Mixed epithelial and stromal tumor of the kidney: a case series of clinical diversity in atypical presentations

Introduction

Background

Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare primary renal neoplasm, accounting for approximately 0.1% to 0.3% of all renal tumors. Its defining feature is the coexistence of epithelial and stromal components in tumor tissue: most cases show benign biological behavior, while a small subset may have borderline properties or malignant potential (1).

According to classic literature, MESTK has a significant gender predilection, predominantly affecting perimenopausal women (with a male-to-female ratio of roughly 1:10). This gender bias supports the hypothesis that its pathogenesis is associated with hormonal levels (especially estrogen and progesterone), as stromal components consistently express estrogen receptor (ER) and progesterone receptor (PR) (2).

Clinically, MESTK lacks specific manifestations and is often detected incidentally. Radiologically, it typically presents as cystic or cystic-solid masses with septations, calcifications, or mild enhancement—features that overlap with common renal tumors [e.g., cystic renal cell carcinoma (RCC), angiomyolipoma], leading to a high rate of preoperative misdiagnosis (3). Currently, definitive diagnosis relies on pathological examination (revealing characteristic biphasic differentiation: cuboidal/flattened/columnar epithelial components and ovarian stroma-like stromal components) and immunohistochemistry (IHC) [epithelial elements positive for paired box gene 8 (Pax-8) and cytokeratin 7 (CK7); stromal elements positive for ER and PR], which are keys for differential diagnosis (4).

Rationale and knowledge gap

Current studies still provide insufficient characterization of the epidemiological features and imaging presentation spectrum of atypical MESTK populations, particularly in male patients; the unifying theme of this study is the clinical features, diagnostic criteria of atypical MESTK cases (males, young females) and the efficacy of robot-assisted laparoscopic partial nephrectomy. Given the insufficient reports on atypical cases and unclear applicability of minimally invasive treatment in existing studies, this research can improve the clinical cognitive system of MESTK. Additionally, the 4 enrolled patients have unique characteristics—3 males and 1 young female (22 years old)—whose demographic profile deviates from the classic epidemiological pattern of MESTK. Their imaging findings also include rare fat-density shadows, making this cohort clinically distinctive.

Due to the rarity of MESTK, a comprehensive understanding of its clinical features remains lacking. The classic epidemiological (gender/age) and radiological characteristics of MESTK do not fully cover atypical cases, which may lead to underrecognition or misdiagnosis in clinical practice.

Objective

By analyzing the clinical data of the 4 atypical MESTK cases and reviewing relevant literature, this study aims to further explore the clinicopathological characteristics, diagnostic criteria, treatment, and prognosis of MESTK. Ultimately, it seeks to provide insights for the management of atypical MESTK cases and enhance clinicians’ overall understanding of the disease.

Case presentation

Study methods

Study design

This is a single-center retrospective case series study, including 4 consecutive MESTK patients admitted to the Department of Urology, Xijing Hospital from January 2019 to December 2024 (no cases excluded, with clear case continuity).

Setting

The study was conducted at the Department of Urology, Xijing Hospital, Fourth Military Medical University (an academic tertiary hospital in Xi’an, Shaanxi, China). The data collection period was from January 2019 to December 2024, with follow-up ending in December 2024 (maximum follow-up duration: 70 months). Of the 1,625 renal tumors identified during the data collection period, 4 were MESTK, accounting for 0.25% of the total. All patient diagnosis, treatment and follow-up were completed in Xijing Hospital.

Participants

Characteristics: among the 4 patients, 3 were male (21, 29, 54 years old) and 1 was female (22 years old); none had comorbidities such as hypertension or diabetes, nor smoking history.

