Neural tumors of the oral cavity

Neural tumors of the oral cavity

oral pathology Editor: CHARLES E. TOMiCH, D.D.S., M.S.D. American Academy of Oral Pathology Indiana University School of Dentistry I I21 West Michigan...

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oral pathology Editor: CHARLES E. TOMiCH, D.D.S., M.S.D. American Academy of Oral Pathology Indiana University School of Dentistry I I21 West Michigan Street Indianapolis, Indiana 46202

Neural tumors of the oral cavity B. A. Wright* and D. Jackson, Newcastle Upon Tyne. England The clinicaland histologic features of benign and malignant neural tumors of the oral cavity and jaws are reviewed. Some rarer histologic variants are mentioned. Particular attention is paid to the two syndromes involving neural tumors of the oral cavity, namely, neurofibromatosis and multiple endocrine neoplasia Ill. A previously unreported case of the latter is presented.

T

umors arising from peripheral nerves in the oral and paraoral tissues are not common. One review of 303 solitary neural tumors stated that 136 patients (45 percent) had their lesions in the head and neck.’ Of these, however, only 30 patients had tumors involving the oral cavity and submaxillary glands. In view of this rarity and the association of certain neural tumors with neurofibromatosis and multiple endocrine neoplasia III (M.E.N. III), it was considered appropriate to review both benign and malignant tumors of neural origin as they pertain to the dentist, the oral surgeon, and the pathologist (Table I). Recent casesseen in our department provide illustrative examples of some of the tumors discussed. REWEW Treuwutlc

or rmputath

neuroms

Traumatic or amputation neuroma may be defined as a nonneoplastic proliferation of nerve fibers, Schwann cells, and fibrous tissue occurring at the proximal end of a severed peripheral nerve. These arise following transsection or crushing injury to a peripheral nerve. The axons, in their myelin sheath, proliferate and, being unable to penetratethe scar tissue, grow laterally or double back on themselves.This producesa tangled massof axons and Schwann cells in densescar tissue. *Now with the Department of Pathology, Health Sciences Centre, University of Western Ontario, London, Ontario, Canada N6A Xl. oo3o4220/80/060509+14S01.40/0

@ 1980 The C. V. Mosby Co.

Table I. Tumors of the peripheral nerves 1. Traumatic neuroma 2. Schwannoma

Ancient schwannoma 3. Solitary neurofibmma 4. Neurofibmmatosis 5. Rare neural tumors: A. Palisaded and encapsulated neuroma B. Nerve she& myxoma

C. Ganglioncurofibmma 6. Multiple endocrine neoplasia III 7. Neurognic sarcoma

Clinically, the traumatic neumma appearsas a small nodule which may be painful on p&p&on. The overlying mucosa is usually normal in appeamnce.The most common sites intraorally are the lip, tongue, and mental nerve area.2Robinson and Slavkin have discussed the concept of amputation neuromas of dental origin (for example, following extraction or trauma to the dental complex). They reported ten cases of amputation neuroma, eight of which were closely associatedwith the alveolar bone. In only one of the eight caseswas there any radiographic evidence of pathosis. All the casesin our files have occurred following elective surgery. Rarely the traumatic neumma may be seen centrally within the mandible (for instance, folIowing a fracture).* Four cases of central traumatic neumma were reviewed by Eversole.J 508

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Fig. 1. Traumatic neuroma. Bundles of neural tissue(arrows) are separatedby bandsof fibrous connective tissue. (Hematoxylin and eosin stain. Original magnification, X55.)

Fig. 2. Schwannoma.Compressedperipheral nerve is presentat the top of the photograph. Beneaththat is Antoni A tissue of the schwannoma. (Hematoxylin and eosin stain. Original magnification, X55.) Histologically, the traumatic neuroma consists of dense masses of fibrous connective tissue, throughout which are bundles of nerve fibers, axons, and Schwann cells (Fig. 1). A trichrome stain may be useful in identifying collagen. We found an alcian blue stain helpful in staining perineural mucins which are not present in the scar tissue. Simple surgical excision is the treatment of choice.

