neurofibroma and neurofibromatosis?

Neurofibromatosis is a genetic condition that causes the development of neurofibromas. A neurofibroma is a tumour which is usually benign. Individuals with neurofibromatosis are most likely to get neurofibromas, but not all individuals with neurofibroma have neurofibromatosis. 

Can neurofibromas cause complications or health issues?

Depending on the location, size, and type, neurofibromas can cause complications such as pain and functional impairment. 

Are there any specific risk factors for neurofibromas?

Individuals with NF1 and NF2 gene mutations are at increased risk; however, there are non-genetic causes that are not fully understood. 

Can neurofibromas affect children and adults differently?

Neurofibromas can affect both adults and children, with varying ranges of severity. 

Are there any new treatments or research advancements for neurofibromas?

There are many ongoing treatments and research. 

Is there a cure for neurofibromatosis?

Currently, there is no cure, but there are many effective treatments available to help manage the symptoms and prevent further complications. 

Summary of neurofibroma

Neurofibromas is a (usually) benign tumour that forms on the nerves with multiple underlying causes. The severity of neurofibroma depends on its type and location. Therefore, it is essential to get early diagnosis and treatment to help manage the symptoms and reduce any further risk of complications. Please seek advice from healthcare professionals if you are concerned or suspect you or someone you know has neurofibroma.