Abstract
Introduction
Kidney cancer ranks 14th among new cancer cases worldwide with approximately 4,34,840 new diagnoses and ranks 16th in mortality with 1,55,953 deaths, as per The International Agency for the Research of Cancer, Global Cancer Observatory Data, 2022. The age-standardised rate (ASR), which adjusts for age to facilitate comparisons across different populations, is 4.4 per 1,00,000 individuals.[1] This data highlights the global prevalence of kidney cancer and underscores the need for ongoing research and public health efforts to address this significant health concern.
Renal cell carcinoma (RCC) has notably doubled its incidence in developed nations during the last 50 years. Most instances of RCC are fortuitously detected through imaging procedures, and survival rates are closely tied to the disease stage upon diagnosis, with a mere 12% five-year survival rate for cases with metastasis. Men account for two-thirds of RCC diagnoses, with mean age at presentation between 55 and 75 years.[2] The case fatality rate in low-income countries is higher than in high-income countries in comparison to the incidence. The disease burden is anticipated to double in the coming decades in developing countries and marginalised communities. Behaviourally modifiable risk factors encompass smoking, obesity, inadequately managed hypertension, dietary choices, alcohol consumption and occupational exposures. To enhance survival rates and diminish disparities, strategies for prevention should encompass addressing lifestyle elements, ensuring regular healthcare access for underserved groups in developing nations and introducing more stringent imaging guidelines for the early detection of RCC.[3–5]
Materials and Methods
The study design was a retrospective observational study conducted in the Department of Histopathology, Apollo Hospital, Chennai, India, from January 2022 to December 2022, with a study population of 116. All radical and partial nephrectomy cases during the study period with the diagnosis of RCC were included. Non-neoplastic reasons, urothelial and mesenchymal neoplasms of the kidneys were excluded.
Aims and Objectives
Following are the aims and objectives of this article:
To calculate the prevalence of RCC in a quaternary care referral centre in South India. To classify RCC based on morphology. To study histomorphological characteristics of RCC.
Methodology
The tissue sample was preserved in a 10% neutral buffered formalin solution, then processed and embedded in paraffin wax. Subsequently, thin sections (4 micrometers thick) were prepared for further analysis
All the cases were reviewed and classified based on the World Health Organization (WHO) 2022 classification of RCC. Genetics and molecular data were not included in the study.
Statistical Analysis
Data entry was done using Microsoft Excel with proper coding. Clinical data was obtained from the electronic medical records of the hospital. Data was analysed by using the statistical software SPSS (IBM, 28.0). Descriptive statistics were presented with frequency (percentage) and mean ± SD (standard deviation) for the categorical and continuous factors, respectively.
Results
A total of 116 patients were diagnosed with RCC during the study period with a prevalence of 38.6%, which included 84 male patients and 32 female patients, accounting for 72.4% and 27.6% of cases respectively with a male-to-female ratio of 2.6:1. The age range of cases was between 17 and 88 years, with a median age of 53 [Table 1].
Demographic factors
Out of 116 patients, 82 patients (70.7% of cases) underwent radical nephrectomy and 34 patients (29.3% of cases) underwent partial nephrectomy. The majority of patients (41.4% of cases) had upper pole tumours, and 34 patients (29.31% of cases) had extensions to adjacent renal poles. Tumour sizes of >4 cm and ≤7 cm (pT1b) constituted the major group (42.2% of cases). Tumour was limited to the kidney in 62.9% of cases, whereas 35.3% of cases were pT3a with involvement of sinus fat or perinephric fat. One case (0.8%) showed infiltration beyond Gerota’s fascia and another one case showed contiguous involvement of adrenal; however, no cases showed metastatic deposit in adrenal gland. Two cases of radical nephrectomy specimens showed involvement of renal sinus fat margin; however, ureteric margin was negative in all the cases. Of the 34 partial nephrectomy specimens received, the mean size of the tumour was 3.89 cm (1.6 cm-5.6 cm), with three cases (8.82%) showing renal sinus, perinephric fat, segmental branch of renal vein involvement, respectively and three other cases showing parenchymal resection margin involvement on microscopic examination.
Clear cell RCC was the major histologic type (83.6% of cases), followed by papillary RCC (7.8% of cases). Lymphovascular invasion within the nephrectomy specimen was present in 13.8% of cases; however, this has no value in clinical management. Regional lymph nodes (hilar and aortic nodes) were identified and submitted in 72 cases, of which only 3.4% of cases showed lymph node involvement where the nuclear grade 4 predominated [Table 2]. Further correlation of the nuclear grade and tumour size, the WHO/ISUP grade 2 predominated with 42.2% of cases, of which 51% of cases the tumour size ranged between >4 and ≤7 cm. Pathological Stage I constituted 50.9% of cases with 33 cases ranging between >4 and ≤7 cm (T1b), and the remaining 26 cases were ≤ 4 cm (T1a). Clear cell RCC predominated in aggressive features such as vascular tumour thrombus, lymph node infiltration, involvement of renal sinus fat, perinephric fat and Gerota’s fascia involvement [Tables 2 and 3]. The Leibovich Risk Score algorithm was used to stratify 68 radical nephrectomy specimens into low-, intermediate- and high-risk groups after they were diagnosed as clear cell RCC [Table 3]. Tumour size, lymph node spread, nuclear grade, histologic tumour necrosis and disease stage all affect this score. Twenty-two, twenty-nine and seventeen of the 68 cases fell into the low-, moderate- and high-risk categories, respectively. This scoring predicts the progression after radical nephrectomy in these cases [Table 4].
