Malignant/Sarcomatous Transformation of Mixed Epithelial and Stromal Tumor of the Kidney: A Case Report

ABSTRACT

Introduction

Malignant transformation of mixed epithelial and stromal tumors of the kidney (MESTK) is extremely rare.

Case Presentation

A 39‐year‐old man with gross hematuria was suspected to have renal cell carcinoma, measuring 13 cm in diameter. No distant metastases were observed. The patient underwent laparoscopic left nephrectomy. Histopathological examination revealed malignant sarcomatous transformation of MESTK. Immunohistochemically, the tumor was positive for PAX8, CD10, and desmin, as well as for estrogen, progesterone, and androgen receptors. Comprehensive genomic profiling did not yield any treatment recommendations or relevant information. The patient will be closely monitored for any signs of recurrence or metastasis.

Conclusion

The associated prognosis for patients with nonmetastatic MESTKs exhibiting malignant transformation is unknown; however, strict follow‐up is recommended due to the histological grade of malignancy and local invasion.

Keynote Message

Malignant transformation of MESTK is extremely rare. A 39‐year‐old man was diagnosed with MESTK exhibiting malignant transformation, measuring 13 cm in diameter.

1. Introduction

Mixed epithelial and stromal tumor (MEST) is a relatively rare neoplasm that exhibits a biphasic growth pattern, consisting of both epithelial and stromal components [1, 2, 3]. MEST of the kidney (MESTK) is typically benign and predominantly occurs in middle‐aged women. In rare cases, malignant transformation, such as sarcomatoid features, has been reported, which indicates poor clinical outcomes [4, 5].

2. Case Presentation

A 39‐year‐old man visited a local doctor, complaining of gross hematuria. The patient was being treated for hypertension, hyperlipidemia, and obesity but had no history of hormone therapy. A large tumor was detected in the upper pole of the left kidney, and the patient was referred to our hospital.

The urine cytology was negative. Computed tomography (CT) urography revealed a 13‐cm tumor located in the upper‐middle pole of the left kidney, comprising both solid and cystic components, with an internal hematoma and communication with the renal collecting system (Figure 1). No distant metastases were observed. Renal MRI revealed findings similar to those observed on CT, including internal necrosis (Figure 1). The imaging findings strongly suggested a renal parenchymal tumor.

FIGURE 1.

CT (a–d) and MRI (e–h) findings. Dynamic CT images (a, b: Arterial phase; c, d: Portal venous phase) revealed a 13‐cm tumor located in the upper‐middle pole of the left kidney. The tumor comprised both solid and cystic components, contained an internal hematoma, and communicated with the renal collecting system (d, arrow). Renal MRI (e: T1WI, f: T2WI, g: DWI, h: DCE‐MRI) revealed findings similar to those observed on CT, including internal necrosis. This tumor contained a mixture of solid and cystic (liquid) components that exhibited high signal intensities on both T1WI (e) and T2WI (f). The solid component and wall predominantly exhibited mildly high signal intensity on T2WI (f). There was also a mixture of low signal intensity areas, likely attributable to hemorrhagic changes (f). The solid component exhibited high signal intensity on DWI (g). The solid component was predominantly composed of nonenhanced areas, with certain regions, such as the edges, exhibiting contrast enhancement (h). The entire tumor was surrounded by a wall that was contrast‐enhanced (h). Most of the walls were thin, but some areas were thickened (h).

The patient underwent laparoscopic left nephrectomy. Macroscopically, a large, whitish tumor measuring 150 × 120 × 100 mm was extensively present within the renal parenchyma and renal pelvis, accompanied by severe hemorrhage and necrosis. A whitish nodular tumor was observed in the space between the renal parenchyma and transitional epithelium of the renal pelvis, with areas of bleeding and necrosis being present (Figure 2).

FIGURE 2.

Macroscopic findings. Whitish, nodular tumors were observed in the space between the renal parenchyma and the transitional epithelium of the renal pelvis (indicated by arrows). Some areas of the tumor showed hemorrhage and necrosis.

Histopathological examination revealed malignant sarcomatous transformation of MESTK (Figure 3). The tumor was continuous with the renal parenchymal medulla and consisted of a mixture of ovarian stroma‐like spindle cell and epithelial components with ductal architecture (ovarian stroma and epithelial components), suggesting a mixed epithelial and stromal tumor. Sarcomatous transformation was also noted. The components of sarcomatous transformation were histologically similar to fibrosarcoma and accompanied by hemorrhage and necrosis. These findings were consistent with malignant MEST. Mitotic figures were prominent, and atypical mitoses were also observed. Immunohistochemically, the tumor was positive for PAX8, CD10, and desmin, as well as for estrogen (ER) and progesterone (PR) receptors. Androgen receptor (AR) was also positive.

FIGURE 3.

