Clinicopathological And Molecular Genetic Characteristics Of Malignant Peripheral Nerve Sheath Tumor

【Purpose】To investigate the clinicopathological features,immunophenotypic,genetic features of Malignant Peripheral Nerve Sheath Tumor(MPNST).The purpose of this study is to improve the understanding of MPNST and provide evidence for clinical diagnosis and prognosis evaluation.【Method】The clinical and histological characteristics of 16 cases of MPNST from the First Affiliated Hospital of Nanjing Medical University between January 2012 and January 2021 were retrospectively reviewed.We reviewed the pathological section and the expressions of S-100,SOX10,CD34,H3K27me3 and SDHB were detected by immunohistochemistry.Finally,the next-generation-sequencing(NGS)technique was performed in 3 cases of MPNST.【Results】There were 16 cases of MPNST,including 6 males and 10 females.The average age of 16 patients was 37.1 years(11-79 years),and the median age was 36 years,including 9 cases of NF1--associated MPNST with a median age of 29 years old and 7 cases of sporadic MPNST with a median age of 46 years old.The maximum diameter of the tumor was 4.5-18 cm,with an average of 9.2cm.Pathologically,14 cases of MPNST were characterized by highly cellular fascicles of spindle cells and the interstitium is dominated by thin-walled vessels,1 case was myxofibrosarcoma-like,1 case was mainly oval tumor cells and the mitotic figures were mostly more than 5 / 10 HPF in 16 patients.Under low power microscope,12 cases feature alternating hypocellular/myxoid and hypercellular areas and perivascular accentuation of cellularity in 13 cases.Four cases show heterologous mesenchymal differentiation,including 3 cases of chondrogenic differentiation and 1case of rhabdomyogenic differentiation.According to FNCLCC,none of the cases were classified as grade 1 tumor,11 cases as grade 2 tumor,and 5 cases as grade 3tumor.Immunohistochemically,tumor cells showed positive of S-100 and SOX10,with the ratio of 62.5% and 43.8% respectively.The percentage of CD34-network loss and H3K27me3-loss were both 81.2%.NGS test revealed that germline mutations of NF1 and SDHA genes and somatic mutations of FAT1,BRAF and KRAS genes in case 6,somatic mutations in NF1,FAT1,FAT3,APC and MUC16 genes in case 5,and somatic mutations of NF1,SUZ12 and NCOR1 genes in case 12,respectively.Among the 16 patients,4 patients died of disease(All the four cases were correspond to an histologic grade 2 category and the four patients had the clinical history of NF-1).【Conclusion】MPNST usually arises in adults and most commonly affects the extremities.The onset age of NF1--associated MPNST was earlier than that of sporadic MPNST.It is easy to diagnose MPNST because it has a wide spectrum of histological morphology,overlaping with a variety of other sarcomas.H3K27me3 is a useful marker in the diagnosis of MPNST,especially in sporadic MPNST.Loss of CD34 positive network could also work as a clue for the indication of malignant transformation.The genetic changes of MPNST are complex,NF1 gene alterations are the most common genetic change,but other genes play a important role in malignant transformation.