Second primary malignancies associated with renal cell carcinoma histological subtypes

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.     

Techniques, safety and accuracy of sampling of renal tumors by fine needle aspiration and core biopsy

PURPOSE: The incidence of renal cell carcinoma is increasing worldwide and there are new treatments for localized as well as metastatic tumors. The traditional role for percutaneous biopsy of renal masses has been limited, and so there is little general experience. There have been concerns about safety and accuracy. This review provides an update on the current techniques, indications and accuracy of needle biopsy of renal tumors. MATERIALS AND METHODS: PubMed and MEDLINE were searched for English language reports of percutaneous needle core biopsy and fine needle aspiration of renal tumors that were published from 1977 to 2006. RESULTS: With the development of new biopsy techniques and wider experience with percutaneous probe ablation therapies the risk of tumor seeding appears negligible. Significant bleeding is unusual and almost always self-limiting. At centers with expertise needle core biopsy with or without fine needle aspiration appears to provide adequate specimens for an accurate diagnosis in more than 90% of renal masses. CONCLUSIONS: Percutaneous biopsy of renal masses appears to be safe and it carries minimal risk of tumor spread. Urologists should consider increasing the indications for renal biopsy of small renal masses that appear to be renal cell carcinoma, especially in elderly and unfit patients. With more experience and followup preoperative biopsy has the potential to decrease unnecessary treatment since up to a third of small renal masses are now reported to be benign at surgery. Percutaneous biopsy may also allow a better selection of renal tumors for active surveillance and minimally invasive ablative therapies. Finally, there is potential for stratifying initial therapy for metastatic renal cell carcinoma by histological subtype and in the future molecular characteristics.     

Renal tumors in end‐stage renal disease: A comprehensive review

The incidence of end‐stage renal disease has increased owing to the greater prevalence of patients with chronic kidney disease and diabetes mellitus. End‐stage renal disease is usually accompanied by acquired cystic disease and is a risk factor for renal cell carcinoma. The present review discusses the etiology of renal cell carcinoma in end‐stage renal disease patients, focusing on two unique renal cell carcinoma histological subtypes: acquired cystic disease‐associated renal cell carcinoma and clear cell papillary renal cell carcinoma. Acquired cystic disease‐associated renal cell carcinoma occurs almost exclusively in patients who underwent hemodialysis, especially long‐term (>10 years) hemodialysis. Its histology is distinctive: a cribriform or sieve‐like architecture with intra‐ or intracystic lumina; tumor cells containing abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli; and most notably, calcium oxalate crystal deposition. Recognition of the crystals is critical for diagnosing acquired cystic disease‐associated renal cell carcinoma. Acquired cystic disease‐associated renal cell carcinoma typically has an indolent clinical course, except in cases with sarcomatoid components. Clear cell papillary renal cell carcinoma also has an indolent course (no cases involving metastasis have been reported to date), and its features resemble those of both clear cell renal cell carcinoma and papillary renal cell carcinoma. Unlike acquired cystic disease‐associated renal cell carcinoma, which occurs only in end‐stage renal disease patients, clear cell papillary renal cell carcinoma occurs in non‐end‐stage renal disease patients as well. Additional renal tumors in end‐stage renal disease patients include anastomosing hemangiomas. Long‐term hemodialysis worsens the prognosis of end‐stage renal disease patients with renal cell carcinoma, regardless of its original histological subtype, presumably by inducing oxidative stress and sarcomatoid transformation.     

