Abdominal computed tomography (CT) with contrast enhancement and three-dimensional reconstruction revealed a slightly hypodense lesion with localized calcification in the upper pole of the left renal parenchyma. The lesion measured approximately 6.9 cm × 5.7 cm × 5.6 cm (Figure 1A) and extended beyond the renal contour. The mass was well-circumscribed, roundish, and encapsulated, with no evidence of peripheral invasion. Scattered calcifications were noted. Contrast-enhanced imaging demonstrated predominantly marginal enhancement with a “centripetal filling” pattern, persistent enhancement during the medullary phase, and heterogeneous enhancement during the cortical phase, with the lesion appearing less dense than the adjacent renal parenchyma (Figures 1B–G). “Centripetal filling” is defined as a dynamic contrast enhancement pattern in which contrast agent gradually spreads from the periphery of the tumor toward the center in multiple CT scans.

The right kidney showed no significant abnormalities in position, size, or morphology, and no focal density abnormalities or abnormal enhancement were observed. The bilateral renal pelvises, calyces, and ureters were not dilated. The bladder was adequately filled, with no abnormalities detected. No significant lymphadenopathy was noted in the abdomen or retroperitoneum. Although RCC was highly suspected, the patient’s blood and urine routine tests were normal, and serum tumor markers showed no abnormalities. Furthermore, imaging indicated that the mass was encapsulated with no evidence of peripheral invasion. Considering the patient’s clinical history, we determined that a radical nephrectomy could lead to excessive loss of renal tissue. As a result, a partial nephrectomy was performed.

Macroscopically, the tumor appeared as a solitary, well-demarcated, solid mass with an intact capsule, clearly separated from the surrounding renal tissue. The cut surface exhibited a grayish-red and grayish-white appearance (Figure 2A). Microscopically, the tumor was well-demarcated from the surrounding tissue, with a thick fibrous capsule evident in some areas. The tumor consisted of a rich capillary network interspersed with stromal cells that had abundant, lightly eosinophilic, or clear cytoplasm. These cells showed mild cytological atypia, with some containing vacuoles of varying sizes, and mitotic figures were rare. The tumor stroma displayed extensive edema, myxoid changes, fibrosis, and focal chondroid metaplasia and calcification. Dilated, thick-walled vessels were observed surrounding the tumor (Figures 2B–D).

Immunohistochemical results showed that cytokeratin-P (CK-P) was negative, smooth muscle actin (SMA) was negative, epithelial membrane antigen (EMA) was negative, Vimentin was strongly positive in stromal cells, S-100 was partially positive in stromal cells, HMB45 was negative, CD34 was positive in vascular endothelial cells, and Ki-67 was approximately 2% positive. Additional immunohistochemical staining revealed: Vimentin was positive, PAX-8 was weakly positive, D2-40 was negative, Calretinin (CR) was negative, Melan-A was negative, and Ki-67 remained approximately 2% positive. Stromal cells were positive for Inhibin-α and Neuron-Specific Enolase (NSE) was weakly positive, while vascular endothelial cells were positive for CD31 and ERG (Figures 3A–D).

VHL disease is associated with mutations in the VHL tumor suppressor gene located on chromosome 3p, and HB is considered a hallmark feature of this condition. The clinical diagnosis of VHL disease is based on the presence of HBs in the CNS or retina, the existence of a typical VHL-associated tumor (such as ccRCC, pheochromocytoma, neuroendocrine tumors, etc.), or a family history of the disease. If these criteria are not met, the condition is classified as sporadic (Karabagli et al., 2007). As such, the patient in this case was diagnosed with sporadic RH.

Regarding the pathogenesis of VHL, Knudson et al. proposed that the development of VHL-associated tumors results from a germline monoallelic defect in the patient, combined with somatic mutations induced by other factors (Knudson, 1991; Kondo and Kaelin, 2001). Current clinical genetic testing methods for detecting germline mutations in families with VHL disease have an accuracy rate of nearly 100%. Therefore, genetic testing is strongly recommended for patients diagnosed with HB, as it plays a crucial role in prognosis, treatment planning, and may also provide valuable information for the patient’s immediate family members (Bisceglia et al., 2018).

