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Percutaneous Renal Biopsies for Small Renal Masses: Complex Tumors on Nephrometry Should Be the First Targets
Original Study
Percutaneous Renal Biopsies for Small Renal Masses: Complex Tumors on Nephrometry Should Be the First Targets Alexandre Ingels,1,4 Eric Barret,1 Rafael Sanchez-Salas,1 Marc Galiano,1 François Rozet,1 Stephane Lenoir,2 Nina Weber,3 François Audenet,1 Xavier Cathelineau1 Abstract Renal mass biopsy for small tumor is a safe procedure. It allows accurate distinction between benign and malignant tumors. This strategy is particularly relevant for nephrometry complex tumors, where biopsies present a higher yield and surgery a higher morbidity. Objective: To assess the diagnostic yield, accuracy, and complications rate for computed tomography (CT)-guided renal biopsies for solid renal masses (SRM); to analyze predictive factors for diagnostic biopsies. Patients and Methods: We performed a single-center, retrospective study based on a pathologic database query for CT-guided, percutaneous renal biopsies. Inclusion criteria included presence of SRM; exclusion criteria included the presence of metastases, non-cT1a or higher cancer (> 4 cm), and non-CT-guided techniques. Of 119 patients who underwent renal biopsies, 40 (34%) were excluded from the study; 79 (66%) biopsy outcomes were analyzed. Clinical, radiologic (RENAL score), and pathologic features were reported. Differences between contributive and noncontributive biopsies were tested with Mann-Whitney U or chi-square tests, as appropriate. Multiple-variable analyses searching for predicting factors of biopsy contribution were performed with binary logistic regressions. Results: CT-guided renal biopsies for SRM present a high yield (88.6%) and high accuracy for differentiating malignant from benign tumors (96%). They are less accurate for histologic subtype (93%) and unreliable for Fuhrman grading (64%). CT-guided renal biopsy is safe (minor complication rate, 2.5%) and helped prevent unnecessary surgery in 30.4% of the cohort. Tumor complexity with high RENAL score was a predictive factor (P ¼ .02) of contributive biopsy. Conclusion: SRM biopsy is a safe, reliable procedure that can help determine the best treatment strategy for patients. It seems more beneficial for nephrometry complex tumors when surgical extirpation is more likely to be complicated. SRM biopsy might be encouraged in clinical practice for complex tumors. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2016 Elsevier Inc. All rights reserved. Keywords: Biopsy, Computed tomography, Diagnostic yield, Renal-cell carcinoma, RENAL nephrometry score
Introduction Improvements in imaging techniques and their widespread use of in routine practice to investigate nonspecific abdominal or musculoskeletal complaints have led to increased detection of asymptomatic renal tumors. Modern series have reported a 65% 1
Urology Department Pathology Department 3 Radiology Department, Institut Montsouris, Paris, France 4 IR4M, CNRS, Univ. Paris Sud, Université Paris-Saclay, Villejuif, France 2
Submitted: Nov 18, 2015; Revised: Feb 9, 2016; Accepted: Feb 14, 2016 Address for correspondence: Eric Barret, MD, Urology Department, Institut Montsouris, 42, boulevard Jourdan, 75014 Paris, France Fax: þ33156616640; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2016.02.006
prevalence of incidental tumors among solid renal masses (SRM). Of these incidental tumors, 38% were localized and < 4 cm.1,2 It has been reported that 20% to 25% of SRM (< 4 cm) are benign.3 On the other hand, an analysis of the Surveillance Epidemiology and End Results database from 1998 to 2003 showed a 5.2% prevalence of metastasis at presentation among 8792 patients with tumors < 4 cm.4 Because of these large oncologic outcomes discrepancies, it is paramount to accurately diagnose malignant tumors and to distinguish histologic subtypes of renal-cell carcinoma (RCC) to define each tumor’s best treatment and follow-up. Although renal biopsy seems to be the way to define tumor features before treatment, its use remains uncommon in daily clinical practice. In a recent population-based medical claims
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Biopsies for Small Renal Masses
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analysis, only 6% of patients undergoing SRM surgical extirpation had a preoperative renal biopsy before surgery.5 The purpose of this study was to determine, from our single-institution experience, the feasibility and accuracy of computed tomography (CT)-guided renal biopsies for SRM (cT1a, M0 tumors), and the impact of tumor complexity on the procedure’s diagnostic yield.
posterior location, distance to collecting system (categorical), exophytic feature (categorical), location relative to polar lines (categorical) as potential predictors. The second model replaces the 3 last criteria by the RENAL score splitting low versus mid and high complexity (4-6 vs. 7-12), the medium/high subsets had been merged because of their restricted sizes.
Patients and Methods
Results
We retrospectively reviewed all percutaneous renal biopsies performed at our institution from January 2007 to December 2012, through a query of our Pathology Department’s procedures database. All human subjects provided written informed consent with guarantees of confidentiality and the study was reviewed by our institutional review board. Renal biopsy was indicated in case of SRM < 4 cm in diameter with lesion enhancement (minimum 15 Hounsfield Unit) after contrast agent injection on CT scan. Exclusion criteria were the presence of metastases, cancer stage higher than cT1a (> 4 cm), and non-CT-guided techniques (eg, ultrasound or perioperative biopsies) and patients unfit for contrastagent injection (renal failure or hypersensitivity). Clinical reports, imaging studies, and pathology reports were studied to determine each patient’s clinical characteristics, including age, sex, weight, height, body mass index (BMI), comorbidities, 30 days after biopsy follow-up, postbiopsy tumor management, 2-month postbiopsy complications, tumor CT features (ie, location: right or left side and RENAL score characteristics), and pathologic features (ie, biopsy contribution, histologic subtype, Fuhrman grade, number of fragments, and immunohistochemistry). Furthermore, when surgery was performed, specimen pathology was compared with that of the initial biopsy specimen. All biopsies were performed using standard sterile techniques and local anesthesia. A single-detector, helical CT scanner with fluoroscopic guidance was used for imaging. All biopsies were performed using coaxial devices with 18-gauge, side-cutting, automated biopsy needles. A biopsy was considered diagnostic if enough tissue was gathered (biopsy length > 1 mm) and pathology report could at least classify the tumor as malignant or benign. Biopsy was considered not diagnostic when it was only composed of fibrotic, serohemorrhagic, necrotic