Baker Alabbadi MD*, Ali Alasmar MD*, Ayman Alqarallah MD*, Nizar Saaydah MD* ABSTRACT

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1 Renal Cell Carcinoma Clinical Presentation and Histopathological Findings: A Retrospective Analysis of a Jordanian Population at King Hussein Medical Center Baker Alabbadi MD*, Ali Alasmar MD*, Ayman Alqarallah MD*, Nizar Saaydah MD* ABSTRACT Objective: To assess renal cell carcinoma cases and analyze the tumor characteristics in terms of clinical presentation, patient s demographics and the histopathological findings. Methods: This retrospective study included 99 patients with renal masses, of both sexes and different age groups, who presented at our urology department at Prince Hussein Center for Urology and Organ Transplant with various clinical presentations. Patients were scheduled for nephrectomies during the period of January st 0 to April st 0. Demographic data were retrieved and reviewed with the histopathological reports obtained from the histopathology department at Prince man laboratory research center. Results: Our patients ranged in age from to 80 years old with male : female incidence ratio of.5:(p). Renal mass was incidentally discovered in 4.4% of cases (p). Radical nephrectomy was performed in 90.9% of cases. Clear cell renal cell carcinoma was diagnosed in.% of patients (p). Conclusion: Clear renal cell carcinoma subtype grade is the most frequent type of renal cell carcinoma in our Jordanian population. Renal cell carcinoma occurs commonly in males, with no metastases in females and with 6.% metastases in males. Key words: Carcinoma, Demographics, Grading, Histopathology, Renal. JRMS March 05; (): 8- / DO: 0.86/00098 ntroduction Renal cell carcinoma occupies 85% of kidney cancers. () The factors most commonly accompanying the increased renal cell carcinoma risk in epidemiological investigations in white people are obesity, hypertension and cigarette smoking, which account for less than half of these cancers. () Renal cell carcinoma comprises 4% of all new primary cancers, and 85% of kidney cancers are renal parenchyma (renal cell) carcinomas. () Renal cell carcinoma (RCC) is twice as frequent in males than females, with the mean age of early sixties. Renal cell carcinoma accounts for -% of all solid neoplasms discovered by ultrasound each year. () Renal cell carcinoma is the 0 th leading cause of cancer deaths globally. () Enhanced radiological technology caused early diagnosis and reduction in the size of tumor, but at the same time there has been an increase in the frequency of big and late stage renal cell carcinoma. Kidney carcinoma frequency is rising *From the Department of Urology, Prince Hussein Bin Abdullah the nd Center, King Hussein Medical Center, (KHMC), Amman-Jordan Correspondence should be addressed to Dr. B. Alabbadi, (KHMC), layanalis@yahoo.com Manuscript received May 5, 04. Accepted August 4, 04 8 Vol. No. March 05

2 .% yearly for men and.% yearly for women. () The diagnostic procedures for co-morbidities can clarify incidental findings of localized renal cell tumors. Most of the cases of renal cell carcinoma are discovered incidentally while performing ultrasound or CT scan for other causes. () The classic triad of presentation includes flank pain, gross hematuria and a palpable abdominal mass and accounts for 6-0% of presentation. () The rising incidence of advanced chronic kidney disease can lead to high kidney medical alert with increased diagnosis of early renal tumors, but unfortunately, the most frequent co-morbidities (HTN and DM) are not generally screened with radiological procedures. This frequency trend suggests that the biology of renal carcinoma can differ. () The objective of this analysis was to assess the demographic and pathological characteristics of RCC diagnosed and treated by members of the Prince Hussein Center for Urology and Organ Transplant and Princess man for laboratory research center during the study period. Methods Our retrospective study included 99 patients who had nephrectomies for renal masses during the period of January st 0 to April st 0. The sample comprised both genders and various age groups, who had presented at our urology department at Prince Hussein Center for Urology and Organ Transplant with different clinical presentations. Approval from our local ethics committee was secured. Certain data were retrieved and reviewed with the histopathological reports obtained from the histopathology department at Prince man center. The demographic characteristics included age, gender, clinical presentation (loin pain, hematuria, incidental), type of nephrectomy, risk factors (smoking, hypertension and obesity) and ABO group data. Renal cell carcinoma characteristics including anatomical and pathological issues were investigated including laterality, tumor location, kidney weight, tumor size, subtype and metastases. The tumor grading was related to age and gender for significance. Data collected from all patients included age, gender, BM (weight and height), histological subtype, the presence of known risk factors for RCC (history of smoking, Hypertension and obesity) and clinical presentation (incidental or symptomatic: hematuria, palpable mass, flank pain, weight loss, fever and night sweats). Body mass index was calculated for all patients by dividing the weight of the patient (kg) by square height (m ). Tumor histology was classified according to the Heidelberg classification. () The subtypes of RCC reported in our investigation included: clear cell, papillary, chromophobe, collecting duct and unclassified carcinomas. Statistical Analysis Descriptive statistics of demographics and pathologic variables were conducted for comparison between groups of patients. The Chisquare test was used to compare the frequency of categorical variables between groups. Students t test or variance was used to compare continuous variables. p was considered significant. Results Of the 99 patients, 6.6% (6) were men and 6.4% (6) were women (p). The male: female incidence ratio was.5:. The age ranged between and 80 years with a mean age of 5.5 years in the whole study (Table ). n terms of clinical presentation, incidental asymptomatic picture was shown in 4.4 %( 4) of cases while symptomatic picture was demonstrated in 56.6% (56) of cases (p>0.05). This type of tumor affected the right kidney in 49.5% (49) of cases and affected the left kidney in 50.5% (50) of cases (p>0.05) (Table ). Smoking history, hypertension and obesity (BM >0 kg/m ) were found in 0.% (n=0),.% (n=) and 66.% (n=66) of patients, respectively. Men (n=) were found to have more the combined three risk factors than women (n=) (p). Computed tomography was the main diagnostic method. The majority of cases were localized tumors 94.9% (n=94) and metastases were reported in 5.% (n=5) of male patients only (one at renal sinus by papillary grade, two with brain vascular involvement by one clear cell RCC grade and one clear cell RCC grade V and two with adrenal involvement by clear cell RCC grade ). Vol. No. March 05 9

