A 42-year-old Chinese female presented with enlarged cervical lymph nodes as the first symptom in May 2020. Ultrasonography showed multiple enlarged lymph nodes in left neck and subclavian region (the maximum size was about 3.8×2.1 cm). CT showed multiple enlarged lymph nodes in left neck, supraclavicular fossa, armpit, retroperitoneum, inguinal region, pelvic cavity and regions around left adrenal region, abdominal aorta and vena cava, extensive irregular soft tissue nodules around retroperitoneal and iliac vessels, multiple lymph nodes which were considered as metastatic lymph nodes (Fig. 1).Left kidney cyst with calcification was also identified (Fig. 1). The immunohistochemical results of neck lymph nodes were CD10(+), PAX-2(+), PAX-8(+), RCC(+), P504S(+), TFE-3(+), CgA(-), Inhibin-a(-), Ki67(+,30%), Napsin A(-), S-100(+), TG(-), TTF-1(-), CA9(+), CD117(YR145) (-), CK7(-), HMB-45(-), AE1/AE3(-), PD-L1(22C3) TPS 20% (Fig. 2). Pathological findings supported metastatic RCC, which was prone to Xp11.2 translocation RCC. Genetic testing showed a breakage of 28% of TFE3 gene, ASPSCR1-TFE3 gene fusion, with a mutation abundance of 20.3%, low tumor mutation burden (TMB-L) and microsatellite stable (MSS). EGFR, ERBB2, ALK, ROS1, MET, RET, BRAF, KIT, PDGFRA, BRCA1/2, KRAS, NRAS, NTRK1/2/3, PALB2 and PIK3CA were not fused, rearranged or mutated. 18F-FDG PET/CT showed low-density nodular with calcification in the upper part of the left kidney (1.5×2.1 cm, SUVmax 3.4), multiple enlarged lymph nodes (diameter of 0.5–7.1 cm, SUVmax 1.9–5.6) in the left of neck, supraclavicular and subclavian fossa, armpit, pectoralis major and submuscular space, mediastinum, T11-L4 vertebral bodies and arteries and muscles around iliac fossa. Osteolytic lesions in the L1, 3 and 4 vertebral bodies was considered as metastases (SUVmax 3.8–4.2) (Fig. 3).
Treatment
The patient was diagnosed as ASPSCR1-TFE3 gene fusion tRCC (left kidney, cT1aN1M1, stage IV) and multiple metastases of lymph nodes, bone and liver. The patient were treated with 200 mg Pembrolizumab infusions per 3 weeks and 5 mg Axitinib orally twice daily. One week later, the patient developed extensive macular rash on face, neck, upper and lower limbs, chest and back, which accounted for nearly 50% of total body surface area. The patient was discontinued of Axitinib treatment. According to the 2020 CSCO guidelines for the management of toxicities associated with immune checkpoint inhibitors, the patient received prednisone acetate orally (0.5 mg/Kg) and rashes completely disappeared after 17 days of hormonotherapy. The treatment was restarted at second cycle, to reduce skin irritant reaction and other related adverse events, the dose of Pembrolizumab was reduced to 100 mg infusions per 3 weeks and 5 mg Axitinib orally twice daily. After two cycles of treatment, the imaging assessment showed lymph nodes at neck reached partial response, abdominal lymph nodes and the left kidney lesions were stable and hepatic lesions achieved complete response (Fig. 4). 18F-FDG PET/CT showed significant no decrease of low-density nodular lesion in left kidney and no abnormal radioactive concentration. Multiple enlarged lymph nodes partially disappeared, and some lymph nodes significantly smaller than before. Radiometabolic activity of multiple osteolytic lesions at the first, third and fourth lumbar vertebras reduced than before image assessment suggested that the scheme was beneficial to patients' disease control, therefore, the treatment was continued to be used.
Up to June 2022, a total of 25 cycles of Pembrolizumab and Axitinib were received, and tumors at left kidney, lymph nodes, liver and bone were assessed as stable disease, partial response, complete response and stable disease, respectively. The adverse events were rash (CTCAE grade 3), secondary hypertension (CTCAE grade 3), secondary hypothyroidism (CTCAE grade 2) and diarrhea (CTCAE grade 1).