ABSTRACT
Purpose:
This study aims to assess the impact of unclassified renal cell carcinoma (uRCC) on clinical, pathological, and oncological outcomes compared with clear cell renal cell carcinoma (ccRCC).
Materials and Methods:
We analyzed the data of 48 uRCC and 688 ccRCC cases, collected from a histopathological database at a single center from July 2011 to August 2019. uRCC cases were confirmed according to the 2016 World Health Organization classification. Baseline characteristics, clinical findings, and oncological outcomes were compared between the groups.
Results:
Patients with uRCC exhibited the same clinical symptoms as ccRCC patients, a higher prevalence of lymphadenopathy (31.2% vs. 15.8%, P < 0.01), and greater sarcomatoid/rhabdoid differentiation on histology (12.5% vs. 5%, P = 0.03) compared to ccRCC patients. Although there was no difference regarding overall metastasis at initial diagnosis, distant lymphadenopathy (16.7% vs. 7.8%, P = 0.04) and liver metastasis (8.9% vs. 2.8%, P = 0.04) were more common in the uRCC group. The two groups had similar high-grade (HG) frequency on histology (62.5% for uRCC vs. 53.7% for ccRCC, P = 0.23). The estimated recurrence-free survival at 48 months was 94.3% for uRCC, 92.5% for low-grade (LG) ccRCC (P = 0.91), and 66.5% for HG ccRCC (P < 0.01). The estimated overall survival at 48 months was 66.1% for uRCC, 87.4% for LG ccRCC (P = 0.75), and 63.4% for HG ccRCC (P < 0.01).
Conclusion:
Our study demonstrates that uRCC has significantly higher rates of lymphadenopathy, sarcomatoid differentiation, and liver metastasis compared to ccRCC. Despite these differences, uRCC presents with similar clinical symptoms and histological grade as ccRCC. Furthermore, uRCC exhibits a recurrence rate comparable to LG ccRCC and an overall survival rate similar to HG ccRCC.
INTRODUCTION
Histological determination is extremely important because of its prognostic and therapeutic implications in kidney tumors. Knowledge in this field has been evolving, with multiple new diagnostic categories added to the mainstream classification system. According to the World Health Organization (WHO) classification on urinary and male genital tumors,[1] renal cell carcinoma (RCC) is the most common type of kidney tumor, comprising over 90%,[2] and includes more than 20 RCC histological subtypes. Clear cell RCC (ccRCC) is the most common RCC subtype, representing approximately 75% of cases. It is noteworthy that the differences among these histological types are reflected in prognosis, therapeutic targets, and cancer-specific survival.[2] Notwithstanding the intense classification effort, a significant portion of RCC cases do not fit in any of the recognized histotypes and remain unclassified RCC (uRCC).[1,2]
Unclassified RCC (uRCC) is a rare and heterogeneous histological subtype of RCC, comprising approximately 2%–6% of all RCC cases.[3,4] The classification includes mixed patterns of more than one recognized subtype, unclassified oncocytic neoplasms, or tumors with pure sarcomatoid histology among other less common findings such as unrecognizable cell types. Due to its diverse histopathological features, the clinical presentation and oncological outcomes of uRCC are still limited and controversial.
We aimed to evaluate the impact of histopathological findings of uRCC on oncological outcomes compared to ccRCC.[1]
MATERIALS AND METHODS
We conducted a retrospective study of patients who underwent radical or partial nephrectomy for kidney cancer between June 2011 and August 2019. Cases were identified from a histopathological database, and only uRCC and ccRCC were included while biopsies, nononcologic cases, or other histological subtypes were excluded.
Surgeries were performed by multiple surgeons at a single institution, and both open and videolaparoscopic cases were included.
All uRCC slides were initially assessed by a random pathologist (general or uropathologist). At the completion of the study, these slides were reviewed by an experienced uropathologist with over 10 years of experience. This review was conducted according to the latest WHO classification system (2016).[1] Cases with unavailable pathology slides or those reclassified as other histological subtypes were excluded. For the confirmation and classification of cases, both histopathological features and immunohistochemistry (IHC) were utilized. Cases were classified using an IHC panel tailored to each case based on its histopathological aspects. In addition, in situ fluorescence hybridization was used when necessary. The IHC markers employed included PAX-8, CK7, CK20, CD117, CD10, AMACR, SDHB, FH, Melan-A, HMB-45, and SMA.
