UROLOGICAL ONCOLOGY Evaluation of Diagnostic Accuracy of Percutaneous Biopsy for Small Renal Masses and First Report of Post-Biopsy Adhesions: A Prospective Study Tunkut Doganca*, Can Obek Purpose: In the present study, we evaluate the biopsy results, complications due to biopsy, and the correlation with the final pathology specimen of 19 patients who had surgery for their small renal masses. Materials and Methods: A total of 19 patients (11 male, 8 female) underwent percutaneous biopsy of their renal mass under ultrasound guidance. All patients subsequently underwent extirpative surgery. Preoperative biopsy results were compared with postoperative specimens in terms of tru-cut and fine needle aspiration biopsies’ histo- pathological accuracy and the complications noted. Results: Average age was 56±10.5 years and tumor size was 37±10.6 mm. Six patients had only fine needle, 4 patients had only tru-cut, and 9 patients had both fine needle and tru-cut biopsies. Malignancy was reported in 14, and benign results in 5 patients. Sensitivity, specificity, PPV and NPV’s were 64%, 100%, 100%, 33% respectively for FNAB. Sensitivity, specificity, PPV and NPV’s were all 100% for tru-cut core biopsy. Two perirenal hemat- oma was detected which resolved spontaneously under conservative therapy. In 11 patients there were adhesions due to biopsy, which caused difficulty of dissection during the operation. Conclusion: In this relatively small series, percutaneous ultrasound guided biopsy to determine the histology of small renal masses achieved a high diagnostic accuracy. FNAB alone has a low diagnostic accuracy with false negative results when compared. However, tru-cut core biopsy has a diagnostic accuracy of %100. Therefore we recommend tru-cut biopsy when histopathological diagnosis is required for small renal masses. Adhesions due to biopsy may cause difficulties during dissection. Keywords: biopsy adhesions; biopsy complications; renal biopsy; renal cancer; small renal masses INTRODUCTION Incidence of small renal masses (< 4cm) (SRM) is in-creasing due to widely use of cross-sectional imag- ing techniques and management of these clinical issue is getting more important and complicated depending on which patients will need therapy and which therapy option is feasible and effective. Biopsy of a renal mass is not the standard of care and is suggested in specific circumstances only. There has been a stage shift within the recent years with renal masses presenting at lower stages and smaller sizes at diagnosis. SRM show heter- ogeneous histological properties with both malign and benign characteristics. Smaller lesions tend to be more benign.(1,2) These patients may potentially be offered a variety of management options changing from obser- vation only to radical surgery. The information which gained by the tissue sampling with accurate biopsies, can be decisive at choosing treatment method. In ad- dition to the change in clinical presentation and man- agement, advances in biopsy and immunohistochemical analysis techniques, along with successful outcomes of renal biopsies have caused an increased interest in the potential role of biopsy in renal masses.(3,4) In the present study, we evaluate diagnostic accuracy Department of Urology, Acibadem Taksim Hospital, Istanbul 34300, Turkey. *Correspondence: Acibadem Taksim Hospital, Department of Urology, Istanbul, Turkey. Mailing Adress: Inonu Mah., Nizamiye Cad. No:1, 34373 Sisli/Istanbul/Turkey. GSM: +905327042325 Fax: +902122190987. tunkutdoganca@gmail.com. Received October 2017 & Accepted July 2018 of two different biopsy techniques (tru-cut and FNAB) and the correlation with the final pathology specimen of 19 patients who had surgery for their small renal mass- es. Also biopsy related complications such as post biop- sy adhesions were noted and discussed. MATERIALS AND METHODS Study Population A total of 20 patients with a renal mass (<5 cm.) who are candidates for extirpative surgery has been offered biopsy. Size of the tumors measured with coaxial imag- ing techniques such as CT and MRI. Nineteen patients accepted the procedure and after consultation with radi- ology department, biopsies were performed. Study Design Cysts with heterogeneity and masses suspected for collecting