Presumably because the scar tissue is eliminated, there is little tendency for recurrence. Schwannoma (neurilemoma) A great deal has been written about the nomenclature of the schwannoma. Although Harkin and Reed5 believed that Schwann cells were histochemically and ultrastructurally indistinguishable from perineural cells,

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evidence suggeststhat the cell of origin for this lesion is indeed the Schwann ~ell.*-~ It would seem appropriate, therefore, to reserve the term schwunnuma for this lesion. The schwannomamay be defined as a benign, encapsulated neoplasm which arises within a nerve and is composedprimarily of Schwanncells in a poorly collagenized stroma. The etiology is unknown, but it is thought that the lesion arises by a proliferation of Schwann cells at one point inside the perineurium, which then causesa displacement and compression of the surrounding normal nerve (Fig. 2). Clinically, the tumor may arise at any age. Some series have reported that the schwannoma is more common in adults, in contrast to the neurofibroma which tends to arise in young children.* Most reports suggest that the majority of tumors arise between the ages of 10 and 40 years,lo* I1 Some series report a female preponderance,“* l2 while others show a slight male dominance.lo Clinically, the tumor appearsas a smooth-surfaced,usually painless, soft-tissue swelling with intact overlying epithelium. There have been approximately 146 schwannomasreported from the oral soft tissueslo-l4 This includes the casesfrom our files but not those of Das Gupta and associates’or of Shklar and Meyers9The casesof Das Gupta and associatesare not included becausethey did not distinguish between schwannoma and solitary neurofibroma, a distinction which we and others” consider essential. Shklar and Meyer gave no clinical details of their cases. Of the 146 cases,just over half (76) occurred in the tongue, twenty-nine in the buccal or vestibular mucosa, and thirteen in the palate (Fig. 3). The remainder were in the gingivae and lip. To date, fourteen casesof intraosseousschwannomahave been reported.15,l6 Thirteen of these cases are from an excellent recent review.15 The most common location for these lesions was the posterior mandible. Although only a few cases are involved, it is of interest to note that eleven out of thirteen (85 percent) of the intraosseousschwannomas occurred in females. The schwannomais usually a solitary lesion. When multiple, however, they may be associatedwith neurofibromatosis.” The differentiation of schwannoma from neurofibroma is essential, becausean apparently ‘ ‘solitary ’ ’ neurofibroma may be a manifestation of neurofibromatosis. In 5 to 16 percent of the patients with neurofibromatosis, malignant changes will occur in one or more lesions.18*ls No such risk is apparent with schwannoma. Histologically, the schwannomais encapsulatedand consists of varying quantities of two types of tissueAntoni A and Antoni B. The Antoni A tissue is charac-

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Fig. 3. Clinical photographof a solitary schwannoma of the palate. terized by palisading of the spindle-shaped Schwann cells around a central acellular area (Fig. 4). This whole structure is known as a Verocay body. The central acellular area has recently been shown to be composed of reduplicated basement membrane and some cytoplasmic processesaIn areasAntoni A tissue shows streaming of the Schwanncells and is not “organized” into Verocay bodies. The second type of tissue, the Antoni B, is less cellular and shows microvacuolation of the intercellular substance(Fig. 5). The nuclei of the Schwann cells appearless elongated than in Antoni A tissue. In these areas the blood vessels may have thickened walls and mast cells may be found.2o The treatment for schwannomasis surgical excision. Recurrence is rare. Malignant change has been reported,21but this is an extremely unlikely event. vAmAurofscHwAmoMA Ancient (mdent nurltomoina) The ancient schwannomawas first described in the thorax by Ackerman and Taylor22in 1951. It is important to the histopathologist in view of the dangers of overdiagnosis. In a recent review of eleven cases,four out of eight lesions collected retrospectively were primarily diagnosed as sarcoma.2J The lesion is well encapsulatedand may contain both Antoni A and Antoni B tissue. Inflammatory cells, fibrous areas, and thick-walled blood vessels are all usually present. Areas of hemorrhage and hemosiderin may be seen. There are many areaswith large atypical and pleomorphic nuclei, some of which may be hyperchromatic (Fig. 6). Mitoses,are not generally a feature of this neoplasm. All three cases from our files were located in the neck, as were two of the eleven cases reported recently. 23 The lesion has been reported intraorally.24*25Both casescited were from the floor of