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

Background: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was preformed to assess the accuracy of pre-and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions.Materials and methods: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand.Results: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard.Conclusions: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma.CommentaryLocal tumor recurrence following nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) may be due to incomplete resection of the primary tumor, occult multicentric disease or the development of a new primary or metastatic focus of RCC in the renal remnant. The risk of multicentric disease in RCC has been evaluated and debated extensively in the literature. RCC generally occurs as a discrete focal lesion rather than an infiltrative process which is seen in carcinoma of the prostate. At issue is whether the molecular events that give rise to malignant transformation affect a discrete segment of the kidney or a broader segment of the renal tubular epithelium. A high incidence of multicentric RCC has been reported in patients with germ line mutations such as those that exist in von Hippel Lindau disease and other forms of hereditary RCC suggesting a global predisposition to malignant degeneration throughout the entire renal parenchyma.The incidence of multicentricity in sporadic RCC has been less clear. Emerging cytogenetic and molecular data suggest that satellite lesions may occasionally arise from the same malignant clone as their corresponding primary lesion and may therefore represent biologically significant intra-renal metastasises. A recent review of published studies comprising over 1100 cases of sporadic RCC indicated an aggregate incidence of 15.2% of tumor multifocality (range 6.5%–28%)[1]. It is important to remember that these studies represent a diverse group of patients and that RCC is in fact a heterogenous group of tumors. The risk of multicentricity is not equal in all patients and appears to be related to other prognostic variables such as tumor histology, stage and grade. For example, papillary RCC is known to be associated with a higher incidence of multifocality than the more common clear cell variant. The risk of multifocal disease also increases with larger tumors, particularly those that extend beyond the renal capsule (pT3+). Finally, some microfocal tumors are of unknown biological significance such as the finding of satellite adenomas. Of importance when considering relative indications for elective NSS is the incidence of multifocality when the primary or index tumor is ⩽ 4 cm. A recent review of the literature indicated that the incidence of multifocality in this setting is approximately 5%.The most worrisome implication of multifocal RCC is that this will predispose to an increased risk of local tumor recurrence following NSS. Although this potential risk must be considered, the relationship between multifocality and local recurrence is neither linear or predictable as suggested by the low overall local recurrence rates reported following NSS in several large series. In nearly 1800 cases of NSS reported in the literature to date, the risk of local tumor recurrence has ranged from 0–10% and is clearly lowest among patients undergoing elective NSS for small (⩽ 4 cm) low stage lesions [1]. The true biologic significance of multicentric renal tumors and their implication for NSS therefore remain to be fully elucidated.[1] Uzzo RG, Novick AC. Nephron-sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18.Andrew C. Novick, M.D.     

Residual stump metastasis from renal cell carcinoma

A rare case of ureteral stump metastasis 8 years after nephrectomy for renal cell carcinoma is reported. Twenty-six such cases are reviewed and the etiology of such lesions is discussed. Nephroureterectomy for renal cell carcinoma may be indicated when the risk of urogenous implantation and/or hematogenous spread is present.     

Renal cell carcinoma detected in a cadaveric donor after orthotopic liver and contralateral renal transplantation in two recipients: four-year follow-up

BACKGROUND: Although rare, renal cell carcinoma has been found during renal recovery for cadaveric organ transplantation. Previously, we reported this incidence to be 0.9%. In one cadaveric donor, the liver and left kidney had been transplanted before the discovery of renal cell carcinoma (T1) in the right kidney. METHODS: We retrospectively reviewed the medical records of two patients who had received cadaveric allografts from a donor with a known renal cell carcinoma. RESULTS: Both patients have been followed for 4 years with blood chemistries and chest x-ray every 3 months for year 1, every 4 months for years 2 and 3, and every 6 months thereafter. They also underwent allograft ultrasound every 6 months and an annual CT scan of the abdomen. Both patients have shown no evidence of metastatic disease throughout their follow-up. DISCUSSION: In the rare instance that a patient receives an organ from a cadaveric donor with a known renal cell carcinoma, it is mandatory to follow these patients closely observing for both allograft recurrence and metastatic disease.     

Contemporary epidemiology of renal cell carcinoma: perspectives of primary prevention

Objective  

Epidemiological research of recent years has produced evidence for a role of lifestyle-associated risk factors in the etiology of renal cell carcinoma (RCC), the most common renal tumor. In this review, we give an overview of recent trends in incidence and mortality and summarize the current knowledge on risk factors of RCC.     

