|Year : 2007 | Volume
| Issue : 1 | Page : 30-35
Facial plexiform neurofibroma in a child with neurofibromatosis type I: A case report
K Patil1, VG Mahima1, SK Shetty2, K Lahari1
1 Department of Oral Medicine and Radiology, J.S.S. Dental College and Hospital, S.S. Nagar, Mysore - 15, India
2 Department of Oral and Maxillofacial Surgery, J.S.S. Dental College and Hospital, S.S. Nagar, Mysore - 15, India
Department of Oral Medicine and Radiology, J.S.S. Dental College and Hospital, S.S. Nagar, Mysore - 15
| Abstract|| |
Plexiform neurofibroma is a non-circumscribed, thick, and irregular benign tumor of the peripheral nerve sheath. It is a virtually pathognomonic and often disabling feature of neurofibromatosis type I. The diffuse and soft nature of plexiform neurofibroma is often compared to 'a bag of worms' and is difficult to distinguish from a vascular malformation or a lymphangioma, thus necessitating thorough clinical and histopathological examination and imaging of the lesion. We present a case of plexiform neurofibroma in a 12-year-old male child.
Keywords: Bag of worms, cafι au lait macules, neurofibromatosis type-I, plexiform neurofibroma, von Recklinghausen′s disease
|How to cite this article:|
Patil K, Mahima V G, Shetty S K, Lahari K. Facial plexiform neurofibroma in a child with neurofibromatosis type I: A case report. J Indian Soc Pedod Prev Dent 2007;25:30-5
|How to cite this URL:|
Patil K, Mahima V G, Shetty S K, Lahari K. Facial plexiform neurofibroma in a child with neurofibromatosis type I: A case report. J Indian Soc Pedod Prev Dent [serial online] 2007 [cited 2015 Feb 28];25:30-5. Available from: http://www.jisppd.com/text.asp?2007/25/1/30/31987
| Introduction|| |
Plexiform neurofibroma is a poorly defined benign tumor of the peripheral nerve sheath, which spreads out just under the skin or deeper in the body. It is a rare tumor and occurs exclusively in patients with neurofibromatosis type-I. Facial plexiform neurofibroma may produce various degrees of cosmetic and functional deformities in the head and neck region. Neurofibromatosis is an autosomal dominant disease with various manifestations including oral manifestations. ,,,
| Case Report|| |
A 12-years-old male child visited the department of Oral Medicine and Radiology with a chief complaint of a swelling on the left side of the face since four years and associated pain since one year. The patient first noticed the swelling four years back, which had an insidious onset and since then it had grown slowly to attain the present size. After an asymptomatic phase of three years the patient had started to experience mild, intermittent dull aching pain in the swelling since one year. There was no history of any regression in size of swelling or any discharge from the swelling. There was no history of trauma to the left side of the face. Symptoms of paresthesia or numbness were not present. The patient had never noticed similar swellings elsewhere in the body. The past medical, surgical, and dental histories were unremarkable. Family history did not reveal any similar complaints in immediate or distant relatives.
General physical examination showed a moderately built and nourished 12-year-old male child with steady gait, and satisfactory vital signs. 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. An irregularly shaped unevenly pigmented brown macule centered over the swelling was noticed, giving the appearance of a cafι au lait macule [Figure - 1],[Figure - 2]. On palpation there was no local rise in temperature. There was mild tenderness and the swelling had a very peculiar consistency, soft in most of the areas with few firm nodular areas, similar to that described in literature as a 'bag of worms'. No pitting was noticed. On auscultation no bruit could be detected. The presence of the swelling with a brown cafι au lait macule over it prompted the examination of the entire skin of the patient. This revealed multiple such macules over his back and arms [Figure - 3],[Figure - 4]. The macules ranged from a few millimeters to around 6 cm in diameter. Borders of the macules were smooth. Intra-oral examination showed no focus of pathology, and the swelling had not extended intra orally. No other significant intra oral findings were noted.
Based on the history and clinical presentation of multiple cafι au lait macules, a working diagnosis of Facial Neurofibroma with neurofibromatosis type I was given. For the facial swelling however, the differential diagnosis included hemangioma, lymphangioma, and arterio-venous malformation.
The patient was subjected to radiographic investigations. The panoramic and posterior-anterior skull views did not reveal any evidence of pathology [Figure - 5],[Figure - 6]. The Doppler ultrasonograph revealed a uniform, loculated hyperechoic mass with no evidence of vascularity within the mass [Figure - 7]. Computed tomography showed an irregular hypodense enhancing soft tissue mass lesion confined to the subcutaneous tissue of the left cheek. No bony involvement was evident. 3-D reconstruction also showed the same features [Figure - 8]. Complete hemogram showed values that were within the normal range.
