COMPARISON OF TRANSRECTAL FINE-NEEDLE ASPIRATION CYTOLOGY AND CORE NEEDLE BIOPSY IN DIAGNOSIS OF PROSTATE CANCER DAVID W. BRE;\NER, M.D.
STEVEN M. SCHLOSSBERG, M.D.
LEOPOLDO E. LADAGA, M.D. MERIEL B. FILLION, B.S.
PAUL F. SCHELLHAMMER, M.D.
From the Departments of Urology and Pathology, Eastern Virginia Medical School, Norfolk, Virginia
ABSTRACT-One hundred sixty-nine transrectal fine-needle aspirations of the prostate gland were performed in 166 patients over a two-year period. The results were compared with simultaneous core needle biopsy performed in all but 4 patients. Forty-seven (28 %) aspirations were either unsatisfactory or inconclusive. Of the remaining 122 (72 %) patients in whom a cytologic diagnosis could be made, core biopsy was available in 120. Aspiration cytology was 87 percent sensitive and 96 percent specific with an o-uerall agreement of 93 percent with core biopsy. No major complications occurred. We conclude that fine-needle aspiration of the prostate is accurate, safe, and costeffective, and greater application of this technique is encouraged.
Although it has been nearly sixty years since fine-needle aspiration of the prostate was first performed in this country by Ferguson, I the technique has only recently begun to gain acceptance in the United States. Popularized by Franzen, Giertz, and Zajicek in 1960,2 prostatic aspiration cytology has been employed widely in Europe. Now reports comparing aspiration cytology and needle core prostate biopsy are emerging in the American literature. 2- 8 We report our experience of simultaneous aspiration cytology and core needle biopsy of the prostate gland to diagnose carcinoma. Material and Methods . BetweE:'n 1984 and 1986, 166 patients had 169 fme-needle aspirations of the prostate performed at the Eastern Virginia Medical Center. All patients had a physical examination or clinical findings suspicious for carcinoma of the prostate. Aspiration was performed from a transrectal ~'pproach using a 22 g~uge Franzen needle and Inger gUlde. The patients were begun on oral
LJHOLOGY
,
MAY 1990
I
VOLc\1E XXXV l\UMBER 5
antibiotics the day prior to aspiration, and these were continued for one to two days. The rectum was prepared with a Betadine enema immediately prior to aspiration. A lO-cc control syringe was attached to the needle and numerous passes under vacuum were made through the area of induration and the surrounding prostatic parenchyma. Qualified cytologic technicians were available to assist the physicians with aspiration and initial processing of the sample when performed in the hospital. Aspirated material was immediately placed on slides, smeared, and fixed. However, the majority of aspirations were done in the office without the assistance of a cytotechnologist . Therefore, material was expressed into carbowax by saline rinse and later prepared by cell block or membrane filter technique. This methodology avoided the occasional problem of suboptimal slide preparations. Fixed slides were stained by the Papanicolaou technique. Material fixed in carbowax was centrifuged for three to five minutes. The supernatant was discarded. A portion of th~ cell
381
aggregate was used to smear additional slidcs. The remainder of the cell button was resuspended in Bouin's solution and centrifuged. The resulting cell button was prepared as a cell block for routine histology. All but 4 patients with interpretable aspirates had a simultaneous transperineal or transrectal core needle biopsy of the prostate for comparison. All aspirates were evaluated by a single pathologist (L. E. L.) and cytotechnologist (M. B. F.) with no know ledge of core biopsy findings or specific clinical impressions. Samples were categorized as either positive for carcinoma, negative for carcinoma, inconclusive, or unsatisfactory for evaluation. Diagnostic criteria for carcinoma are as follows: * Most important criteria Dyshesion Cellularity Major Criteria Indistinct cell borders Nuclear membrane irregularity Eosinophilic nucleoli Anisonucleosis Minor criteria Polarization of nuclei Nuclear crowding Micro-acini Results One hundred sixty-nine patients underwent fine-needle aspiration of the prostate. Cancer was diagnosed in 43 (25 0/0) samples, whereas findings were considered benign in 79 (47 % ) . Nineteen (11 0/0) samples gave inconclusive results. Twenty-eight (17 0/0) were unsatisfactory for evaluation. Overall, 122 (72 0/0) of the aspirations led to a definitive diagnosis. Only 2 fine-needle aspirations with inconclusive results and 2 aspirations with cytologic diagnosis did not have histologk verification. Thirty-nine of 43 (91 0/0) positive aspirations were confirmed by histology; 3 (7 0/0) were falsely positive. Conversely, 72 (92 % ) of 79 negative cytologic specimens were histologically confirmed; 6 (8 %) were false-negatives as carcinoma was found on core biopsy. Patients with inconclusive cytologic results were found to have positive histology in 6 (32 % ) and negative histology in 11 (.58 % ) . *Information derived from: Kline, T.S.: Guides to Clinical piration Biopsy: Prostate, Igaku~Shoin, :\ cw York, 198.5.
