Neurofibroma |
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Multiple facial nodules in
patient with neurofibromatosis. (courtesy of Dr. B. Neville, Charleston, SC) |
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The most common of the peripheral nerve tumors
is the benign neurofibroma, derived from an admixture of Schwann
cells and perineural fibroblast proliferations. Multiple
lesions are seen in persons with von Recklinghausen neurofibromatosis
(neurofibromatosis type I) and certain melanotic macules are considered
by some to be a variant of neurofibroma. An epidemiologic investigation
has determined a prevalence rate of 1 lesion per 25,000 adults (Table
1).
Clinical Features
The oral or pharyngeal neurofibroma is usually diagnosed in teenagers and young adults, although all ages are susceptible. There is no gender predilection and most examples arise from the tongue, buccal or labial mucosa. The lesion presents as a slowly enlarging, painless, soft nodule which is readily movable if situated immediately beneath the mucosa but is less so when located in deeper tissues. Many lesions feel like a "bag of worms" on palpation.
Typically less than 2 cm. in largest diameter at the time of diagnosis (Figures 1 & 2), some lesions have reached more than 8 cm. in size, and even larger oral lesions have been reported in patients with von Recklinghausen neurofibromatosis. Larger lesions may be lobulated or may produce a generalized local enlargement, such as macroglossia. Neurofibromas have been reported as well-demarcated radiolucencies within the jawbones, usually within the mandible, in patients with neurofibromatosis (Figure 3).
Von Recklinghausen neurofibromatosis is a hereditary condition which occurs in one of every 2,000-3,000 adults and is associated with multiple neurofibromas of the skin, mucous membranes and visceral tissues. Surface lesions may number in the hundreds and will vary from small, firm papules to huge, baggy, pendulous masses (elephantiasis neuromatosa); two-thirds of affected individual have only mild involvement.
Oral involvement in neurofibromatosis is seen in approximately 70% of cases, usually represented by a generalized enlargement of fungiform papillae of the tongue (50% of cases) and by1-3 relatively small submucosal nodules of neurofibroma (25% of cases). Pendulous examples of neurofibroma have not been reported for oral or pharyngeal sites.
Another feature of this syndrome is the presence
of melanotic macules of the skin, called café au lait ("coffee
with milk") spots. These macules are smooth, dark brown or tan, and measure
from a few millimeters to several centimeters across. They are usually congenital
but may develop during the first years of life; they do not occur on oral
or pharyngeal mucosa. The macule is characterized by an increase in melanin
pigment in the basal cell layer of the epidermis, but some authorities consider
it to be a variant of neurofibroma. Lisch nodules, translucent
brown macules of the iris, are seen in almost all persons affected by
neurofibromatosis. Various other anomalies affect the central nervous system
and the skeleton, producing sometimes severe bony deformities, CNS tumors,
macrocephaly, seizures, and mental deficiency.
Pathology and Differential Diagnosis
The neurofibroma consists of a cellular proliferation of randomly arranged spindle-shaped cells with elongated, wavy nuclei and few, if any, of the Verocay bodies so characteristic of the neurilemoma (Figures 4 & 5). The neural cells are associated with a variable amount of background stroma, usually a loose fibrosis with areas of myxoid matrix (Figure 6). Occasional areas show lesional cells in a whorled pattern reminiscent of pacinian bodies or the storiform pattern of fibrous histiocytoma. Mast cells are often abundant and can be helpful in the diagnosis; these can be more readily demonstrated with the Giemsa or toluidine blue stains, or can be detected immunohistochemically using antibody to the serine proteinase, chymase.
Sparsely distributed and usually small axons are frequently seen to traverse the tumor, especially with the use of silver stains. Tumorous proliferation may occur outside the perineurium, in which case there is poor demarcation from the surrounding fibrovascular tissues, or it may occur within the perineurium, resulting in a fibrous capsule or pseudoencapsulation of the neural mass.
Distinguishing the neurofibroma from benign
fibrous proliferations is usually not difficult because the latter lack the
unique wavy appearance of lesional cell nuclei. Those entities with myxoid
stroma, especially the myxoid lipoma, nodular fasciitis
and focal mucinosis, are more problematic, but again lack the thin,
wavy nuclei of the neurofibroma. Palisaded encapsulated neuroma
usually has parallel cellular streams or fascicles, a feature uncommon in
neurofibroma. Nuclear pleomorphism and mitotic activity is moreover, quite
unusual in the neurofibroma, thereby aiding in its differentiation from malignant peripheral nerve sheath tumor.
Treatment and Prognosis
Solitary neurofibroma not associated with a syndrome is surgically excised with minimal risk of recurrence. The malignant transformation potential of this tumor when not associated with a syndrome is minimal to nonexistent, but as many as 12% of persons affected by neurofibromatosis will develop cancer, usually neurofibrosarcoma or malignant neurilemoma (malignant schwannoma) transforming from a long-term neurofibroma of the skin of the trunk or extremities. Oral lesions in neurofibromatosis very seldom transform into sarcoma but may become large enough to interfere with proper function. Genetic counseling and evaluation of other family members should be performed for those suspected to be affected by a syndrome.