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Fig. 4. Photomicrographshowing the palisading of Schwann cells and the Verocay bodies as seenin the Antoni A tissue of schwannoma. (Hematoxylin and eosin stain. Original magnification, x.55.)

Fig. 5. Schwannoma. This shows the microvacuolation and fibrillary nature of Antoni B tissue. A thick-walled blood vessel is present (top right). A mast cell is indicated (arrow). (Hematoxylin and eosin stain. Original magnification, X 135.)

the mouth. The nuclear atypia should not be interpreted as evidence of malignancy. NEUROFI6ROMA AND NEUROFIBROMATOSIS Neurofibromas seem to occur in two forms: first, the circumscribed solitary neurofibroma which is not associated with neurofibromatosis and the second group which comprises all the various forms seen in neu-

rofibromatosis. The distinction is basically a cAinical one, because histologically it is often difficult to differentiate a solitary neurofibroma from a manifesta tion of neurofibromatosis. Solitary neurofibroma The solitary neurofibroma is a benign, slowly growing, relatively circumscribed but nonencapsulate :d neo-

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Fig. 6. Ancient schwannoma.Note nuclear pleomorphism and hyperchromatism. (Hematoxylin and eosin stain. Original magnification, X 135.)

Flg. 7. A solitary neurofibroma. The top of the field is nonlesional collagen. This may be contrastedwith the wavy nature of tumor collagen fibers (bottom of field). The nuclei here are fusiform. (Hematoxylin and eosin stain. Original magnification, X 80.)

plasm, originating in a nerve and consisting of Schwann cells, perineural cells, and varying amounts of mature collagen. By definition, the patient must have none of the other manifestations of neurofibromatosis. One article did not distinguish between solitary neurofibroma and schwannoma.’ We believe that this distinction must be made so that when a histologic diagnosis of neurofibroma is rendered the other stigmata of

neurofibromatosismay be sought. Although Das Gupta and colleagues’ analyzed all their casestogether, they did state that the patients diagnosed as having “solitary” neurofibromas had no clinical evidence of neurofibromatosis. The neurofibroma is thought to arise by a local increase in endoneurial matrix which spreads the Schwann cells apart. At the same time, the Schwann

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Fig. 9. The intraoral lesion of the patient with neurofibromatosis illustrated in Fig. 8.

Fig. 8. A view of the body of a patient with neurofibromatosis showing multiple discrete neurofibromas and cafk. au lait spots (arrows).

cell cylinders elongate, become tortuous, and increase in number. Presumably, perineural cells and cells with fibrogenic potential are also involved. There is little information available about the relative frequency of solitary oral neurofibromas and oral manifestations of neurofibromatosis. One article by Shklar and Meyer9 reviewed sixteen oral neurofibromas, of which eleven were solitary and five (31 percent) were oral manifestations of neurofibromatosis. Of the nineteen neurofibromas reported by Cherrick and Eversole l* four (20 percent) were manifestations of neurofidromatosis. Of the neurofibromas in our files, 60 percent were associated with von Recklinghausen’s disease of skin. Although small numbers of casesare involved, these data imply that between 20 and 60 percent of intraoral neurofibromasmay be associatedwith neurofibromatosis. Clinically, the solitary neurofibromas are submucosal, nontender, discrete masses.They may occur at any age. The tongue, buccal mucosa, and vestibular area are the most common sites, The excellent review by Ellis, Abrams, and Melrose15 cites