Data collection
Demographic and clinical characteristics were collected, including age, body mass index, race, Charlson Comorbidity Index, tumor side, symptoms, computed tomography (CT) tumor size, preoperative creatinine level, lymphadenopathy (regional lymphadenopathy was addressed as “lymphadenopathy,’ while distant lymphadenopathy was classified as “metastasis” according to the Tumor, Node, Metastasis (TNM) 8th edition), presence of metastasis, and type of surgery, as well as pathology data, including Fuhrman grade, tumor size, pT3 characteristics, sarcomatoid/rhabdoid differentiation, necrosis, tumor thrombus, margin status, positive nodes, pT, pN, and pM. Postoperative outcomes, such as 6-month creatinine level, disease recurrence, and death, were also collected. Fuhrman Grades I and II were merged as low grade (LG), and Grades III and IV were merged as high grade (HG) for survival analysis. All patients, regardless of whether they had ccRCC or uRCC, followed the same institutional follow-up schedule. Follow-up assessments included regular clinical evaluations, imaging studies, and laboratory tests conducted at consistent intervals postsurgery.
The authors confirm the availability of, and access to, all original data reported in this study.
Sample size consideration
In this study, we did not perform a formal sample size calculation. Instead, we included all eligible cases of uRCC and ccRCC that were available in our histopathological database within the time frame from June 2011 to August 2019. This approach was intended to maximize the representation of both uRCC and ccRCC cases, given the rarity of uRCC and the importance of capturing a comprehensive cohort for comparison.
Statistical analysis
Fisher’s exact test was used to analyze categorical variables, which were described with frequencies and percentages. Continuous variables were described with mean and standard deviation and analyzed with the Wilcoxon signed-rank test. The Kaplan–Meier estimator was used for time-to-event analysis of disease recurrence and overall survival, and the log-rank test was used to compare survival between the groups. We used Cox proportional hazards regression for multivariate regression models and included all statistically and clinically significant results. We compared the uRCC group to the ccRCC group and to the LG or HG ccRCC groups for survival analysis. All tests were two-sided, and statistical significance was considered at P < 0.05.
RESULTS
Study population
After querying the histopathological database for kidney cancer in the selected time frame, we identified 688 ccRCC cases and 83 uRCC cases, while 617 other renal cancer subtypes were excluded. After pathology review, patients whose cancer was reclassified and those without available slides were dismissed, remaining 48 uRCC cases [Figure 1].
Figure 1.
Case selection (original). uRCC: Unclassified renal cell carcinoma, ccRCC: Clear cell renal cell carcinoma
The uRCC and ccRCC groups were comparable in age, body mass index, race, Charlson comorbidity Index, preoperative symptoms, preoperative serum creatinine level, side of tumor, tumor size, type of surgery (radical or partial nephrectomy), and presence of tumor thrombus [Table 1]. Lymphadenopathy identified on preoperative CT scan was more frequent in the uRCC than ccRCC group (31.2% vs. 15.8%, P < 0.01). Despite no significant differences in the presence of metastasis at diagnosis or symptoms related to metastasis, the uRCC group had a higher incidence of liver metastasis than the ccRCC group (8.9% vs. 2.8%, P = 0.04).
Table 1.
