An MPNST is a relatively rare but highly malignant sarcoma of soft tissues . It primarily occurs with a peak incidence between the ages of 30 and 60 years of life in the general population with equal frequency in males and females, although these tumors may occur at a much younger age . The case reported here is a 20-year-old girl, indicating that age predisposition is contributory factor of disease.
MPNSTs are associated with inherited abnormalities, such as the loss of neurofibromatosis 1 (NF1) gene protein. NF1 is an autosomal dominant disorder that represents the most common human cancer genetic susceptibility syndrome with an incidence of approximately 1 in 3,000 . NF1 is characterized by multiple areas of cutaneous hyperpigmentation, axillary freckling, numerous neurofibromas, optic gliomas, bone dysplasia, iris hamartomas termed Lisch nodules, and a family history of NF1 in a first-degree relative, and it is diagnosed in the presence of any two of these seven criteria . Half of MPNSTs derive from nerves affected by NF1, and the other half occurs in the general population. Among the other half of MPNSTs that occur in the general population, approximately 40% are sporadic and the remaining 10% arise secondary to previous irradiation . Inferior outcomes have been observed in radiotherapy-induced MPNSTs compared to sporadic or NF1-related MPNSTs [11, 12]. Our patient had no clinical manifestation of any of the features of NF1 mentioned above, nor did she have any history of radiotherapy. Therefore, her case was considered as sporadic.
The histopathological features of MPNSTs are nonspecific. In general, tumors are composed almost entirely of compact spindle cells with variable hyperchromatism and pleomorphism arranged in intersecting fascicles . In our case, histopathological examination showed that most areas are less cellular areas, with background myxoid degeneration and chronic inflammatory cell infiltration. In some densely cellular areas, the cells showed marked atypia, mitosis, and necrosis, and tumor tissue infiltrated the surrounding rhabdoid muscles. However, due to the uncertainty of histological diagnoses, immunohistochemical is essential for the definitive diagnosis of MPNST. The immunohistochemical results of our patient showed that S-100, SOX-10, Ki-67(10+) were all expressed in less cellular areas, while expression of Ki-67(80+), but not S-100 and SOX-10, was observed in densely cellular areas. Studies have shown that the immunoreactivity for S100 and SOX-10 proteins indicates Schwann cell origin and support a diagnosis of cellular schwannoma [14–16]. However, the sensitivities of S100 and SOX10 expression for the diagnosis of MPNST were not high, which suggests downregulation of Schwannian markers in MPNST [13, 17, 18].
MPNSTs involve a high rate of metastasis via the bloodstream, while with infrequent but possible lymphatic spread . Furthermore, there is a high rate of recurrence, with up to 50% local recurrence and up to 33% metastases to the lungs and bone [20, 21]. According to several previously published studies, the five-year survival of head and neck MPNST ranges from 16–52%, with better prognosis associated with complete resection, size < 5 cm, high histological differentiation, and low Ki-67 labelling index [22–27]. Our patient was considered to have residual tumor, size > 5 cm, lung metastasis at the initial diagnosis, and Ki-67 was > 80%, and the survival time was only about six months after various treatments, which was considered to be caused by the high degree of malignancy and rapid progression of the tumor.
As with most soft tissue sarcomas, extensive resection is the primary treatment for MPNST [28–30]. Due to the high incidence of local recurrence in MPNSTs after surgery, adjuvant radiotherapy usually plays an indispensable role in local disease control [31, 32]. However, its role in reducing the incidence or improving survival in patients with distant metastases remains controversial [33–36]. In the present case, postoperative radiotherapy was delivered because of the extension of the tumor to the left atlas, which could harbor microscopic residual disease. However, the rapid progression of the lesion occurred within a short period of time before radiotherapy, and the patient did not have time for radiation therapy and had to undergo a second operation. However, three weeks after the second operation, the patient showed rapid progress again. After a multidisciplinary discussion, the patient was given radiotherapy combined with cisplatin and epirubicin chemotherapy. At the beginning, the patient's symptoms were not significantly relieved, but the patient's symptoms were significantly improved after the addition of antiangiogenesis treatment with Anlotinib. After the end of radiotherapy, reexamination showed that the lesions in the patient's head and neck were smaller than before, while the lung lesions were advanced. However, the patient's clinical symptoms were significantly improved and she by then was capable of moving independently. Considering the severe digestive tract reaction of the patient with cisplatin, we tried to give epirubicin combined with temozolomide intravenous chemotherapy, but the efficacy was unsatisfactory.
Currently, chemotherapy is only used for inoperable or very large tumors (> 5–8 cm in size), incompletely resected cases, or patients with metastatic or recurrent disease . Fortunately, the fact that the patient remained asymptomatic locally after two months of completion of radiotherapy combined with anlotinib indicates a possible benefit of the adjuvant postoperative radiotherapy combined with anlotinib, which might provide an alternative to the treatment of MPNST. Anlotinib is a novel, orally administered tyrosine kinases inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR) signaling by selectively targeting VEGFR-2, -3 and fibroblast growth factor receptor 1 to 4 [38, 39]. Recent studies showed a median progression-free survival and overall survival of 5.6 and 12 months, respectively, in patients with advanced soft tissue sarcoma treated with anroitinib . Here, we, for the first time, demonstrate the clinical application of anlotinib combined with radiotherapy in the treatment of MPNST.