Neurofibroma

Neurofibromas are benign (WHO grade 1) peripheral nerve sheath tumours that are usually solitary and sporadic. There is, however, a strong association with neurofibromatosis type 1 (NF1), particularly for the plexiform subtype. 

Neurofibromas are generally divided into five morphological forms ^1-8:

• localised/nodular intraneural neurofibroma

• localised/nodular cutaneous neurofibroma

• diffuse cutaneous neurofibroma 

• plexiform neurofibroma 

• massive diffuse soft tissue neurofibroma

Diffuse cutaneous neurofibromas, plexiform neurofibromas and massive diffuse soft tissue neurofibromas have distinct radiological appearances and are therefore discussed separately. Localised cutaneous neurofibromas are generally not a radiological diagnosis, appearing as incidental findings on scans of patients with neurofibromatosis type 1. 

As such, the remainder of this article is a general discussion focussing on the most common localised intraneural neurofibromas which are by far the most common form of neurofibroma, representing 90% of these lesions ².

Epidemiology

Peak presentation of sporadic localised intraneural neurofibromas is between 20 and 30 years of age ⁵ with no sex predilection. When in the setting of neurofibromatosis type 1 they appear earlier, generally in early childhood ⁶. 

Associations

The majority of localised intraneural neurofibromas are solitary and sporadic and not associated with neurofibromatosis type 1. However, when multiple neurofibromas are present (or plexiform neurofibromas) then the diagnosis of neurofibromatosis type 1 is almost assured.

Clinical presentation

The clinical presentation of localised intraneural neurofibromas is non-specific and the result of either mass effect on surrounding lesions (or palpable lump) or neurogenic dysfunction. 

Pathology

They are considered WHO grade 1 tumours in the 5^th edition (2021) WHO classification of CNS tumours ⁶.

Macroscopic appearance

Unlike schwannomas, neurofibromas are not encapsulated and infiltrate between the nerve fascicles, making resection difficult. They primarily affect superficial cutaneous nerves, but occasionally affect larger deep-seated nerves. 

Microscopic appearance

Localised intraneural neurofibromas are composed of Schwann cells and fibroblasts, containing a rich network of collagen fibres.

Immunophenotype

• S100 positive in the Schwann cells

• CD34 positive in the stroma ⁶

Radiographic features

General imaging features of neurofibromas:

CT

• well-defined hypodense mass

• minimal or no contrast enhancement

MRI

• T1: hypointense

• T2

  • hyperintense

  • target sign

    • a hyperintense rim and central area of a low signal may be seen

    • this is thought to be due to a dense central area of collagenous stroma

    • although this sign is highly suggestive of neurofibroma, it is occasionally also seen in schwannomas and malignant peripheral nerve sheath tumours

  • fascicular sign

• T1 C+ (Gd): heterogeneous enhancement

Treatment and prognosis

For lesions not associated with neurofibromatosis type 1:

• localised and diffuse lesions may be treated surgically

• however, as neurofibromas infiltrate between nerve fascicles, they are unable to be separated from the parent nerve and complete excision requires the sacrifice of the nerve

• deep-seated lesions are therefore often managed conservatively

• local recurrence after excision is uncommon and malignant transformation is rare ²

For lesions associated with neurofibromatosis type 1:

• due to the multiplicity of lesions, unless debilitating symptoms are present, treatment of patients with neurofibromatosis type 1 is often non-surgical

• plexiform neurofibromas are particularly difficult to resect, often leading to incomplete resection

• recurrence after resection is frequent

• plexiform neurofibromas demonstrate a significant potential for malignant transformation

Complications

Although neurofibromas are usually indolent tumours they sometimes have atypical features (atypical neurofibroma) and uncommonly undergo malignant transformation (malignantperipheral nerve sheath tumour). Malignant change of sporadic localised intraneural neurofibromas is most frequently seen in large neurofibromas, and even then it only occurs in 5-10% of tumours ⁶. 

Note, when atypical features are encountered in the setting of neurofibromatosis type 1, then the term atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) should be used ⁶.