Diagnostic value of 18F-FDG PET-CT in detecting malignant peripheral nerve sheath tumors among adult and pediatric neurofibromatosis type 1 patients

Purpose Detecting malignant peripheral nerve sheath tumors (MPNSTs) remains difficult. 18F-FDG PET-CT has been shown helpful, but ideal threshold values of semi-quantitative markers remain unclear, partially because of variation among scanners. Using EU-certified scanners diagnostic accuracy of ideal and commonly used 18F-FDG PET-CT thresholds were investigated and differences between adult and pediatric lesions were evaluated. Methods A retrospective cohort study was performed including patients from two hospitals with a clinical or radiological suspicion of MPNST between 2013 and 2019. Several markers were studied for ideal threshold values and differences among adults and children. A diagnostic algorithm was subsequently developed. Results Sixty patients were included (10 MPNSTs). Ideal threshold values were 5.8 for SUVmax (sensitivity 0.70, specificity 0.92), 5.0 for SUVpeak (sensitivity 0.70, specificity 0.97), 1.7 for TLmax (sensitivity 0.90, specificity 0.86), and 2.3 for TLmean (sensitivity 0.90, specificity 0.79). The standard TLmean threshold value of 2.0 yielded a sensitivity of 0.90 and specificity of 0.74, while the standard SUVmax threshold value of 3.5 yielded a sensitivity of 0.80 and specificity of 0.63. SUVmax and adjusted SUV for lean body mass (SUL) were lower in children, but tumor-to-liver ratios were similar in adult and pediatric lesions. Using TLmean > 2.0 or TLmean < 2.0 and SUVmax > 3.5, a sensitivity and specificity of 1.00 and 0.63 can be achieved. Conclusion 18F-FDG PET-CT offers adequate accuracy to detect MPNSTs. SUV values in pediatric MPNSTs may be lower, but tumor-to-liver ratios are not. By combining TLmean and SUVmax values, a 100% sensitivity can be achieved with acceptable specificity.

Spinal Cord Tumors—Our 5-Year Experience

Purpose To study the demography, incidence, symptoms, histopathology, postoperative complications and recovery in operated patients of spinal tumor. Overview of Literature Primary spinal cord tumors (SCT) are an uncommon entity. According to their location, spinal tumors are conveniently classified as extradural (ED) and intradural (ID), although some can be both inside and outside the dura. ID tumors can be intradural extramedullary (IDEM) or intramedullary SCT (IMSCT). Methods This is a retrospective study of 122 patients with spinal tumors who were surgically treated at the department of neurosurgery from 2014 to 2019 over a period of 5 years. Study Design This is a retrospective study. Results Out of 122 patients, there were 19 patients with ED tumor, 73 had IDEM, and 30 had IMSCT. As many as 73 patients were males and the rest of the 49 patients were females. Mean age at time of surgery was 40.79 years. The thoracic region of spinal canal was most frequently involved (64; 52.4%). The common clinical symptom was motor weakness (90 cases; 73.77%). Majority of the patients had symptoms for duration of 6 to 12 months. Schwannomas were the most common tumor among IDEM and extradural location. Ependymomas were the most common type in IMSCT. We observed significant improvement in most of our cases. Four patients deteriorated at 3 months follow- up. Conclusions There was a higher male:female ratio for all spinal cord tumors except meningiomas. There was also a higher proportion of nerve sheath tumors, and a lower proportion of meningiomas and neuroepithelial tumors. These results are similar to other studies from Asian countries.

Malignant Peripheral Nerve Sheath Tumors—A Comprehensive Review of Pathophysiology, Diagnosis, and Multidisciplinary Management

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. Although occurring at an incidence of 0.001% in the general population, they are relatively common in individuals with neurofibromatosis type 1 (NF1), for whom the lifetime risk approaches 10%. The staging of MPNSTs is complicated and requires close multi-disciplinary collaboration. Their primary management is most often surgical in nature, with non-surgical modalities playing a supportive, necessary role, particularly in metastatic, invasive, or widespread disease. We, therefore, sought to provide a comprehensive review of the relevant literature describing the characteristics of these tumors, their pathophysiology and risk factors, their diagnosis, and their multi-disciplinary treatment. A close partnership between surgical and medical oncologists is therefore necessary. Advances in the molecular characterization of these tumors have also begun to allow the integration of targeted RAS/RAF/MEK/ERK pathway inhibitors into MPNST management.

