Plexiform neurofibroma is a subcutaneous or dermal tumor of the peripheral nerve sheath surrounding one or more nerve fascicles. It can occur in isolation or in patients with neurofibromatosis type 1. This tumor is usually benign although a small minority can undergo a malignant transformation. Diagnosis relies on ultrasound, computed tomography, magnetic resonance imaging, and histopathological evaluation.
Presentation
The name plexiform neurofibroma (PN) is derived from its appearance in the form of a network or a plexus surrounding branches of a peripheral nerve. It is typically a benign tumor and is composed of Schwann cells, perineurial components, fibroblasts, and hematopoietic cells surrounded by collagenous or myxoid stroma [1]. Although it can occur anywhere on the body, the head and neck region are the commonest sites [2].
Clinically, patients present with an irregular, tortuous subcutaneous or dermal mass resembling a "bag of worms" [3]. Other symptoms and signs depend on the mass effect of this swelling and it is essential to exclude extrinsic compression on neighboring structures or bone abnormalities. Tissue damage can lead to pain and sensorimotor deficits even in benign PN [4].
Although a plexiform neurofibroma is not pathognomonic of neurofibromatosis type 1 (NF -1), it is suggestive of the condition as it is found in up to 30% patients with NF-1. So the physician should look for features of NF-1 in patients with a plexiform neurofibroma.
Approximately 5% of PN can undergo malignant transformation. These patients present with pain, neurological deficits, and a rapid tumor growth, especially during puberty and pregnancy [3].
Entire Body System
- Anemia
These patients may present with epigastric pain, motility disorders, dyspepsia, anemia, hematemesis, intussusception, volvulus, intestinal perforation or bowel obstruction. [7] Zacharia et al ., while reviewing MRI findings of the abdominopelvic neurofibromatosis [ijdvl.com]
[…] neurofibromatosis type I, but other features are required to diagnose NF-1. [3] Familial multiple café au lait spots have been observed without NF-1 diagnosis. [7] They can be caused by vitiligo in the rare McCune–Albright syndrome. [8] Legius syndrome Fanconi anemia [en.wikipedia.org]
Small bowel Partial enterectomy Died due lung adenocarcinoma Park ( 15 ) 11/M Abdominal discomfort Ileum Partial tumor resection No clinical evidence of tumor growth after 10 months Rezende et al. ( 18 ) 42/M Abdominal discomfort, black stools, and anemia [scielo.br]
There were no signs of icterus, clubbing or anemia. Extra oral examination revealed a diffuse swelling on the left side of the face over the zygomatic region. The swelling measured approx 5x5 cm in size and had indistinct borders. [jisppd.com]
- Precocious Puberty
It is indicated for optic nerve pallor, visual changes, proptosis, or precocious puberty. Consider MRI scans of the head if headaches increase in frequency or intensity over time. Brain tumours are more common in NF2 than in NF1. [patient.info]
Precocious puberty in children with neurofibromatosis type 1. J Pediatr. 1995 Mar. 126(3):364-7. [Medline]. Hughes RJ, Scoble JE, Reidy JF. [emedicine.medscape.com]
Musculoskeletal
- Fracture
A bone graft is where a fracture in the bone is repaired by taking a small section of bone from another part of the body and using it to "plug" the fracture. The grafted section of bone will grow into the surrounding bones. [nhs.uk]
If tibial dysplasia is suspected and confirmed through an X-ray, a child should be referred to an orthopedist for orthopedic care directed towards the prevention and management of fractures. [understandingnf1.org]
Fracture can occur spontaneously or after trivial injury, and NF should be considered as a differential for non-accidental injury. The thoracic cage may be asymmetrical with flaring or prominence of the inferior ribs. [patient.info]
Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1). J Med Genet. 2009 Apr. 46(4):259-65. [Medline]. Smith A, Araoz PA, Kirsch J. Coronary arterial aneurysms in neurofibromatosis 1: case report and review of the literature. [emedicine.medscape.com]
Skin
- Hyperpigmentation
The substantial clinical and histologic overlap between neurotized congenital melanocytic nevi and the subset of plexiform neurofibromas with hyperpigmentation and hypertrichosis of the overlying skin (pigmented neurofibroma) has led to considerable confusion [ncbi.nlm.nih.gov]
The presence of hyperpigmentation and hypertrichosis simulated giant hairy naevus in our case. Orbital and periorbital regions of the face are the commonest sites of involvement [5], however in our case involvement of lower extremity was noticed. [ijdvl.com]
