Renal Tumor Biopsy Technique.

OBJECTIVE: To review hot issues and future direction of renal tumor biopsy (RTB) technique. DATA SOURCES: The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015. STUDY SELECTION: We included all the relevant articles on RTB technique in English, with no limitation of study design.
RESULTS: Computed tomography and ultrasound were usually used for guiding RTB with respective advantages. Core biopsy is more preferred over fine needle aspiration because of superior accuracy. A minimum of two good-quality cores for a single renal tumor is generally accepted. The use of coaxial guide is recommended. For biopsy location, sampling different regions including central and peripheral biopsies are recommended.
CONCLUSION: In spite of some limitations, RTB technique is relatively mature to help optimize the treatment of renal tumors.

INTRODUCTION

The incidence of renal tumor has been rising in the past few decades, with the greatest increase in small renal masses (<4 cm, SRMs).[1] Not all SRMs are renal cell carcinoma (RCC), with approximate 20–30%[23] confirmed with benign pathology. Although imaging tests, such as computed tomography (CT) or magnetic resonance imaging (MRI) with contrast, have a pretty high diagnostic yield of renal cancer, the heterogeneity of RCC makes the imaging test incapable to predict the tumor behavior. Previous studies demonstrated that only 20–30% of renal cancers present aggressive malignant potential.[45] The problem of RCC overtreatment has caused general attention. Renal tumor biopsy (RTB) could provide tumor issue that might be useful to find some predictors of the natural history of RCC. In the era of individual treatment, RTB has been attracting clinician's attention. In this review, we will discuss the hot issue and future direction of RTB technique.

WHY RENAL TUMOR BIOPSY SHOULD BE PERFORMED?

Although modern imaging technique has been well developed in the differentiation of benign and malignant tumors, only relying on images without pretreatment histology is not reliable to decide treatment. Up to 30% of SRMs removed by surgery are benign when pretreatment histology is not obtained.[678] The accuracy of biopsy in identifying a lesion as benign or malignant is more than 90%,[29101112131415161718] which is higher than traditional imaging examination.[19] In addition, pretreatment biopsy can obviously decrease unnecessary surgeries for benign disease. Neuzillet et al. demonstrated that 15 out of 88 patients (17%) were avoided to undergo unnecessary surgeries after biopsies, 14 were benign disease, and another was lymphoma.[10] Wood et al. also avoided surgeries for benign disease in 32 out of 73 patients (44%) after biopsies.[20] Recent studies about active surveillance (AS) of SRMs especially in patients who were unfit for surgery showed that only a small portion of SRMs have the potential of fast growing or metastasis.[2122232425262728] However, not all the SRMs are suitable for AS. It is generally believed that low-grade clear-cell RCC, papillary type 1, and chromophobe tumors carry more favorable prognoses.[29] High-grade RCC presented fast growth rate during AS and implied a worse prognosis.[30] Hence, for patients with renal tumors treated by conservative therapy, obtaining histological information before making treatment decision may be more appropriate.

SAFETY AND COMPLICATION

Traditionally, safety is one of the concerns that limited the widespread use of renal tumors biopsy. The possible complications of RTB include bleeding, tumor seeding along the needle tract, infection, pneumothorax, and arteriovenous fistula. Of all the complications, tumor seeding along the needle tract is the most feared potential complication. However, the risk of this complication with urologic malignancy is below 0.01%.[13] In the recent studies, a few cases of tumor seeding along the needle tract for RTB were reported.[210111214203132333435] Another concern about safety is the risk of intratumoral and perinephric bleeding. Previous studies showed that significant bleeding was unusual; most of the bleeding was limited without compromise of hemodynamic stability.[29101112142031323435] Other complications of RTB were rare and treatable. On the whole, with the technique improved, RTB has been relatively safe now. Recent studies on the renal needle core biopsies and fine needle aspiration (FNA) revealed very few or no major complications, which were defined as the need of transfusion, more than 24-h admission, embolization, or surgical intervention.[2101112203132333435]

INDICATION

Traditionally, RTB was used to rule out lymphoma, renal abscess or metastatic nature of renal mass with a known nonrenal malignancy and to confirm the histological diagnosis for system therapies. Based on the recent data of RTB,[29101112142031323435] the indication of RTB has been expanding at present. However, there was still no overall consensus about when to perform RTB. For now, the indications of RTB are mainly based on local practice patterns and investigative interest.

