EUROPEAN UROLOGY 57 (2010)

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1 EUROPEAN UROLOGY 57 (2010) available at journal homepage: Kidney Cancer Hybrid Renal Cell Carcinomas Containing Histopathologic Features of Chromophobe Renal Cell Carcinomas and Oncocytomas Have Excellent Oncologic Outcomes Matthias Waldert a, *, Tobias Klatte a, Andrea Haitel b, Mehmet Ozsoy a, Joerg Schmidbauer a, Michael Marberger a, Mesut Remzi a a Department of Urology, Medical University of Vienna, Vienna, Austria b Department of Pathology, Medical University of Vienna, Vienna, Austria Article info Article history: Accepted May 5, 2009 Published online ahead of print on May 18, 2009 Keywords: Chromophobe renal cell carcinoma Hybrid renal cell carcinoma Oncocytoma Renal tumor biopsy Abstract Background: Modern histopathology is able to differentiate chromophobe renal cell carcinomas (crccs), oncocytomas, and chromophobe oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear. Objective: To determine the clinical course of hybrid RCC. Design, setting, and participants: Ninety-one surgically treated tumors, originally classified as oncocytoma or crcc, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells). Interventions: Radical tumor nephrectomy or nephron-sparing surgery. Measurements: Recurrence-free and tumor-specific survival. Results and limitations: Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were crccs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pt3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for crcc was pt1 in 50% of tumors (n = 17), pt2 in 23.5% of tumors (n = 8), and pt3a in 26.5% of tumors (n = 9). Low-grade RCC was found in 76.5% of tumors (n = 26), and vascular invasion was found in 11.8% of tumors (n = 4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two crccs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and crcc were 100%, 100%, and 97%, respectively. Conclusions: Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses. # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Tel ; Fax: address: matthias.waldert@meduniwien.ac.at (M. Waldert) /$ see back matter # 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 662 EUROPEAN UROLOGY 57 (2010) Introduction Until recently, solid renal tumors were treated either by radical nephrectomy or by nephron-sparing surgery. Recently, more and more small renal tumors are incidentally found, especially in older patients, and alternative treatment options (energy-ablative treatment and active surveillance) have been developed. Studies focusing on the natural history of small renal tumors showed excellent cancer-specific survival rates [1], rare progression [2], and no growth or minimal growth during follow-up, favoring nephron-sparing surgery as the standard treatment of these lesions [3 5]. All of these studies were small, were retrospective, and were performed in highly selected patients; this led to the hypothesis of overtreatment, and surveillance strategies were introduced recently [6]. Since we have no reliable selection criteria, renal tumor biopsy (RTB) gained popularity, and minimally invasive treatment options seemed to be safer for tumor control [7]. The use of RTB is intended to filter out benign lesions preoperatively. Drawbacks of RTB include unclear histopathology results and uncertainty as to whether an oncocytoma found on biopsy is a safe diagnosis. The reported incidence rate of oncocytomas varies from 3.2% to 7% [8]. In the 2004, the World Health Organization (WHO) classified renal-tumor oncocytomas as benign neoplasms. Reports, however, exist in the literature of malignant oncocytomas and metastatic oncocytomas, which led to the concept of grading these tumors [9]. But many of these oncocytomas may have been inappropriately categorized because eosinophilic chromophobe renal cell carcinomas (crccs) have overlapping cytoarchitecturial features and exhibit a low metastatic potential [10]. CRCC is the third most common carcinoma of renal tubular epithelium. Its incidence rate varies from 3.6% to 10.4% of all resected tumors [11]. A relationship between these lesion types exists because crcc frequently coexists within the same kidney or in the contralateral kidney of oncocytoma patients [12]. Additionally, hybrid renal-cell neoplasms containing areas of crcc and oncocytoma have been described. In RTB, hybrid renal cell carcinomas (RCCs) can only be found by chance; thus, RTB cannot exclude hybrid RCCs when showing oncocytomas [13]. In this study we reviewed and reevaluated all cases of oncocytoma and crcc resected at our institution to identify cases of hybrid RCC tumors and to study the clinical behavior of these entities compared with pure oncocytomas and crccs. To distinguish these three entities, the expression of cytokeratin 7 (CK7) was measured [14]. 