382
As~
In this series. therefore, the sensitiyih of fine-needle aspiration of the prostate is 87 'percent with a specificity of 96 percent. 0\'('ra1l agreement betvyeen cytology and histology \\a5 93 percent (p = 0.689- vVilcoxon rank sum). Of 120 patients with a definitive cytologic diagnosis, 9 (8 o/c) were proved to be incorrect. There were 3 false-positive and 6 false-negative interpretations. In all 3 of the patients incorrectly diagnosed as having cancer by cytology, benign prostatic hyperplasia was found on biopsy and rebiopsy. No clinical changes suggesting carcinoma subsequently occurred. However, 2 of these 3 patients also had histologic evidence of chronic prostatitis. Of the 6 false-negative determinations, all had biopsyproved cancer. Of these, one tumor was well differentiated, 1 moderately differentiated, and 4 poorly differentiated. No other pathologic findings were evident in these patients. Comment It has been our experience that fine-needle aspiration of the prostate is technically simple to perform, with minimal discomfort to the patient during or after the procedure. Rectal bleeding after the aspiration has not been encountered. It is likely that repetitive passes of the fine needle through the prostatic parenchyma provide a more global assessment of the gland than the isolated core biopsy. The simplicity, cost, comfort, and ease of performance of fine-needle aspiration of the prostate may justify the investigation of minimally suspicious lesions and perhaps in some cases might lead to an earlier diagnosis. The slow acceptance of fine-needle aspiration in this country is likely a result of concerns about its diagnostic accuracy. In our series, the sensitivity of the test was 87 percent while the specificity was 96 percent. Overall agreement with core biopsy was 93 percent. We believe this is indicative of a clinicallv valid test. Our results are compared with those of others in Table I. These figures were computed to tak~ into account sensitivity, specificity, and o\'~ralf agreement only when a definitive diagnoslS "malignant" or "benign" was made by the pathologist and histologic confirmation was tained. It does not take into account sa!11~r that were reported as "inconclusive," "inSL1 \cient for diagnosis," or diagnostic of a noncan cerous process. Overall, the sensitivity r~~gi~' from 55 percent to 100 percent, the speclfic. il from 78 percent to 97 percent, and the avera
°
°t
d
UROLOGY
I
MAY 1990
i
VOLUME
xxxv.
:H 5 Nll\IBL
Sensitivity, specificity, and o/jerall TAlll]: 1. rrrccmcnt of prostatic needle aspiration cytology Or compared with histology
-------Series
---Percent--Date Pts. Sens. Spec. Agree.
