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A case of pyelocalyceal diverticulum urothelial carcinoma that was difficult to distinguish from cystic renal cell carcinoma preoperatively

Introduction Pyelocalyceal diverticulum is a rare disease sometimes difficult to distinguish from cysts. We report a case of urothelial carcinoma originating from a pyelocalyceal diverticulum, difficult to distinguish from cystic renal cell carcinoma preoperatively. Case presentation A 51‐year‐old Japanese man complained of gross hematuria. Computed tomography revealed a solid mass in one of the many cystic lesions in the left kidney. He was diagnosed with left cystic renal cell carcinoma and underwent retroperitoneal laparoscopic nephrectomy. Pathological examination revealed high‐grade invasive urothelial carcinoma arising within the renal pyelocalyceal diverticulum. The definitive diagnosis was high‐grade invasive urothelial carcinoma (pT3). In retrospect, the retrograde pyelography findings indicated the cyst and urinary tract connection. Residual ureterectomy and adjuvant chemotherapy were later performed. The patient has since been recurrence‐free. Conclusion Whether cystic renal cell carcinoma is suspected on imaging, pyelocalyceal diverticulum should be considered a differential diagnosis, though unlikely to be encountered in daily practice.


Case presentation
A 51-year-old Japanese man developed gross hematuria. He visited a local hospital where he underwent abdominal computed tomography, which revealed many cysts with calcification inside the left kidney. He was then referred to our hospital for further examination. A blood test showed no abnormal findings. Urinary cytology yielded a pseudo-positive result (class 3). However, dynamic contrast-enhanced computed tomography revealed a mass, which showed enhancement in the early phase and appeared washed out in the late phase, in a cyst at the upper pole of the left kidney ( Fig. 1). Magnetic resonance imaging revealed a tumor with an abnormal signal on a diffusion-weighted image (Fig. 2). Retrograde pyelography showed no wall irregularity at the left renal pelvis, and urinary cytology of samples from the left pelvis and urinary tract yielded negative results. He was diagnosed with left cystic renal cell carcinoma (cT1N0M0) and underwent retroperitoneal laparoscopic nephrectomy. The surgical specimen showed a cystic lesion filled with papillary formation (Fig. 3). Microstones and brownish liquid retention were also observed inside the cystic lesion. Pathological examination revealed that the wall of the cystic lesion was covered with urothelial cells and high-grade urothelial carcinoma with renal parenchymal invasion. In immunohistochemical staining, GATA3, p63, and p40 were positive and PAX8 was negative. The definitive pathological diagnosis was urothelial carcinoma originating from the renal pyelocalyceal diverticulum, invasive urothelial carcinoma, high-grade (G3), and pT3. An additional residual ureterectomy and two courses of gemcitabine and cisplatin adjuvant chemotherapy were performed. Pathological examination showed no malignant findings of the residual ureter, and no recurrence was observed during the 12-month follow-up.

Discussion
A pyelocalyceal diverticulum is a cystic cavity connected to the renal calyx, and it is composed of urothelial cells. It is a relatively rare disease with a reported incidence of only 0.21-0.6% on retrograde pyelography. Urothelial carcinoma developing in the pyelocalyceal diverticulum, as in the present case, is a very rare disease, with only 11 cases reported in Japan (Table 1). [3][4][5][6][7][8][9][10][11][12][13] Of these 11 cases, four were diagnosed as cystic renal cell carcinoma on preoperative examination,   and these cases were difficult to distinguish from those of cystic kidney cancer on preoperative examination, as in the present case. However, a subsequent reanalysis of the preoperative retrograde pyelography findings revealed a connection between the urinary tract and the pyelocalyceal diverticulum (Fig. 4). In all previous reports, patients preoperatively diagnosed with urothelial carcinoma of the pyelocalyceal diverticulum had positive urinary cytology results or findings of a connection with the urinary tract. These examinations may be useful for  diagnosis. There have been few reports of urothelial carcinoma of the pyelocaliceal diverticulum, and the characteristics of the disease are not clear. However, some cases have reported progress without recurrence after surgical treatment.
We think that conventional treatment may be as effective as urothelial carcinoma.
Although not detected in the current case, the presence of stones is useful in differentiating the pyelocalyceal diverticulum from cysts. A pyelocalyceal diverticulum is often known to be associated with stones, but it is also sometimes associated with "milk of calcium." 10,12,14,15 Milk of calcium is a fluid shadow of microstones composed of calcium, which could be detected as a calcified shadow like a half-moon along the horizontal plane on imaging performed in the standing or supine position. In this case, we could not obtain the findings of milk of calcium. Nevertheless, if the findings of milk of calcium are obtained, physicians should proceed with preoperative examinations considering the possibility of a pyelocalyceal diverticulum.

Conclusions
We experienced a case of urothelial carcinoma originating from the pyelocalyceal diverticulum, which was difficult to distinguish from cystic renal cell carcinoma preoperatively. Although it is unlikely to be encountered this disease in daily practice, even if cystic renal cell carcinoma is diagnosed based on preoperative imaging findings, the retrograde pyelography findings should be reanalyzed to distinguish it from urothelial carcinoma in the pyelocalyceal diverticulum particularly when urinary cytology yields false-positive or positive results.
Moreover, if we obtain findings suggestive of stones such as milk of calcium, a pyelocalyceal diverticulum should be positively considered as a differential diagnosis.