2. Materials and methods From September 1994 to January 2008, 91 unilateral solid renal tumors were primarily treated surgically, with the final histology being oncocytoma, crcc, or hybrid RCC. For this study, hematoxylin and eosin (H&E) stained slides of all tumors were reviewed by one uropathologist. Tumors were categorized based on morphologic classification, according to the recommendations of the International Union against Cancer and the WHO s Classification of Tumors [15]. In crccs, grading was performed according to the system of Fuhrman [15]. In total, 45 tumors were classified as pure oncocytomas, 32 tumors were classified as crccs, and 14 tumors were classified as having mixed features or as being hybrid RCCs. For further differential diagnoses of oncocytomas and hybrid RCCs, additional gross sections were cut from each paraffin-embedded tumor and were analyzed using CK7 staining by immunohistochemistry (Dako, Wien, Austria). In this regard, only distinct membranous staining was considered to be a positive reaction. Faint diffuse cytoplasmatic staining without unequivocal membranous reaction (which can be seen in some oncocytomas) was considered to be a negative reaction. Oncocytomas that expressed CK7 in >10% of cells were reclassified as hybrid RCCs. With this definition, two oncocytomas were reclassified as hybrid RCCs (4.4%). Follow-up was done every 6 mo in both oncocytoma patients and crcc patients. Follow-up consisted of physical examination, routine laboratory evaluation, and ultrasound. In case of crcc, a computed tomography (CT) scan was done every 6 mo; in case of oncocytoma, a CT scan was done yearly. Survival curves were plotted using the Kaplan- Meier method, and life tables were applied to calculate survival rates. 3. Results After slide review and immunohistochemical evaluation, 43 tumors were classified as pure oncocytomas. In this cohort, mean patient age was yr (range: yr). Tumors were located on the left side in 58% of patients, and tumors were found in males at a rate of 48%. Only one tumor was multifocal (two pure oncocytomas). Mean tumor size was cm (range: cm). Twenty-seven tumors were treated with nephron-sparing surgery, and 16 tumors were treated with radical nephrectomy (Table 1). Thirty-four patients were diagnosed with crcc. Mean age was yr (range: yr). Tumors were located in 62% of patients on the left side, and tumors were found in males at a rate of 41%. Mean tumor size was cm (range: cm). Three tumors were multifocal. Eight tumors were treated with radical nephrectomy, and 26 tumors were treated with nephron-sparing surgery. Of the 34 patients, 27 patients (80%) were asymptomatic at diagnosis, and the remaining 8 patients presented with local symptoms. Pathologic stage at surgery and Fuhrman grade are shown in Table 2. None of the 34 patients had metastatic disease at diagnosis. The lymph node status was pnx in 21 patients (62%), pn0 in 12 patients (35%), and pn1 in 1 patient (3%, microscopic metastasis). The characteristics of the 16 hybrid RCCs (17.6%) are shown in Table 1. Two (12.5%) of these tumors were originally classified as oncocytomas. Final histology showed Table 1 Characteristics of patients with oncocytoma, chromophobe renal cell carcinoma (crcc), and hybrid renal cell carcinoma (RCC) Oncocytoma crcc Hybrid RCC No. of patients Age, yr SD Male/female, % 48/52 41/59 63/37 Left/right kidney, % 58/42 62/38 65/35 Tumor size, cm Metastasis, no Multifocality, no yr tumor-specific survival, %

3 EUROPEAN UROLOGY 57 (2010) Table 2 Stage and grade distribution in chromophobe renal cell carcinoma (crcc) and hybrid renal cell carcinoma (RCC) in percent and number of patients 10 pt1 tumors, 4 pt2 tumors, and 2 pt3a tumors. Fourteen tumors were classified as low grade, whereas two tumors were classified as high grade (Table 2). In our series the mean follow-up was mo. The overall survival rate at 3 yr was 93%. The rates of 3-yr tumorspecific survival for oncocytoma, hybrid RCC, and crcc were 100%, 100%, and 97%, respectively ( p-value was not significant). In the crcc group, two patients with high-grade crcc and spindle-cell features developed tumor recurrence. One patient presented with pt3a disease, developed visceral metastasis after 25 mo, and subsequently died 3 mo later. The other patient had pt3a pn1 disease and developed a singular bone metastasis after 118 mo that was resected. The patient remained alive after 138 mo of follow-up. 4. Discussion crcc (n = 34) Hybrid RCC (n = 16) pt stage pt1a, no. (%) 13 (38%) 8 (50%) pt1b, no. (%) 4 (12%) 2 (12.5%) pt2, no. (%) 8 (23%) 4 (25%) pt3a, no. (%) 9 (27%) 2 (12.5%) Nx/pN0, no. (%) 33 (97%) 16 (100%) pn1, no. (%) 1 (3%) 0 High Fuhrman grade (G3/G4), no. (%) 8 (23.5%) 2 (12.5%) With today s