A study reported chromosomal abnormalities in 10 cases of sporadic cerebellar HB without VHL disease using comparative genomic hybridization. The abnormalities included losses in chromosomes 3 (70%), 6 (50%), 9 (30%), and 18q (30%), as well as gains in chromosome 19 (30%) (Sprenger et al., 2001). Another study observed chromosomal abnormalities in 7 out of 22 cases of HBs, both with and without VHL (Lemeta et al., 2002). However, in existing reports on RH, no significant abnormalities were detected in 10 tumor patients using polymerase chain reaction for VHL gene exons, loss of heterozygosity on chromosome 3p, fluorescence in situ hybridization for chromosome 3p deletion, or next-generation sequencing (Wang et al., 2022). Furthermore, patients who did not undergo genetic testing were not reported to have a family history of VHL or related clinical symptoms (details in Table 1). Therefore, we conclude that there is currently insufficient evidence to support the hypothesis that RH is associated with VHL.

Imaging plays an increasingly important role in diagnosing renal masses and monitoring therapeutic outcomes. CT is the preferred modality for evaluating renal tumors, while magnetic resonance imaging (MRI) and ultrasonography are typically reserved for patients with renal insufficiency or contrast sensitivity. Additionally, percutaneous biopsy can be considered part of the imaging-based evaluation for renal masses, particularly in cases with uncertain etiology, as it provides additional diagnostic information.

In this case, CT revealed a heterogeneously enhanced, roundish solid mass with scattered calcifications, predominantly located along its periphery. While Nonaka et al. previously described calcifications localized within cystic spaces, the calcifications in our case were primarily concentrated at the tumor margins (Nonaka et al., 2007). Contrast-enhanced imaging demonstrated marked enhancement of the peripheral solid component (maximum CT value ∼230 HU; abdominal aorta CT value ∼248 HU), with cortical phase enhancement approaching aortic CT values (Figure 1B). During the medullary phase (CT value ∼160 HU) and excretory phase (CT value ∼146 HU), enhancement diminished slightly (Figures 1C–D). The central hypodense area on non-contrast scans exhibited mild delayed enhancement during cortical, medullary, and excretory phases (CT values ∼37, 42, and 69 HU, respectively), demonstrating progressive “centripetal filling” (Figures 1E–G).

Based on existing literature, the imaging characteristics of RH can be summarized as follows: 1. RH shows no significant sex or renal laterality predilection and predominantly occurs at the upper or lower poles of the kidney (see Table 1) (Nonaka et al., 2007). 2. RH is a benign tumor, typically well-encapsulated, roundish, and sharply marginated. Larger tumors may protrude outward or compress the renal pelvis/calyces inward but lack invasion or metastatic features (He et al., 2021). 3. On CT, RH may present with hyper-, hypo-, or isodense internal components. Some tumors may exhibit cystic degeneration, necrosis, calcifications, or stromal edema. 4. MRI reports on RH remain limited. Current studies suggest T2-weighted hyperintensity resembling hepatic cavernous hemangiomas. Although MRI is a key tool for diagnosing HBs in other locations (e.g., the spine), its application in RH remains underutilized (Capitanio and Montorsi, 2016). He et al. observed significant peripheral enhancement during the cortical phase, “progressive persistent enhancement” during medullary and excretory phases, and a “centripetal filling pattern,” occasionally progressing to complete filling (He et al., 2021).