Eligibility criteria

Inclusion criteria: (I) pathologically confirmed MESTK; (II) complete medical records (epidemiology, imaging, pathology, follow-up). Exclusion criteria: (I) complicated with other malignant tumors; (II) missing medical records. Criteria for defining atypical MESTK: (I) age <45 years; (II) male gender; (III) imaging findings with fat density shadows. Meeting any of the above criteria is sufficient for classifying a case as atypical. Among the 4 patients in this study, 3 met the “male gender” criterion, and 1 patient (a 22-year-old female) met the “age <45 years” criterion; all were classified as atypical cases.

Intervention

The intervention was robot-assisted laparoscopic partial nephrectomy using the Da Vinci surgical system. Rationale for selection: (I) tumor diameter ≤4.9 cm, meeting the indication for partial nephrectomy; (II) benign tumor, minimally invasive treatment could preserve renal function. The operation was performed by the same team of urologists, without adjuvant drug therapy.

Follow-up

Follow-up method: outpatient follow-up once every 3 months within 1 year after surgery, and once every 6 months thereafter. Follow-up content: (I) physical examination (presence of low back pain, abdominal mass); (II) laboratory tests [serum creatinine, estimated glomerular filtration rate (eGFR)]; (III) imaging examinations [abdominal enhanced computed tomography (CT)/magnetic resonance imaging (MRI) to assess tumor recurrence]. Follow-up duration: 23–70 months (average: 48 months).

Ethical statement

All procedures performed in this article were in accordance with the ethical standards of the Ethics Committee of Xijing Hospital, Fourth Military Medical University, and with the Helsinki Declaration and its subsequent amendments. All enrolled patients signed the informed consent form for the use of clinical data in scientific research before surgery, agreeing to the use of their clinical data, imaging data, and pathological data in this study. A copy of the written consent is available for review by the editorial office of this journal. The data has been subjected to desensitization during use to protect patient privacy. We present this article in accordance with the AME Case Series reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-684/rc).

Case information

Table 1 summarizes the demographic, symptomatic, tumor-specific, imaging, pathological, surgical, and follow-up data of the 4 patients.

Case 1

Contrast-enhanced CT of the kidneys revealed an irregular cystic hypodense mass in the left kidney, measuring 2.0 cm × 3.0 cm × 3.4 cm, with a few septa showing enhancement, scattered calcifications, and well-defined margins. The left renal mass involved the renal pelvis (Bosniak IIF) (Figure 1A,1B).

Figure 1 The representative photomicrographs of the renal contrast-enhanced CT, pathological examination, and IHC for Case 1. (A) Representative axial image of contrast-enhanced renal CT. (B) Representative coronal image of contrast-enhanced renal CT. The orange arrow indicates the location of the left renal tumor. (C) Renal tumor, H&E staining. (D) Renal tumor, Pax-8 IHC. (E) Renal tumor, Pax-2 IHC. (F) Renal tumor, CK7 IHC. (G) Renal tumor, CAIX IHC. (H) Renal tumor, GATA3 IHC. (I) Renal tumor, p504S IHC. (J) Renal tumor, ER (SP1) IHC. (K) Renal tumor, PR (SP2) IHC. Scale bar: 100 µm. CAIX, carbonic anhydrase IX; CK7, cytokeratin 7; CT, computed tomography; ER, estrogen receptor; GATA3, GATA binding protein 3; H&E, hematoxylin and eosin; IHC, immunohistochemistry; p504S, alpha-methylacyl-CoA racemase; Pax, paired box gene; PR, progesterone receptor.

Postoperative pathology showed that (Figure 1C-1K), microscopically, local renal tissue contained fibrous cyst wall-like structures lined by a single layer of cuboidal epithelium, consistent with a mixed epithelial-stromal tumor. Immunohistochemical staining results were as follows: Pax-8 (epithelial component: positive), Pax-2 (epithelial component: positive), CK7 (epithelial component: positive), carbonic anhydrase IX (CAIX) (negative), GATA binding protein 3 (GATA3) (positive), alpha-methylacyl-CoA racemase (p504S) (negative), ER (SP1) (stromal component: positive), PR (SP2) (negative). During 70 months of postoperative follow-up, no recurrence was observed.