Clinical parameters
aTwo radical nephrectomy and three partial nephrectomy cases.
Comparison between tumour size with T category and stage
*Chi-square/Fisher’s exact test; Boldface indicates statistical significance.
Leibovich risk score algorithm to predict progression after radical nephrectomy in patients with clear cell RCC
Discussion
According to the Surveillance, Epidemiology, and End Results (SEER) database, nearly 50% of patients with RCC are aged between 55 and 75, with a median presentation age of 64.[2] In our study, the median age at presentation was 53 (46–62.7). A lower median age at presentation of 56.6, 54 and 56 years, respectively, has also been reported in some other Indian research.[6–8]
The male-to-female ratio is 2:1 in developed world literature. However, for all patients presenting with RCC, we found it to be 2.6:1. Research on the Indian population has revealed a comparable increased incidence of this malignancy in men.[7,8]
In our study, about 83.6% of the patients had clear cell RCC [Figure 1] which is comparable to the percentage reported in Western literature, and according to two Indian investigations, this was 89.3% and 71.3%, respectively.[8,9] On the other hand, clear cell RCC accounted for 63.3% in a study conducted by Mandrekar et al. from January 2016 to June 2019 and a relatively less number in the study from Beirut, Lebanon with 59.1% of cases.[10,11]
Pathological Stage I was the most common presentation among the operated patients (50.9%), followed by Stage III (38.8%). According to SEER data, 60%–70% of their patients arrive in Stage I. In reality, tumours smaller than 2 and 2–4 cm are mostly responsible for the rise in kidney cancer incidence that has been observed in industrialised countries over the past ten years.[12] Our study’s earlier stage of presentation may have been caused by improved healthcare facilities, medical fitness tests given to candidates before hiring them, yearly physicals and improved awareness of annual preventive health checkups where a reasonable proportion of tumours is unintentionally found. Also, the increased numbers are due to the quaternary referral centre bias.
Regarding tumour laterality, in this study, 60 cases (51.7%) involved the right kidney, and 56 cases (48.3%) the left kidney. Humera and Kehar reported similar findings showing that the right kidney was involved more frequently than the left.[13] Given that no other studies placed any attention on laterality and that studies have also shown that the left kidney is more frequently affected than the right; this finding may have been coincidental.[14]
In the fifth edition of the WHO classification of RCC, there are new categories of molecularly defined renal tumours, and the classification is a dynamic process with emerging entities and ongoing research with reclassification. Morphological data remains clinically relevant information in the treatment of RCC, especially the sarcomatoid and rhabdoid morphology, which confers an increased benefit from immune-oncology agents [Figure 2]. In our study, grade 4 included 12.1% of cases, with 3.4% of cases showing focal sarcomatoid (<10%) and 6.03% of cases revealed focal rhabdoid morphology (<5%) as compared to other studies.[15,16] However, limitations relying only on morphology include potentiality for misdiagnosis, lack of molecular information and convergent morphological features. As with many cancers, RCCs may share similar morphological features with other types of renal neoplasms or metastatic tumours. For instance, clear cell RCC might share some characteristics with certain subtypes of urothelial carcinoma. Without additional molecular techniques, there’s a risk of misdiagnosis, leading to inappropriate treatment.
Microscopic images
All partial nephrectomy cases were done for a mean tumour size of 3.89 cm, of which three cases (8.82%) showed microscopic extension into renal sinus, perinephric fat and segmental branch of renal vein, respectively. Another three cases showed parenchymal resection margin involvement on microscopic examination. Follow-up details were not available for these patients.
Limitation
This is a retrospective observational study, and most of our patients are referred for surgery and return to their native places for further clinical management. Hence, detailed follow-up analysis could not be performed.
Conclusion
To summarise, clear cell RCC is the most common type of RCC in our study group, and the median age at presentation was 53 years, with approximately 37% demonstrating aggressive features.
Footnotes
Acknowledgements
To the research department Apollo Main Hospital Chennai.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Funding
The authors received no financial support for the research, authorship and/or publication of this article.
Institutional ethical committee approval number
This study was approved by Instituitional Ethical Committee under approval number [ASH-C-S-027/10-23].
Informed consent
All participants were made to sign a written informed consent before their enrolment in the study.
Consent for publication
All the authors and participants gave their written consent for publication.
Code availability
No code was used in the study.
Credit author statement
Githa Rachel Oommen participated in data collection, literature review, investigation, supervision, analysis and manuscript preparation.
Suganthi Krishnamurthy participated in conceptualisation, design and supervision in analysis and manuscript editing.
All the authors have reviewed and approved the manuscript.
Data availability
All the data analysed for this study have been presented in the manuscript.
Previous publication/presentation
Nil.
Use of artificial intelligence
The use of artificial intelligence is not relevant to this article, as it does not involve AI technologies or methodologies in its analysis or conclusions.