PROSPECTIVE ANALYSIS OF INTRAOPERATIVE FROZEN NEEDLE BIOPSY OF SOLID RENAL MASSES IN ADULTS

0022-5347/99/1624-1282/0

Vol. 162. 1282-1285, October 1999 Printed in U.S.A.

THEJDIRVAL OF UROLCGY Copyright Q 1999 by AMERICxv UROLOCICAL ASSOCL\TION. Ih’C

PROSPECTIVE ANALYSIS OF INTRAOPERATIVE FROZEN NEEDLE BIOPSY OF SOLID RENAL MASSES IN ADULTS CHRISTOPHER B. DECHET, THOMAS SEBO, GEORGE FARROW, MICHAEL L. BLUTE, DONALD E. ENGEN AND HORST ZINCKEF From the Departments of Urology and Pathology, Maya Clinic, Rochester, Minnesota

ABSTRACT

Purpose: We prospectively determined the accuracy of intraoperative needle biopsy of solid renal masses. Materials and Methods: A total of 103 patients diagnosed with a solid renal mass and scheduled for surgery were prospectively evaluated. Radical or partial nephrectomy was performed, and biopsy of the surgical specimen was done twice through the tumor using a n 18 gauge biopsy gun. Biopsy specimens of 106 tumors were sent for frozen sectioning, stained with hematoxylin and eosin, and reviewed by 2 independent pathologists blinded to each other and whole tissue specimens. Biopsy results were compared to whole tissue specimens. Results: Specimens were obtained from 60 radical and 46 partial nephrectomy cases. Malignant neoplasms were present in 91 cases (86%).Overall, 15 cases (14%)were benign, of which 11 were oncocytomas. If lesions 4 cm. or less only were included in analysis, the incidence of benign lesions increased to 22%. Overall accuracy of the 2 pathologists was 76 and 80%.Nondiagnostic rates were 11 and 17%.Both observers incorrectly diagnosed 4 malignant lesions (5%)as benign, and incorrectly diagnosed 3 and 5 benign lesions (21 and 36%), respectively, as malignant. Analysis of values for both observers yielded a sensitivity of 77 and 84%, specificity 60 and 73%, positive predictive value 94 and 96%, and negative predictive value 69 and 73%. Conclusions: Overall frozen needle biopsy was accurate in more than 75%of cases and showed a n excellent positive predictive value for carcinoma of more than 94%.Unfortunately, there was a large degree of inaccuracy for benign lesions and we do not recommend the routine use of intraoperative frozen needle biopsy to guide surgical decision making. KEYWORDS:kidney neoplasms; biopsy, needle; nephrectomy; predictive value of tests

Traditionally, solid renal masses have been treated with radical nephrectomy. However, not all solid renal masses are malignant, nor is radical excision necessary for satisfactory long-term results.’ Identifjmg cases preoperatively on radiographic imaging andor fine needle aspiration or biopsy is presently not possible. Additionally, with the more prevalent use of ultrasonography and computerized tomography the number of asymptomatic and incidentally detected solid renal masses has increased.’ Clinical significance, tumor characteristics and treatment remain controversial. The incidence of benign lesions in this group may be increased and treatment with radical nephrectomy in many cases would be excessive. Many patients who undergo renal exploration and radical nephrectomy would benefit from partial nephrectomy if a diagnosis could be made with certainty. Nephron sparing surgery would be ideal for benign lesions, such as oncocytomas. Intraoperative needle biopsy of solid renal masses with immediate frozen tissue sectioning and analysis could help identify patients who may benefit from nephron sparing surgery or radical nephrectomy if specific tumor histology could be determined. We prospectively evaluated a series of patients to determine the value of intraoperative frozen needle biopsies of solid renal masses. Accepted for publication April 9, 1999. * Requests for reprints: 200 First St. S.W., Rochester, Minnesota, 55905. Editor’s Note: This article is the third of 5 published in this issue for whicb category 1 CME credits can be earned. In-

structions for obtaining credits are given with the questions on pages 1450 and 1451.