Patient’s demographics and preoperative characteristics
| Variable | ccRCC (n=688), n (%) | uRCC (n=48), n (%) | P |
|---|---|---|---|
| Age (years), mean±SD | 60.4±11.4 | 62.4±12.5 | 0.12 |
| BMI (kg/m2), mean±SD | 28.8±6.4 | 27.3±5.4 | 0.03 |
| Gender | |||
| Female | 264 (38.5) | 19 (40.4) | 0.87 |
| Male | 422 (61.5) | 28 (59.6) | |
| Side | |||
| Right | 343 (49.85) | 25 (52.1) | 0.88 |
| Type of surgery | |||
| Partial nephrectomy | 328 (47.7) | 23 (47.9) | 1 |
| Radical nephrectomy | 360 (52.3) | 25 (52.1) | |
| Charlson score, mean±SD | 2.5±2.0 | 2.6±1.5 | 0.44 |
| Race | |||
| Caucasian | 513 (74.5) | 37 (77.1) | 0.43 |
| African American | 167 (24.2) | 10 (20.8) | |
| Other | 8 (1.1) | 1 (2.1) | |
| Symptoms | |||
| Asymptomatic | 383 (56.0) | 27 (56.3) | 1 |
| Pain | 164 (24.0) | 17 (35.4) | 0.08 |
| Hematuria | 153 (22.3) | 5 (10.4) | 0.06 |
| Weight loss | 96 (14.0) | 5 (10.4) | 0.66 |
| Palpable mass | 55 (8.1) | 5 (10.4) | 0.58 |
| Serum creatinine (mg/dL), mean±SD | 1.1±0.6 | 1.1±0.4 | 0.35 |
| Tumor size (CT) (cm) | |||
| Mean±SD | 6.9±4.1 | 7.6±4.7 | 0.59 |
| ≤7 | 415 (60.3) | 29 (60.4) | |
| >7 | 273 (39.7) | 19 (39.6) | |
| Lymphadenopathy | 109 (15.8) | 15 (31.2) | <0.01 |
| Metastasis | 114 (16.5) | 10 (20.8) | 0.43 |
| Paraneoplastic symptoms | 10 (1.4) | 0 | 1 |
| Metastatic symptoms | 27 (3.9) | 5 (10.9) | 0.05 |
| Metastasis sites | |||
| Distant lymphadenopathy | 54 (7.8) | 8 (16.7) | 0.04 |
| Liver | 21 (3.1) | 4 (8.3) | 0.04 |
| Lung | 72 (10.5) | 6 (12.5) | 0.47 |
| Adrenal | 25 (3.6) | 2 (4.2) | 0.79 |
| Bone | 26 (3.8) | 2 (4.2) | 0.85 |
| Central nervous system | 5 (0.7) | 1 (2.1) | 0.38 |
| Tumor thrombus | 72 (10.4) | 2 (4.2) | 0.15 |
BMI=Body mass index, CT=Computed tomography, SD=Standard deviation, ccRCC=Clear cell renal cell carcinoma, uRCC=Unclassified renal cell carcinoma
Aggressiveness and tumor characteristics
In our cohort, advanced-stage tumors (≥T3) were observed in 46.8% of ccRCC cases and 39.6% of uRCC cases. Adjacent organ involvement, classified as T4, was more prevalent in uRCC cases (4.2%) compared to ccRCC (1.8%).
Metastasis characteristics
Metastasis was a significant concern, with total metastasis rates of 16.5% for ccRCC and 20.8% for uRCC. Distinct patterns were observed between the two groups. Distant lymphadenopathy, classified as metastasis, was more prevalent in uRCC cases at 16.7% compared to 7.8% in ccRCC cases (P = 0.04). The uRCC group also had a higher incidence of liver metastasis at 8.3%, compared to 3.1% in the ccRCC group (P = 0.04). The most common metastatic sites in uRCC were distant lymphadenopathy (16.7%), lung metastasis (12.5%), and liver metastasis (8.3%). Lung metastasis and other less common sites, including the adrenal glands, bones, and the central nervous system, did not show significant differences [Table 1].
Management and ancillary procedures
Metastasis-directed therapy was undertaken in 5.1% (35/688) of ccRCC and 6.3% (3/48) of uRCC patients. Specifically, metastasectomy was performed in 4.2% (29/688) of ccRCC and 2.1% (1/48) of uRCC cases. Adjuvant therapy was administered to 49% of metastatic cases, with 76% receiving pazopanib as part of their treatment regimen, including 16.7% (8/48) of uRCC cases and 12.8% (88/688) of ccRCC cases.
Pathology findings
The uRCC and ccRCC groups showed a similar frequency of high histological grade (62.5% vs. 53.7%, P = 0.23). The sarcomatoid/rhabdoid component was more frequent in the uRCC than ccRCC group (12.5% vs. 5%, P = 0.03). The groups did not differ in tumor size, presence of tumor necrosis, positive surgical margins, tumor thrombus, pT3 characteristics (renal vein or involvement of its branches, perirenal or sinus fat invasion, and pelvicalyceal system invasion), or TNM staging [Table 2].
Table 2.
