Abstract
Malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive soft tissue malignancy associated with neurofibromatosis type 1. Although MPNST most commonly occurs in the extremities and trunk, it is rare in the head and neck region and extremely rare in the oral cavity, including the palate. MPNSTs arise from Schwann cells, de novo or from benign neural tumors. MPNSTs often occur between the ages of 30 and 50 years closely associated with neurofibromas. The median survival rate of the patients is 46-58% over ten years. Diagnosis is based on medical history and clinical examination, and treatment includes surgery, radiotherapy, and sometimes chemotherapy. Prognosis varies depending on location, size, and metastasis. We report an elderly female with a MPNST of the palate presenting with an exophytic lesion with details of clinicoradiographic and histopathologic features and long-term follow-up. This report describes a rare case of palatal MPNST and reviews the relevant literature.
Introduction
Malignant peripheral nerve sheath tumor (MPNST), also known as neurofibrosarcoma, neurogenic sarcoma, or malignant schwannoma, is a soft tissue sarcoma with poor prognosis, aggressive behavior, limited therapeutic intervention, 1 and high recurrence rate in local regions. 2 MPNST is a rare malignant neoplasm that accounts for 5 to 10 percent of all soft tissue cancers and 0.001% of the incidence in the general population. 3 Head and neck MPNST (HN-MPNST) accounts for 4% of all head and neck soft tissue sarcomas, 4 HN-MPNST also represents 8-16% of all MPNST cases.5,6 The most important etiologic factor for MPNST is the presence of neurofibromatosis type 1, as 50% of MPNST patients report a history of this disease. 1 The primary treatment for this disease is surgical excision. 1 Although MPNST can rarely occur in the head and neck region, most commonly involving the parotid gland, involvement of the oral cavity is extremely rare. In this article, we present a case of MPNST in the palate, an unusual location for this lesion.
Case report
An 80-year-old female with no history of systemic disease and no reported history of tobacco use, including smoking or chewing, was referred to an oral and maxillofacial surgeon around mid-2022. The patient noticed a swelling on the palate. Extraoral examination revealed no swelling or asymmetry in the facial area (Figure 1). Intraoral examination revealed an epiphytic, lobulated, sessile, ulcerated mass in the hard palate with a soft consistency (Figure 2). Clinical view, a female aged in her mid-80s with no swelling or asymmetry in the face. Intraoral view, showed a soft, lobulated, and sessile mass on the hard palate, exhibiting ulceration and epiphytic growth.
The patient was admitted to the Department of Oral and Maxillofacial Surgery in a hospital in another country. In 2022, she underwent surgery to remove a small palatal mass; the pathology report revealed undifferentiated sarcoma.
In 2023, the patient was referred to one of the hospitals of Tehran University of Medical Sciences, the Department of Oral and Maxillofacial Surgery, because of suffering from the recurrence of the lesion in the hard palate. A spiral neck computed tomography (CT) scan (with contrast) (Figure 3) showed a homogeneous mass approximately 30*13 mm in size in the right hard palate with mild bony remodeling and erosion in the underlying areas, with no obvious extension of the mass into the pharyngeal lumen or nasal cavity. The muscular structures had regular shapes and configurations. The vascular structures were intact with smooth walls. No significant cervical peripheral lymphadenopathy (LAP) is depicted; both thyroid lobules were normal in size and shape. CT-scan, a uniform mass located in the right hard palate, exhibiting mild bony remodeling and erosion in the adjacent area, without any noticeable extension.
A spiral chest CT scan (with contrast) revealed an ill-defined right hilar soft tissue with obliteration of the right middle pulmonary artery. There were some irregularly bordered nodular lesions of varying size (up to 19 mm) at the Right Middle Lobe (RML) and Right Lower Lobe (RLL). Passive segmental collapse was noted in the upper segment of the RLL and in the medial segment of the RML. Some calcified left hilar lymph nodes with some large pericardiophrenic LAPs (SAD=12mm) were also present. Some centriacinar ground glass nodules were also seen in the RML, which could indicate active infections. No pleural effusion was noted. The differential diagnosis was an old TB infection and a neoplastic process. The size of the large cardiac vessels was within normal limits. No definitive evidence of metastatic disease was identified, and pulmonary findings were considered indeterminate.