Case 2

Contrast-enhanced renal CT demonstrated a 4.9 cm × 2.6 cm cystic mass in the right kidney, with minimal enhancement of the solid components and internal septations (Bosniak IIF) (Figure 2A,2B).

Figure 2 The representative photomicrographs of the renal contrast-enhanced CT, pathological examination, and IHC for Case 2. (A) Representative axial image of contrast-enhanced renal CT. (B) Representative coronal image of contrast-enhanced renal CT. The orange arrow indicates the location of the right renal tumor. (C) Renal tumor, H&E staining. (D) Renal tumor, CAIX IHC. (E) Renal tumor, CD10 IHC. (F) Renal tumor, CD34 IHC. (G) Renal tumor, CK7 IHC. (H) Renal tumor, D2-40 IHC. (I) Renal tumor, ERG IHC. (J) Renal tumor, GATA3 IHC. (K) Renal tumor, p504S IHC. (L) Renal tumor, Pax-8 IHC. (M) Renal tumor, ER (SP1) IHC. (N) Renal tumor, PR (SP2) IHC. (O) Renal tumor, WT1 IHC. Scale bar: 100 µm. CAIX, carbonic anhydrase IX; CK7, cytokeratin 7; CT, computed tomography; ER, estrogen receptor; ERG, ETS-related gene; GATA3, GATA binding protein 3; H&E, hematoxylin and eosin; IHC, immunohistochemistry; p504S, alpha-methylacyl-CoA racemase; Pax, paired box gene; PR, progesterone receptor; WT1, Wilms tumor 1.

Postoperative pathology revealed that (Figure 2C-2O), microscopically, there were focal cystic changes in the renal parenchyma, with cyst walls lined by a single layer of flattened or cuboidal epithelium; ovarian-like stroma and calcifications were observed within local cyst walls, supporting a diagnosis of mixed epithelial-stromal tumor. Immunohistochemical staining results were as follows: CAIX (negative), CD10 (negative), CD34 (vascular component: positive), CK7 (positive), D2-40 (negative), ETS-related gene (ERG) (negative), GATA3 (epithelial component: positive), p504S (negative), Pax-8 (epithelial component: positive), ER (SP1) (stromal component: positive), PR (SP2) (stromal component: positive), Wilms tumor 1 (WT1) (stromal component: positive). No recurrence was noted during 46 months of follow-up.

Case 3

Contrast-enhanced renal CT showed a 3.4 cm × 4.2 cm × 4.6 cm patchy mixed-density lesion in the right kidney, with focal fat density shadows (Figure 3A,3B).

Figure 3 The representative photomicrographs of the renal contrast-enhanced CT, pathological examination, and IHC for Case 3. (A) Representative axial image of contrast-enhanced renal CT. (B) Representative coronal image of contrast-enhanced renal CT. The orange arrow indicates the location of the right renal tumor. (C) Renal tumor, H&E staining. (D) Renal tumor, CK (AE1/AE3) IHC. (E) Renal tumor, Pax-8 IHC. (F) Renal tumor, CK7 IHC. (G) Renal tumor, CD10 IHC. (H) Renal tumor, ER (SP1) IHC. (I) Renal tumor, PR (SP2) IHC. (J) Renal tumor, Vimentin IHC. Scale bar: 100 µm. CK, cytokeratin; CT, computed tomography; ER, estrogen receptor; H&E, hematoxylin and eosin; IHC, immunohistochemistry; Pax, paired box gene; PR, progesterone receptor.

Postoperative pathology identified scattered glandular structures consistent with a mixed epithelial-stromal tumor. Immunohistochemical staining results were as follows: CK (AE1/AE3) (epithelial component: positive), Pax-8 (epithelial component: positive), CK7 (epithelial component: positive), CD10 (stromal component: positive), ER (SP1) (stromal component: positive), PR (SP2) (stromal component: positive), Vimentin (both epithelial and stromal components: positive) (Figure 3C-3J). No recurrence was observed during 23 months of follow-up.