The patient was then referred for incisional biopsy to the department of Oral and Maxillofacial Surgery, which was performed under general anesthesia. An oro-tracheal intubation was performed with a cuffed endotracheal tube. The surgical site was prepared with povidone iodine solution and the patient was draped. Incision for the procedure was marked in the pre-auricular region with temporal extension using modified Ward's technique and was cross-hatched. The incision was deepened to the subcutaneous plane and the skin flap was raised superficial to the parotid fascia till the anterior aspect of the gland. Multiple white, nodular masses, about 0.5 cm in size were noted on the parotid fascia, which were excised and sent for histopathological examination. The nodular masses were noted to be freely mobile with no extension into the parotid gland. Hemostasis was achieved, a vacuum drain placed and closure was done with 4-0 vicryl and 4-0 prolene sutures. The patient was then extubated and the post-operative period was uneventful.
The histopathological sections showed a lesion composed of bundles of nerve fibers arranged in a concentric manner with areas of myxoid changes. Schwann cells and fibroblasts were also seen. A histopathological diagnosis of Plexiform Neurofibroma was established [Figure - 9].
The case was then submitted to a physician and pediatrician to rule out other features of neurofibromatosis-I and also to rule out the possibility of any systemic involvement. The patient however was in good health with none of the clinical stigmata of the disease. A final diagnosis of facial plexiform neurofibroma associated with neurofibromatosis type-I was arrived at. It was decided that the patient be kept under observation and be reviewed once in every 6 months for as long as possible.
| Discussion|| |
Plexiform neurofibromas are benign tumors that spread out either just under the skin or deeper in the body. They originate from nerve sheath cells, subcutaneous or visceral peripheral nerves and can involve multiple fascicles. The term plexus refers to a combination of interlaced parts or a network. Plexiform neurofibromas are uncommon and occur almost exclusively in about 5-15% patients with neurofibromatosis-I.  Two types of plexiform neurofibromas have been recognized (i) Diffuse type/ elephantiasis neurofibromatosa and (ii) nodular type. 
They can arise anywhere along a nerve and have poorly defined margins. They may appear on the face, legs, or spinal cord and frequently involve the cranial and upper cervical nerves. The cranial nerves most commonly involved in plexiform neurofibromas are the fifth, ninth and tenth nerves.  They can be quite disfiguring and hemifacial hypertrophy can occur secondary to a plexiform tumor involvement.  These tumors are known to cause symptoms ranging from minor discomfort to extreme pain. ,, The consistency of the lesion has been compared to that of a 'bag of worms' because of the presence of soft areas interspersed with firm nodular areas and this very consistency was well appreciable in the lesion seen in our patient. They sometimes show vascular nature causing dangerous bleeding and may complicate surgical procedure. There appears to be an increase in the size of these tumors during puberty and pregnancy. ,
Neurofibromatosis is the term used to describe a group of genetic disorders that primarily affect the cell growth of neural tissues. At least eight forms of neurofibromatosis have been recognized, the most common form being neurofibromatosis type I (NF-I), or von Recklinghausen's disease of the skin. This accounts for about 90% of the cases. NF-I is estimated to occur in one of every 3000 births. There is no sex predilection. It is an autosomal dominant disease caused by a spectrum of mutations in the NF-I gene. It has one of the highest spontaneous mutation rates among genetic diseases. Only 50% of these patients have a positive family history of the disease and the remaining represent spontaneous mutations. ,,,,, This was the case in our patient.
The criteria for diagnosis of neurofibromatosis have been proposed by the National Institutes of Health Consensus Development Conference in 1988. The diagnostic criteria for Neurofibromatosis type I are met if a patient has two or more of the following features:
- Six or more cafι au lait macules over 5 mm in greatest diameter in prepubertal persons and over 15 mm in greatest diameter in post-pubertal persons.
- Two or more neurofibromas of any type or one plexiform neurofibroma.
- Freckling in the axillary or inguinal regions.
- Optic glioma.
- Two or more Lisch nodules (Iris hamartomas).
- A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis.
- A first-degree relative (parent, sibling or offspring) with neurofibromatosis type-I, based on the above criteria. ,
Other possible abnormalities that may be seen include central nervous system tumors, macrocephaly, mental deficiency, seizures, short stature and sclerosis. Sexual precocity is seen in 3-5% of effected children. ,, The patient in discussion fulfilled two of the above criteria; he had numerous cafι au lait macules and one plexiform neurofibroma.
The classical cafι au lait macule is said to have a smoother border when associated with neurofibromatosis than those seen in the McCune-Albright syndrome More Details. It has been accepted that any patient with six or more cafι au lait macules greater than 15 mm in diameter is likely to have neurofibromatosis until proven otherwise. Whitehouse D. in 1966 modified this for children to five or more spots greater than 5 mm in diameter. Less than 1% of healthy children may have three or more of such macules, although 1 to 2 cafι au lait macules are encountered in healthy individuals without any signs of the disease. Although most individuals who develop neurofibromatosis are not born with cafι au lait macules, these may develop during the first three years of life, prompting patients to seek medical attention for their child. 