material, normal parenchyma, and/or muscle tissue. All specimens were prepared with hematoxylin and eosin staining. Immunohistochemistry was performed when information from histologic studies was lacking or there was doubt about other primitive tumors. RCC markers used were CD10, vimentin, cytokeratin 7 or cytokeratin commune, AMACR and epithelial membrane antigen. Marker’s choices were at the pathologist’ discretion. Statistical analyses were performed with IBM SPSS 22 (IBM Corp, Armonk, NY). Data were described with the mean and standard deviation for continuous data with normal repartition, median and interquartile range in case of nonnormal repartition, and frequencies for categorical data. The nonparametric MannWhitney U test was used for continuous variables and chi-square test for categorical variables to compare groups between diagnostic and nondiagnostic biopsies. Cross-sectional analysis of multiple independent variables was performed with a binary logistic regression to search for predictive factors of contributive biopsies, the first model tested gender, age, BMI, tumor size, tumor side, anterior/
One hundred nineteen patients underwent biopsies for renal masses. Of these, 40 were excluded from the analysis because of metastatic stage (n ¼ 11), tumor size > 4 cm (n ¼ 2), or because the biopsy was performed per-operatively or with an ultrasound guidance technique (n ¼ 27); 79 biopsy specimens were analyzed. Patients and tumor characteristics are reported in Table 1. The mean standard deviation age of the population was of 66.2 11.6 years. The median tumor size was 25 mm (interquartile range, 18.5-32 mm). There were no major complications; 2 (2.5%) Clavien grade 2 complications were managed on an outpatient basis (1 patient had lumbar pain associated with fever and 1 had acute bladder retention). Of 79 biopsies, 70 (88.6%) were diagnostic and 9 (11.4%) nondiagnostic. Pathologic evaluation included immunohistochemistry staining in 56 cases (70.9%) reported in Table 2. Forty-seven tumor specimens (67.1%) from the 70 diagnostic biopsies were malignant and 23 (32.9%) were benign. The Fuhrman grade was estimated as grade II for 32 tumors (68.1% of malignant tumors), grade III for 7 tumors (14.9%), and not appreciable because of insufficient cells in biopsy material for 8 tumors (17.0%). Twenty-three tumors (32.9%) were benign: 14 (20.0%) were oncocytoma, 5 (7.1%) angiomyolipoma, 1 (1.4%) cystic adenoma, 1 (1.4%) tuberculosis, 1 (1.4%) interstitial nephritis, and 1 (1.4%) scarring tissue. Twenty-nine patients had an extirpative procedure allowing pathologic comparison between biopsy and surgical specimens. Two of those biopsies were nondiagnostic; after surgical excision, one specimen was diagnosed as clear-cell carcinoma and the other as papillary carcinoma. Ultimately, specimens from 27 biopsies were compared with final surgical specimens.
Clinical Genitourinary Cancer Month 2016
Diagnosis of Malignancy We found 25 malignant and 2 benign tumors on biopsy versus 24 malignant and 3 benign on final pathology. One tumor diagnosed as chromophobe carcinoma was found to be an oncocytoma after the partial nephrectomy specimen was analyzed. The sensitivity, specificity, and accuracy of diagnoses determined from biopsy specimens were 100%, 67%, and 96%, respectively.
Histology Of the 27 tumors, 25 (93%) were accurately classified histologically. In addition to the oncocytoma originally classified as a chromophobe carcinoma, one tumor originally diagnosed as clearcell carcinoma was reclassified on histology as a papillary carcinoma.
Fuhrman Grade The 25 malignant biopsy specimens were assessed for Fuhrman grade (2 biopsy specimens were diagnosed as oncocytoma, 2 were not contributive). The chromophobe RCC confirmed as oncocytoma could not be compared, since oncocytomas are not graded.
Alexandre Ingels et al Table 1 Clinical and Radiologic Characteristics of Patients (n [ 79) and Tumors Characteristic
Value
Gender Male
54 (68%)
Female
25 (32%)
Age at Diagnosis (years) Median
Among 79 patients, 53 (67.1%) received an active treatment, 24 (30.4%) were managed by surveillance, and 2 (2.5%) were lost to follow-up. In the treatment group, there were 44 (83.0%) RCCs, 2 (3.8%) oncocytomas, and 7 (13.2%) biopsies were not contributive. Among the treated patients, 38 (71.7%) underwent surgery (25 [47.1%] nephron-sparing surgeries, 11 [20.7%] radical nephrectomies), and 15 (28.3%) underwent percutaneous cryoablative procedures.
67.2
Quartile 25-75
60.8-75.5 2
Body Mass Index (kg/m ) Median Quartile 25-75
26.7 24.2-29.4
Tumor Side Left
36 (46%)
Right
43 (54%)
Tumor Size (mm) Median Quartile 25-75
25 18.5-32
Unknown Exophytic Properties 50% or more
36 (46%)
Less than 50%
16 (20%)
Entirely endophytic
24 (30%)
Unknown
3 (4%)
Distance Tumor-Collecting System/Sinus 7 mm
37 (47%)
Between 4 and 7 mm
10 (13%)
4 mm
27 (34%)
Unknown
5 (6%)
Anterior/Posterior Location Anterior
18 (24%)
Posterior
47 (59%)
Undetermined
9 (11%)
Unknown
5 (6%)
Location Relative to Polar Lines Outside polar lines
21 (27%)
Crosses polar lines
10 (13%)
>50% across or crosses axial midline
43 (54%)
Unknown
5 (6%)
RENAL Nephrometry Score Low (4-6)
34 (46%)
Moderate (7-9)
29 (39%)
High (10-12)
Tumor Management
9 (15%)
Five (25.9%) biopsies did not gather enough cells to enable tumor grading; of these, surgical specimen analysis concluded that 4 were Fuhrman grade II and 1 was grade III. Fuhrman grade could be determined accurately in specimens from 16 biopsies (64.0%; 13 were grade II, and 3 were grade III). Three (12.0%) tumors were upgraded from grade II to grade III. No tumors were downgraded from biopsy to surgery.
RENAL Score CT-scan features of tumors were available in 74 cases. For 5 patients, the prebiopsy injected CT-scan was not accessible and the noninjected per-biopsy images did not allow a reliable calculation of the RENAL score. The nephrometry’s characteristics of the population including exophytic properties, nearness to collecting system or sinus, anterior/posterior location, and location relative to polar lines are reported in Table 1. On RENAL score, 34 (46%) tumors harbored a low complexity (4-6), 29 (39%) were moderate (7-9), and 9 (15%) were highly complex (10-12). We studied the influence of clinical and radiologic data on biopsy yield. The moderate and highly complex tumors (7-12) had a better yield than the low complexity (4-6): 82% versus 98% (P ¼ .026). On binary regression, only the RENAL score was significantly higher among the diagnostic biopsy group (mean score, 7.1 vs. 5.3; P ¼ .02). There were no significant differences among the other parameters studied: gender (P ¼ .274), BMI (P ¼ .214), tumor side (ie, right or left side) (P ¼ .514), tumor size (P ¼ .941), exophytic location (P ¼ .414), distance to sinus (P ¼ .083), anterior/posterior location (P ¼ .280), and location relative to polar lines (P ¼ .068). Binary logistic regression confirmed the RENAL score as the sole predictive factor of contributive biopsy (P ¼ .036; odds ratio ¼ 1.78).