twenty-two intraosseousneurofibromas, including their own cases. Nineteen of these could be classified as solitary, becausethe patients had no evidence of neurofibromatosis. The posterior mandible was the most common location, most patients were under 45 years of age, and the female-to-maleratio was much lower than for intraosseousschwannoma(1.2: 1). Histologically, the solitary neurofibroma is well demarcatedfrom the surrounding connective tissue. This is in contrast to many neurofibromas of neurofibromatosis. The tumor cells are elongated, fusiform, and often have “comma-shaped” nuclei. They are set in a myxomatous, microvacuolated matrix of wavy collagen fibers (Fig. 7). Mast cells, said to be more numerous than in the Antoni B tissue of the schwannoma, are common and may constitute a useful diagnostic pointer.20Blood vessel walls are often thickened. One ultrastructural study reported that the neurofibroma seemedto contain more mature collagen than did the schwannoma; fibrous long spacing collagen was also seen.6 The treatment for solitary neurofibromasis excision. Although one report noted an association of solitary neurofibromasand schwannomaswith unrelated malignancies (for example, breast and gastrointestinal cancer’), the malignant potential of solitary neurofibroma is not known. It may be negligible, as in schwannoma. It is unlikely to be as high as is reported with neurofibromatosis. Neurofibromatosis of skin)

(von Recklinghausen’s

disease

Neurofibromatosis is an autosomal dominant condition consisting of multiple neurofibromas, skin pigmentation, bony abnormalities, and a predilection to develop neurofibrosarcomasin about 5 to 16 percent of all cases.In addition, there is an increasedincidence of pheochromocytoma. The syndrome has a remarkably

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Fig. 10. The histology of the lesion illustrated in Fig. 9. There is no distinct border between the neurofibrotna and the surface epithelium. Note the ahnotmal peripheral nerve at the bottom of the field. (Hematoxylin and eosin stain. Original magnification, X 33.) variable expressivity, and about half the casesare said to be spontaneous mutations.26 One recent article2’

quotes evidence that a more detailed examination of parents and siblings of patients with so-called spontaneous mutations may show some abnormalities. The classic pigmented skin lesion of neurofibromatosis is the cafe au lait spot. This is said to have a smoother border when associatedwith neurofibromatosis than those seen in the McCune-Albright syndrome.26It has been generally acceptedthat any person with more than six cafe au lait spots greater than 1.5 cm. in diameter has neurofibromatosis until proven otherwise.28Whitehouse has modified this for children to five or more spots greater than 0.5 cm. Examination of the cafe au lait spots in patients with neurofibromatosis revealed that there were more DOPApositive melanocytes than in the surrounding skin, whereas freckles contained fewer melanocytes than in the surrounding skin. 3o In addition, the melanocytes from cafe au lait spots contained giant melanin granules.30This latter finding has been challenged by Silvers and associates,31who stated that the absenceof giant pigment granules in cafe au lait spots should not rule out a diagnosis of neurofibromatosis. Roughly 20 to 30 percent of patients with neurofibromatosis have axillary freckling. 28This freckling is not seen in patients without neurofibromatosis2* The ophthalmologic literature contains reference to cafe au lait spots and nodules of the irides bilaterally as being characteristic of neurofibromatosis.32Nordmann

and Brini32 cite three studies in which thirty-one of thirty-three, twenty-nine of thirty-one and, their own, ten of eleven patients with neumfibromatosis had bilateral pigmentation and nodules of the hides. Pigmentation of the fundus has also been seen in neurofibromatosis.33 The radiographic manifestations of neurofibromatosis, especially in children, have been the subjectof an excellent, comprehensivereviewa2?Theseinclude macrocranium, macroencephaly, cervical kyphosis, and bowing and pseudarthrosis, especially of the tibia. Acoustic neuromas and optic nerve gliomas have also been associatedwith neurofibromatosis.27 The neurofibromas, when seenperipherally, seemto occur in two separateclinical patterns: (1) as multiple discrete nodules (Fig. 8) and (2) as great pendulous, often pigmented, massesof tissue. Oral mucosal involvement is not common. Stones3*puts the incidence of oral lesions of neurofibromatosis at about 2 percent, while Gorlin, Pindborg, and [email protected] state that it is probably between 4 and 7 percent. Baden and coauthors,35quoting Berberg, state that approximately 6 percent of eighty-four patients with neurofibromatosis had oral involvement. The mucosal lesions may be solitary (Fig. 9) or multiple, as in the case reported by Simpson .36Unilateral oral involvement seems to be the more usual presentation, as seen in Fig. 9 and in the

