Introduction/Background NTRK genes encode tyrosine receptor kinases (TRK), proteins promoting cellular proliferation and survival. NTRK fusions are implicated in solid tumours including gynaecological sarcomas lacking diagnostic features of any sarcoma subtype. In 2020, UK NICE approved a histology-independent TRK-inhibitor drug, larotrectinib, for treatment of such tumours in both children and adults.

Methodology We present the case of a 49-year old female who presented with recurrence of an NTRK1-TPM3 fusion positive cervical sarcoma nine months following primary total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO).

Results The patient was initially referred with a large cervical mass measuring 9 cm on imaging. Biopsy demonstrated high grade malignant tumour of spindle cell morphology. She underwent TAH and BSO. Specimen microscopy revealed a poorly differentiated sarcoma composed predominantly of spindle cells, with moderate/severe pleomorphism and brisk mitotic activity. Pan-TRK immunohistochemistry was positive, FISH revealed an NTRK1 translocation and next-generation sequencing confirmed an NTRK1-TPM3 fusion. Postoperative CT revealed no residual tumour and the patient was placed under close surveillance. Nine months later, the patient presented with vaginal bleeding. A 7 cm upper vaginal mass was seen on examination, which was diagnosed as NTRK-positive leiomyosarcoma recurrence. CT showed the presence of pulmonary metastases. Although four cycles of doxorubicin were administered, the pulmonary masses continued to progress. Larotrectinib was administered as an alternative therapy due to the tumours’ NTRK positivity. The patient received 12 cycles of larotrectinib 100 mg BD over 10 months. This led to reductions in lung metastases size and no progression of the pelvic mass. Two years postoperatively, the patient remains stable and continues to be monitored.

Conclusion Excellent durable response and improved survival was achieved. Testing for NTRK should be done and NTRK inhibitors considered for advanced gynaecological sarcomas. Future research will further assess the efficacy of TRK-inhibition therapy as primary, neoadjuvant and adjuvant treatment.