Neurofibrosarcoma

The patient underwent a right mastectomy, achieving a surgical clearance. After 3 months, he passed away with malignant pleural effusion due to lung metastasis.

This case report presents a highly unusual case of a primary high-grade malignant peripheral nerve sheath tumor (MPNST) of esophagus, a neoplasm of extreme rarity, with fewer than twenty histologically confirmed cases reported worldwide to date; detailing the successful management of this tumor through Orringer's transhiatal esophagectomy, complemented by comprehensive histopathologic and immunohistochemical evaluation. Our report emphasizes the crucial the role of immunohistochemistry, specifically the diagnostic value of S100, SOX10, and the exclusion of gastrointestinal stromal tumors markers (DOG1, CD117) in distinguishing MPNST, from morphologically similar esophageal submucosal tumors.

This review provides updates to understand the currently known spectrum of PK-related lesions, with emphasis on those occurring more rarely, to aid proper diagnoses and treatment. The aim is to contribute to a better holistic classification.

In summary, FAP is robustly overexpressed in MPNSTs at transcript and protein levels, potentially concentrates in high-risk tumor cell states, and is detectable by targeted PET imaging. These findings identify FAP as a clinically relevant biomarker for malignancy in NF-1-associated tumors and support implementation of FAP-directed diagnostics and therapeutics in peripheral nerve sheath tumor work-up.

Our study identifies HMGB1 as a key oncogenic driver in NF1-MPNST progression, functioning through direct transcriptional activation of E2F2 to promote cell cycle progression and tumor malignancy. These findings position HMGB1 as both a prognostic biomarker and a promising therapeutic target for NF1-associated MPNSTs.

This study suggests that pan-TRK immunostaining may be useful for confirming neural differentiation in MPNST. However, whether its positivity reflects NTRK rearrangements or neural differentiation must be carefully assessed in combination with various immunohistochemical and molecular tests.

Two patients developed local recurrences and are alive with disease, while the remaining three had no evidence of disease. We describe an unclassified fibromyxoid mesenchymal neoplasm of uncertain malignant potential characterized by recurrent biallelic NF1 LOF and widespread genomic LOH.

In summary, this study suggests that patients with NF1-associated MPNSTs experience worse outcomes. NF1 associated MPNSTs were larger and arose in locations less amenable to negative (R0) resections. Among resectable tumors, CIDM, the primary driver of survival in patients initially diagnosed with localized disease, was correlated to tumor size but not NF1 status.

A phase II is currently exploring this combination in leiomyosarcoma and malignant peripheral nerve sheath tumors. Trial registration: NCT04595994.

Given the palliative nature of surgery and the short postoperative follow-up, the clinical outcome remains uncertain. This case highlights the diagnostic challenges of retroperitoneal MPNST, particularly in patients with NF1, and underscores the importance of early recognition and multidisciplinary management when curative resection is not achievable.

P=N/A, N=80, Active, not recruiting, Johns Hopkins University | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

We propose combining MDK blockade with MEK, SHP2, or immune checkpoint inhibitors, using serum MDK and phospho-signaling as pharmacodynamic markers. We emphasize the near‑term opportunity in NF1‑OPG and MPNST while drawing lessons from NF1‑altered tumors outside the nervous system that reinforce combination strategies for neuro‑oncology.