References (Chronologic Order)
Note: General references can be found by clicking on that topic to the left.
Shapiro SD, et al. Neurofibromatosis: oral and radiographic manifestations. Oral Surg Oral Med Oral Pathol 1984; 58:493-498.
D'Ambrosio JA, Langlais RP, Young RS. Jaw and skull changes in neurofibromatosis. Oral Surg Oral Med Oral Pathol 1988; 66:391-396.
Johnson MD, Kamso-Pratt J, Federspiel CF, Whetsell WO. Mast cell and lymphoreticular infiltrates in neurofibromas. Arch Pathol Lab Med 1989; 113:1263-1270.
Neville BW, Hann J, Narang R, Garen P. Oral neurofibrosarcoma associated with neurofibromatosis type I. Oral Surg Oral Med Oral Pathol 1991; 72:546-561.
Alatil C, Oner B, Unur M, Erseven G. Solitary plexiform neurofibroma of the oral cavity - a case report. Internat J Oral Maxillofac Surg 1996; 25:379-380.
Devarebeke SJ, Deschepper A, Hauben E, et al. Subcutaneous diffuse neurofibroma of the neck - a case report. J Laryngol Otol 1996; 110:182-184.
Pique E, Olivarese M, Farina MC, et al. Pseudoatrophic macules - a variant of neurofibroma. Cutis 1996; 57:100-102.
Sahota JS, Viswanatha A, Nayak DR, Hazarika P. Giant neurofibroma of the tongue. Internat J Ped Otorhinolaryngol 1996; 34:153-157.
Tsutsumi T, Oku T, Komatsuzaki A. Solitary
plexiform neurofibroma of the submandibular salivary gland. J Laryngol Otol 1996; 110:1173-1175.
Table 1: Gender-specific
prevalence rates per 1,000 population for selected oral masses and surface
alterations in U.S. adults, ranked by total frequency. Modified from Bouquot JE.
Common oral lesions found during a mass screening examination. J Am Dent
Assoc 1986; 112:50-57, and Bouquot JE, Gundlach KKH. Oral exophytic lesions
in 23,616 white Americans over 35 years of age. Oral Surg Oral Med Oral
Pathol 1986; 62:284-291. Diagnosis Number of lesions per 1,000
population* Males Females Total Leukoplakia 43.2 20.9 28.9 Torus palatinus 13.2 21.7 18.7 Irritation fibroma 13.0 11.4 12.0 Fordyce granules 17.7 5.2 9.7 Hemangioma 8.4 4.1 5.5 Papilloma 5.3 4.2 4.6 Epulis fissuratum 3.5 4.4 4.1 Varicosities, lingual 3.5 3.4 3.5 Papillary hyperplasia 1.7 3.8 3.0 Mucocele 1.9 2.6 2.5 Enlarged lingual tonsil 2.4 1.2 1.6 Lichen planus 1.2 1.1 1.1 Buccal exostosis 0.9 0.9 0.9 Median rhomboid glossitis 0.8 0.5 0.6 Epidermoid cyst 0.7 0.4 0.5 Oral melanotic macule 0.5 0.3 0.4 Oral tonsils (except lingual) 0.5 0.3 0.4 Lipoma 0.2 0.1 0.2 Ranula 0.2 0.1 0.2 Buccinator node, hyperplastic 0.1 0.1 0.1 Pyogenic granuloma 0.0 0.07 0.04 Nasoalveolar cyst 0.0 0.07 0.04 Neurofibroma 0.0 0.07 0.04
Torus
mandibularis
9.6
7.9
8.5
Erythema,
inflammatory
4.5
4.8
4.7
Fissured
tongue
3.5
3.1
3.2
Benign
migratory glossitis
3.4
3.0
3.1
Aphthous
ulcer
3.3
3.0
3.1
Herpes
labialis (herpes simplex)
2.4
2.6
2.5
Traumatic
ulcer
2.1
2.1
2.1
Angular
cheilitis
1.8
1.9
1.9
Smokeless
tobacco keratosis
4.3
0.2
1.7
Hematoma or
ecchymosis
2.0
1.4
1.6
Chronic
cheek bite
0.7
1.4
1.2
Squamous
cell carcinoma
2.5
0.1
0.9
Amalgam
tattoo
0.6
1.0
0.9
Leaf-shaped
fibroma
0.4
1.2
0.9
Hairy
tongue
1.2
0.3
0.6
Nicotine
palatinus
1.2
0.2
0.6
Atrophic
glossitis (smooth tongue)
0.6
0.5
0.6
Leukoedema
0.4
0.3
0.3
Gingival
hyperplasia
0.1
0.1
0.1
* total examined population = 23,616 adults over 35 years of age
