Identification of Dual STRN-NTRK2 Rearrangements in a High Grade Sarcoma, With Good Clinical Response to First-Line Larotrectinib Therapy

BACKGROUND: Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA. CASE PRESENTATION: We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass showed a high-grade mesenchymal neoplasm with features reminiscent of a solitary fibrous tumor, but negative for STAT6. In-house next-generation sequencing gene fusion panel showed two in-frame STRN-NTRK2 fusions, which contain the same 5\u27 partner sequence (exon 1-3) of STRN, and the 3\u27 fusion partner starting from either the exon 15 or the exon 16 of NTRK2. Due to the large size and location of the tumor, first-line neoadjuvant therapy with larotrectinib was initiated. The patient has an excellent clinical response with an 83% tumor size reduction by imaging. The tumor was subsequently completely resected. After 130 days, larotrectinib was reinitiated for lung metastasis (up to 7 cm), and a complete resolution was achieved. When compared with NTRK1 and NTRK3, NTRK2 fusions are the least common. Of note, the only other report in the literature on NRTK2 fusion-positive sarcoma also showed solitary fibrous tumor (SFT)-like morphology, and the patient responded well to larotrectinib as the second line adjuvant therapy. CONCLUSIONS: In conclusion, the identification of NTRK2 fusions in patients with soft tissue tumors could significantly improve the clinical outcome through selective NTRK inhibitor therapy, especially in the first-line setting. Prompt RNA-based NGS testing at initial diagnosis may benefit these patients. Our case is among the first few in the literature on NTRK2 fusion sarcoma with first-line larotrectinib therapy in the primary and metastatic setting, with good clinical response and minimal side effects

A Rare Metastatic Mesenteric Malignant PEComa with TSC2 Mutation Treated with Palliative Surgical Resection and Nab-Sirolimus: A Case Report

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas. CASE PRESENTATION: Here, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient\u27s excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease. CONCLUSIONS: This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus

15th Annual Pancreatic Cancer and Related Diseases Patient Symposium

On Saturday, November 14, 2020, patients/survivors and their friends and family logged in from 167 different locations to join our multi-disciplinary team for our 15th Annual (1st Virtual!) Symposium. The group discussed the latest in medical therapies, surgical options, and innovative research for pancreatic cancer. PROGRAM Welcome and Program Overview Charles J. Yeo, MD, FACS Samuel D. Gross Professor and Chair of Surgery Report of the 2019-2020 Annual Jefferson Pancreas Tumor Registry Survey Theresa P. Yeo, PhD, MPH, MSN, AOCNP Adjunct Associate Professor and Co-Director Jefferson Pancreas Tumor Registry Clinical Trials in Pancreatic Cancer Harish Lavu, MD, FACS Professor of Surgery Section Chief, Hepatopancreatobiliary Surgery Co-Director, Jefferson Pancreas Tumor Registry Recent Data on Adjuvant and Neoadjuvant Chemotherapy in Pancreatic Adenocarcinoma Atrayee Basu Mallick, MD Clinical Assistant Professor of Medical Oncology Moving Research Forward: Promising Work Amid COVID-19 Aditi Jain, PhD Research Instructor Questions & Answers W. Kim Foster Pancreatic Cancer Pilot Grant Recognition Survivor Tribute Photo & Survivor Testimonia