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Case Report III

A Rare Case of Malignant Peripheral Nerve Sheath Tumor of the Anterior Mandible

G.Thirilosanan, Z.Qayyum, A.M.Attygalla and P.R.Jayasooriya

AbstractMalignant peripheral nerve sheath tumor (MPNST) is an extremely rare aggressive sarcoma arising from any peripheral nerve or from cells associated with the nerve sheath. The etiology is unknown. Its occurrence in the head and neck region is 10-15%. The tumor is usually found in extremities and trunk. Here, we report a rare case of MPNST occurring in the anterior mandible of a 30 year old lady. It was histopathology revealed that the presence of spindle shaped cells with abundant cytological atypia and the positivity of S-100 protein existed. The patient was managed by radical resection and the defect area was restored by a free fibula flap with adjuvant radiotherapy. Surgical resections stands as the mainstay of treatment with clear margins confirmed through frozen biopsy. Adjuvant radiotherapy plays an important role in reducing local recurrence. Prognosis of a patient with MPNST is poor with a five years survival rate of 16-52%. Considering the prognosis, early detection always helps to reduce mortality and morbidity. Long terms follow up with monitoring for recurrence and dissemination is mandatory.

The case report highlights the clinical presentation, diagnosis and management of a rare aggressive sarcoma.

Key words: Malignant peripheral nerve sheath tumor; Sarcoma; Frozen biopsy; Adjuvant radiotherapy

IntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are uncommon diversity of soft tissue sarcomas (STS). These originate from peripheral nerves or from cells associated with the nerve sheath, such as Schwann cells, perineural cells or fibroblasts.1, 2

MPNSTs incorporate approximately 5-10% of all soft tissue sarcomas and are commonly seen in thee xtremities and trunk.3 It occurs rarely in head and neck region with a frequency of 10-15% according to the literature.1,4They occur either spontaneously or in association with neurofibromatosis type 1 (NF1).5A very few cases of MPNST in the mandible unassociated with NF1 have been reported. The etiology is unknown. It usually occurs in the 20-50 years age group and shows a more or less equal sex distribution.5

Sri Lanka Dental Journal 2017; 47(01) 38-44

G.Thirilosanan(Correspondence)Z.QayyumA.M.Attygalla

P.R.Jayasooriya

Registrar in OMFS, (Correspondence) Department of Oral and Maxillofacial Surgery Dental Teaching Hospital Peradeniya, ganesarajahthirilosanan@gmail.comDeparment of Oral and Maxillofacial Surgery Dental Teaching Hospital PeradeniyaSenior Lecturer and Consultant, Department of Oral and Maxillofacial Surgery Dental Teaching Hospital PeradeniyaProfessor and Consultant, Department of Oral Pathology Faculty of Dental Sciences, Peradeniya

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Pain and swelling is the common presentation and the diagnosis may be missed unless the clinical suspicion is high, but an immunohistochemistry test for S-100 protein could often confirm the diagnosis.6

MPNSTs tend to behave aggressively with a high rate of recurrence and metastasize like other STSs even though surgical resection stands as the main foundation of treatment; the role of adjuvant treatment is as yet unclear.7-9 Local recurrent rate for MPNSTs have been reported to range from 40-65% and metastasis rate has similarly been reported to range from 40-68%.10,11 5 years survival rate has been reported range from 16-52%.11Prognosis depends on the tumor size, the histological grade and the resection margin while at surgery.9

To the best of our knowledge, only a very few cases of MPNST of the anterior mandible have been reported in literature.12Reconstruction of anatomic configuration of anterior mandible is important in terms of airway function and facial esthetics. Therefore, surgical management of this case is even more challenging. Here we report a case of a rare intra osseous MPNST of mandible which showed an aggressive clinical presentation and its management, besides a review of the literature.

Case reportA 30-years- old female patient was referred to the Oral andMaxillofacial unit with an aggressively enlarging bony lesion in the anterior mandible. Her history revealed severe pain in relation to the right side of the mandible with a gradually enlarging mass of 4 months duration. There was no relevant past medical or surgical history and she denied any family history suggestive of neurofibromatosis.Extra oral examination revealed remarkable facial asymmetry associated with a soft, diffused and tender swelling measuring approximately

5x7x4 cm with reddish skin color (over the chin area) extending from symphyseal region to right side body of the mandible (Fig 1). There was no lymphadenopathy or signs of neurofibromatosison general examination.

Intra orally the swelling extended from 33 to 46 with irregular ulcerated area over right side of parasymphyseal region (Fig 2). Swelling was tender and soft in consistency along with mobility of the teeth.

Cone beam computed tomography (CBCT) revealed extensive destruction of the anterior mandible extending from 34 to 46 (Fig 3). There was bony erosion of lower buccal, lingual and alveolar aspects. Computerized tomography (CT) scan divulged an enhancing lesion in the anterior mandible without significant lymph node enlargement. Metastatic workup included of CT thorax, CT abdomen and skeletal radiographs which were normal.Incisional biopsy showed unencapsulated tumor composed of spindle shaped cells arranged into storiform pattern with marked cytological atypia. Immunohistochemistry stain for S -100 protein was positive in tumor cells (Fig 4). Cytokeratin, smooth muscle actin (SMA) and desmin were negative. Based on these finding, it was diagnosed as high-grade MPNST.