Inflammatory pseudotumors of the kidney: a case report

Inflammatory pseudotumors are uncommon benign tumors of unknown etiology which may develop at several anatomical sites, e.g., the airways and gastrointestinal tissues, soft tissues, the orbit, the spleen, or the lymph nodes. The renal site is extremely rare, and presents the problem of differential diagnosis as the clinical and radiological aspects of this tumor are similar to those of an adenoma or an angiomyolipoma, and suggest the presence of a carcinoma, in particular a cystic renal carcinoma which is also a rare form of tumor. There is therefore a risk that this benign lesion could be misdiagnosed. Due to the good prognosis associated with this type of tumor, in cases where the definitive diagnosis has been established no surgical procedure is necessary. However, the difficulty in making this diagnosis preoperatively means that in general the organ has to be surgically removed so that a histological analysis can be made and the negative or positive findings confirmed. In the present study, the case of an inflammatory pseudotumor of the kidney has been described. In this instance, radical nephrectomy of the left kidney was carried out as the disease was presumed to be renal cell adenocarcinoma. However, the histopathological analysis was negative as regards malignancy, and indicated the presence of an inflammatory pseudotumor. This article raises the question of the problem in establishing a preoperative definitive diagnosis, as a correct diagnosis is often only confirmed following nephrectomy (in cases where the contralateral kidney is healthy).     

Prevalence of renal cell carcinoma: A nation-wide survey in Japan, 2002

OBJECTIVE: To investigate the incidence of renal cell carcinoma, classified by sex, age group and region in Japan, following a 5-year interval after a previous survey performed in 1997. METHODS: The survey was conducted between the beginning of January 2002 and the end of December 2002. A total of 1288 institutions in all 47 prefectures throughout Japan were requested to register cases. RESULTS: There were 7405 persons with renal cell carcinoma, consisting of 5063 males and 2342 females. Crude incidence rates were 8.2 and 3.6 per 100 000 population for men and women, respectively. Incidence rates in the Hokkaido region were highest followed by the Shikoku region. CONCLUSIONS: Despite incidence of renal cell carcinoma increasing to 7405 from the 6358 persons in 1997, statistical data reported by the Ministry of Health, Labor and Welfare indicate that rising age-adjusted death rate for this tumor reached a ceiling in the past decade. Early detection may have contributed to this current trend; however, further epidemiological research is required to fully elucidate this.     

Familial renal cell carcinoma: hereditary or coincidental?

The familial clustering of some cancers may be related to genetic factors, shared carcinogenic exposure among relatives or chance association. In cases of familial renal cell carcinoma identifying those persons at risk for renal tumors is difficult. There have been 28 family aggregates of renal carcinoma reported since 1961 but an abnormality in the constitutional karyotype has been demonstrated in the members of only 1 of these families. Since 1980 we have identified 5 more families in which a total of 12 relatives had renal cell carcinoma. However, peripheral blood karyotypes obtained from the 7 patients and 5 unaffected relatives whom we studied showed no significant abnormalities. With current laboratory techniques it is not possible to differentiate reliably familial renal tumors occurring by chance from those hereditary tumors posing a threat to remaining relatives. Therefore, in families with multiple cases of renal cell carcinoma we recommend that screening be conducted as has been suggested for families with von Hippel-Lindau's disease, with an initial renal ultrasound for family members at age 30 years and repeat examinations every 2 to 3 years.     

Changing incidence of non-melanoma skin cancer in New Zealand

Background: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the commonest types of non‐melanoma skin cancer (NMSC). The incidence of NMSC has been increasing globally with Australia recording a 1.5‐fold increase over the last 17 years. The incidence of NMSC in New Zealand is currently unknown. Given that Australia and New Zealand share similar latitude, sun exposure levels, and other risk factors, it is conceivable this increase has also occurred in New Zealand. This study aimed to provide an analysis of the incidence of NMSC within the Central Region of New Zealand based on longitudinal data derived from pathology reports. Methods: This retrospective study examined the pathology records of 26 411 patients who underwent surgical excision for 54 004 NMSC lesions which were histologically confirmed, over a 10‐year period from 1 January, 1997 to 1 January, 2007, within the Central Region of New Zealand. Results: Over the study period, 50 411 primary NMSC lesions were excised. The age‐standardized incidence for NMSC, BCC and SCC was 406, 299 and 118 per 100 000, respectively. Since 1999, the annual incidence of BCC and SCC has increased by 4.0% and 1.1%, respectively, with the greatest increases seen in the population over the age of 50 years. Conclusion: New Zealand has one of the highest incidence of NMSC in the world. The high and increasing incidence of NMSC underscores the importance for the development and implementation of a national health‐care delivery model, and a commitment to continued monitoring of the NMSC problem.     