3 Table : Demographic characteristics of patients Females Males P Number 6 6 Age Range Mean Clinical presentation ncidental Loin pain Hematuria Loin pain + hematuria Nephrectomy Radical Partial Risk factors Smoking Obesity Hypertension Combined ABO group A B AB O (58.%) 0(.8%) 5(.9%) 0(0%) > >0.05 > (4.6%) 9(0.%) (.5%) (4.8%) Table. Renal cell carcinoma characteristics (anatomical and pathological) Females Males P Kidney side Right Left Kidney pole Upper Lower Middle Whole Kidney weight Least Heighest Tumor size Least Heighest Subtype Clear cell Chromophobe Papillary Undifferentiated with sarcomatoid Collecting duct g 500g ---- cm cm Metastasis 0 5 Grade V Of the total patients 90.9% (n=90) underwent radical nephrectomy while 9.% (n=9) underwent partial nephrectomy (Table ). The most frequent subtype of RCC was clear cell subtype affecting.% (n=) of patients ( females and 44 males), followed by the papillary with 4.% (n=4) of patients ( female and males) and the chromophobe subtype with 0.% (n=0) of patients ( females and 4 males). Sarcomatoid differentiation was recorded in.0% of patients (n=), one female (grade ) and males (grade 4). One male patient (.0%) had multilocular cystic RCC grade for which he underwent partial nephrectomy (Table V). 0 Vol. No. March 05

4 Table. Tumor grading with age P Female CC CP Male CP CC CC CC CP CCV CC CC CC CP CCV PAP PAPV SARCV Cystic CC: clear cell, CP: chromophobe, PAP: papillary, SARC: sarcomatoid Table V: Tumor grading with gender Clear cell (CC) V Chromophobe(CP) PAPLLARY(PAP) V SARCOMATOD(SARC) CC CC CP CP PAP CP CC 4 CC CC PAP PAPV CCV CC 4 CCV SARC CC 4 CP CCV PAP CC 5 PAP CC 4 CC 4 PAP CP CC CC Female Male P V Cystic 0 Table V: Overall incidence if RCC grading Female Male P Grade 5 Grade 0 Grade 0 Overall renal cell carcinoma grading was most commonly found in males grade (n=0, 0.%) with a total of 4 (4.5%) including males and females (Table V). Discussion Although some tumors have a clear and specific induced effect cause, renal cell carcinoma is not of these. There are clinical, professional and material factors incriminating in renal cell carcinoma tumorigenesis such as smoking, asbestos, organic solvents, viral infections, radiation therapy and others. (4) An increased frequency of RCC (. fold risk ratio) in smokers was shown directly related to number of cigarettes and inversely with age of beginning of smoking due to carcinogen dimetilnitrosamine. Smoking was reported in 0% of RCC cases. (4) n our investigation, smoking was shown to have a frequency of 0.% in our Jordanian population diagnosed as renal cell carcinoma. This was regarding tobacco importance in RCC genesis but it was shown that smoking increases.84 fold the Vol. No. March 05

