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Medicina Oral, Patología Oral y Cirugía Bucal (Ed. impresa)

versión impresa ISSN 1698-4447

Med. oral patol. oral cir. bucal (Ed.impr.) vol.9 no.1  ene./feb. 2004


Intraosseous intraneural perineurioma: Report of a case
with morphological, immunohistochemical and fish study



We report a case of an intramandibular intraneural perineurioma developed in the left dentary nerve. This tumour is rare and shows a typical histological, immunohistochemical and ultrastructural appearance: concentric whorls of perineurial cells EMA+ and PS100- around nerve fibers. This tumour must be distinguished from extraneural or soft tissue perineurioma, also composed of perineurial cells, with distinct clinical presentation and histological appearance, and from localized hypertrophic neuropathy, a reactive process frequently identified with intraneural perineurioma. Cytogenetic evidence for the neoplastic nature of this tumour is also presented in this report.

Key Words: Perineurioma, nerve sheath tumour, localized hypertrophyc neuropathy, ultrastructural, immunohistochemistry, cytogenetics.


Perineuriomas (PN) are rare benign nerve sheath neoplasms composed exclusively of well-differentiated perineurial cells (1). For years this term has been applied to two distinct variants, one an extraneural soft tissue tumour, the extraneural perineurioma or soft tissue perineurioma, the other an architecturally complex intraneural process, the intraneural perineurioma, although it has been used also for a reactive hyperplastic perineurial proliferation, the localized hypertrophic neuropathy (2-4). The recent demonstration of its relationship with abnormalities of chromosome 22 clearly support the view that PN are neoplastic rather than reactive (2,5). Some cases of malignant or "atypical" PN have been described (6).

Extraneural perineuriomas are generally small, well-circunscribed but not encapsulated tumours that frequently present as solitary superficial nodules in subcutaneous tissues of the trunk or limbs. Intraneural perineuriomas are cylindrical or nodular enlargement of an isolated peripheral nerve described in many regions of the body but rarely in head and neck region. Although benign nerve sheath tumours are commonly found in the maxillofacial area, intraosseous presentation is very rare (2,5,7), and most of them are schwannoma and neurofibroma. Only four cases of PN have been described involving cranial nerves and only one in mandibular nerve (7).

We present a case of intraosseous intraneural perineurioma that appeared in the dentary nerve of the mandible, with morphological diagnostic confirmed by immunohistochemical, ultrastructural and fluorescence in situ hybridization (FISH) analysis.


A 64-year-old man presented with a swollen left hemimandible that had been expanding over a 6-month periode. Panoramic radiographic examination and computed tomographic scan were (Fig. 1,2) performed and revealed a large osteolytic, unilocular, demarcated lesion of the left mandibular horizontal ramus; the cortex of the mandible showed reabsorption at the border of the lesion. The first diagnosis was probable ameloblastoma and the patient underwent surgery. An interpapillar incision was performed to expose the mandibular bone whose cortex appeared "blow up" by the endosteal lesion. A fleshy dense tumour englobing dentary nerve was enucleated and, after careful curettage of the bone cavity, the mucosal flap was replaced and sutured. The postoperative period was free of complications.

Gross examination of the surgical specimen showed a fragmented tumour that occuped an area of 2x1,5 cm, formed by grayish-white material with a firm texture. This material was fixed in 10% neutral buffered formalin and embedded in paraffin by routine techniques. Four m sections were stained by the HE and PAS methods.

Microscopically all fragments were composed of spindle-shaped cells that were relatively uniform in size and shape, arranged in intersecting fascicles and whorls (Fig 3,4). Varying in size, these whorls were composed of somewhat onion skin-like arrangements of tumour cells . Cellularity as well as the amount of intercellular matrix varied among the areas, some of which featured irregular zones of myxoid change. No palisading pattern was noted. No pleomorphic tumour cells nor atypical mitotic figures were seen. Residual dentary nerve trunk was visible at the periphery of some fragments.

With the morphological diagnostic of probable intraneural perineurioma, immunohisto-chemical, ultrastructural and (FISH) studies were performed in order to confirm it.

Immunohistochemistry was performed on representative paraffin sections using the avidin-biotin peroxidase complex (ABC) method. Primary antisera used were directed against EMA (Dako M613, USA, 10/500), S100 protein (Dako L1845, USA, pred), neurofilament protein (Biogenesis 6670-0154, USA), neurospecific enolase (Biogenex MU055-VC, USA, 10/1000), CD57 (Becton-Dickinson 7390, USA), collagen IV (Biogenex N079032, USA, 10/400), CD34 (Becton-Dickinson 7660, USA, 10/500),a.smooth-muscle actin (Dako MO851, USA, 10/200), desmin (Dako M760, USA, 10/500), vimentin (Shandon 402255, USA, pred) and p53 protein (Dako M7001, USA, 10/500). The sections were treated according to standard protocols. Negative and positive controls were included.