Discussion In most of cancers, performing a biopsy to obtain pathologic evidence of malignancy prior to any decision on treatment is mandatory and highly recommended. The urology community has been reluctant to adopt this strategy for renal tumors for several reasons: safety, poor diagnostic yield, and the low impact on therapeutic strategy. These reasons must be discussed within the current background of RCC. The most concerning possible adverse events associated with renal biopsies are tumor seeding and bleeding. Dissemination through access puncture is extremely rare, particularly with the widespread use of coaxial needles that prevent contact between potentially malignant material and tissue along the biopsy line. To our knowledge, only 6 cases of tumor seeding have been reported in the literature and none when coaxial needles were used.6 The rate of adverse events in our series was very low: 2.5% were nonsevere complications (Clavien-Dindo score 2), and there were no severe complications. This is consistent with previous series, which generally have reported adverse events in < 8% cases.7 Only Lechevallier et al7 reported a high rate of complications (38%); however, this series was published in 2000, and safety has certainly improved since then. Diagnostic yield and accuracy have reached acceptable levels of performance to lead clinicians in their therapeutic decisions. This
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Biopsies for Small Renal Masses Table 2 Main Marker Expression for 56 Tumors Requiring Immunohistochemical Analysisa Marker CD10 Vimentin CK7 CKc EMA P-504S Smooth muscle actin HMB45
Clear Cell (n [ 23) 14/14 (100%) 21/21 (100%) 0/22 (0%) 21/21 (100%) 8/8 (100%) 1/1 (100%) NT NT
Papillary (n [ 8) 4/4 8/8 8/8 1/1 6/6 5/5
(100%) (100%) (100%) (100%) (100%) (100%) NT NT
Chromophobe (n [ 10) 1/1 0/7 7/8 9/9 5/5 1/1
(100%) (100%) (88%) (100%) (100%) (100%) NT NT
Oncocytoma (n [ 12)
Angiomyolipoma (n [ 1)
Undifferentiated (n [ 2)
0/1 (0%) 0/7 (0%) 2/12 (17%) 11/11 (100%) 8/8 (100%) 0/1 (0%) NT NT
NT NT NT NT NT NT 1/1 (100%) 1/1 (100%)
NT 2/2 (100%) 0/1 (0%) 2/2 (100%) NT NT NT NT
Abbreviations: CK ¼ cytokeratin; CKc ¼ common cytokeratin; EMA ¼ epithelial membrane antigen; HMB ¼ human melanoma black; NT ¼ not tested; SMA ¼ smooth muscle actin. a Results reported for each biopsy-based diagnosis.
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improvement came with the development of radiology techniques providing high-quality CT and ultrasound images, but improvement also came with the evolution of pathology skills and validation of new biomarkers (Figure 1). Indeed, among the 79 biopsies reported, 56 (70.9%) required immunohistochemical staining to determine the final diagnosis precisely. The main, routinely used biomarkers have been validated over the last decade and certainly have increased the accuracy of determining tumor malignancy and histologic subtype. In our study, the procedure yield (88.6%) was similar to that of previous reports, which range from 80% to 96%.8-11 CT-guided renal biopsy can distinguish malignant from benign tumors with an accuracy of 96%; it is less reliable for classifying tumor histology (ie, clear cell, papillary, or chromophobe). However, Fuhrman grading of biopsy specimens, with an accuracy of 64% in our study (and 12% when upgrading from biopsy to surgical specimen), should only be considered for high grade (ie, the biopsy can be used to diagnose a high-grade tumor but cannot rule it out). These results are consistent with the literature, in which accuracy ranges for malignancy, RCC subtyping, and grading were 86% to 100%, 86% to 100%, and 63.5% to 76%, respectively.6 Renal biopsies had been considered as having a low impact on therapeutic strategies when most tumors were diagnosed at an advanced symptomatic stage and with very little doubt about the malignant status. At that time, the tumor was extirpated whenever possible. Today, this paradigm has to be reconsidered for 2 reasons. First, as imaging modalities became routine tools to investigate common symptoms (eg, abdominal or back pain), asymptomatic SRM have been discovered with increasing incidence.12 Those SRM are becoming more common, with the significant rate of benign tumors often hardly distinguishable from that of malignant tumors on imaging,13 has to be considered. In our series, 32.9% of SRM were benign masses, a finding consistent with previous series.14 Benign tumors are harmless, and performing surgery in this setting would expose patients to adverse events. In our series, we stopped the imaging follow-up for the benign tumors. In 2 cases, we have decided to not operate clear-cell carcinomas because of patients’ poor performance status and small tumor size. In that situation, a CT-scan was performed regularly to control the evolution. Eventually, the biopsies changed our strategy since we did not treat the benign lesion. However, it did not affect the choice between ablative and surgical procedures. From this perspective, renal
Clinical Genitourinary Cancer Month 2016
biopsies might prevent many unnecessary invasive treatments, lowering procedure-related morbidity for patients and costs for the health-care system. Second, treatment of renal tumors has evolved. From radical nephrectomy as an unique option, we shifted to a comprehensive panel of acceptable strategies. Active surveillance and thermal ablations are nonextirpative alternatives to radical or partial nephrectomy in the setting of a poor surgical candidate.15 When indicated, renal biopsy is a unique opportunity to obtain a pathologic diagnosis for these patients and is recommended by the current European Association of Urology guidelines.15 In this report, biopsy findings led to the decision to not operate in 24 cases (30.4%); thermal ablation (percutaneous cryoablation) represented 28.3% of active treatments. In their recent review, Volpe et al6 stated that renal biopsy had an impact on tumor management in 24.3% to 68.9% of cases. The RENAL score is an algorithm meant to evaluate tumor complexity and topography.16 Based on a contrast-enhanced CT examination, it scores the size, distance to sinus, polar lines, and level of inclusion of the tumor into the