Spindle Cell Sarcoma

CONCLUSIONS PPOS can present as a lesion smaller than 2 cm. An integrated imaging-pathology workup and early resection can yield favorable short-term outcomes.

Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of RET-specific inhibitors against RET-altered sarcomas.

This study demonstrates GFPT2's diagnostic utility in MESO, effectively overcoming tumour heterogeneity challenges. It distinguishes malignant mesothelial lesions from benign/borderline ones (RMH/WDPMT), differentiates epithelioid MESO from epithelioid malignances(NSCLC/HGSOC/EHE) and aids in sarcomatoid MESO versus spindle cell tumours (SFT/AF/SS/LMS/MPNST/sarcomatoid carcinoma), though limited for DDLPS. In summary, GFPT2 is a promising novel antibody demonstrating 85.2% sensitivity and 94.7% specificity.

Thus, our findings suggest that in-frame TERT fusions may drive the pathogenesis of a group of mostly low-grade unclassified sarcomas with fibroblastic/myofibroblastic differentiation. In contrast, TERT fusions may also be detected in other common sarcoma types co-occurring with numerous genomic alterations, likely representing a secondary driver event.

S100, SOX10, neurofilament and desmin are typically negative. While perineuriomas behave in a benign fashion, complete surgical excision is recommended.

Even in uncommon locations like the thigh, DFSP should be considered in cases of chronic, atypical skin lesions. For the best results, interdisciplinary care, extensive excision, and early diagnosis are essential.

A multidisciplinary approach combining radical surgery and adjuvant RT is crucial; however, the rapid distant progression highlights the critical need for more effective systemic treatment options and the integration of genetic profiling to guide personalized therapies. Further comprehensive research is essential to optimize management strategies and improve the limited survival outcomes associated with this rare and challenging malignancy.

We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

This case underscores the importance of integrating molecular diagnostics into the evaluation of atypical spindle cell tumors, particularly those presenting with aggressive clinical features despite low-grade histology. Early identification of NTRK fusions enables timely initiation of TRK inhibitor therapy, offering durable disease control and functional recovery. Broader awareness and implementation of molecular testing can greatly enhance the management of rare pediatric sarcomas.

In children with NTRK fusion-positive sarcomas, upfront TRK inhibition yielded faster, deeper responses and eliminated mutilating surgery in our cohort. These data support TRK inhibitors as preferred neoadjuvant options, particularly to facilitate non-morbid resections and to avoid functional disability.

Awareness of its histologic and immunophenotypic features is critical to avoid misdiagnosis and overtreatment. Accurate recognition may prevent unnecessary radical surgical or oncologic interventions.

Notably, the presence of cartilage foci within a RMS-like neoplasm represents a strong clue to an underlining DICER1 alteration. The rarity of this presentation in the nasal fossa at this age, coupled with its implications for diagnosis, treatment, and familial screening, emphasizes the need for awareness of the morphology patterns of DICER1-associated neoplasms across diverse anatomical sites.