5 risk of progression of the disease postoperatively. (4) Diet and obesity may increase the risk of renal cell carcinoma in addition to chronic renal failure, hypertension and dialysis. (5) Diuretics may cause a high frequency of RCC in patients with chronic intake. Hydrochlorothiazide and furosemide cause tubular cell adenomas and adenocarcinomas of the kidney. (6) Obesity may induce about 0% of renal cancers. The relative risk was increased. folds in males and. folds in females. () n our study, the frequency of obesity was 66.%, accounting 0.% in females and 6.4% in males. High level of endogenous estrogen in the obese patient is the incriminating agent. Obesity induces arterionephrosclerosis which can make renal tubules more susceptible to carcinogens. Hypertension can be considered as significant for the development of kidney cancer by inducing metabolic and functional changes in the renal tubular cells producing carcinogenesis. (8) Hypertension was seen in 4.% in females and in 49.5% in males in our study, accounting for.% of our total study group exposed to RCC. Hypertension is known to be a general risk factor for some types of cancers because hypertension and cancer share some frequent risk factors such as smoking, diabetes, obesity and others. A recent analysis demonstrated the excess cancer risk to be around 0-0%. Combining these risk factors, we found that.% of our patients, had combined these three factors, which we consider that these should alert the practitioner in his research. t is very difficult to find a direct cause regarding any cancer. To answer this question, a comprehensive epidemiological study is required during a long duration of time with careful follow up. Discrepancies in age, sex and geographic distribution were included in cancer origin. Most of renal cell carcinoma are sporadic and 4% are familiar (5) with a hereditary pattern. Worldwide among urological tumors, renal cell carcinoma occupies the third place in frequency after prostate carcinoma and transitional cell carcinoma of bladder. Renal cell carcinoma represents % of adult malignancies, occupying the 0 th place in males and 4 th place in females with a male to female ratio of :. (9) The male:female ratio in our study is.:. The peak frequency occurs in the 6 th decade with 80% of cases occurring within the years old inhabitants. () Renal cell represents 85-90% of renal parenchymal malignancies. () Since 90, frequency of RCC has been increasing from 0. to 4. /00000 in females and from.6 to 9.6 /00000 in males. (0) ncreasing frequency is explained by easier diagnosis (routine use of CT scan) and not by genuine increased frequency of RCC. Renal cell carcinoma is found incidentally in.5% of the autopsies. (0) Clear cell renal carcinoma is the most frequent subtype accounting for 0-80% of cases, then comes the papillary with 0-0 % of cases, chromophobe with 5% of cases and finally the collecting duct and the unclassified types with an incidence of <% of cases. Different grades and stages are encountered postoperatively with variable outcome and prognostic value. n Brazil, Aguinaldo et al., showed that male patients predominated and the mean age was near 60 years. Most of the patients presented with localized disease (% with RCC stage ). Abdominal CT scan was used in 9.% of patients for diagnostic purposes. () Most of the patients worldwide are presented with localized disease (% with stage ). () They found that the proportion of patients with metastatic disease was 9.5% (in our study it was 5.%) and that males present with more advanced disease at diagnosis than females, as in our study. n their study it was demonstrated that there was no association between stage and the presence of risk factors which were smoking, hypertension and obesity, the same factors as in ours. Although they did not find an association between the presence of clear cell histology and more advanced disease, we found that metastases were due to clear cell pathology, although the number was not significant. Limitations of the Study A limitation of the study was the small number and limited to one center. We believe that this study must be generalized to include more subjects at different regions of Jordan and in various centers to have a general view of such disease. Conclusion Regarding RCC, the etiology and risk factors are not fully understood. There is proof that some conditions, drugs, habits or genetics can play a Vol. No. March 05

6 role in development of RCC in Jordanian population, although international research show controversial results. Future campaigns need to be done to reduce smoking, obesity and hypertension in our Jordanian population to decrease hopefully the incidence of renal cell carcinoma. References. Rebecca S, Jiemin MA, Zhaohul Z, et al. Cancer statistics. Ca Cancer J Clin 04; 64: Loren L, Robert ET, Joseph MC. Renal cell cancer among African Americans:an epidemiologic review. BMC Cancer 0; :. Kovacs G, Akhtar M, Beckwith BJ, et al. The Heidelberg classification of renal cell tumors. J Pathol 99; 8: Hunt JD, van der Hel OL, McMillan GP, Boffetta P, et al. Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 4 studies. nternational J of Cancer 005; 4(): Pascual D, Borque A. Epidemiology of kidney cancer. Adv Urol 008; Franz HM. Risk factors for renal cell carcinoma:hypertension or diuretics? Kidney international 005; 6:4-5.. Amling CL. The association between obesity and the progression of prostate and renal cell carcinoma. Urol Oncol 004; (6): Joanne SC, Kendra S, Barry G, et al. Hypertension and risk of renal cell carcinoma among white and black Americans. Epidemiology 0; (6): McLaughlin JK, Lipworth L. Epidemiologic aspects of renal cell cancer. Semin Oncol 000; (): Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 006. Annals of Oncology 00; 8(): Aguinaldo CN, Stenio de CZ, Otavio ACC, et al. Epidemiologic characteristics of renal cell carcinoma in Brazil. nternational Brazil J Urol 00; 6(). Vol. No. March 05