Description of a neural sheath tumor of the trigeminal nerve: immunohistochemical and electron microscopy study

c a s e r e p o r t Bijan Khademi


INTRODUCTION
Sarcomas of the head and neck region are a rare and diverse group of neoplasms, accounting for less than 1% of all neoplasms that occur in this area. 1 Primary neurogenic tumor of the nose and paranasal sinuses account for only 4% of all neural tumors of the head and neck region. 2 Malignant peripheral nerve sheath tumor (MPNST) of the trigeminal nerve affecting the sinonasal region is rare, and a search in PubMed revealed only 20 cases reported so far. The extremities, trunk, chest and retroperitoneum are the most common primary sites for this aggressive neoplasm. 3,4 Here, we describe a case with malignant peripheral nerve sheath tumor (MPNST) of the maxillary sinus, studied by means of electron microscopy.

CASE REPORT
A 41-year-old woman presented with a 10-month history of progressive toothache that was followed by painful swelling of the left cheek, epistaxis, nasal obstruction and discharge. On examination, a tender swelling of the left cheek was found. Intraoral examination showed an ulcerative, hard mass in the left upper alveolar ridge. There was some left orbital edema.
Computed tomography (CT) scans showed a space-occupying lesion arising from the left maxillary sinus, causing expansion of the left maxillary sinus. This mass extended medially to the nasal cavity, superiorly to the fl oor of the left orbit, and inferiorly to the left upper alveolar ridge ( Figure 1). A biopsy from the maxillary sinus revealed spindle cell sarcoma, suggestive of peripheral nerve sheath tumor ( Figure 2). Electron microscopy revealed elongated ovoid tumor cells with thin cytoplasmic processes within a collagen matrix ( Figure  3). The presence of basal lamina around the cells, tonofi laments in the cytoplasm and branching of the nucleus were diagnostic of MPNST ( Figure 4). Immunohistochemistry studies demonstrated moderate focal positivity for S100 ( Figure 5) and vimentin ( Figure 6), thus confi rming the diagnosis of MPNST of the trigeminal nerve.
The patient underwent left maxillectomy with curative intent. However, the disease was too extensive: gross residual tumor was left behind and complete tumor clearance could not be obtained surgically. Because of the persistent gross residual disease, the patient received a combination of chemotherapy and radiation therapy. The chemotherapy course consisted of 4 cycles of cyclophosphamide (1000 mg/m 2 ), vincristine sulfate (1.4 mg/m 2 ) and doxorubicin (50 mg/m 2 ) once every three weeks. By the end of the fourth cycle of treatment, there had still not been any signifi cant clinical response to the chemotherapy. Therefore, the patient was treated with a radical radiation therapy using an anterior and lateral paired wedged fi eld technique, and a dose of 70 Gy was delivered in 35 daily fractions. Complete response was achieved by the end of the radiation therapy. During 26 months of follow-up after terminating the radiotherapy, there was no evidence of locoregional and distant failure.

DISCUSSION
Sarcomas account for 24% of all nonsquamous cell malignant tumors of the sinonasal region. 5 MPNST, also known as malignant schwannoma, malignant neurilemoma, neurogenic sarcoma, and neurofi brosarcoma, is a rare neoplasm that originates in Schwann's cells of the nerve sheath. 3 Most nerve sheath tumors of the nose and paranasal sinuses arise from the ophthalmic and maxillary branches of the trigeminal nerve and its terminal branches, although it is often difficult to identify exactly which nerve is involved. The

CORE
Metadata, citation and similar papers at core.ac.uk most common sites for these tumors are the ethmoid and maxillary sinuses. Other sites are the nasal cavity and the sphenoid sinus. The frontal sinus is the least common site. 6,7 MPNSTs can arise de novo or as a result of the malignant transformation of a neurofi broma (Von Recklinghausen's disease). These tumors occur in all age groups and in both sexes, but the peak incidence is between the second and fourth decades of life. The tumor has no predilection for sex and race. 8 The clinical presentation differs according to the site involved, but the most common symptoms are unilateral nasal obstruction, epistaxis, pain in the facial region and swelling of the facial and orbital region. The other complaints presented include mucopurulent rhinorrhea, hyposmia and headache. 9 It must be remembered that nasal obstruction has a wide variety of clinical differential diagnoses and, in cases of spontaneous extrusion of the teeth in the maxillary alveolar arch, the pathological lesion in the maxillary sinus must be investigated.

Histopathological Histopathological characteristics characteristics
Histologically, MPNST has no classical appearance and it is often confounded with other tumors such as fi brosarcoma, rhabdomyosarcoma, esthesioneuroblastoma, poorly differentiated lymphoma and amelanotic melanoma. 10,11 It is diffi cult to use optical microscopy alone to differentiate MPNST from other spindle cell sarcomas, especially if its origin from a nerve trunk cannot be identifi ed. The interpretation is based on optical microscopy sampling as well as the clinical and gross anatomical contexts of each case, while immunohistochemistry fi ndings of S100 and vimentin are diagnostic. Electron microscopic investigation may yield important clues for fi nal diagnosis of MPNST. Intracytoplasmic tonofi laments and collections of densecore granules 12,13 have been found in most cases of MPNST. The latter was not seen in the present case. Long-spaced collagen has been seen in other benign or malignant neurogenic tumors. The overall ultrastructural features that differentiate      Schwann cell origin from other spindle cells are characterized by long, slender cytoplasmic processes enveloping each other and other cells. These processes are outlined by a discrete basal lamina and also tonofi laments and dense core granules in the cytoplasm of tumor cells. 12,13 On the other hand, the electron microscopic fi ndings from other tumors that are diagnosed differentially from MPNST are histologically distinct and well defi ned.

Clinical course and Clinical course and treatment treatment
Local recurrence is the major cause of treatment failure and poor overall survival in these patients. 5 Regional metastasis is infrequent. Sarcomas involving the sinonasal region may have an indolent course for longlasting periods, and may present with only nasal obstruction or drainage in the absence of orbital involvement. Combined therapy is the cornerstone of treatment for most soft tissue sarcomas of the head and neck region. 14 Wide surgical resection is the primary treatment for neurogenic sarcomas. Because of the tendency for neurogenic sarcomas to recur locally, postoperative radiation therapy is recommended by many physicians. 15 Radiation therapy signifi cantly improves survival for patients with T4 lesions. 14 Doxorubicin-based adjuvant chemotherapy appears to improve disease-free survival and probably improves overall survival in adults with localized resectable head and neck soft tissue sarcoma. However, the role of adjuvant chemotherapy in neurogenic sarcomas remains poorly defi ned. 15,16 CONCLUSION The paranasal sinuses are not a common location for MPNST, but if the clinical and radiological investigations and the gross and histological fi ndings are consistent with MPNST, electron microscopy is suggested for confi rmation of the fi nal diagnosis.