Kinase fusion positive intra-osseous spindle cell tumors: A series of eight cases with review of the literature Journal Article
| Authors: | Suurmeijer, A. J. H.; Xu, B.; Torrence, D.; Dickson, B. C.; Antonescu, C. R. |
| Article Title: | Kinase fusion positive intra-osseous spindle cell tumors: A series of eight cases with review of the literature |
| Abstract: | Mesenchymal spindle cell tumors with kinase fusions, often presenting in superficial or deep soft tissue locations, may rarely occur in bone. Herein, we describe the clinicopathologic and molecular data of eight bone tumors characterized by various kinase fusions from our files and incorporate the findings with the previously reported seven cases, mainly as single case reports. In the current series all but one of the patients were young children or teenagers, with an age range from newborn to 59 years (mean 19 years). Most tumors (n = 5) presented in the head and neck area (skull base, mastoid, maxilla, and mandible), and remaining three in the tibia, pelvic bone, and chest wall. The fusions included NTRK1 (n = 3), RET (n = 2), NTRK3 (n = 2), and BRAF (n = 1). In the combined series (n = 15), most tumors (73%) occurred in children and young adults (<30 years) and showed a predilection for jaw and skull bones (40%), followed by long and small tubular bones (33%). The fusions spanned a large spectrum of kinase genes, including in descending order NTRK3 (n = 6), NTRK1 (n = 4), RET (n = 2), BRAF (n = 2), and RAF1 (n = 1). All fusions confirmed by targeted RNA sequencing were in-frame and retained the kinase domain within the fusion oncoprotein. Similar to the soft tissue counterparts, most NTRK3-positive bone tumors in this series showed high-grade morphology (5/6), whereas the majority of NTRK1 tumors were low-grade (3/4). Notably, all four tumors presenting in the elderly were high-grade spindle cell sarcomas, with adult fibrosarcoma (FS)-like, malignant peripheral nerve sheath tumor (MPNST)-like and MPNST phenotypes. Overall, 10 tumors had high-grade morphology, ranging from infantile and adult-types FS, MPNST-like, and MPNST, whereas five showed benign/low-grade histology (MPNST-like and myxoma-like). Immunohistochemically (IHC), S100 and CD34 positivity was noted in 57% and 50%, respectively, while co-expression of S100 and CD34 in 43% of cases. One-third of tumors (4 high grade and the myxoma-like) were negative for both S100 and CD34. IHC for Pan-TRK was positive in all eight NTRK-fusion positive tumors tested and negative in two tumors with other kinase fusions. Clinical follow-up was too limited to allow general conclusions. © 2023 Wiley Periodicals LLC. |
| Keywords: | immunohistochemistry; adolescent; adult; child; clinical article; human tissue; preschool child; protein expression; aged; bone neoplasms; child, preschool; middle aged; bone tumor; young adult; genetics; clinical feature; cancer localization; patient selection; follow up; cancer grading; cd34 antigen; tumor volume; protein tyrosine kinase; tumor marker; sarcoma; fluorescence in situ hybridization; fibrosarcoma; infant; infant, newborn; newborn; fusion gene; oncogene proteins, fusion; bone; protein s 100; receptor protein-tyrosine kinases; spindle cell sarcoma; malignant peripheral nerve sheath tumor; tumor classification; b raf kinase; soft tissue neoplasms; soft tissue tumor; myxoma; proto-oncogene proteins b-raf; fusion; braf gene; oncogene ret; protein tyrosine kinase a; ret; receptor, trka; humans; human; male; female; article; rna sequencing; neurofibrosarcoma; biomarkers, tumor; ntrk3 gene; ntrk1 gene; ntrk; raf1 gene; oncogene fusion protein |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 63 |
| Issue: | 1 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2024-01-01 |
| Start Page: | e23205 |
| Language: | English |
| DOI: | 10.1002/gcc.23205 |
| PUBMED: | 37782551 |
| PROVIDER: | scopus |
| PMCID: | PMC11250992 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Cristina R. Antonescu -- Source: Scopus |
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