0022-5347/04/1715-1802/0 THE JOURNAL OF UROLOGY® Copyright © 2004 by AMERICAN UROLOGICAL ASSOCIATION

Vol. 171, 1802–1805, May 2004 Printed in U.S.A.

DOI: 10.1097/01.ju.0000120147.51090.2b

ACCURACY AND CLINICAL ROLE OF FINE NEEDLE PERCUTANEOUS BIOPSY WITH COMPUTERIZED TOMOGRAPHY GUIDANCE OF SMALL (LESS THAN 4.0 CM) RENAL MASSES YANN NEUZILLET, ERIC LECHEVALLIER, MARC ANDRE, LAURENT DANIEL AND CHRISTIAN COULANGE From the Department of Urology, Hospital Salvator (YN, EL, CC), and Departments of Radiology (MA) and Pathology (LD), Hospital de la Timone, Marseille, France

ABSTRACT

Purpose: We evaluated the accuracy and clinical role of fine needle percutaneous biopsy of solid renal masses 4.0 cm or smaller with helical computerized tomography (CT) guidance. Materials and Methods: In 88 consecutive patients (mean age 61 years) 88 biopsies were performed. Median tumor size was 2.8 cm. Tumor biopsy was performed with an 18 gauge needle using helical CT guidance in an outpatient setting. At least 2 whole cores per tumor were obtained. Results: Biopsy material was insufficient for analysis in 3 (3.4%) procedures. Median tumor size of failed biopsies was 3.0 cm. There were 5 (5.6%) biopsies which revealed fibrosis and were considered inconclusive. A benign lesion was found in 14 (15.9%) biopsies. In the 66 biopsies positive for malignancy there were 65 cases of renal cell carcinoma and 1 lymphoma. A total of 62 patients underwent surgery. Biopsy changed tumor management in 42 (47.8%) patients who avoided radical nephrectomy, 13 of whom had a lesion which did not require surgery, 1 with a lymphoma and 28 who were treated with partial nephrectomy. Biopsy accuracy for histopathological tumor type and Fuhrman nuclear grade was 92% and 69.8%, respectively. No substantial morbidity occurred. Conclusions: Fine needle biopsy of small renal masses could select benign lesions for which observation might be an alternative to surgery. The accuracy of fine needle biopsy in identifying histological tumor type was high. However, biopsy was less accurate in evaluating Furhman grade. Biopsy with helical CT guidance could be a key point in tailored management of small solid renal masses and provide important information to those patients harboring renal masses. KEY WORDS: biopsy, fine-needle; tomography, spiral computed; carcinoma, renal cell

In some series the incidence of benign lesions in renal masses smaller than 4 cm is higher than in masses greater than 4 cm. Renal cell carcinoma (RCC) smaller than 4.0 cm has a lower pathological stage and is associated with improved survival after removal of the involved kidney.1 Elective partial nephrectomy in patients with a unifocal tumor of 4 cm or less is an appropriate oncological procedure.2 After nephron sparing surgery, cancer-free survival is better in this setting compared to that of patients with larger tumors.3 In our previous study4 we reported that fine needle biopsy with helical computerized tomography (CT) guidance was accurate for the histopathological evaluation of renal masses without major morbidity. In this study we evaluated the accuracy and the clinical role of helical CT guided percutaneous biopsy for the management of solid renal masses smaller than 4.0 cm. MATERIAL AND METHODS

At our institution renal masses less than 4.0 cm were indications for CT guided biopsy. Patients who were referred to our institution underwent an imaging evaluation with ultrasonography and CT performed by a single radiologist (MA). Patients with a Bosniak category I or II cystic mass

