Prostate biopsies containing prostate intraepithelial neoplasia and

Original Article
Prostate biopsies containing prostate intraepithelial neoplasia
and atypical small acinar proliferation: what to do?
Biópsias prostáticas contendo neoplasia intraepitelial e proliferação acinar atípica: o que fazer?
Fernando Korkes1, Suellen Ka Gi Mo2, Cristiane Sayuri Koza de Jesus3, Marilia Germanos Castro4
ABSTRACT
RESUMO
Objective: The aim of the study was to assess the frequency
of high-grade prostate intraepithelial neoplasia and atypical
small acinar proliferations on a contemporary series, and their
relation to posterior diagnosis of prostate cancer. Methods: A
retrospective study was conducted with 6,490 consecutive men
submitted to extended prostate biopsies between 2000 and 2005
at a single institution. Of these, 400 men (6.16%) had atypical
small acinar proliferation or high-grade prostatic intraepithelial
neoplasia, and 43 had at least one follow-up biopsy. Results: The
overall incidence of high-grade prostatic intraepithelial neoplasia
was 4.6% and 1.4% for atypical small acinar proliferation. Highgrade prostatic intraepithelial neoplasia plus atypical small acinar
proliferation occurred in 0.11% of men. The detection rates of
prostate cancer on repeated biopsies were of 38.5 and 53.6% for
high-grade prostatic intraepithelial neoplasia and atypical small
acinar proliferation, respectively. All patients with high- grade
prostatic intraepithelial neoplasia plus atypical small acinar
proliferation who had a repeated biopsy were diagnosed with
prostate cancer. There was a higher risk of diagnosing prostate
cancer in a site close to previous atypical small acinar proliferation
(OR = 5.93; p = 0.015). Conclusions: After high-grade prostatic
intraepithelial neoplasia or atypical small acinar proliferation
finding on extended biopsies, close follow-up is recommended,
and repeated biopsies should be done according to clinical data
as well. Rebiopsies should be strongly recommended when the
association high- grade prostatic intraepithelial neoplasia plus
atypical small acinar proliferation is present, or when atypical
small acinar proliferation is found only after the second biopsy.
Repeated biopsies after an atypical small acinar proliferation
finding should be always randomized, but sites of atypical small
acinar proliferation should be more extensively sampled.
Objetivo: O objetivo do estudo foi avaliar a frequência de neoplasia
intraepitelial prostática de alto grau e de proliferações atípicas de
pequenos ácinos em uma série atual, e sua relação com o diagnóstico
de câncer de próstata. Métodos: Foi realizado estudo retrospectivo
com 6.490 homens submetidos consecutivamente a biópsia estendida
de próstata entre 2000 e 2005. Destes, 400 (6,16%) apresentaram
proliferações atípicas de pequenos ácinos ou neoplasia intraepitelial
prostática de alto grau, e 43 foram submetidos à rebiópsias. Resultados:
A incidência de neoplasia intraepitelial prostática de alto grau foi de
4,6% e, de proliferações atípicas de pequenos ácinos, 1,4%. Neoplasia
intraepitelial prostática de alto grau mais proliferações atípicas de
pequenos ácinos ocorreu em 0,11% dos homens. Detecção de câncer
de próstata em rebiópsias ocorreu em 38,5 e 53,6% dos homens
com neoplasia intraepitelial prostática de alto grau e proliferações
atípicas de pequenos ácinos, respectivamente. Todos os homens
com neoplasia intraepitelial prostática de alto grau mais proliferações
atípicas de pequenos ácinos apresentaram câncer de próstata em
rebiópsias. Observou-se um risco elevado de detecção de câncer de
próstata próximo ao local onde ocorreram proliferações atípicas de
pequenos ácinos previamente (OR = 5,93; p = 0,015). Conclusões:
Após o achado de neoplasia intraepitelial prostática de alto grau ou
proliferações atípicas de pequenos ácinos em biópsias estendidas,
seguimento cauteloso é recomendado, e rebiópsias devem ser
realizadas de acordo com dados clínicos. Rebiópsias são fortemente
recomendadas quando há associação da neoplasia intraepitelial
prostática de alto grau mais proliferações atípicas de pequenos ácinos,
ou quando proliferações atípicas de pequenos ácinos são encontradas
a partir da segunda biópsia repetida. Rebiópsias após proliferações
atípicas de pequenos ácinos devem ser randomizadas, porém locais
onde ocorreu o achado de proliferações atípicas de pequenos ácinos
devem ser mais extensivamente representados.
