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

• Neurofibroma of Soft Tissue

What is 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
• There are clinically 5 types of Neurofibromas (based on presentation) and these include:
  • Localized skin form - localized cutaneous Neurofibroma
  • Diffuse skin form - diffuse cutaneous Neurofibroma
  • Localized intraneural Neurofibroma
  • Plexiform intraneural Neurofibroma
  • Massive, diffuse, soft tissue plexiform Neurofibroma
• The risk factors for the development of Neurofibroma is unknown in many cases. In some cases, multiple tumors may indicate the presence of neurofibromatosis type 1 (NF-1); solitary tumors are not associated with this genetic disorder
• Neurofibromas usually manifest in young men and women. They do not present any significant signs and symptoms in many cases. However, the tumors may involve the spinal nerves, cranial nerves, or small nerves of the skin causing associated signs and symptoms
• A treatment of Neurofibroma may be undertaken, if they are of cosmetic concern to the individual. In such cases, a simple surgical excision is sufficient treatment. The prognosis is excellent on removal of the Neurofibroma, since it is a benign tumor in many cases
• Some tumors forms are known to be premalignant, which may adversely affect the prognosis, if suitable treatment is not undertaken. The prognosis may also depend upon the presence of associated NF-1 (if present)

Who gets 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
• Both males and females are affected and 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 Neurofibroma? (Predisposing Factors)

• No definitive risk factors for solitary Neurofibroma have been currently identified. A majority of the tumors (about 90% of them) are solitary
• However, if more than one tumor is present, then an association with neurofibromatosis type 1 (NF-1) is observed. 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

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 Neurofibroma? (Etiology)

The cause of 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)
• In localized intraneural and plexiform Neurofibroma, 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 Neurofibroma?

In many cases, significant signs and symptoms of Neurofibroma may not be observed. However, the following may be noted, in some cases:

• In about 90% of the cases, the tumors are single that occur sporadically and not as part of a syndrome (non-syndromic tumors)
• In individuals with neurofibromatosis type 1, multiple tumors are seen. In such cases, the frequently observed tumors are the localized type of Neurofibroma
• In many cases, the tumors are solid, firm, and mobile (when felt by touch)
• All different forms of Neurofibromas can be painful
• Deep Neurofibromas involving major nerves can be quite large
• The most common site of the tumor is the skin (cutaneous Neurofibroma) - which usually involves the small nerves
• The second most site is around the spinal cord, involving the spinal nerves and spinal nerve plexus. This is followed by involvement of the cranial nerves
• Cutaneous Neurofibromas may range in size from 2 mm to 2 cm (average size 0.5 cm). The skin surface around the tumors may be pale tan
• Diffuse cutaneous Neurofibromas appear as plaque-like thickening of skin. The skin over such tumors may show increased pigmentation
• Intraneural Neurofibromas can cause a localized, nodular enlargement of a nerve
• Massive diffuse, soft tissue plexiform tumors are manifested as large-sized tumors. With these tumors, sometimes a bag-like thickening of skin is noted. The skin over large tumors may show increased pigmentation

If multiple tumors are noted, then it may occur against a background of neurofibromatosis type 1. In such cases, the associated signs and symptoms of NF-1 is observed.

How is Neurofibroma Diagnosed?

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

• Complete physical examination with evaluation of medical history
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Imaging studies, such as CT/MRI scans, of the affected region
• 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:

• Dermatofibrosarcoma protuberans
• Malignant peripheral nerve sheath tumor
• Neurotized nevus
• Schwannoma
• Spindle cell lipoma
• Superficial angiomyxoma
• Traumatic neuroma

Note:

• If there are multiple Neurofibroma tumors, then it is an important diagnostic indicator for the presence of neurofibromatosis type 1 (NF1) disorder
• On examination of the tumor specimen under the microscope by a pathologist, if there are melanin-containing pigmented cells, then it is called a pigmented Neurofibroma. These tumors are mostly benign

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 Neurofibroma?

Generally, no significant complications arise from Neurofibroma; however, in some cases, the following may be observed:

• These tumors may present cosmetic concerns, in which case a surgery may be proposed
• Diffuse cutaneous Neurofibroma: Often these tumors penetrate into the subcutaneous fat under the skin (which impedes surgical excision). This may prevent a complete removal of the tumor
• Massive tumors can infiltrate surrounding tissue
• Some forms of Neurofibroma are known to be precancerous, especially when large nerves are involved and the presence of neurofibromatosis type 1 is noted
• Complications may arise due to NF1 (if present)

How is Neurofibroma Treated?

In majority of cases, Neurofibromas are asymptomatic and no treatment may be required; or, they may be treated for cosmetic issues. The treatment depends upon the type of Neurofibroma and the signs and symptoms the individual may have.

The treatment measures adopted for Neurofibroma may include:

• The healthcare provider may chose to regularly monitor the tumor, if they are asymptomatic
• A complete surgical excision and removal can result in a cure. A complete removal of diffuse cutaneous Neurofibroma may be difficult, because the tumor is known to penetrate deep into the subcutaneous tissues
• Treatment of underlying neurofibromatosis type 1 (if present) may be necessary
• Follow-up care with regular screening and check-ups are important

How can Neurofibroma be Prevented?

Current medical research has not established a definitive method to prevent the formation of sporadic 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 Neurofibroma? (Outcomes/Resolutions)

• The prognosis depends on the clinical presentation of Neurofibroma. The common skin Neurofibromas are benign and are not known to transform into any malignancy. However, other types of Neurofibromas can turn malignant over time
• In general, the prognosis of Neurofibroma is excellent on its complete excision and removal. Since many are benign tumors, the prognosis is excellent, even if only periodic observation is maintained
• The localized skin forms are mostly benign; even the massive soft tissue tumors are typically benign
• Plexiform Neurofibroma and solitary intraneural Neurofibroma that involves large nerves can be premalignant. Such malignancies are increased in those with neurofibromatosis type 1 disorder
• Generally, diffuse cutaneous Neurofibromas do not become malignant; only rare cases of malignant transformation have been reported
• The prognosis of Neurofibromas associated with NF1, depends upon the severity of the signs and symptoms of the genetic disorder

Additional and Relevant Useful Information for Neurofibroma:

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