Mixed epithelial and stromal tumor (MEST) is a rare renal neoplasm first reported by Pawade et al. in 1993 and is estimated to constitute approximately 0.2% of all renal tumors (1). From a histological perspective, MEST is composed of solid and cystic components and predominantly affects perimenopausal women (2), although cases in children and male patients have also been reported (3). MEST may be difficult to distinguish radiologically from cystic renal cell carcinoma or urothelial carcinoma of the renal pelvis (2), and understanding its diverse imaging features is important for appropriate clinical management and treatment decision-making (4). Although malignant variants of MEST have been reported (5), the tumor is regarded as a benign entity.

Regarding living-donor kidney transplantation, recipients with a history of malignant tumors are considered to be at increased risk of recurrence owing to postoperative immunosuppression (6). Therefore, a tumor-specific waiting period after curative treatment is recommended before transplantation (7). To our knowledge, reports on the management of MEST in candidates awaiting kidney transplantation are limited.

Here, we aimed to report a case of a patient with end-stage renal disease and bilateral renal pelvic masses who underwent left nephroureterectomy, was pathologically diagnosed with MEST, and subsequently had living-donor kidney transplantation without a waiting period, yet with a favorable clinical outcome.

A 52-year-old Japanese woman had been undergoing maintenance hemodialysis for end-stage renal disease secondary to mesangial proliferative glomerulonephritis for 1 year before her initial presentation to our hospital. She desired kidney transplantation, and computed tomography performed as part of the pre-transplant work-up revealed bilateral renal pelvic masses. She was referred to our Institution for further evaluation.

Voided urine cytology was classified as atypical urothelial cells. After referral, retrograde pyelography was performed, and bilateral selective urine cytology ranged from negative to suspicious for high-grade urothelial carcinoma. Contrast-enhanced computed tomography demonstrated enhancing solid lesions in the bilateral renal pelvises (Figure 1).

Ureteroscopic evaluation was proposed to obtain a definitive diagnosis; however, given the patient’s firm preference for early kidney transplantation, she opted for surgical treatment. In addition, 3 months after her initial visit, robot-assisted left nephroureterectomy was performed. The operative time was 146 min, and the estimated blood loss was 5 ml.

Postoperatively, she developed Clostridioides difficile colitis, which was successfully treated with antibiotics; nevertheless, this prolonged her hospital stay. She was discharged on postoperative day 22.

Histopathological examination revealed proliferation of various-sized tubular structures and stromal components, without evidence of malignancy (Figure 2). Immunohistochemistry indicated that the stromal cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) (Figure 3), focally positive for CD10, but negative for melanosome-associated antigen (detected by HMB45 antibody). The epithelial cells were positive for GATA binding protein 3 (GATA3) and paired box 8 (PAX8) (Figure 4). Based on these findings, the tumor was diagnosed as MEST.

Although malignancy of the contralateral renal pelvic lesion could not be completely ruled out, it was considered highly likely to be MEST. Given the patient’s firm desire for prompt transplantation, open right nephrectomy, followed by living-donor kidney transplantation to the right iliac fossa, was performed 6 months after the left nephroureterectomy. The donor was her husband, whose blood type was O, and the recipient’s blood type was A. Donor-specific antibodies were not detected preoperatively. Standard immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, and rituximab was administered according to our institutional protocol.

The operative time was 229 min, and the estimated blood loss was 69 ml. The total ischemic time was 53 min, and the warm ischemic time lasted 4 min. The graft had a single renal artery and vein. The renal artery was anastomosed end-to-side to the external iliac artery, and the renal vein was connected end-to-side to the external iliac vein.

The postoperative course was uneventful, and the patient was discharged on postoperative day 9. Histopathological examination of the right kidney confirmed MEST, similar to the left renal tumor, with no evidence of malignancy (Figure 5).

Renal graft function improved promptly after transplantation. A protocol graft biopsy performed 3 months postoperatively showed no evidence of rejection. At 1-year follow-up, the patient maintained stable graft function with no evidence of tumor recurrence or metastasis.

In the present case, bilateral renal pelvic tumors were identified, the patient underwent robot-assisted nephroureterectomy and the tumors were pathologically diagnosed as MEST. Based on this diagnosis, living-donor kidney transplantation was performed without a waiting period, and the procedure was successful. The postoperative course has been uneventful, with no deterioration of graft function or evidence of rejection up to 1 year after transplantation. To our knowledge, this is the first report of living-donor kidney transplantation in a patient bearing MEST.

