Neurofibrosarcoma

Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.

Our findings support the Notch pathway as a druggable target in MPNSTs. Our identification of PRC2-regulated genes and pathways could result in more novel therapeutic approaches.

It is crucial to assess the potential for heterogeneous differentiation in MPNST during pathological diagnosis. In the treatment of MPNST with heterogeneous differentiation, particularly in cases with significant tumor bulk, surgeons must anticipate potential hemorrhagic complications and adopt a cautious approach to surgical intervention.

Our findings confirmed a unique hypermethylation pattern present during malignant transformation. This study highlights the potential to be investigated further as biomarkers in clinical settings for early MPNST detection in patients with NF1.

NF1-associated MPNSTs have larger tumor volumes, higher SUVs and MIB-1 proliferation indices, and a shorter overall survival period. Nevertheless, surgery can improve symptoms, particularly medication-resistant pain, and should also be considered in advanced disease for symptom control/improvement.

P1, N=8, Not yet recruiting, University of Minnesota

Finally, we functionally validate a candidate extracellular matrix protein, periostin (POSTN), in human MPNST. This work provides insight into how the microenvironment may regulate MPNST initiation and progression.

No abstract available

Next-generation sequencing revealed multiple differential features between SF- MPNST, D-MPNST, SCM, and DM, including tumor mutation burden, mutational signatures, and differentially expressed genes. These findings help advance our understanding of disease pathogenesis and improve diagnostic modalities.

We also propose renaming "low-grade MPNST" to "ANNUBP with increased proliferation" to avoid the use of the "malignant" term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms.

Early diagnosis of MPNST is crucial. In patients with NF1, even mild symptoms can indicate MPNST.

Our results indicate that PN can be newly detected in pediatric patients over time, even if no PN were detected on initial MRI scans. Therefore, it seems reasonable to perform at least a second MRI in pediatric NF1 patients at transition to adulthood, even if they did not display any tumor burden on initial MRI, and when the MRI was performed significantly under the age of 18. With this approach, tumors that may have developed between scans can be detected and patients at risk for complications can be identified.

No abstract available

Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs.

LLS30 effectively disrupts the Gal-1/Ras interaction, resulting in significant anti-tumor and anti-metastatic effects in MPNST models. These findings indicated that targeting Gal-1 with LLS30 offers a promising therapeutic approach for treating MPNSTs and may also be applicable to other malignancies where Gal-1 and Ras are key oncogenic drivers.

More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.

Preoperative multidisciplinary assessment, intraoperative electrophysiological monitoring, and advanced surgical assistance devices significantly enhance surgical efficacy and safety. Future research should continue to explore new surgical techniques and improve postoperative management strategies to achieve more precise and personalized treatment for NF1 patients.

Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.

MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.

FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.

Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.

Though surgery is the traditional mainstay of treatment for these tumors, the discovery of the genetic and molecular basis of these diseases in recent decades has prompted investigation into targeted therapies. Here, we give a clinical overview of spinal nerve sheath tumors, their imaging features, current management practices, and explore ongoing advances in systemic therapies.

On an 8-month follow-up, he had no neurological deficit, with a Karnofsky performance score of 90 points. Surgical evidence of SAH in lumbar spine intradural MPNST is a novel finding.

The aim of multimodality approaches is to optimize both local and systemic control while keeping to a minimum acute and late treatment morbidity. Advances in the understanding of the underlying biology of MPNSTs in both sporadic and NF-1-related contexts are essential for the management and implementation of novel therapeutic approaches.

Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness.

In conclusion, radiation-induced secondary malignancies are a significant late side effect of radiation therapy that can profoundly impact treatment decision-making and requires a high index of suspicion during post radiation surveillance. Malignant peripheral nerve sheath tumor serves as a pertinent example, highlighting the importance of considering long-term risks when developing optimal management plans for cancer patients.

This case stands out due to its unique presentation, characterized by a predominantly spindle cell morphology with certain epithelioid features. It is imperative to recognize this condition for an accurate diagnosis, emphasizing the spindle cell-type MPNST and highlighting its exceptionally poor prognosis.

Finally, the role of FOXM1 in suppressing anti-tumor immunity and potentially thwarting immune-based therapies is considered. We suggest that future therapeutic strategies targeting the oncogenic network of CDK4/6, MEK, PD-L1, and FOXM1 represent exciting future treatment options for MPNST patients.

Immunohistochemically, positive S-100 and vimentin; Ki67 levels of 40%; and negative CD34, CK AE1/AE3, and SMA were identified. The aforementioned findings definitively diagnosed primary aortic malignant peripheral nerve sheath tumor, which has been never reported in the literature.

Histological and immunohistochemical detections aid in the differential diagnosis of LPF-NTs. Complete surgical resection is the preferred treatment for LPF-NTs.

Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.

P1, N=9, Completed, Mayo Clinic | Recruiting --> Completed | N=30 --> 9 | Trial completion date: Sep 2024 --> Apr 2024 | Trial primary completion date: Sep 2024 --> Apr 2024

Malignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising of TAM with high expression of PD-L1, which are associated with inferior outcomes. These findings suggest a clinical potential of immune modulating therapeutics that can unleash an anti-tumor immune response.

In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.

Our findings suggest that the combination of MEKi and PDGFR and/or RAF dimer inhibitors can overcome MEKi resistance and may serve as a novel targeted therapeutic strategy for NF1-deficient MPNST patients, which in turn could impact future clinical investigations for this patient population.

Transcriptomic analysis of corin-treated MPNST cells demonstrates specific increases in genes associated with axonogenesis and neuronal differentiation as well as altered extracellular matrix; additionally, corin treatment is shown to inhibit MPNST invasion in vitro. These results underscore the critical role of the LHC complex in facilitating MPNST growth and progression and suggest that targeting the LHC complex represents a promising therapeutic approach for this aggressive malignancy.

P2, N=1, Terminated, M.D. Anderson Cancer Center | N=40 --> 1 | Trial completion date: May 2025 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: May 2025 --> Aug 2024; PI Request

Thus, this case expands NUT fusion sarcomas' histologic and immunohistochemical profile to include mimicking a malignant peripheral nerve sheath tumor (MPNST). Additionally, it indicates that the NSD3::NUTM1 fusion can drive sarcoma genesis.

Malignant peripheral nerve sheath tumor (MPNST) is an extremely rare malignancy with neural differentiation potential. The lifetime risk of developing MPNST in NF-1 patients is 8%-13%.

Such entities may benefit from alternative treatments or strategies to overcome SLFN11 deficiency-related drug resistance. Our approach and results should serve as a foundation for future biomarker-associated clinical trials.

A primary total knee arthroplasty was performed with a cemented-stemmed hinged knee implant. At 6 months post-surgery, the patient had a dramatic improvement in her pain and quality of life.

P1/2, N=580, Recruiting, Mirati Therapeutics Inc. | N=370 --> 580