What are the other Names for this Condition? (Also known as/Synonyms)

• Plexiform Neurofibroma of Soft Tissue
• Plexiform Neurofibromatosis

What is Plexiform Neurofibroma? (Definition/Background Information)

• A neurofibroma is a type of peripheral nerve sheath tumor (PNST). This tumor may arise from the nerves underneath the skin surface, or from nerves deep within the body
• Plexiform Neurofibroma is an uncommon form of neurofibroma that is slow-growing and asymptomatic. A majority of these tumors are benign
• The tumor has the potential to infiltrate into the surrounding soft tissues. Plexiform Neurofibromas usually occur in a major nerve. It predominantly affects young children
• Study reports indicate that Plexiform Neurofibroma is unique to those with neurofibromatosis type 1 (NF-1). In such cases, the presence of multiple tumors, sited anywhere in the body, may be observed
• A treatment of Plexiform Neurofibroma may be undertaken, if they present cosmetic concern to the individual or if the symptoms are severe. In such cases, a surgical excision is sufficient treatment
• In most cases, the prognosis is excellent on removal of Plexiform Neurofibroma, since it is a benign tumor in a majority. However, some tumors are known to undergo malignant transformation, in which case the prognosis may be guarded

Who gets Plexiform Neurofibroma? (Age and Sex Distribution)

• Neurofibromas generally begin to appear during teenage and young adulthood (age range 15-20 years). But, they may be seen in individuals of any age group
• Plexiform Neurofibromas are usually seen in children. In rare cases, they may be observed at the time of birth
• Both males and females are affected; no preference for any gender is seen
• This condition is observed worldwide; there is no ethnic or racial predisposition

What are the Risk Factors for Plexiform Neurofibroma? (Predisposing Factors)

• Plexiform Neurofibroma is associated with neurofibromatosis type 1 (NF-1). NF-1 is a genetic condition that is characterized by skin pigmentation and the formation of non-cancerous tumors that affect the central nervous system. 1 in 3-4 individuals with NF-1 have this tumor type (syndromic Plexiform Neurofibroma)
• Rarely, these tumors are present in individuals without NF-1 (non-syndromic Plexiform Neurofibroma)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Plexiform Neurofibroma? (Etiology)

The cause of Plexiform Neurofibroma is due to genetic mutations.

• Currently, studies indicate defects in the following gene: NF1 gene
• Additionally, the following chromosomal aberration is noted:
  • Mutations in chromosome 17 due to loss of 17q (long arm); this is observed frequently
  • Mutations in chromosome 19 due to loss of 19p and 19q (on short arm and long arm respectively)
  • Mutations in chromosome 22 due to loss of 22q (long arm)
• Frequently, deletion in 9p is noted. It is also sometimes associated with abnormalities in the following genes:
  • CDKN2A
  • CDKN2B
  • MTAP

The above genetic abnormalities can be detected using molecular studies, which may play a significant role in identifying the tumor type, and in some cases, helping the healthcare provider take appropriate treatment decisions.

Note: The presence of multiple neurofibromas may indicate neurofibromatosis type 1, which is an autosomal dominant genetic disorder.

What are the Signs and Symptoms of Plexiform Neurofibroma?

The signs and symptoms of Plexiform Neurofibroma may include the following:

• Plexiform Neurofibromas are benign tumors (in most cases) of the peripheral nerves. They are known to locally infiltrate into the adjoining tissue structures
• Single or multiple tumors may be observed that usually involve a major nerve
• Plexiform Neurofibromas commonly occurs as a soft tissue mass, anywhere in the body. They can grow to fairly large sizes
• The frequent sites include the head and neck region, arms, legs, chest, and abdomen
• Pain is generally felt at the sites of involvement
• Deep neurofibromas involving major nerves can grow to large sizes

The associated signs and symptoms of neurofibromatosis type 1 may include:

• Hyperpigmented macules on the skin
• Axillary or inguinal freckles
• Multiple tumors: More than one form of neurofibroma tumor may be present
• Presence of tumors that affect the eye
• Long bone abnormalities

How is Plexiform Neurofibroma Diagnosed?