MATERIALS AND METHODS

From August 1996 to October 1997,103 patients diagnosed with a solid renal mass and scheduled for surgery were prospectively identified. Radical or partial nephrectomy was performed and biopsy of the surgical specimen was done twice through the tumor using an 18 gauge biopsy gun. Tissue samples of 106 tumors were sent for frozen sectioning, and stained with hernatoxylin and eosin. The specimens were reviewed by 2 independent pathologists blinded to each other and whole tissue specimens. Biopsy results were compared to whole tissue specimens by an independent observer. Final whole tissue specimen results were categorized as malignant or benign. Frozen biopsy data from the 2 independent pathologists were categorized as malignant, benign or nondiagnostic. Any biopsy result designated as suspicious for, consistent with or indicating malignancy was designated as malignancy. Similar criteria were used for benign lesions. Confidence intervals (CIS)for sensitivity, specificity, positive predictive values and negative predictive values were based on Feller approximations. The estimated kappa value was used to assess interobserver reliability. RESULTS

The 70 men and 33 women (2.1:l) ranged in age from 21 to 85 years (mean 61). Radical nephrectomy was performed in 60 patients (57%) and partial nephrectomy in 46 (43%). Tumor size ranged from 1 t o 18 cm. (median 4.6) (table 1). Of the 106 tumors 91 (86%) were malignant, and the majority were renal cell carcinoma. Overall 15 of 106 tumors (14%) were benign, and the majority were oncocytomas which comprised a 10% overall occurrence for all tumors.

1282

1283

INTRAOPERATIVE FROZEN NEEDLE BIOPSY OF SOLID RENAL MASSES

TABLE1. Tumor cliaracteristics No Tumors 4 Cni or Less (9: 1

No. Tumors (%I ~

Cases Biopsies Malignant: Renal cell Ca Transitional cell Ca Lymphoma Metastatic lung Ca Collecting duct tumor Neuroendocrine tumor Small cell Ca Benign: Oncocvtoma Metanephric adenoma Fibrous tumor Benign cyst

103 106 91 (86) 84 1 2 1 1 1 1 15 (14) 11 (10 overall) 1 1 2

48 50 39 35 1 2 0 1

(78)