system malignancies were excluded. All patients underwent surgery after the biopsy and final pathological results were compared with the biopsy re- sults. Inefficient tissue samples, normal renal parenchy- ma, extrarenal tissue, blood cells and necrosis were ac- cepted as inadequate biopsy result. Biopsy related early and late complications were also noted and a post-op questionnaire for the surgeons was used to determine if the biopsy procedure affected and challenged the surgi- Urology Journal/Vol 16 No. 4/ July-August 2019/ pp. 357-360. [DOI: http://dx.doi.org/10.22037/uj.v0i0.4215] cal procedure. Sensitivity, specificity, positive and neg- ative predictive values were also calculated. Informed consent was obtained from all patients which had been approved by the local ethics committee (Istanbul Uni- versity Ethics Committee, file no: 01.09.20/s11) Biopsy Technique All biopsies were performed under local anesthesia with the guidance of ultrasonography (USG). Patients were evaluated for hemorrhagic diathesis and routine biochemical tests were performed before the procedure. Fine needle biopsy (FNB) in 6, tru-cut biopsy in 4, and FNB+tru-cut biopsies were performed in 9 patients. Main concern about performing tru-cut biopsy was ex- cessive vascularity of the tumor or nearness to the renal hilum. A cytopathologist evaluted FNAB samples in the procedure room simultaneously and FNA biopsies were repeated up to 3 times according to the informa- tion from the cytopathologist. Tru-cut biopsies were performed by 18gauge needle. Both center and periph- eral zones of the tumors were tried to be sampled. Sep- arate tru-cut sampling technique were chosen instead of co-axial technique. Necessity of using a trocar needle thicker than 18 gauge was the main concern in terms of higher possibility of bleeding. Patients were observed for two hours with ultrasonography in case of hemato- ma formation. RESULTS There were 11 male and 8 female patients with average age of 56 (± 10.5) years. Average tumor size was 36 mm (20-50) (± 10.6). Mean time between biopsy and operation was 26.4 (± 7.2) days. Nine of the tumors were right and 10 of them were left sided. Final patho- logical results were 16 renal cell carcinoma (RCC), 2 oncocytoma and 1 glomus tumor. Immunohistochem- ical techniques used in 4 specimens (%21. 2 of them were oncocytomas and 2 RCCs). (Table 1) FNB results were inefficient in 2, benign in 6 and ma- lign in 7 patients. Only 2 of 6 benign results were cor- related with final pathology (4/6 false negative results). Tru-cut samples were always adequate for histological evaluation. Two benign and 11 malignant results were reported. All of these results show consistency with the final pathology. (FNAB and Tru-Cut needle biopsy re- sults are presented in Table 2) Sensitivity, specificity, positive and negative predictive values were %64, %100, %100 and %33 for FNAB re- spectively. There were no false negative or false posi- tive results in tru-cut, so all of the above values were %100. (Table 2) Complications Two patients with post-biopsy hematomas (3 and 4 cm) managed conservatively and required no intervention. No clinical infection, pleural injury or pneumo/heamo- thorax were observed. There were adhesions in 11 patients (%61) which made the surgical procedure difficult according the post-op surgeon questionnaires. These adhesions also compro- mised tumor margins to be properly determined during surgery. In absence of validated or generally accepted adhesion scores for retroperitoneal surgery, effect of adhesions were evaluated with a simple questionnaire after the operation by the operating surgeon who de- fined the effects of biopsy on increased difficulty of dissection as minimal, moderate or severe. In 11 proce- dures, surgeons’ statements were as 2 moderate and 9 Percutaneous biopsy for renal masses-Doganca et al. Table 1. Demographic data of patients and histological diagnosis for each biopsy type and final pathology. Patient no. Gender Age FNAB Tru-Cut Final Pathology 1 M 55 RCC - RCC 2 F 46 BENIGN - RCC 3 F 50 INADEQUATE BENIGN BENIGN 4 F 68 BENIGN - RCC 5 F 52 BENIGN RCC RCC 6 F 33 RCC RCC RCC 7 F 62 - RCC RCC 8 F 56 BENIGN RCC RCC 9 M 64 RCC RCC RCC 10 M 44 RCC - RCC 11 F 63 RCC RCC RCC 12 M 60 - RCC RCC 13 