Predicting cancer-control outcomes in patients with renal cell carcinoma

PURPOSE OF REVIEW: Several novel treatment modalities have been introduced for patients across all renal cell carcinoma stages. Observation or a variety of minimally invasive approaches can be applied to small renal masses. Conversely, aggressive loco-regional resections may be performed for locally advanced disease. Cytoreductive partial nephrectomy has become an alternative to radical nephrectomy. Finally, targeted therapies improve cancer control in unresectable or metastatic renal cell carcinoma. The variety of modes and stages at presentation and the number of treatment options may render medical decision-making highly complex. Various prognostic models and nomograms can assist with treatment decision-making in patients with renal cell carcinoma. RECENT FINDINGS: The multivariable risk-factor approach to renal cell carcinoma-specific mortality has been pioneered. In 1999 was proposed a multivariate model for prediction of individual survival in patients with metastatic renal cell carcinoma. Since then several prenephrectomy and postnephrectomy models have been developed. These models can be distinguished according to their target populations, discriminant properties (accuracy of predictions) and confirmed validity within independent cohorts. SUMMARY: We give a comparative outline of these model characteristics within existing tools. Our work provides the clinician with a complete list of such tools, including comparisons of their relative advantages and disadvantages.     

Familial papillary renal cell tumors and subsequent cancers: a nationwide epidemiological study from Sweden

PURPOSE: Familial risks in papillary renal cell carcinoma and association with second primary malignancies were studied using the nationwide Swedish Family Cancer Data Base. MATERIALS AND METHODS: Cancer data obtained from the Swedish Cancer Registry from 1961 to 1998 included 1,733 cases of papillary renal cell carcinoma. The standardized incidence ratio was used to measure cancer risk. RESULTS: Only 5 families were identified in which a parent had papillary renal cell carcinoma and an offspring had kidney cancer (nonsignificant SIR 1.51 for offspring). Discordant tumor sites associated with papillary renal cell carcinoma in the 2 generations were the upper aerodigestive tract and bladder (SIR 2.53, 95% CI 1.08 to 4.58 and 2.14, 95% CI 1.02 to 3.68, respectively). There was an overall increase in the risk of second primary malignancies of the lung, prostate and bladder and for non-Hodgkin's lymphoma and leukemia in patients with papillary renal cell carcinoma. The risk for a second primary tumor of the bladder associated with papillary renal cell carcinoma during the followup of 1 to 10 years was about 15 times higher than that associated with adenocarcinoma, which is the most common histological type of kidney cancer. The SIR was significantly higher in females than in males (59.67, 95% CI 40.23 to 82.94 versus 18.76, 95% CI 14.51 to 23.56). CONCLUSIONS: In addition to the familial association of these 2 cancer sites, the high risk of a second primary cancer of the bladder in patients with papillary renal cell carcinoma may reflect a common genetic alteration.     

Renal cancer and malformations in relatives of patients with Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with five loci identified thus far. The spectrum of disease includes diverse malformations of the kidney and lower urinary tract. The incidence of BBS is approximately 1/100,000 with a predicted heterozygote frequency of 1/160, and it has been suggested that heterozygotes are at increased risk of obesity and hypertension. METHODS: We describe renal disease in relatives of 109 UK BBS patients. Using PCR with fluorescent microsatellite markers we amplified DNA derived from renal tumours of affected parents to determine whether there was loss of heterozygosity at any of four BBS loci and two other gene loci associated with clear cell renal cell carcinoma (CC-RCC). RESULTS: CC-RCC was diagnosed in three of 180 BBS parents and there was loss of heterozygosity at BBS1 (11q13) in the tumour tissue of one of these subjects. In addition, there was a high incidence of renal agenesis in siblings of BBS patients and two BBS families were identified with apparently dominant inheritance of renal malformations. In one family we were able to demonstrate that renal malformations segregated with the BBS2 locus (16q21). CONCLUSIONS: Since all parents and two-thirds of siblings of BBS patients must be heterozygous for BBS mutations, our observations may implicate BBS genes in the pathogenesis of both renal cancer and malformations, both disorders of precursor cell growth and differentiation. We suggest these observations may have important implications for screening potential BBS carriers for kidney disease and may lead to a greater understanding of the aetiology of renal disease in the general population.     