0

0 11 (22) 9 (18 overall) 1 0 1

TABLE2. Fine needle biopsy results No. Pathologist A

No. Pathologist B

Malignant Type Pathology diagnosis

Benign Final Trace

70 4 17 91

3 11 1 15

Malignant Benign Nondiagnostic Totals

~~~~~~

Malignant True Diagnosis 76 4 11 91

Benign True Diagnosis 5 9

1 15

TABLE3. Statistical analysis

9% Sensitivity % Specificity % Pos. predictive value % Neg. predictive value

Interobserver reliability

Likewise, pathologist B correctly diagnosed 85 of 106 cases with an overall accuracy of 80%.A total of 12 biopsies (11%) were considered nondiagnostic, 4 malignant lesions were considered benign and 5 benign lesions were thought t o be malignant. Of the l l oncocytomas 9 (82%)were correctly diagnosed and the remainder were believed to be renal cell carcinoma. Statistical analysis included sensitivity, specificity, and positive and negative predictive values with confidence intervals (table 3). When the values of the 2 pathologists were averaged, sensitivity and specificity were 81 and 67%,respectively. The positive predictive values for the pathologists were 96 and 94% with narrow confidence intervals, and the negative predictive values were 73 and 69% with large confidence intervals. Calculated false-negative (sensitivity 1) and false-positive (specificity 1) rates were 20 and 3470, respectively. The 2 pathologists were in agreement 83% of the time.

Pathologist

Am

95%CI AIE

77/84 73/60 96/94 73/69 0.83

67-85/74-90 45-92/32-84 8%99/8&98 44-92/39-91 0.71-0.94

Of 106 tumors 50 (47%)were 4 cm. or less. Of these tumors 11 (22%)were benign, including 9 oncocytomas, yielding an 18% overall incidence for solid renal masses 4 cm. or less only. Frozen needle biopsy results for both pathologists are listed in table 2. Pathologist A correctly diagnosed 70 malignant and 11 benign lesions yielding an overall accuracy of 76%.A total of 18 biopsies (17%)were considered nondiagnostic, 4 malignant lesions were considered benign and 3 benign lesions were believed to be malignant. Excluding from analysis all tumors except oncocytomas, 8 of 11 (73%)were correctly diagnosed on frozen needle biopsy and the remainder were thought to be renal cell carcinoma (clear cell type).

DISCUSSION

Radical nephrectomy has been the traditional approach t o solid renal masses. However, not all solid renal masses are malignant and these patients would benefit from nephron sparing surgery if possible. As the number of incidentally detected solid renal masses increases due to widespread radiographic imaging," the incidence of benign tumors appears to be increasing. Silver et a1 in a recent review of 636 nephrectomies noted 92 benign lesions (14.5%h3Analysis of a number of cases of small solid renal tumors (less than 3 cm.) indicates that approximately 10 to 15% are oncocytomas.4~5 In this prospective study of 106 solid renal masses treated with surgical resection 15 (14%)were benign. Oncocytomas comprised the majority with an overall 10% incidence of all solid renal masses. If only renal tumors 4 cm. or less were included in analysis, the incidence of benign tumors increased to 22%.Again, the majority were oncocytomas with an 18% overall incidence for all renal masses 4 cm. or less. Given this high incidence of benign tumors, especially among solid renal masses 4 cm. or less, radical nephrectomy in all cases seems excessive. Presently it is impossible to identify these cases preoperatively through radiographic imaging andor fine needle biopsy or aspiration. It appears that intraoperative needle biopsy of these solid renal masses with immediate frozen tissue sectioning could help identify patients who may benefit from nephron sparing surgery or radical nephrectomy if specific tumor histology could be determined. A number of authors have advocated such an approach.6-8

TABLE4. Needle biopsylaspiration studies of renal masses lT ';

Total No. Confirmed

Cases

Pathology r%)

References

Nosher et al" Helm et all" Juul et all' Orell et all2 Nadel et all" Pilotti et al" Leimanls Haubeck et all6 Torp-Pederson et al" Torp-Pederson et all7.* Cristallini et all" Abe and Saitohlg.* Mondal and Ghosh'" Niceforo and Coughlin" Kelley et a P Campbell et alZ3

21 31 30 1 83 30 124 113 169 134 134 72 36 92 23 43 25

No.

. ., -

17 (55)

-

56 (67) 1 (3) 23 (19) 62 (57)

61 (46) 61 (46) 27 (381 21 (60) 92t100) 6 (26) 11 (26) 25 (100)

10 25 218 69 15 61 83 137 85 85 37 26 81 15 40 25

No. Confirmed Malignant Pathology ( % )

No. Benign Cases

-

11 5 83 14 15 63 30 32 49 49 35 10 11 8 3 0

16 (64) -