modern imaging and the widespread use of imaging methods such as ultrasound and CT scans, more and smaller renal tumors are diagnosed. The largest increase in incidence is in tumors <4 cm[16]. Patients are often elderly and unfit, and little is known about the natural history of these lesions when left untreated [7]. Fine-needle biopsy as described in three prospective studies had a sensitivity for the diagnosis of malignancy from 80% to 92%; the falsepositive rate was nearly zero [17 19]. RCC subtyping was correct in 78 92% of tumors. The most frequent complication of RTB is hemorrhage, which, in most cases, occurs without clinical evidence and is self-limiting. The rate of serious adverse events was <1%. One of the major problems discussed was the hybrid RCC that contained crcc and oncocytoma parts. The crcc part can only be hit during biopsy by chance. Cases of oncocytoma with progression or metastases could be due to hybrid RCCs that were missed by inadequate sectioning of the removed tissue. Oncocytotic cells are found in numerous RCCs, such as crcc, the granular cell variant of RCC, and the eosinophilic variant of papillary type RCC (type 2). Liu et al reported that all oncocytomas were vimentin negative, whereas granularcell RCC and eosinophilic papillary RCC were vimentin positive. CRCCs are also vimentin negative, but they can be differentiated from oncocytomas by Hale s colloid-ferrous staining. C-kit and CK7 are also able to reveal hybrid RCCs, as shown in the study by Liu et al [14]. In the two hybrid tumors initially classified as oncocytomas, no CK7 staining was done at the first pathologic evaluation. In this study, crcc showed a 3-yr tumor-specific survival rate of 97%. Only 2 out of 32 crccs developed metastases. Both were high-grade and high-stage tumors, and one of them was initially node positive. Both were pure crccs with spindle-cell features without oncocytotic areas. One patient died because of visceral metastasis 28 mo after surgery. Our findings are consistent with those reported in other series, which showed 5-yr tumor-specific survival rates of 81 91% [11,20,21]. In this series, 16 patients had hybrid RCCs. As reported by Mai et al, there are many similar microscopic features between oncocytomas and crccs. Tumors can show a mixture of areas typical of oncocytoma and crcc, and tumors can have patches of chromophobe cells scattered over different areas or cells that show features intermediate between oncocytomas and crccs [22]. Diagnoses based on conventional H&E staining can be difficult because of the overlapping morphologic characteristics, but diagnoses can be made by employing Hale s colloidal staining and CK7. Hybrid RCCs may represent a morphologic spectrum of both tumor entities, and the concept of a common origin of crcc and renal oncocytoma from intercalated cells of the collecting tubules seems feasible. Overall, 14 out of 16 hybrid RCCs were classified as crcc because they had up to 90% oncocytotic cells. Two out of 16 tumors were primarily classified as oncocytomas, and only after reevaluation could their true status be determined. Patients with hybrid RCCs were slightly older (69 yr vs 63 yr, p > 0.05) and showed a male predominance (63%). But does this presence of crcc areas affect prognosis? Lack of data concerning the natural history of hybrid RCCs and pure oncocytomas or crccs are arguments for surgery. Although benign, oncocytomas can still be associated with significant morbidity. Dechet et al noted tumor-related constitutional symptoms in 15% of patients and gross hematuria in 12% of patients in a series of 138 oncocytomas [23]. Only two series are available on the evolution of oncocytomas that were not surgically treated [10,13]. In a series reported in 1991, the diagnosis of oncocytoma was made radiologically, with no histologic evaluation; this is clearly inadequate [24]. Twelve suspected oncocytomas were followed with a mean follow-up of 7 yr, and none of these tumors increased in size. So the investigators concluded that oncocytomas were benign tumors with no further evolution when the final size is reached. In contrast, Neuzillet et al reported on 15 RTBproven oncocytomas that showed an increase in size. Six of their 15 patients needed surgery. These patients were significantly younger, and one patient showed a crcc at final histology. Yet none of these studies specifically addressed the issue of hybrid RCCs, which is important, because advocates against RTB could argue that showing oncocytoma at RTB is inadequate and that about 18% of tumors will have crcc at final histology. In the prospective series of Schmidbauer et al, initially 13 oncocytomas were diagnosed using RTB. Final histology at surgery showed 11 oncocytomas (84.6%) and 2 hybrid RCC tumors (15.4%) [17].