The results showed a strong positive immunoreactivity for EMA and vimentin, and negative reactivity for S100 protein in cells forming the onion bulbs (Fig 5). Reactivity for S100 protein was seen only in Schwann cells at the center of whorls. NF stain also showed the presence of axons at the center of onion bulbs. NSE, collagen IV, CD57, actin, desmin and CD34 were all negatives in tumoral cells. S100 protein, NSE and NF were positive in residual dentary nerve trunk, and EMA was also positive in the perineurium of this nerve.

A little sample of unparaffined formalin-fixed material was recuperated and, after washing, it was post-fixed in 4% glutaraldehyde and then processed for ultrastructural study. After selection of the appropriate blocks, ultrathin sections were stained and examinated with a Zeiss EM-109T transmission electron microscope by one of us (M.C.). Ultrastructurally, cellular preservation was suboptimal for assessment. However the spindle cells rimmed by incomplete basal lamina could still be well visualized in a rich collagenous background. Rough endoplasmic reticulum, intermediate filaments and pinocytic vesicles were ocassionally found. Interdigitating cytoplasmic processes were not found.

FISH analysis of isolated nuclei derived from 50 m paraffin sections was performed by two of us (F.S. and B.E.) using a dual-colour, locus specific LSI BCR/ABL probe mixture (VYSIS, Inc, Downers Grove, USA) following the proceedings supplied by the manufacturer. Slides were analyzed in a fluorescent Nikon (Eclipse 600) microscope with a triple band pass filter. One hundred nuclei were analyzed. A deletion of the bcr locus (22q11) in 75 nuclei was observed (Fig. 6).


Perineurioma is a benign peripheral nerve sheath tumour of perineurial cell origin. It was described in 1978 by Lazarus and Trombetta (8) using highly specific ultrastructural features of perineurial cells as a diagnostic criterion. With the advent of immunohistochemistry the finding that the cells of this tumour routinely express EMA and are negative for S100 protein provided further evidence confirming the perineurial cell nature.

Perineuriomas had been previously reported as "intraneural neurofibroma", "hypertrophic neurofibrosis", "hypertrophic mononeuropathy", "localized hypertrophic neuropathy" and "localized hypertrophic mononeuropathy" (7) and they appear to be identical to the lesion called "storiform perineurial fibroma" (3,9). In the last decade two distinct variants of perineurioma have been recognized: a soft tissue tumour, the extraneural perineurioma (ENPN) (3,5) and an intraneural proliferation or intraneural perineurioma (INPN) (2).

Although benign peripheral neurogenic tumours often occur in oral and perioral regions, intraosseous neural tumours of the jaws are quite rare. The majority of these tumours appear in the mandible, being schwannoma and neurofibroma the most frequents (10,11). INPN in this zone is very rare. In the most recent reviews only 22 cases of ENPN and 34 of INPN were recorded (2,5). Fetsch el al (12) described 19 cases of sclerosing perineurioma, a distinctive variant of ENPN. Posteriorly 9 cases of malignant PN and other isolated cases of benign ENPN and INPN have been published (6,13,14). Only five cases of perineurioma among a total of 88 were intraosseous, affecting craneal nerves in four cases and peripheral nerve (mandibular) in only one. Our case was intraosseous and affected a peripheral nerve (dentary).

Although ENPN and INPN show morphological similarities and share a common immunohistochemical and ultrastructural phenotype, they are quite distinct in terms of their clinical presentation and histological appearance. ENPN is a benign, well-circunscribed tumour presenting as a solitary subcutaneous nodule and INPN takes the form of segmental fusiform enlargement of a nerve. Microscopically ENPN consists of a proliferation of spindle-shaped cells with slender processes arranged in whorls and storiform patterns within collagenous and sometimes myxoid stroma and INPN is characterized by onion bulb-like arrangement of perineurial cells around axons and their Schwann sheaths (1-3). Immunohistochemically in both cases the neoplastic cells are positive for EMA and negative for S100 protein, providing a strong support for the perineurial nature of these tumors, in contradistinction to the other more commonly encountered nerve sheath tumors which are typically S100 protein positive and EMA negative (1-3). Ultrastructurally both lesions are also similar, with cells showing features more typical of perineurial cells than of Schwann cells. They contain pinocytic vesicles connected with the cellular membrane and hemidesmosomes; the basement membrane is absent or only partially developed (5,8).