Apart from the above indication, some new concepts about the indication of RTB were proposed. An international panel recommended pretreatment biopsies for every patients intending to receive ablative therapies[36] as histological information was needed for making treatment decision and adequate surveillance strategy. For synchronous or metachronous renal tumors, these lesions have shown the potential for different histology in the sporadic setting.[3738] Hence, for patients with synchronous renal tumors, it is appropriate to perform RTB for all lesions rather than depending on the histology of one renal mass. AS for renal mass has been gradually accepted with encouraging results.[39] Because RTB could help identify the suitability of AS and make risk-stratified surveillance schedule, the panel recommended RTB before performing AS.[36]

IMAGE GUIDANCE SYSTEMS

RTB is usually performed using ultrasound (US)- or CT-guidance. To our knowledge, there are few data supporting which of these methods yield the best results.

US is a useful technique for visualizing the tumor lesion and has the advantages of real-time needle placement, multi-planar imaging, low cost, visualization of vascular structures, and no harmful side effects of radiation.[40] Furthermore, proper experience biopsy with US-guidance is a very quick technique which takes less time than CT- or MRI-guided biopsies. To further improve the reflectivity and visualization of the needle, the surface of needle can be coated or scored by screw and Teflon.[41] Another major benefit of US is that the machines are portable and examinations can be performed at the bedside when necessary. The main disadvantage of US is that not all renal masses can be visualized with this technique, particularly in patients with small and/or endophytic renal lesions and in very obese patients. Some of these problems can be overcome by using intravenous contrast-enhancement with micro-bubbles.[42] However, as the micro-bubbles wash out in just a few minutes, this only gives the operator a short time-window to perform the biopsy. In addition, US is a very operator-dependent technique and there is a significant learning curve, which may affect the final imaging results.[43] In many centers with extensive experience in the US, biopsies are primarily performed with US-guidance and CT is reserved for patients in whom US is not feasible.

CT is also frequently used for RTB and many centers use CT-guidance as the primary technique for RTB.[44] CT has a higher sensitivity for SRMs than US, particularly when lesions are endophytic. The technique of CT-guided biopsy is less operator-dependent than US-guided biopsy although considerable skill is required for adequately biopsy.[43] The detection of renal lesions is improved by using intravenous contrast medium when performing CT.[45] Similar to contrast-enhanced US, CT contrast medium can only provide images during a limited time-window. However, as renal lesions often show a hypodense appearance as compared to normal renal parenchyma on delayed phase CT-imaging, the time-window for needle placement is often sufficient. Moreover, when the renal lesion shows a contour change on CT, the use of contrast medium is not always required for visualization of the lesion. Many of the newer generation CT-scanners are equipped with CT-fluoroscopy technology which enables real-time or almost real-time imaging during needle placement. Otherwise, the patient has to be moved in and out of the bore. With fluoroscopy, the procedure time is decreased and may increase the yield of CT-guided biopsies by more accurate needle placement as well as better use of the relatively short time-window after intravenous contrast injection in which the tumor shows optimal visibility. Laser guidance may also be of benefit in decreasing procedure time and increasing the accuracy of needle placement.[3146] There are also some disadvantages associated with the use of CT, such as impaired accuracy of needle placement due to the patients' respiratory motion or difficulties for patients maintaining a fixed position while in prone position during the procedure.

NEEDLE CORE VERSUS FINE NEEDLE ASPIRATION BIOPSY

Core biopsy and FNA are the two most common methods of obtaining renal tumor issue. Core biopsy systems are available with needle diameters ranging from 14- to 20-gauge. Most commonly biopsies are performed using 16- or 18-gauge needles, and these are preferred over FNA because of superior accuracy.[51247] The tissue obtained from core biopsy allows for the assessment of tissue architecture and histologic subtype. A recent meta-analysis on the percutaneous biopsy for renal masses shows that the accuracy of core biopsy distinguishing benign from malignant tumors was 88.9% on the basis of series published before 2001 and vastly improved to 96% between 2001 and 2009.[19] A recent published paper with a large series demonstrated the accuracy rate of core biopsy is up to 94%.[48]

FNA is commonly performed by a 20-gauge needle or smaller. FNA is less accurate than core biopsy.[4749] Although FNA has some diagnostic value, there is a major limitation in differentiating histological subtype for FNA, and its rate of inadequate sampling is not negligible.[1047] Hence, there is a controversy on the value of FNA. If biopsy is indicated, 90% of the clinicians choose core biopsy rather than FNA.[50]

NUMBER OF NEEDLE CORES FOR SINGLE AND MULTIPLE TUMORS

Currently, no consensus has been reached with regard to the optimal number of biopsies that should be performed for renal tumors. Renal tumors are heterogeneous, so multiple biopsy cores should be considered to prevent sampling errors. In an ex vivo investigation, investigators showed that adding core numbers improves the diagnostic yield, with a similar rate for two-core (63%) and three-core (67%) RTB.[51] Neuzillet et al. reported on 88 RTBs with at least two-core samplings resulting in a total of 90.9% diagnostic yield.[10] Similarly, Wang et al. analyzed 110 RTBs and demonstrated that biopsy with at least two cores resulted in 91% diagnostic yield.[52] Although increasing the number of cores is associated with improved diagnostic yield, and biopsy with at least two cores can result in a considerably higher diagnostic yield, ultimately it is the quality of the core that defines the success of RTB. Currently, a minimum of two good-quality cores for a single renal tumor is generally accepted.