� They can cause massive enlargement of the entire extremity, hypertrophy of the long bones, and redundancy and hyperpigmentation of skin. PF may display increased cellularity as well as nuclear atypia. [webpathology.com]
Plexiform neurofibroma with overlying hyperpigmentation and hypertrichosis on the leg of a child with NF1. Lesion initially misdiagnosed as a congenital melanocytic nevus. [clinicaladvisor.com]
Five PNF in four children exhibited hyperpigmentation while the other two had hair excess in the tumor area. Two children had two and the other five had one PNF each. Size of tumors varied from 2 cm to 8 cm in greatest diameter (table 1 ). [wjso.biomedcentral.com]
- Skin Lesion
lesion Prevalence not common Prognosis benign Neurofibroma is an uncommon skin lesion in the peripheral nerve sheath tumour grouping. [librepathology.org]
Though large plexiform neurofibromas are thought to be diagnostic of NF1, a plexiform pattern may be seen in solitary skin lesions that are of little clinical significance. [dermnetnz.org]
lesion Bloom syndrome Chédiak–Higashi syndrome Congenital naevus Gaucher disease Hunter syndrome Jaffe–Campanacci syndrome Maffucci syndrome Multiple mucosal neuroma syndrome Noonan syndrome Silver–Russell syndrome Watson syndrome Tuberous Sclerosis [en.wikipedia.org]
- Subcutaneous Mass
In conclusion, considering neurofibroma (NF) as differential diagnosis for subcutaneous masses in head and neck area is critical for early diagnosis and treatment procedure. [ncbi.nlm.nih.gov]
Clinically, it presents as a subcutaneous mass which feels like a "bag of worms". Most of the time, it is a superficial cutaneous/subcutaneous lesion, but it can occur almost anywhere in the body. Symptoms may be related to local mass effect. [radiopaedia.org]
Multiple subcutaneous masses are seen in the right pelvic region. No abnormal bones or internal organs are observed. [journal.ac]
- Cutaneous Manifestation
Riccardi VM (1981) Cutaneous manifestation of neurofibromatosis: cellular interaction, pigmentation, and mast cells. Birth Defects Orig Artic Ser 17(2):129–145 PubMed Google Scholar 34. [link.springer.com]
Urogenital
- Incontinence
[…] compresses the spinal cord or nerve roots include: Changes in sensation (pain, numbness, tingling) Changes in movement (clumsiness in the hands, trouble walking) Changes in bowel or bladder function (a sense of urgency when urinating, bowel or bladder incontinence [columbianeurosurgery.org]
Generally, the bladder is affected, with occurrence of obstructive symptoms, urinary incontinence, flank pain, hematuria or polyuria (4). The approach to be adopted is still to be established and the objective is the management of symptoms (1,5). [rb.org.br]
Patients should be asked about incontinence. At each visit, minor changes in the sensory or motor examination should be documented carefully. [emedicine.medscape.com]
Neurologic
- Peripheral Neuropathy
Adverse reactions included transient somnolence in four, evanescent rash in two, and reversible mild peripheral neuropathy in two patients. Four patients showed less than 25% reduction in the tumor size. [n.neurology.org]
Peripheral nerve tumors. In: Dyck PJ, Thomas PK, eds. Peripheral neuropathy. 3 rd ed. Philadelphia: WB Saunders; 1993. p. 1623-39. [ Links ] 3. Nambi GI, Gupta AK, Kumaran S. Plexiform neurofibroma of the finger. [scielo.br]
- Cranial Neuropathy
Medical charts were reviewed to determine tumor characteristics (size, location, pathologic properties), patient characteristics (age at NF diagnosis and age at first operation), associated symptoms at presentation (cranial neuropathy, airway compromise [jamanetwork.com]
Workup
Beside history and physical examination, the workup of PN depends on radiological studies and histopathological evaluation. Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) are helpful in the diagnosis.
Ultrasonographic appearance is a target shaped mass with a hyperechoic center and resembling a cyst. However, the mass demonstrates a continuous peripheral nerve and this finding is confirmatory of a nerve sheath tumor [5]. Ultrasound cannot differentiate between a benign and malignant lesion.
MRI is the gold standard study as it is able to delineate the extent of the tumor as well as its origin from the nerve sheath [6]. Plexiform neurofibroma appears as a lesion in the form of a target with hyperintense T2 and a hypointense central signal [7]. MRI also helps to exclude sarcoma, schwannoma, lymphatic and venous malformations. In the case of a malignant transformation, the MRI will reveal an edematous zone around the lesion with cysts within the tumor while a tumor diameter exceeds five centimeters [8].
Positron emission tomography (PET) scan and CT scan can be performed if a biopsy is planned [9] [10].