Molecular genetic parameters in pathogenesis and prognosis of testicular germ cell tumors

Aim of this review article was to critically analyze the recently described cytogenetic and molecular markers for testicular germ cell tumors with regard to their clinical utility. The isochromosme i(12p) represents the most common and characteristic cytogenetic finding which already appears in testicular carcinoma in situ. A number of proto-oncogenes (cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, their role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial testicular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromosomal loci encoding potential testicular tumor susceptibility genes have been identified, the genetic basis of testicular cancer pathogenesis is still unknown. With regard to molecular prognostic risk factors most of the reported data on proliferation markers, tumor suppressor genes, proteases and adhesion molecules have to be confirmed in prospective randomized trials prior to their widespread clinical use. Based on the available data on prospective studies the percentage of embryonal carcinoma and vascular invasion appear to be the most significant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compared to all other histological components appear to be most promising in the research for prgnosticators of metastatic disease. In conclusion, the increasing knowledge of molecular genetic events involved in pathogenesis and prognosis of testicular germ cell tumors will not only help to better understand development and progression of testicular cancer, but it will also define new approaches to classification and management of germ cell tumors     

Improvement in survival of patients with renal cell carcinoma--the role of the serendipitously detected tumor

A review of 212 cases of renal cell carcinoma diagnosed during a 40-year period revealed an increasing number of cases detected during imaging studies performed for nonurological reasons. These so-called incidentally detected renal cell carcinomas are increasing in incidence, generally of low stage and associated with significantly improved survival, and they constitute the majority of the patients with improved prognosis during the recent 2 decades. The clinical course and disease stage in patients who continue to present with symptoms of the disease have not changed in the last 40 years. These data suggest that with currently available treatments for renal cell carcinoma a principal method to improve the prognosis of this disease would be through earlier detection. Low disease incidence would mitigate against morphological screening but case finding techniques may prove useful.     

Familial renal carcinoma: clinical evaluation, clinical subtypes and risk of renal carcinoma development

PURPOSE: Familial renal carcinoma is defined as families with 2 or more individuals with renal cell carcinoma without evidence of known hereditary renal carcinoma syndromes. To better characterize this familial cancer we reviewed renal carcinoma families evaluated at the National Cancer Institute between 1990 and 2004 to identify distinctive features of these families. We also determined the risk of renal carcinoma in first-degree relatives of affected family members. MATERIALS AND METHODS: We evaluated 141 at risk asymptomatic relatives of affected individuals from 50 families with 2 or more members with renal carcinoma. Histology slides of renal tumors from affected family members were reviewed. At risk members from renal carcinoma families were screened for occult renal neoplasms by renal ultrasound and computerized tomography. DNA from select families was tested for germline mutations of known renal carcinoma genes when clinically indicated and constitutional cytogenetic analysis was performed to search for germline chromosome alterations. RESULTS: Familial renal carcinoma families could be subdivided into subtypes based on tumor multiplicity and renal tumor histology. Of 141 at risk members of renal carcinoma families screened for occult renal tumors 2 were found to have occult renal tumors, which were identified as renal oncocytoma and a solid tumor that was not resected, respectively. No histologically confirmed occult renal carcinomas were detected in at risk family members. Several families previously classified as having familial renal carcinoma were found on further evaluation to have hereditary renal cancer syndromes. CONCLUSIONS: Familial renal carcinoma is a heterogeneous clinical and pathological entity. Familial renal carcinoma was subdivided into groups based on tumor multiplicity and tumor pathology. The empirical risk of histologically documented renal carcinoma in first-degree relatives who were members of familial renal carcinoma families was less than 1:141. One renal oncocytoma and 1 small solid renal tumor were detected.     

