Neuroma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [14]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[15] Maria Fernanda Villarreal, M.D. [16]

Synonyms and keywords: Traumatic neuroma; Morton neuroma; Amputation neuroma; Pseudoneuroma; Morton’s metatarsalgia; Plantar interdigital neuroma; Morton's intermetatarsal neuroma; Morton's entrapment; Morton's disease; Morton's neuropathy; Morton's neuralgia; Intermetatarsal neuroma; Intermetatarsal space neuroma; Intermetatarsal nerve entrapment; Interdigital neuroma; Interdigital nerve compression; Interdigital nerve enlargement; Joplin's neuroma; Plantar neuroma; Scar neuroma

Overview

Neuroma (Neuro- is from the Greek for nerve) is defined as a benign tumor of a nerve. However, neuroma commonly refers to any tumor of cells of the nervous system. Neuromas form part of the peripheral nerve sheath tumors and belong to Reactive class of tumors. Neuroma was first described by Thomas Morton in 1876. Neuromas may be classified according to histopathological features into 3 groups: Morton's neuroma, traumatic neuroma, and neoplasic neuromas. The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis. Neuroma is more commonly observed among patients aged between 15 to 50 years old. Neuroma is more commonly observed among middle aged adults. Females are more commonly affected with neuroma than males. The female to male ratio is approximately 5:1. Common risk factors in the development of neuroma include improper footwear and high impact sports (e.g., rock-climbing, ballet dancing). A major complication of neuroma is chronic neuropathic pain. On ultrasound, neuroma is characterized as a well-defined, hypoechoic lesion located in the intermetatarsal space proximal to the metatarsal head. Patients with neuroma usually appear with antalgic posture. Physical examination may be remarkable for tenderness to palpation and dysesthetic pain. Surgical excision is the treatment of choice for patients with neuroma; this surgical intervention is associated with a relatively favorable success rate, approximately 80%. The recurrence rate after surgery is as high as 50%.

Historical Perspective

  • The term neuroma originates from the following two Greek words:
  • In 1876, Neuroma was first described by Thomas Morton

Classification

Classification of neuroma
Types of neuroma Characteristic features Neoplastic nature
Morton neuroma[5][6][7][8][9][10]
  • Symptomatic collapse of the transverse arch by perineural fibrosis around a plantar digital nerve of the foot due to traction and increased pressure/chronic compression on the interdigital nerve
  • Usually located:
    • Third intermetatarsal space (between third and fourth metatarsals) or
    • At the bifurcation of the fourth plantar digital nerve
  • Also known as:
    • Morton’s metatarsalgia
    • Plantar interdigital neuroma
    • Morton's intermetatarsal neuroma
    • Morton's entrapment
    • Morton's disease
    • Morton's neuropathy
    • Morton's neuralgia
    • Intermetatarsal neuroma
    • Intermetatarsal space neuroma
    • Intermetatarsal nerve entrapment
    • Interdigital neuroma
    • Interdigital nerve compression
    • Interdigital nerve enlargement
    • Joplin's neuroma
    • Plantar neuroma
Non-neoplastic
Traumatic neuroma[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]
  • Arises from nerve injury (often as a result of surgery) leading to interrupted axons termed as neurotmesis
  • Regenerating axons lack an endoneurial tube to follow, resulting in a painful and tender mass of disorganized axons
  • Occurs at the end of injured nerve fibers as a form of unregulated nerve regeneration
  • Subtype of traumatic neuroma, called "Joplin neuroma" (a compression traumatic neuroma)
  • Occurs most commonly near a scar
  • Often very painful
  • Also known as:
    • Amputation neuroma
    • Pseudoneuroma
    • Scar neuroma
Palisaded encapsulated neuroma/solitary circumscribed neuroma
  • Nonpigmented, painless, small, firm nodules
  • Present in proximity to mucocutaneous junctions, usually face
  • Benign but can be mistaken for basal cell carcinoma
  • Surgical removal is the curative treatment
Mucosal neuroma[4][28]
  • Associated with MEN2B (inherited autosomal dominant trait caused by a single mutation in RET proto-oncogene)
  • Grossly present as:
  • Diffusely enlarged lips
  • Tongue nodules
  • Thickened eyelids (diffusely or nodularly), in the first or second decade of life
  • Comprised of markedly enlarged nerve fibers on microscopy
  • No specific treatment
Neoplasic neuroma
  • Solid nodular mass
  • Usually, separate from nerve fibers
Neoplastic
Acoustic neuroma [29]
  • It's a misnomer
  • It's actually a Vestibular Schwannoma
  • Slow-growing, benign tumor of acoustic nerve
  • Symptoms usually start after the age of 30 and include:
    • Dizziness
    • Persistent headaches
    • Vertigo
    • Loss of balance
    • Tinnitis
    • Numbness
    • Pain/weakness on one side of face
    • Blurred/double vision (temporary)
    • Ataxia
    • Hoarseness of voice
    • Dysphagia
Ganglioneuroma
  • Tumor of sympathetic nerve fibers arising from neural crest cells
Pacinian neuroma[30][31][32][33]
  • Very rare
  • Painful
  • Benign hyperplastic tumor of Pacinian corpuscles (mechanoreceptors responsible for sensitivity to vibration and pressure)
  • Sometimes associated with history of local trauma

