PMC7446438_01
Computed tomography imaging of patient's abdominal tumor over time. (A) Initial imaging. (B) Development of aortic pseudo-aneurysm. (C) Baseline before enrollment, postsurgery. (D) After 1.6 months of larotrectinib treatment. (E) After 14 months of larotrectinib treatment.
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Computed tomography of her abdomen and pelvis revealed a large (9.6 x 7.4-cm), unresectable, retroperitoneal mass encasing the aorta and involving the vertebral bodies (Fig 1A). After two cycles of chemotherapy, disease progression continued, and an aortic pseudo-aneurysm developed within the mass, which led to displacement of the inferior vena cava and ureteral impingement (Fig 1B). Baseline disease evaluation revealed the presence of a pulmonary metastasis, multiple enlarging positron emission tomography (PET)-avid tumors (largest 1.5 x 5.3 cm) within the retroperitoneal surgical bed, and massive ascites that was presumed to be malignant (Fig 1C). Repeat imaging at the end of cycle 1, which was confirmed after cycle 2, demonstrated resolution of PET avidity of all tumors, resolution of ascites, and significant reduction in the size of the residual pulmonary metastases and retroperitoneal tumors consistent with a partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Figs 1D and 1E).
Surgical resection of retroperitoneal sarcoma. (A) Retroperitoneal tumor before resection. (B) Tumor bed after resection, with residual tumor invading the vertebral bodies. (C) Status postreconstruction of the aorta. (D) Excised tumor specimen, including the aortic bifurcation.
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She underwent exploratory laparotomy with resection of a 13.5 x 10.5 x 6.5-cm tumor, resection and reconstruction of the abdominal aorta, ligation and resection of the inferior vena cava, resection of sigmoid colon with end colostomy, and placement of bilateral ureteral stents (Fig 2).
Pathology of patient's tumor from resection. (A) Transverse section of the mass with aneurysmal cavity around the aorta. (B) Hematoxylin and eosin stain that shows epithelioid/rhabdoid cells with eccentric, pleomorphic nuclei; occasional nucleoli and abundant eosinophilic cytoplasm; and a single mitosis. (C) Immunohistochemistry for INI-1 that shows retained nuclear positivity in the neoplastic cells. (D) Immunohistochemistry for pan-Trk that shows membranous and cytoplasmic positivity in the neoplastic cells. (E) STRN-NTRK2 fusion identified in tumor sample by next generation sequencing. (F) RNA sequencing reads that support the STRN-NTRK2 fusion.
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Histologically, the tumor consisted of sheets of epithelioid cells with large eccentrically placed nucleus, occasional nucleoli, and abundant eosinophilic cytoplasm, mimicking rhabdoid cells (Fig 3). Sequencing revealed a novel STRN-NTRK2 fusion in which the kinase domain of NTRK2 is joined in frame to STRN (Figs 3E and 3F).
Timeline. IE, ifosfamide and etoposide; NGS, next-generation sequencing; NRSTS, nonrhabdomyosarcoma soft tissue sarcoma; PET, positron emission tomography; RECIST, Response Evaluation Criteria in Solid Tumors; VAdriaC, vincristine, doxorubicin, and cyclophosphamide.
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By 14 days after initiation of larotrectinib, the patient was noticeably less fatigued (LPS of 70), the ascites had resolved by physical examination, and her back pain had resolved (Fig 4).