normal parenchyma. It correlates with the surgeon’s choice for approach, perioperative and postoperative complications, and oncologic and renal function outcomes after nephrectomy.17-20 The impact of the RENAL score has also been studied for thermal ablation in terms of oncologic and functional outcomes, with controversial results.21-24 To our knowledge, the impact of the RENAL score on biopsy yield has not been studied before. Surprisingly, we found a high RENAL score was significantly associated with contributive biopsies. Each RENAL parameter failed to have significant association when considered alone, possibly because of the small cohort size. However, when merged into the multiparametric score, there was a significant association. Acknowledging this, renal biopsy may be of primary interest for complex tumors in cases where preventing unnecessary high-risk surgery in patients with benign tumors is paramount. The difficulty in differentiating chromophobe RCC from oncocytoma on histology and by immunohistochemistry is a common issue for pathologists. Surgical extirpation of a tumor is probably a wise choice when a doubtful pathology report cannot clearly distinguish between the 2. Although high (88.6%), SRM biopsy yields can be improved. Development in imaging techniques and new technologies allowing instantaneous histologic analysis of
Alexandre Ingels et al Figure 1 Assessment of Tumors and Biomarkers. Patient A Had 26 mm Tumor Located in Left Kidney (A1) Harboring Clear-Cell Pathologic Findings: Compact Architecture of Cells With Clear Cytoplasm, Distinct but Clear Cell Boundaries on 20 3 10 Magnification HES (A2), Vimentin Positive (A3, 40 3 10) and CK7 Negative (A4, 40 3 10) Expressions. Patient Was Treated by Cryoablation. Patient B Had 21 mm Tumor Located in Right Kidney (B1) Harboring Angiomyolipoma Pathologic Findings: Triphasic Architecture With Myoid Spindle Cells, Mature Adipose Cells, and Dysmorphic Thick-Walled Blood Vessels on 20 3 10 Magnification HES (B2), AML Positive (B3, 40 3 10) and HMB45 Positive (B4, 40 3 10) Expressions. Patient C Had 30 mm Tumor Located in Right Kidney (C1) Harboring Papillary Type 1 Findings: Papillae Covered by Larger Cells With Abundant Eosinophilic Granular Cytoplasm on 20 3 10 Magnification HES (C2), CK7 Positive (C3, 20 3 10) and AMCR Positive (C4, 20 3 10) Expressions. Patient Was Treated by Nephron-Sparing Tumorectomy.
Abbreviations: AMCR ¼ Alpha-Methylacyl-CoA Racemase; AML ¼ Acute Myeloid Leukemia; CK ¼ Cytokeratin; HES ¼ Hematoxylin Eosine Safran; HMB ¼ Human Melanoma Black.
tumor tissue and better guidance during tumor targeting25 might help improve diagnostic accuracy. This study had several limitations, including a small population and a retrospective design representing a selection bias. The confirmation of renal biopsy-specimen pathology was done with operated patients only. Most benign tumors diagnosed on biopsy were not extirpated; this second selection bias could underestimate the number of false-negative diagnoses.
Conclusion Biopsy of renal masses might be performed routinely in the setting of small tumors to avoid unnecessary morbid surgical procedures. For tumors with a high RENAL score, preventing surgery for a potentially challenging case might decrease the risk of adverse events. However, the efficacy of renal biopsy needs to be improved. Surgery may be indicated in some situations when there is difficulty distinguishing oncocytoma from chromophobe RCC.
Clinical Practice Points We already know that small renal mass biopsy of the kidney is a
safe and useful procedure. However, the urology community remains reluctant to adopt this strategy. In addition to new confirmative data in this sense, our study showed that more nephrometry complex tumors present a higher yield of contributive biopsies. This finding should encourage systematic biopsies of complex small renal masses before considering surgical extirpation.
Disclosure The authors have stated that they have no conflict of interest.
References 1. Lee CT, Katz J, Shi W, et al. Surgical management of renal tumors 4 cm or less in a contemporary cohort. J Urol 2000; 163:730-6.
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Biopsies for Small Renal Masses 2. Nakatani T, Yoshida N, Iwata H, et al. Clinicopathological study of renal cell carcinoma. Oncol Rep 2003; 10:679-85. 3. Frank I, Blute ML, Cheville JC, et al. Solid renal tumors: an analysis of pathological features related to tumor size. J Urol 2003; 170(6 pt 1):2217-20. 4. Nguyen MM, Gill IS. Effect of renal cancer size on the prevalence of metastasis at diagnosis and mortality. J Urol 2009; 181:1020-7. 5. Lowrance W, Larson S, Anis-Alibozek A, et al. Real-world presurgical characteristics and postsurgical morbidity of 10,404 Americans undergoing nephrectomy for renal tumors. Paper presented at: International Kidney Cancer Symposium; Chicago, IL; October 2011. 6. Schmidbauer J, Remzi M, Memarsadeghi M, et al. Diagnostic accuracy of computed tomographyeguided percutaneous biopsy of renal masses. Eur Urol 2008; 53:1003-11. 7. Lechevallier E, André M, Barriol D, et al. Fine-needle percutaneous biopsy of renal masses with helical CT guidance. Radiology 2000; 216:506-10. 8. Neuzillet Y, Lechevallier E, Andre M, et al. 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; 171:1802-5. 9. Volpe A, Finelli A, Gill IS, et al. Rationale for percutaneous biopsy and histologic characterisation of renal tumours. Eur Urol 2012; 62:491-504. 10. Phé V, Yates DR, Renard-Penna R, et al. Is there a contemporary role for percutaneous needle biopsy in the era of small renal masses? BJU Int 2012; 109:867-72. 11. Marconi L, Dabestani S, Lam TB, et al. Systematic review and meta-analysis of diagnostic accuracy of percutaneous renal tumour biopsy. Eur Urol 2016; 69:660-73. 12. Kane CJ, Mallin K, Ritchey J, et al. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008; 113:78-83. 13. Smith PA, Marshall FF, Fishman EK. Spiral computed tomography evaluation of the kidneys: state of the art. Urology 1998; 51:3-11. 14. Remzi M, Ozsoy M, Klingler HC, et al. Are small renal tumors harmless? Analysis of histopathological features according to tumors 4 cm or less in diameter. J Urol 2006; 176:896-9.
