Case 4: A 50-year-old male presented with abdominal pain and discomfort without obvious inducement in May 2019. The pain was paroxysmal and dull, which accompanied by lower abdomen swelling. The pain was obvious when fasting, and it was relieved after eating. In June 2020, abdominal pain significantly worsened than before. CT examination at a local hospital showed multiple retroperitoneal lymphadenopathies, and B-ultrasonography showed a lymph node cyst in the left neck and supraclavicular fossa. A biopsy of the left cervical lymph node was performed on June 28, 2020. The postoperative examination revealed a malignant tumor in the left neck, and poorly differentiated squamous cell carcinoma was considered ( Figure 4A ). The patient visited Hunan Cancer Hospital on July 8, 2020 for further treatment. CT examination revealed multiple lymphadenopathies in the left supraclavicular area, mediastinum, hilum, retroperitoneum, and right iliac vessels. Head MRI examination showed no obvious occupying in the nasopharyngeal region. We consulted the local hospital regarding the pathological sections and combined IHC, and considered the diagnosis of malignant tumors, which tend to be poorly differentiated metastasis. Because IHC provides no clear indication, it is difficult to determine the tumor type. It is recommended to check the kidney, lung, liver, prostate, etc. in detail. IHC demonstrated a result of CK (+++), CK7 (-), CK20 (-), Villin (-), TTF1 (-), SATB-2 (+), MelanA (+/-), NapsinA (-), P40 (-), CR (-), CK5/6 (-), CDX-2 (-), S-100 (-), Des (-), SOX-10 (-), and HMB45 (-). PET-CT was performed to understand the general condition, results showed multiple swollen lymph nodes on the double supraclavicular, mediastinum, double lung hilum, right posterior of the right diaphragm, retroperitoneal area, and right iliac vessels, and abnormal radioactive concentration was seen in the corresponding positions, no obvious abnormality in the head, neck, chest and abdomen organs. To further clarify the source of the tumor, the 90-gene expression assay was performed, and the results suggested that the tumors on the left cervical lymph node maybe a metastasis from kidney tumors ( Figure 4B ). We then performed a renal MRI examination and found a nodule at the lower pole of the right kidney with a diameter of approximately 1.4 cm, considering the possibility of renal cancer. For further confirmation, a CT-guided kidney biopsy was performed on August 11, 2020. The cytological results showed cancer cells in the kidney puncture smear ( Figure 4C ), but no clear malignant tumor was found in the pathological section. Because the kidney mass was small (approximately 1 cm), the pathological diagnosis of renal biopsy still could not be further confirmed. Combined with the results of genetic testing and cytology, we considered the possibility of renal cancer, and the patient was treated with the targeted drug pazopanib. On September 18, 2020, the patient returned to the hospital for review. CT of the chest and abdomen showed a nodule with a density of 1.3x1.1 cm in the lower pole of the right kidney, which was smaller than before. At present, he is in stable condition and is undergoing immunotherapy.