Case 4

Contrast-enhanced renal CT revealed a 1.7 cm × 1.8 cm × 2.2 cm cystic hypodense lesion in the left kidney with clear margins, containing a few strip-like septa with mild enhancement (Bosniak IIF) (Figure 4A,4B).

Figure 4 The representative photomicrographs of the renal contrast-enhanced CT, pathological examination, and IHC for Case 4. (A) Representative axial image of contrast-enhanced renal CT. (B) Representative coronal image of contrast-enhanced renal CT. The orange arrow indicates the location of the left renal tumor. (C) Renal tumor, H&E staining. (D) Renal tumor, CK7 IHC. (E) Renal tumor, CK20 IHC. (F) Renal tumor, Pax-8 IHC. (G) Renal tumor, ER (SP1) IHC. (H) Renal tumor, PR (SP2) IHC. (I) Renal tumor, WT1 IHC. (J) Renal tumor, Desmin IHC. (K) Renal tumor, SMA IHC. Scale bar: 100 µm. CK7, cytokeratin 7; CK20, cytokeratin 20; CT, computed tomography; ER, estrogen receptor; H&E, hematoxylin and eosin; IHC, immunohistochemistry; Pax, paired box gene; PR, progesterone receptor; SMA, smooth muscle actin; WT1, Wilms tumor 1.

Postoperative pathology showed that (Figure 4C-4K), microscopically, the lesion consisted of cystic cavities of varying sizes, with walls lined by a single layer of columnar epithelium and surrounding ovarian-like stroma, consistent with a mixed epithelial-stromal tumor. Immunohistochemical staining results were as follows: CK7 (epithelial component: positive), cytokeratin 20 (CK20) (negative), Pax-8 (epithelial component: positive), ER (SP1) (scattered positivity in epithelial component; positive in stromal component), PR (SP2) (stromal component: positive), WT1 (stromal component: positive), Desmin (stromal component: positive), smooth muscle actin (SMA) (stromal component: positive). No recurrence was noted during 53 months of follow-up. Additionally, the IHC findings for all 4 patients are summarized in Table 2.

Adherence and loss to follow-up

All patients fully adhered to the surgery and follow-up plan. The average intraoperative blood loss was 80 mL (range, 50–120 mL), with no intolerance such as nausea, vomiting or severe pain [visual analogue scale (VAS) pain score ≤3] postoperatively. Loss to follow-up rate was 0% (all 4 cases completed follow-up).

Complications and adverse events

No postoperative complications (e.g., bleeding, urine leakage, perirenal hematoma, infection) or unanticipated adverse events (e.g., anesthetic allergy, postoperative thrombosis) occurred in any patient; the average postoperative hospital stay was 5 days (range, 4–6 days). And all patients maintained ≥95% eGFR preservation rate at 1 month postoperatively, demonstrating the renal function-protective effect of the surgical procedure (Table 3).

Discussion

Key findings

MESTK is a rare primary renal tumor (0.1–0.3% of all primary renal tumors) with classic epidemiological characteristics of perimenopausal female predilection (male-to-female ratio, 1:10) and hormone-related pathogenesis (supported by ER/PR expression in stroma) (5). However, the 4 cases in this study showed atypia, and these cases consisted of 3 males (21, 29, 54 years old) and 1 young female (22 years old, non-perimenopausal), suggesting that its distribution may be broader than the classic understanding. However, due to the small sample size, it is not yet able to redefine the epidemiological characteristics. Clinically, all 4 cases were incidentally detected (only 1 had occasional low back pain), consistent with the literature describing MESTK as asymptomatic (6,7).

