Distal seminal vesicle invasion by prostate adenocarcinoma does not occur in isolation of proximal seminal vesicle invasion or lymphovascular infiltration.

Abstract

Seminal vesicle (SV) invasion by prostatic adenocarcinoma is a poor prognostic indicator. Despite this, there are currently no guidelines regarding SV sampling in radical prostatectomy specimens. This study examines the distribution of invasive prostatic adenocarcinoma in SVs and makes recommendations regarding sampling procedures.
The SVs from 773 consecutive radical prostatectomy specimens were serially sectioned and blocked entirely, with sections grouped into the proximal, mid and distal thirds of the glands. The site of invasive prostatic carcinoma within the muscular wall of the SV and its presence in the ejaculatory duct was recorded.
SV invasion (pT3b) was present in 56 (7.2%) cases. Patients ranged in age from 52 to 73 years (mean 64 years), with a serum prostatic specific antigen ranging from 3.7 to 46 ng/mL (mean 10.6 ng/mL). Fourteen patients (25%) had a palpable nodule or induration on digital rectal examination. Ejaculatory duct involvement was present in 49 cases. Forty-seven of 49 (95.9%) cases with ejaculatory duct involvement also had SV invasion. The mean tumour volume was 5.53 cm(3) (range 1.0-12.1 cm(3)). The tumours had a Gleason score of 4 + 3 in five cases, 4 + 3 with tertiary pattern 5 in 12 cases, 8 in two cases and 5 + 4/4 + 5 in 37 cases. All but one of the SV positive cases (98.2%) had involvement of the proximal third (15 right, 17 left and 23 both) of the gland, 35 of which (63.6%) had infiltration only of the proximal SV. For the remainder, 11 also had mid third and nine had mid and distal third involvement. Lymphovascular invasion within the prostate was seen in 71.4% of cases. In one of these cases involvement of the distal right SV was present in the absence of involvement of the proximal or mid SV.
In this study, as distal SV invasion in the absence of proximal SV invasion was found in <2% of cases, we conclude that sampling of the proximal third of the SVs is sufficient to identify virtually all cases of tumour infiltration into the SVs. If lymphovascular invasion is present in the absence of proximal SV invasion, then the remaining parts of the SV must be examined. Also, in cases with involvement of the ejaculatory duct, thorough examination of the SV is warranted.

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P R O S T A T E
Distal seminal vesicle invasion by prostate adenocarcinoma does not
occur in isolation of proximal seminal vesicle invasion or
lymphovascular infiltration
HEMAMALI SAMARATUNGA*{, DINITHI SAMARATUNGA{, JOANNA PERRY-KEENE{,
MICHAEL ADAMSON*, JOHN YAXLEY{ AND BRETT DELAHUNTx
*Aquesta Pathology, {University of Queensland, and {Royal Brisbane Hospital, Brisbane, Queensland,
Australia; xDepartment of Pathology and Molecular Medicine, Wellington School of Medicine and Health
Sciences, University of Otago - Wellington, Wellington, New Zealand
Summary
Aims: Seminal vesicle (SV) invasion by prostatic adeno-
carcinoma is a poor prognostic indicator. Despite this, there
are currently no guidelines regarding SV sampling in
radical prostatectomy specimens. This study examines
the distribution of invasive prostatic adenocarcinoma in
SVs and makes recommendations regarding sampling
procedures.
Method: The SVs from 773 consecutive radical prostatect-
omy specimens were serially sectioned and blocked entirely,
with sections grouped into the proximal, mid and distal thirds
of the glands. The site of invasive prostatic carcinoma within
the muscular wall of the SV and its presence in the
ejaculatory duct was recorded.
Results: SV invasion (pT3b) was present in 56 (7.2%)
cases. Patients ranged in age from 52 to 73 years (mean
64 years), with a serum prostatic specific antigen ranging
from 3.7 to 46 ng/mL (mean 10.6 ng/mL). Fourteen patients
(25%) had a palpable nodule or induration on digital rectal
examination. Ejaculatory duct involvement was present in
49 cases. Forty-seven of 49 (95.9%) cases with ejaculatory
duct involvement also had SV invasion. The mean tumour
volume was 5.53 cm3(range 1.0–12.1 cm3). The tumours
had a Gleason score of 4þ3 in five cases, 4þ3 with
tertiary pattern 5 in 12 cases, 8 in two cases and 5þ4/
4þ5 in 37 cases. All but one of the SV positive cases
(98.2%) had involvement of the proximal third (15 right, 17
left and 23 both) of the gland, 35 of which (63.6%) had
infiltration only of the proximal SV. For the remainder, 11
also had mid third and nine had mid and distal third
involvement. Lymphovascular invasion within the prostate
was seen in 71.4% of cases. In one of these cases
involvement of the distal right SV was present in the
absence of involvement of the proximal or mid SV.
