Background. Peripheral nerve sheath malignancies (PNSM) are a rare and aggressive group of sarcomas that can occur sporadically, after radiation therapy, or related to neurofibromatosis type 1. Loss of function of NF1, TP53, and CDKN2A genes is thought to contribute to the progression of benign neurofibroma to PNSM and is a poor prognostic sign. The optimal management of patients with this disease is currently unresolved, and specific prognostic factors have not been established. Aim. To analyze the results of surgical treatment in patients with PNSM and establish prognostic factors of overall and recurrence-free survival rate. Materials and methods. The retrospective and prospective studies enrolled adult patients with histologically confirmed PNSM treated between 1998 and 2021 at the N.N. Blokhin National Medical Research Center for Oncology. Surgical intervention was performed on 61 patients, 38 (62%) females and 23 (38%) males. The most common PNSM localization was paravertebral (22 [36%] patients), followed by retroperitoneal (14 [23%] patients), and upper and lower extremities (13 [21%] and 12 [20%] patients, respectively). Results. For PNSM patients with a history of surgery, the median overall survival (OS) was 46 months (95% confidence interval 26.165.9). The 3-year and 5-year OS was 46% and 31%, respectively. The median recurrence-free survival (RFS) was 27 months (8.745.3), and 3-year and 5-year RFS was 26% and 13%, respectively. Median OS for grade 1 malignancies was not achieved, while grade 2 and grade 3 malignancy was 53 and 33 months, respectively (p=0.033). The median RFS for grade 1, 2, and 3 tumors was 119, 43, and 15 months, respectively (p=0.078). Patients who underwent radical (R0) surgery had higher RFS (p=0.006) and OS (p0.0001). After radical (R0) surgery, the median OS was not achieved; after nonradical (R1/R2) surgery, the median was 34 months. The median RFS was 124 months after R0-resection and 48 months after R1/R2. Conclusion. The most significant prognostic factors in PNSM patients are the radicality of the surgery performed and the malignancy grade. In our study, tumor size and localization did not affect the long-term treatment results.

Introduction. Malignant peripheral nerve sheath tumors (MPNSTs) belong to a rare heterogeneous group of aggressive neoplasms of mesenchymal origin. The relationship between the PD-L1 expression and development and prognosis of MPNSTs has not yet been determined. In addition, it is yet to explore the role of tumor microenvironment, in particular tumor-associated macrophages, in solid tumors. The aim of the study was to determine the relationship between (1) PD-L1 expression and the nuclear marker of PU.1 expression in stromal cells and (2) overall survival (OS) and recurrence-free survival (RFS) in patients with MPNSTs. Materials and methods. The retrospective study included 46 adult patients with MPNSTs who underwent surgical or combined treatment from 1998 to 2021 at the N.N. Blokhin Oncology Research Center. We analyzed clinical and morphological parameters as well as the outcomes of surgical treatment. Immunohistochemistry was used to detect the expression of PD-L1, PU.1, and Ki-67. Results. We found positive PD-L1 staining in 28% of cases. PU.1 expression was observed in all samples. We showed a statistically significant correlation between PU.1 and PD-L1 expression levels. At a median follow-up of 37 months, PD-L1 positive status was associated with a lower median OS and RFS in the group of patients with grade III tumors (p=0.0003 and p=0.004, respectively). The median OS for tumors with high and low number of PU.1+ cells was 21 and 78 months, respectively (p<0.0001). Conclusion. To the best of our knowledge, this is the first study to describe the prognostic value of the macrophage marker PU.1 in patients with MPNST. High levels of PU.1+ cells, regardless of the tumor grade, and PD-L1 expression >1% of tumor cells in the patients with poorly-differentiated MPNSTs, produced a negative effect on OS and RFS. The analyzed expression of these markers can be used in prognostic tests and developing novel therapeutic treatment options. Keywords: malignant peripheral nerve sheath tumor, PD-L1 immunohistochemistry, PU.1, surgical treatment