MESTK typically presents as cystic/cystic-solid masses with septations, calcifications, or mild enhancement on CT/MRI, easily misdiagnosed as cystic RCC, angiomyolipoma, or renal pelvic carcinoma (8,9). This study further identified specific misdiagnosis scenarios. Three of these cases involved Bosniak IIF lesions (cyst-dominant with septations/calcifications and minimal enhancement) that mimicked cystic RCC, one included rare fat density shadows that were confused with angiomyolipoma, and one involved the renal pelvis and resembled renal pelvic carcinoma.

Definitive diagnosis relies on “epithelial-stromal biphasic differentiation”, which is characterized by epithelial components (cuboidal/flattened/columnar epithelium) positive for Pax-8 and CK7 (excluding RCC via negative CAIX/p504S) and stromal components (ovarian-like in 2 cases) positive for ER/PR (supporting hormone-related pathogenesis), with occasional WT1/SMA/Desmin/CD10 expression (10-13).

All 4 benign cases underwent robot-assisted laparoscopic partial nephrectomy (feasible for benign tumors ≤4.9 cm, preserving renal function), consistent with nephron-sparing surgery recommendations (14,15). Robot-assisted technology improved precision and reduced complications, especially for complex locations (e.g., renal pelvis involvement) (16). No recurrence was observed during follow-up, aligning with the favorable prognosis of benign MESTK (17).

In addition, for pediatric and adolescent MESTK, a total of 9 cases have been reported, with patients aged 3–14 years and no significant gender difference (5 females and 4 males). Symptoms are mainly abdominal mass, abdominal pain, and hematuria, with occasional atypical manifestations (such as cough and vomiting) caused by tumor compression. Pathologically, it is characterized by epithelial-stromal biphasic differentiation, and treatment mainly relies on nephron-sparing surgery (18).

Strengths and limitations

Strengths

This study addressed gaps in classic epidemiological data by reporting atypical cases (males, young females), expanding understanding of MESTK’s age/gender distribution. It provided a detailed analysis of the causes of imaging misdiagnosis, particularly the rare fat density manifestation (not fully covered in prior studies), providing new insights for differential diagnosis. Additionally, it integrated clinical, imaging, pathological, and immunohistochemical data, with clear surgical rationale and complete follow-up, ensuring result reliability.

Limitations

As a retrospective case series with only four patients, the study inherently lacks statistical power and generalizability. In addition, lack of long-term (≥5 years) follow-up data, unable to fully verifying long-term recurrence or malignant transformation risks. The pathological mechanism of fat density in MESTK (mucinous degeneration vs. lipid deposition) was not definitively confirmed, requiring more cases for validation.

Comparison with similar research

Regarding epidemiology, classic literature emphasizes perimenopausal female dominance (male-to-female ratio, 1:10) (5), while this study’s 3 males and 1 young female suggest a broader gender/age spectrum, supplementing underreported atypical demographic data. For imaging, prior studies focus on cystic/cystic-solid masses with septations/calcifications (8); this study adds rare fat density as a new misdiagnosis trigger, expanding the known imaging spectrum of MESTK. In terms of treatment, similar research supports nephron-sparing surgery for benign MESTK (15); this study specifically validates the applicability of robot-assisted laparoscopic partial nephrectomy, consistent with the trend of minimally invasive renal tumor surgery. As for prognosis, findings are consistent with literature reporting that benign MESTK has a low recurrence rate (17), but this study’s follow-up duration is shorter than large-sample long-term studies, requiring further alignment with extended follow-up data.