M 68 BENIGN - BENIGN 14 M 65 - RCC RCC 15 M 50 BENIGN BENIGN BENIGN 16 M 66 RCC - RCC 17 M 40 INADEQUATE RCC RCC 18 M 52 RCC RCC RCC 19 F 69 - RCC RCC Abbreviations: FNAB, Fine needle aspiration biopsy; F, female; M, male; RCC, renal cell carcinoma Final Pathology, malignant Final Pathology, benign Total FNAB, malignant pathology 7 0 7 FNAB, benign pathology 4 2 6 Total (FNAB) 11 2 13 Tru-cut, malignant pathology 11 0 11 Tru-cut, benign pathology 0 2 2 Total (Tru-cut) 11 2 13 Abbreviations: FNAB, Fine needle aspiration biopsy Table 2. Pathological diagnosis for FNAB and Tru-cut biopsy. Vol 16 No 04 July-August 2019 358 severe adhesions. Frozen section evaluation of tumors showed two positive surgical margin status and result- ed in re-excision which also caused prolonged ischemia time. Adhesions were mainly detected in biopsy tracts but in some patients minor hemorrhagies and possible desmoplastic reactions caused severe adhesions also in perirenal fat tissues. During the early follow up after biopsies, there were no significant hypotension. Pain scores were mild (all < 6 via Visual Analog – Numeric Pain Scale) and didn’t required any painkillers except paracetamol and non- steroids. One patient developed high fever in first 24th hours. Ultrasonographic evaluation of biopsy site didn’t show any abnormalities such as hematoma, collection or ab- scess formation. During follow-up, fever was respon- sive to oral hydration and paracetamol therapies and there was no need for prolonged antibiotic therapy. Macroscopic hematuria were observed in two patients with endophytic renal masses but there were no need for urethral catheterization due to excessive bleeding or urinary clots. None of the patients required blood trans- fusion. Postoperative period of 9 patients who had severe post-biopsy adhesions were not eventful. Prolonged ischemia time because of positive surgical margins at initial excision were not influential on postoperative creatinine levels. Two patients had high fever in first 48 hours with no positive bacterial growth in urine and blood cultures and were evaluated as possible atelecta- sis related fever which solved in first 48 hours of anti- biotic therapy. Complications are presented in Table 3 with Clavien Classification. DISCUSSION Renal biopsy has not been routinely performed because of historical fear about hemorrhagic complications and tumor seeding. Low diagnostic results due to poor tech- niques and inefficient instruments also caused draw- backs about performing biopsy for SRMs.(1) Biopsy can be performed with fine-needle or tru-cut biopsy needle under ultrasonography, computerize to- mography or magnetic resonance imaging. Size, nature (necrotic areas or satellite lesions) and location of the lesion is important to determine sampling areas and numbers.(5) According to EAU guidelines, biopsy is not recom- mended routinely for renal masses. Role of biopsy is currently limited to masses which are candidate for ac- tive surveillance or ablative therapies.(6) Publications before 2001 on renal biopsy reported 88.9% accuracy and 0-25% false negative results.(7-9) However these discouraging results are primarily be- cause of inadequate sampling.(10) Technical failure is also as high as 8.9%. In series published after 2001, accuracy was increased to 96% with better imaging techniques and better sampling with developments of biopsy needles.(1,5,11) Immunohistochemistry is also used around 50% for evaluation of biopsy samples.(3,4) Immunohistochemical techniques were also used in 4 patients in our study to determine histology. Latest retrospective cohort study including 529 pa- tients’ data represented a diagnostic yield at 90%, reaching 94% when a repeat biopsy was performed af- ter a failed one. Benign lesions were 20% likewise in other publications.(12) There are limited studies in the literature that compares the biopsy results with the surgical specimens. SRM biopsy may not identify the whole mass because of par- tial sampling and heterogeneous nature of renal masses. (13,14) Appropriate biopsy technique is another important issue besides mass’ characteristics. In recent studies, USG and CT imaging modalities were mostly used.