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Introduction: Expression of the NTRK gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with NTRK fusion gene-positive parotid carcinoma. Case description: The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a nextgeneration sequencer was performed, and the ETV6-NTRK3 fusion gene was identified. Entrectinib, an NTRK inhibitor, was immediately administered at a dose of 600 mg/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib. Conclusion: The NTRK fusion gene should always be checked in the presence of salivary gland secretory carcinoma. [ABSTRACT FROM AUTHOR]

Significant improvements in the survival rates of paediatric cancer have been achieved over the past decade owing to recent advances in therapeutic and diagnostic strategies. However, disease progression and relapse remain a major challenge for the clinical management of paediatric angiosarcoma. Comprehensive genomic profiling of these rare tumours using high-throughput sequencing technologies may improve patient stratification and identify actionable biomarkers for therapeutic intervention. Here, we describe the clinical, histopathological, immunohistochemical and molecular profile of a novel and precision medicine-informed case where a KHDRBS1-NTRK3 fusion determined by next-generation sequencing-based comprehensive genomic profiling led to complete and sustained remission (clinical and radiological response) in an otherwise incurable disease. Our patient represents the first paediatric angiosarcoma harbouring a targetable NTRK3 fusion in the literature and demonstrates the first example of targeting this alteration in angiosarcoma using larotrectinib, an NTRK inhibitor. Clinical and radiological remission was achieved in under two months of therapy, and the patient is currently in complete remission, 4 month after stopping larotrectinib therapy, which was given over 17 months with only mild side effects reported. Therefore, this remarkable case exemplifies the true essence of precision-based care by incorporating conventional pathology with the why, when, and how to test for rare oncogenic drivers and agnostic biomarkers in paediatric angiosarcoma. [ABSTRACT FROM AUTHOR]

A 26-year-old man presented with a tumor in the left soleus muscle. The tumor was diagnosed as a locally advanced leiomyosarcoma. The patient was treated with irradiation followed by wide resection. One year after surgery, the patient presented with multiple lung metastases. Despite aggressive sequential chemotherapy, systemic metastatic tumors continued to develop. To explore therapeutic options for the patient, we performed DNA-based CGP with FoundationOne ® CDx (F1). F1 identified an out-of-strand rearrangement of the NOS1AP::NTRK1 gene, which has not been previously reported. In contrast, RNA sequencing revealed an in-frame LMNA::NTRK1 gene, which is an oncogenic fusion gene.

Dermatofibrosarcoma protuberans (DFSP) is a rare and infiltrative soft tissue tumor. Our report details a distinctive case of DFSP with pan-TRK positivity in the right nasal dorsum of a 46-year-old female. Histological analysis identified NTRK fusion gene involvement in this patient, detectable through pan-TRK immunostaining. The case underscores the significance of comprehensive management for pan-TRK-positive DFSP in challenging facial locations, indicating the potential efficacy of TRK inhibitors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Teshima et al.)

Neurotropic tropomyosin receptor kinase (NTRK) gene rearrangements have been reported in limited cases of sarcomas; however, to date, there has been only one report of such rearrangements in malignant peripheral nerve sheath tumors (MPNSTs). Herein, we describe a 51-year-old male patient with a buttock tumor arising from the sciatic nerve, which was diagnosed as MPNST with positive S-100 staining, negative SOX10 staining, and loss of trimethylation at lysine 27 of histone H3 (H3K27me3) confirmed by immunohistochemistry. Soon after the resection of the primary tumor, the patient was found to have pulmonary and lymph node metastases. Chemotherapy with eribulin and trabectedin showed limited effects. However, the patient responded rapidly to pazopanib, but severe side effects caused discontinuation of the treatment. RNA panel testing revealed a novel fusion gene between Small Nuclear Ribonucleoprotein U1 Subunit 70 (SNRNP70) gene and NTRK3 gene. Furthermore, loss of NF1, SUZ12, and CDKN2A genes was confirmed by DNA panel testing, which is compatible with a histological diagnosis of MPNST. SNRNP70 possesses a coiled-coiled domain and seems to induce constitutive activation of NTRK3 through dimerization. In fact, immunohistochemistry revealed diffuse staining of pan-TRK within tumor cells. Treatment with entrectinib, which is an NTRK inhibitor, showed a quick and durable response for 10 months. Although NTRK rearrangements are very rare in MPNST, this case highlights the importance of genetic testing in MPNST, especially using an RNA panel for the detection of rare fusion genes., (© 2022 Wiley Periodicals LLC.)

Mammary analogue secretory carcinoma is a rare malignant tumor of the salivary glands that typically involves the major glands. The aim of the current study is to report a rare case of mammary analogue secretory carcinoma that presented with left cervical lymphadenopathy. A 59-year-old lady presented with left cervical lymphadenopathy. Tissue biopsy and immunohistochemistry revealed metastatic carcinoma, favoring ovarian origin. Staging workup was performed and, ultimately, the patient was treated as having a carcinoma of unknown primary. After showing partial response to therapy, left side neck dissection was performed. Based on better assessment of the histologic picture and a broader panel of immunohistochemistry performed on the excision specimen, the final diagnosis was that of mammary analogue secretory carcinoma. Mammary analogue secretory carcinoma is usually an indolent salivary gland carcinoma, with the majority of patients presenting with a slow-growing, painless mass measuring approximately 2 cm in size, and a reported duration ranging from 2 months to several years. In certain cases, pain and facial paralysis have been reported. It could also be found incidentally during radiologic assessment for thyroid illness or routine dental screening. Diagnosing mammary analogue secretory carcinoma is challenging, and this should be in the differential diagnosis list of metastatic carcinomas to cervical lymph nodes. • Mammary analogue secretory carcinoma (MASC) is a rare malignant salivary gland neoplasm. • MASC has similar histologic and molecular characteristics to breast secretory carcinoma. • MASC was first reported in 2010 by Skalova et al. • In this report, a brief review regarding this condition is discussed. [ABSTRACT FROM AUTHOR]