Pathophysiology

  • The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis[1]
  • The pathogenesis of traumatic neuroma is characterized by:[34][18][35]
    • Tangle of neural fibers and connective tissue that develops following a peripheral nerve injury
    • Interruption in continuity of nerve causing wallerian degeneration (loss of axons in proximal stump and retraction of axons in distal segment), followed by exuberant regeneration of nerve and formation of mass of Schwann cells, axons and fibrous cells
    • Chronic reactive fibroinflammatory disorganized regeneration around a nerve after an injury (such as traction injury or chronic repetitive stress)
  • Morton neuroma is characterized by being located in the 3rd web-space, between 3rd and 4th metatarsal heads,[36] or sometimes in the second or fourth interspaces
  • Another subtype of traumatic neuroma is terminal neuroma (also known as "stump neuroma") which can occur after transection of the nerve (e.g. limb amputation)
  • There are no genetic mutations associated with the development of neuroma
  • On gross pathology, characteristic findings of neuroma, include:[37][38]
  • On microscopic histopathological analysis, characteristic findings of neuroma, include:[37][38]
    • Extensive fibrosis around and within the nerve
    • Digital artery
    • Thrombosis
    • Arterial thickening
S-100 Immunostain of Palisaded and Encapsulated Neuroma Source: Ed Uthman at flickr
Histopathology of Palisaded and Encapsulated Neuroma Source: Ed Uthman at flickr
Histopathology of Palisaded and Encapsulated Neuroma [1]
Histopathology of Palisaded and Encapsulated Neuroma [2]

Histopathology of traumatic neuroma

  • Numerous well formed small nerve twigs
  • Limited soft tissue infiltration
  • Contains axons in haphazardly arranged nerves within mature collagenous scar with entrapped smooth muscle
Traumatic neuroma Source: Libre Pathology
Traumatic neuroma [3]
Traumatic neuroma [4]
Traumatic neuroma [5]
Traumatic neuroma [6]

Histopathology of Morton neuroma

  • On gross pathology, morton neuroma resembles traumatic neuroma
  • On histopathology, it is comprised of:
    • Degenerated/demyelinated axons
    • Vascular hyalinization
    • Fibrosis
H&E stain of Morton's neuroma, low magnification [7]
H&E stain of Morton's neuroma, High magnification [8]
H&E stain of Morton's neuroma, Intermediate magnification [9]
H&E stain of Morton's neuroma, Intermediate magnification [10]
H&E stain of Morton's neuroma, High magnification [11]
H&E stain of Morton's neuroma, very high magnification [12]
H&E stain of Morton's neuroma, Intermediate magnification [13]

Common sites of involvement by traumatic neuroma

  • Most common oral locations are:
    • Tongue
    • Near mental foramen of mouth
  • Rarely involves:
    • Head
    • Neck

Causes

Differentiating Neuroma from other Diseases

  • Neuroma must be differentiated from other diseases that cause forefoot pain and numbness such as:[1][38]