(15- 17) We preferred USG for guidance because of its ac- cessibility and cost effectiveness. Also, biopsy needle types are important factors to achieve right diagnosis. There are some studies who stop using FNAB and con- tinue with only with tru-cut needles because of high percentage of inadequate sampling and low specificity results with FNAB.(3) FNAB achieved the right diagno- sis in only 9 of 15 patients in our study with a accuracy rate of 69%. However, final pathology correlation was 100% for tru-cut samples. Pathologist were not blind for the preoperative biopsy results when evaluating fi- nal specimens. Correct subtyping of RCC’s are up to 94% in literature with a 91% for clear cell, 91% for papillary type and 100% for chromophobe RCC.(1) Fuhrman grading is ad- equate only in 70% and 83%, with the reason of tumor heterogeneity.(1,7) In our study pathologists could report 9 biopsy samples’ Fuhrman grades with a 100% corre- lation with final specimen. Surgical challenge caused by post biopsy adhesions were never reported in literature. There were 11 mod- erate to severe adhesions in our study. Two of these pa- tients had hematoma, which were detected after biopsy and it’s uncertain that if these adhesions were related to hematoma formation or traumatic effect of biopsy nee- dle at the tract. In one case, severe adhesion of perirenal fat tissue to the tumor, make difficult to determine safe surgical margins between tumor and parenchyma and resulted with conversion to open surgery from laparos- copy. Retroperitoneal adhesions are mainly considered about retroperitoneal laparoscopic surgical procedures and are often related with previous percutaneous stone Pt. No. Biopsy Complication (Clavien Grade) Management Surgery Complication (Clavien Grade) Management 1 Fever (I) Antipyretics None - 2 None - None - 3 Hematoma formation (I) Conservative Prolonged ischemia time (I) Conservative 4 None - Prolonged ischemia time (I) Conservative 5 Hematoma formation (I) Conservative None - 6 Hematuria (I) Conservative None - 7 Hematuria (I) Conservative None - 8 None - Fever (I) Antibiotics 9 None - None - Table 3. Classification of biopsy and surgery complications based on modified Clavien classification for patients who had developed severe adhesions after biopsy. Percutaneous biopsy for renal masses-Doganca et al. Urological Oncology 359 surgery or nephrostomy tube placement in case of hy- dronephrosis. These adhesions are generally firm and allow blunt dissection during laparoscopic intervention. Patients with SRM are candidates for nephron sparing surgery and determining safe surgical margin between tumor and renal tissue is essential during partial ne- phrectomy. Post-biopsy adhesions in case of hardening the clear surgical dissection and obtaining a clear cleav- age may cause a rational drawback to perform biopsy. Small sample size is a major limitation for our study. Biopsy related complications such as hematoma forma- tion was low, but within this small patient group, it’s not suitable to discuss on percentages. However, there was a significant adhesion rate which needs to be men- tioned. Retroperitoneal adhesions wre not studied and classified as intraperitoneal adhesions so far in the liter- ature. Adhesions may be grouped as filmy/strong, needs blunt/sharp dissection, or vascularized. In our study, adhesion levels were examined by surgeons’ feedback which is a highly subjective method. Biopsy technique may effect the development of post-biopsy adhesions. We chose separate tru-cut sampling from tumors, which means more than one access was needed. Using a tro- car needle, which is thicker than 18 gauge as a co-axial technique may reduce access numbers but also increase bleeding possibility. Histopathological nature of adhe- sions were not determinable in our study, with lack of histologic sampling from adhesions. Fibrotic processes after biopsy related to tissue trauma or post bleeding formation are the main possible causes for these. But small size of groups did not allow us to compare these two techniques in terms of adhesion formation rate. However, high incidence of adhesions encouraged us on reporting. In the present study sensitivity, specificity results were accordant with the literature. There were no major com- plications. 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