54 (78) 1 (7) 31 (49) 51 (61) -

63 (74) 63 (741 22 (68) 21 (81) 81 (100) 4 (27) 8 (20) 25 (100)

No. Confirmed

%

Benign Pathology ( Q )

Sensiti,,ity

-

1 (17)

-

2 (14) 0 (0) 2 (3) 13 (43) -

12 1241 12 (24) 2 (6) 0 10) 11 (100) 2 (25) 3 (100) 0

If values were not specified by the authors, we provided them based on a review of the original articles.

* Results obtained with needle biopsy versus aspiration techniques.

100 90 88 90 93 93 92 87 92 88 89 96 100 80 100 62

No. 1 Specificity True Pos. 100 83 81 93 100

96 94 88 85 100 97 100 82 100 0

-

No. No. No True False- FakeNeg. Pos. Neg.

10 11 0 1 9 5 1 185 61 14 62 13 1 13 15 0 60 63 1 76 16 2 112 28 4 76 41 7 60 38 0 33 34 1 24 10 0 7 7 9 2 1 2 8 0 4 0 0 3 1 0 0 0

0

2 25 0

1 0

3 17 7 8

4 1 0 3 0 6

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INTRAOPERATNE FROZEN NEEDLE BIOPSY O F SOLID RENAL MASSES

While multiple published reports exist on the use of percutaneous fine needle aspiration of biopsy of renal masses, few series include many solid benign renal masses, are prospective in nature or have confirmed pathology following biopsy. We address these issues as our study was prospective, had a significant number of benign masses and had confirmed pathology for all cases. Table 4 summarizes the published reports of percutaneous fine needle aspiration or biopsy of renal Most series include results obtained from aspiration and only 2 have confirmed pathology for all cases of needle 1of which includes benign cases.2o The majority of published reports include gross histological specimens in less than 50% of cases, and the majority of benign tumors appear to be cystic structures and not solid masses. In addition, final pathological confirmation is generally less than 25%. Overall results reveal sensitivities and specificities between 62 to 100% and 0 to loo%, respectively. Unfortunately, confidence intervals are not reported and, based on the number of benign cases, specificities would most likely have large confidence intervals. Our data are within these broad reported ranges. Overall accuracy was more than 7 5 8 , sensitivity 81% and specificity 67%. In approximately 15% of cases inadequate tissue was obtained for pathological evaluation. The positive predictive value for carcinoma of more than 94%) was excellent but approximately 5% of all malignant tumors with adequate tissue for evaluation were considered benign. In the only other prospective study involving solid renal masses results were false-negative in 6 of 16 cases with adequate tissue for e ~ a l u a t i o n In . ~ ~our study there was also a large degree of inaccuracy with regard to benign lesions, precisely those tumors which would benefit from correct identification and nephron sparing surgery. The negative predictive values were only 73 and 69% with observers A and B incorrectly diagnosing 20 and 36% of benign lesions as malignant. In conclusion, the large degree of inaccuracy for the prediction of benignity and false-positive rates of more than 20% indicate that decision making based on intraoperative frozen needle biopsy results is not recommended.

11. Juul, M., Torp-Pedersen, S., Grenvall, S., Holm, H. H., Koch, F. and Larsen, S.: Ultrasonically guided fine needle aspiration biopsy of renal masses. J. Urol., 133 579, 1985. 12. Orell, S. R., Langlois, S. L. and Marshall, V. R.: Fine needle aspiration cytology in the diagnosis of solid renal and adrenal masses. Scand. J. Urol. Nephrol., 1 9 211, 1985. 13. Nadel, L., Baumgartner, B. R. and Bernardino, M. E.: Percutaneous renal biopsies: accuracy, safety, and indications. Urol. Radiol., 8 67,1986. 14. Pilotti, S.,Rilke, F., Alasio, L. and Garbagnati, F.: The role of fine needle a d r a t i o n in the assessment of renal masses. Acta. Cytol., 32: 1, i988. 15. Leiman. G.: Audit of fine needle aspiration cytology of 120 renal lesions. Cytopathology, 1: 65, 1990. 16. Haubeck, A,, Lundorf, E. and Lauridsen, K. N.: Diagnostic strategy in renal mass lesions. Scand. J . Urol. Nephrol., 137: 35, 1991. 17. Torp-Pederson, S.,Juul, N., Larsen, T., Karstrup, S., Sehested, M. and Glenthoj, A,: US-guided fine needle biopsy of solid renal masses-comparison of histology and cytology. Scand. J. Urol. Nephrol., 137: 41, 1991. 18. Cristallini, E. G., Paganelli, C. and Bolis, G. B.: Role of fineneedle aspiration biopsy in the assessment of renal masses. Diagnosis Cytopath., 7: 32, 1991. 19. Abe, M. and Saitoh, M.: Selective renal tumour biopsy under ultrasonic guidance. Brit. J . Urol., 7 0 7, 1992. 