AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Special Article
Surgical Pathology Examination of the
Prostate Gland
Practice Survey by American Society of Clinical Pathologists
LAWRENCE D. TRUE, MD
The American Society of Clinical Pathologists surveyed 395 members
who represented the spectrum of anatomic pathology practice among
the membership. The results of how respondents fix, section, process,
and report radical prostatectomy specimens, transurethral prostatec-
tomy specimens, and needle biopsy specimens is presented, with a commentary based on the current medical literature. (Key words: Prostate
gland; Practice survey; Radical prostatectomy; Needle biopsy;
Transurethral resection) Am J Clin Pathol 1994;102:572-579.
The American Society of Clinical Pathologists Quality Management Practice Review Committee is sponsoring publication of a
series of articles commenting on procedures used by pathologists during the examination of various surgical specimens.
Committee-sponsored survey results sene as the basis for discussion and commentary by an expert in the field. Although this
information may prove useful informing a practice parameter,
it is not the intention of the author or the committee to identify
this information as a practice parameter. The publication of
this article does not necessarily represent the opinions or endorsement by the ASCP Board of Directors.
The American Society of Clinical Pathologists (ASCP) surveyed 395 pathologists for methods used in handling and reporting the pathology of prostate specimens. The prostate
gland was selected as the first in a series of organs to be surveyed. Because it is the site of a cancer that is currently receiving great attention, the choice of the prostate gland is timely.
Over the past 5 years the incidence and mortality rate of prostate cancer have increased progressively. Prostate cancer is
currently the most common cancer affecting males in the
United States.1,2
RESULTS WITH DISCUSSION
Survey
The survey questions and results with commentaries are presented below. Responses are given as the percentage of respondents who answered yes for each respective question. Neither
the results of the survey nor the commentary are intended to
endorse specific practices, even for those particular practices
that were undertaken by the majority of respondents.
RADICAL PROSTATECTOMY SPECIMENS
Specimen
Dimensions
Record specimen weight? 95% yes
Record specimen measurements? 97% yes
Weighing and measuring the three specimen axes are done
by > 95% of responding pathologists. Although recording the
weight of radical resection specimens is important for documentation, particularly when supplemented by comments
concerning the completeness of resection, (eg, that the seminal
vesicles are intact and not fragmented), the value of recording
dimensions in addition to weight is of less obvious value. Because the resected prostate is an irregular structure, symmetric
in only one axis—about the sagittal plane—linear measurements are less accurate and reproducible than is specimen
weight.
MATERIALS A N D METHODS
Survey
Findings
Audience
Members were selected to represent a variety of practice settings. Of the 395 pathologists surveyed, 273 (69%) returned
completed surveys. The practice characteristics of the respondents are expressed as the percentage of all responding pathologists (Tables 1 and 2).
Specimen Handling
and
Fixation6'9
Freeze sample for storage? 28% yes
Cut specimen before fixing? 40% yes
Inject specimen with fixative before cutting? 3% yes
From the University of Washington Medical Center, Seattle, WashFix specimen overnight? 53% yes
ington.
A relatively large number of pathologists (40%) cut the specimen before fixation. A disadvantage of cutting unfixed prostate
Manuscript received August 9, 1993, revision accepted February 21,
is bulging of prostatic parenchyma above the cut surface. Such
1994.
bulging makes the taking of intact sections of uniform thickAddress reprint requests to Dr. True: Department of Pathology, RCness more difficult. The majority (53%) of pathologists fix the
72, University of Washington Medical Center, Seattle, WA, 98195.
572
TRUE
Prostate Gland:
TABLE 1. SIZE AND LOCATION OF PRACTICE
OF RESPONDENTS
NO. Of
Beds
Nonuniversity
Hospital (°/o)
University or
UniversityAffiliated
Hospital (%)
<100
100-299
300-500
>500
9
35
21
7
<1
4
10
8
2
2
<1
0
72
23
5
Total (%)
Private
Laboratory
(o/o)
Total
(%)
12
41
32
15
prostate overnight. Alternative options include overnight suspension of the prostate in fixative, and injection of fixative into
the uncut prostate with subsequent overnight fixation. Although the latter method is used by only 3% of respondents, the
quality of fixation with this method is excellent. With respect to
overnight suspension of the uncut specimen in fixative, because formaldehyde diffuses relatively slowly into such a solid
organ as the prostate, the inner areas of prostate glands handled
in this manner may be partially autolyzed.