Treatment
A correct diagnosis is an essential starting point in the treatment of neurofibromas and a misdiagnosis may lead to an inappropriate treatment. [ncbi.nlm.nih.gov]
Prognosis
[…] 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 [dovemed.com]
MPNST are soft tissue sarcomas that arise from peripheral nerves, being one of the most aggressive malignancies in humans with extremely poor prognosis. MPNST frequently arise from a previously undetected plexiform neurofibroma (PNF). [ncbi.nlm.nih.gov]
If a new treatment becomes available, some sub-group of patients within a certain stage may suddenly have a much better prognosis. If you find such a treatment, then you have a much better prognosis! [cancerguide.org]
MRI Reported signal characteristics include: T1: hypointense T2: hyperintense +/- hypointense central focus (target sign) T1 C+: mild enhancement Treatment and prognosis Although generally benign tumors, there is a significant potential for malignant [radiopaedia.org]
Etiology
In addition, we review the literature with respect to etiology, current treatment strategies, and the issue of surveillance for this complex lesion occurring in the pediatric population. [ncbi.nlm.nih.gov]
The etiology of sporadic neurofibromas is unknown. Systemic Implications and Complications Solitary neurofibromas are benign and not associated with any systemic complications. [clinicaladvisor.com]
(Etiology) The cause of Plexiform Neurofibroma is due to genetic mutations. [dovemed.com]
Neurofibromas can also be distinguished on histopathological examination by multiple different characteristics, including the presence of nerve fibers within the tumor. [10] Etiology Neurofibromas are peripheral nerve sheath neoplasms derived from a combination [eyewiki.aao.org]
Epidemiology
Clinical and epidemiologic features in NF1 Neurofibromatosis: phenotype, natural history, and pathogenesis Friedman JM, Riccardi VM. Clinical and epidemiologic features in NF1. In: Riccardi VM, editor. [researchgate.net]
Epidemiology Both sex can be affected. Neurofibromas are rare in children, but start develop in puberty. Up to thousands of neurofibromas can develop in one adult NF1 patient. [atlasgeneticsoncology.org]
Affiliations Department of Pediatrics University of Maryland, Baltimore, Maryland, USA Rosa Nguyen Department of Neurology, University Hospital Hamburg-Eppendorf, Hamburg, Germany Rosa Nguyen & Victor-Felix Mautner Department of Epidemiology and Public [nature.com]
However, surgical resection has a risk of nerve injury, pain may persist after removal of the tumour(s) and tumours may regrow at the same site. [ 1 ] Epidemiology [ 6 ] Both type 1 and type 2 NF are inherited as autosomal dominant conditions but, for [patient.info]
Pathophysiology
(A detailed review of what is known about the pathophysiology of various clinical features in NF1, including neurofibromas.) Packer, RJ, Gutmann, DH, Rubenstein, A, Viskochil, D, Zimmerman, RA. [clinicaladvisor.com]
We outline the pathophysiology of button battery-induced trauma and present key radiological features of button batteries that are important in preventing delayed diagnosis after pediatric ingestion. [researchgate.net]
Prevention
Recognition of this disease process and differentiating it from malignant transformation can prevent unnecessary surgery. [ncbi.nlm.nih.gov]
"Once we know the critical steps in the process, then we can design inhibitors to block each step in an effort to prevent or slow tumor formation." [news-medical.net]
References
- Marocchio LS, Oliveira DT, Pereira MC, et al. Sporadic and multiple neurofibromas in the head and neck region: a retrospective study of 33 years. Clin Oral Investig 2007;2013:165–169
- Ji Y, Xu B, Wang X, et al. Surgical treatment of giant plexiform neurofibroma associated with pectus excavatum. J Cardiothoracic Surg 2011;2013:119
- Murphey MD, Smith WS, Smith SE, Kransdorf MJ, Temple HT. From the archives of the AFIP: imaging of musculoskeletal neurogenic tumors: radiologic-pathologic correlation. Radiographics. 1999;19:5:1253–1280.
- Korf BR. Malignancy in neurofibromatosis type 1. Oncologist. 2000;5:6:477–485.
- Reynolds DL, Jacobson JA, Inampudi P, et al. Sonographic characteristics of peripheral nerve sheath tumors. American Journal of Roentgenology. 2004;182:3:741–744
- Fuchs B, Spinner RJ, Rock MG. Malignant peripheral nerve sheath tumors: an update. Journal of Surgical Orthopaedic Advances. 2005;14:4:168–174.
- Lin J, Martel W. Cross-sectional imaging of peripheral nerve sheath tumors: characteristic signs on CT, MR imaging, and sonography. American Journal of Roentgenology. 2001;176:1:75–82
- Wasa J, Nishida Y, Tsukushi S, et al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas. American Journal of Roentgenology. 2010;194:6:1568–1574.
- Ferner RE, Golding JF, Smith M, et al. [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Annals of Oncology. 2008;19:2:390–394.
- Bredella MA, Torriani M, Hornicek F, et al. Value of PET in the assessment of patients with neurofibromatosis type I. American Journal of Roentgenology. 2007;189:4:928–935.