Though renal cell carcinoma (RCC) accounts for 2% of global cancer diagnoses and deaths, its incidence is increased dramatically in the developed world over the past half-century, and today it is the ninth most common neoplasm in the United States of America as well as in our region, Saudi Arabia.[1,2] This increased incidence is accompanied by better survival in developed countries.
The total number of deaths related to renal cancer is <25% of the total cases of kidney and renal pelvic failure. Data from Saudi Arabia showed that kidney cancer represent 3.4% of total cancer cases with a low percentage of cancer-related deaths[4,5] compared to other malignancies. The 5-year survival rate for patients with RCC is up to 55% for tumor stage III and reaches up to 70% for stages I and II.[6,7] The association of RCC with systemic diseases of high prevalence in many societies is well described[7,8] and the histopathological changes of these diseases are proved in a good percentage of cases of neoplastic nephrectomy. In addition to the pathological impact of coexisting comorbidities, the residual renal parenchyma will undergo further changes caused by the increased functional burden.[10,11]
The excellent outcome of renal carcinoma, in addition to the reasonable possibility of the presence of pathological changes associated with comorbities, draw our attention to the need for proper evaluation of the nonneoplastic kidney parenchyma in neoplastic nephrectomies to optimize the medical management. This approach will maximize renal function for patients who had nephrectomy due to a neoplastic process. In our study, we focus on studying this precious part of the specimen. We document pathological changes and measure to what extent these changes are taken care of, examined, and conducted in the reports in our center.
All cases of partial nephrectomy, radical nephrectomy, and nephroureterectomy due to kidney and pelvic kidney tumors performed at King Abdulaziz University Hospital between January 2010 and December 2019 were reviewed. 190 cases were performed during that period. Partial nephrectomy with a rim of nonneoplastic kidney <5 mm around the tumor, cases of pelvic and/or ureteral obstruction by the tumor, specimen with inadequate sampling of the background kidney, and cases with unavailable pathology slides or blocks were excluded from the study. A total of 124 cases were reviewed and 65 cases were excluded due to the described factors. The glass slides of the specimens were retrieved from the pathology laboratory filing store and examined. The light microscopic examination focused on sections selected from the renal parenchyma that is located far from the tumor. The glomerular, vascular, and tubulointerstitial pathological changes were re-evaluated and documented. These sections were stained by (H and E) , periodic acid-Schiff stain, silver stain (jones methenamine), and Masson’s trichrome. Some of the cases required Cong-red staining. The clinical data and pathology reports of the patients were recovered from the hospital’s electronic records. The extent to which surgical pathologists had evaluated and reported the changes in the nonneoplastic portion of the kidney parenchyma, which was reflected in the pathology reports, is also studied. This study has been approved by the Unit of Biomedical Ethics at King Abdulaziz University Hospital on 11th October 2021, (Reference No 486-21).
Of the total of 124 patients, 73 (59%) were men and 51 women (41%). The mean patients’ age was 53 ± 13.6. The youngest two patients were a 24-year-old female, who had a nephrectomy due to papillary RCC while the other one was a male patient who had nephrectomy due to chromophobe RCC. The oldest patient was a woman diagnosed at 89 years of age with clear-cell carcinoma. Histological findings are summarized in Table 1. Well-developed diabetic nephropathy in 8 (6%) patients. The findings of diabetic nephropathy were mentioned in the report of a case only. One of the diabetic nephropathy cases was accompanied by acute pyelonephritis with micrabscess. The latter pathology was only mentioned in the report. A variable degree of arteriosclerosis was identified in 16 (13%) patients, mild in 6 cases, moderate in 7 cases, and severe in three cases. These vascular changes were found to be reported in only one of the cases in which arteriosclerosis was severe. Oxalosis was found in 2 (~2%) patients. It was mild in one of the patients, while severe in the other. The latter patient has developed an end-stage renal disease due to oxalosis and was already on dialysis for 2 years before his tumor was discovered. He had clear-cell carcinoma. This significant finding was overlooked during pathological evaluation in both cases of oxalosis. Significant interstitial inflammation was present in three patients, all of which were well described in the final pathology report. One of these cases showed necrotizing granuloma that has been further assessed by special stains for the fungal and tuberculous micro-organism by the reporting pathologist. Pyelonephritis was identified in two cases. This finding was well addressed in the pathological report of these two cases. The completion of the kidney examination and reporting regarding the evaluation of the nonneoplastic portion of the kidney was assessed in every single case. We found that this portion of the kidney was well sampled in 118 (95%) of nephrectomies and nephroureterectomies. However, the histological status of this part of the kidney was illustrated in the synoptic report in only 31 (25%) cases included in the study.
