The histologic spectrum of soft tissue spindle cell tumors with <i>NTRK3</i> gene rearrangements
Bibliographic record
Abstract
NTRK3-rearranged tumors other than infantile fibrosarcomas (IFSs) harboring the canonical ETV6-NTRK3 fusions are uncommon, and include mainly inflammatory myofibroblastic tumors and gastrointestinal stromal tumors. Herein, we describe an additional subset of seven tumors sharing NTRK3 gene rearrangements. The cohort included five females and two males (age range 1-67 years). Tumors were located in extremities, trunk, retroperitoneum, or intra-abdominal. In all tumors, fluorescence in situ hybridization (FISH) revealed rearrangements in NTRK3 accompanied by NTRK3 amplification in two cases. In three cases, RNA sequencing identified a fusion transcript composed of NTRK3 exon 14 fused to ETV6, TFG, and TPM4, respectively, retaining the NTRK3 kinase domain. All tumors were positive for pan-TRK by immunohistochemistry (IHC). Two cases showed low- to intermediate-grade histology composed of monomorphic spindle cells arranged in a patternless architecture, stromal bands, and perivascular rings of hyalinized collagen and coexpression of S100 and CD34. The remaining five cases were high-grade fascicular monomorphic spindle cell sarcomas, morphologically somewhat reminiscent of either malignant peripheral nerve sheath tumors (MPNSTs) or fibrosarcomas (FSs). Two high-grade NTRK3 sarcomas showed aggressive clinical behavior with development of lung metastases. Identification of high-grade NTRK3-rearranged sarcomas is clinically important, since the development of selective NTRK inhibitors has opened new avenues for targeted therapy. Although IHC for pan-TRK can be applied as a screening tool, molecular studies are recommended for a conclusive diagnosis of NTRK-rearranged neoplasms.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".