NTRK3 positive

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.

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Here we describe and characterize in depth a case of ETV6-NTRK3 gene fusion-positive secretory carcinoma of the salivary glands and corresponding organoid cultures that responded and subsequently acquired resistance to TRK targeting therapy with larotrectinib. This case-culture-characterization illustrates the advances made in precision oncology, but also exposes important caveats in using organoids to predict treatment response.

In certain cases, morphology is atypical and mammaglobin is immunohistochemically positive in only individual tumor cells. Therefore, the diagnosis should be supported with morphology, immunohistochemical staining, and molecular feature preferably.

This study provides new insights and facilitates our current understanding of clinicopathological features and survival outcomes of different fusion oncogenes in PTCs. It may help clinicians better counsel the patients and tailor appropriate treatment decisions.

As targeted therapy, that is, selective TRK inhibitors are available for treatment of metastatic disease, NTRK3 fusion status is not only diagnostic, but also required to plan treatment. Pan-TRK immunohistochemistry serves as a viable cost-effective, easy to apply surrogate marker for NTRK3 fusion, particularly in diagnostic laboratories lacking easy access to molecular testing on cytological material.

This study showed that pan-TRK staining has high sensitivity and specificity for SC with NTRK3 fusion. Whereas pan-TRK IHC is a useful screening method, further studies are needed to assess the value of RET IHC as a second sequential step.

It is necessary to establish an appropriated differential diagnosis between salivary gland tumors. MASC is a low-grade malignancy cancer that sometimes can evolve to a high-grade tumor that might produce local and distance dissemination. Most times, these tumors are only treated by surgical resection and evaluating by a multidisciplinary team the need of more treatments. In our case, the patient showed a primary parotid tumor, removed surgically with free edges, and being identified as MASC. We decided to underwent neck dissection and discovered a second MASC focus on cervical salivary gland; however, there was no nodal dissemination. The patient remains disease-free after 14 months from last surgery. It is important to keep studying genetic therapy targets to ETV6-NTRK3 to obtain a new therapy line to treat those cases that require.

NTRK fusions are rare; however, with emerging therapeutic options targeting these fusions, detection is vital. Reflex testing for KRAS mutations and subsequent RNA-based screening could help identify these cases in PDAC.

Our study demonstrate the feasibility, but also the cost-effectiveness, of a multistep but rapid diagnostic strategy based on non-sequencing methods to identify rare and targetable kinase fusions in patients with advanced CRCs as well as the high prevalence of these kinase fusions in MLH1 MSI-High wild-type CRCs. Nevertheless, confirmatory RNA-sequencing analyses are necessary in case of low FISH positive nuclei percentage to rule out FISH false-positive results.

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The tumor followed an aggressive clinical course and the patient eventually succumbed to her disease 14?months after diagnosis. The histomorphologic and molecular genetic features of this tumor are discussed, including its ability to mimic kinase-rearranged infantile or adult fibrosarcomas at extramammary sites and the theragnostic importance of its distinction from conventional metaplastic spindle cell carcinomas in the breast.

The authors describe the adjuvant maintenance larotrectinib treatment after definitive surgical resection in 2 toddlers with NTRK fusion-positive malignancies (ETV6-NTRK3 fusion-positive undifferentiated embryonal sarcoma of the kidney and NACC2-NTRK2 fusion-positive anaplastic astrocytoma). Both are alive, in remission, developing normally and tolerating larotrectinib 15 months later, thus extending the NTRK inhibitor therapeutic spectrum by describing the adjuvant maintenance larotrectinib treatment in children with NTRK fusion-positive cancers associated with high recurrences.

All cases of NTRK1 and NTRK3 fusion-positive pediatric tumors robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10/SMA immunohistochemical expression may suggest the presence of NTRK fusion partner genes. LMNA-NTRK1 fusion sarcoma might be a low-grade subtype of infantile fibrosarcoma. Interestingly, more than half of the infantile fibrosarcoma cases were positive for S100 protein and CD10. The follow-up period of TPR-NTRK1 and LMNA-NTRK1 fusion-positive tumors are not enough to predict prognosis. However, ETV6-NTRK3 fusion-positive infantile fibrosarcomas showed an excellent prognosis with no evidence of disease for an average of 11.7 years, after gross total resection of the tumor.