A giant occipital malignant peripheral nerve sheath tumor in non-neurofibromatosis person: A rare case and review of literature

Introduction: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive tumor which is often associated with neurofibromatosis type-1 (NF-1). This rare tumor is often associated with nerve roots and bundles in the extremities. Occipital MPNST is rare. Giant size occipital scalp MPNST is extremely rare in literature. The size of tumor often becomes difficult to treat. We present one of the most gigantic occipital MPNSTs (14 × 27 × 44 cm) published in the literature. Case Report: A 27-year-old lady who presented with a huge occipital mass and a history suggestive of bilateral pathological fracture of the tibia. At presentation her occipital mass measured 14 × 27 × 44 cm. Cranial computed tomography (CT) showed evidence of calvarial erosion. She had subtotal tumor resection with histology suggestive of MPNST while immunohistochemistry was positive for S-100. She was referred to the oncology unit for chemoradiation. Conclusion: Huge occipital MPNST presents management challenges because treatment is difficult. This giant MPNST has been added to the body of knowledge while the search for the ultimate solution continues. JKC Emejulu1, SPU Nkwerem2, OC Ekweogwu2, IV Okpalike3, RC Nwosu3, CL Okwunze4 Affiliation: 1Professor, Department of Surgery, Nnamdi Azikiwe University, Awka, Nigeria; 2Lecturer, Department of Surgery, Nnamdi Azikiwe University, Awka, Nigeria; 3Senior Resident, Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria; 4Resident, Department of Surgery, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria. Corresponding Author: Professor JKC Emejulu, Department of Surgery, Nnamdi Azikiwe University, Awka, Nigeria; Email: judekenny2003@yahoo.com Received: 13 May 2020 Accepted: 01 July 2020 Published: 20 August 2020


INTRODUCTION
The malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive tumor of the connective tissues surrounding the nerves. This tumor, occasionally referred to as malignant schwannoma, malignant neurilemmoma, neurofibrosarcoma, and neurogenic sarcoma, constitutes 5-10% of all sarcomas in adults [1,2]. It is found in 50% of neurofibromatosis type-1 (NF-1), an autosomal dominant disorder, while the others are sporadic in occurrence or radiation induced [1]. This rare tumor is often associated with nerve roots and bundles in extremities and pelvis. Malignant peripheral nerve sheath tumors are uncommon in the head [3]. An early presentation may make a wide local excision curative; other treatment modalities include chemotherapy and radiotherapy [4].
We present a case of a giant, grotesque occipital malignant nerve sheath tumor which was recently managed in our service ( Figure 1) and also review the literature.

CASE REPORT
A 27-year-old right handed woman with a posterior scalp swelling of six months duration, which was insidious in onset and progressively increasing in size, associated with intermittent dull pains. There was no associated irrational talk, seizure, altered level of consciousness, visual impairment, double vision, or hemi-body weakness. There was neither associated café-au-lait spots nor skin lesions. About five months following the onset of symptoms, she developed bilateral closed tibial fractures following a minor fall. There was no history of fever or preceding trauma before the onset of symptoms. She had no history suggestive of anorexia or weight loss. There was a history of herbal medication initially but, because of the progression of the mass, she sought orthodox treatment.
At presentation, she was fully conscious and alert, and was not in any obvious distress. She was slightly overweight, otherwise, her general clinical condition was unremarkable. There was a huge, tense, cystic soft tissue, left paramedian occipital mass, extending to the middle. The mass was 14 × 27 × 44 cm in dimension ( Figure  1), and slightly tender. It did not transilluminate and there was no associated skin nodules or pigmented skin patches. She had normal bilateral visual acuity. There was bilateral lower extremity edema and deformities with splints and crepe bandage in situ. X-ray images showed a left upper-third tibial fracture and right lower-third femoral fracture.
Cranial computed tomography showed a left parietal extra-axial mass with an underlying calvarial defect (barely short of the sagittal suture), with a mixed density extracranial component (hypodense-isodense) that was heterogeneously contrast enhancing ( Figure 2). There was an unremarkable metastatic work-up.
A diagnosis of left occipital scalp mass with intracranial extension was made. The plastic surgery was also invited to review. She was subsequently worked up and had craniectomy and subtotal gross tumor excision through a midline scalp incision ( Figure 3). The tumor capsule was peeled off the overlying redundant skin. The adjoining periosteum was completely excised, edges of bony defect nibbled till healthy bone was encountered (see arrow in Figure 4) and residual tumor which was adherent to the dura coagulated and the infiltrated dura excised. Dural defect was repaired with a harvested occipital fascia. The redundant and denuded skin was trimmed to size ( Figure  5). Tumor specimen and postoperative cranial computed tomography are shown in Figures 6 and 7, respectively. Histology report was diagnostic of a MPNST, while immunohistochemistry was positive for S-100, but negative for epithelial membrane antigen (EMA) and desmin. She was, subsequently, referred to the radiooncology. Cranioplasty was planned as a second-stage procedure. She had radiotherapy and two courses of ifosfamide and epirubicin before she was lost to follow up.
The etiology of MPNST has remained largely unknown, however, there are some genetic mutations so far identified with MPNST, and they include NF-1 and TP53. Both therapeutic and environmental radiation exposures have also been associated with this rare tumor [26,27]. The NF-1 which is located on chromosome 17q11 codes for neurofibromin is known to take part, ultimately, in the inhibition of the p21ras signaling pathway. The loss of this regulatory pathway has been observed in transformation of the NF-1 to MPNST. Other genetic mutations observed     include the T53 point mutation or deletion, deletion of the CDKN2A, RB1 tumor suppression gene [28,29]. Yuan et al. have also noted excessive expression of some biomarkers, particularly S-100 and Ki67 in MPNSTs patients [30]. The biomarkers help in easy distinction between benign nerve sheath tumor and the malignant variety.
The MPNSTs are highly invasive and readily metastatic, the index case presented with bilateral pathological femoral fractures and obvious calvarial erosion in 6-month history, making complete cure a difficult task.
Complete surgical resection with margin ≥2 cm is important for complete resection. Radical resection with adjuvant radiotherapy is the mainstay of treatment [31]. Generally, in MPNSTs that are high grade, large (>5 cm), surgically inaccessible, or metastatic, complete resection is often difficult, hence subtotal resection may be what is achievable [29,31].
Adjuvant radiotherapy is recommended for patient with large high grade tumor (>5 cm) or with microscopically (R1) or macroscopically (R2) positive resected tumor margins as a postoperative measure to reduce local recurrence and control pains [29]. Grotesque tumor size (14 × 27 × 44 cm) with calvarial erosion and dura infiltration, as well as distant metastasis, precludes cure. Late presentation to health care services may account for this tumor size which is one of the largest scalp MPNST in non-neurofibromatosis case published.
Chemotherapy and immunotherapy may also be useful therapeutic strategies [14,25]. The use of chemotherapy in MPNST has not be very rewarding [1].
The index case had subtotal gross total tumor resection followed by chemoradiation. Local recurrence rate and metastasis are at 40-65% and 40-68%, respectively [32]. In NF-1 patients, MPNST is the most common cause of mortality.

CONCLUSION
Management of a giant occipital MPNST remains a daunting task. Late presentation of patient with tumor makes treatment a difficult task. We believe that this case report will also add to the body of knowledge and data available for MPNST while the search for the ultimate cure for huge occipital MPNST continues.