NTRK-Rearranged Mesenchymal Tumor in Non-NF1 24yo male, S/P Multiple Resections, Chemotherapy, and Radiotherapy

University of Pennsylvania

Eric Zager

A 24 y.o. otherwise healthy male without a family history of neurofibromatosis initially developed a painless 1.5cm left neck mass in 2019. He then developed further fullness and mild paresthesias in the left arm and fingers. Imaging in November 2019 revealed a 4.5 x 5.9 x 8.7 cm mass along the left neck involving the C3-C5 nerve roots as well as a left supraclavicular mass measuring 5.8 x 3.8 x 3.8 cm. He underwent biopsy of the lateral mass which revealed neurofibroma. Over three months, the mass grew, and he developed neck pain. He underwent partial debulking at OSH in February 2020 with final pathology consistent with benign neurofibroma. Intraoperative reports noted significant hypervascularity of the tumor. There was significant residual disease, and he was referred to our center. At that time, repeat imaging revealed essentially complete regrowth and progression of the lesion to 10cm over a 2-month period. PET demonstrated SUV max 12.8. The supraclavicular mass was stable in size with SUV max 8.2. After multidisciplinary review, additional tissue diagnosis was recommended and revealed a low grade epithelioid and spindle cell tumor with NTRK1 translocation, without evidence of sarcoma. He underwent a multidisciplinary second surgery at our center following a preoperative angiogram with limited embolization due to vertebral artery vascular contributions. A lateral approach for debulking of the tumor was performed May 2020 with residual disease extending into the C3-5 foramina with encasement of the vertebral artery. Pathology was consistent with recurrent NTRK-rearranged mesenchymal tumor. He was neurologically intact. He underwent testing of the NF1 gene which was negative. He was followed closely with imaging and two months later was noted to have increased in size of the posterior paravertebral residual tumor. Given the tumor mutation revealing LMNA/NTRK1 exon 2/exon 11 fusion positivity, he was started on Larotrectinib per his oncologist in August 2020. Subsequent MRI revealed marked cytoreduction of residual mass. The left supraclavicular mass also reduced in size to 3 cm. He was maintained on Larotrectinib with stable imaging for two years until September 2022 when he demonstrated new areas of enhancement. He underwent needle biopsy which demonstrated known tumor pathology. PET showed increased size in mass with max SUV of 11.5. In the setting of significant regrowth of tumor despite previously effective chemotherapy additional surgical resection was recommended by multidisciplinary team and the patient underwent a third debulking surgery in March 2023. Tumor pathology was stable, but regrowth was noted on imaging one month later. He was started on a clinical trial for a novel TRK inhibitor (repotrectinib) which was started May 2023. However, in January 2024, significant regrowth of tumor was observed to 6.5cm and he was transitioned back to Larotrectinib. The left supraclavicular lesion measured 2.6 cm and was stable. Given the marked regrowth of tumor, he underwent a fourth resection in February 2024. Pathology was stable and imaging showed only a small area of residual enhancement. The supraclavicular mass increased to 3.5cm. He ultimately underwent adjuvant post-op radiation to the tumor resection bed as well as the supraclavicular mass (in preoperative dosing) in May 2024. He is due to obtain imaging presently which will guide further treatment and likely surgical resection of the supraclavicular mass. He remains neurologically intact.