The treatment was decided by a multi-disciplinary team comprising the Oral andMaxillofacial Surgeon, Oncologist , Oral Pathologist , Anesthetists, Prosthodontist andthe Dietician. The treatment plant included radical surgery and adjuvant radiotherapy. Our patient underwent wide local excision including anterior mandibulectomy and reconstruction of the surgical defect by fibula free flap (Fig 5-7). The patient received adjuvant radiotherapy from fifth week post operatively in two phases. In the first phase 50Gy was given in the fraction of 2Gy/Day. Remaining 10 Gy was given in the similar fraction in second phase.The

A Rare Case of Malignant Peripheral Nerve Sheath Tumor of the Anterior Mandible

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patient did not attend the follow-up clinic after one year.

Discussion.MPNSTs are defined by the World Health Organization as a subcategory of soft tissue sarcomas from a peripheral nerve or showing a nerve sheath differentiation, with the exception of tumors originating from the epineurium or the peripheral nerve vasculature.1 MPNSTs was also known previously as malignant schwannoma, malignant neurofibroma, neurofibrosarcoma, malignant neurolemmoma and a neurogenic sarcoma may develop in a pre-existing neurofibroma or denovo.1,2 In around 10% of the cases MPNST can also arise subsequent to radiation at that site.13 It occurs in about 2-5% of NF1 patients compared to an incidence of 0.001% in the general population.3

MPNSTs generally occur in adulthood, typically between the ages of 20 and 50 years of age.5. Approximately 30-40% of cases have been reported to occur in the first 3 decade of life.3It shows a more or less equal sex distribution.5

MPNSTs are mainly present in the buttocks, thighs, brachial plexus, Para spinal region and commonly associated from major nerve trunks such as the sciatic nerve, brachial plexus and sacral plexus3; inferior alveolar nerve involvement is very rare.

Head and neck region involvement is seen in only 10-15% of cases; when head and neck tumors do occur it main lyinvolves the parotid or infratemporal fossa.1, 4 Some literature reviews have reported cases involving the posterior mandible, maxilla, labial mucosa and temporal region.1-4 MPNST arising in the anterior mandible is very infrequent and to our knowledge about 16 cases are reported in the mandible among that only 2 cases presented in the anterior mandible.4, 12

The case describe here was a thirty years female

with an anterior mandibular swelling with no evidence of NF1 or previous radiation. According to the literature,it tends to grow slowly but in this case appeared as a rapid growth associated with pain and swelling. This tumor can metastasize by hematogenous and perineural spread and lymph node metastasis is rare.7.No local lymphatic or systemic metastasis were observed in the present case.The MRI is useful to locate the site and define the tumor extension but it does not reliably determine malignant transformation.14 Positron emission tomography (PET) with computed tomography (CT) is considered a potentially useful, non-invasive method for detecting malignant changes in a lesion.14 In this case,the patient underwent CBCT and CT face, chest and abdomen; it hold the evidence of erosion and widening of the mandible with no evidence of distant metastasis.

Histopathological diagnosis can be made by tru-cut needle biopsy, incisional biopsy or excisional biopsy. Fine needle aspiration cytology is inadequate for the assessment of tumor type and grade.6.Since the clinical differential diagnosis of this patient included alveolar carcinoma, odontogenic tumor and nerve sheath tumor, she underwent an incisional biopsy which was reported as high grade MPNST.

Histopathologically, MPNST consist of fascicles of atypical spindle shaped cells, which can resemble fibrosarcoma and leiomyosarcoma. Some tumors have epitheloid appearance. Heterogenous elements like glandular structures, cartilage and skeletal muscle fibers can be present. In 50-70% of the MPNSTs, scattered tumor cells express S100 protein.2,6. In our case of MPNST expressed inspindle shaped cells arranged in to storiform pattern with marked cytological atypia. Immunohistochemistry stains for S100 protein was positive.

MPNSTs have been reported to be aggressive and

G.Thirilosanan, Z.Qayyum, A.M.Attygalla and P.R.Jayasooriya

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have a high tendency to metastasize to distal sites and recur locally. According to theliterature guide line Lymphatic spread in sarcoma are rare.15 As a result, its management may require a radical block dissection and sometimes even radiation therapy.7-9.This patient underwent wide local surgical resection with anterior mandibulectomy. To improve the patient’s quality of life, the defect was restored with a free fibula flap. Fibula free flap is a versatile reconstruction method after anterior mandibular resection and it has adequate length to restore the massive defect area.16. Surgically resected margins were ensured free of tumor with use of frozen biopsy technique.

Adjuvant radiotherapy (RT) is recommended for all high grade lesions. Our patient was given radiotherapy to a total dose of 60Gy. The role of chemotherapy is usually limited to the locally advanced and metastatic disease. Contribution of chemotherapy for MPNST is still under

assessment.8, 17

The present case was treated with surgery and adjuvant radiotherapy. Patient’s recovery was unremarkable. She remained disease free for a period of one year post operatively and did not attend the clinic thereafter.