Pathology findings
| Variable | ccRCC (n=688), n (%) | uRCC (n=48), n (%) | P |
|---|---|---|---|
| Tumor size (cm), mean±SD | 6.4±3.7 | 7.9±5.4 | 0.18 |
| Tumor grade | |||
| Low | 319 (46.3) | 18 (37.5) | 0.23 |
| High | 369 (53.7) | 30 (62.5) | |
| Sarcomatoid and/or rhabdoid component | 35 (5.0) | 6 (12.5) | 0.03 |
| Necrosis | 241 (42.6) | 15 (45.5) | 0.85 |
| Microvascular invasion | 188 (27.3) | 9 (18.7) | 0.19 |
| Tumor thrombus | 83 (12) | 4 (8.3) | 0.43 |
| Positive surgical margins | 82 (11.9) | 9 (18.7) | 0.16 |
| pT | |||
| ≤ T2 | 366 (53.1) | 29 (60.4) | 0.16 |
| ≥ T3 | 322 (46.8) | 19 (39.6) | |
| pN | |||
| N0 | 113 (16.4) | 5 (10.4) | 0.15 |
| N1 | 17 (2.5) | 3 (6.3) | |
| Nx | 558 (81.1) | 40 (83.3) | |
| pM | |||
| M0 | 604 (87.9) | 41 (85.4) | 0.67 |
| M1 | 83 (12.1) | 7 (14.6) |
SD=Standard deviation, ccRCC=Clear cell renal cell carcinoma, uRCC=Unclassified renal cell carcinoma
Postoperative outcomes
The ccRCC and uRCC groups did not differ in recurrence rate (15.1% vs. 4.3%, P = 0.07) or death rate (25.9% vs. 33.3%, P = 0.3) [Table 3]. The overall survival at 48 months was 74.1% for ccRCC and 66.1% for uRCC cases. The mean overall survival time was 72 months and 50 months, respectively (P = 0.05). The median overall survival time was 71 months for the uRCC group and not reachable for the ccRCC group [Figure 2a].
Table 3.
Postoperative outcomes
| Variable | ccRCC (n=688), n (%) | uRCC (n=48), n (%) | P |
|---|---|---|---|
| Serum creatinine (mg/dL), mean±SD | 1.3±0.9 | 1.3±0.6 | 0.42 |
| Recurrence+ | 103 (15.1) | 2 (4.3) | 0.07 |
| Death | 178 (25.9) | 16 (33.3) | 0.3 |
+Patients who underwent cytoreductive surgery were excluded from recurrence analysis, uRCC=8 (17%), ccRCC=88 (12.9%). SD=Standard deviation, ccRCC=Clear cell renal cell carcinoma, uRCC=Unclassified renal cell carcinoma
Figure 2.
Kaplan–Meier estimator and log-rank test for clear cell renal cell carcinoma and unclassified renal cell carcinoma: (a) Overall survival. (b) Recurrence-free survival (Original). RCC: Renal cell carcinoma uRCC: Unclassified renal cell carcinoma, ccRCC: Clear cell renal cell carcinoma
Recurrence-free survival at 48 months was 79.6% for ccRCC and 94.3% for uRCC, and the mean recurrence-free survival time was 70 months and 12 months, respectively (P = 0.08) [Figure 2b].
On further separating the ccRCC group into LG and HG and comparing to uRCC, the overall survival at 48 months was 66.1% for uRCC, 87.4% for LG ccRCC (P = 0.75), and 63.4% for HG ccRCC (P < 0.01) [Figure 3a]. Recurrence-free survival rate at 48 months was 94.3% for uRCC, 92.5% for LG ccRCC (P = 0.91), and 66.5% for HG ccRCC (P < 0.01) [Figure 3b].
Figure 3.