and patients with radiological suspicion of angiomyolipoma or transitional cell tumor5 did not undergo biopsy and were excluded from study. Bleeding risks identified from clinical history and laboratory tests were contraindications to inclusion in the study. Percutaneous biopsy was performed by a single operator (MA) according to the previously described technique4 using an 18 gauge needle allowing a 1.7 ⫻ 0.1 cm core to be obtained. Biopsy was performed with helical CT guidance with the patient under local anesthesia of the track. The patient was in prone position. The biopsy site was chosen in the peripheral area of the tumor and biopsy in necrotic area was avoided. The tip of the needle was placed 0.1 cm outside the tumor to obtain a sample of the renal capsule in the core. With this technique the outer cannula of the needle had little contact with the tumor to minimize the possibility of tumoral track seeding. At least 2 cores per tumor were obtained. CT was performed immediately after needle removal to check for post-biopsy complications. All biopsies were performed in an outpatient clinic setting. Histopathological evaluation of the cores was performed with hematoxylin and eosin staining after the cores were fixed in Bouin’s solution (LD). RCC was graded according to the Furhman nuclear system. Nonrenal cell tumors were stained with specific techniques (Hale staining) as well as immunohistochemical staining. The observation of fibrosis on biopsy was not considered a failed biopsy but was considered inconclusive. Parameters evaluated in the study were patient age and gender, tumor size, left or right kidney tumor location, cen-

Accepted for publication November 21, 2003. Nothing to disclose. Editor’s Note: This article is the third of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1916 and 1917. 1802

ACCURACY AND CLINICAL ROLE OF FINE NEEDLE BIOPSY OF SMALL RENAL MASSES

tral or cortical tumor location, unilateral or bilateral tumor involvement, benign or malignant lesion histopathology, type of malignant lesion and Fuhrman nuclear grade of the RCC. Patients with localized N0M0 tumors underwent surgery. Partial nephrectomy was performed for cortical, low grade, chromophobic or clear cell RCC. Due to a high incidence of multifocality6, 7 papillary RCC was treated with radical nephrectomy. A final histopathological analysis was performed and included the same parameters used in biopsy samples. Perirenal and peritumoral fat was analyzed specially to detect tumor track seeding. For statistical analysis Student’s t test was performed to compare continuous variables. The chi-square test and Fisher’s exact test were performed to compare qualitative variables. A difference was considered to be significant at p ⬍0.05. In patients who underwent surgery final biopsy results and final histopathological findings were compared, and biopsy accuracy was calculated.

TABLE 1. Patients with failed biopsy Pt Age

Tumor Size (cm)

Outcome

56 2.5 Radical nephrectomy, grade II clear cell RCC 83 3 Lost to followup 56 3.5 Radical nephrectomy, grade II clear cell RCC Tumor location right cortical in all cases.

TABLE 2. Histological findings on biopsy and patient outcome Histopathological Finding Benign biopsies: Oncocytoma Angiomyolipoma Cystadenoma Inconclusive biopsies: fibrosis

No.

Outcome (No.)

10 3 1

Surveillance, stable disease Surveillance, stable disease Radical nephrectomy, cystadenoma

5

Radical nephrectomy, grade II clear cell RCC (2); partial nephrectomy, grade I papillary RCC (1); surveillance, stable disease (2)

RESULTS

Between June 1995 and March 2003, 88 consecutive patients who met study inclusion criteria agreed to undergo biopsy. Informed consent was obtained and 88 biopsies were performed. Mean patient age ⫾ SD was 61.32 years ⫾ 13.19 (median age 64, range 21 to 88). Of the patients 55% were male. Median tumor size was 2.80 cm (range 0.2 to 4, fig. 1). Of the tumors 45% were in the right kidney and 4 (4.5%) had a central location. The tumor was on a renal transplant by the iliac fossa in 1 patient. In 3 (3.4%) of 88 biopsies material was not sufficient for histopathological examination (failed biopsy, table 1, fig. 2). Of 88 lesions 14 (15.9%) biopsies were benign and 5 (5.7%) were inconclusive. The histopathological findings are summarized in table 2. A total of 66 (75%) of 88 lesions were malignant. The histopathological findings are summarized in table 3. Fuhrman grading was not possible in 4 cases because of an insufficient number of tumor cells in the biopsy speci-