reports by Baden and associates,35Simpson,3Band Freeman and Standish. 37The tongue is commonly involved.35 A recent report by Lorson and [email protected]

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Fig. 11. A plexiform neumfibroma showing myxomatous peripheral nerve contained within perineurium and surrounded by neurofibroma. (Hematoxylin and eosin stain. Original magnification, X33.)

Fig. 12. Nerve sheathmyxoma. This shows the fibrous septaand intervening myxomatous areas. (Hematoxylin and eosin stain. Original magnification, X33.)

stressed the bony manifestations in the jaws. They reported a deep coronoid notch together with sphenoidal and orbital dysplasia in their patient. Freeman and Standish3’ reported sphenoidal involvement in their case, but a lateral jaw radiograph disclosed a normal coronoid notch. Only three of twenty-two intraosseous neurofibromas reviewed were associated with neurofibromatosis . I5

Histologically, the lesions show the same features as those described in solitary neurofibroma except that usually no distinct margin is found between the neurofibroma and the surrounding tissue (Fig. 10). The lesions may be of a plexiform type, that is, distorted masses of myxomatous peripheral nerve still contained within perineurium and surrounded by neurofibroma (Fig. 11). Harkin and Reed” suggest that the plexiform

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Fig. 13. A high-power view of the specimen presentedin Fig. 12 showing stellate and syncytial multinucleate cells. (Hematoxylin and eosin stain. Original magnification, x 135.)

Fig. 14. A ganglion-like cell found in an ancient schwannoma.(Hematoxylin and eosin stain. Original magnification,

X

350.)

neurofibroma seems to occur only with neurofibromatosis. Indeed, they state: “The patient who has a plexiform neurofibroma is considered to have neurofibromatosis even if it is the sole manifestation of the disease. ” The treatment of neurofibromatosis is mainly symptomatic, consisting of surgical removal of lesions for functional or cosmetic reasons. A number of patients (between 5.5 and 16 percent) with neurofibro-

matosis will have malignant changes in one or more of their lesions.‘*, Is, 3g* 4o The prognosis, once rnalignancy has developed, is considered poor.40 RARE NEURAL TUkM)RS OF THE HEAD AND [email protected] PaHsaded, erwm$mum ltewoma

This tumor was first described by Reed, Fine, and Meltzer,41 who classified the lesion as a true neuroma

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syncytium may be seen(Figs. 12 and 13). Palisading of nuclei and structures resembling pressure receptors have been reported.4gThe tumor stains intensely with alcian blue. Webb4g found ultrastructural features which suggestedthat the cell of origin for this neoplasm is the perineural cell. This has been confirmed by Sist and Greene, who also described Schwann cells and .;ells resembling perineural cells but with no basement membrane. The lesion appearsto be benign. Ganglioneurofibroma

Fig. 15. Multiple discrete mucosal neuromas in a patient with multiple endocrine neoplasia III.

becausethe proportion of axons to Schwann cell fascicles is approximately 1: 1. This presence of a large number of axons in a well-encapsulated lesion differentiates it from a schwannoma. One case has been reported in the dental literature by Tomich and M011.~~ The tumor is considered to consist of an overgrowth of axons and sheathcells within the perineurium. It has a predilection to occur around the eyes and lips.41, 42 Histologically, the lesion is well encapsulated. There are myxomatous areas and areas of palisading which may resemble Antoni A tissue. Axons are present in Schwann cell fascicles. Nuclear streaming may also be seen. In view of the encapsulation, the lesion can be enucleated. Nerve sheath myxoma