Kaplan–Meier estimator and log-rank test for low grade Fuhrman (LGF) clear cell renal cell carcinoma (ccRCC), high grade Fuhrman (HGF) ccRCC, and unclassified renal cell carcinoma: (a) Overall survival. (b) Recurrence-free survival (original). RCC: Renal cell carcinoma uRCC: Unclassified renal cell carcinoma, ccRCC: Clear cell renal cell carcinoma
DISCUSSION
Kidney cancer is the sixth most commonly diagnosed oncological disease in men and the tenth in women, representing 3% to 5% of all diagnosed cancer.[5] Kidney cancer incidence is increasing in part because of the spread and easier access to CT and magnetic resonance imaging.[6,7] As a result, a higher number of incidental renal masses are being identified, representing up to 60% of cases. This has led to the detection of smaller tumors, with 87% being less than 3 cm at diagnosis, and consequently, earlier detection of kidney cancer.[8]
RCC represents more than 90% of the diagnosed cancers. It encompasses a vast scope of histological subtypes that differ in tumor staging, grading, and cancer-specific survival, directly affecting prognosis. The most common RCC subtypes are ccRCC (70%–80%), papillary RCC (10%–15%), and chromophobe RCC (4%–5%). The remaining 10% includes over 10 recognized rare subtypes, which encompass uncommon, familial, sporadic types, and renal pelvis carcinoma. Additionally, there is a group that does not fit into any of the well-recognized subtypes and is therefore classified as uRCC.[1]
The incidence of uRCC, which represents a histologically heterogeneous group of kidney cancers, is estimated to be between 2% and 6% of all RCC cases. This subtype may exhibit a range of features, including mixed patterns of recognized subtypes, unclassified oncocytic neoplasms, pure sarcomatoid histology, mixtures of epithelial and stromal elements as well as mucin production and unrecognizable cell types.[9] Limited and controversial data exist regarding the clinical presentation and outcomes associated with uRCC. Historically, uRCC is associated with aggressive biological behavior, frequently presenting with metastasis at diagnosis and a worse overall survival compared to ccRCC.[10,11] Nevertheless, recent data suggest that uRCC may exhibit advanced clinical characteristics and more aggressive pathologic patterns than ccRCC, despite a similar oncological outcome. Moreover, the prognosis for uRCC appears to be influenced by the same factors as those for the usual forms of RCC, including tumor size, Fuhrman grade, and microvascular invasion.[12,13]
In this retrospective study, we sought to evaluate the impact of uRCC on oncological outcomes in comparison to ccRCC. To ensure accurate classification, an experienced pathologist conducted a pathological review of the uRCC cases based on the latest available WHO classification. From the initial database (1388 patients), the prevalence of ccRCC was 49.5%, uRCC 3.5%, and other subtypes 47%. The uRCC prevalence in our series is consistent with the literature, ranging from 1% to 5.2%.[10,11,12,13]
In our study, there was no significant difference in the proportion of asymptomatic patients at diagnosis between the uRCC and ccRCC groups (56% vs. 56.3%, respectively). This finding contrasts with earlier studies, which reported lower rates of asymptomatic uRCC patients (ranging from 16% to 23%).[10,11]
We found uRCC cases associated with higher lymphadenopathy incidence than ccRCC cases (32.6% vs. 15.8, P < 0.01). Comparative studies also found a higher rate of lymphadenopathy in uRCC than ccRCC,[10,11,14] and its prevalence ranged from 13% to 51%.[10,11,12,13,14,15] However, we found no difference in local tumor involvement (≥T3 46% uRCC vs. 39.3% ccRCC, P = 0.16). Karakiewicz et al. showed a more aggressive local staging for uRCC than ccRCC cases (≥T3 70% vs. 37%). Our series agrees with the latest literature, showing a prevalence of ≥ T3 uRCC tumors from 28% to 41%.[11,14,15] In addition, our study revealed no significant difference in the overall prevalence of metastasis at diagnosis between uRCC and ccRCC cases (20.8% vs. 16.8%, P = 0.43). However, there was a higher incidence of liver metastasis in the uRCC compared to the ccRCC group (8.9% vs. 2.8%, P = 0.04) and distant lymphadenopathy (16.7% vs. 7.8%, P = 0.04). The literature showed a downward trend over time in the prevalence of metastasis. Earlier studies demonstrated a more aggressive pattern, with metastasis present at initial diagnosis as high as 54% to 87%.[10,11] In contrast, recent data show a markedly lower prevalence of metastasis, ranging from 2.9% to 9%.[12,15] Crispen et al. (2010)[14], the last published comparative study of uRCC and ccRCC, reported similar results, with metastasis observed in 21% of uRCC cases compared to 14.3% in ccRCC cases. In our study, distant lymphadenopathy was the most common site of metastasis (16.7%), followed by lung (12.5%) and liver (8.3%). The literature disagrees regarding the preferred site of metastasis related to uRCC, with reports of metastasis to the lung,[12] bone,[10] and adrenal gland.[15] This variability in the preferred metastatic site might be explained by the heterogeneity of the uRCC group, reflecting the diverse and complex nature of this subtype of RCC.