Conclusions: In this study, as distal SV invasion in the
absence of proximal SV invasion was found in 52% of
cases, we conclude that sampling of the proximal third of the
SVs is sufficient to identify virtually all cases of tumour
infiltration into the SVs. If lymphovascular invasion is present
in the absence of proximal SV invasion, then the remaining
parts of the SV must be examined. Also, in cases with
involvement of the ejaculatory duct, thorough examination of
the SV is warranted.
Key words: Seminal vesicle sampling, radical prostatectomy, prostatic
adenocarcinoma, seminal vesicle invasion.
INTRODUCTION
Seminal vesicle (SV) invasion by prostate adenocarcinoma
has been shown to be a poor prognostic indicator, with a
high risk of prostate specific antigen (PSA) failure after
radical prostatectomy and reduced cancer-specific survi-
val.1–4As a consequence, accurate pathological staging of
cancer in radical prostatectomy specimens requires de-
tailed examination of SVs to determine if invasion by
tumour is present. In published series SV infiltration was
found in 14.3–24.6% of cases;4–7however, in these studies
differing methods of sampling were employed and, in
particular, it is unclear whether or not the entire SVs were
examined. In other studies, where no sampling details
were provided, the incidence of SV invasion was found to
be 11–17.47%.1,2,8
Inaseparatestudy,involvementoftheSVs,intheabsence
of direct invasion from the prostate, was noted in 12% of
cases and, given the absence of observed direct invasion, this
was considered to represent metastatic disease.5As part of
this study the authors classified the mechanisms of SV
invasion according to the route of tumour infiltration with:
(1) direct spread of cancer along the ejaculatory duct
complex into the SVs, (2) direct invasion at the prostatic
base by extension into the peri-SV soft tissue and into the
wall of the SV, and (3) metastatic involvement, being
described.
In view of the variability in the manner of tumour spread
to SVs, there is insufficient guidance in the literature as to
how the SVs should be sampled so as to detect all cases with
tumour infiltration. In particular, there are currently no
recommendationsastowhetherornottheentireSVsneedto
be sampled and examined.
This study was undertaken in order to examine the
incidence and distribution of SV invasion through systema-
tic and detailed sampling of a large series of radical
prostatectomy specimens. A further objective of the study
was the development of recommendations regarding the
Pathology (June 2010) 42(4), pp. 330–333
Print ISSN 0031-3025/Online ISSN 1465-3931 # 2010 Royal College of Pathologists of Australasia
DOI: 10.3109/00313021003767330

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optimum method of sampling SVs in surgical specimens, so
as to ensure that no instance of tumour infiltration is
overlooked.
MATERIALS AND METHODS
A total of 773 radical prostatectomy specimens, accessioned consecutively
from patients treated for clinically localised prostate cancer from
November 2008 to January 2010, were retrieved from the surgical
pathology files of Aquesta Pathology. Clinical data were obtained from
the referring clinician and it was determined that none of the patients had
undergone hormone therapy or radiation therapy prior to undergoing
radical prostatectomy.
Immediately after removal, each prostate gland was transported to the
pathology laboratory where it was weighed and measured. After fixation in
10% neutral buffered formalin, the radical prostatectomy specimen was
painted with two colours to indicate the right and left sides. The prostate
gland was sectioned and embedded in its entirety. Specifically, the SV and
vas deferens were removed by a transverse section taken as close as possible
to the prostatic base and weighed. The next transverse slice, which
represented the prostate base, was serially sectioned in a vertical
parasagittal plane, allowing visualisation of the entire superior surface of
the gland. The body of the prostate was serially sectioned at 4 mm intervals
in a transverse plane perpendicular to the rectal surface. The apical slice
was then serially sectioned in a vertical parasagittal plane. Each SV was
transversely sliced and the entire gland was blocked, being divided into
proximal, mid and distal thirds. All submitted lymph nodes were also
completely sampled. On histological examination of the prostate gland, the
location of each tumour nodule was noted. The highest Gleason score of a
tumour nodule was taken to be the final Gleason score of the carcinoma in
each case.9The tumour volume was estimated using a three-dimensional
volume estimation method,10and the tumours were assigned a pT staging
category following examination for extra prostatic extension, resection
margin involvement, and involvement of SVs and lymph nodes. SV
invasion was reported when the muscular wall of the SV was infiltrated by
carcinoma. Where present, tumour involvement of the ejaculatory duct was
also noted.