This tumor was first describedas such by Harkin and Reed,5although reports of similar lesions prior to that time used the term pacinian neurojibroma.43 Subsequent [email protected] retained that term, presumably becausemany areasof the lesions resembled pacinian corpuscles. The literature contains six casesin the oral cavity.45-4*One was in the tongue,45and one was in the anterior maxilla. This latter case was called pacinian neurofibroma.46Tomich,47 in his article on oral focal mucinosis, mentions two cases of nerve sheath myxoma, one in the tongue and one in the buccal mucosa. These caseshave recently been reviewed by Sist and Greene,48who added two casesof their own, one from the buccal mucosaand one from the retromolar area. In addition, one of us (B.A.W.) has seena caseinvolving the palate of a 15-year-old girl. Too few cases of nerve sheathmyxoma have beenreported to permit us to draw any conclusions as to clinical presentation. Histologically, the tumor consists of well-defined lobules of myxomatous tissue separatedby fibrous septa. The cellularity varies, but stellate or hyperchromatic bipolar cells are present. Multinucleated cells appearing as a

(ganglioneuroma)

This lesion generally occurs in children and young adults, is usually found in the posterior mediastinum, and is thought to arise by differentiation of immature neuroblasts.l7 Occasionally, however, lesions which histologically resembleganglioneurofibromasare found in the floor of the mouth and in the neck. In the neck these lesions may possibly represent nonneoplastic sympathetic ganglia or perhaps involvement of a sympathetic ganglion by neurofibroma.5j l7 In the floor of the mouth, the parasympathetic ganglia may be involved. It should be noted that Thoma and Goldman50 presenteda very unusual case of a lesion with numerous ganglion cells arising centrally within the mandible following avulsion of the mandibular nerve. There are no absolute histologic criteria to differentiate a ganglioneurofibroma from a nonneoplastic ganglion or involvement of a ganglion by neurofibroma. However, binucleate or multinucleate ganglion cells are quite common in ganglioneurofibroma but would be extremely rare in the other two entities to be included in the differential diagnosis. In addition, ganglion-like cells may be seen in ancient schwannomas from the neck (Fig. 14). Multiple endocrine neoplasia Ill (M.E.N. Ill)

Multiple endocrine neoplasia, an autosomal dominantly inherited syndrome, is characterizedby multiple mucosal neuromas, medullary carcinoma of the thyroid, pheochromocytoma, and marfanoid habitus. It was apparently first described in 1922-l92326but more recently amplified by Williams and Pollock.51 Gorlin and Mirkin52 reviewed forty-four cases,and Khairi and associates,53 who further defined the syndrome, reviewed forty-one cases, including their own four. The basic defect appearsto be hyperplasia and neoplasia of neural crest derivatives. CASE REPORT

A 9-year-old boy of asthenicbuild wasreferredfor evaluation of multiple nodules on the tongue (Fig. 15), upper lip, and gingivae. He was in good health and in no apparent distress. Biopsy revealed that the lesions were plexiform neuromas--that is, bundles of atypical hyperplastic nervous tissue within the perineurium and not surrounded by neu-

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Fig. 16. Histologic featuresof the lesions illustrated in Fig. 15. Note the hyperplastic bundles of peripheral nerve contained within the perineurium and surrounded by normal connective tissue. (Hematoxylin and eosin stain. Original magnification, X 33.) rofibroma (Fig. 16). (One recent repor?54called these lesions plexiform neurofibmmas, which they are not.) A tentative diagnosis of M.E.N. III wasmadeon the basis of the biopsy findings, and the patient was referred for evaluation of his thyroid gland. Although no gross abnormality was found, the stimulated serum calcitonin levels were 26 ng./ml. and 8.9 ng./ml. on two occasions. This compareswith a normalof