Keywords: Prostate; Biopsy, needle; Prostatic intraepithelial neoplasia;
Prostatic neoplasms
Descritores: Próstata; Biópsia por agulha; Neoplasia prostática
intraepitelial; 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 professor of the Department of 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 of the Department of 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: [email protected]
Received on: May 16, 2009 – Accepted on: Sep 30, 2009
einstein. 2009; 7(4 Pt 1):411-4
412
Korkes F, Mo SKG, Jesus CSK, Castro MG
INTRODUCTION
High-grade prostate intraepithelial neoplasia (HGPIN)
and small acinar proliferations (ASAP) are thought
to have important prognostic significance due to their
potential as markers for concurrent or future prostate
adenocarcinoma (PCa)(1-2). HGPIN was defined
as abnormal proliferative change in preexisting,
architecturally normal prostatic ducts and acini with
nuclear atypia similar to that seen in PCa. However,
HGPIN lacks invasion of the basement membrane of
the prostatic glands. Recent 12-core biopsies studies
have demonstrated that the risk of finding PCa after the
diagnosis of HGPIN is lower than previous studies with
sextant biopsies advocated (20 to 30%)(3-4).
ASAP includes a number of atypical lesions that are
suspicious for but not diagnostic of PCa. Near 50% of
cases of ASAP end with clinically detected PCa(1,5).
OBJECTIVE
The aim of this study was to evaluate the current
frequency of (HGPIN) and ASAP on extended prostate
needle biopsies, as well as their relation to posterior
diagnosis of PCa.
METHODS
A retrospective study was conducted with 6,490
consecutive men submitted to extended prostate needle
core biopsies between January 2000 and December
2005, at a single service.
All men had undergone extended biopsies
(minimum of 12 cores), and all cases were examined
by a genitourinary pathologist (MGC). The slides
were examined for the presence of HGPIN and ASAP.
HGPIN is defined as abnormal proliferative change in
preexisting architecturally normal prostatic acini and
ducts with nuclear atypia similar to that seen in prostate
cancer(6). ASAP is not a specific diagnosis, it includes a
number of atypical lesions that are suspicious for but
not diagnostic of cancer. This group of lesions includes
cancer mimickers and many cases of focal carcinoma(6).
We identified 400 men (6.16%) with ASAP or HGPIN
diagnoses on prostate needle biopsies. Of these 400
men, 43 had undergone at least one follow-up biopsy,
and they represent our study group. The remaining
either did not accept a second biopsy or were lost to
follow-up.
Medical records were reviewed to determine: the
number of repeat biopsies; the site of initial diagnosis
as well as that of subsequent tumors; patient age; and
biopsy technique. Statistical analysis was performed
using the Statistical Package for the Social Sciences
software (SPSS 13.0 for Mac OS X, SPSS Inc., Chicago,
einstein. 2009; 7(4 Pt 1):411-4
Illinois). Pearson’s χ2 test was used to compare data.
Statistical significance was determined at p < 0.05. The
institutional review board approved the present study.
RESULTS
Overall incidence of HGPIN was 4.65% (n = 302), while
the incidence of ASAP was 1.40% (n = 91). HGPIN +
ASAP at the same biopsy occurred in 0.11% (n = 7)
of men. As the repeat biopsy population, 43 men were
analyzed and underwent a total of 96 biopsies (average
2.2 each, range 2 to 4); 13 men with an initial diagnosis of
HGPIN had a total of 25 biopsies (average 2.1, range 2 to
3); 28 men with an initial diagnosis of ASAP had a total
of 63 biopsies (average 2.3, range 2 to 4); and two men
with initial diagnosis of HGPIN + ASAP had 4 biopsies.
PCa detection rates on repeated biopsies were of
38.5 and 53.6% for HGPIN and ASAP, respectively.
All patients with HGPIN + ASAP who had a repeated
biopsy were diagnosed with PCa (Table 1). Mean time
between biopsies was nine months.
Table 1. Prostate cancer diagnosis following finding of high-grade prostate
intraepithelial neoplasia, atypical small acinar proliferations and high-grade
prostate intraepithelial neoplasia plus atypical small acinar proliferations in
extended biopsies
HGPIN
Biopsies
PCa at repeated biopsy
PCa - 2nd biopsy
PCa - 3rd biopsy
PCa - 4th biopsy
ASAP
(n = 13) (n = 28)
% (n)
38.5 (5)
80.0 (4)
0
20.0 (1)
ASAP+
HGPIN
(n = 2)
% (n)
% (n)
53.6 (15) 100.0 (2)
86.6 (13) 100.0 (2)
6.7 (1)
6.7 (1)
-
p-value
OR
0.245
0.171
0.760
0.802
2.81
3.53
0.548
0.442
HGPIN: high-grade prostate intraepithelial neoplasia; ASAP: atypical small acinar proliferations; ASAP + HGPIN:
high-grade prostate intraepithelial neoplasia plus atypical small acinar proliferations; PCa: prostate cancer.
