Final Diagnosis -- Trigeminofacial Malignant Epithelioid Schwannoma



Malignant peripheral nerve sheath tumours (MPNST) are uncommon primary malignant tumours of peripheral nerves. Intracranial examples are rare with only 7 documented cases including the present report1-5. MPNSTs arising in distal extracranial branches of the trigeminal nerve are slightly more common6.7, but differ significantly in their presentation and accessibility to surgical resection which impacts on their prognosis. Of several reported examples of malignant schwannomas in the sinonasal region, the case of Fernandez et al.8 is the only malignant epithelioid schwannoma (MES). We present the case of a 42 year old male who developed a MES in cranial nerves V and VII.

Definition and epidemiology
MPNSTs are defined as soft tissue tumours of putative Schwann cell lineage with anaplastic features in the form of high cellularity, cellular and nuclear pleomorphism, a high mitotic rate and necrosis. Unfortunately, a large number of terms have been applied to such lesions: malignant schwannoma, malignant neurofibroma, malignant neurilemmoma, malignant mesenchymoma of nerve sheath origin, neurofibrosarcoma and neurogenic sarcoma. These tumours comprise a small fraction of all peripheral nerve tumours and are rare lesions in the head and neck. Most of the latter are found in distal branches of the trigeminal nerve. MPNSTs outside the head and neck are most commonly found in the setting of neurofibromatosis type I (NF1) and often arise within neurofibromas9. They have been reported to develop within a schwannoma10 or ganglioneuroma11 and in association with radiation therapy12.

MPNSTs typically present with pain and abrupt neurological symptoms due to rapid enlargement. The infiltrating tumours cause a fusiform expansion of the involved nerve(s) and are often bulky at the time of presentation especially when growing in relatively unrestricting sites (eg. retroperitoneum). Examples affecting cranial nerves are understandably smaller at the time of presentation.

Large calibre nerves are most frequently involved, especially in the extremities, neck, mediastinum and retroperitoneum. Intracranial nerves are rarely involved. Only 7 cases have been reported in the literature including the present case (Table 1). The trigeminal nerve was involved in five cases (one of which also involved cranial nerves 3,4 and 6) and the facial and acoustic nerves in two cases each. It is noteworthy that none of the seven intracranial examples had NF1 or a family history of NF1 which is in sharp contrast to those arising in more peripheral sites. The literature also suggests that all head and neck lesions (intra or extracranial) are less likely to be associated with NF1 than lesions elsewhere in the body13. Furthermore, Laskin et al13 found that cases of MES were less likely than other MPNST subtypes to be associated with NF1.

Intracranial involvement is associated with a poor prognosis and hematogenous metastasis is not uncommon. However, malignant epithelioid schwannomas (and other MPNSTs) that are amenable to resection carry a more favourable prognosis13. Our patient is recurrence-free 13 months after a gross total resection


Author Age (y) Sex Site Rx Survival (m)
Liewnicz 49 M right V3,
left V and VII
p-Sx, Rad (6600 rad) 48
Levy - 1 69 M right V Sx, Rad (6000 rad) 10 *
Levy - 2 67 F right V Sx 1 **
Karmody 70 M right V p-Sx,Rad (6000 rad), Cx (Bleo) 36
Best 24 F right VIII Sx 1.5
Kudo 54 M right VIII Sx 4
Present Case 42 M left V3, VII Bx, Rad 16
Average 53.6 5M / 2F - - 16
* at time of publication
** unrelated post-op complications (sepsis)

Gross examination typically reveals a fusiform or plexiform enlargement of the nerve. The epineurium is often intact and forms a thin capsule. The cut surface is homogenous and grey, without the usual heterogeneous appearance of a schwannoma. The microscopic appearance is variable within and between lesions, and depends upon the tumour's tendency for differentiation or metaplasia along several lines (Table 2).

TABLE 2 - MPNST Differentiation and Subtypes

1. Rhabdomyoblastic differentiation - (Triton tumour)
2. Epithelial structure formation - (Malignant epithelioid schwannoma)
3. Epithelial (glandular) formation with mucin production - (Malignant glandular schwannoma)
4. Melanocytic differentiation - (Malignant melanocytic schwannoma)
5. Neuroblastic differentiation - (PNET)

The general features include high cellularity and a high mitotic index although the number of mitoses may be few in some examples. Tumour cells are typically arranged in interwoven fascicles or cords and may display a herringbone pattern. Whorls and structures resembling tactile corpuscles may be seen. The individual tumour cells are plump spindle cells with serpiginous nuclei. Nuclear pleomorphism and hyperchromatism are consistent features. At the tumour margins, individual neoplastic cells can be seen to infiltrate nerve fascicles.