~
1966 1979 1983 1983 1983 1983 1984 1986 1986 1986 1986
ESpOS(1
. I J0 Jjn ef Cl . 4 Sharifi et al. 3 Hosking et al. 11 Zattoni ct al. Anandan et a l . 12 Maier ct ar. 13 Carter ct al. H Chodak ct al. 6 Ljung et al. 5 Whelan ct al. 7 Brenner ct al. *
157 428 248 74 195 200 391 94 47 94 26 120
91 68 55 75 98 98 80 82 98 94 100 87
97 78 91 84 92 79 93 97
95 73
r\/A 81 96 88 87 88
N/A
N/A
97 85 96
96 92 93
----;'This series
agreement of aspiration findings with histology from 73 percent to 96 percent. Our figures are in good agreement with those of the other series and reflect the success that has been documented with fine-needle aspiration of the prostate. Of 169 aspirations, a diagnosis was made in 122 (72 % ), leaving 28 (17 0/0) samples unsatisfactory and 19 (11 0/0) inconclusive. Nonpiagnostic results are variably reported in other series. Unsatisfactory results are likely due to inexperience of the physician collecting the sample or the technician fixing the slides. Unsatisfactory results may be followed with a repeat aspiration for a better sample with no significant risk of morbidity. By performing aspiration before core biopsy, we reduced our number of unsatisfactory specimens by eliminating blood cell contamination. Inconclusive results are most commonly due to atypia (without frank evidence of carcinoma), prostatitis, or poor cellularity of the sample. It is likely that inconclusive results will lessen with increasing experience of the pathologist, as well as good communication of the Clinical findings between the clinician and pathologist. If on repeated aspiration the findings remain nondiagnostic, tissue for histologic examination should be obtained. ~I~ree patients in our series had cytologically P?Sltlve aspirates in glands that could not be histologically shown to harbor carcinoma. In 2 f t.hese patients prostatitis was diagnosed histotglcall~', and we believe that was responsible ~.r ~he ll1correct cytologic diagnosis. In cases of C lntcally known or suspected prostatitis, anti-
r
UIl(lLOC;Y
,
MAY 1990
VOLCME XXXV, NUMBER"
biotic therapy should be instituted and aspiration performed at a later date. In numerous series,35.S initial false-positive cytologies 'were subsequently proved accurate with repeated core biopsies, surgery, or autopsy. It was the initial biopsies that were falsely negative. \Ve also had 6 false-negative aspirations in adequate samples. As stated by Ljung, Cherrie, and Kaufman 5 differentiating atypia from lowgrade malignancy can be difficult. This could result in falsely negative interpretations. However, well-differentiated tumor was found in only 1 of 6 such patients: 4 were poorly differentiated and 1 was moderately differentiated. We presume that a faulty direction of the needle was responsible in each of these cases. Complications are undoubtedly fewer with fine-needle aspiration than with transrectal or transperineal core biopsy, which may have significant morbidity.14-17 We are unaware of any major complications in our 166 patients, and others have had similar experience. 7 - 9,13 Zattoni et aZ. lI reported a 2 percent incidence of hematuria or fever in 511 patients. Ljung et al. 5 noted the occurrence of a prostate abscess in a diabetic patient after aspiration. Esposti,9 though, had no complications in 1,430 aspirations. It is unlikely that special cleansing procedures or antibiotics would prevent the occasional complication that will occur with fine-needle aspiration. In our cases, patient preparation was due to planned simultaneous core biopsy. The trauma to the prostate gland induced by core biopsy may cause difficulties with the patient's subsequent care, Walsh 17 has noted that, in the course of a nerve-sparing radical prostatectomy, proper development of the plane between the rectum and prostate with division of the rectourethral muscle seems to be significantly hampered by scarring and fibrosis that he attributes to core biopsy of the prostate. It is not unreasonable to postulate that, by the same mechanism of scarring, changes might occur in the prostate gland that could hamper accuracy of prostatic ultrasound which is now employed frequently as a staging modality in contemporary practice, We believe that it is unlikely that fine-needle aspiration will be shown to cause these problems. The introduction of the bioptic needle gun which is able to obtain tissue cores via the transrectal or transperineal route using either ultrasonic or tactile guidance in a virtually
383
1. Ferguson RS: Prostatic neoplasms. Their diagnosis by needle puncture and aspiration, Am J Surg 9: 507 (1930). 2. Franzen S, Giertz G, and Zajicek J: Cytological diagnosis of prostatic tumors by transrectal aspiration biopsy, Br JUro132: 193 (1960).
3. Hosking DH, Paraskevas ~1. Hellsten OR. and Ran",.\ EW. The cytological diagnosis of prostatic carcinoma by trall~rl'l't'lj fine needle aspiration. ] Urol 129: 998 (\983). ' 4. Sharifi R, et ai: Evaluation of cytologic techniljlll'S for diagnosis of prostate cancer. Urology 21: 417 (1983). 5. Ljung B, Cherrie R, and Kaufman JJ: Fine needle aspira_ tion biopsy of the prostate gland: a study of 103 cases with hi,sto. logical follow-up, J Urol 135: 955 (1986). 6. Chodak G\N, et ai: The role of transrectal aspiratiun biopsv in the diagnosis of prostatic cancer, ] Urol 135: 299 (1!l8(j). . 7. Whelan JP, Chin ]L, Sharpe JR, and Davis IR: 1ransrectal needle aspiration versus transperineal needle biopsy in ciia;;n
STEVEN M. SCHLOSSBERG, M.D.