For patients with a history of malignancy, Kidney Disease Improving Global Outcomes recommends a waiting period before kidney transplantation, depending on the cancer type (7). For upper tract urothelial carcinoma, a waiting period of 2 years after nephroureterectomy is recommended for patients with localized tumors and 5 years for cases with invasive tumors. For renal cell carcinoma, a waiting period is not necessarily required in the case of incidentaloma cancer (<3 cm) that have been completely excised with negative margins. In contrast, a waiting period of approximately 2 years is generally recommended for patients with localized tumors and 5 years for those with invasive tumors (7). In the present case, as the diagnosis was MEST (a benign tumor) and no specific Kidney Disease Improving Global Outcomes guidance exists, transplantation without a waiting period was performed after a careful discussion with the patient.

Although MEST is regarded as benign, a few cases with malignant transformation have been reported. To our knowledge, 28 cases with malignant features have been reported (5, 8-28). The median age was 55.5 (range=42.5-67) years, and 75% of the patients were female. Some cases demonstrated extension into the renal vein or inferior vena cava, and others developed distant metastases. In cases with recurrence or metastasis, chemotherapy or radiotherapy has been administered, and tumor shrinkage has been reported for treatment with doxorubicin plus ifosfamide (22). From a pathological perspective, sarcomatous transformation of the stromal component was observed in 79% (22 cases); nevertheless, malignant changes in the epithelial component have also been described. In our case, the epithelial and stromal components showed no malignant features. Moreover, no reports have described cases initially diagnosed as benign MEST to subsequently demonstrate malignant transformation upon recurrence. MEST is usually unilateral; only three bilateral cases have been reported, and none showed malignant features (29-31). Although MEST is a rare entity and may not always be managed in the same manner as other benign tumors, based on these findings, living-donor kidney transplantation without a waiting period was considered feasible in the present case. However there have been seven reported cases of MEST with malignant features that developed recurrence after surgery, with a median time to recurrence of 4 months (range=2-12 months) and a maximum of 24 months (8, 10, 11, 17, 22, 28). In the present case, the follow-up period was limited to 1 year; therefore, careful long-term surveillance is warranted. Furthermore, follow-up adherence among living kidney donors has been reported to be potentially associated with graft survival and recipient survival (32), suggesting that long-term follow-up of donors may be necessary.

The precise pathogenesis of MEST remains unclear. However, it predominantly occurs in perimenopausal women (2), frequently shows positivity for ER and PgR in the stromal component (ER positive in 62% and PgR positive in 85%) (33), and has been reported in men receiving estrogen therapy for prostate cancer (16). These observations suggest that hormonal stimulation promotes the proliferation of hormone-sensitive stromal cells, leading to the formation of a biphasic tumor incorporating epithelial elements (34). Malignant transformation may occur through additional genetic alterations or aging-related factors during this process. Although immunosuppressive agents are associated with an increased risk of malignancy (6), MEST emerges primarily through hormonal mechanisms. Therefore, whether immunosuppression contributes to the malignant transformation of MEST remains unclear. While immunosuppressive therapy is associated with increased malignancy risk, no evidence suggests that benign MEST undergoes malignant transformation under immunosuppression. To our knowledge, this is the first reported case of immunosuppressive therapy in a patient with bilateral MEST.

We reported a case of successful living-donor kidney transplantation without the recommended waiting period in a patient with renal pelvic tumors pathologically diagnosed as MEST. In carefully selected patients with confirmed MEST without malignant features, kidney transplantation without a waiting period may be considered. Nevertheless, careful long-term follow-up remains essential.

The Authors declare no conflicts of interest.

Keisuke Nakai was involved in patient care, reviewed the literature, collected the patient data, and prepared the manuscript. Yuki Kobari prepared and revised the manuscript. Toshio Takagi revised the manuscript. Mayu Hakozaki and Yoji Nagashima performed the pathological evaluation and interpretation. Takashi Ikeda, Saito Ayaka, Daigo Okada, Arisa Wada, Hironori Fukuda, Takayuki Nakayama, Kohei Unagami, Kazuhiko Yoshida, Toshihito Hirai, Tomokazu Shimizu, Junpei Iizuka, and Hideki Ishida were involved in the clinical management of the patient. All Authors have read and approved the final version of the manuscript.

The Authors thank Editage for editing the manuscript.

During the preparation of this manuscript, a large language model (ChatGPT, OpenAI) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures or visual data were generated or modified using generative AI or machine learning–based image enhancement tools.