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Biópsias prostáticas contendo neoplasia intraepitelial e proliferação acinar atípica: o que fazer?

Biópsias prostáticas contendo neoplasia intraepitelial e proliferação acinar atípica: o que fazer?

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Published by fkorkes
Prostate biopsies containing prostate intraepithelial neoplasia
and atypical small acinar proliferation: what to do?
Prostate biopsies containing prostate intraepithelial neoplasia
and atypical small acinar proliferation: what to do?

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Published by: fkorkes on Nov 18, 2011
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01/26/2013

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Original article
einstein. 2009; 7(4 Pt 1):411-4
Prostate biopsies containing prostate intraepithelial neoplasiaand atypical small acinar prolieration: what to do?
Biópsias prostáticas contendo neoplasia intraepitelial e prolieração acinar atípica: o que azer?
Fernando Korkes
1
, Suellen Ka Gi Mo
2
, Cristiane Sayuri Koza de Jesus
3
, Marilia Germanos Castro
4
 
aBStract
Objv:
The aim o the study was to assess the requencyo high-grade prostate intraepithelial neoplasia and atypicalsmall acinar prolierations on a contemporary series, and theirrelation to posterior diagnosis o prostate cancer.
Mhods:
Aretrospective study was conducted with 6,490 consecutive mensubmitted to extended prostate biopsies between 2000 and 2005at a single institution. O these, 400 men (6.16%) had atypicalsmall acinar prolieration or high-grade prostatic intraepithelialneoplasia, and 43 had at least one ollow-up biopsy.
rsus:
Theoverall incidence o high-grade prostatic intraepithelial neoplasiawas 4.6% and 1.4% or atypical small acinar prolieration. High-grade prostatic intraepithelial neoplasia plus atypical small acinarprolieration occurred in 0.11% o men. The detection rates oprostate cancer on repeated biopsies were o 38.5 and 53.6% orhigh-grade prostatic intraepithelial neoplasia and atypical smallacinar prolieration, respectively. All patients with high- gradeprostatic intraepithelial neoplasia plus atypical small acinarprolieration who had a repeated biopsy were diagnosed withprostate cancer. There was a higher risk o diagnosing prostatecancer in a site close to previous atypical small acinar prolieration(OR = 5.93; p = 0.015).
cousos:
Ater high-grade prostaticintraepithelial neoplasia or atypical small acinar prolierationinding on extended biopsies, close ollow-up is recommended,and repeated biopsies should be done according to clinical dataas well. Rebiopsies should be strongly recommended when theassociation high- grade prostatic intraepithelial neoplasia plusatypical small acinar prolieration is present, or when atypicalsmall acinar prolieration is ound only ater the second biopsy.Repeated biopsies ater an atypical small acinar prolierationinding should be always randomized, but sites o atypical smallacinar prolieration should be more extensively sampled.
Kywods:
Prostate; Biopsy, needle; Prostatic intraepithelial neoplasia;Prostatic neoplasms
reSUMO
Objvo:
O objetivo do estudo oi avaliar a requência de neoplasiaintraepitelial prostática de alto grau e de prolierações atípicas depequenos ácinos em uma série atual, e sua relação com o diagnósticode câncer de próstata.
Méodos:
Foi realizado estudo retrospectivocom 6.490 homens submetidos consecutivamente a biópsia estendidade próstata entre 2000 e 2005. Destes, 400 (6,16%) apresentaramprolierações atípicas de pequenos ácinos ou neoplasia intraepitelialprostática de alto grau, e 43 oram submetidos à rebiópsias.
rsudos:
 A incidência de neoplasia intraepitelial prostática de alto grau oi de4,6% e, de prolierações atípicas de pequenos ácinos, 1,4%. Neoplasiaintraepitelial prostática de alto grau mais prolierações atípicas depequenos ácinos ocorreu em 0,11% dos homens. Detecção de câncerde próstata em rebiópsias ocorreu em 38,5 e 53,6% dos homenscom neoplasia intraepitelial prostática de alto grau e prolieraçõesatípicas de pequenos ácinos, respectivamente. Todos os homenscom neoplasia intraepitelial prostática de alto grau mais prolieraçõesatípicas de pequenos ácinos apresentaram câncer de próstata emrebiópsias. Observou-se um risco elevado de detecção de câncer depróstata próximo ao local onde ocorreram prolierações atípicas depequenos ácinos previamente (OR = 5,93; p = 0,015).
cousõs:
 Após o achado de neoplasia intraepitelial prostática de alto grau ouprolierações atípicas de pequenos ácinos em biópsias estendidas,seguimento cauteloso é recomendado, e rebiópsias devem serrealizadas de acordo com dados clínicos. Rebiópsias são ortementerecomendadas quando há associação da neoplasia intraepitelialprostática de alto grau mais prolierações atípicas de pequenos ácinos,ou quando prolierações atípicas de pequenos ácinos são encontradasa partir da segunda biópsia repetida. Rebiópsias após prolieraçõesatípicas de pequenos ácinos devem ser randomizadas, porém locaisonde ocorreu o achado de prolierações atípicas de pequenos ácinosdevem ser mais extensivamente representados.
Dsos:
Próstata; Biópsia por agulha; Neoplasia prostáticaintraepitelial; Neoplasias da próstata
Study carried out at the Division of Urology and Department of Pathology of the Faculdade de Ciências Médicas da Santa Casa de São Paulo – FCMSCSP, São Paulo (SP), Brazil.
1
Assistant proessor o the Department o Urology at Faculdade de Medicina do ABC – FMABC, Santo André (SP), Brazil.
2
Resident at Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo – FCMSCSP, São Paulo (SP), Brazil.
3
Resident at Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo – FCMSCSP, São Paulo (SP), Brazil.
4
Assistant physician o the Department o Pathology at Faculdade de Ciências Médicas da Santa Casa de Misericórdia São Paulo – FCMSCSP, São Paulo (SP), Brazil.Corresponding author: Fernando Korkes – Rua Pirapora, 167 – Ibirapuera – CEP 04008-060 – São Paulo (SP), Brasil – Tel.: 11 3884-2233 – e-mail: korkes@terra.com.brReceived on: May 16, 2009 – Accepted on: Sep 30, 2009
 