In our case both morphological and immunohistochemical profile are typical of perineurioma;. The S100 protein-positive cells in the periphery of the tumour identified a residual nerve trunk, confirming the intraneural location of the lesion..The etiology of perineuriomas is unknown. It is commonly suggested that trauma, ischemia, inflammation, nerve entrapment or genetic disorder may be the cause of these lesions by inducing a perineurial reaction, but the evidence for this assumption is not convincing (2,3,7). In the case here presented, there was no previous history of trauma or of another predisposing condition.

Whereas ENPN was always considered a soft tissue neoplasm, INPN was considered a reactive process similar to localized hypertrophic neuropathy (3,4). The recent demonstration of the clonal nature of both lesions and its association with abnormalities of chromosome 22 has strengthened the view that INPN is, like ENPN, neoplastic in nature (2,5). In 1995 Emory et al (2) confirmed it by demonstrating abnormalities of chromosome 22 on cytogenetic and FISH analysis in eight cases of INPN, and in 1997 Giannini et al (5) demonstrated deletion of part or all chromosome 22 in four ENPN, supporting the view that the long arm of this chromosome contains a tumour supressor gene involved in the pathogenesis of nerve sheat tumours (2,5) and that both INPN and ENPN are part of a spectrum of perineural neoplasia. Using FISH, our case also exhibits loss of the centromere of chromosome 22.

In conclusion, based on morphological, ultrastructural, and immunohistochemical features and in FISH analysis, INPN should be considered a benign peripheral nerve sheath tumour distinguishable from localized hypertrophic neuropathy and from other benign neural tumours (neurofibroma, schwannoma). We present in this paper a characteristical case of intraneural perineurioma in a very rare location.


1. Requena L, Sangüeza OP. Benign neoplasms with neural differentiation: a review. Am J Dermatopathol 1995;17:75-96.         [ Links ]

2. Emory TS, Scheithauer BW, Hirose T, Wood M, Onofrio BM, Jenkins RB. Intraneural perineurioma. A clonal neoplasm associated with abnormalities of chromosome 22. Am J Clin Pathol 1995; 103:696-704.         [ Links ]

3. Tsang WYW, Chan JCK, Chow LTC, Tse CCH. Perineurioma: an uncommon soft tissue neoplasm distinct from localized hypertrophic neuropathy and neurofibroma. Am J Surg Pathol 1992;16:756-63.         [ Links ]

4. Simmons Z, Mahadeen ZI, Kothari MJ, Pwers S, Wise S, Towfighi J. Localized hypertrophic neuropathy: magnetic resonance imaging findings and long-therm follow-up. Muscle Nerve 1999;22:28-36.         [ Links ]

5. Giannini C, Scheithauer BW, Jenkins RB, Erlandson RA, Perry A, Borell TJ et al. Soft-tissue perineurioma. Evidence for an abnormality of chromosome 22, criteria for diagnosis and review of the literature. Am J Surg Pathol 1997;21:164-73.         [ Links ]

6. Hirose T, Scheithauer BW, Sano T. Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical and ultrastructural study of seven cases. Am J Surg Pathol 1998;22:1368-78.         [ Links ]

7. Li D, Schauble B, Moll C, Fish U. Intratemporal facial nerve perineurioma. Laryngoscope 1996;106:328-33.         [ Links ]

8. Belli E, Becelli R, Matteini C, Ianetti G. Schwannoma of the mandible. J Craniofac Surg 1997;8:413-6.         [ Links ]

9. Ellis GL, Abrams AM, Melrose RJ. Intraosseous benign neural sheath neoplasms of the jaws. Oral Surg 1977;44:731-43.         [ Links ]

10. Lazarus SS, Trombetta LD. Ultrastructural identification of a benign perineurial cell tumor. Cancer 1978;41:1823-9.         [ Links ]

11. Mentzel T, Dei Tos AP, Fletcher CDM. Perineurioma (storiform perineurial fibroma): clinico-pathological analysis of four cases. Histopathology 1994;25:261-7.         [ Links ]

12. Fetsch JF, Miettinen M. Sclerosing perineurioma. A clinicopathologic study of 19 cases of a distinctive soft tissue lesion with a predilection for the fingers and palms of young adults. Am J Surg Pathol 1997;21:1433-42.         [ Links ]

13. Karaki S, Mochida J, Lee YH, Nishimura K,Tsutsumi Y. Low-grade malignant perineurioma of the paravertebral column, transfroming intoa high-grade malignancy. Pathol Int 1999;49:820-5.         [ Links ]

14. Zamecnik M, Michal M. Malignant peripheral nerve sheath tumor with perineurial cell differentiation (malignant perineurioma). Pathol Int 1999;49:69-73.         [ Links ]

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