Explanations of findings

With respect to epidemiological atypia, the small sample size may cause selection bias, but the presence of male and young female cases also implies that MESTK’s age/gender distribution was previously underestimated—classic studies may have missed atypical cases due to narrow screening criteria. Regarding asymptomatic clinical manifestations, MESTK’s benign biological behavior (slow growth, no early invasion/compression) explains its incidental detection, indicating symptom-based diagnosis is unreliable. For imaging misdiagnosis, cystic/cystic-solid features overlap with common renal tumors; rare fat density (unreported in most studies) is easily confused with angiomyolipoma, while renal pelvic involvement mimics renal pelvic carcinoma—these reflect MESTK’s imaging heterogeneity, requiring multi-modality (imaging + clinical + pathology) confirmation. In terms of pathological and immunohistochemical significance, Pax-8/CK7 positivity confirms epithelial origin, ER/PR positivity supports hormone-related pathogenesis (5), and negative CAIX/p504S effectively excludes RCC (11), forming a specific diagnostic panel for MESTK. However, current research has not yet identified molecular or receptor expression evidence beyond ER/PR that could more substantively support the hormone-related pathogenesis. For the treatment rationale, robot-assisted laparoscopic partial nephrectomy balances precision (reducing complications) and nephron preservation (protecting renal function), making it suitable for benign MESTK ≤4.9 cm; long-term follow-up is necessary due to potential (though rare) malignant transformation (17).

Implications and actions needed

Implications

Regarding clinical cognition, this study’s findings break the stereotype that MESTK occurs “exclusively in perimenopausal females”, reminding clinicians to consider MESTK in asymptomatic males and young patients to avoid missed diagnosis. For imaging diagnosis, this study highlights rare fat density and renal pelvic involvement as new misdiagnosis risks, prompting radiologists to integrate demographic features (e.g., male/young) into differential diagnosis. In terms of pathological practice, it confirms the value of “Pax-8/CK7 + ER/PR + CAIX/p504S negative” as a specific immunohistochemical panel for MESTK, improving diagnostic accuracy. As for treatment optimization, this study validates robot-assisted laparoscopic partial nephrectomy as an effective option for benign MESTK, promoting minimally invasive surgery in clinical practice.

Actions needed

Regarding clinical screening, MESTK screening should be expanded to include asymptomatic males and young adults, especially those with incidental renal masses. For the imaging workflow, correlation with clinical demographics and preoperative pathological biopsy is recommended for cystic or cystic-solid renal masses with septations, calcifications, or rare fat density. In terms of pathological detection, standardization of the detection protocol combining epithelial-stromal biphasic differentiation and the specific immunohistochemical panel is recommended for suspected MESTK cases. As for research advancement, multi-center, large-sample studies should be conducted to verify MESTK’s true age/gender spectrum and the pathological mechanism of fat density; additionally, a long-term follow-up database should be established to monitor recurrence and malignant transformation. Meanwhile, more MESTK-related molecular biology studies should be conducted to elucidate the pathogenic mechanisms and biological characteristics of MESTK at the molecular level. With respect to guideline updates, atypical demographic features, rare imaging manifestations, and robot-assisted surgical recommendations should be incorporated into MESTK clinical guidelines to standardize diagnosis and treatment.

Conclusions

In conclusion, the clinical diagnosis and treatment of MESTK require comprehensive judgment based on non-specific imaging findings, pathological features of biphasic differentiation, and immunohistochemical markers. The 4 cases in this study supplement clinical data on male and young patients, suggesting that MESTK may have individual variations in epidemiological characteristics. Based on the limited single-center data of this study, clinicians should include MESTK in the differential diagnosis when evaluating renal cystic/cystic-solid masses in asymptomatic male patients or those aged <45 years to reduce the risk of missed diagnosis. However, this conclusion requires further validation through multi-center, large-sample studies.

Acknowledgments

We thank the staff at Department of Urology of Xijing Hospital for their help in completing the study.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-684/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-684/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-684/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this article were in accordance with the ethical standards of the Ethics Committee of Xijing Hospital, Fourth Military Medical University, and with the Helsinki Declaration and its subsequent amendments. All enrolled patients signed the informed consent form for the use of clinical data in scientific research before surgery, agreeing to the use of their clinical data, imaging data, and pathological data in this study. A copy of the written consent is available for review by the editorial office of this journal. The data has been subjected to desensitization during use to protect patient privacy.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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