RESULTS
SV invasion (pT3b) was present in 56 (7.2%) cases (Fig.
1A,B). These patients ranged in age from 52 to 73 years
(mean 64 years) and their serum PSA ranged from 3.7 to
46 ng/mL (mean 10.6 ng/mL). Fourteen (25%) patients
had a palpable nodule or induration on digital rectal
examination. Ejaculatory duct involvement (Fig. 2A,B) was
present in 49 cases. The base of the prostate was involved
by carcinoma in all 56 cases. Forty-seven (95.5%) of the 49
cases with ejaculatory duct involvement also had SV
invasion. Lymphovascular invasion and surgical margin
involvement were present in 40 (71.4%) and 18 (32%)
cases, respectively. In no case with carcinoma in the
lymphovascular spaces of the SV was there absence of
muscle invasion.
All but one of the cases with SV infiltration by tumour
had involvement of the proximal third of the SV (15 right,
17 left, and 23 both), of which 35 (63.6%) had only
proximal SV infiltration. Of the other cases with SV
invasion, 11 had involvement of the mid third and nine
had involvement of the mid and distal thirds of the gland.
In the remaining case there was involvement of the
muscularis of the distal right SV in the absence of tumour
infiltration in the proximal or mid third of the SV or the
ejaculatory duct. In this case lymphovascular invasion was
seen in the prostate gland and extraprostatic tissue and
there was no evidence of direct invasion into the distal SV
from extraprostatic carcinoma. Lymph nodes were sub-
mitted from 20 cases, including this latter case, and none of
these contained metastatic carcinoma.
For all the cases with SV infiltration by tumour, the
mean tumour volume was 5.53 cm3(range 1.0–12.1 cm3).
The Gleason score was 4þ3 in five cases, 4þ3 with tertiary
pattern 5 in 12 cases, 4þ4 in two cases and 5þ4/4þ5 in 37
cases.
DISCUSSION
SV invasion has been shown to be a poor prognostic
indicator in patients with prostatic adenocarcinoma, with a
high risk of cancer progression after radical prostatect-
omy.1–4As a consequence it is clear that, where present, SV
invasion by tumour should not be overlooked during the
examination of radical prostatectomy specimens. In view of
this it is surprising that there are currently no evidence-
based recommendations regarding the optimum method of
SV sampling to be employed in order to ensure detection of
all tumour positive cases.
In published series, where the incidence of SV infiltration
by tumour was investigated, differing methods of SV
sampling were reported; importantly, in none of these
was there total embedding of the glands.
Fig. 1
the muscular wall. (A) Low magnification, (B) high magnification.
Seminal vesicle with infiltration of prostatic adenocarcinoma into
SEMINAL VESICLE SAMPLING
331

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In a series of 122 radical prostatectomy specimens, the
examination of two or three sequential sections of the
proximal SVs showed SV invasion in 24% of cases.7
Following examination of at least three sections of the SVs
up to the mid part of the gland, SV invasion was found in
21% of 312 patients who had undergone radical prosta-
tectomy for T1–T3 carcinoma.5In both of these studies,
there is no indication as to whether or not the distal part of
the SV was examined histologically. In a further study, in
which the SVs were bisected in the coronal plane with half
of each gland being submitted for microscopy, SV
infiltration was seen in 23% of cases.6In this series it was
noted that the distal tip of the gland was not examined in
all cases. Similarly, Stein et al.4found tumour involvement
of one or both SVs in 14% of cases. In this study, the
glands were sliced vertical to the long axis and sections were
taken from the base of the SVs; however, it is unclear what
proportion of the complete SVs were sampled. Finally, in
other studies where SV invasion was found in 11–17.47%
of cases, no information was provided regarding the
protocols employed for sampling of the SV.1,2,8
The incidence of carcinomatous involvement of SVs in
the current study was found to be 7.24%. Although the
entire SVs were examined, the incidence of tumour invasion
is much lower than that previously reported.1–8A major
reason for this is likely to be that the earlier cases were
more than 10 years old and pre-date widespread PSA
screening. With detection through PSA screening, it is
assumed that our cases were diagnosed at a lower stage.