Regarding topographic diagnosis of PCa, we observed
a significant higher risk of diagnosing PCa close to where
ASAP was detected, in comparison to patients with initial
finding of HGPIN (OR = 10.1; p = 0.036; Table 2). If
considered only the cases in which cancer was detected
exactly in the same place, this difference was even clearer
for ASAP versus HGPIN (OR = 5.93; p = 0.015).
Table 2. Topography of prostate cancer in comparison to initial findings in
repeated biopsies
Topography
Same quadrant
Same side, different
quadrant
Opposite side
HGPIN
ASAP
ASAP +
HGPIN
(n = 5)
(n = 15)
(n = 2)
% (n)
20.0 (1)
% (n)
80.0 (12)
% (n)
0.0 (0)
60.0 (3)
13.3 (2)
100.0 (2)
20.0 (1)
6.7 (1)
0.0 (0)
p-value
OR
0.036
10.3
HGPIN: high-grade prostate intraepithelial neoplasia; ASAP: atypical small acinar proliferations; ASAP + HGPIN:
high-grade prostate intraepithelial neoplasia plus atypical small acinar proliferations.
Prostate biopsies containing prostate intraepithelial neoplasia and atypical small acinar proliferation: what to do?
DISCUSSION
Most epidemiologic studies evaluating HGPIN
and ASAP as risk factors for PCa were from a time
when sextant biopsies (six samples) were routinely
performed(1,7). Nowadays, the minimum number
considered for a proper PCa screening is 12 samples
(extended biopsy). In this context, recent studies have
demonstrated that the incidence of HGPIN and ASAP
is different from the previously stated, as well as the risk
of a subsequent diagnosis of PCa(3-5,8-10).
Our study has some important findings. First, the
incidence of HGPIN on prostate biopsy was of 4.6%,
reproducing the results of recent studies on extended
biopsies(5). HGPIN was associated with a 38.5% chance
of PCa detection in repeated biopsies, and there was
a significant lower risk of detecting cancer in the
topography of previous HGPIN versus ASAP (20
versus 80%; p = 0.036). However, this risk must also
be compared to the risk of finding cancer in a repeated
biopsy after a benign diagnosis, which ranges from 10.0
to 30.0%(11-13). Other series diagnosed PCa in 10 to
57%(1,14-15) of repeated biopsies after HGPIN(11-13,16-17). In
the present series with extended biopsies, the diagnosis
of PCa was made in 13.2 to 30.5%(3-5,12). We found a
higher rate of PCa than these authors, and a higher rate
than after benign diagnosis, but still lower than observed
for ASAP. Therefore, further studies evaluating other
factors, such as the number of involved cores and
morphologic patterns, might help to determine which
of the men with HGPIN are at significantly higher
risk of harboring carcinoma and would benefit from
rebiopsies(18).
Second, ASAP occurred in 1.4% of the extended
prostate biopsies, what is also similar to larger series(1,5,1415)
. The risk of diagnosing PCa on repeated biopsies was
of 53.6%, comparable to recent series (range from 37.0
to 51.0%)(3-5,19). There was also a significant higher risk of
detecting the PCa close to the site of ASAP (p = 0.001;
OR = 10.8). Therefore, patients with ASAP at prostate
biopsies are at increased risk of future PCa detection,
and it is recommended that ASAP foci should be more
extensively sampled on repeated biopsies. As the risk
of PCa is higher in patients with ASAP, it is generally
recommended that rebiopsies are taken after three to
six months(6).
Third, for patients who had ASAP in the first biopsy,
the risk of detecting PCa was 50.0%. However, in all
cases (n = 3) in which ASAP was found only after the
second biopsy, a subsequent biopsy diagnosed PCa.
Although there were few cases of association HGPIN +
ASAP, this finding seems to be related to an even higher
rate of future detection of PCa than isolated HGPIN or
ASAP, as previously reported(9).
413
Our study has several limitations. Even though a
large number of biopsies were evaluated (6,490), the
number of patients with HGPIN and ASAP was much
lower. Therefore, the relatively small number of men for
subsequent analysis limits the power of the study. Also,
it is important to note that a high subset of patients were
lost to follow-up and did not undertake rebiopsy after
HGPIN or ASAP, which can raise a concern of followup bias. However, the strength of our study is that a
large number of patients in a contemporary extended
biopsy series could be evaluated.
CONCLUSION
In conclusion, following the finding of HGPIN or
ASAP on extended prostate biopsies, close followup is recommended, and repeated biopsies should be
performed according to clinical data. Rebiopsies should
be strongly recommended when the association HGPIN
+ ASAP is present or when ASAP is found only after
the second biopsy. Repeated biopsies after an ASAP
finding should be always randomized, but foci of ASAP
finding should be more extensively sampled.
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