LEOPOLDO E. LADAGA, M.D. MERIEL B. FILLION, B.S.
PAUL F. SCHELLHAMMER, M.D.
From the Departments of Urology and Pathology, Eastern Virginia Medical School, Norfolk, Virginia
ABSTRACT-One hundred sixty-nine transrectal fine-needle aspirations of the prostate gland were performed in 166 patients over a two-year period. The results were compared with simultaneous core needle biopsy performed in all but 4 patients. Forty-seven (28 %) aspirations were either unsatisfactory or inconclusive. Of the remaining 122 (72 %) patients in whom a cytologic diagnosis could be made, core biopsy was available in 120. Aspiration cytology was 87 percent sensitive and 96 percent specific with an o-uerall agreement of 93 percent with core biopsy. No major complications occurred. We conclude that fine-needle aspiration of the prostate is accurate, safe, and costeffective, and greater application of this technique is encouraged.
Although it has been nearly sixty years since fine-needle aspiration of the prostate was first performed in this country by Ferguson, I the technique has only recently begun to gain acceptance in the United States. Popularized by Franzen, Giertz, and Zajicek in 1960,2 prostatic aspiration cytology has been employed widely in Europe. Now reports comparing aspiration cytology and needle core prostate biopsy are emerging in the American literature. 2- 8 We report our experience of simultaneous aspiration cytology and core needle biopsy of the prostate gland to diagnose carcinoma. Material and Methods . BetweE:'n 1984 and 1986, 166 patients had 169 fme-needle aspirations of the prostate performed at the Eastern Virginia Medical Center. All patients had a physical examination or clinical findings suspicious for carcinoma of the prostate. Aspiration was performed from a transrectal ~'pproach using a 22 g~uge Franzen needle and Inger gUlde. The patients were begun on oral
LJHOLOGY
,
MAY 1990
I
VOLc\1E XXXV l\UMBER 5
antibiotics the day prior to aspiration, and these were continued for one to two days. The rectum was prepared with a Betadine enema immediately prior to aspiration. A lO-cc control syringe was attached to the needle and numerous passes under vacuum were made through the area of induration and the surrounding prostatic parenchyma. Qualified cytologic technicians were available to assist the physicians with aspiration and initial processing of the sample when performed in the hospital. Aspirated material was immediately placed on slides, smeared, and fixed. However, the majority of aspirations were done in the office without the assistance of a cytotechnologist . Therefore, material was expressed into carbowax by saline rinse and later prepared by cell block or membrane filter technique. This methodology avoided the occasional problem of suboptimal slide preparations. Fixed slides were stained by the Papanicolaou technique. Material fixed in carbowax was centrifuged for three to five minutes. The supernatant was discarded. A portion of th~ cell
381
aggregate was used to smear additional slidcs. The remainder of the cell button was resuspended in Bouin's solution and centrifuged. The resulting cell button was prepared as a cell block for routine histology. All but 4 patients with interpretable aspirates had a simultaneous transperineal or transrectal core needle biopsy of the prostate for comparison. All aspirates were evaluated by a single pathologist (L. E. L.) and cytotechnologist (M. B. F.) with no know ledge of core biopsy findings or specific clinical impressions. Samples were categorized as either positive for carcinoma, negative for carcinoma, inconclusive, or unsatisfactory for evaluation. Diagnostic criteria for carcinoma are as follows: * Most important criteria Dyshesion Cellularity Major Criteria Indistinct cell borders Nuclear membrane irregularity Eosinophilic nucleoli Anisonucleosis Minor criteria Polarization of nuclei Nuclear crowding Micro-acini Results One hundred sixty-nine patients underwent fine-needle aspiration of the prostate. Cancer was diagnosed in 43 (25 0/0) samples, whereas findings were considered benign in 79 (47 % ) . Nineteen (11 0/0) samples gave inconclusive results. Twenty-eight (17 0/0) were unsatisfactory for evaluation. Overall, 122 (72 0/0) of the aspirations led to a definitive diagnosis. Only 2 fine-needle aspirations with inconclusive results and 2 aspirations with cytologic diagnosis did not have histologk verification. Thirty-nine of 43 (91 0/0) positive aspirations were confirmed by histology; 3 (7 0/0) were falsely positive. Conversely, 72 (92 % ) of 79 negative cytologic specimens were histologically confirmed; 6 (8 %) were false-negatives as carcinoma was found on core biopsy. Patients with inconclusive cytologic results were found to have positive histology in 6 (32 % ) and negative histology in 11 (.58 % ) . *Information derived from: Kline, T.S.: Guides to Clinical piration Biopsy: Prostate, Igaku~Shoin, :\ cw York, 198.5.
