Renal Cell Carcinoma with Fibromyomatous Stroma: A Case Report

Introduction

Renal epithelial tumors represent the seventh most common cancer in men (271 249 new cases globally) and the tenth most common in women (160 039 new cases globally), with a male to female ratio of approximately 2: 1. The mean age of patients with these tumors is 65 years. About 70% of cases are diagnosed in countries with high socioeconomic standards. Risk factors include obesity, smoking, hypertension, and acquired cystic kidney disease due to end-stage renal disease. Genetic susceptibility is estimated to account for about 3% of cases [1,2].

The most common manifestation is hematuria, and a clinical triad of costovertebral pain, palpable mass, and hematuria is seen in about 10% of patients. Due to increased use of imaging, incidental renal cell carcinoma is detected in about 40% of cases [1,3].

Different subtypes of renal epithelial tumors include clear cell renal cell carcinoma, chromophobe renal cell carcinoma, clear cell papillary renal cell carcinoma, papillary renal cell carcinoma, collecting duct carcinoma, eosinophilic solid renal cell carcinoma, and cystic renal cell carcinoma, among others [2–4].

Renal cell carcinoma with fibromyomatous stroma (RCC FMS) was added as a new category in the 2016 World Health Organization (WHO) classification as renal cell carcinoma with (angio) leiomyomatous stroma. It is a newly described rare subtype of renal cell carcinoma (<20 cases reported in total). It has a wide age range of presentations (33–77 years of age) [5,6]. Clinically, tumors usually present as solitary cortical renal masses, pain, or hematuria, with the following characteristic histologic and molecular findings: a) tumor cells with abundant clear cytoplasm; b) thick fibromuscular septae imparting multilobular appearance; and c) biallelic inactivation of the TCEB1 gene. These tumors also lack VHL mutations, hypermethylation, or loss of heterozygosity at 3p, which are characteristic of clear cell renal cell carcinoma [7–10].

Grossly, the tumor presents as a unifocal cortical mass with traversing greyish-white bands corresponding to the fibromyomatous stroma, with the tumor size usually ranging from 1.5–3.5 cm [11,12]. Microscopically, the tumor imparts a multinodular appearance due to separating bundles of smooth muscles and fibrosis. Nodules are formed of tubules, alveolar nested patterns, and solid areas, with rare occurrences of cystic and tubule-papillary features. Tumor cells almost always have clear voluminous cytoplasm, prominent cell borders, and low nuclear grade: WHO/International Society of Urological Pathology (ISUP) grade 1 or 2. These tumors demonstrate no evidence of vascular or extensive tissue invasion, nor is there evidence of necrosis or mitotic overactivity [13].

Immunohistochemical examination is of great importance to pathologists to be able to differentiate these tumors from morphologic mimics. RCC FMS tumor cells exhibit a strong and widespread positivity for CK7, AMACR, CD10, AE1/AE3, PAX-8, and CAIX, while the stroma is positive for mesenchymal markers like smooth muscle actin, caldesmon, desmin, and vimentin [13].

At the molecular level, these tumors can be classified into 2 major distinct molecular subtypes: the first type is characterized by somatic mutations in genes such as tuberous sclerosis complex 1 (TSC1), tuberous sclerosis complex 2 (TSC2), or mammalian target of rapamycin (MTOR), which involve the TSC/MTOR pathway. The second major subtype is characterized by elongin C/transcription elongation factor B (ELOC/TCEB1) mutation, which is often linked with monosomy of chromosome 8 [14,15].

Differential diagnosis includes conventional clear cell renal cell carcinoma, which is differentiated by positivity for CK7 and AMACR (both of which are usually negative in clear cell renal cell carcinoma); clear cell papillary renal cell carcinoma, which usually shows cup-shaped positivity for CAIX and no separating bundles of fibromyomatous stroma; and finally, MiT family translocation renal cell carcinoma, which shows negative staining for CK7 and CAIX [16].

RCC FMS is an indolent tumor with a good prognosis compared with some other types of kidney cancer, due to its generally less-aggressive nature. This less-aggressive nature is due to its inherent biological behavior, characterized by slower growth and no reported recurrences of metastasis. Proper treatment entails partial or radical nephrectomy [16].

This study aims to contribute to the understanding of the clinical presentation, diagnostic challenges, and implications for prognosis for RCC FMS.

Case Report

We are discussing a case involving a 59-year-old male patient who arrived at the Urology Department of Al Hada Military Hospital with hematuria. The patient’s urine analysis showed red blood cells of more than 100 per high-power field, with blood sugar, urine analysis, complete blood picture, and liver and kidney functions showing no abnormal results. Radiological examination revealed a heterogeneous, rounded mass with enhancement located at the upper pole of the right kidney, measuring approximately 2×2 cm, that appeared hypervascular as compared with the renal parenchyma. The rest of the right kidney was unremarkable, with a renal stone noted at the lower calyx measuring 5 mm (Figure 1). A partial nephrectomy was done.