Microscopic findings. The tumor was continuous with the renal parenchymal medulla (RM) and contained a combination of ovarian stroma‐like spindle cell components and epithelial components exhibiting ductal architecture (OS/EC: Ovarian stroma and epithelial components) (a, hematoxylin–eosin staining). This composition demonstrated features characteristic of mixed epithelial and stromal tumor. Additionally, sarcomatous transformation (ST) was observed. Malignant transformation exhibits a histological appearance similar to that of fibrosarcoma. Mitotic figures were prominent, and atypical mitoses were also observed (b, arrow). Images b‐g are serial sections showing a mixed epithelial and stromal tumor on the left, with sarcomatous transformation toward the right. Immunohistochemically, the tumor was positive for PAX8 (EC, upper left) (c), CD10 (OS and sarcoma) (d), and desmin (part of OS and sarcoma) (e), as well as androgen receptor (AR) (OS/EC and sarcoma) (f) and weakly positive for estrogen receptor (ER) (OS/EC and sarcoma) (g).

Comprehensive genomic profiling (CGP) testing was performed using the GenMineTOP Cancer Genome Profiling System (KONICA MINOLTA, INC., Tokyo, Japan). The tumor mutation burden was 2.7 mutations per megabase, indicating a low tumor mutation burden. No genetic abnormalities, including copy number variations, gene fusions, or exon skipping, were detected. No genetic abnormalities corresponding to secondary findings of germline variants were identified.

The patient has remained free of metastasis for 6 months since surgery. The patient will be closely monitored with whole‐body MRI every 3 to 6 months to detect any signs of recurrence or metastasis.

3. Discussion

MESTK is an extremely rare and predominantly benign renal tumor that primarily develops in middle‐aged and elderly women [1, 2, 3]. MEST and adult cystic nephroma are classified as part of the “mixed epithelial and stromal tumor family” in the 2022 WHO Classification of Renal Tumors (5th edition) [6]. Very few cases of MESTK have been reported in men [7, 8]. Development of this tumor is considered to be associated with a prolonged history of estrogen replacement therapy and steroid medication use; however, the present patient had no history of hormonal abnormalities or hormone therapy. The clinical presentations of MESTK include palpable masses, flank pain, hematuria, or symptoms resembling a urinary tract infection. In the present case, the patient visited a local hospital due to macroscopic hematuria and was diagnosed with a left renal tumor.

MESTs exhibit complex morphology due to the combination of epithelial (cysts) and stromal (solid parts) components. On imaging tests, masses display both cystic and solid components, which make it challenging to differentiate MESTK from other renal cystic lesions [9]. They are typically classified as Bosniak category (classification of malignant potential of renal cysts) III or IV on imaging [10]. The present case was classified as Bosniak category IV. We previously reported a case in which MESTK was considered a differential diagnosis preoperatively, based on CT findings of cystic tumor in a perimenopausal woman [11]. However, the present case involved a male patient, and it was difficult to predict MESTK from preoperative images.

Radiological distinctions between benign and malignant MESTKs are not well defined. However, malignancy is suspected when imaging reveals invasion or destruction of the renal pelvis or ureter, when solid components predominate over cystic areas, or when irregular nodules are observed [5]. In this case, communication with the renal collecting system was observed, and imaging also indicated the presence of a malignant tumor (Figure 1). While urothelial carcinoma is an important differential diagnosis, in this case, the urine cytology was negative, and the imaging findings strongly suggested a renal parenchymal tumor.

Macroscopically, MESTKs contain varying proportions of cystic and solid components [3]. The solid components are grayish‐white and firm, while the cystic components are multilocular, with cavities of various sizes and smooth inner walls, typically located within the renal parenchyma. Hemorrhage, necrosis, and fatty infiltration of renal sinuses are rare. However, in the present case, severe bleeding and necrosis were observed, macroscopically differing from typical MESTK, and the findings strongly suggested malignant transformation (Figure 2).

Microscopically, large cystic, multicystic, small cystic, and tubular morphologies are more common in the tumor's epithelial component, while papillary and other structures are rare [3]. The stromal component consists of a mixture of sparsely cellular and densely cellular areas, containing spindle‐shaped cells in varying proportions. In the present case, the renal parenchymal medulla was associated with a mixture of ovarian interstitial‐like spindle cell components and epithelial components exhibiting ductal structures (Figure 3). Immunohistochemically, MESTK is positive for ER, PR, desmin, CD10, and smooth muscle actin in interstitial cells, and positive for cytokeratin in epithelial cells [3]. In this case, the tumor was positive for PAX8, CD10, and desmin, as well as for ER and PR (Figure 3). AR, typically observed in male MESTK patients, was also positive. AR expression has been reported in male cases of MESTK, but the underlying mechanism remains unknown [3]. However, the report of MESTs of the efferent testicular ductules within the genitourinary tract has demonstrated AR expression, suggesting that the sex hormone environment plays a crucial role in regulating AR expression [12].

MESTKs with malignant transformation are considered extremely rare tumors, with sarcomatoid transformation being the most common form of malignancy [4]. Pathologically, malignant transformation of MESTK is diagnosed when highly atypical sarcomatous or carcinomatous components are identified within a benign MESTK. In such cases, the presence of benign MESTK provides clear evidence for differential diagnosis.

The associated prognosis for patients with nonmetastatic MESTKs exhibiting malignant transformation is currently unknown; however, strict follow‐up is recommended due to the histological grade of malignancy and local invasion. The present patient will be closely monitored for any signs of recurrence or metastasis.

4. Conclusion

MESTKs with malignant transformation are considered extremely rare tumors, with sarcomatoid transformation being the most common form of malignancy. CGP did not yield any treatment recommendations or relevant information in the present patient.

Disclosure

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.