20. Mondal, A. and Ghosh, E.: Fine needle aspiration cytology (FNAC) in the diagnosis of solid renal masses-a study of 92 cases. Indian J . Path. Microbiol., 3 5 333, 1992. 21. Niceforo, J . and Coughlin, B. F.: Diagnosis of renal cell carcinoma: value of fine- needle aspiration cytology in patients with metastases or contraindications to nephrectomy. AJR, 161: 1303,1993. 22. Kelley, C. M., Cohen, M. B. and Raab, S. S.: Utility of fine-needle aspiration biopsy in solid renal masses. Diagnosis Cytopath., 1 4 14,1996. 23. Campbell, S.C., Novick, A. C., Herts, B., Fischler, D. F., Meyer, J., Levin, H. S. and Chen, R. N.: Prospective evaluation of fine needle aspiration of small, solid, renal masses: accuracy and morbidity. Urology, 5 0 25, 1997.

REFERENCES

1. Morgan, W. R. and Zincke, H.: Progression and survival after renal-conserving surgery for renal cell carcinoma: experience in 104 patients and extended followup. J . Urol., 144:852,1990. 2. Konnack, J . W.and Grossman, H. B.: Renal cell carcinoma as an incidental finding. J . Urol., 134: 1094,1985. 3. Silver, D. A., Morash, C., Brenner, P., Campbell, S. C. and Russo, P.: Pathologic findings at the time of nephrectomy for renal mass. Ann. Surg. Oncol., 4 570, 1997. 4. Smith, S. J., Bosnick, M. A., Megibow, A,: J., Hulnick, D. H., Horii, S. C. and Raghavendra, B. N.: Renal cell carcinoma: Earlier discovery and increased detection. Radiology, 170 699, 1989. 5. Levine, E., Huntrakoon, M. and Wetzel, C. H.: Small renal neoplasms: clinical pathologic and imaging features. h e r . J. Roentgenol., 153 69,1989. 6. Pfannkuch, F., Leistenschneider W. and Nagel, R.: Problems of assessment in the surgery of renal adenomas. J. Urol., 125 95, 1981. 7. Blight, E. M., Jr.: Renal adenoma: therapeutic implications. Urology, 24: 255, 1984. 8. Maatman, T. J., Novick, A. C., Tancinco, B.: F., Vesoulis, Z., Levin, H. S., Montie, J . E. and Montague, D. K.: Renal oncocytoma: a diagnostic and therapeutic dilemma. J . Urol., 132: 878,1984. 9. Nosher, J . L., Amorosa, J . K., Leiman, S. and Plafker, J.: Fine needle aspiration of the kidney and adrenal gland. J. Urol., 128 895, 1982. Burwood, R. J., Harrison, N. W. and Melcher, D. H.: 10. Helm, C. W., Aspiration Cytology of Solid Renal Tumours. Brit. J . Urol., 5 5 249,1983.

EDITORIAL COMMENT The authors performed needle biopsy of renal tumors after nephrectomy with the hope of better selecting patients for partial nephrectomy or nephron sparing surgery. Although this procedure does not completely simulate a preoperative diagnostic percutaneous needle biopsy of the kidney, it allowed the authors to attempt to assess the accuracy of needle biopsy. During the last 10 years much clinical evidence has been presented that suggests that for carefully selected patients partial nephrectomy offers excellent rates of local tumor control with low rates of local recurrence when performed of necessity as well as in the strategy of nephron sparing. Due to a stage migration from effective abdominal imaging by computerized tomography and ultrasound, the excellent prognosis of small renal tumors, whether treated with partial or radical nephrectomy, has initiated a change in the American Joint Committee on Cancer staging system to include those 7 cm. or less as T1 tumors. The decision to perform partial nephrectomy is based mainly on tumor size and location as well as age and patient condition. There appears to be little question that tumors 4 cm. or less are equally well treated with partial or radical nephrectomy. This approach is safe and effective across all histological subtypes with varying metastatic potentials ranging from conventional clear cell carcinoma to the nearly benign oncocytoma. Oncocytoma is the most benign variant of renal cortical neoplasms that retain a low but real metastatic potential.' That as many a s 40% of renal cancers (size notwithstanding) have a reduced metastatic potential based on histology other than conventional clear cell carcinoma provides added incentive to perform partial nephrectomy when possible. This approach, when technically and medically feasible, is being liberally applied a t our center. The authors provide clear information that even under ideal biopsy circumstances (not clinical) needle biopsy does not have sufficient accuracy (75%) to make a diagnosis of histological type that would ultimately change management. Despite direct access to the tumors, of 103 biopsies 30 were considered nondiagnostic, further suggesting that using current technology biopsy techniques cannot distinguish benign from malignant renal tumors. When considering