uRCC cases exhibited a higher rate of sarcomatoid/rhabdoid component than ccRCC cases (12.5% vs. 5%, P = 0.03). Similar results were found by Crispen et al. (2010), but other studies did not analyze this specific feature. This architectural feature tends to appear in more undifferentiated subtypes, thus contributing to tumor aggressiveness. Conversely, we found a similar frequency of histological HG tumors in the uRCC and ccRCC groups (62.5% vs. 53.7%, P = 0.23). Previous comparative studies showed a higher prevalence (from 45% to 86.8%) of HG tumors when comparing uRCC to ccRCC.[10,11,14] Moreover, we found no difference between the groups in the presence of coagulative necrosis, whereas Crispen et al. (2010) found a significant association for coagulative necrosis (63.2% uRCC vs. 28.7% ccRCC, P < 0.01). Our two groups did not differ in tumor size and microvascular invasion, even though they influence the prognosis of kidney cancer.
The two groups did not differ in recurrence-free survival (94.3% uRCC vs. 79.6% ccRCC, P = 0.08) and overall survival (66.1% vs. 74.1%, P = 0.06), with a median overall survival time of 71 months for the uRCC group.
The uRCC may work as less differentiated cells or at least as a less differentiated architecture, leading to a possible worse prognosis. Thus, we further divided the ccRCC group into LG and HG tumors and compared to the uRCC group. The uRCC group showed a similar behavior to the LG ccRCC group in recurrence-free survival (94.3% uRCC, 92.5% LG ccRCC, and 66.5% HG ccRCC at 48 months, P < 0.01) and a similar behavior to the HG ccRCC in overall survival (66.1% uRCC, 63.4% HG ccRCC, and 87.4% LG ccRCC at 48 months, P < 0.01). In contrast, earlier studies showed a more aggressive pattern.[10] Zisman et al. showed an overall median survival for uRCC as low as 4.3 months, although most cases were already metastatic at the beginning of the study (87% of the uRCC group). More recent comparative articles found uRCC associated with poor prognosis and overall survival at 5 years (32.6% vs. 43% ccRCC).[11,14]
The apparent contradiction between higher recurrence-free survival and shorter time to recurrence with higher rates of lymph node and liver metastases can be explained by several factors. Our analysis suggests that despite a shorter time to recurrence and higher rates of lymph node and liver metastases, the uRCC cases in our study might have unique clinical or pathological features contributing to a relatively better recurrence-free survival. These factors include variations in tumor biology, tumor heterogeneity, treatment responses, or differences in patterns of disease progression that were not fully captured in our analysis. Tumor heterogeneity may play a significant role, as the diverse histological subtypes and molecular characteristics within uRCC could lead to different clinical behaviors and outcomes. For instance, some tumors might have a shorter recurrence period (with lymphadenopathy and metastasis), while others may not have recurrence at all.
Here, we aimed to approach some clinical and surgical aspects of a complex issue using ccRCC as a referential parameter for comparative analysis. We found some significant differences between both the groups. uRCC demonstrated a higher prevalence of lymphadenopathy and a greater incidence of sarcomatoid/rhabdoid components compared to ccRCC. In terms of histological grade, uRCC was similar to ccRCC. Additionally, uRCC exhibited a comparable disease recurrence rate to LG ccRCC and an overall survival rate similar to that of HG ccRCC. In contrast to earlier studies, our series is the largest from a single center with all uRCC cases being revised by an experienced uropathologist according to the most updated version of the WHO classification (2016) at the time.
Our study provides valuable insights into the clinical and oncological outcomes of uRCC compared to ccRCC. However, we recognize that the sample size for uRCC in our analysis is relatively small. This limitation is inherent to the rarity of uRCC cases. Despite our efforts to include all eligible uRCC cases within the study period, the relatively small sample size could impact the robustness of our survival analysis and the generalizability of our findings.
CONCLUSION
Our study sheds light on the clinical presentation and oncological outcomes of uRCC compared to ccRCC. Despite its rarity, uRCC remains a challenging entity to diagnose and manage due to its heterogeneous and complex histology. Our findings suggest that uRCC presents with higher rates of lymphadenopathy, sarcomatoid/rhabdoid differentiation, and liver metastasis when compared to ccRCC. Moreover, our study suggests that uRCC has a similar histological grade as ccRCC, similar disease recurrence rate as LG ccRCC, and comparable overall survival as HG ccRCC. Our study underscores the challenge and importance of accurate pathological diagnosis and stratification of RCC. Further studies are warranted to confirm our findings and explore potential molecular and genetic differences between uRCC subtypes and their relation to ccRCC.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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