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15. Ljungberg B, Cowan NC, Hanbury DC, et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010; 58:398-406. 16. Kutikov A, Uzzo RG. The RENAL nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol 2009; 182:844-53. 17. Rosevear HM, Gellhaus PT, Lightfoot AJ, et al. Utility of the RENAL nephrometry scoring system in the real world: predicting surgeon operative preference and complication risk. BJU Int 2012; 109:700-5. 18. Kutikov A, Smaldone MC, Egleston BL, et al. Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL nephrometry score. Eur Urol 2011; 60:241-8. 19. Stroup SP, Palazzi K, Kopp RP, et al. RENAL nephrometry score is associated with operative approach for partial nephrectomy and urine leak. Urology 2012; 80: 151-6. 20. Mehrazin R, Palazzi KL, Kopp RP, et al. Impact of tumour morphology on renal function decline after partial nephrectomy. BJU Int 2013; 111:E374-82. 21. Schmit GD, Thompson RH, Kurup AN, et al. Usefulness of RENAL nephrometry scoring system for predicting outcomes and complications of percutaneous ablation of 751 renal tumors. J Urol 2013; 189:30-5. 22. Seideman CA, Gahan J, Weaver M, et al. Renal tumour nephrometry score does not correlate with the risk of radiofrequency ablation complications. BJU Int 2013; 112:1121-4. 23. Okhunov Z, Shapiro EY, Moreira DM, et al. RENAL nephrometry score accurately predicts complications following laparoscopic renal cryoablation. J Urol 2012; 188:1796-800. 24. Blute ML Jr, Okhunov Z, Moreira DM, et al. Image-guided percutaneous renal cryoablation: preoperative risk factors for recurrence and complications. BJU Int 2013; 111(4 pt B):E181-5. 25. Wagstaff PG, Ingels A, de Bruin DM, et al. Percutaneous needle based optical coherence tomography for the differentiation of renal masses: a pilot cohort. J Urol 2015, http://dx.doi.org/10.1016/j.juro.2015.12.072 [Epub ahead of print].
Percutaneous Renal Biopsies for Small Renal Masses: Complex Tumors on Nephrometry Should Be the First Targets Alexandre Ingels,1,4 Eric Barret,1 Rafael Sanchez-Salas,1 Marc Galiano,1 François Rozet,1 Stephane Lenoir,2 Nina Weber,3 François Audenet,1 Xavier Cathelineau1 Abstract Renal mass biopsy for small tumor is a safe procedure. It allows accurate distinction between benign and malignant tumors. This strategy is particularly relevant for nephrometry complex tumors, where biopsies present a higher yield and surgery a higher morbidity. Objective: To assess the diagnostic yield, accuracy, and complications rate for computed tomography (CT)-guided renal biopsies for solid renal masses (SRM); to analyze predictive factors for diagnostic biopsies. Patients and Methods: We performed a single-center, retrospective study based on a pathologic database query for CT-guided, percutaneous renal biopsies. Inclusion criteria included presence of SRM; exclusion criteria included the presence of metastases, non-cT1a or higher cancer (> 4 cm), and non-CT-guided techniques. Of 119 patients who underwent renal biopsies, 40 (34%) were excluded from the study; 79 (66%) biopsy outcomes were analyzed. Clinical, radiologic (RENAL score), and pathologic features were reported. Differences between contributive and noncontributive biopsies were tested with Mann-Whitney U or chi-square tests, as appropriate. Multiple-variable analyses searching for predicting factors of biopsy contribution were performed with binary logistic regressions. Results: CT-guided renal biopsies for SRM present a high yield (88.6%) and high accuracy for differentiating malignant from benign tumors (96%). They are less accurate for histologic subtype (93%) and unreliable for Fuhrman grading (64%). CT-guided renal biopsy is safe (minor complication rate, 2.5%) and helped prevent unnecessary surgery in 30.4% of the cohort. Tumor complexity with high RENAL score was a predictive factor (P ¼ .02) of contributive biopsy. Conclusion: SRM biopsy is a safe, reliable procedure that can help determine the best treatment strategy for patients. It seems more beneficial for nephrometry complex tumors when surgical extirpation is more likely to be complicated. SRM biopsy might be encouraged in clinical practice for complex tumors. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2016 Elsevier Inc. All rights reserved. Keywords: Biopsy, Computed tomography, Diagnostic yield, Renal-cell carcinoma, RENAL nephrometry score
Introduction Improvements in imaging techniques and their widespread use of in routine practice to investigate nonspecific abdominal or musculoskeletal complaints have led to increased detection of asymptomatic renal tumors. Modern series have reported a 65% 1
Urology Department Pathology Department 3 Radiology Department, Institut Montsouris, Paris, France 4 IR4M, CNRS, Univ. Paris Sud, Université Paris-Saclay, Villejuif, France 2
Submitted: Nov 18, 2015; Revised: Feb 9, 2016; Accepted: Feb 14, 2016 Address for correspondence: Eric Barret, MD, Urology Department, Institut Montsouris, 42, boulevard Jourdan, 75014 Paris, France Fax: þ33156616640; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2016.02.006
prevalence of incidental tumors among solid renal masses (SRM). Of these incidental tumors, 38% were localized and < 4 cm.1,2 It has been reported that 20% to 25% of SRM (< 4 cm) are benign.3 On the other hand, an analysis of the Surveillance Epidemiology and End Results database from 1998 to 2003 showed a 5.2% prevalence of metastasis at presentation among 8792 patients with tumors < 4 cm.4 Because of these large oncologic outcomes discrepancies, it is paramount to accurately diagnose malignant tumors and to distinguish histologic subtypes of renal-cell carcinoma (RCC) to define each tumor’s best treatment and follow-up. Although renal biopsy seems to be the way to define tumor features before treatment, its use remains uncommon in daily clinical practice. In a recent population-based medical claims
Clinical Genitourinary Cancer Month 2016
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Biopsies for Small Renal Masses
2
-
analysis, only 6% of patients undergoing SRM surgical extirpation had a preoperative renal biopsy before surgery.5 The purpose of this study was to determine, from our single-institution experience, the feasibility and accuracy of computed tomography (CT)-guided renal biopsies for SRM (cT1a, M0 tumors), and the impact of tumor complexity on the procedure’s diagnostic yield.
posterior location, distance to collecting system (categorical), exophytic feature (categorical), location relative to polar lines (categorical) as potential predictors. The second model replaces the 3 last criteria by the RENAL score splitting low versus mid and high complexity (4-6 vs. 7-12), the medium/high subsets had been merged because of their restricted sizes.
