Extracranial Head and Neck, Peripheral Nerve Tumors: A 10-Year Experience at NCI, Egypt

Background: Peripheral nerve tumors (PNT) originate from the neural crest and typically formed from Schwann cell sheath. Considering the number of nerves in this area, they form a very small percentage of neoplastic lesions of the head & neck. A solitary mass in the lateral neck frequently confronts the surgeon. An uncommon cause for such a nodule is a neoplasm arising from nerve tissue with PNTs being the commonest of them to face. Aims: To study the clinico-pathological characteristics, presentations, surgical approaches, postoperative complications & outcome of management. Materials & Methods: a single institution combined retrospective & prospective study. A retrospective analysis of all cases presented NCI-Cairo University with H&N extracranial PNST candidate for surgery from Jan 2009 until the end of Dec 2015 & prospective analysis of all cases with the same presentation presented to the NCI from Jan 2016 until the end of June 2019. 23 cases were included. Data were collected then analyzed. Results: Mean age was 34.7 years with female to male ratio 1.9:1. Mean size was 5.4 cm. Commonest presentation was asymptomatic neck lump located laterally in the neck (9 cases, 39%). CT scanning was done in 17 cases (74%). As regard pathology, we have only 4 malignant cases (17%). Most tumors (9 cases, 39%) originated from cranial nerves. 18 cases (78%) were resected through the neck. Complication occurred in 13 cases (56%), most of them during The vast majority of H&N extracranial PNTs are benign. Proper diagnosis is mandatory for ideal treatment. Complete R0 resection may not always be jus-tified, therefore intracapsular or debulking procedures may have a role. The Malignant counterpart of PNTs (MPNST) is highly aggressive. They are treated with multimodality approach involving surgery with CTH & RT.


Introduction
Embryologically, Peripheral nerve tumors (PNTs) originate from the neural crest and are typically formed from Schwann cell sheath. These cells of the sheath originate from a specialized population of neuro-mesenchymal cells, giving rise to the commonest subtypes; schwannomas and neurofibromas. Therefore, they may be named as peripheral nerve sheath tumors instead (PNSTs).
These common two entities can arise from any cranial nerve, any spinal root with a sheath, any motor or sensory nerve, except I and II cranial nerves as they harbor no Schwann cell sheath & are considered direct extension of the CNS [1].
They comprise two categories with either benign or malignant behavior. The benign category includes: neurofibroma, schwannoma, perineuroma, cellular and mixed-type neurothecoma, nerve sheath myxoma and granular cell tumors. Neurofibroma & schwannoma are the commonest; they compromise about 40% of cases. Benign non-neoplastic nerve tumors (Traumatic neuromas) can also occur. They are best called reactive, occurring after any nerve injury causing interrupted axons (neurotmesis). Regenerating axons lack endoneural tube to follow, which results in a mass of disorganized axons that is painful and tender [3] [4].
Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon but are devastating tumors of peripheral nerve, representing only 10% of PNSTs. Their incidence in the general population is only 0.001%. They are classified as malignant soft tissue sarcomas and can arise from a pre-existing plexiform neurofibromas or perineuriomas, or from normal nerves. They do not arise from schwannomas. 10% MPNSTs can occur as secondary neoplasms 10 to 20 years after radiation therapy. They may also appear in 22% to 50% of patients with neurofibromatosis type 1 (NF1), the rest being sporadic [5] [6]. depending on their location and size. They may be associated with other diseases, such as multiple endocrine neoplasia (MEN) or neurofibromatosis type I.
Pain will occur in the region of the tumor and any nerve the tumor involves, but pain may not be specific enough to discern the particular involved nerve. Neurologic deficits of sensory and motor function correspond to the nerve in which the tumor originates or which it is compressing, and will often be most useful in localizing the tumor. A Tinel sign over a nerve or tumor may also assist in localization to a particular nerve [12].
Considering they are relatively rare, these tumors should be considered in preoperative differential diagnosis, as other primary neck tumors may present as an asymptomatic neck mass; moreover, their resection may require neural reconstruction, and the surgeon must be prepared for this possibility. A critical issue regarding the treatment is the proper diagnosis, which is based on clinical  Ethical clearance for the conduction of this study was obtained from our institute ethical committee.

Results
This study included 23 cases with PNTs (benign & malignant).
Patients' age ranges from 2 to 78 years while mean age is 34.7 years. Females predominated this study (15 cases, 65%) with female to male ratio of 1.9:1. mean tumor size was 5.4 cm (ranged from 3 to 10 cm).

Management
Surgical management was the main line of treatment in our study conducted in all patients (23 cases). The majority of our patients (18 cases, 78%) were attacked through the neck. only 2 patients (9%) presented with maxillary fullness & epistaxis underwent a trans-sinus biopsy through Caldwell-Luc procedure followed by total maxillectomy as a result of complete sinus destruction combined by reconstruction with obturator prothesis application. Intracapsular enucleation was done 3 cases (13%) with a preoperative diagnosis of cervical neurofibroma. 2 cases (9%) with neurofibroma presented with pathological bone erosions in C5 and C6 vertebral bodies as a result of pressure necrosis. These patients underwent resection of the mass with its origin from C5 root together with parts of the eroded C5 & C6 vertebral body which required posterior spinal fixation with vertebral plates and screws.
Post-resection adjuvant radiotherapy (RT) was received in the 4 cases (17%) of MPNST to decrease local recurrence.

Discussion
Peripheral Serhrouchni KI et al. reported that PNT can arise at any age with no age or race prevalence while other studies reported peculiar age prevalence to the fifth decade of life [16].
Benign PNTs mainly schwannomas are indolent slowly growing tumors, almost often are encapsulated tumor and isolated. They are always connected to the nerve of origin which sometimes cannot be identified clearly [17].
Diagnostic difficulties may arise sometimes during histopathology as features of the pseudo-epitheliomas hyperplastic lesions can be confused with the early well-differentiated oral cavity squamous cell carcinoma [20].
Regarding MPNST, Loree et al. reported that local recurrence correlated with tumor size and resection margin status. All cases received post operative RT to decrease rate local recurrence.
None of our cases experienced local recurrence but all the relapsed four cases (17%) presented with systemic failure in lungs or bone for which they receive chemotherapy in form of (Adriamycin-ifosfamide) as for soft tissue sarcomas and palliative radiation for bone metastasis.
Tumor grade predict for development of distant metastases. Negative margins are crucial for obtaining local control with adjuvant radiotherapy that may be beneficial in this group of patients with such an aggressive tumor. Salvage surgery may be feasible for those patients with local recurrence [9] [20].
Although, imaging studies should clarify the nerve of origin which provides a clear decision by the patient for any functional sequelae following surgery, this is not usually achieved. Cytology may be of assistance; in most cases the technique of aspiration puncture is inconclusive. The specificity of imaging studies is also not high. These investigations are of benefit mainly evaluation of the vascularization of tumors, but may be less useful for diagnosis of the tumor's nerve of origin [7] [8] [21].
Among the differential diagnoses that should be encounterd, reactive or me-  (Figures 1-3).

Conclusion
The vast majority of extracranial PNTs are benign. Proper diagnosis through a H. A. Shokralla, A. E. Fathalla   high index of suspicion & optimum preoperative evaluation. Ideal treatment involves complete R0 resection; however, debulking procedures may have a definite role. Malignant counterpart of the PNTs (MPNST) is aggressive and is treated with radical surgical resection followed by radiation therapy. Chemotherapy is reserved for metastatic disease.