The previous slides and paraffin blocks were not available for rechecking because of the migration of the patient. An incisional biopsy was performed; the macroscopic features were ‘two dome-shaped white cream-colored solid tissues covered by ulcerated mucosa, measuring totally 1.6 * 0.8 * 0.5 cm, the section showing a non-homogeneous solid white soft surface. The microscopic features showed a malignant hypercellular mesenchymal neoplasm consisting of ovoid to spindle-shaped cells proliferating in long and short interlocking fascicles and storiform patterns in a hypo- to hyper-cellular manner in scant myxoid to fibrotic stroma. Significant atypia and numerous atypical mitotic figures were evident (Figure 4(a) and (b)). The superficial parakeratotic stratified squamous epithelium of the oral mucosa was invaded and ulcerated by the tumor cells. Regional mucinous minor salivary glands acini were affected by tumor cells. There were various differential diagnosis consisting of poorly differentiated carcinoma, melanoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, and other sarcomas. Immunohistochemical (IHC) analysis demonstrated negativity for pan-cytokeratin (PanCK), HMB45, and desmin, thereby excluding poorly differentiated carcinoma, malignant melanoma, and leiomyosarcoma, respectively. α-SMA positivity was confined to stromal vessels. Strong tumoral expression of vimentin (diffuse) and S-100 (scattered) supported the diagnosis of malignant peripheral nerve sheath tumor. Tumor cells demonstrated scattered CD34 positivity, and the Ki-67 labeling index was approximately 70%, indicating a high proliferative activity. (Figure 4(c)–(f)). The final diagnosis was a high-grade malignant spindle cell neoplasm with IHC features consistent with malignant peripheral nerve sheath tumor. Microscopic view, (a) proliferation of spindle cells with mild atypia (magnification ×100); (b) proliferation of spindle cells with prominent nuclear atypia and scattered atypical mitotic figures (magnification ×400); (c) strong positive immunostaining in tumoral cells in vimentin (magnification ×200); (d) areas of positive immunostaining for S-100 in tumoral cells (magnification ×200); (e) background vessels showed positive staining for α-SMA (magnification ×200); (f) Ki67 showed proliferation activity in about 70% of the tumoral cells (magnification ×200).
About two months after the recurrence, surgical removal of the lesion with safe margins was performed as the main treatment for the patient (Figure 5). Final microscopic evaluation of the lesion confirmed the initial diagnosis of MPNST. Now, after 3 years, the patient is alive and has no signs of recurrence or distant metastasis. Consent form for treatment and also publishing was obtained from the patient, and all patient details have been de-identified. Removed mass with a safe margin.
Method
Conducted in 2025, tumor locations data extracted from articles’ texts or figures, all sizes are in cm and shows tumor in its biggest dimension in clinical examinations.
RHP: Right hard palate, +ve: positive, -ve: negative, AntP: Anterior of the palate, LHP: Left hard palate, CSE: Complete surgical excision, ext: extended, PP: Posterior palate, HP: Hard Palate, HPY: hard palatectomy, PRM: Partial resection of the maxilla, FNA: Fine needle aspiration, RND: Radical neck dissection, SMA: Smooth Muscle Actin, ALK: Anaplastic lymphoma kinase.
Literature review
Two of the cases had neurofibromatosis type 1, and both showed cutaneous signs such as nodules. Follow-ups of these patients revealed that they died of the disease. The youngest and oldest reported patients were 13 and 79 years old, respectively.
The palate may also be the primary site of the tumor, or it may spread to the palatal region. The most common primary sites that may be involved were the palate and the cheeks. S100 was always one of the targets in IHC testing showing positive immunoreaction in all cases except one.
Based on the reviewed reports, dentists and oral hygienists were an important part of the healthcare system to recognize and refer these patients early.
Discussion
Malignant peripheral nerve sheath tumor can arise as a malignant transformation of a benign nerve sheath tumor or de novo from a peripheral nerve. 29 This lesion has an overall survival rate of 46-58% in 10 years. 30 MPNST is strongly associated with neurofibromatosis type 1 (NF1), and patients with internal plexiform neurofibroma have an approximately 20-fold increased risk of developing this malignancy. 31 Etiologically, MPNSTs can be divided into these three types: 1- sporadic, 2- neurofibromatosis type 1 (NF1), and 3- due to radiotherapy, 32 with the last type having the rarest rate and a poorer prognosis. 33
MPNSTs most commonly occur in the extremities (arms, legs, and most commonly sciatic nerve), 34 whereas involvement of the head and neck region (HN-MPNST) is uncommon. In HN-MPNST, the first tumor signs occur in the autonomic and peripheral nerves in 46% of all cases, in the connective/soft tissue regions in 31.5%, and in the nasal and paranasal areas in 9.6%. The mean age of HN-MPNST is higher than that of MPNSTs occurring in other parts of the body (49 YO – 46 YO, respectively), but there is no significant difference in the mean survival rate between these two groups. In terms of sex predilection, HN-MPNST is more likely to occur in males (60%) than MPNST in other sites (45%). 35 MPNST in the paranasal sinuses and hard palate is also reported very rare. 8 In contrast to typical head and neck MPNST patterns, the present case involves an elderly female patient with tumor involvement of the hard palate, an exceedingly rare site for this entity.