Patients and Methods
Results
We retrospectively reviewed all percutaneous renal biopsies performed at our institution from January 2007 to December 2012, through a query of our Pathology Department’s procedures database. All human subjects provided written informed consent with guarantees of confidentiality and the study was reviewed by our institutional review board. Renal biopsy was indicated in case of SRM < 4 cm in diameter with lesion enhancement (minimum 15 Hounsfield Unit) after contrast agent injection on CT scan. Exclusion criteria were the presence of metastases, cancer stage higher than cT1a (> 4 cm), and non-CT-guided techniques (eg, ultrasound or perioperative biopsies) and patients unfit for contrastagent injection (renal failure or hypersensitivity). Clinical reports, imaging studies, and pathology reports were studied to determine each patient’s clinical characteristics, including age, sex, weight, height, body mass index (BMI), comorbidities, 30 days after biopsy follow-up, postbiopsy tumor management, 2-month postbiopsy complications, tumor CT features (ie, location: right or left side and RENAL score characteristics), and pathologic features (ie, biopsy contribution, histologic subtype, Fuhrman grade, number of fragments, and immunohistochemistry). Furthermore, when surgery was performed, specimen pathology was compared with that of the initial biopsy specimen. All biopsies were performed using standard sterile techniques and local anesthesia. A single-detector, helical CT scanner with fluoroscopic guidance was used for imaging. All biopsies were performed using coaxial devices with 18-gauge, side-cutting, automated biopsy needles. A biopsy was considered diagnostic if enough tissue was gathered (biopsy length > 1 mm) and pathology report could at least classify the tumor as malignant or benign. Biopsy was considered not diagnostic when it was only composed of fibrotic, serohemorrhagic, necrotic material, normal parenchyma, and/or muscle tissue. All specimens were prepared with hematoxylin and eosin staining. Immunohistochemistry was performed when information from histologic studies was lacking or there was doubt about other primitive tumors. RCC markers used were CD10, vimentin, cytokeratin 7 or cytokeratin commune, AMACR and epithelial membrane antigen. Marker’s choices were at the pathologist’ discretion. Statistical analyses were performed with IBM SPSS 22 (IBM Corp, Armonk, NY). Data were described with the mean and standard deviation for continuous data with normal repartition, median and interquartile range in case of nonnormal repartition, and frequencies for categorical data. The nonparametric MannWhitney U test was used for continuous variables and chi-square test for categorical variables to compare groups between diagnostic and nondiagnostic biopsies. Cross-sectional analysis of multiple independent variables was performed with a binary logistic regression to search for predictive factors of contributive biopsies, the first model tested gender, age, BMI, tumor size, tumor side, anterior/
One hundred nineteen patients underwent biopsies for renal masses. Of these, 40 were excluded from the analysis because of metastatic stage (n ¼ 11), tumor size > 4 cm (n ¼ 2), or because the biopsy was performed per-operatively or with an ultrasound guidance technique (n ¼ 27); 79 biopsy specimens were analyzed. Patients and tumor characteristics are reported in Table 1. The mean standard deviation age of the population was of 66.2 11.6 years. The median tumor size was 25 mm (interquartile range, 18.5-32 mm). There were no major complications; 2 (2.5%) Clavien grade 2 complications were managed on an outpatient basis (1 patient had lumbar pain associated with fever and 1 had acute bladder retention). Of 79 biopsies, 70 (88.6%) were diagnostic and 9 (11.4%) nondiagnostic. Pathologic evaluation included immunohistochemistry staining in 56 cases (70.9%) reported in Table 2. Forty-seven tumor specimens (67.1%) from the 70 diagnostic biopsies were malignant and 23 (32.9%) were benign. The Fuhrman grade was estimated as grade II for 32 tumors (68.1% of malignant tumors), grade III for 7 tumors (14.9%), and not appreciable because of insufficient cells in biopsy material for 8 tumors (17.0%). Twenty-three tumors (32.9%) were benign: 14 (20.0%) were oncocytoma, 5 (7.1%) angiomyolipoma, 1 (1.4%) cystic adenoma, 1 (1.4%) tuberculosis, 1 (1.4%) interstitial nephritis, and 1 (1.4%) scarring tissue. Twenty-nine patients had an extirpative procedure allowing pathologic comparison between biopsy and surgical specimens. Two of those biopsies were nondiagnostic; after surgical excision, one specimen was diagnosed as clear-cell carcinoma and the other as papillary carcinoma. Ultimately, specimens from 27 biopsies were compared with final surgical specimens.
Clinical Genitourinary Cancer Month 2016
Diagnosis of Malignancy We found 25 malignant and 2 benign tumors on biopsy versus 24 malignant and 3 benign on final pathology. One tumor diagnosed as chromophobe carcinoma was found to be an oncocytoma after the partial nephrectomy specimen was analyzed. The sensitivity, specificity, and accuracy of diagnoses determined from biopsy specimens were 100%, 67%, and 96%, respectively.
Histology Of the 27 tumors, 25 (93%) were accurately classified histologically. In addition to the oncocytoma originally classified as a chromophobe carcinoma, one tumor originally diagnosed as clearcell carcinoma was reclassified on histology as a papillary carcinoma.
Fuhrman Grade The 25 malignant biopsy specimens were assessed for Fuhrman grade (2 biopsy specimens were diagnosed as oncocytoma, 2 were not contributive). The chromophobe RCC confirmed as oncocytoma could not be compared, since oncocytomas are not graded.
Alexandre Ingels et al Table 1 Clinical and Radiologic Characteristics of Patients (n [ 79) and Tumors Characteristic
Value
Gender Male
54 (68%)
Female
25 (32%)
Age at Diagnosis (years) Median
Among 79 patients, 53 (67.1%) received an active treatment, 24 (30.4%) were managed by surveillance, and 2 (2.5%) were lost to follow-up. In the treatment group, there were 44 (83.0%) RCCs, 2 (3.8%) oncocytomas, and 7 (13.2%) biopsies were not contributive. Among the treated patients, 38 (71.7%) underwent surgery (25 [47.1%] nephron-sparing surgeries, 11 [20.7%] radical nephrectomies), and 15 (28.3%) underwent percutaneous cryoablative procedures.
67.2
Quartile 25-75
60.8-75.5 2
Body Mass Index (kg/m ) Median Quartile 25-75
26.7 24.2-29.4
Tumor Side Left
36 (46%)
Right
43 (54%)
Tumor Size (mm) Median Quartile 25-75
25 18.5-32
Unknown Exophytic Properties 50% or more
36 (46%)
Less than 50%
16 (20%)
Entirely endophytic
24 (30%)
Unknown
3 (4%)
Distance Tumor-Collecting System/Sinus 7 mm
37 (47%)
Between 4 and 7 mm
10 (13%)
4 mm
27 (34%)
Unknown
5 (6%)
Anterior/Posterior Location Anterior
18 (24%)
Posterior
47 (59%)
Undetermined
9 (11%)
Unknown
5 (6%)
Location Relative to Polar Lines Outside polar lines
21 (27%)
Crosses polar lines
10 (13%)
>50% across or crosses axial midline
43 (54%)
Unknown
5 (6%)
RENAL Nephrometry Score Low (4-6)
34 (46%)
Moderate (7-9)
29 (39%)
High (10-12)
Tumor Management
9 (15%)
Five (25.9%) biopsies did not gather enough cells to enable tumor grading; of these, surgical specimen analysis concluded that 4 were Fuhrman grade II and 1 was grade III. Fuhrman grade could be determined accurately in specimens from 16 biopsies (64.0%; 13 were grade II, and 3 were grade III). Three (12.0%) tumors were upgraded from grade II to grade III. No tumors were downgraded from biopsy to surgery.
