無原發腫瘤的轉移性腎臟癌-兩個案例報告

曾浩翔¹、尤律婷²、張菡^2,7、黃煒軒³, 林維卿^4,5,6，張兆祥^1,2

¹中國醫藥大學附設醫院 泌尿部; ²中國醫藥大學醫學系; ³長安醫院 泌尿科; ⁴中國醫藥大學附設醫院 影像醫學部; ⁵中國醫藥大學 醫學系 生物醫學影像科; ⁶中國醫藥大學附設醫院 人工智能創新中心; ⁷中國醫藥大學附設醫院 病理部

Metastatic renal cell carcinoma without primary tumor: Report of two cases

Hao Xiang Chen¹, Lu-Ting Yu², Han Chang^2,7, Wei-Hsuan Huang³, Wei-Ching Lin^4,5,6,  Chao-Hsiang Chang^1,2

¹ Department of Urology, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; ² School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan; ³ Department of Urology, Everan Hospital, Taichung 41159, Taiwan; ⁴ Department of Medical Imaging, China Medical University Hospital, Taichung, Taiwan; ⁵ Department of Biomedical Imaging and Radiological Science, School of Medicine, China Medical University, Taichung, Taiwan; ⁶ AI Innovation Center, China Medical University Hospital, Taichung, Taiwan; ⁷ Department of Pathology, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan

Introduction:

Cancer of unknown origin is a rare disease and cancer of unknown origin-renal cell carcinoma is rarely identified and only consisted of 5% of cancer of unknown primary origin. The disease prognosis is typically poor because of no standard and effective therapy. To our review, 23 cases have been reported and treated with conventional chemotherapy or tyrosine-kinase inhibitors alone; accordingly, most patients showed partial response or progression diseases with short survival time. Herein, we presented two cases of metastatic renal cell carcinoma without a primary origin. One case was papillary type and another one was clear cell type.

Case presentation:

Case 1: A 63-year-old man with a medical history of coronary artery disease, hypertension, and stage 4 chronic kidney disease presented with persistent neck pain for two months. He sought medical attention at an otolaryngologist clinic due to the presence of a painful neck mass. The neck mass showed a non-mobile, left supraclavicular lymph node measuring 1.2 cm in the greatest dimension. The lymph node biopsy exhibited large epithelioid tumor cells with ovoid nuclei, occasional prominent nucleoli, eosinophilic cytoplasm, and arranged in a mixed acinar, papillary, and infiltrating pattern. These tumor cells showed positive reactivity to CK and PAX8 and negativity to GATA3, p63, and TTF-1 using IHC studies. The tumor morphology and immunohistochemistry staining characteristics were diagnosed as metastatic papillary renal cell carcinoma. Imaging studies of abdominal and chest CT revealed many enlarged lymph nodes in various locations throughout the body, including the left gastric chain, common hepatic chain, retro-caval space, celiac axis, para-aortic region, aorto-caval space, mesentery, bilateral Gerota fascia, inferior-mesentery-artery chain, perirectal space, bilateral common iliac chains, bilateral hypogastric chains, bilateral external iliac chains, bilateral obturator spaces, and both inguinal regions. The imaging also showed left renal vein thrombosis extending from the renal vein to the inferior vena cava, as well as the involvement of the left adrenal vein. There was no evidence of a solid renal mass on either side of the kidney. The patient was further treated as metastatic renal cell carcinoma, International-Metastatic-RCC-Database-Consortium (IMDC) intermediate risk with systemic therapy of pembrolizumab followed by cabozantinib+ nivolumab then added ipilimumab due to progression.

Case 2:

A 71-year-old man presented low back pain lasting for 2 months. Imaging studies revealed one osteolytic lesion in the spine lumbar 4 vertebral body and another one on the left iliac bone. Biopsies of the L4 and left iliac bone lesions revealed epithelioid tumor cells with clear cytoplasm and oval nuclei in a delicate vascular stroma, and IHC analysis showed positive reactivity to CK, PAX8, CD10 and CA-IX, and negativity to NKX3.1, p63, CK7, and AMACR, compatible with the pathologic diagnosis of metastatic clear cell renal cell carcinoma.

The patient underwent PET/CT revealed no other lesions in addition to the two bone metastases. Laboratory data, including hemoglobin, corrected calcium, neutrophil counts, and platelets, were all within normal limits, and Karnofsky performance score was 100%. MRI showed no tumor in the bilateral kidneys. According to the IMDC classification, the patient received systemic therapy with cabozantinib 40 mg daily from September 2022 until the present. In addition, palliative intensity modulated radiation therapy to L4 spine and left iliac bone metastases for 36Gy/12Fr. Now the patient has remained stable for 6 months

Conclusion: Our case demonstrated two cases of metastatic renal cell carcinoma without primary tumor treated with a combination of immunotherapy and tyrosine kinase inhibitor. More studies will be warranted to determine the efficacy of combination therapy in metastatic RCC without primary origin.