382
As~
In this series. therefore, the sensitiyih of fine-needle aspiration of the prostate is 87 'percent with a specificity of 96 percent. 0\'('ra1l agreement betvyeen cytology and histology \\a5 93 percent (p = 0.689- vVilcoxon rank sum). Of 120 patients with a definitive cytologic diagnosis, 9 (8 o/c) were proved to be incorrect. There were 3 false-positive and 6 false-negative interpretations. In all 3 of the patients incorrectly diagnosed as having cancer by cytology, benign prostatic hyperplasia was found on biopsy and rebiopsy. No clinical changes suggesting carcinoma subsequently occurred. However, 2 of these 3 patients also had histologic evidence of chronic prostatitis. Of the 6 false-negative determinations, all had biopsyproved cancer. Of these, one tumor was well differentiated, 1 moderately differentiated, and 4 poorly differentiated. No other pathologic findings were evident in these patients. Comment It has been our experience that fine-needle aspiration of the prostate is technically simple to perform, with minimal discomfort to the patient during or after the procedure. Rectal bleeding after the aspiration has not been encountered. It is likely that repetitive passes of the fine needle through the prostatic parenchyma provide a more global assessment of the gland than the isolated core biopsy. The simplicity, cost, comfort, and ease of performance of fine-needle aspiration of the prostate may justify the investigation of minimally suspicious lesions and perhaps in some cases might lead to an earlier diagnosis. The slow acceptance of fine-needle aspiration in this country is likely a result of concerns about its diagnostic accuracy. In our series, the sensitivity of the test was 87 percent while the specificity was 96 percent. Overall agreement with core biopsy was 93 percent. We believe this is indicative of a clinicallv valid test. Our results are compared with those of others in Table I. These figures were computed to tak~ into account sensitivity, specificity, and o\'~ralf agreement only when a definitive diagnoslS "malignant" or "benign" was made by the pathologist and histologic confirmation was tained. It does not take into account sa!11~r that were reported as "inconclusive," "inSL1 \cient for diagnosis," or diagnostic of a noncan cerous process. Overall, the sensitivity r~~gi~' from 55 percent to 100 percent, the speclfic. il from 78 percent to 97 percent, and the avera
°
°t
d
UROLOGY
I
MAY 1990
i
VOLUME
xxxv.
:H 5 Nll\IBL
Sensitivity, specificity, and o/jerall TAlll]: 1. rrrccmcnt of prostatic needle aspiration cytology Or compared with histology
-------Series
---Percent--Date Pts. Sens. Spec. Agree.