einstein. 2009; 7(4 Pt 1):411-4412
Korkes F, Mo SKG, Jesus CSK, Castro MG
intrODUctiOn
High-grade prostate intraepithelial neoplasia (HGPIN)and small acinar prolierations (ASAP) are thoughtto have important prognostic signifcance due to theirpotential as markers or concurrent or uture prostateadenocarcinoma (PCa)
(1-2)
. HGPIN was defnedas abnormal prolierative change in preexisting,architecturally normal prostatic ducts and acini withnuclear atypia similar to that seen in PCa. However,HGPIN lacks invasion o the basement membrane o the prostatic glands. Recent 12-core biopsies studieshave demonstrated that the risk o fnding PCa ater thediagnosis o HGPIN is lower than previous studies withsextant biopsies advocated (20 to 30%)
(3-4)
. ASAP includes a number o atypical lesions that aresuspicious or but not diagnostic o PCa. Near 50% o cases o ASAP end with clinically detected PCa
(1,5)
.
OBJectiVe
The aim o this study was to evaluate the currentrequency o (HGPIN) and ASAP on extended prostateneedle biopsies, as well as their relation to posteriordiagnosis o PCa.
MetHODS
 A retrospective study was conducted with 6,490consecutive men submitted to extended prostate needlecore biopsies between January 2000 and December2005, at a single service. All men had undergone extended biopsies(minimum o 12 cores), and all cases were examinedby a genitourinary pathologist (MGC). The slides were examined or the presence o HGPIN and ASAP.HGPIN is defned as abnormal prolierative change inpreexisting architecturally normal prostatic acini andducts with nuclear atypia similar to that seen in prostatecancer
(6)
. ASAP is not a specifc diagnosis, it includes anumber o atypical lesions that are suspicious or butnot diagnostic o cancer. This group o lesions includescancer mimickers and many cases o ocal carcinoma
(6)
.We identifed 400 men (6.16%) with ASAP or HGPINdiagnoses on prostate needle biopsies. O these 400men, 43 had undergone at least one ollow-up biopsy,and they represent our study group. The remainingeither did not accept a second biopsy or were lost toollow-up.Medical records were reviewed to determine: thenumber o repeat biopsies; the site o initial diagnosisas well as that o subsequent tumors; patient age; andbiopsy technique. Statistical analysis was perormedusing the Statistical Package or the Social Sciencessotware (SPSS 13.0 or Mac OS X, SPSS Inc., Chicago,Illinois). Pearson’s
χ
2
test was used to compare data.Statistical signifcance was determined at p < 0.05. Theinstitutional review board approved the present study.
reSUltS
Overall incidence o HGPIN was 4.65% (n = 302), whilethe incidence o ASAP was 1.40% (n = 91). HGPIN + ASAP at the same biopsy occurred in 0.11% (n = 7)o men. As the repeat biopsy population, 43 men wereanalyzed and underwent a total o 96 biopsies (average2.2 each, range 2 to 4); 13 men with an initial diagnosis o HGPIN had a total o 25 biopsies (average 2.1, range 2 to3); 28 men with an initial diagnosis o ASAP had a totalo 63 biopsies (average 2.3, range 2 to 4); and two men with initial diagnosis o HGPIN + ASAP had 4 biopsies.PCa detection rates on repeated biopsies were o 38.5 and 53.6% or HGPIN and ASAP, respectively. All patients with HGPIN + ASAP who had a repeatedbiopsy were diagnosed with PCa (Table 1). Mean timebetween biopsies was nine months.
tb 1.
Prostate cancer diagnosis ollowing fnding o high-grade prostateintraepithelial neoplasia, atypical small acinar prolierations and high-gradeprostate intraepithelial neoplasia plus atypical small acinar prolierations inextended biopsies
BopssHgPinaSaPaSaP+HgPinp-vuOr(= 13)(= 28)(= 2)% ()% ()% ()
PCa at repeated biopsy38.5 (5)53.6 (15)100.0 (2)0.2452.81PCa - 2
nd
biopsy80.0 (4)86.6 (13)100.0 (2)0.1713.53PCa - 3
rd
biopsy06.7 (1)-0.7600.548PCa - 4
th
biopsy20.0 (1)6.7 (1)-0.8020.442
HGPIN: high-grade prostate intraepithelial neoplasia; ASAP: atypical small acinar prolierations; ASAP + HGPIN:high-grade prostate intraepithelial neoplasia plus atypical small acinar prolierations; PCa: prostate cancer.
Regarding topographic diagnosis o PCa, we observeda signifcant higher risk o diagnosing PCa close to where ASAP was detected, in comparison to patients with initialfnding o HGPIN (OR = 10.1; p = 0.036; Table 2). I considered only the cases in which cancer was detectedexactly in the same place, this dierence was even cleareror ASAP
 versus
HGPIN (OR = 5.93; p = 0.015).
tb 2.
Topography o prostate cancer in comparison to initial fndings inrepeated biopsies
topophyHgPinaSaPaSaP +HgPinp-vuOr(= 5)(= 15)(= 2)% ()% ()% ()
Same quadrant20.0 (1)80.0 (12)0.0 (0)0.03610.3Same side, dierentquadrant60.0 (3)13.3 (2)100.0 (2)Opposite side20.0 (1)6.7 (1)0.0 (0)
HGPIN: high-grade prostate intraepithelial neoplasia; ASAP: atypical small acinar prolierations; ASAP + HGPIN:high-grade prostate intraepithelial neoplasia plus atypical small acinar prolierations.
 