Conclusion.MPNST of the anterior mandible is a very rare tumor. The goal of management of MPNST is to obtain adequate negative margin with surgery to gain optimum clearance ofthe tumor. Frozen section biopsy remains a valuable tool. However, it should be taken into account that surgical defect reconstruction with the appropriate flap plays animportant role in enhancing the quality of life of these patients. MPNST has the worst prognosis, as there is high incidence of local recurrence. The role of radio therapy remains as an adjuvant therapy. Early detection always helps and reduces mortality and morbidity.

A Rare Case of Malignant Peripheral Nerve Sheath Tumor of the Anterior Mandible

Figure 4.H &E stain of lesion

Figure1.Extra oral swelling of the anterior mandible

Figure 2.Intra oral appearance of lesion.

Figure 3.CBCT image of MPNST of anterior mandible

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Figure7.Post-operative frontal view skin

Figure 6.Harvestedfibular free flap with peddle & reconstruction plate

G.Thirilosanan, Z.Qayyum, A.M.Attygalla and P.R.Jayasooriya

Figure 5.Anatomical landmarks of fibular donor site

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1.

2. Neiville BW, Damm DD. Oral and maxillofacial pathology-connective tissue lesions. Saunders.2002; 482.

3. D.H. Kim, J.A. Murovic, R.L. Tiel, G. Moes, D.G. Kline, A series of 397 peripheralneural sheath tumors: 30-year experience at louisiana state university healthsciences center, J. Neurosurg.2005; 102: 246

4. ShymaPS, Gangothri S, Reddy KS, Basu D, Ramkumar A. Malignant peripheral nerve sheath tumor of mandible: A case report and review of literature. J Neurol Res 2011; 1(5): 219-222.

5. ColmeneroC, Rivers T, Patron M, Sierra I, Gamallo C. Maxillofacial malignant peripheral nerve sheath tumors. J Craniomaxillofac Surg. 1991; 19(1): 40-60.

6. Weiss SW, Langloss JM, Enzinger FM. Value of S-100protein in the diagnosis of soft tissue tumors with particularreference to benign and malignant Schwann celltumors. Lab Invest. 1983; 49(3): 299-308.

7. Collin C, Godbold J, Hajdu S, Brennan M. Localizedextremity soft tissue sarcoma: an analysis of factors affectingsurvival. J ClinOncol. 1987;5(4):601-612

8. McConnell YJ, Giacomantonio CA, Malignant triton tumors-completesurgical resection and adjuvant radiotherapy

associated with improved survival, J. Surg.Oncol.2012;106 :51.

9. Ali NS, Junaid M, Aftab K. Malignant Peripheral Nerve Sheath Tumour of Maxilla.JColl Physician Surg Pak 2011;21:420–2.

10. B.S. Ducatman, B.M. Scheithauer, D.G. Piepgras, H.M. Reiman, D.M. Ilstrup,Malignant peripheral nerve sheath tumors: a clinic pathologic study of 120cases, Cancer 57 (1986) 2006–2021.

11. E. Wanebo, J.M. Malik, S.R. VandenBerg, H.J. Wanebo, N. Driesen, et al . , Malignant peripheral sheath tumors A clinic pathologic study of 28 cases, Cancer 71 (1993) 1247–1252

12. Khan MH, Khwaja KJ, Salati NA,& Anwar M. Malignant peripheral nerve sheath tumor of mandible in a young female a case report. Annals of dental speciality.2014;2(4) 155-157

13. Ducatman BS, Scheithauer BW. Post irradiationneurofibrosarcoma. Cancer. 1983; 51(6): 1028-1033.

14. Chhabra A, Soldatos T, Durand DJ, Carrino JA, Mc-Carthy EF, Belzberg AJ. The role of magnetic resonanceimaging in the d iagnos t ic eva lua t ion of malignantperipheral nerve sheath tumors. Indian J Cancer.2011; 48(3): 328-334.

15. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: soft tissue sarcoma: version 3 [Internet]. Washington: National Comprehensive Cancer Network, c2012 [cited 2013 Jun 15].

A Rare Case of Malignant Peripheral Nerve Sheath Tumor of the Anterior Mandible

References

EnzingerFM, Weiss SW.Malignant Tumors Of Peripheral Nerves. In: Enzinger FM, Weiss SW, Editors. Soft tissue tumors. St. Louis: Mosby; 1995.p.889-928

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16. Hidalgo DA, Pusic AL. Free Flap

Mandibular Reconstruction: A 10-Year Fo l low Up S tudy. P las t i c andReconstructive Surgery. 2002; 110(2): 438-449. Moretti VM, Crawford EA, Staddon AP, Lackman RD, Ogilvie CM. Early

outcomes for malignant peripheralnerve sheath tumor treated with chemotherapy. Am JClinOncol. 2011; 34(4): 417-421.

17. Punjabi AP, Haug RH, Chung-Park Moon JA, Likavek M. J OralMaxillofacSurg 1996; 54:765—9.

G.Thirilosanan, Z.Qayyum, A.M.Attygalla and P.R.Jayasooriya