The specimen, received at the laboratory of the Histopathology Unit, consisted of a partial nephrectomy specimen received in formalin. It consisted predominantly of renal capsular tissue with attached perinephric fat and a small rim of renal tissue measuring 9×9×4 cm and weighing 60 grams, with an attached, small, well-defined mass measuring 2.5×2.5×2 cm. Cut sections of the mass were greyish yellow and hemorrhagic, with areas of cystic changes and focal rubbery-to-firm greyish-white areas. The tumor was located 1.5 cm from the renal margin. Sectioning of the attached fat showed no evidence of tumor deposits.

Microscopically, the sections showed a fairly defined non-encapsulated renal neoplasm formed of nests, solid areas, and alveolar arrangement of epithelioid tumor cells, transected by thick fibromuscular bands. The tumor cells had voluminous clear cytoplasm, well-defined cell borders, and central rounded non-atypical nuclei (WHO/ISUP grade 1). Areas of cystic degeneration could also be seen. There was no evidence of lymphovascular invasion, tissue necrosis, or abundant mitotic activity. The surgical margins, as well as attached perinephric fat, were tumor-free. The surrounding renal tissue showed moderate chronic interstitial nephritis and focal global glomerular sclerosis (Figures 2, 3).

In terms of immunohistochemistry, the tumor cells showed strong cytoplasmic positivity for CK7 and moderate cytoplasmic positivity for AMACR (Figure 4). Staining for CD10 showed positive membranous staining of the tumor cells, while PAX-8 showed positive nuclear staining (Figure 5). The fibromyomatous stroma showed positive staining for smooth muscle actin, while both the tumor cells and the surrounding stroma were positive for vimentin (Figure 6).

Thus, the constellation of histological and immunohistochemical findings justified the diagnosis of RCC FMS. The pathological stage classification was pT1aNxMx according to the tumor, node, metastases (TNM) classification of Brierley et al, 8th edition [17].

Discussion

Renal cell carcinoma with (angio) leiomyomatous stroma is recognized as a unique category within the WHO classification of renal epithelial tumors published in 2016. However, there is still a debate regarding whether it constitutes a unique entity or a heterogeneous group of renal cell carcinomas with similar or overlapping morphological characteristics. Additionally, its link to tumors in the context of tuberous sclerosis complex has not been extensively studied [14]. The epidemiological profile of RCC FMS remains poorly understood due to its rarity. Nonetheless, available data suggest that it primarily impacts individuals aged 30 to 80, with a slight predominance in men [18].

We identified the clinical, radiological, pathological, and immunohistochemical characteristics of a renal neoplasm that turned out to be RCC FMS. Our case was diagnosed on January 2025 in a 59-year-old male patient who presented with hematuria; his characteristics match the reported sex and age range for that disease entity. Grossly, in contrast to the cut surface in clear cell renal cell carcinoma, which shows golden-yellow areas showing hemorrhage or necrosis, the cut surface of RCC FMS is characterized by solid white tissue with a “leiomyoma-like” appearance [19]. The same macroscopic finding was observed in our case.

Microscopically, renal cell carcinoma tumors are composed of 2 components: epithelial and fibromyomatous tissues. The former is formed of tubules, nodules, and papillary structures, which are lined by cells that are clear to moderately eosinophilic, with cytoplasm that is abundant. The grade of the nuclei is usually 1–2, in accordance with the WHO/ISUP histological grading system for renal cell carcinomas [20]. In our case, the tumor was predominantly formed of nests and tubules, with the epithelial cells having exclusively clear cytoplasm. The stromal component is polyclonal and reactive, and is characterized by leiomyomatous or fibromyomatous appearance [21]. This type of non-neoplastic and reactive stroma, and similar stromal features, were observed in our case.

At the immunohistochemical level, RCC FMS tumor epithelial cells are positive for pan-cytokeratin, CK7, epithelial membrane antigen (EMA), CD10, and PAX8, while smooth muscle actin and desmin exhibit positivity within the stromal component [8]. Our tumor showed positivity of epithelial cells for CK7, AMACR, CD10, and PAX-8, while the stromal component was positive for smooth muscle actin and vimentin.

At the molecular level, these types of tumors, according to the study performed by Shah et al, can be classified into 2 distinct main molecular subtypes: the first type is characterized by somatic mutations in genes such as TSC1, TSC2, or MTOR, which are part of the TSC/MTOR pathway. The second type shows mutation in ELOC/TCEB1, which is often linked with monosomy of chromosome 8 [14]. Previous studies have found no mutation of the VHL gene, nor trisomy 7, nor trisomy 17, in both subgroups [22].

Our patient was followed up until July 2025, and showed no evidence of relapse or metastases.

Limitations

Molecular testing for renal epithelial tumors may not be uniformly available across all pathology laboratories; consequently, it is essential to meticulously consider the histological and immunohistochemical findings associated with renal tumors.

Conclusions

This case report presents evidence that supports recognizing RCC FMS as a new subtype of renal cell carcinoma, characterized by unique morphologic, immunohistochemical, and molecular features that set it apart from more prevalent types of renal epithelial tumors, such as clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. Due to its rarity and good prognosis compared with other renal tumors, attention should be paid when dealing with renal epithelial tumors that exhibit the usual features of other epithelial tumors but have abundant fibromyomatous stroma. In addition, molecular testing can be attempted to confirm the histologic nature of the tumor.