As with any peripheral nerve tumor (PNT), a complete history and clinical examination are the most important sources of information for diagnosis. Physical features may include soft tissue mass, pain, and loss of sensation. Unlike benign peripheral nerve tumors, MPNSTs have a progressive neurological deficit and a rapid growth rate. 36 Zhou et al. noted the loss of sensation, pain, a soft tissue mass, and laxity at the tumor site (in the reported case, the hand) are symptoms, but none of these features can determine the type of nerve tumor. Typically, PNTs move vertically to the nerve axis, but they are fixed on the axis of the nerve. 37
In radiographic evaluation it is common to see some features including edema around the lesion, cystic necrosis, and disorganized margins. Lesion size cannot differentiate benign from malignant types alone. Radiologic findings are usually supportive rather than diagnostic. 38 A previously reported case showed a well-defined, lobulated lesion with relative T1 hyperintensity and T2 hypointensity on MRI. 39 Our reported case was assessed by CT, demonstrating a homogeneous palatal mass with mild bony remodeling.
Histologically, MPNST is characterized by hypercellular spindle cell proliferation with numerous atypical mitotic figures and prominent cellular atypia, pleomorphism, and increased N/C ratio. 40 In some variants, it may show heterogeneous elements, including skeletal muscle differentiation, cartilage, bone, or glandular structures; marbling may also be seen. 29 Rhabdomyoblastic differentiation may also be associated with a poor prognosis, but NF1 status does not affect. 41 IHC markers are mainly S100 and SOX10, but even they are limited in their ability to show MPNST. 42 Some studies suggest that these two markers can be seen in 50% of MPNSTs 29 ; other markers are p16, p75NTR, p53, neurofibromin, and EGFR. 42 In 2019, Senthilkumar et al. reported a case of MPNST using S100 and Ki67. Both markers were strongly positive (S100 in 95% of tumor cells and Ki67 in 10-15% of tumor cells). 43 S100 and SOX10 lack specificity for neural origin and may be expressed in other spindle cell sarcomas; therefore, a broad immunohistochemical panel is essential to exclude alternative malignancies, such as malignant melanoma or rhabdomyosarcoma. In the present case histopathological reported features of MPNST, including spindle cell morphology and S-100 positivity were observed. However, despite a markedly high Ki-67 labeling index (approximately 70%), the clinical outcome was favorable, contrasting with the poor prognosis commonly described in the literature.
MPNSTs that occur in the trunk have a worse prognosis than hands and feet.44,45 However, it is said that NF1 does not influence the prognosis and is not associated with poor prognosis in some articles. 41 On the other hand, in some other studies it plays a significant role in a poor prognosis, do its size, location, metastasis and grading. 46 Usually, surgery is the primary treatment, but the type of surgery may vary from case to case; patients may need aggressive or conservative surgery, and adjuvant radiotherapy with a dose of ≥ 60 Gy can control the tumor locally.47,48 Chemotherapy is usually accepted for metastatic cases. 49 Kaplan reported a case of MPNST in 2013 in which vemurafenib was presented as a beneficial systemic treatment for this lesion. 50 In our case, after consultation with the oncologist, adjuvant chemotherapy was not required for the patient because of free margins. A limitation of this case report is the absence of serial surveillance imaging during follow-up, due to the patient’s migrant status and difficulty visiting the surgeon and undergoing clinical examination. Therefore, long-term follow-up and the patient assessment were primarily based on calling and self-assessment.
Conclusion
MPNST is a rare soft tissue tumor that can occur in all parts of the body, but it is less common in the head and neck region. Malignant peripheral nerve sheath tumors have a difficult diagnosis and require clinical, histologic, and radiologic evaluations. Surgery and adjuvant radiotherapy are commonly used for local situation control. In this report, we present a patient suffering from MPNST in the hard palate. The tumor was diagnosed based on accurate physical examinations, radiographic patterns, histopathological features, and immunohistochemical findings. The patient underwent surgery, and fortunately after 3 years of follow-up, there is no evidence of recurrence.
Footnotes
Ethical considerations
This study was approved by the Ethics Committee of BY Research Ethic committees of school of dentistry – Tehran University of Medical Sciences (IR.TUMS.DENTISTRY.REC.1404.095).
Consent to participate
Written informed consent obtained from the patient.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
The data underlying this article cannot be shared publicly to protect patient privacy. Data are available from the corresponding author upon reasonable request.