einstein. 2009; 7(4 Pt 1):411-4
Prostate biopsies containing prostate intraepithelial neoplasia and atypical small acinar prolieration: what to do?
413
DiScUSSiOn
Most epidemiologic studies evaluating HGPINand ASAP as risk actors or PCa were rom a time when sextant biopsies (six samples) were routinelyperormed
(1,7)
. Nowadays, the minimum numberconsidered or a proper PCa screening is 12 samples(extended biopsy). In this context, recent studies havedemonstrated that the incidence o HGPIN and ASAPis dierent rom the previously stated, as well as the risko a subsequent diagnosis o PCa
(3-5,8-10)
.Our study has some important fndings. First, theincidence o HGPIN on prostate biopsy was o 4.6%,reproducing the results o recent studies on extendedbiopsies
(5)
. HGPIN was associated with a 38.5% chanceo PCa detection in repeated biopsies, and there wasa signifcant lower risk o detecting cancer in thetopography o previous HGPIN
 versus
ASAP (20
 versus
80%; p = 0.036). However, this risk must alsobe compared to the risk o fnding cancer in a repeatedbiopsy ater a benign diagnosis, which ranges rom 10.0to 30.0%
(11-13)
. Other series diagnosed PCa in 10 to57%
(1,14-15)
o repeated biopsies ater HGPIN
(11-13,16-17)
. Inthe present series with extended biopsies, the diagnosiso PCa was made in 13.2 to 30.5%
(3-5,12)
. We ound ahigher rate o PCa than these authors, and a higher ratethan ater benign diagnosis, but still lower than observedor ASAP. Thereore, urther studies evaluating otheractors, such as the number o involved cores andmorphologic patterns, might help to determine whicho the men with HGPIN are at signifcantly higherrisk o harboring carcinoma and would beneft romrebiopsies
(18)
.Second, ASAP occurred in 1.4% o the extendedprostate biopsies, what is also similar to larger series
(1,5,14-15)
. The risk o diagnosing PCa on repeated biopsies waso 53.6%, comparable to recent series (range rom 37.0to 51.0%)
(3-5,19)
. There was also a signifcant higher risk o detecting the PCa close to the site o ASAP (p = 0.001;OR = 10.8). Thereore, patients with ASAP at prostatebiopsies are at increased risk o uture PCa detection,and it is recommended that ASAP oci should be moreextensively sampled on repeated biopsies. As the risko PCa is higher in patients with ASAP, it is generallyrecommended that rebiopsies are taken ater three tosix months
(6)
.Third, or patients who had ASAP in the frst biopsy,the risk o detecting PCa was 50.0%. However, in allcases (n = 3) in which ASAP was ound only ater thesecond biopsy, a subsequent biopsy diagnosed PCa. Although there were ew cases o association HGPIN + ASAP, this fnding seems to be related to an even higherrate o uture detection o PCa than isolated HGPIN or ASAP, as previously reported
(9)