RENAL Score CT-scan features of tumors were available in 74 cases. For 5 patients, the prebiopsy injected CT-scan was not accessible and the noninjected per-biopsy images did not allow a reliable calculation of the RENAL score. The nephrometry’s characteristics of the population including exophytic properties, nearness to collecting system or sinus, anterior/posterior location, and location relative to polar lines are reported in Table 1. On RENAL score, 34 (46%) tumors harbored a low complexity (4-6), 29 (39%) were moderate (7-9), and 9 (15%) were highly complex (10-12). We studied the influence of clinical and radiologic data on biopsy yield. The moderate and highly complex tumors (7-12) had a better yield than the low complexity (4-6): 82% versus 98% (P ¼ .026). On binary regression, only the RENAL score was significantly higher among the diagnostic biopsy group (mean score, 7.1 vs. 5.3; P ¼ .02). There were no significant differences among the other parameters studied: gender (P ¼ .274), BMI (P ¼ .214), tumor side (ie, right or left side) (P ¼ .514), tumor size (P ¼ .941), exophytic location (P ¼ .414), distance to sinus (P ¼ .083), anterior/posterior location (P ¼ .280), and location relative to polar lines (P ¼ .068). Binary logistic regression confirmed the RENAL score as the sole predictive factor of contributive biopsy (P ¼ .036; odds ratio ¼ 1.78).
Discussion In most of cancers, performing a biopsy to obtain pathologic evidence of malignancy prior to any decision on treatment is mandatory and highly recommended. The urology community has been reluctant to adopt this strategy for renal tumors for several reasons: safety, poor diagnostic yield, and the low impact on therapeutic strategy. These reasons must be discussed within the current background of RCC. The most concerning possible adverse events associated with renal biopsies are tumor seeding and bleeding. Dissemination through access puncture is extremely rare, particularly with the widespread use of coaxial needles that prevent contact between potentially malignant material and tissue along the biopsy line. To our knowledge, only 6 cases of tumor seeding have been reported in the literature and none when coaxial needles were used.6 The rate of adverse events in our series was very low: 2.5% were nonsevere complications (Clavien-Dindo score 2), and there were no severe complications. This is consistent with previous series, which generally have reported adverse events in < 8% cases.7 Only Lechevallier et al7 reported a high rate of complications (38%); however, this series was published in 2000, and safety has certainly improved since then. Diagnostic yield and accuracy have reached acceptable levels of performance to lead clinicians in their therapeutic decisions. This
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Biopsies for Small Renal Masses Table 2 Main Marker Expression for 56 Tumors Requiring Immunohistochemical Analysisa Marker CD10 Vimentin CK7 CKc EMA P-504S Smooth muscle actin HMB45
Clear Cell (n [ 23) 14/14 (100%) 21/21 (100%) 0/22 (0%) 21/21 (100%) 8/8 (100%) 1/1 (100%) NT NT
Papillary (n [ 8) 4/4 8/8 8/8 1/1 6/6 5/5
(100%) (100%) (100%) (100%) (100%) (100%) NT NT
Chromophobe (n [ 10) 1/1 0/7 7/8 9/9 5/5 1/1
(100%) (100%) (88%) (100%) (100%) (100%) NT NT
Oncocytoma (n [ 12)
Angiomyolipoma (n [ 1)
Undifferentiated (n [ 2)
0/1 (0%) 0/7 (0%) 2/12 (17%) 11/11 (100%) 8/8 (100%) 0/1 (0%) NT NT
NT NT NT NT NT NT 1/1 (100%) 1/1 (100%)
NT 2/2 (100%) 0/1 (0%) 2/2 (100%) NT NT NT NT
Abbreviations: CK ¼ cytokeratin; CKc ¼ common cytokeratin; EMA ¼ epithelial membrane antigen; HMB ¼ human melanoma black; NT ¼ not tested; SMA ¼ smooth muscle actin. a Results reported for each biopsy-based diagnosis.
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improvement came with the development of radiology techniques providing high-quality CT and ultrasound images, but improvement also came with the evolution of pathology skills and validation of new biomarkers (Figure 1). Indeed, among the 79 biopsies reported, 56 (70.9%) required immunohistochemical staining to determine the final diagnosis precisely. The main, routinely used biomarkers have been validated over the last decade and certainly have increased the accuracy of determining tumor malignancy and histologic subtype. In our study, the procedure yield (88.6%) was similar to that of previous reports, which range from 80% to 96%.8-11 CT-guided renal biopsy can distinguish malignant from benign tumors with an accuracy of 96%; it is less reliable for classifying tumor histology (ie, clear cell, papillary, or chromophobe). However, Fuhrman grading of biopsy specimens, with an accuracy of 64% in our study (and 12% when upgrading from biopsy to surgical specimen), should only be considered for high grade (ie, the biopsy can be used to diagnose a high-grade tumor but cannot rule it out). These results are consistent with the literature, in which accuracy ranges for malignancy, RCC subtyping, and grading were 86% to 100%, 86% to 100%, and 63.5% to 76%, respectively.6 Renal biopsies had been considered as having a low impact on therapeutic strategies when most tumors were diagnosed at an advanced symptomatic stage and with very little doubt about the malignant status. At that time, the tumor was extirpated whenever possible. Today, this paradigm has to be reconsidered for 2 reasons. First, as imaging modalities became routine tools to investigate common symptoms (eg, abdominal or back pain), asymptomatic SRM have been discovered with increasing incidence.12 Those SRM are becoming more common, with the significant rate of benign tumors often hardly distinguishable from that of malignant tumors on imaging,13 has to be considered. In our series, 32.9% of SRM were benign masses, a finding consistent with previous series.14 Benign tumors are harmless, and performing surgery in this setting would expose patients to adverse events. In our series, we stopped the imaging follow-up for the benign tumors. In 2 cases, we have decided to not operate clear-cell carcinomas because of patients’ poor performance status and small tumor size. In that situation, a CT-scan was performed regularly to control the evolution. Eventually, the biopsies changed our strategy since we did not treat the benign lesion. However, it did not affect the choice between ablative and surgical procedures. From this perspective, renal
Clinical Genitourinary Cancer Month 2016