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men. Ten (11.3%) patients had a malignant lesion at biopsy and did not undergo surgery, 9 patients had RCC and serious competitive morbidity, and 1 patient had lymphoma. Upon biopsy results 14 patients had no surgery, 13 of whom had a benign lesion on biopsy and 1 had renal lymphoma. The remaining 9 patients with malignant lesions (9 RCC) on biopsy who did not undergo surgery because of serious comorbidity remained under surveillance and symptomatic treatment. A total of 62 surgeries were performed and are summarized in table 4. A radical nephrectomy was performed in all 4 patients with central RCC. There were no false-positive biopsy findings. Histopathological results are summarized in table 5. The accuracy of biopsy for the diagnosis of malignant tumors was 92% (58 of 63). Biopsy accuracy for histopathological tumor type was 92% (58 of 63). Furhman nuclear grades on biopsy and on final specimen examination are summarized in table 6. Tumors were graded erroneously between biopsy and surgical specimen as low (I or II) or high (III or IV) in 13.1% (8 of 61) cases. The accuracy of biopsy for grade evaluation was 69.8% (44 of 63, fig. 3). No patient had a clinical hematoma or underwent surgery for post-biopsy complications or infection. No patient had postbiopsy pain necessitating medical treatment or hospital admission. In patients who underwent surgery there was no sign that biopsy complicated the nephrectomy. No track seeding was reported on final histopathological analysis. DISCUSSION

FIG. 1. Tumor size of 88 masses

Asymptomatic renal masses are being discovered with increasing incidence because of the increasing use of imaging modalities. Lesions less than 4.0 cm could be more frequently benign8, 9 and indistinguishable from malignant lesions on radiological examination.5 Nephron sparing surgery can be

FIG. 2. Results of biopsy and management of 88 renal masses

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ACCURACY AND CLINICAL ROLE OF FINE NEEDLE BIOPSY OF SMALL RENAL MASSES TABLE 3. Histological findings on biopsy and patient outcome

Biopsy Finding No.

No.

No. Outcome Radical Nephrectomy

Clear cell RCC: 49 Grade I 20 8 Grade II 24 10 Grade III 3 2 Grade IV 0 Unknown grade 2 0 Papillary RCC: 10 Grade I 3 3 Grade II 6 3 Grade III 1 1 Grade IV 0 Unknown grade 0 Chromophobic RCC: 6 Grade I 0 Grade II 2 1 Grade III 2 0 Grade IV 0 Unknown grade 2 1 (grade II) Lymphoma found on 1 malignant biopsy and patient was treated with chemotherapy.

TABLE 4. Indications for surgery No. Radical Nephrectomy

No. Partial Nephrectomy

RCC: Clear cell Papillary Chromophobic

20 7 2

21 3 3

Totals Cystadenoma Fibrosis Failed biopsy

29 1 2 2

27 0 1 0

Biopsy Results

indicated in tumors less than 4.0 cm with favorable carcinogenic results.2 We evaluated the accuracy of and impact on tumor management of fine needle biopsy of solid renal masses 4.0 cm or smaller with new biopsy technologies. Biopsy core size was 1.7 ⫻ 0.1 cm which allows for specific histopathological procedures such as immunohistochemical staining or lymphoma immunophenotyping. Immunohistochemical staining for cytokeratin 7 may be useful for the differential diagnosis of renal oncocytoma and chromophobe

TABLE 5. Histological findings on biopsy and final examination in 62 surgical cases Histopathological Finding

No. Biopsy

No. Final Examination

No. Accurate Biopsies/ Total No. (%)

Clear cell RCC: Grade I 17 15 12/17 (70%) Grade II 20 23 13/20 (65%) Grade III 2 6 2/2 Grade IV 0 1 Unknown 2 0 grade Papillary RCC: Grade I 3 1 0/3 Grade II 6 9 6/6 Grade III 1 1 1/1 Grade IV 0 0 Unknown 0 0 grade Chromophobic RCC: Grade I 0 0 Grade II 2 2 0/2 Grade III 1 3 1/1 Grade IV 0 0 Unknown 2 0 grade Cystadenoma On final examination there were 5 failed or inconclusive biopsies.

