Unusual Presentation of Malignant Peripheral Nerve Sheath Tumour of Mandible as a Colossal Tumour After Neoadjuvant Chemotherapy

Abstract

The uniqueness of this case is the presentation of malignant peripheral nerve sheath tumors arising from the mandible as a colossal tumor of size of about 28 cm and weight of 1.5 kg after the first cycle of neoadjuvant chemotherapy. Role of neoadjuvant chemotherapy remains controversial and can be avoided if margin negative resection is feasible.

Introduction

Here we outline an unusual presentation of Malignant peripheral nerve sheath tumors (MPNST) arising from the mandible with rare occurrence in a young male without Neurofibromatosis 1 (NF1). The uniqueness of this case is the presentation as a colossal tumor of size of about 28 cm and weight of 1.5 kg, when the patient was reviewed after the first cycle of neoadjuvant chemotherapy. MPNST are rare tumors and its prevalence in the general population is approximately 0.001% compared to 0.1% in NF1 patients [1]. Surgical management is the only curative-intent treatment. The role of neoadjuvant chemotherapy remains controversial and can be avoided if margin negative resection is feasible.

Case Report

A 35-year-old male presented with intraoral swelling and pain in the teeth for 3 months duration. On intraoral examination, there was a firm lobulated submucosal swelling near the central arch of mandible extending to floor of mouth approximately of size 10*8 cm, with associated loosening of teeth, edematous lip and stretched erythematous external skin of mentum (Fig. 1a). Clinically there was no lymphadenopathy or signs of NF1. Computed tomography (CT) of neck and paranasal sinuses showed 8.5*6.3 cm lytic lesion in the right half of the body and central arch of the mandible with area of necrosis and internal vascularity. Biopsy showed proliferation of spindle cells with mitosis. Immunohistochemistry showed vimentin, S100 positivity, focal positivity for TLE1 and was negative for cytokeratin and CD34.Immunohistochemistry (IHC) features were suggestive of a malignant peripheral nerve sheath tumor, Grade 2. The patient was planned for Neoadjuvant chemotherapy (ifosfamide and epirubicin) after tumor board discussion (TBD) and review of literature, in an attempt to save mentum, skin and lip. The patient presented back to us after first cycle chemotherapy with large exophytic swelling of size 24*15 cm involving the entire central arch extending to the floor of the mouth and pushing the entire lower lip (Fig. 1b,c). Now PET-CT scan was done which showed a 26*13 cm lesion arising from the mandible with its destruction with no evidence of nodal or distant metastasis (Fig. 1d). The patient underwent wide excision with adequate margin which included en-bloc segmental mandibulectomy (up to angle of mandible on either side), removal of entire lower lip, involved skin of mentum and neck, part of floor of mouth, and bilateral level 1 nodal tissue (Fig. 2a). Reconstruction of the mandibular arch was done with plates and soft tissue coverage achieved by Pectoralis Major Myocutaneous flap (Fig. 2b,c).

Fig. 1.

Preoperative Images (a) Pre NACT (b) Post NACT (c) Intra-operative view (d) PET scan images showing tumour

Fig. 2.

Intraoperative and postoperative images (a) Defect after resection of tumour (b)Mandibular plating (c)PMMC flap for soft tissue coverage (d)Follow up at 6 months

Resected tumor weighed 1.5 kg and was 28*15*12 cm size on gross examination. Grossly there was a unifocal tumor with predominant myxoid areas with focal areas of hemorrhage, necrosis, and cysts. The tumor was infiltrating the mandible but the overlying skin was uninvolved. Microscopy showed high-grade spindle cell tumor (FNCLCC grade 3) with mitosis in 20/10 high-power fields and necrosis < 50%. All resected mucosal, bony cut ends and marrow were free of tumor with 3-dimensional margins > 1 cm. Because of the large size and high-grade tumor, the patient underwent adjuvant radiotherapy as per tumour board discussion. Follow-up at 6 months after surgery was uneventful and there was no evidence of local and systemic recurrences (Fig. 2d). And functional outcomes in terms of speech and swallowing were acceptable.

Discussion

The uniqueness of this case is the presentation of MPNST of the mandible as a remarkably large tumor. MPNST is a rare infiltrating tumor and approximately 50% arise in individuals with Neurofibromatosis Type I (NF1) and the rest occur sporadically or secondary to prior radiation therapy [1]. The prevalence of MPNST in the general population is approximately 0.001% compared to 0.1% in individuals with NF1. Mostly MPNST arises from major nerve trunks (sciatic nerve, brachial plexus, and sacral plexus) and hence it's common in extremities and the trunk [2]. Only about 8–16% occur in the head and neck region, with very rare presentation in the jaws (maxilla > mandible) [3, 4].MRI is the gold standard in imaging of peripheral nerve tissue. CT is important for the planning of reconstructive options. Diagnosis of MPNSTs is usually based on histopathology aided by IHC. Approximately 50–90% of MPNSTs are positive for S-100 protein [3]. For localized disease, the only known curative treatment involves surgery [5]. The use of adjuvant or neoadjuvant chemotherapy in the treatment of MPNST remains controversial [1, 6].

In our case, in the prospect of a large tumor, we planned for neoadjuvant chemotherapy (NACT) with the intent of preserving the lower lip and skin of the mentum. Being a rare tumor concrete evidence for NACT was lacking, though some evidence revealed benefit for NACT with ifosfamide and epirubicin. Response was seen in sporadic MPNST as per SARC006 trial [5, 6]. After the first cycle of chemotherapy the patient presented back to us when bleeding occurred with a colossal tumor. Even though large size is a poor prognostic factor, being a localized disease with bleeding surgical excision was planned.

Radiation has been practiced as adjuvant to reduce the risk of local recurrence (LR), though it does not prolong the overall survival (OS) [2, 4, 5]. The results of chemotherapy are controversial. LR and distant metastasis (DM) are common in MPNST. 5-year LR and DM rates were 49% each [5].Prognosis of MPNST is poor, notably if it cannot be fully resected. Large tumors, truncal lesions, positive surgical margins, high-grade tumors, S100 negativity, and p53-positivity are all negative prognostic factors, as is the presence of NF1 [4, 5]. The 5-year OS rate for head and neck MPNSTs is 15–65% [4].

Conclusion

MPNST are rare locally aggressive tumors which when neglected can become prodigious. Surgical management is the only curative-intent treatment. The role of neoadjuvant chemotherapy remains controversial and can be avoided if margin negative resection is feasible.

Abbreviations

MPNST

Malignant peripheral nerve sheath tumors

NF1

Neurofibromatosis 1

NACT

Neoadjuvant chemotherapy

IHC

Immunohistochemistry

CT

Computed tomography

LR

Local recurrence

OS

Overall survival

DM

Distant metastasis

Author Contributions

All authors contributed to the study conception and design. Material preparation was performed by Dipin and Priyank Rathod. The first draft of the manuscript was written by Dipin. All authors read and approved the final manuscript.

Funding

Nil.

Data Availability

Transparent data available.

Compliance with Ethical Standards

Conflict of interest

Authors declare there is no conflict of interest.

Consent to Participate

Informed consent was obtained.

Consent for Publication

Authors affirm that patient informed consent for publication of the images and participant has consented to the submission of the case report to the journal.

Ethical Approval

This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the IRB of the institute who determined that our study did not need ethical approval.

Informed Consent

The authors affirm that human research participants provided informed consent for publication of the images. The participant has consented to the submission of the case report to the journal.