The imaging features observed in this case align with previously reported characteristics of PRNRP and RCC-FMS but also illustrate the complexities of differentiating these entities from more common renal tumors. The right kidney mass exhibited typical PRNRP findings, including small size, exophytic growth, heterogeneous enhancement, and cystic components with high pre-contrast attenuation (4, 5). These features, while suggestive of PRNRP, overlap with other hypovascular tumors such as fat-poor angiomyolipoma or papillary renal cell carcinoma (6, 7). The left kidney mass demonstrated the hallmark stromal heterogeneity of RCC-FMS, with mixed attenuation on CT and peripheral/septal enhancement, mimicking cystic or necrotic changes seen in clear cell RCC (8, 9). The absence of macroscopic fat helped exclude AML, while the lack of marked hypervascularity distinguished it from conventional clear cell RCC.

The coexistence of these two distinct tumors in a single patient further complicated the preoperative diagnosis (10). PRNRP’s indolent behavior and RCC-FMS’s variable clinical course necessitated careful imaging-pathologic correlation to avoid misclassification and overtreatment. This case emphasizes the importance of considering rare tumor subtypes in the differential diagnosis of renal masses, particularly when imaging features deviate from typical patterns.

Histopathological and immunohistochemical analyses were instrumental in establishing the definitive diagnoses of both tumors. The right renal tumor exhibited the classic morphological features of PRNRP, including papillary architecture, eosinophilic cytoplasm, and the pathognomonic apical nuclear polarity. Immunohistochemically, the tumor demonstrated a characteristic profile with strong and diffuse positivity for CK7 and GATA3, focal positivity for CK20 and TFE3, and negativity for AMACR, CA IX, and CD10. The tabulated data from 385 cases revealed that PRNRP is defined by near-constant expression of GATA3 (98.96%), CK7 (97.18%), and EMA (100%), while typically showing low rates of positivity for AMACR (41.05%), CD10 (29.83%), and Vimentin (11.92%). The Ki-67 proliferation index was low at approximately 2%. Furthermore, molecular analysis confirmed a KRAS exon 2 mutation, which is a molecular hallmark of PRNRP, being present in 82.97% (268/323) of reported cases (Table 1), while no mutations were detected in NRAS or BRAF V600.

In contrast, the left renal tumor was diagnosed as RCC-FMS, histologically characterized by nests of clear cells embedded within a prominent fibromyomatous stroma. Its immunohistochemical profile was distinct, showing positivity for PAX-8, CA IX, and CD10, partial positivity for CK7, and negativity for AMACR and CD117. The Ki-67 index was also low at approximately 3%. Although specific molecular testing for mTOR pathway genes was not performed in our case, the existing literature indicates frequent alterations in the TSC/MTOR pathway in RCC-FMS (Table 2), which is characterized by frequent expression of CK7 (100%), CD10 (87.5%), Vimentin (100%), and CA IX (100%) in the limited number of cases with available data.

While PRNRP, RCCFMS, and adrenal adenomas are distinct entities, their co-occurrence in this patient—who also has a history of an adrenal adenoma surgically removed some time ago—raises the possibility of underlying connections, though the temporal distance may make a direct relationship less certain. Several hypotheses could be considered, such as a shared embryonic origin where localized developmental anomalies or dysregulated signaling pathways like Wnt/β-catenin might simultaneously affect adrenal and renal tissues (38). Alternatively, a paracrine influence from the adrenal adenoma, potentially secreting unrecognized growth factors such as IGF or VEGF, could foster a microenvironment conducive to renal tumor development (39). A common genetic susceptibility, whether germline or somatic, might also lower the threshold for tumor formation in both organs (40). Nevertheless, the possibility of coincidence cannot be ruled out.

The concurrent diagnosis of a KRAS-driven PRNRP and a TSC/mTOR pathway-associated RCC-FMS, accompanied by an adrenal adenoma, forms a distinctive clinical scenario. This rare constellation of tumors raises important questions regarding potential common pathogenic mechanisms. Although their well-defined molecular profiles confirm these as separate entities, their simultaneous emergence points toward a possible shared systemic predisposition. Comprehensive molecular analysis may determine whether their coexistence signifies a meaningful pathogenic link or a remarkable coincidence, potentially yielding new insights into multi-organ tumorigenesis and enriching our understanding of such complex presentations.

The indolent behavior of PRNRP and the generally favorable prognosis of RCC-FMS guided the decision for nephron-sparing surgery, which is curative in most cases. This approach aligns with current recommendations for small, localized renal tumors with low malignant potential.

For PRNRP, the primary treatment is surgical resection. Partial nephrectomy is the preferred approach for most small tumors (typically <4 cm), as it completely removes the tumor while preserving healthy renal tissue and minimizing the risk of postoperative renal insufficiency (29, 2). In cases of larger or more complex tumors, or when partial nephrectomy is not feasible, radical nephrectomy may be considered. For elderly patients, those with significant comorbidities, or limited life expectancy, active surveillance with regular imaging may be appropriate, especially for small, slow-growing tumors. Ablation therapies (e.g., radiofrequency or cryoablation) represent alternatives for patients who are unfit for or decline surgery (31). For advanced or metastatic PRNRP, targeted therapy and immunotherapy may be considered, although specific agents targeting common mutations like KRAS are not yet established.

For RCC-FMS, surgical resection remains the primary and often curative treatment. Partial nephrectomy is suitable for smaller, favorably located tumors, aligning with its typically indolent course, while radical nephrectomy may be required for larger or complex lesions (9). Active surveillance is a viable option for small tumors, elderly patients, or those with significant comorbidities, particularly when biopsy confirms low-grade, indolent behavior. Given the association of RCC-FMS with alterations in the TSC/MTOR pathway, mTOR inhibitors (e.g., everolimus, temsirolimus) represent a potential targeted therapeutic option for advanced, metastatic, or inoperable cases, though clinical data remain limited (2). Accurate diagnosis is crucial, as RCC-FMS must be distinguished from other renal cell carcinomas (e.g., clear cell RCC, clear cell papillary RCC, ELOC-mutated RCC) with different management strategies and prognoses.

However, the presence of bilateral synchronous tumors necessitated individualized risk stratification: PRNRP’s negligible metastatic risk justified conservative resection, while RCC-FMS’s rare aggressive potential warranted close surveillance. This case also highlights the importance of multidisciplinary collaboration. Radiologists, urologists, and pathologists must work together to integrate imaging findings, histopathology, and molecular data to optimize diagnostic accuracy and treatment planning. For instance, intraoperative frozen section analysis could aid in confirming tumor margins and subtypes, ensuring appropriate surgical extent.

The rarity of these tumors limits the generalizability of findings, and the absence of long-term follow-up precludes definitive conclusions about outcomes. Prospective multicenter studies and larger cohorts are needed to refine diagnostic criteria and establish evidence-based management guidelines. Advanced imaging techniques, such as multiparametric MRI or radiomics, may further improve preoperative differentiation of rare renal neoplasms.