Neurofibromas are the most common benign tumors of NF-I. They can develop at any point along a nerve and often form by late adolescence. These tumors are nodular and may be brown, pink or skin colored and soft to firm to touch. They may have a pathognomonic buttonhole invagination when pressed with a finger. Three subtypes of neurofibromas exist: cutaneous, subcutaneous and plexiform. Cutaneous and subcutaneous varieties are not specific for neurofibromatosis, whereas the plexiform variety is specific for the disease. ,
Roughly 20-30% of patients with neurofibromatosis have axillary freckling, known as Crowe's sign. Both axillary freckling and inguinal freckling may develop during puberty. Areas of freckling and regions of hypertrichosis occasionally overlay plexiform neurofibromas. This freckling is not seen in patients without neurofibromatosis. Nodules (Lisch nodules) and cafι au lait macules of the iris bilaterally have been described as characteristic of neurofibromatosis in ophthalmological literature. ,
Oral manifestations may occur in as high as 72% of the cases. The most common reported finding is enlargement of fungiform papillae seen in about 50% of all affected patients. However, the specificity of these findings for neurofibromatosis is unknown. Macroglossia is also known to occur. Only about 25% of the patients may show solitary or multiple oral neurofibromas. The tongue, lips, palate, buccal mucosa, gingiva and floor of the mouth are involved. ,,, In contrast, our case did not show any of these oral manifestations.
Radiographic manifestations of neurofibromatosis, especially in children, have been reviewed comprehensively. These include macrocranium, macroencephaly, cervical kyphosis, bony dysplasia, sclerosis, enlarged acoustic canal and bowing, and pseudoarthrosis, especially of the tibia. Oral radiographic findings may include enlargement of the mandibular foramen, enlargement and branching of the mandibular canal, increased bone density, concavity of the medial surface of the ramus, increased dimension of the coronoid notch and cyst like lesions. ,,,,, Our case did not show any of these manifestations.
Neurofibromas are composed of Schwann cells, fibroblasts, mast cells and vascular components. Histologically the neurofibromas occurring in neurofibromatosis show the same features as solitary neurofibromas except that usually no distinct margin is found between the neurofibroma and surrounding tissue.  On microscopy plexiform neurofibromas have a loose myxoid background with a low cellularity. They consist of poorly organized mixture of nerve fibrils with extensive interlacing of the nerve tissue. Small axons may be seen among the proliferating Schwann cells and perineural cells. These distorted masses of myxomatous peripheral nerve are still contained within perineurium and surrounded by neurofibroma. The tumor is immunoreactive for S-100 protien. ,,
Though surgery is the mainstay of treatment for solitary neurofibromas, in case of plexiform neurofibromas this is not a cure, because of the invasive nature and location of the tumors, which prevent complete resection. Plexiform neurofibroma is usually entwined with normal tissues and presents problems for the surgeon. Moreover, surgery is not undertaken unless the tumor turns symptomatic or disfiguring leading to an aesthetic problem. This is especially true in case of children. Resection of benign plexiform neurofibromas should be considered with great caution due to the significant chance of bleeding and injury. The lesions tend to recur after removal. ,,, The lesion in our patient caused only mild pain and was not of a major aesthetic concern. Hence, it was decided to keep the patient under observation and review him once every 6 months for as long as possible.
Alternatives to surgery that have been tried are retinoic acid therapy, angiogenesis inhibitors such as interferon-and thalidomide. Oral farnesyl protein transferase inhibitors and cytokine modulators are also under trial. About 5% of the plexiform neurofibromas may turn malignant, usually into malignant peripheral nerve sheath tumors. 
There is no specific therapy for NF-I. The treatment is often directed towards prevention or management of complications. Facial neurofibromas can be removed for cosmetic or functional purpose. Plexiform neurofibromas are rare and are seen in only about 5-15% cases with NF-I. 50% of the cases of NF-I are inherited as autosomal dominant traits; this emphasizes the role of genetic counseling for such patients. In patients with NF-I there is a propensity for the neurofibromas to undergo malignant transformation at a higher rate than that observed for comparable tumors in the general population. This is especially true for plexiform neurofibromas. ,,,
| Conclusion|| |
Although characteristically benign, plexiform neurofibromas can cause pain, disfigurement and functional changes and more importantly, may turn malignant. There appears to be no clear correlation between any two of the multiple features associated with NF-I. This makes it difficult to accurately predict the progress of the disease in a person at the present time. The one salient feature found in all cases of NF-I is its progressive nature. Thus the general trend in each case is towards a worsening of the disease. The role of a cognizant clinician lies in early diagnosis of the condition and alerting the patient about its future complications. Long term follow up of such cases is mandatory. Psychological counseling along with instilling of self confidence in such patients can possibly reduce their suffering and help them improve their quality of life.
| Acknowledgment|| |
Dr Sunila, Professor and H.O.D, Dept. of Pathology, J.S.S. Medical Hospital, Mysore. Dr. Kumarswamy, Asst. Prof., Dept. of Oral Pathology, J.S.S. Dental College and Hospital, Mysore.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9]
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