Does Biopsy before Excision Have Contribution to Clinical Results in Patients with Schwannoma? A Single-Center Prospective Observational Study

Introduction: This study aimed to investigate whether tru-cut biopsy before excision contributes to clinical outcomes in patients diagnosed with limb schwannoma. Materials and methods: Tru-cut biopsy was performed before excision in patients diagnosed with schwannoma of the extremity in clinical and radiological evaluations. All patients underwent total excision with microsurgical methods. Demographic data, complications of tru-cut biopsy, treatments, and clinical results were analyzed. Results: Data for 17 patients (9 males and 8 females) were analyzed. The mean age was 49.8 years. No complications related to tru-cut biopsy were observed. The mean preoperative and postoperative VAS scores were 4.3 and 0.4, respectively. One patient developed postoperative neurological complications. No recurrence was observed in any patient. Conclusions: In schwannomas of the extremities, tru-cut biopsy before excision is an applicable and reliable option. The preoperative diagnosis is ascertained as schwannoma, and the outcomes of making the excision with microsurgical techniques are quite good.


INTRODUCTION
Peripheral nerve sheath tumours (PNST) are sporadic. The most common type of PNST is schwannoma, also known as neurilemma or perineural fibroblastoma. Schwannomas most commonly involve the brachial plexus and spinal nerves; limb locations are rare. 1 In schwannomas located in the extremities, the presence of a mass accompanying sensory impairment in the nerve distribution area or positive Tinel's sign in the nerve line is helpful in the clinical diagnosis. In all patients, contrast magnetic resonance imaging (MRI) is recommended to identify the size, borders, anatomical location, and nature of the lesion. 2 A clinical diagnosis is difficult in patients with a pre-diagnosed schwannoma in the extremity. However, a biopsy is applied in suspicion of malignancy or if clinical and radiological diagnoses are inconclusive. When a soft tissue sarcoma goes unseen or is not treated with the right algorithm, clinical results may lead to amputation, the only option to prevent mortality. 3 Folia Medica I 2022 I Vol. 64 I No. 1 The treatment of symptomatic schwannomas in the extremities is surgical excision. There is a risk of neurological deficits during surgical excision, for which the surgeon should be prepared. There are studies retrospectively analyzing the clinical results of schwannomas after surgical excision. In some of these studies, the diagnosis was made clinically or radiologically, while a biopsy was performed in some others. [2][3][4] However, the effect of diagnostic procedures on prognosis has not been investigated in previous studies. There is not enough evidence regarding the possible benefits or harms of tru-cut biopsy, a method applied to make a diagnosis before surgery.

AIM
This study aimed to investigate whether tru-cut biopsy contributes to clinical outcomes in patients diagnosed with schwannoma of the extremity. Another objective was to observe the possible complications of biopsy.

MATERIALS AND METHODS
This prospective study was carried out in the Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Orthopedics and Traumatology Clinic. Ethical approval was obtained from the ethics committee of the same hospital. Patients referred to our hospital (a tertiary oncology center) with a differential diagnosis of schwannoma between January 2018 and December 2019, and patients with confirmed schwannoma in our hospital were included in the study.
The patients' histories included swelling, pain, and neurological symptoms. In the presence of pain, its character, spread, and degree were queried. Pain severity was assessed with a visual analog scale (VAS). A diagnosis of neurofibromatosis or a previous history of schwannoma operation from localization was surveyed. In the physical examination, the presence of swellings, sensory functions, and muscle strength was evaluated, and a Tinel's test was performed if necessary.
Contrast-enhanced MRI and/or superficial tissue ultrasound for existing mass lesions were evaluated. Additionally, an EMG test was performed if deemed necessary.
Inclusion criteria were the presence of a limb-located benign peripheral nerve sheath tumour (BPNST) or schwannoma in the clinical and radiological differential diagnosis and the patient's acceptance to participate in the study. Exclusion criteria were tru-cut biopsy returning as non-schwannoma, a relapsing schwannoma, a surgical history in another hospital for the mass, the presence of neurofibromatosis, a follow-up plan without total excision after biopsy, and the absence of patient consent.
After the tru-cut biopsy, patients were followed up for related complications during the examination of the pathology material and the planning of the excision. Total excision was performed in all patients where the truecut biopsy indicated schwannoma. The dimensions of the excised material after complete excision were measured and recorded. After the excision surgery, the improvement rates of patients' symptoms were examined. During the follow-up, the pain was assessed with the VAS score. Concerning recurrence and complications, follow-up visits were planned at 1, 3, and 6 months, and then annually. All patients were followed up for at least 6 months.

Statistical analysis
All statistical analyses were made with the IBM SPSS 22.0 statistical software (IBM Corp., Armonk, NY, USA). Descriptive statistics were presented as mean ± standard deviation, frequency, and percentage.