According to the Society of American Cancer, the estimated number of kidney and renal pelvis new cancers cases in 2020 is 73.750 among both sexes. 45,520 among males, and 28,230 among females. The estimated deaths for male patients are 9860 and for female patients are 497 in the year 2020. The total number of deaths related to renal cancer is 14,830 for both sexes, <25% of the total number of cases of kidney and renal pelvic tumors. Data from the Saudi Cancer Registry released in 2020 stated that the incidence of kidney cancer is 3.4% of total cancer cases, which is estimated to be 24,485 cases. Furthermore, according to the global cancer observatory, Saudi Arabia’s 2020 report showed that the number of new cases of kidney cancer is 909 among both genders with a cancer-related death rate of 2.9%. This death rate is low in comparison to the deaths due to other tumors such as liver, breast, and colon cancer, in which the cancer-related deaths are 8.5%, 8.4%, and 8.3%, respectively. All over the world, advances in medical care and radiological modalities lead to earlier detection of renal tumors, which in addition to improved surgical techniques have resulted in a dramatic improvement in oncological outcomes. Data from the national cancer institute showed that the 5-year survival rate for kidney tumors is 70% for stage I and II, between 30% and 55% for stage III, and drops to 5% for stage IV. For renal pelvic tumors, the 5-year survival rate is 100% for localized tumors not invading beyond the lamina propria, 80% for localized tumors without subepithelial invasion, between 20% and 30% for tumors infiltrating the pelvic wall, and reaches to as low as 5% for tumor invading beyond the renal pelvis. The stages of renal tumors in our center are mentioned in Table 2. As shown in that table, most of our cases are in stages I to III in which patients are expected to live a longer life. Diabetes millets, hypertension, smoking, certain medications, advanced renal disease, and obesity are known risk factors for RCC, so it will not be a surprise that the kidney with renal tumor could suffer from the pathological consequences of these conditions in a significant portion of patients.[7,8] Huang et al. have proved that 26% of the patients with renal carcinoma have suffered from preexisting chronic kidney disease. Not only that, removal of a single kidney or portion of a kidney will lead to a compensatory burden on that potentially diseased residual renal parenchyma to serve the body.[10–11] This association between renal tumor and medical renal problems, in addition to the amplified functional burden on the residual renal parenchyma, has attracted our attention to the significance of examining the nonneoplastic renal parenchyma to assess the need for medical intervention and continuous care by the nephrologist. This approach, together with the excellent oncologic outcomes described for most kidney tumor patients, will eventually maximize the preservation of renal function in our renal tumor patients, especially in centers like our own in which the majority of renal tumor patients fall into the category of long-term survivors. In a recent large population study that involved 1012 cases from southeastern and central Europe, 17.4% of the cases showed variable degrees of glomerular scarring, interstitial fibrosis, inflammation, tubular atrophy, and vascular changes which are were described collectively as chronic renal parenchymal changes. The other previous studies that covered the nonneoplastic kidney showed that diabetic nephropathy was identified in (7%–20%) of the cases, arterionephrosclerosis was present in up to 22% of the cases. Amyloidosis was noted in up to 3% of the cases. Pauci immune glomerulonephritis was identified in <1% of cases.[13–18] Among our patients, 35 (28%) patients showed pathological changes. 20 (16%) of them had hypertensive vascular changes with variable degrees of subsequent hypertensive nephropathy. 8 (6%) of them had diabetic nephropathy, which may not reflect the prevalence of diabetes and hypertension in our population.[19,20] Although these findings were significant, they were described in the report of a small portion of the cases. Severe oxalosis was found in a case associated with clear-cell carcinoma. This patient was 56-years-old at the time of cancer diagnosis and had been on hemodialysis for 2 years before diagnosis with clear-cell carcinoma. There was no clinical diagnosis of oxalosis and his end stage renal disease (ESRD) condition was described in clinical data as idiopathic. The cases with the other tubulointerstitial diseases were well identified, investigated, and described in the pathology report. Synoptic reporting of neoplastic cases has become widely accepted. The most commonly adopted one is the college of American pathologists protocols, which is used in our center too. Evaluation of the nonneoplastic kidney parenchyma is considered a mandatory item in nephroureterectomy specimens in that protocol since 2010, which used to be an optional entity before that time. In Henriksen et al., and Salvatore et al., it was found that 60% to 88% of renal pathology diagnoses were missed during the initial examination of the nephrectomy specimen.[14,16] Furthermore, a European survey of genitourinary pathologists, revealed that over 25% of the pathologist do not evaluate the nonneoplastic kidney parenchyma, although a portion of the tissue is properly sampled for every specimen. Although synoptic reporting of neoplasm using the CAP protocol is largely applied in our center, reviewing the reports showed that the adherence to the mandatory reporting of the pathological condition of the nonneoplastic portion of the kidney is low. The nonneoplastic kidney parenchyma was mentioned in only 31 (25%) of the reports and only 7 (22%) of the disease process was accurately identified and mentioned. The factors behind this deficiency in reporting need to be explored and treated to optimize the patients’ outcome and not to miss a finding with significant consequences on the patients’ management taking the case of severe oxalosis as an example. These large percentages of reporting deficiency indicate that the evaluation of this portion of nephrectomies is largely overlooked by reporting pathologists in different parts of the world.