The differential diagnosis includes neurofibroma, schwannoma, cellular schwannoma, other sarcomas and metastatic melanoma or carcinoma. MPNSTs are distinguished from cellular schwannomas which will not show the degree of anaplasia, proliferative rate and aggressive clinical picture.

Immunohistochemical findings in MPNSTs have been well documented in the literature. Wick et al14 showed that S-100 was positive in 56%, Leu7 in 58% and Myelin basic protein in 42% of tumours. Laskin et al.13 studied 26 cases of MES and found that 80% were S-100 and NSE positive and all were negative for cytokeratins and HMB-45. Helpful negative results include cytokeratin, especially in epithelioid and glandular variants, and HMB-45 (Table 3).

TABLE 3 - Comparative Immuno/EM Profile of MES DDx

Tumour Type S-100 Cytokeratin HMB45 / MAA EM
Schwannoma +++ - +/- basal lamina, type IV collagen
Neurofibroma ++/+ - +/- " "
MPNST (other than MES) +++/- - +/- " "
Melanoma ++/+ - +++ melanosomes
Carcinoma - +++ - desmosomes

Ultrastructural examination reveals features of schwannian derivation, including redundant basement membrane material, mesaxon formation, dense cytoplasmic bodies and Luse bodies.

MPNST make up a tiny fraction of primary tumours of peripheral nerves. The malignant counterpart to the neurofibroma and schwannoma is rare outside the setting of neurofibromatosis type I with two important exceptions reemphasized by the present example: MPNST involving the head and neck are less commonly associated with NF-1, MES are less commonly associated with NF-1.

The malignant epithelioid schwannoma subtype exhibits a different biology than do other MPNSTs. This is partly reflected in their morphology, but perhaps more importantly, in their weaker association with NF-1. Their site of origin, immunohistochemical staining pattern and ultrastructural morphology are consistent with a Schwannian origin. As with other malignant soft tissue tumours, prognosis correlates best with resectability.


  1. Liwnicz BH (1979) Bilateral trigeminal neurofibrosarcoma: case report. J Neurosurg 50:253-256
  2. Levy WJ, Ansbacher L, Byer J, Nutkiewicz A, Fratkin J (1983) Primary malignant nerve sheath tumor of the Gasserian ganglion: a report of two cases. Neurosurgery 13:572-576
  3. Karmody CS (1979) Malignant schwannoma of the trigeminal nerve. Otolaryngol Head Neck Surg 87:594-598
  4. Best PV (1987) Malignant triton tumour in the cerebellopontine angle: report of a case. Acta Neuropathol 74:92-96
  5. Kudo M, Matsumoto M, Terao H (1983) Malignant nerve sheath tumor of acoustic nerve. Arch pathol Lab Med 107:293-297
  6. Robertson I, Cook MG, Wilson DF, Henderson DW (1983) Malignant schwannoma of cranial nerves. Pathology 15:421-429
  7. Jacobiec FA, Font RL, Zimmerman LE (1985) Malignant peripheral nerve sheath tumors of the orbit: a clinicopathologic study of eight cases. Tr Am Ophth Soc 83:332-366
  8. Fernandez PL, Cardesa A, Bombi, JA, Palacin A, Traserra J (1993) Malignant sinonasal epithelioid schwannoma. Vichows Archiv A Pathol Anat 423:401-405
  9. Burger PC, Scheithauer BW (1994) Atlas of Tumor Pathology: Tumors of the Central Nervous System. AFIP, Washington D.C. 340-341
  10. Woodruff JM, Selig AM, Crowley K, Allen PW (1994) Schwannoma (neurilemoma) with malignant transformation: a rare distinctive peripheral nerve tumor. Am J Surg Path 18:882-895
  11. Ricci A, Parham DM, Woodruff JM, Callihan T, Green A, Erlandson RA (1984) Malignant peripheral nerve sheath tumors arising from ganglioneuromas. Am J Surg Path 8:19-29
  12. Foley KM, Woodruff JM, Ellis FT, Posner JB (1979) Radiation-induced malignant and atypical peripheral nerve sheath tumors. Ann Neurol 7:311-318
  13. Laskin WB, Weiss SW, Bratthauer GL (1991) Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma). Am J Surg Path 15:1136-1145
  14. Wick MR, Swanson PE, Scheithauer BW, Manivel JC (1987) Malignant peripheral nerve sheath tumor: an immunohistochemical study of 62 cases. Am J Clin Pathol 87:425-433
Contributed by D.A. DeRubeis, J. Woulfe, D. Rosso, S. Lownie, L. Parnes, D. Lee, M.J. Strong, R.R. Hammond


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