RESULTS
Of the patients with suspected schwannoma in the clinical and radiological examinations, 17 patients with schwannoma were confirmed by pathological examination.
Of the patients, 9 (52.9%) were males, their mean age was 49.8 years (range 9-76). The anamnesis and clinical examinations of the admitted patients are summarized in Table 1. There were also patients presenting with only palpable mass or pain. The mean VAS score was 4.3 (range 0-9). In addition to these symptoms, two patients had numbness (Table 1).
Imaging findings are presented in Table 1, which were in the form of smooth contoured, contrast-enhancing mass lesions in the MRI, with hypointensity in the T1 sequence and hyperintensity in the T2 sequence. In some patients, the nerve of origin was detected in the images. Additionally, one patient had a target finding (Table 1).
Total excision was performed in all patients per the microsurgery principles after verifying the tru-cut biopsy diagnosis as schwannoma. No complication related to the tru-cut biopsy procedure was seen in any patient in the clinical evaluation before the total excision.
The size of the excised tumour, the relationship of the lesion with the nerve, the interventions, and follow-up results are reported in Table 2. During excision, five patients had one or more fascicles entering or exiting the tumour, requiring more careful dissection, and in one of these patients, complete excision of the nerve (anterior interosseous nerve) was required ( Table 2). Nerve reconstruction surgery was planned for this patient. However, the patient did not accept the intervention stating that he was contented with this state and did not want any additional operations.
In the follow-up after total excision, one patient (case 15) left the follow-up before six months. This patient was excluded at this stage (

DISCUSSION
Due to the relationship of the lesion with small or large nerve branches, there is a risk of neurological complications in interventions such as biopsy or excision. This study aimed to examine whether the application of tru-cut biopsy before excision would cause such a hazard. An additional aim was to determine whether the total excision after making a definitive diagnosis according to microsurgery principles instead of performing an excisional biopsy to a preliminary-diagnosed lesion has a positive effect on clinical results, especially neurological complications. No complication was observed in any patient due to the tru-cut biopsy. The results were excellent after the total excision, and complications were low. Levi et al. 5 compared direct excision and post-biopsy (open biopsy or needle biopsy) excision in symptomatic BPNSTs and found that the risk of complications increased 2.7 times in the patients who underwent biopsy before excision. They reported that these complications could be due to bleeding of the tumour or damage to its fascicles during the biopsy procedure. 5 In this study, all patients underwent a single biopsy (tru-cut biopsy), and no complications occurred. A control group could not be created because of the tumour's rarity. In patients with post-excision pain, it is difficult to understand whether the pain is due to the tru-cut biopsy. A decrease but no loss of pain was reported after excisional biopsy. 6 Schwannomas are manageable tumours with rare mor-tality, and the only valid, current treatment is surgery. Results after excision are quite good. 6 The prognosis of the untreated patient group is unknown. Therefore, surgical treatment or follow-up decision is difficult. In this study, one patient was followed up because she did not accept the operation.
The main goal of treatment in schwannoma is the excision of the tumour by preserving neurological functions. For this reason, excision is performed by microsurgical methods. In some cases, it may even be necessary to completely sacrifice the nerve for a total tumour removal. 7 In such cases, performing subtotal excisions to protect the nerve frequently results in recurrences. 8 In cases where the nerve is protected and excision is performed with microsurgical methods, there are risks of increasing the existing pain, sensory deficits, or developing new neurological deficits. 9 In the current study, the nerve had to be sacrificed in one patient, and one case had neurological symptoms after excision. Furthermore, pain decreased but did not completely disappear in some patients.
Schwannomas are often seen in the middle-aged population, there is no sex preference, and they have a slow growth. 9 In this study, the mean age was 49 years, and no significant sex difference was observed. Schwannomas often present with pain, mass, neurological findings, or combinations of these. 3,5 Pain and/or swelling were the most common symptoms, and some cases were accompanied by neurological findings. Generally, it was seen that patients presented with long-standing and recently increasing complaints.
Benign peripheral nerve sheath tumours are generally seen sporadically. Some cases are associated with the autosomal dominant syndrome neurofibromatosis type 1. 10 In this study, patients associated with neurofibromatosis type 1 were excluded.
This study had some limitations. Firstly, the number of cases was rather limited due to the very low incidence of this tumour. For the same reason, a control group could not be created, and no comparison could be made. Besides, the primary purpose of this study was to monitor complications rather than relapse. Hence, the minimum follow-up period was determined as 6 months. One-year follow-up was considered as the minimum duration for relapse monitoring, and four patients could not complete the one-year follow-up.

CONCLUSIONS
A tru-cut biopsy before excision is a feasible and reliable option in schwannomas located in the extremities. The results of ascertaining the diagnosis as schwannoma preoperatively and excision with microsurgery methods are quite good.