biopsies might prevent many unnecessary invasive treatments, lowering procedure-related morbidity for patients and costs for the health-care system. Second, treatment of renal tumors has evolved. From radical nephrectomy as an unique option, we shifted to a comprehensive panel of acceptable strategies. Active surveillance and thermal ablations are nonextirpative alternatives to radical or partial nephrectomy in the setting of a poor surgical candidate.15 When indicated, renal biopsy is a unique opportunity to obtain a pathologic diagnosis for these patients and is recommended by the current European Association of Urology guidelines.15 In this report, biopsy findings led to the decision to not operate in 24 cases (30.4%); thermal ablation (percutaneous cryoablation) represented 28.3% of active treatments. In their recent review, Volpe et al6 stated that renal biopsy had an impact on tumor management in 24.3% to 68.9% of cases. The RENAL score is an algorithm meant to evaluate tumor complexity and topography.16 Based on a contrast-enhanced CT examination, it scores the size, distance to sinus, polar lines, and level of inclusion of the tumor into the normal parenchyma. It correlates with the surgeon’s choice for approach, perioperative and postoperative complications, and oncologic and renal function outcomes after nephrectomy.17-20 The impact of the RENAL score has also been studied for thermal ablation in terms of oncologic and functional outcomes, with controversial results.21-24 To our knowledge, the impact of the RENAL score on biopsy yield has not been studied before. Surprisingly, we found a high RENAL score was significantly associated with contributive biopsies. Each RENAL parameter failed to have significant association when considered alone, possibly because of the small cohort size. However, when merged into the multiparametric score, there was a significant association. Acknowledging this, renal biopsy may be of primary interest for complex tumors in cases where preventing unnecessary high-risk surgery in patients with benign tumors is paramount. The difficulty in differentiating chromophobe RCC from oncocytoma on histology and by immunohistochemistry is a common issue for pathologists. Surgical extirpation of a tumor is probably a wise choice when a doubtful pathology report cannot clearly distinguish between the 2. Although high (88.6%), SRM biopsy yields can be improved. Development in imaging techniques and new technologies allowing instantaneous histologic analysis of
Alexandre Ingels et al Figure 1 Assessment of Tumors and Biomarkers. Patient A Had 26 mm Tumor Located in Left Kidney (A1) Harboring Clear-Cell Pathologic Findings: Compact Architecture of Cells With Clear Cytoplasm, Distinct but Clear Cell Boundaries on 20 3 10 Magnification HES (A2), Vimentin Positive (A3, 40 3 10) and CK7 Negative (A4, 40 3 10) Expressions. Patient Was Treated by Cryoablation. Patient B Had 21 mm Tumor Located in Right Kidney (B1) Harboring Angiomyolipoma Pathologic Findings: Triphasic Architecture With Myoid Spindle Cells, Mature Adipose Cells, and Dysmorphic Thick-Walled Blood Vessels on 20 3 10 Magnification HES (B2), AML Positive (B3, 40 3 10) and HMB45 Positive (B4, 40 3 10) Expressions. Patient C Had 30 mm Tumor Located in Right Kidney (C1) Harboring Papillary Type 1 Findings: Papillae Covered by Larger Cells With Abundant Eosinophilic Granular Cytoplasm on 20 3 10 Magnification HES (C2), CK7 Positive (C3, 20 3 10) and AMCR Positive (C4, 20 3 10) Expressions. Patient Was Treated by Nephron-Sparing Tumorectomy.
Abbreviations: AMCR ¼ Alpha-Methylacyl-CoA Racemase; AML ¼ Acute Myeloid Leukemia; CK ¼ Cytokeratin; HES ¼ Hematoxylin Eosine Safran; HMB ¼ Human Melanoma Black.
tumor tissue and better guidance during tumor targeting25 might help improve diagnostic accuracy. This study had several limitations, including a small population and a retrospective design representing a selection bias. The confirmation of renal biopsy-specimen pathology was done with operated patients only. Most benign tumors diagnosed on biopsy were not extirpated; this second selection bias could underestimate the number of false-negative diagnoses.
Conclusion Biopsy of renal masses might be performed routinely in the setting of small tumors to avoid unnecessary morbid surgical procedures. For tumors with a high RENAL score, preventing surgery for a potentially challenging case might decrease the risk of adverse events. However, the efficacy of renal biopsy needs to be improved. Surgery may be indicated in some situations when there is difficulty distinguishing oncocytoma from chromophobe RCC.
Clinical Practice Points We already know that small renal mass biopsy of the kidney is a
safe and useful procedure. However, the urology community remains reluctant to adopt this strategy. In addition to new confirmative data in this sense, our study showed that more nephrometry complex tumors present a higher yield of contributive biopsies. This finding should encourage systematic biopsies of complex small renal masses before considering surgical extirpation.
Disclosure The authors have stated that they have no conflict of interest.
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15. Ljungberg B, Cowan NC, Hanbury DC, et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010; 58:398-406. 16. Kutikov A, Uzzo RG. The RENAL nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth. J Urol 2009; 182:844-53. 17. Rosevear HM, Gellhaus PT, Lightfoot AJ, et al. Utility of the RENAL nephrometry scoring system in the real world: predicting surgeon operative preference and complication risk. BJU Int 2012; 109:700-5. 18. Kutikov A, Smaldone MC, Egleston BL, et al. Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL nephrometry score. Eur Urol 2011; 60:241-8. 19. Stroup SP, Palazzi K, Kopp RP, et al. RENAL nephrometry score is associated with operative approach for partial nephrectomy and urine leak. Urology 2012; 80: 151-6. 20. Mehrazin R, Palazzi KL, Kopp RP, et al. Impact of tumour morphology on renal function decline after partial nephrectomy. BJU Int 2013; 111:E374-82. 21. Schmit GD, Thompson RH, Kurup AN, et al. Usefulness of RENAL nephrometry scoring system for predicting outcomes and complications of percutaneous ablation of 751 renal tumors. J Urol 2013; 189:30-5. 22. Seideman CA, Gahan J, Weaver M, et al. Renal tumour nephrometry score does not correlate with the risk of radiofrequency ablation complications. BJU Int 2013; 112:1121-4. 23. Okhunov Z, Shapiro EY, Moreira DM, et al. RENAL nephrometry score accurately predicts complications following laparoscopic renal cryoablation. J Urol 2012; 188:1796-800. 24. Blute ML Jr, Okhunov Z, Moreira DM, et al. Image-guided percutaneous renal cryoablation: preoperative risk factors for recurrence and complications. BJU Int 2013; 111(4 pt B):E181-5. 25. Wagstaff PG, Ingels A, de Bruin DM, et al. Percutaneous needle based optical coherence tomography for the differentiation of renal masses: a pilot cohort. J Urol 2015, http://dx.doi.org/10.1016/j.juro.2015.12.072 [Epub ahead of print].