Epidemiology and Demographics

  • Neuroma is a uncommon disease[38]

Age

  • Neuroma is more commonly observed among patients aged between 15 to 50 years old[38]
  • Neuroma is more commonly observed among middle aged adults

Gender

  • Females are more commonly affected with neuroma than males
  • The female to male ratio is approximately 5:1[38]

Race

  • There is no racial predilection for neuroma

Risk Factors

  • Common risk factors in the development of neuroma include:[37]
  • Improper footwear/tight shoes
  • High-impact sports (e.g., rock-climbing, ballet dancing)
  • Overpronation

Natural History, Complications and Prognosis

  • The majority of patients with neuroma are symptomatic at the time of diagnosis[1]
  • Early clinical features include neuropathic pain or local tenderness
  • If left untreated, the majority of patients with neuroma may progress to develop difficulty walking and limping
  • A significant complication of neuroma is chronic neuropathic pain
  • Prognosis is generally good, and the survival rate of patients with neuroma is 99%[39][40]

Diagnosis

Symptoms

Physical Examination

  • Patients with neuroma usually appear with antalgic posture[1]
  • Physical examination may be remarkable for:
  • Tenderness to palpation
  • Limitation of range of motion
  • Dysesthetic pain
  • Mulder's sign:
    • Clicking sensation in the involved interspace on palpation with simultaneous squeezing of metatarsal joints

Laboratory Findings

  • There are no specific laboratory findings associated with neuroma[37]

Imaging Findings

MRI

  • On MRI, characteristic findings of neuroma include:[42][43][44][45][46][47][48][49][7][50][51][7]
    • Dumbbell/ovoid-shaped lesion at a similar position to that described on ultrasound
    • T1: typically low-to-iso signal
    • T2: typically low signal but can sometimes be intermediate in signal
    • T1 C+ (Gd): tends to show intense enhancement
  • On MRI, characteristic findings of traumatic neuroma include:[1]
    • Fusiform swelling of a nerve or a bulbous mass at a nerve end
    • The parent nerve of some small nerve may difficult or impossible to discern
    • T2/STIR:inhomogeneous hyperintensity (may have a hypointense rim)
    • T1 C+ (Gd): variable contrast enhancement
Morton neuroma MRI Source: Radiopedia

Ultrasound

  • Ultrasound can help distinguish neuroma from:[52][53][54]
    • Intermetatarsal bursal swelling or
    • Synovitis in adjacent joints
  • On ultrasound, neuroma is characterized by the following findings:[1][55][56][57][58][59][60][61][62][6][63]
    • Round to ovoid
    • Well-defined, hypoechoic lesion
    • Located in the intermetatarsal space proximal to the metatarsal head
  • On ultrasound, traumatic neuroma is characterized by the following findings:[1]
    • Swollen nerve (mass-like)
    • Hypoechoic
    • Loss of normal fibrillar pattern
    • Usually small, but may be as large as 5 cm

Treatment

Medical Therapy

Conservative therapy for Morton neuroma

  • Morton neuroma should be managed conservatively before proceeding to expensive diagnostic procedures
  • Conservative measures for pain relief include:[64][65][66][67][68][69]
    • Decreasing pressure on the metatarsal heads by using:
      • Metatarsal support
      • Metatarsal bars
      • Metatarsal pads
      • Padded shoe insert (it's important to place inserts properly just proximal to the metatarsal head)
      • Orthotics
      • Specialized orthopedic shoes
      • Broad-toed shoe allowing spread of metatarsal heads
      • Determine proper shoe width while standing with the help of a professional shoe fitting device
    • Strength exercises for intrinsic foot muscles

Non-conservative medical therapy

Surgery

  • Surgery is the mainstay of therapy for neuroma[88][89][90][91][92][93][94][95][96][97][98][99][100][39]
  • Surgical excision is the treatment of choice for patients with neuroma; this surgical intervention is associated with a relatively favorable success rate, approximately 80%
  • The recurrence rate after surgery is as high as 50%

Prevention

  • There are no primary preventive measures available for neuroma[1]
  • Secondary prevention measures include: personal hygiene measures, such as wearing ergonomic shoes

References

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