NTRK3 positive

This case illustrates an example of pediatric precision oncology in a neonate with an ETV6::NTRK3 (+) congenital IFS of the head and neck region and provides further reference for the use of larotrectinib in the neonatal period.

Case Presentation and We report two cases with RAI-resistant lung metastases treated with larotrectinib: 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation)...In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of -0.060. As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.

The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered...The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

Pan-TRK IHC shows some utility as a diagnostic and surrogate marker for NTRK screening however, physiologic or non-specific expression may lead to false-positive results.

We also advocate the use of molecular techniques in rare tumors of uncertain type or differentiation, to increase understanding and possibilities of reproducible classification of these rare neoplasms. Pathologists and oncologists should recognize this entity, which leads to a direct approach for detecting NTRK fusion for appropriate treatment.

DOG1 was positive in 6/11 (28.5 %) tumors. In conclusion, MUC4 is a useful addition to a diagnostic immunohistochemical panel for SC, and to distinguish it from close potential mimickers such as acinic cell carcinoma, especially in practice settings where molecular testing is unavailable.

DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible.

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.

An individual therapy for surgical treatment of IIFS is recommended. This comprises marginal resection in instead of the golden standard "wide resection" in selected cases.

The leukemic clonal evolution might be revealed through transcriptome sequencing and overcome by drugs with universal targets. Our case demonstrated that both comprehensive profiling techniques (such as transcriptome sequencing, multiparameter flow cytometry, and digital droplet polymerase chain reaction) and a multimodality treatment strategy were critical for anticipating an early relapse and personalized therapy of R/R T-cell leukemia.