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors

Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.

Targeted Therapies for the Neurofibromatoses

Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their spontaneous counterparts. Focus has shifted to therapy aimed at minimizing symptoms given the risks of persistent, multiple tumors and new tumor growth. In this review, we will highlight the translation of preclinical data to therapeutic trials for patients with neurofibromatosis, particularly neurofibromatosis type 1 and neurofibromatosis type 2. Successful inhibition of MEK for patients with neurofibromatosis type 1 and progressive optic pathway gliomas or plexiform neurofibromas has been a significant advancement in patient care. Similar success for the malignant NF1 tumors, such as high-grade gliomas and malignant peripheral nerve sheath tumors, has not yet been achieved; nor has significant progress been made for patients with either neurofibromatosis type 2 or schwannomatosis, although efforts are ongoing.

PATH-02. TWO CASES WITH MULTIPLE HYBRID NERVE SHEATH TUMORS WITH ERBB2 MUTATIONS

Hybrid nerve sheath tumors are new disease entity incorporated in WHO classification of tumors of the central nervous system 2016 version that includes benign peripheral nerve sheath tumors with combined features of more than one conventional type. Ronellenfitsch et al recently reported one case with ERBB2 D769Y mutation with good clinical response to lapatinib in 2020. We report two cases with imaging findings of multiple peripheral nerve sheath tumors with pathology proven hybrid nerve sheath tumors with ERBB2 mutations. Patient 1 has neurofibroma/schwannoma hybrid nerve sheath tumor with ERBB2 D769Y mutation and patient 2 has plexiform neurofibroma/schwannoma hybrid nerve sheath tumor with ERBB2 V777L mutation. Both of our patients have similar clinical features with adult-onset multiple peripheral nerve sheath tumors without other systemic features of neurofibromatosis type1 or vestibular schwannomas or family history. Hybrid nerve sheath tumors are newly recognized disease and more than half of the cases have multiple peripheral nerve sheath tumors, suggestive of tumor syndrome. Patients with multiple peripheral nerve sheath tumors without systemic features of neurofibromatosis type1 or vestibular schwannomas should be screened for genetic/molecular tests including ERBB2 mutation that might provide treatment options for these patients.

INNV-04. A MULTI-INSTITUTIONAL CLINICAL AND MRI REPOSITORY OF NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PERIPHERAL NERVE SHEATH TUMORS

BACKGROUND Individuals with neurofibromatosis type 1 (NF1) frequently have peripheral nerve sheath tumors (PNST), including plexiform neurofibromas (PNF), atypical neurofibromas (ANF), and malignant peripheral nerve sheath tumors (MPNST). These tumors reflect a histologic spectrum from benign to malignant. Various clinical and MRI-based features are proposed as risk factors for MPNST development based on small single-institution studies. A major barrier to study these risk factors is collation and annotation of multi-center serial MRIs. To address this, we created a standardized database of clinical data and longitudinal MRIs from NF1-associated PNST from nine international NF1 referral centers. METHODS Clinical data from NF1 patients are collected in Research Electronic Data Capture databases housed at Massachusetts General Hospital and Washington University, including demographic information, genotype, disease course, treatment history, and survival. ANF and MPNST require histologic confirmation whereas a diagnosis of PNF can also be made based on clinical/radiographic stability. Longitudinal MRIs predating the histologic diagnosis are uploaded to a HIPAA-compliant cloud-based system. RESULTS Data from 200 patients (87 females, 113 males) with 217 tumors (75 PNF, 40 ANF, 102 MPNST) have been collected. 280 regional and 108 whole-body MRIs have been identified. Median age at the time of histologic diagnosis is 30 years (range 5-64). All tumors are histologically confirmed except for 6 PNF which remained stable over time. Median follow-up time is 32 months. Of 147 patients with available survival data, 32 (21.7%) have died from MPNST progression; estimated median overall survival is 20 months. CONCLUSIONS In this ongoing work, we have assembled one of the largest systematically annotated clinical and MRI repositories of NF1-associated PNST from pediatric and adult NF1 patients. The data will be accessible to outside researchers which will promote interdisciplinary and multi-center collaborations. Active efforts include the identification of radiomic MRI features to differentiate between PNF and MPNST.