The patient, an 89-year-old male, presented with a one-week history of painless gross hematuria and was admitted to the hospital on July 24, 2024. Upon admission, comprehensive diagnostic evaluations, including abdominal ultrasound and CT urography, were conducted. Imaging revealed a soft tissue mass measuring 30 × 30 mm on the right side of the bladder wall, with a broad base of attachment and significant enhancement on contrast-enhanced scans, indicating a high likelihood of malignancy. Additional findings included multiple cystic lesions in both kidneys, with the largest cyst measuring approximately 70 × 53 mm, exhibiting well-defined margins and no significant enhancement. The prostate also demonstrated localized uneven enhancement. Given the clinical findings, further diagnostic procedures were undertaken, and a tissue biopsy was obtained for histopathological examination.

The specimen comprised a pile of gray-white and gray-red tissue, measuring 1.4 × 0.7 cm, with a fragile texture. Microscopically, the majority of the tumor exhibited clear nest-like structures with abundant capillaries between the nests, reminiscent of renal clear cell carcinoma. The tumor cells displayed clear cytoplasm, with most nuclei centrally located, although some showed nuclear displacement. The nuclei exhibited mild atypia, being large with distinct nucleoli (Figure 1a). In addition to the clear cell nests, areas of typical invasive urothelial carcinoma were observed, characterized by an increased nuclear-to-cytoplasmic ratio, marked nuclear atypia, and reduced cell adhesion, with tumor cells infiltrating the bladder muscle layer as nests or single cells (Figure 1b). The clear cell nests constituted more than 70% of the entire tumor.

a HE 200 × : Section shows clear tumor cells arranged in a nest-like pattern. b HE 200 × : Section shows muscle-invasive tumor of classical bladder cancer and clear tumor cells (The left side is the clear cell area, and the right side is the classic area). c CK7 200 × : CK7 highlights the clear tumor cells and classical bladder cancer. d GATA-3 200 × : GATA-3 highlights the clear tumor cells and classical bladder cancer. e PAS 400 × : Glycogen staining is positive in clear tumor cells and classical bladder cancer. f PAS-D 400 × : Glycogen staining is negative in clear tumor cells, glycogen staining is positive in classical bladder cancer. HE hematoxylin and eosin, PAS periodic acid–Schiff, PAS-D periodic acid–Schiff with diastase

Subsequently, immunohistochemical staining was performed on the tumor tissue. The results revealed that CK7 (Figure 1c), P63, and GATA-3 (Figure 1d) were positively stained in both the clear cell nests and the classic invasive urothelial carcinoma areas. CD10 was positively stained in the clear cell nests, while CK20 was positively stained in the classic areas and negatively in the clear cell nests. RCC, PAX-8, CAIX, and PSA were all negative in both the clear cell nests and the classic invasive urothelial carcinoma. To verify the presence of glycogen in the cytoplasm of the clear cells, special staining with PAS (Figure 1e) and PAS-D (Figure 1f) was conducted. The PAS staining showed the presence of glycogen granules in the cytoplasm of the tumor cells, while PAS-D staining did not, confirming that the clear tumor cells contained glycogen.

Based on the diagnostic criteria, the patient was accurately diagnosed with clear cell (glycogen-rich) urothelial carcinoma.