lessthan 50 pg./ml. An electivethyroidectomyrevealedtwo areasof medullarycarcinoma.Threeyearslater a plexiform neuromawasremovedfrom theleft vocalcord.Thepatientis alive and well at the ageof 16 years,with no evidenceof pheochromocytoma. This case illustrates the typical location of the mucosal neuromas-tongue, lips, and gingivae. (The palpebral conjunctiva and eyelid margins are often involved.26) It also demonstratesthe most important aspect of the syndrome for the dentist, the oral surgeon, and the oral pathologist, namely, that the mucosal lesions precedethe development of medullary carcinoma of the thyroid and pheochromocytoma. Thus, early diagnosis can be life saving. Namgmic

swcoma

In few other areasof pathology are criteria for diagnosis as indistinct, confused, or imprecise as in the area of malignant neural tumors. It is not our intention to add to this confusion, and thus we adopt a relatively simple approach. Neurogenic sarcomafalls broadly into two categories: (1) malignant change in lesions of neurofibromatosis, designatedby Harkin and Reed5as neurofibrosar-

coma and (2) malignant neural tumors diagnosed, in the absenceof neurofibromatosis, on the basis of surgical or (in the case of the mandible) radiographic evidence of origin from a nerve trunk or those neoplasmswhich, on histologic examination, show one of the recognized neural patterns (for example, malignant epithelioid schwannoma). Neurogenic sarcoma is not a common diagnosis if the above criteria are used. In the oral cavity it appears to be more common centraily within the mandible than in soft tissues.4*js This is hardly surprising in view of the presence of a large peripheral nerve within the mandible. As stated previously, malignant transformation of neurofibromas in neurofibromatosis occurs in approximately 5.5 to 16 percent of the cases. Croker and Greenstein,5fi reporting a case of malignant schwannoma of the stomach in a patient with neurofibromatosis, have discussedthe use of electron microscopy in differentiating the lesion from leiomyosarcoma. A recent case of malignant schwannoma of the lingual

nerve in a patient apparently with neurofibromatosis has been reported by Wassermanand co-authors.57Upton, Hayward, and KerP reported a case located centrally within the mandible in a patient with no evidence of neurofibromatosis. There are not enough cases to permit us to draw any firm conclusions as to age and sex distribution of neurogenic sarcomain the oral cavity or mandible.4 Fig. 17 shows a radiograph of a patient with a malignant schwannoma. There is enlarge-

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Fig. 17. Radiograph showing an enlarged mental foramen and widening and loss of delineation of the mandibular canal in a patient with malignant schwannoma.

Fig. 18. Malignant schwannoma from the case illustrated in Fig. 17. Note the high degree of cellularity, the hyperchromatic nuclei with streaming, and the attempt at palisading in the center of the field. (Hematoxylin and eosin stain. Original magnification, X55.)

ment of the mental foramen and widening and loss of delineation of the mandibular canal. We consider this good radiographic evidence of origin from a nerve. The histologic appearance was that of a malignant schwannoma (Fig. 18). Histologically, neurogenic sarcoma is a highly cellular neoplasm comprising plump spindle-shaped cells, usually with elongated cytoplasmic processes. The cells are often arranged in characteristic streaming or swirling patterns (Fig. 18). Areas showing more collagenous stroma or myxomatous change may be present. There may be varying degrees of nuclear pleomor-

phism, and mitoses are often numerous. Atypical cellular areas in neurofibromas, especially in patients with neurofibromatosis, may connote malignant change. One histologic type of malignant tumor shows round to polyhedral cells which are sometimes arranged in nests reminiscent of melanoma. This pattern has tentatively been classified as malignant epithelioid schwannoma by Harkin and Reed.5 The treatment of choice for neurogenic sarcoma is wide surgical excision. The prognosis for tumors in the oral cavity and jaws is difficult to determine. The case reported by Upton, Hayward, and Kerr5-s showed no

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recurrence 3?4 years later, while the patient described by Wassermanand associates5’died 21 months after initial diagnosis. CONCLUSION