4 664 EUROPEAN UROLOGY 57 (2010) If hybrid RCCs show the same excellent results as oncocytomas, as shown in this study, an RTB showing oncocytoma also shows a reasonable risk for further active surveillance. It is, however, very important to inform the patient in advance that there is an 18% risk that CK7-positive cells, and thus a hybrid RCC, can be found. Of course, it is impossible to talk about the natural history of hybrid RCCs because all tumors are treated surgically, and it is also unclear whether the finding of >10% CK7-positive cells is correct. Whether the oncocytotic-to-chromophobe cell ratio has a clinical significance and determines biological behavior cannot be determined. Bigger prospective studies with larger patient cohorts are needed to determine whether there is cut-off over which prognosis significantly changes. Prognoses in our cohort were excellent and were comparable to those of pure oncocytomas, with a 3-yr tumor-specific survival rate of 100% despite two pt3a tumors and two high-grade lesions. Regarding tumor size, there was no statistical significant difference in tumor size between the three entities. If technically feasible, nephron-sparing surgery for benign tumors seems feasible even for tumors >4 cm. No study results are yet available on the uses of ablative therapy in oncocytomas or in hybrid RCCs. This can also hypothesized for hybrid RCCs. As shown by our series, the clinical course of these tumors after surgery is benign, so minimally invasive ablative procedures or surveillance in selected patients after careful counseling may be options. Yet there are several limitations in this study: It is confined to a single institution, and it is a retrospective study. Follow-up in this series was mo, and thus only 3-yr cancer-specific survival data can be given. Due to the low incidence of hybrid RCC, numbers are small, and we have no follow-up on oncocytomas or hybrid RCCs that are not surgically treated. The importance of surgery for the prognosis of hybrid RCC is unclear. Multi-institutional, prospective studies with larger patient cohorts and longer follow-up are needed to further address these issues. 5. Conclusions Hybrid RCCs are more common than expected. Patients with oncocytomas on RTB should be informed that there is a 15 18% risk that the tumor might be a hybrid RCC. Survival in this cohort is 100% for both hybrid RCCs and oncocytomas. They may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses. Author contributions: Matthias Waldert had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Waldert, Klatte, Remzi, Haitel, Marberger. Acquisition of data: Haitel, Ozsoy, Schmidbauer. Analysis and interpretation of data: Waldert, Klatte, Remzi. Drafting of the manuscript: Waldert, Klatte, Remzi. Critical revision of the manuscript for important intellectual content: Marberger. Statistical analysis: Waldert, Remzi, Schmidbauer. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: None. Other (specify): pathologic slide review: Haitel. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. References [1] Beisland C, Hjelle KM, Reisæter LAR, Bostad L. Observation should be considered as an alternative in management of renal masses in old and comorbid patients! Eur Urol 2009;55: [2] Van Poppel H, Joniau S. Is surveillance an option for the treatment of small renal masses? Eur Urol 2007;52: [3] Ozsoy M, Klatte T, Waldert M, Remzi M. Surveillance for the management of small renal masses. Adv Urol 2008, article [4] Chawla SN, Crispen PL, Hanlon AL, Greenberg RE, Chen DY, Uzzo RG. The natural history of observed enhancing renal masses: metaanalysis and review of the world literature. J Urol 2006;175: [5] Becker F, Suttmann H, Siemer S, Stöckle M. Is there a place for surveillance in the management of small renal tumors? Nat Clin Pract Urol 2006;3: [6] Volpe A, Jewett MA. The role of surveillance for small renal masses. Nat Clin Pract Urol 2007;4:2 3. [7] Remzi M, Marberger M. Renal tumor biopsies for evaluation of small renal tumors: why, in whom, and how? Eur Urol 2009;55: [8] Romis L, Cindolo L, Patard JJ, et al. Frequency, clinical presentation and evolution of renal oncocytomas: multicentric experience from a European database. Eur Urol 2004;45:53 7. [9] Aslam MI, Spencer L, Garcea G, et al. A case of liver metastasis