.Our study has several limitations. Even though alarge number o biopsies were evaluated (6,490), thenumber o patients with HGPIN and ASAP was muchlower. Thereore, the relatively small number o men orsubsequent analysis limits the power o the study. Also,it is important to note that a high subset o patients werelost to ollow-up and did not undertake rebiopsy aterHGPIN or ASAP, which can raise a concern o ollow-up bias. However, the strength o our study is that alarge number o patients in a contemporary extendedbiopsy series could be evaluated.
cOnclUSiOn
In conclusion, ollowing the fnding o HGPIN or ASAP on extended prostate biopsies, close ollow-up is recommended, and repeated biopsies should beperormed according to clinical data. Rebiopsies shouldbe strongly recommended when the association HGPIN+ ASAP is present or when ASAP is ound only aterthe second biopsy. Repeated biopsies ater an ASAPfnding should be always randomized, but oci o ASAPfnding should be more extensively sampled.
reFerenceS
1. Iczkowski KA, MacLennan GT, Bostwick DG. Atypical small acinar prolierationsuspicious or malignancy in prostate needle biopsies: clinical signifcance in33 cases. Am J Surg Pathol. 1997;21(12):1489-95.2. Epstein JI. How should atypical prostate needle biopsies be reported?Controversies regarding the term “ASAP”. Hum Pathol
 .
1999;30(12):1401-2.3. Schlesinger C, Bostwick DG, Iczkowski KA. High-grade prostatic intraepithelialneoplasia and atypical small acinar prolieration: predictive value or cancer incurrent practice. Am J Surg Pathol. 2005;29(9):1201-7.4. Leite KR, Mitteldor CA, Camara-Lopes LH. Repeat prostate biopsies ollowingdiagnoses o prostate intraepithelial neoplasia and atypical small glandprolieration. Int Braz J Urol. 2005;31(2):131-6.5. Girasole CR, Cookson MS, Putzi MJ, Chang SS, Smith JA Jr, Wells N, et al.Signifcance o atypical and suspicious small acinar prolierations, and highgrade prostatic intraepithelial neoplasia on prostate biopsy: implicationsor cancer detection and biopsy strategy. J Urol. 2006;175(3 Pt 1):929-33;discussion 933.6. Epstein JI, Herawi M. Prostate needle biopsies containing prostaticintraepithelial neoplasia or atypical oci suspicious or carcinoma: implicationsor patient care. J Urol. 2006;175(3 Pt 1):820-34.7. Rosen S, Upton M. ASAP. Atypical small acinar prolierations. Hum Pathol.1999;30(12):1403; author reply 1404.8. Ashley RA, Inman BA, Routh JC, Mynderse LA, Gettman MT, Blute ML.Reassessing the diagnostic yield o saturation biopsy o the prostate. Eur Urol.2008;53(5):976-83.9. Scattoni V, Roscigno M, Freschi M, Briganti A, Fantini GV, Bertini R, et al.Predictors o prostate cancer ater initial diagnosis o atypical small acinarprolieration at 10 to 12 core biopsies. Urology. 2005;66:1043-7.10. Moore CK, Karikehalli S, Nazeer T, Fisher HA, Kauman RP, Jr, Mian BM.Prognostic signifcance o high grade prostatic intraepithelial neoplasiaand atypical small acinar prolieration in the contemporary era. J Urol.2005;173(1):70-2.

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