Spindle cell neoplasms with novel LTK fusion - Expanding the spectrum of kinase fusion-positive soft tissue tumors.

AIMS: Kinase fusion-positive soft tissue tumors represent an emerging, molecularly defined group of mesenchymal tumors with a wide morphologic spectrum and diverse activating kinases. Here, we present two cases of soft tissue tumors with novel LTK fusions. METHODS AND RESULTS: Both cases presented as acral skin nodules (big toe and middle finger) in pediatric patients (17-year-old girl and 2-year-old boy). The tumors measured 2 and 3 cm in greatest dimension. Histologically, both cases exhibited bland-looking spindle cells infiltrating adipose tissue and accompanied by collagenous stroma. One case additionally displayed perivascular hyalinization and band-like stromal collagen. Both cases exhibited focal S100 staining, and one case had patchy coexpression of CD34. Targeted RNA-seq revealed the presence of novel in-frame MYH9::LTK and MYH10::LTK fusions, resulting in upregulation of LTK expression. Of interest, DNA methylation-based unsupervised clustering analysis in one case showed that the tumor clustered with dermatofibrosarcoma protuberans (DFSP). One tumor was excised with amputation with no local recurrence or distant metastasis at 18-month follow-up. The other case was initially marginally excised with local recurrence after one year, followed by wide local excision, with no evidence of disease at 10 years of follow-up. CONCLUSIONS: This is the first reported case series of soft tissue tumors harboring LTK fusion, expanding the molecular landscape of soft tissue tumors driven by activating kinase fusions. Furthermore, studies involving a larger number of cases and integrated genomic analyses will be warranted to fully elucidate the pathogenesis and classification of these tumors.

Novel MAP4::RAF1 Fusion in a Primary Bone Sarcoma: Expanding the spectrum of RAF1 Fusion Sarcoma.

Soft tissue tumors with RAF1 fusion had been emerging as a group of tumors with peculiar histology and immunoprofile. While a case series and rare case reports of RAF1 translocated sarcoma had been reported, to our knowledge a primary bone tumor with RAF1 translocation and fusion partner with MAP4 had not been described in the literature. The patient was a 60-year-old lady, with strong family history of breast cancer, who presented with pathological fracture of right humerus. X-ray revealed a 9.7 cm juxta-articular lesion of the proximal humerus, which was expansile and lytic with a non-sclerotic well defined border distally, radiologically suggestive of a giant cell tumor of bone. Excision was performed after initial biopsy. Histology showed a monomorphic low grade spindle cell lesion with prominent hyalinized stroma. Immunohistochemistry demonstrated diffuse CD34 staining, with focal staining for S100. Gene sequencing for histone 3 H3 genes was negative for hotspot mutation. Targeted RNA-seq sequencing revealed the presence of MAP4::RAF1 fusion, which was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridization (FISH) break-apart probes involving both genes. The overall features were consistent with a primary bone sarcoma with RAF1 fusion. This report expanded the spectrum of RAF1 fusion sarcoma and was the first report documenting its primary occurrence in bone.

Case report on metastatic pelvic bone tumor treated with frozen autograft by liquid nitrogen.

INTRODUCTION AND IMPORTANCE: Frozen autograft recycling has been used for biological reconstruction of bone defects following tumor excision, more commonly in extremities. We report on the histological outcome of a pelvic recycled frozen autograft. CASE PRESENTATION: We investigated the pelvic frozen autograft removed in 2 years and 8 months after surgery because of soft tissue recurrence in pelvic floor. The autograft bone showed no evidence of revitalization and was non-viable with patchy inflammation, and no residual tumor. There was only fibrous union but the autograft bone remained mechanically stable. CLINICAL DISCUSSION: We confirmed the clearance of tumor cells with the treatment with liquid nitrogen. The union at the host-graft junction might be affected by the previous radiotherapy, the presence of infection, the small contact area limited by the anatomy, and the inadequate compression across the osteotomy interface with the fixation. CONCLUSION: Frozen autograft treated by liquid nitrogen can be used safely for biological reconstructions after pelvic tumor excision.