from an oncocytoma with a focal area of chromophobe renal cell carcinoma: a wolf in sheep s clothing. Int J Surg Pathol 2009;17: [10] Davis CJ, Sesterhenn IA, Mostofi FK. Renal oncocytoma: clinicopathological study of 166 patients. J Urogenital Pathol 1991;1: [11] Klatte T, Han KR, Said JW, et al. Pathobiology and prognosis of chromophobe renal cell carcinoma. Urol Oncol 2008;26: [12] Licht MR, Novick AC, Tubbs RR, Klein EA, Levin HS, Streem SB. Renal oncocytoma: clinical and biological correlates. J Urol 1993;150: [13] Neuzillet Y, Lechevallier E, Andre M, Daniel L, Nahon O, Coulange C. Follow-up of renal oncocytoma diagnosed by percutaneous tumor biopsy. Urology 2005;66: [14] Liu L, Qian J, Singh H, Meiers I, Zhou X, Bostwick DG. Immunohistochemical analysis of chromophobe renal cell carcinoma, renal oncocytoma, and clear cell carcinoma: an optimal and practical panel for differential diagnosis. Arch Pathol Lab Med 2007;131: [15] Stoerkl S, Eble JN, Adlakha K, et al. Classification of renal cell carcinoma: workgroup no. 1. Union International contre le cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 1997;80: [16] Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Rising incidence of small renal masses: a need to reassess treatment effect. J Nat Cancer Inst 2006;98:

5 EUROPEAN UROLOGY 57 (2010) [17] Schmidbauer J, Remzi M, Memarsadeghi M, et al. Diagnostic accuracy of computed tomography-guided percutaneous biopsy of renal masses. Eur Urol 2008;53: [18] Neuzillet Y, Lechevallier E, Andre M, Daniel L, Coulange C. Accuracy and clinical role of fine needle percutaneous biopsy with computerized tomography guidance of small (less than 4.0 cm) renal masses. J Urol 2004;171: [19] Lechevallier E, André M, Barriol D, et al. Fine-needle percutaneous biopsy of renal masses with helical CT guidance. Radiology 2000;216: [20] Cindolo L, de la Taille A, Schips L, et al. Chromophobe renal cell carcinoma: comprehensive analysis of 104 cases from multicenter European database. Urology 2005;65: [21] Patard JJ, Leray E, Rioux-Leclercq N, et al. Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. J Clin Oncol 2005;23: [22] Mai KT, Dhamanaskar P, Belanger E, Stinson WA. Hybrid chromophobe renal cell neoplasm. Pathol Res Pract 2005;201: [23] Dechet CB, Bostwick DG, Blute ML, Bryant SC, Zincke H. Renal oncocytoma: multifocality, bilateralism, metachronous tumor development and coexistent renal cell carcinoma. J Urol 1999;162:40 2. [24] Remzi M, Katzenbeisser D, Waldert M, et al. Renal tumour size measured radiologically before surgery is an unreliable variable for predicting histopathological features: benign tumours are not necessarily small. BJU Int 2007;99: Editorial Comment on: Hybrid Renal Cell Carcinomas Containing Histopathologic Features of Chromophobe Renal Cell Carcinomas and Oncocytomas Have Excellent Oncologic Outcomes Axel Bex The Netherlands Cancer Institute, Division of Surgical Oncology, Department of Urology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands a.bex@nki.nl The objective of Waldert and co-authors [1] was to determine the clinical course of hybrid renal cell carcinomas (RCCs). The authors acknowledge that the evidence is biased by retrospective analysis of a cohort that had definite surgical treatment and a thorough histologic diagnosis based on the entire tumour specimen. The untreated natural histories of oncocytomas andofhybridrccsmaywellbedifferent. In their study, chromophobe RCCs (crccs) were larger tumours, and 27% were pt3 versus only 12.5% of hybrid RCCs. While this finding may reflect the more aggressive course of crccs, it may simply represent the inherent bias of any retrospective analysis. This study is not a prospective evaluation of patients with similar criteria. If the group of hybrid RCCs had contained 27% pt3 tumours, would the 3-yr survival still be 100%? Ultimately, the numbers are too small and a 3-yr follow-up is too short to conclude that survival of hybrid RCCs and of oncocytomas are equivalent. Despite reports that lead time and length biases may be associated with overtreatment of small renal tumours [2], surveillance strategies should be addressed with caution. Only few surveillance series of biopsy-proven oncocytomas exist, and a significant proportion of cases described in the literature lack