The spectrum of neural tumors, benign and malignant, which can occur in and around the oral cavity has been reviewed. The salient features of two syndromes involving neural tumors of the oral cavity have been discussed, and illustrative examples of each have been presented. A case of malignant schwannoma with radiographic evidence of origin from the mandibular nerve has been presented. We wish to thankMr. H. T. Oliver for preparingthe illustrations.

and Mr. T. B. Conroy

REFERENCES 1. Das Gupta, T. K., Brasfield, R. D., Strong, E. W., and Hajdu, S. I.: Benign Solitary Schwannomas (Neurilemomas), Cancer 24: 355-366, 1969. 2. Shafer, W. G., Hine, M. K., and Levy, B. M.: A Textbook of Oral Pathology, ed. 3, Philadelphia, 1974, W. B. Saunders Company, pp. 189-191. 3. Robinson, M., and Slavkin, H. C.: Dental Amputation Neuromaa, J. Am. Dent. Assoc. 70: 662-675, 1965. 4. Eversole, L. R.: Central Benign and Malignant Neural Neoplasms of the Jaws: A Review, J. Oral Surg. 27: 716-721, 1969. 5. Harkin, J. C., and Reed, J. J .: Tumors of the Peripheral Nervous System, 2nd series, Fast. 3, Washington, 1969, Armed Forces Institute of Pathology, pp. 29, 51, 60-64, 148, 149. 6. Fisher. E. R.. and Vuzevski. V. D.: Cvtoeenesis of Schwannoma (Neurilemoma), Neurolibroma, Dermatofibroma, Dermatofibrosarcoma as Revealed by Electronmicroscopy, Am. J. Clin. Pathol. 49: 141-154, 1%8. 7. Waggener, J. D.: Ultra-structure of Benign Nerve Sheath Tumors, Cancer 19: 699-709, 1966. 8. Chen, S.-Y., and Miller, A. S.: Neurofibmma and Schwannoma of the. Oral Cavity, ORAL SURG. 47: 522-528, 1979. 9. Shklar, G., and Meyer,I.: Neurogenic Tumors of the Mouth and Jaws, ORAL SURG. 9: 1075-1093, 1963. 10. Hatziotis, J. Ch., and Asprides, H.: Neurilemoma (Schwannoma) of the Oral Cavity, ORAL SURG. 24: 510-526, 1967. 11. Cherrick, H. M., and Eversole, L. R.: Benign Neural Sheath Neoplasm of the Oral Cavity, ORAL SURG. 32: 900-909, 1971. 12. Oberman, H. A., and Sullenger, G.: Neurogenous Tumors of the Head and Neck, Cancer 20: 1992-2001, 1967. 13. Gallo, W. J., Moss, M., Shapiro, D. N., and Gaul, J. V.: Neurilemoma; a Review of the Literature and Report of Five Cases, J. Oral Surg. 35: 235-236, 1977. 14. Swangsilpa, K., Winther, J. E., and Nybroe, L.: Neurilemmomas in the Oral Cavity, J. Dent. 4: 237-241, 1976. 15. Ellis, G. L., Abrams, A. M., and Melrose, R. J.: Intraosseous Benign Neural Sheath Neoplasms of the Jaws, ORAL SURG. 44: 731-743, 1977. 16. Barker, B. F., and Dunlap, C. L.: Intraosseous Benign Nerve Sheath Neoplasms of the Jaws: A Review of the Literature and Case Report, presented to the thirty-third annual meeting of the American Ac&emy of Oral Pathology, San Diego, Calif.-1979. 17. At&l, M. R., Hart, W. R., and Olsen, J. R.: Tumors of the Peripheral Nervous System.Hum. Pathol. 1: 503-551, 1970. 18. Preston, F. W., Walsh, W. S., and Clarke, T. H.: Cutaneous Neurofibromatosis (von Recklinghausen’s Disease): Clinical Manifestations and Incidence of Sarcoma in 61 Male Patients, Arch. Surg. 64: 813-827, 1952. ,

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