A diagnosis of Plexiform Neurofibroma may involve the following procedures and tests:

• Complete physical examination with evaluation of medical history
• Imaging studies, such as X-ray, CT, MRI scans of the affected region
• Sequencing of the NF1 gene through molecular testing
• Tissue biopsy: A tissue biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

A differential diagnosis may be undertaken to eliminate the following tumor types prior to a definitive diagnosis: 

• Filariasis
• Hemangioma
• Lymphangiomatosis
• Macrodystrophia lipomatosa
• Massive subperiosteal hematoma

Note:

• If there are multiple neurofibroma tumors, then it is an important diagnostic indicator for the presence of neurofibromatosis type 1 (NF1) disorder
• Radiological imaging studies may not help always distinguish between benign Plexiform Neurofibroma and malignant Plexiform Neurofibroma (or MPNST)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Plexiform Neurofibroma?

The complications of Plexiform Neurofibroma may include:

• Malignant transformation of the neurofibromas: 5-10% of the tumors may undergo malignant transformation. In such cases, when it becomes malignant, it is called a malignant peripheral nerve sheath tumor (MPNST). A malignant transformation may be indicated by the presence of the following features:
  • Sudden growth in size of tumor
  • Tumor getting more firm in consistency
  • Overlying skin gets ulcerated
  • Sudden increase in pain
  • Sudden increase in signs and symptoms associated with the involved nerve, such as weakening of the arm (if the arm nerve is affected), and weakening of the legs (if the leg nerve is affected)
• Currently, there are no well-established treatment measures available for malignant Plexiform Neurofibromas
• Cosmetic disfigurement
• It compromises the function of the affected part of the body
• Pain from the tumor can be debilitating
• Massive tumors can infiltrate surrounding tissue: Some tumors may be large and involve and entire arm or leg (about 30-90 cm in overall size). Such large tumors are sometimes known as elephantiasis neuromatosa
• Tumor recurrence following its surgical removal
• Complications may arise due to NF1 (if present) including bone disorders, short stature, tumors affecting the central nervous system and the gastrointestinal system causing severe signs and symptoms

How is Plexiform Neurofibroma Treated?

The treatment measures adopted for Plexiform Neurofibroma may include:

• The healthcare provider may choose to regularly monitor the tumor, if they are asymptomatic. A ‘wait and watch’ approach may be employed
• Surgery may be undertaken in case of severe signs and symptoms and/or cosmetic concerns
• In case of malignancy developing in a background of Plexiform Neurofibroma, additional therapy in the form of radiation and chemotherapy may be provided on a case-by-case basis
• Clinical trials to develop new treatment (biologic therapy) are currently underway
• Treatment of underlying neurofibromatosis type 1 (if present) may be necessary
• Long-term follow-up care with regular screening and check-ups are important

How can Plexiform Neurofibroma be Prevented?

Current medical research has not established a definitive method to prevent the formation of sporadic Plexiform Neurofibroma. However, if the tumors are present against a background of neurofibromatosis type 1, then the following may be considered:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Plexiform Neurofibroma? (Outcomes/Resolutions)

• In general, the prognosis of Plexiform Neurofibroma is excellent on its complete excision and removal, since many are benign tumors
• In many affected individuals, surgery is successful with no nerve dysfunction of the involved nerve being noted
• The prognosis of neurofibromas associated with NF1, depends upon the severity of the signs and symptoms of the genetic disorder
• Plexiform Neurofibromas may undergo malignant transformations to malignant peripheral nerve sheath tumors. Such malignancies are increased in those with neurofibromatosis type 1 disorder
• If the tumor becomes malignant, then the 5-year survival rate is about 16% in individuals with NF-1 (syndromic Plexiform Neurofibroma) and 53% in those without NF-1 (non-syndromic Plexiform Neurofibroma)

The prognosis of malignant tumors, in general, depends upon a set of several factors that include: 

• Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
• Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
• Age of the individual: Older individuals generally have poorer prognosis than younger individuals
• Individuals with bulky disease have a poorer prognosis
• Involvement of the lymph node can adversely affect the prognosis
• Involvement of vital organs may complicate the condition
• The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
• Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
• Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond
• Progression of the condition makes the outcome worse

Additional and Relevant Useful Information for Plexiform Neurofibroma:

There is no definitive proof that certain types of diet may influence the development of Neurofibromas.