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)|
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|
|Present Case||42||M||left V3, VII||Bx, Rad||16|
|Average||53.6||5M / 2F||-||-||16|
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).
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).
|Tumour Type||S-100||Cytokeratin||HMB45 / MAA||EM|
|Schwannoma||+++||-||+/-||basal lamina, type IV collagen|
|MPNST (other than MES)||+++/-||-||+/-||" "|
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.