Malignant infiltration of the SV is defined as involve-
ment of the muscular wall of the extraprostatic portion
of the SV.11There has been some confusion regarding
this in previous studies and some have included cases
showing intraprostatic SV invasion.1This is of impor-
tance as it has been shown that intra-prostatic SV
invasion does not have the same poor prognosis as
extraprostatic SV invasion.1,12The consensus has there-
fore been to use the term ‘ejaculatory duct invasion’ for
tumour extending into what had been called ‘intrapro-
static SV invasion’ by some. In our series, 47 of 49
(95.9%) cases with ejaculatory duct involvement also had
SV invasion. As the remaining two cases did not have
tumour spread to the SV, it is clear that it cannot be
assumed that this isan
infiltration. Despite this, tumour in the ejaculatory duct
is associated with a high risk of SV invasion and as a
consequence it is particularly important that SVs be
sampled adequately to confirm or refute this. In needle
biopsies it is often impossible to differentiate SV from
ejaculatory duct tissue, and if tumour is present, it would
be erroneous to assume that this invariably indicates
invasion of SV. These cases can be noted in the report as
having ‘ejaculatory duct/seminal vesicle invasion’.
In this current study the SVs were examined in a
systematic manner with complete sampling of both SVs
from proximal to distal. We found that involvement of the
distal SV in the absence of infiltration of the proximal SV
occurred very rarely, being present in only one case. In this
specimen there was extensive infiltration of lymphovascular
spaces in the prostate and it is likely that the tumour in the
distal SV was the result of metastatic spread.
Our results are somewhat similar to the findings of two
other studies.6,13In a study by Villers et al., which
examined half of each prostate blocked in the coronal
plane, an orderly pattern of tumour spread from the mid
base region to directly involve the SVs was found in 46 of
47 cases.6Only one case had apparently discontinuous
metastasis to the SV but, as only one longitudinal half of
each SV was sampled, it is not possible to rule out that even
in this case the tumour in the SV was the result of direct
extension. In another study, 6.7% of cases had discontin-
uous infiltration of the SV; however, the distribution of the
tumour in the SV was not described.13In this study there is
also difficulty in distinguishing between invasion by
extraprostatic extension and invasion through the ejacula-
tory duct complex.
The risk of SV invasion and tumour progression are
related to clinical stage, serum PSA, Gleason score, and the
zonal location of cancer.6,8,11,13,14This information can be
used to predict the risk of SV invasion before radical
prostatectomy; however, it is not possible to predict this
with certainty in individual cases. In view of this it is clear
that the SVs must be surgically excised and examined in all
cases. Although it is to be expected that ipsilateral
involvement of the SV on the side of the dominant
carcinoma is more common, again this cannot be predicted
accurately by needle biopsy, further necessitating examina-
tion of both SVs.
invariable markerof SV
Fig. 2
Low magnification, (B) high magnification.
Ejaculatory duct with infiltrating prostatic adenocarcinoma. (A)
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SAMARATUNGA et al.Pathology (2010), 42(4), June

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AlthoughOhorietal.5foundthemechanismofSVinvasion
to be of prognostic significance, others have not found this to
be the case.13As there are no reports to indicate that the
location of tumour within the SV is of prognostic significance,
it is apparent that no important prognostic information is
likely to be lost if the distal SV is not examined.
In this study, we have shown that infiltration of the mid
or distal SV is exceptionally rare in the absence of tumour
infiltrating the proximal part of the SV. Detailed sampling
of the proximal third of the SVs will identify virtually all
cases of tumour infiltration into the more distal parts of the
glands. If invasion of lymphovascular spaces is present,
with no evidence of tumour in the proximal SV, then the
SVs must be examined in entirety. In cases with ejaculatory
duct involvement, SV invasion is frequently, but not
invariably, present. In such instances thorough examina-
tion of the SV is warranted.
Address for correspondence: Associate Professor H. Samaratunga, Aquesta
Pathology, 1/51 Douglas Street, Milton, Qld 4064, Australia. E-mail:
hema@aquesta.com.au
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