Are preoperative complete blood count parameters in peripheral nerve sheath tumors useful diagnostic tools?

OBJECTIVES: This study aims to evaluate the diagnostic value of complete blood count (CBC) parameters in patients with peripheral nerve sheath tumors (PNSTs). PATIENTS AND METHODS: A total of 181 patients (83 males, 98 females; median age: 44 years; range, 15 to 83 years) who underwent surgical treatment for PNSTs in our tertiary oncology center between January 2010 and December 2019 were retrospectively analyzed. Eighty-two patients were diagnosed with a neurofibroma, 79 with a schwannoma, and 20 with a malignant PNST (MPNST). The patient group was evaluated as malignant (n=20) and benign (n=161). Age- and sex-matched patients admitted to our outpatient clinic of orthopedic and traumatology with non-specific symptoms other than tumor, infection, fracture, and rheumatological or hematological diseases were included as the control group (n=165). Data including age, sex, definitive histopathological diagnosis, and pre-treatment CBC values were obtained from the hospital records. Pre-treatment CBC values such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated for both malignant and benign groups and control groups. Diagnostic values of NLR, PLR, and LMR between PNST groups were assessed using the receiver operating characteristic (ROC) curve analysis. RESULTS: Neurofibroma, schwannoma, and MNPST groups had significantly higher median NLR, compared to the control group (p<0.001), while the median LMR was significantly lower in these groups (p<0.05). However, the median PLR was higher only in the MPNST group, compared to the control group (p<0.001). Post-hoc analyses revealed that median NLR, PLR, and LMR ratios were similar in PNST groups, compared to the control group. In addition, the median NLR, PLR, and LMR ratios were similar between malignant and benign patient groups. The highest area under the curve (AUC) was found for NLR (AUC=0.756) and LMR (AUC=0.716) in the MPNST group. CONCLUSION: Our study results suggest that NLR, PLR, and LMR may have an added value in the early diagnosis of PNSTs and are valuable for differentiating patients from healthy individuals, although their value in differential diagnosis is still unclear.

Identification of serum microRNAs in genome-wide serum microRNA expression profiles as novel noninvasive biomarkers for malignant peripheral nerve sheath tumor diagnosis.

Recent studies found that serum microRNAs (miRNAs) could serve as stable and noninvasive biomarkers for disease diagnosis. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNAs in distinguishing malignant peripheral nerve sheath tumor (MPNST) patients with and without neurofibromatosis type 1 (NF1) from NF1 patients. A total of 100 patients with NF1, 93 sporadic MPNST patients, and 71 NF1 MPNST patients were enrolled in this two-stage, case-control study. Solexa sequencing was used to screen for miRNAs that expressed differentially in three pooled serum samples from 10 NF1 patients, 10 sporadic MPNST patients, and 10 NF1 MPNST patients. The detected serum miRNAs then were validated in 90 patients with NF1, 83 patients with sporadic MPNST, and 61 NF1 MPNST patients by individual quantitative reverse transcriptase polymerase chain reaction assays. Eight serum miRNAs altered more than fivefold by Solexa sequencing between MPNST patients (with and without NF1) and NF1 patients. MiR-801 and miR-214 increased both in sporadic MPNST patients and NF1 MPNST patients when compared with NF1 patients. The sensitivity and the specificity of sporadic MPNST detection by the two-miRNA signature were 0.747 and 0.856, respectively. MiR-24 was only significantly up-regulated in NF1 MPNST patients. The combination of the three miRNAs (MiR-801, miR-214, and miR-24) could distinguish NF1 MPNST patients from NF1 patients with a sensitivity of 0.820 and a specificity of 0.844. The serum-based miRNA expression profiles could serve as novel noninvasive biomarkers in sporadic MPNST and NF1 MPNST detection.

A retroperitoneal NF1-independent malignant peripheral nerve sheath tumor with elevated serum CA125: case report and discussion.

Malignant peripheral nerve sheath tumors (MPNSTs) are usually located in the trunk, extremities, head, or neck, and most occur with neurofibromatosis type 1 (NF1; von Recklinghausen's disease). No biomarkers have previously been found to be associated with their progression. Retroperitoneal NF1-independent MPNSTs are rare; they are considered to be less aggressive and to have better prognoses compared to NF1-related tumors. Currently, en bloc excision is the only consensus treatment approach. In a 27-year-old male with a giant retroperitoneal MPNST and no stigmata or family history of neurofibromatosis type-1 (NF1), a remarkable elevation of serum CA125 was detected. The high-grade tumor displayed a striking progression: the primary lesion, 25 cm in diameter, recurred in its previous site as a 17-cm MPNST less than 50 days after total excision. Subsequent treatment with microwave ablation and huachansu, a traditional Chinese medication, proved ineffective, and the patient died within 3 months. Our case suggests that retroperitoneal MPNSTs can deteriorate rapidly even if NF1 independent, that aggressive treatment may not benefit large high-grade MPNSTs, and that novel and effective treatment is urgently needed. Our case also suggests the possibility of using serum tumor markers in the early detection and monitoring of MPNSTs.

Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors.

Malignant solid tumors remain a significant clinical challenge, necessitating innovative therapeutic approaches. Oncolytic viral therapy is a nonmutagenic, biological anticancer therapeutic shown to be effective against human cancer in early studies. Because matrix metalloproteinases (MMP) play important roles in the pathogenesis and progression of cancer, we sought to determine if "arming" an oncolytic herpes simplex virus (oHSV) with an MMP-antagonizing transgene would increase virus-mediated antitumor efficacy. We generated oHSVs that express human tissue inhibitor of metalloproteinases 3 (TIMP3) or firefly luciferase and designated them rQT3 and rQLuc, respectively. We evaluated the antitumor efficacy of these viruses against neuroblastoma and malignant peripheral nerve sheath tumor (MPNST) xenografts. Relative to rQLuc, rQT3-infected primary human MPNST and neuroblastoma cells exhibited equivalent virus replication but increased cytotoxicity and reduced MMP activity. In vivo, rQT3-treated tumors showed delayed tumor growth, increased peak levels of infectious virus, immature collagen extracellular matrix, and reduced tumor vascular density. Remarkably, rQT3 treatment reduced circulating endothelial progenitors, suggesting virus-mediated antivasculogenesis. We conclude that rQT3 enhanced antitumor efficacy through multiple mechanisms, including direct cytotoxicity, elevated virus titer, and reduced tumor neovascularization. These findings support the further development of combined TIMP-3 and oncolytic virotherapy for cancer.