Partial Nephrectomy

Surveillance

9 10 0

3 4 1

2 (1 grade I, 1 grade II)

0

0 3 0

0 0 0

1 1

0 1

1 (grade II)

0

renal cell carcinoma when results of Hale’s colloidal iron staining are uncertain.10 Solid variants of papillary RCC lack true papillae but have specific histological, immunohistochemical and genetic features.11 Helical CT guidance can be used to define the optimal site of biopsy accurately and to avoid necrotic areas. The helical technique allows fast image acquisition. By using CT fluoroscopy, which allows biopsy gun activation in real-time mode, we discovered that in some cases the needle pushes the tumor instead of penetrating it. This phenomenon could explain the high failure rate in small tumors observed in our previous study.4 In this study we checked the quality of the core. If core length was less than 10 mm or the core was torn we performed another biopsy. At least 2 whole core biopsies per tumor were obtained. In our current series of solid renal masses 4.0 cm or smaller, the success rate of fine needle renal biopsy was 96.6%. In 100 renal tumor biopsies Imaide and Saitoh had a similar success rate at 97%.12 The sensitivity and specificity of renal tumor biopsy reported in the literature were 70% to 92% and 100%, respectively, with accuracy close to 90%,13 similar to that of our present series. In our series biopsy revealed a benign lesion in 14 (15.9%) patients. Clinical management was altered due to this result in 42 (47.8%) of the 88 biopsies 13 patients with lesions not requiring surgery, 1 patient with a lymphoma and 28 treated with partial nephrectomy. Without biopsy all patients might be candidates for radical nephrectomy. We selected partial nephrectomy for cortical, low grade, clear cell and chromophobic RCC. In cases of central, high grade (due to high pT3 incidence) or papillary RCC (due to multifocality), radical nephrectomy was performed. At our institution oncocytoma and cystadenoma are not indications for surgery and are followed radiologically. In these settings biopsy was used to select patients for whom surgery was not mandatory. According to these criteria 15 (17.0%) patients did not need surgery (14 with benign lesions and 1 with lymphoma) and 20 (22.7%) may require partial nephrectomy. Based on biopsy results Wood et al avoided surgery in 32 (44%) of 73 patients.14 No patients in our series underwent surgery. Thus we were not able to compare biopsy results to the final analysis of the lesions removed after surgery. However, no cancer was suspected at surveillance in patients with a benign biopsy. The biopsy could be useful in identifying benign lesion candidates for observation. In our series a malignant lesion, mainly RCC (74%), was identified in 75% of biopsy specimens. On the biopsy core the histopathological tumor type could be accurately identified as clear cell RCC, papillary RCC or chromophobic RCC, as well as other types of malignant renal tumor. In our series there

ACCURACY AND CLINICAL ROLE OF FINE NEEDLE BIOPSY OF SMALL RENAL MASSES TABLE 6. Fuhrman grades on biopsy and final examination in 56 surgical cases of RCC Statistical Finding Mean 95% CI Min No. Max No. Median

Biopsy

Final Examination

1.72 1.08, 2.35 1 3 2

1.95 1.24, 2.65 1 4 2

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CONCLUSIONS

Fine needle biopsy of solid renal masses 4.0 cm or smaller with helical CT guidance is an accurate tool for the pathological evaluation of renal masses. It can be performed in an outpatient setting with a low morbidity rate. Biopsy is accurate for histopathological evaluation, but is less effective for preoperative Fuhrman nuclear grading. Biopsy can be mandatory for patients with solid renal tumors less than 4.0 cm. In these cases histopathological evaluation with biopsy is necessary for tumor management and patient information.

REFERENCES

FIG. 3. Fuhrman grade on biopsy and on final examination (FE) for clear cell RCC, chromophobic RCC and papillary RCC for which surgery was performed.