Renal cell carcinoma with widespread metastasis in 19 years old young male – A rare case report

Introduction and importanceRenal cell carcinoma is the most common malignant tumor of the kidney which occurs more frequently in men and older people than in women and young adults. Renal cell carcinoma is the second most common renal malignancy diagnosed among pediatric and adolescent patients comprising of 2% to 6% of renal cancers.Case presentationA 19 years old young adult male came with a history of epigastric and back pain, hematuria and weight loss. Per abdominal examination showed a palpable mass in the epigastric and left hypochondriac region. Radiological imaging showed diffuse infiltration of renal interstitium with multiple hypodense lesions in left kidney, renal vein infiltration, and lytic destruction of vertebral bodies and left superior pubic ramus. Fine needle aspiration cytology and trucut biopsy was taken which confirmed renal cell carcinoma, clear cell type with bone metastasis.Clinical discussionAlthough most renal cell carcinoma is sporadic and relatively uncommon in young adults, the incidence of renal cell carcinoma in this age group has steadily increased. Young adults are less likely to receive diagnosis of renal cell carcinoma incidentally. A few reported pediatric series have shown that renal cell carcinoma is highly aggressive, tends to be invasive, and metastasizes to the lungs and bones.ConclusionYoung adult with clear cell renal cell carcinoma showing wide spread metastasis is rare. Since, young age is an independent prognostic factor for cancer-specific survival, early diagnosis of the tumor will be beneficial for patients.     

Is adrenalectomy a necessary component of radical nephrectomy? UCLA experience with 511 radical nephrectomies

PURPOSE: We determine the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluate the role of adrenalectomy as part of radical nephrectomy. MATERIALS AND METHODS: The records of 511 patients undergoing radical nephrectomy with ipsilateral adrenalectomy for renal cell carcinoma at our medical center between 1986 and 1998 were reviewed. Mean patient age was 63.2 years (range 38 to 85), and 78% of the subjects were males and 22% were females. Patients were divided into subgroups of 164 with localized (stage T1-2 tumor, group 1) and 347 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. Staging of tumors was performed according to the 1997 TNM guidelines. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared to postoperative histopathological findings to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. RESULTS: Of the 511 patients 29 (5.7%) had adrenal involvement. Average size of the adrenal tumor was 3.86 cm. (standard deviation 1.89). Tumor stage correlated with probability of adrenal spread, with T4, T3 and T1-2 tumors accounting for 40%, 7.8% and 0.6% of cases, respectively. Upper pole intrarenal renal cell carcinoma most likely to spread was local extension to the adrenal glands, representing 58.6% of adrenal involvement. In contrast, multifocal, lower pole and mid region renal cell carcinoma tumors metastasized hematogenously, representing 32%, 7% and 4% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 8.9 cm., range 3 to 17) and adrenal involvement (independent of stage) was not statistically significant. Renal vein thrombus involvement was demonstrated in 8 of 12 cases (67%) with left and 2 of 9 (22%) with right adrenal involvement. Preoperative CT demonstrated 99.6% specificity, 99.4% negative predictive value, 89.6% sensitivity and 92.8% positive predictive value for adrenal involvement by renal cell carcinoma. CONCLUSIONS: With a low incidence of 0.6%, adrenal involvement is not likely in patients with localized, early stage renal cell carcinoma and adrenalectomy is unnecessary, particularly when CT is negative. In contrast, the 8.1% incidence of adrenal involvement with advanced renal cell carcinoma supports the need for adrenalectomy. Careful review of preoperative imaging is required to determine the need for adrenalectomy in patients at increased risk with high stage lesions, renal vein thrombus and upper pole or multifocal intrarenal tumors. With a negative predictive value of 99.4%, negative CT should decrease the need for adrenalectomy. In contrast, positive findings are less reliable given the relatively lower positive predictive value of this imaging modality. Although such positive findings may raise suspicion of adrenal involvement, they may not necessarily indicate adrenalectomy given the low incidence, unless renal cell carcinoma with risk factors, such as high stage, upper pole location, multifocality and renal vein thrombus, is present.