follow-up [3,4]. Gudbjartsson and co-workers described oncocytomas that can cause significant discomfort [5], such as haematuria (32%), abdominal pain (29%), and weight loss (10%). The small longitudinal study of Neuzillet and coworkers [3] probably provides the best available evidence of what to expect from surveillance. Fifteen patients with biopsyproven oncocytomas were followed with watchful waiting. Six eventually needed surgery. The increase in tumour size appeared with variable velocity, and rapid growth was the indication for surgery. The authors concluded that monitoring should not miss the time for nephron-sparing surgery. Frequent controls with imaging and a risk of nephrectomy have to be balanced against early interventions. References [1] Waldert M, Klatte T, Haitel A, et al. Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinomas and oncocytomas have excellent oncologic outcomes. Eur Urol 2010;57: [2] Black WC, Ling A. Is earlier diagnosis really better? The misleading effects of lead time and length biases. AJR Am J Roentgenol 1990;155: [3] Neuzillet Y, Lechevallier E, Andre M, et al. Follow-up of renal oncocytoma diagnosed by percutaneous tumor biopsy. Urology 2005;66: [4] Perez-Ordonez B, Hamed G, Campbell S, et al. Renal oncocytoma: a clinicopathologic study of 70 cases. Am J Surg Pathol 1997;21: [5] Gudbjartsson T, Hardarson S, Petursdottir V, et al. Renal oncocytoma: a clinicopathological analysis of 45 consecutive cases. BJU Int 2005;96: DOI: /j.eururo DOI of original article: /j.eururo

6 666 EUROPEAN UROLOGY 57 (2010) Editorial Comment on: Hybrid Renal Cell Carcinomas Containing Histopathologic Features of Chromophobe Renal Cell Carcinoma and Oncocytoma Have Excellent Oncologic Outcomes Frank Becker University Clinics of Saarland, Department of Urology, Kirrbergerstr, D Homburg/Saar, Germany I thank Waldert et al for this interesting manuscript, which exposes a rare and infrequently described renal tumour entity, the oncocytic hybrid renal cell carcinoma (RCC), a malignant renal tumour with a coincidence of chromophobe RCC and oncocytoma. This tumour seems to be present in a larger percentage of renal masses than previously assumed, and there seems to be a large estimated number of unreported cases with tumours misleadingly classified and undercategorised as entirely pure oncocytomas [1]. For this reason, urologists supporting pretherapeutic renal tumour biopsy (RTB) should consider the following issues. The main task of RTB is to filter out benign tumours, mainly oncocytomas (3.2 7% of all renal tumours [2]), to avoid unnecessary surgery, but RTB does not always lead to positive histopathologic findings, particularly in small tumours or cystic lesions. Moreover, RTBs bear a marginal but existent risk for complications [3]. If an oncocytoma is confirmed by RTB, there is still the possibility that a hybrid RCC is hidden within the tumour [4]. The chromophobic fractions of these tumours show only a low malignant potential, and the cancer-specific survival (CSS) of these hybrid RCCs is reported at 100% in this article. But the described mean follow-up of 50 mo is too short (only CSS after 3 yr is described) to describe the long-term behaviour of this tumour type. Furthermore, the natural history of this tumour type, based on a conservative and observant therapy, cannot be estimated through this study, as all patients underwent surgery [1]. Thus, the reader should not hastily conclude that patients with hybrid RCC are suitable for active surveillance. For this conclusion, further data on the natural course of this entity are lacking. References [1] Waldert M, Klatte T, Haitel A, et al. Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinoma and oncocytoma have excellent oncologic outcomes. Eur Urol 2010;57: [2] Romis L, Cindolo L, Pattard JJ, et al. Frequency, clinical presentation and evolution of renal oncocytomas: multicentric experience from a European database. Eur Urol 2004;45:53 7. [3] Lechevallier E, André M, Barriol D, et al. Fine-needle percutaneous biopsy of renal masses with helical CT guidance. Radiology 2000;216: [4] Neuzillet Y, Lechevallier E, André M, Daniel L, Nahon O, Coulange C. Follow-up of renal oncocytoma diagnosed by percutaneous tumour biopsy. Urology 2005;66: DOI: /j.eururo DOI of original article: /j.eururo