no was misclassification of RCC histological type by the biopsy. Biopsy can reliably identify lesions with a high risk of multicentricity, such as papillary RCC, for which a partial nephrectomy might be questionable. Surgery was performed in 56 N0M0 tumors. In these 56 cases there were 2 failed biopsies and 3 inconclusive biopsies. RCC was found on final analysis in the 5 false-negative biopsies. In the other 51 cases (95%) biopsy findings were correlated with final histopathological findings. All but 4 (6%) cases of RCC could not be graded according to the Fuhrman nuclear system on core biopsy because of an insufficient number of tumor cells. Biopsy grade had a weak correlation with final tumor grade. This lack of correlation was due to the heterogeneity of tumors. However, no tumor was graded erroneously by more than 1 point. Biopsy seems less accurate in determining the aggressive potential of a malignant lesion. When RCC was pooled in low (I or II) and high (III or IV) grades biopsy accuracy was improved. Herts and Baker,13 and Cajulis et al15 reported a good concordance of grading between biopsy and final analysis, but our series had few high grade tumors. Biopsy result is critical information for patients with renal masses. If the result is benign the urologist can explain to the patient that surgery is not mandatory and followup can be tailored according to benign lesion type. In addition, if biopsy is malignant, the need for surgery is explained to the patient and the type of surgical procedure, partial or radical nephrectomy, can be presented in advance according to histological cell type and tumor grade. Biopsy has become a key point of information for patients harboring a renal mass.

1. Hafez, K. S., Novick, A. C. and Butler, B. P.: Management of small solitary unilateral renal cell carcinomas: impact of central versus peripheral tumor location. J Urol, 159: 1156, 1998 2. Uzzo, R. G. and Novick, A. C.: Nephron sparing surgery for renal tumors: indications, techniques and outcome. J Urol, 166: 6, 2001 3. Hafez, K. S., Fergany, A. F. and Novick, A. C.: Nephron sparing surgery for localized renal cell carcinoma: impact of tumor size on patient survival, tumor recurrence and TNM staging. J Urol, 162: 1930, 1999 4. Lechevallier, E., Andre, M., Barriol, D., Daniel, L., Eghazarian, C., De Fromont, M. et al: Fine-needle percutaneous biopsy of renal masses with helical CT guidance. Radiology, 216: 506, 2000 5. Smith, P. A., Marshall, F. F. and Fishman, E. K.: Spiral computed tomography evaluation of the kidneys: state of the art. Urology, 51: 3, 1998 6. Amin, M. B., Corless, C. L., Renshaw, A. A., Tickoo, S. K., Kubus, J. and Schultz, D. S.: Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases. Am J Surg Pathol, 21: 621, 1997 7. Kletscher, B. A., Qian, J., Bostwick, D. G., Andrews, P. E. and Zincke, H.: Prospective analysis of multifocality in renal cell carcinoma: influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy. J Urol, 153: 904, 1995 8. Campbell, S. C., Novick, A. C., Herts, B., Fischler, D. F., Meyer, J., Levin, H. S. et al: Prospective evaluation of fine needle aspiration of small, solid renal masses: accuracy and morbidity. Urology, 50: 25, 1997 9. Bosniak, M. A.: Problems in the radiologic diagnosis of renal parenchymal tumors. Urol Clin North Am, 20: 217, 1993 10. Leroy, X., Moukassa, D., Copin, M. C., Saint, F., Mazeman, E. and Gosselin, B.: Utility of cytokeratin 7 for distinguishing chromophobe renal cell carcinoma from renal oncocytoma. Eur Urol, 37: 484, 2000 11. Renshaw, A. A., Zhang, H., Corless, C. L., Fletcher, J. A. and Pins, M. R.: Solid variants of papillary (chromophil) renal cell carcinoma: clinicopathologic and genetic features. Am J Surg Pathol, 21: 1203, 1997 12. Imaide, Y. and Saitoh, M.: Clinical implication of selective renal tumor biopsy. Hinyokika Kiyo, 41: 745, 1995 13. Herts, B. R. and Baker, M. E.: The current role of percutaneous biopsy in the evaluation of renal masses. Semin Urol Oncol, 13: 254, 1995 14. Wood, B. J., Khan, M. A., McGovern, F., Harisinghani, M., Hahn, P. F. and Mueller, P. R.: Imaging guided biopsy of renal masses: indications, accuracy and impact on clinical management. J Urol, 161: 1470, 1999 15. Cajulis, R. S., Katz, R. L., Dekmezian, R., el-Naggar, A. and Ro, J. Y.: Fine needle aspiration biopsy of renal cell carcinoma. Cytologic parameters and their concordance with histology and flow cytometric data. Acta Cytol, 37: 367, 1993