This enhancement pattern has not been reported in other renal tumors and aligns with our findings, suggesting it may be a distinctive imaging feature of RH. The “centripetal filling” phenomenon may be attributed to the tumor’s rich capillary network, which leads to cortical-phase CT values comparable to those of the adjacent aorta. Dynamic or multiphase scans reveal enhancement patterns resembling cavernous hemangiomas, likely due to slow intratumoral blood flow and prolonged contrast retention (Figures 4A,B). The heterogeneous enhancement could be related to recurrent intratumoral hemorrhage and fibrosis. However, due to the limited number of detailed imaging reports on RH, larger multicenter studies are required to validate these findings.

Clear cell and papillary RCCs account for 90% of solid renal malignancies, with ccRCC representing approximately 70% (Srigley et al., 2013). Malignant renal tumors are often accompanied by clinical signs such as flank pain, hematuria, lymph node or distant metastases, and renal pelvic or calyceal invasion, which help differentiate them from RH. CCRCC typically appears on CT and MRI as a solitary, roundish, solid or cystic intrarenal mass, occasionally lobulated, and often containing calcifications. Contrast-enhanced imaging reveals marked heterogeneous enhancement with prominent arterial phase enhancement. Although imaging reports for RH are limited, some features of RCC overlap with those of RH, complicating the differentiation between the two.

A key distinction is the “wash-in, wash-out” enhancement pattern observed in ccRCC (Figures 5A–C). On MRI, ccRCC typically exhibits iso-/hypointense T1 signals, hyperintense or mixed T2 signals, and a hypointense pseudocapsule (Nazari et al., 2020; Ishigami et al., 2014). Papillary RCC often presents as a homogeneous solid mass with well-defined margins, distorting renal contours. It generally shows low vascular density, frequent cystic degeneration or hemorrhage, and rare calcifications. Unenhanced imaging may mimic benign lesions, and some cases demonstrate minimal CT enhancement but marked MRI enhancement, with hypointense T2-weighted signals (Mendhiratta et al., 2021; Couvidat et al., 2014; Walker et al., 2019).

Contrast-enhanced ultrasonography (CEUS) is widely used for renal mass characterization. CCRCC usually displays early hyperenhancement, late washout, pseudocapsule presence, and heterogeneous enhancement that intensifies with tumor size. Papillary RCC often shows slow wash-in, rapid wash-out, homogeneous hypoenhancement, and visible pseudocapsules (Wei et al., 2019; Xue et al., 2015; Gulati et al., 2015). In addition, PET/CT, with its high sensitivity and precise localization, is increasingly used for disease imaging based on molecular and metabolic tumor characteristics. While reported in VHL disease-associated RCC, ccRCC, pheochromocytoma, and multiorgan involvement, no studies have yet explored its utility in RH (Oh et al., 2012; Rizzo et al., 2023; Kaji et al., 2007).

Renal biopsy is a crucial tool for diagnosing focal renal lesions and guiding treatment strategies. It exhibits high sensitivity (97.5%) and specificity (96.2%) for diagnosing malignancies, with a diagnostic accuracy exceeding 90%, showing strong concordance with nephrectomy results. However, statistics indicate that up to one-fifth of renal masses smaller than 4 cm resected by nephrectomy are benign. The underutilization of renal biopsy contributes to approximately 6,000 unnecessary nephrectomies annually (Campbell et al., 2017; Lim et al., 2019; Patel et al., 2018).

According to existing case reports of RH, including this case, a total of 32 cases have been documented. Of these, 8 patients underwent partial nephrectomy, 13 received radical nephrectomy, 1 underwent radiofrequency ablation, and the remaining cases lacked specified treatment details. Notably, only 1 patient underwent renal biopsy (see Table 1).

At high magnification, RH typically shows a well-defined border with an abundant capillary network and stromal cells, which may exhibit marked pleomorphism. Caution is necessary when differentiating RH from RCC with a distinct vascular system, AML, adrenocortical carcinoma, and pheochromocytoma. CCRCC of the kidney is a key factor in the survival of patients with VHL disease and is a malignant tumor in its own right (Maher et al., 2011; Zhou et al., 2019).

