According to data from the Department of United States Cancer Statistics, kidney cancer has already become the third most common carcinoma of urinary cancers. In 2021, nearly 70,000 new renal-derived cancer cases were reported around the USA (1). Histologically, approximately ninety percent of kidney tumors are renal cell carcinomas (RCCs). Other remaining subtypes, including adenocarcinoma and squamous cell carcinoma, account for less than ten percent of kidney cancers (2). Renal leiomyosarcoma (LMS), first reported in 1,967, is classified as a rare and aggressive mesenchymal tumor that accounts for nearly 0.1% of all renal malignancies and is associated with early invasion and metastasis (3, 4). The published literature reveals that LMS is likely to occur in females with a mean age of 50–60 years (5). Overall, LMS is always correlated with a poor prognosis because of its high tendency for local recurrence and hematogenous spread (6).

LMS are malignant neoplasms that arise from the mesenchyme in the smooth muscle of various organs and account for approximately 10%–20% of all types of soft tissue sarcomas (STSs) (7). Renal LMS is likely to arise from intrarenal blood vessels and the renal pelvis (5). According to etiologic research, few predisposing factors for renal LMS have been recognized to date (8). Moreover, compared with other commonly diagnosed solid tumors, almost all categories of LMS exhibit a lower sensitivity, with a less than 30% overall rate of medical therapeutic reactions (9).

Currently, among all kinds of screening tools, magnetic resonance imagingmagnetic (MRI) may have the greatest potential in diagnosing LMS. According to the published literature, low apparent diffusion coefficient (ADC) values, irregular margins and intermediate/hyperintensity in T2-weighted images may be common characteristics of LMS (10). However, only histopathological examination could be the gold standard for diagnosing renal LMS. The characteristics of renal LMS are consistent with those of other locations, which exhibit cellular pleomorphism accompanied by foci of tumor necrosis. The typical microscopic features are characterized by an interlacing pattern of spindle cells and smooth muscle cells. In addition, immunohistochemistry results always reveal positive markers of muscle origin, which is consistent with the findings in our case (5).

At present, the most useful treatment for early renal LMS is surgical intervention with negative margins. Owing to the high local recurrence rate of LMS, radical nephrectomy should first be considered rather than simple partial nephrectomy unless the renal LMS has been identified as low grade through pathological examination (11). For primary renal LMS with a large tumor size, local invasive metastasis, or medium- or high-pathologic grade, radical or extended radical nephrectomy combined with perioperative and postoperative neoadjuvant treatments (including radiotherapy and chemotherapy) can be selected, which needs coordination by the surgeon and the radiation oncologist. Published studies have shown that R0 or R1 resection after neoadjuvant radiotherapy in patients diagnosed with intermediate/high-grade retroperitoneal soft tissue sarcoma (RSTS) can lead to favorable 5-year survival (12). Other studies revealed that for retroperitoneal/intra-abdominal STS where local recurrence can cause undue morbidity, radiotherapy (RT), including intensity-modulated RT and protons, might improve the comprehensive therapeutic effect. However, according to data from the STRASS trial (one of the randomized studies that evaluated neoadjuvant radiotherapy for retroperitoneal STS), whether neoadjuvant radiotherapy could become a standard application for STS treatment is still controversial (13, 14). However, although an updated meta-analysis involving 1,953 participants revealed that adjuvant chemotherapy has advantages in decreasing the overall recurrence rate of overall resectable localized STS (15), available comprehensive evaluations of neoadjuvant therapy for simple resectable renal LMS are still lacking. Neoadjuvant chemotherapy with doxorubicin and dacarbazine may have a positive effect on retroperitoneal LMS according to an unfinished prospective randomized controlled trial, but the final analysis of prognostic outcomes is still ongoing (16). In addition, chemotherapy with single agents or anthracycline-based combination regimens has been widely used among patients with unresectable or metastatic STS (17). For various histologic subtypes of unresectable or metastatic STS, gemcitabine in combination with docetaxel, vinorelbine, or dacarbazine has been confirmed to be effective. In addition, a new DNA-binding agent, trabectedin, has been shown to lead to greater progression-free survival than dacarbazine in the treatment of patients with LMS (18, 19). Moreover, according to the literature, targeted therapy could also delay the progression of LMS. A multitarget tyrosine kinase inhibitor, pazopanib, has already been demonstrated to be effective in prolonging the median progression-free survival (PFS) of patients with multiple advanced STS subtypes (20–22). However, the overall prognosis of advanced STS patients is still poor (17). Owing to the limited sample size, the comprehensive efficacy of renal LMS treatment still needs long-term research.

The progression and prognosis of renal LMS have been demonstrated to be associated with genetic factors. Studies have reported that the expression of the p16, p53, MED12, PRUNE2 and c-Myc tumor suppressor proteins might hold potential value in the prognostic assessment of renal LMS (23–25). In addition, a recent study revealed that TRPV4 may significantly promote the progression of leiomyosarcoma. TRPV4 is a nonselective cation channel that allows the passage of Ca²⁺. It contributes to the progression of LMS by directly stimulating the FAK pathway and indirectly activating the FAK/PI3K/AKT/GSK3β signaling pathway by promoting ECM1 expression and secretion, which may provide new ideas and targets for the clinical treatment of renal LMS in the future (26).

Currently, the diagnosis of various types of renal tumors primarily relies on imaging evaluations, such as contrast-enhanced CT and renal MRI. Totally, it is difficult for surgeons to distinguish between RCCs and renal LMS based solely on imaging examinations. Possible features that differentiate renal LMS from RCCs on CT scans are that LMS may expand to large sizes without lymphadenopathy, and tumor calcification rarely occurs (27). Moreover, the typical contrast-enhanced CT feature of RCCs demonstrates a “fast-in and fast-outfast-in and fast-out” pattern, which performs a marked enhancement in the arterial phase and a rapid washout in the delayed phase. By contrast, due to the less tumor vasculature, LMS may demonstrates a different venous phase with gradual enhancement of contrast agent (28, 29). Unfortunately, specific imaging characteristics has not been observed in renal LMS due to its rarity (6). Thus, image-guided percutaneous renal mass biopsy is still a significant and safe perioperative tool for renal LMS diagnosing (30). In addition, intraoperative frozen section examination may also guide the selection of surgical approaches.

Renal LMS is extremely rare and lethal. To date, the most effective treatment remains radical surgical intervention. Even if LMS has metastasized locally or to distant sites, although radiotherapy, chemotherapy or targeted therapies may delay its progression, the overall prognosis remains unfavorable. Thus, further research on renal LMS is warranted in the future.