~
1966 1979 1983 1983 1983 1983 1984 1986 1986 1986 1986
ESpOS(1
. I J0 Jjn ef Cl . 4 Sharifi et al. 3 Hosking et al. 11 Zattoni ct al. Anandan et a l . 12 Maier ct ar. 13 Carter ct al. H Chodak ct al. 6 Ljung et al. 5 Whelan ct al. 7 Brenner ct al. *
157 428 248 74 195 200 391 94 47 94 26 120
91 68 55 75 98 98 80 82 98 94 100 87
97 78 91 84 92 79 93 97
95 73
r\/A 81 96 88 87 88
N/A
N/A
97 85 96
96 92 93
----;'This series
agreement of aspiration findings with histology from 73 percent to 96 percent. Our figures are in good agreement with those of the other series and reflect the success that has been documented with fine-needle aspiration of the prostate. Of 169 aspirations, a diagnosis was made in 122 (72 % ), leaving 28 (17 0/0) samples unsatisfactory and 19 (11 0/0) inconclusive. Nonpiagnostic results are variably reported in other series. Unsatisfactory results are likely due to inexperience of the physician collecting the sample or the technician fixing the slides. Unsatisfactory results may be followed with a repeat aspiration for a better sample with no significant risk of morbidity. By performing aspiration before core biopsy, we reduced our number of unsatisfactory specimens by eliminating blood cell contamination. Inconclusive results are most commonly due to atypia (without frank evidence of carcinoma), prostatitis, or poor cellularity of the sample. It is likely that inconclusive results will lessen with increasing experience of the pathologist, as well as good communication of the Clinical findings between the clinician and pathologist. If on repeated aspiration the findings remain nondiagnostic, tissue for histologic examination should be obtained. ~I~ree patients in our series had cytologically P?Sltlve aspirates in glands that could not be histologically shown to harbor carcinoma. In 2 f t.hese patients prostatitis was diagnosed histotglcall~', and we believe that was responsible ~.r ~he ll1correct cytologic diagnosis. In cases of C lntcally known or suspected prostatitis, anti-
r
UIl(lLOC;Y
,
MAY 1990
VOLCME XXXV, NUMBER"
biotic therapy should be instituted and aspiration performed at a later date. In numerous series,35.S initial false-positive cytologies 'were subsequently proved accurate with repeated core biopsies, surgery, or autopsy. It was the initial biopsies that were falsely negative. \Ve also had 6 false-negative aspirations in adequate samples. As stated by Ljung, Cherrie, and Kaufman 5 differentiating atypia from lowgrade malignancy can be difficult. This could result in falsely negative interpretations. However, well-differentiated tumor was found in only 1 of 6 such patients: 4 were poorly differentiated and 1 was moderately differentiated. We presume that a faulty direction of the needle was responsible in each of these cases. Complications are undoubtedly fewer with fine-needle aspiration than with transrectal or transperineal core biopsy, which may have significant morbidity.14-17 We are unaware of any major complications in our 166 patients, and others have had similar experience. 7 - 9,13 Zattoni et aZ. lI reported a 2 percent incidence of hematuria or fever in 511 patients. Ljung et al. 5 noted the occurrence of a prostate abscess in a diabetic patient after aspiration. Esposti,9 though, had no complications in 1,430 aspirations. It is unlikely that special cleansing procedures or antibiotics would prevent the occasional complication that will occur with fine-needle aspiration. In our cases, patient preparation was due to planned simultaneous core biopsy. The trauma to the prostate gland induced by core biopsy may cause difficulties with the patient's subsequent care, Walsh 17 has noted that, in the course of a nerve-sparing radical prostatectomy, proper development of the plane between the rectum and prostate with division of the rectourethral muscle seems to be significantly hampered by scarring and fibrosis that he attributes to core biopsy of the prostate. It is not unreasonable to postulate that, by the same mechanism of scarring, changes might occur in the prostate gland that could hamper accuracy of prostatic ultrasound which is now employed frequently as a staging modality in contemporary practice, We believe that it is unlikely that fine-needle aspiration will be shown to cause these problems. The introduction of the bioptic needle gun which is able to obtain tissue cores via the transrectal or transperineal route using either ultrasonic or tactile guidance in a virtually
383
1. Ferguson RS: Prostatic neoplasms. Their diagnosis by needle puncture and aspiration, Am J Surg 9: 507 (1930). 2. Franzen S, Giertz G, and Zajicek J: Cytological diagnosis of prostatic tumors by transrectal aspiration biopsy, Br JUro132: 193 (1960).
3. Hosking DH, Paraskevas ~1. Hellsten OR. and Ran",.\ EW. The cytological diagnosis of prostatic carcinoma by trall~rl'l't'lj fine needle aspiration. ] Urol 129: 998 (\983). ' 4. Sharifi R, et ai: Evaluation of cytologic techniljlll'S for diagnosis of prostate cancer. Urology 21: 417 (1983). 5. Ljung B, Cherrie R, and Kaufman JJ: Fine needle aspira_ tion biopsy of the prostate gland: a study of 103 cases with hi,sto. logical follow-up, J Urol 135: 955 (1986). 6. Chodak G\N, et ai: The role of transrectal aspiratiun biopsv in the diagnosis of prostatic cancer, ] Urol 135: 299 (1!l8(j). . 7. Whelan JP, Chin ]L, Sharpe JR, and Davis IR: 1ransrectal needle aspiration versus transperineal needle biopsy in ciia;;n
