Table 1 Clinicopathological comparison of our two cases of TPR-NTRK1 and LAMA-NTRK1 fusion-positive sarcomas and 6 cases of our infantile fibrosarcoma
From: Clinicopathological findings of pediatric NTRK fusion mesenchymal tumors
| Â | TPR-NTRK1 fusion-positive pediatric sarcoma | LMNA-NTRK1 fusion-positive pediatric sarcoma | ETV6-NTRK3 fusion-positive Inflammatory myofibroblastic tumor | ETV6-NTRK3 fusion-positive pediatric sarcoma |
|---|---|---|---|---|
Age/Gender | 12 y/ male | 3 y/ male | 6 mo/female | Median age: 2.6 months (range: 1.6 ~ 5.6 months), M: F = 5:1 |
Site | Dura, parieto-occipital | Forehead dermis and subcutaneous tissue | Left lower lobe of lung | Tongue, buttock, shoulder, foot, abdominal cavity, and sacro-coccygeal area |
Size | 6.0 × 5.0 × 3.0 cm | 4.0 × 3.5 × 3.0 cm | 5.6 × 3.5 × 3.0 cm | Range: 1.4–4.5 cm in biggest diameter |
Histology | Mixed oval to spindle cells | Spindle cells intermixed with prominent lymphoplasma cells | Spindle myofibroblastic cells with prominent lymphoplasma cells | Mostly spindle cells, with no prominent inflammatory cell infiltration |
Histological grade | High-grade | Low-grade | Low-grade | High-grade (cellular) |
Nuclear pleomorphism | Relatively uniform cells without pleomorphism | Uniform cells without pleomorphism | Uniform cells without pleomorphism | Uniform cells without pleomorphism |
Tumor necrosis | Absent | Absent | Abent | Absent |
Mitotic rate | 25/10 HPFs | 0/10 HPFs | 1/ 10 HPFs | 10/10HPFs ~ 40/10 HPFs |
Ki67 labeling index | 36.0% | 18.2% | 37% | 15 ~ 60% |
Immuno-positive markers | Trk/CD34/Nestin/vimentin/p53 | Trk/ S100/CD34/Nestin/vimentin/ | Trk/SMA/vimentin | Trk/Nestin/vimentin, S100 (3/6 cases)/CD10(4/5 cases) |
Trk positive pattern | Nucleus | Nuclear membrane | Cytoplasmic | Cytoplasm and nucleus |
Genetic abnormalities other than NTRK1 fusion | NTRK1 amplification (copy number: 11), H3F3A amplification (copy number: 12) | absent | absent | Absent |
Final diagnosis | Undifferentiated sarcoma | Infantile fibrosarcoma, low grade | Inflammatory myofibroblastic tumor | Infantile fibrosarcoma, cellular |
Treatment | Surgery+ vincristine, doxorubicin, cyclophosphamide (6 cycles)/ifosramide, carboplatin, etoposide (6 cycles), alternative, total 12 cycles | Surgery only | Surgery only | Surgery + vincristine, actinomycin D, cyclophosphamide (X11 or 26 cycles) |
Outcomes and follow-up | NED (1.4 years) | NED (0.8 years) | NED (0.3 years) | 5 patients: NED (for average 11.7 years, range: 6.0–17.4 years) 1 patient: Follow-up loss |
Known mesenchymal tumors with this type of fusion | Lipofibromatosis, adult uterine undifferentiated sarcoma | Infantile fibrosarcoma, lipofibromatosis-like neural tumor, Undifferentiated sarcoma, Cellular mesoblastic nephroma | Infantile fibrosarcoma | Infantile fibrosarcoma, inflammatory myofibroblastic sarcoma |