Macroscopically, ccRCC typically exhibits a golden-yellow hue due to its high lipid content. Microscopically, it is characterized by a distinctive microvascular network and nests of neoplastic cells with clear cytoplasm. The recent reporting of ccRCC cases displaying RH-like features has introduced a new challenge in differentiating these two entities (Lei et al., 2023; Setia et al., 2020). Some scholars have raised concerns about whether RH represents a true RH distinct from ccRCC, or if it merely reflects a spectrum of diffuse hemangioblastoma-like differentiation within ccRCC (Montironi et al., 2014).

Immunohistochemistry plays a crucial role in resolving diagnostic challenges. Inhibin-α, S100, and NSE are reliable markers for confirming RH, while PAX8, PAX2, CD10, and EMA are typically consistently positive in ccRCC. However, there have been reports of RH cases exhibiting positivity for PAX8, PAX2, CD10, and EMA. Additionally, scholars suggest that hemangioblastoma-like components in ccRCC may also express inhibin-α. Therefore, when the diagnosis is challenging based on morphology and the initial immunoprofile, additional immunohistochemical staining for pan-cytokeratin, S100, NSE, and inhibin-α is essential (Zhao et al., 2013; Yin et al., 2012).

PAX8 and PAX2 are cell lineage-specific transcription factors involved in the regulation of important molecular pathways in kidney development and are expressed in many renal diseases such as RCC (Wang et al., 2022; Chi and Epstein, 2002). CD10, on the other hand, is highly suggestive of a proximal tubular cell origin and is considered a marker for clear cell and papillary RCC (Yin et al., 2012). Thus, Zhao et al. proposed that differences in the immunophenotype of HBs outside the CNS correlate with differences in site of origin (Zhao et al., 2013; Yin et al., 2012). Research indicates that CNS HBs exhibit consistent expression of glucose transporter 1 (GLUT1) in their vascular endothelial cells, mirroring the GLUT1 expression pattern observed in normal CNS vasculature. In contrast, RHs demonstrate a lack of GLUT1 expression in their endothelial cells, aligning instead with the GLUT1-negative profile characteristic of normal peripheral blood vessels (Yin et al., 2012; Lee et al., 2024).

Therefore, based on the available reports, we believe that the appearance of changes in the RH immune profile is associated with heterogeneous origins or differentiation. Microscopically, epithelioid AML may also exhibit large, thick-walled vessels and polygonal cells. However, the presence of “spidery” cytoplasm and frequent perivascular hyalinization may help differentiate it from RH. Additionally, HMB45 and MelanA are usually positive in AML, which can further aid in distinguishing it from RH (Nese et al., 2011).

Patients with RH often present clinically as asymptomatic or with abdominal pain and hematuria. In such cases, adrenocortical carcinoma and the rarer pheochromocytoma can be distinguished by their more specific clinical manifestations. Adrenocortical carcinoma often presents with signs and symptoms of hormone overdose, while pheochromocytoma is characterized by persistent or paroxysmal hypertension, often accompanied by headaches and palpitations. These conditions can be differentiated from RH in conjunction with other laboratory tests (Else et al., 2014). Additionally, there have been several reports of cases in which rhabdomyosiform features have been observed microscopically. This necessitates a strict differentiation between RH and other tumors with rhabdomyosiform features, such as RCC with rhabdomyosiform features, malignant rhabdomyomas (e.g., AML, HMB45+ and MelanA+), ccRCC with rhabdomyosiform features (PAX8+, PAX2+, and CD10⁺), and pheochromocytomas (synaptophysin+, chromogranin+, and α-inhibin+), among others (Oberhammer et al., 2019; Xu et al., 2017). Since different tumors can present with multiple histological manifestations due to morphological variability, it is essential to accumulate comprehensive RH case reports. Accurate histologic/pathologic results are crucial for improving the accuracy of renal biopsy, standardizing the process of RH diagnosis and treatment, and reducing overtreatment (Table 2).