The recent well-described improvement in the surgical oncological outcome of the nephrectomies and nephroureterectomies, which is translated into prolonged survival rate of the patients with kidney and kidney pelvic tumors mandates the optimum evaluation and reporting of the nonneoplastic renal parenchyma by the reporting pathologists. This step is essential and required to assess the need for an early arrangement of follow-up by nephrologists. This approach aims to preserve the function of the residual renal parenchyma and avoid the potential worsening of any preexisting medical renal condition.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal AC>. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 2018;68:394–424.
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7–30.
7. Correa AF, Lane BR, Rini BI, Uzzo RG. Ch. 66 –Cancer of the kidney DeVita VT, Hellman S, Rosenberg SA Cancer:Principles and Practice of Oncology 11th ed Philadelphia, PA Lippincott Williams &Wilkins 2019.
8. Karami S, Daughtery SE, Schwartz K, Davis FG, Ruterbusch JJ, Wacholder S, et al. Analgesic use and risk of renal cell carcinoma:A case-control, cohort and meta-analytic assessment. Int J Cancer 2016;139:584–92.
9. Huang WC, Levey AS, Serio AM, Snyder M, Vickers AJ, Raj GV, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours:A retrospective cohort study. Lancet Oncol 2006;7:735–40.
10. Choi DK, Jung SB, Park BH, Jeong BC, Seo SI, Jeon SS, et al. Compensatory structural and functional adaptation after radical nephrectomy for renal cell carcinoma according to preoperative stage of chronic kidney disease J Urol 2015;194:910–5.
11. Choi SY, Yoo S, You D, Jeong IG, Song C, Hong B, et al. Adaptive functional change of the contralateral kidney after partial nephrectomy. Am J Physiol Renal Physiol 2017;313:F192–8.
12. Abedi-Ardekani B, Nasrollahzadeh D, Egevad L, Banks RE, Vasudev N, Holcatova I, et al. Morphological findings in frozen non-neoplastic kidney tissues of patients with kidney cancer from large-scale multicentric studies on renal cancer. Virchows Arch 2021;478:1099–107.
13. Bijol V, Mendez GP, Hurwitz S, Rennke HG, Nosé V. Evaluation of the nonneoplastic pathology in tumor nephrectomy specimens:Predicting the risk of progressive renal failure. Am J Surg Pathol 2006;30:575–84.
14. Henriksen KJ, Meehan SM, Chang A. Non-neoplastic renal dis- eases are often unrecognized in adult tumor nephrectomy specimens:A review of 246 cases. Am J Surg Pathol 2007;31:1703–8.
15. Henriksen KJ, Meehan SM, Chang A. Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy specimens:Common, harmful, yet underappreciated. Arch Pathol Lab Med 2009;133:1012–25.
16. Salvatore SP, Cha EK, Rosoff JS, Seshan SV. Nonneoplastic renal cortical scarring at tumor nephrectomy predicts decline in kidney function. Arch Pathol Lab Med 2013;137:531–40.
17. Garcia-Roig M, Gorin MA, Parra-Herran C, Garcia-Buitrago M, Kava BR, Jorda M, et al. Pathologic evaluation of non-neoplastic renal parenchyma in partial nephrectomy specimens. World J Urol 2013;31:835–9.
18. Vanatta PR, Silva FG, Taylor WE, Costa JC. Renal cell carcinoma and systemic amyloidosis:Demonstration of AA protein and review of the literature. Hum Pathol 1983;14:195–201.
19. Alotaibi A, Perry L, Gholizadeh L, Al-Ganmi A. Incidence andprevalence rates of diabetes mellitus in Saudi Arabia:An overview. J Epidemiol Glob Health 2017;7:211–8.
20. El Bcheraoui C, Memish ZA, Tuffaha M, Daoud F, Robinson M, Jaber S, et al. Hypertension and its associated risk factors in the kingdom of Saudi Arabia, 2013:A national survey. Int J Hypertens 2014;2014:564679.
21. Srigley JR, Amin MB, Delahunt B, Campbell SC, Chang A, Grignon DJ, et al. Protocol for the examination of specimens from patients with invasive carcinoma of renal tubular origin. Arch Pathol Lab Med 2010;134:e25–30.
22. Algaba F, Delahunt B, Berney DM, Camparo P, Compérat E, Griffiths D, et al. Handling and reporting of nephrectomy specimens for adult renal tumours:A survey by the European Network of Uropathology. J Clin Pathol 2012;65:106–13.