COAXIAL TECHNIQUE

Core biopsy is by many operators performed through a coaxial needle or cannula. The use of a coaxial guide has been proven to increase the diagnostic yield of biopsy and improve the standardization of sampling.[53] Appelbaum et al. reported a 15% increase of the biopsy success rate without increasing the complication rate.[54] However, the effect of coaxial technique on biopsy success rate is still yet to be confirmed by large studies. Due to the large size and rigidity of the coaxial guiding needle, locating and positioning the needle are facilitated both on US and CT. The coaxial needle allows for multiple needle biopsies with only one access through the skin and underlying tissues, thereby minimizing the risk of need tract seeding.[55] Moreover, with the use of a coaxial needle, there is no need for needle reposition after one pass with the biopsy needle, which may reduce the procedure time and decrease patients' discomfort.

LOCATION OF BIOPSY

There is no standard pattern of selecting the biopsy location; however, in general, necrotic and cystic areas should be avoided. Hobbs et al.[51] investigated the impact of sampling location on the diagnostic accuracy of renal mass biopsy in an ex vivo study and found the cancer identification rate could be increased by an additional central or peripheral core, and they recommend at least two peripheral cores for RTB.

It is generally accepted that selecting the location of biopsy should depend on the tumor size. For large tumors (>4 cm), the incidence of central necrosis is higher and proper sampling pattern will be of greater importance when compared with smaller tumors.[56] An international multidisciplinary panel recommended sampling different regions including central and peripheral biopsies for large tumors.[36] Abel et al. reported 122 biopsies in 117 renal tumors ≥ cT2 and recommend a multi-quadrant biopsy technique for large renal tumors, which is defined as sampling from at least four separate solid enhancing areas within the tumor.[57] Both US and contrast-enhanced CT may show central areas of hypo-echogenicity or nonenhancement in renal tumors and these findings should be taken into account when planning image-guided biopsy.

For tumors ≤4 cm, also referred as SRMs, the rate of nondiagnostic biopsy seems to be higher than that of larger renal masses. Wunderlich et al. reported 250 fine needle RTBs and demonstrated that for tumors smaller than 4 cm, the individual accuracy of a central and peripheral biopsy is 83.3% and 75%, respectively.[56] The accuracy rate could go up to 96.7% when both peripheral and central biopsies are used concurrently.[56] However, it should be noted that peripheral biopsy for SRMs may not obtain enough tissue because of the small lesion size.

FUTURE DIRECTIONS

Previous studies have confirmed the prognostic value of molecular and genetic markers in RCC such as Ki-67, p53, vascular endothelial growth factor receptor, and loss of 9p.[5859] Biopsy could help attain tissue samples suitable for molecular or genetic tests. In virtue of these tests, we may better differentiate renal tumors with more metastatic potential and can use the information to optimize individual patient management of RCC. Hence, further studies investigating the molecular and genetic information from RTB are warranted.

There are still some limitations of RTB at present. The heterogeneity of renal tumors consistently hinders the accuracy of RTB, and a common biopsy cannot reflect the complex nature of such tumors. Grade heterogeneity in the same renal tumor exists in up to 25% of cases,[13] which contribute to the suboptimal accuracy for grade assessment. For hybrid tumors, such as one that includes the oncocytoma area in a RCC, conventional renal biopsy method could correctly provide diagnostic information only when the biopsy samples the hybrid area by chance. The multi-quadrant method proposed by Abel et al. may be a promising way to solve the problem of renal tumor heterogeneity;[57] however, this method still needs to be replicated in further studies. In addition, oncocytoma diagnoses continue to be a challenge in the clinical practice, and the special case of such challenge is the differential diagnosis: oncocytoma, low-grade chromophobe RCC, hybrid oncocytoma-chromophobe RCC lesion, and papillary type 2 (eosinophilic) RCC.[19] More accurate methods that could resolve this diagnostic problem are required.

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Conflicts of interest

There are no conflicts of interest.