We report the case of a 73-year-old man who died of systemic metastasis of RCC, not otherwise specified, with treatment-resistant fever and polyarthralgia. The patient was diagnosed with autosomal dominant polycystic kidney disease at 34 years of age after developing lateral abdominal pain due to a ureteral stone. At 47 years of age, he started continuous ambulatory peritoneal dialysis, which was changed to hemodialysis 3 times a week at 52 years of age. At 54 years of age, he underwent renal artery embolization according to a previously published method (4) to reduce the size of an enlarged kidney. At age 55 years, he received a kidney transplant in China (no donor information is available). Thereafter, the size of the left kidney decreased, but the right kidney did not decrease much in size and showed cyst-like dilatation of the renal pelvis due to the presence of a ureteral stone; however, the patient's symptoms improved after 3 drainage procedures, and no further treatment was needed. At the age of 68 years, the patient developed fever, polyarthritis in the joints of both hands and feet, and elevated CRP (2.4 mg/dl). Tests for rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative, and he was diagnosed with seronegative RA and started on adalimumab. Adalimumab was effective, and the patient's arthralgia and fever subsided; therefore, the treatment was continued. At the age of 70 years, the arthralgia worsened again, and the patient was switched to baricitinib. At 72 years of age, the cyst-like lesions in the right kidney again increased in size, and drainage was performed (Figs. 1 and 2). Cytological analysis of the fluid content did not reveal any malignancy. Nevertheless, the patient was admitted for the resection of the enlarged right kidney.

Immediately after transplantation, treatment commenced with prednisolone (5 mg), tacrolimus (3 mg), and mycophenolate mofetil (1,500 mg). After 3 years, prednisolone was discontinued due to a favorable response to treatment, while the tacrolimus dose was increased to 4 mg, and the mycophenolate mofetil dose was reduced to 750 mg. This treatment regimen was then maintained. Over the 17 years following renal transplantation, the peripheral blood lymphocyte count remained within the range of 1,020-1,500/4,800-5,600/µl. However, three months prior to the current admission, there was a notable decrease in the lymphocyte count to 812-913/5,800-8,300/µl.

On admission, the patient was 168 cm tall and weighed 54 kg. His blood pressure was 117/74 mmHg (with no administration of antihypertensive medication), and his body temperature was 37.6°C. No heart murmur was heard, and no edema was observed. The laboratory findings were as follows: Red blood cell count, 470×10⁴/µl (reticulocyte, 1.22%); hemoglobin, 12.0 g/dl; white blood cell count, 8,300/µl (segment, 83%; lymphocyte, 10.3%); total protein, 6.3 g/dl; albumin, 2.8 g/dl; serum urea nitrogen, 14 mg/dl; serum creatinine, 0.86 mg/dl; HbA1c, 6.0%; erythrocyte sedimentation rate, 60 mm/h; CRP, 3.05 mg/dl; total complement activity (assessed as CH50), 44 U/ml (reference range, >30 U/ml); complement 3, 104 mg/dl (reference range, 86–160 mg/dl); complement 4, 32 mg/dl (reference range, 17–45 mg/dl); immunoglobulin (Ig) G, 1,189 mg/dl (reference range, 861–1,747 mg/dl); IgA, 308 mg/dl (reference range, 110–410 mg/dl); and IgM, 76 mg/dl (reference range, 52–270 mg/dl). Tests for rheumatoid factor and anti-cyclic citrullinated peptide antibody were negative, and immunological tests were negative for anti-nuclear antibody, anti-neutrophil cytoplasmic antibody (MPO/PR3), and other major autoantibodies. The erythropoietin level was 32.9 mIU/ml (normal; 4.2–23.7 mIU/ml).

The resected right native kidney measured 22.5×16.8×11.7 cm in size and weighed 2,300 g. Most of the renal parenchyma was occupied by an invasive tumor measuring 15.9×7.6 cm in diameter. The tumor extended into the renal vein to form a tumor embolus. The cut surface of the tumor was massively necrotic and dark brown in color (Fig. 3A).

Histologically, there was infiltrative proliferation of poorly connected, highly pleomorphic tumor cells with marked necrosis. The cell nuclei were large and irregular, ranging from dark-toned nuclei to nuclei with intranuclear pseudoinclusions. The tumor cells were large, with ubiquitous nuclei and abundant acidophilic cytoplasm. These findings corresponded to a rhabdoid change, a term used because the cells resemble those found during rhabdogenesis. Neutrophils were observed inside the tumor cells, a finding referred to as emperipolesis (Fig. 3B). A neutrophilic infiltrate was observed around the tumor cells (Fig. 3C). No components were suggestive of an underlying histological type of RCC.

Immunohistochemically, the tumor cells were focally positive for cytokeratin 7, an α-methylacyl-CoA racemase; positive for cytokeratin AE1/AE3, cathepsin K, transcription factor E3 (TFE3), PAX8, and fumarate hydratase; and negative for carbonic anhydrase 9, anaplastic lymphoma kinase, and S-(2-succino)-cysteine. Furthermore, the tumor cells were weakly positive for IL-6 (Fig. 3D). Although TFE3-rearranged RCC was suspected, break-apart fluorescent in situ hybridization did not reveal a rearrangement of the TFE3 gene. Based on these findings, the tumor was classified as RCC, not otherwise specified.

The patient's fever and arthralgia temporarily remitted after the operation. However, 2 months later, they returned, and systemic metastases of RCC developed, along with increasing pleural effusions. The CRP level was 6.17 mg/dl, the white blood cell count was 22,800/µl (segment, 86%), and the serum IL-6 level was 83.9 pg/ml (normal value, <7.0). Treatment with nivolumab was initiated but had little effect, and the patient died 2 weeks later (Fig. 1).