In choosing among these options, the most important criterion is good fixation because all of the methods previously cited
can be applied in an efficient and timely manner.
Margin
Identification10'12
Use ink to identify margins? 86% yes
Identify margin with method other than inking? 17% yes
Distinguish surfaces with inks of different colors? 29% yes
Most pathologists (86%) use ink to indicate the surgical margin in sections. Inking is important because the surface of the
prostate is fibroconnective tissue that does not form a discrete
histologic boundary with the extraprostatic, pelvic soft tissue.
Inking should be done in a manner that minimizes contamination by ink of nonmarginal tissue. By immersing the inked
gland, either unfixed or fixed, into a "mordant," such as
Bouin's solution or acetic acid, ink will be "fixed" to the surface. Contamination by ink of sites that are not margins will
thus be minimized.
Because proximity of tumor to margin cannot be predicted
based on the gross appearance of the cut surface of the prostate,
the entire surface should be inked. Inking each lobe a different
color helps retain orientation as sections are obtained and provides a cross-check for section location. About 30% of respondents ink with different colors. Further microscopic orientation can be provided by incising the most anterior and
posterior aspect of each block.
Sectioning
the
Prostate13'25
Section prostate coronally? 82% yes
Label each section by site of origin? 88% yes
Submit section of prostate-seminal vesicle junction? 94% yes
Describe size and location of abnormalities? 97% yes
Embed entire gland for sectioning? 12% yes
Embed 1 to 4 blocks? 5% yes
Embed 5 to 8 blocks? 19% yes
573
Practice Survey
Embed 9 to 12 blocks? 29% yes
Embed > 12 blocks? 34% yes
Modify number of blocks based on initial findings? 87% yes
Embed entire apex? 64% yes
Embed all bladder neck tissue? 62% yes
Submit all lymph nodes, labeled by location? 99% yes
The majority of respondents use the following approach:
Coronal Sectioning of I he Entire Gland (82%). Serial coronal
sections, parallel to an initial en-face section of the apex, are
taken until the junction of seminal vesicles with the prostate is
approached. After sections of the base of the seminal vesicles
are obtained, the remaining sections may be either parallel to
an en-face section of the bladder neck, or they may continue to
be parallel to the apical section. The en-face sections are then
sectioned in the sagittal plane and embedded (see Appendix).
Another option is to embed the en-face section flat as a single
section.3
Labelling of Each Section by Site of Origin (88%). Adoption
of a systematic approach to labelling will minimize inaccuracies. One such method involves consistent assignment of numbers to blocks in a hierarchical manner, so that lower numbers
designate more distal, more anterior, and right lobe, respectively (see Appendix). Another option is to process the prostate
gland as sequential whole mount sections. The dilemma of
choosing between whole mount sections and quadrant sections
is one of balancing aesthetics and greater ease in examining
sections against the cost of time and materials and the logistical
problem of storing glass slides of unconventional size. The only
significant difference in the histopathology of these two different processing methods is that whole mounts are often thicker
sections.4'5
Sections of the Seminal Vesicles at Their Junctions With the
Prostate (94%). Sectioning this region of the seminal vesicles is
important because cancer involves the seminal vesicles by direct extension from the prostate. Furthermore, the presence of
tumor in a seminal vesicle is a criterion of higher pathologic
stage (see Appendix).
Description ofthe Size and Location of A ny Gross A bnormalilies (97%). Most pathologists describe gross abnormalities. Although carcinoma can sometimes be identified macroscopically, the gross appearance of the prostate is of little value in
predicting absence of tumor.
There is not yet a consensus among pathologists as to
whether the whole gland should be embedded for sectioning.
The rationale for total embedment of the prostate is based on
the fact that the gross appearance of the sectioned prostate is an
unreliable guide for tumor distribution. Whether the greater
time and materials involved in prosecting and examining sections of totally embedded prostate is worthwhile is uncertain.
Even totally embedding a prostate does not mean that the margins will be completely sampled, unless serial sections are made
of each block.6
The majority of respondents (52%) process fewer than 13
blocks. Two schemes that involve only partial sampling of the
TABLE 2. SIZE OF WORK LOAD OF RESPONDENTS
<2,500
9
2,500-5,000
22
5,000-10.000
31
10,000-20,000
>20,000
32
Values are percentages. Column headings are no. of surgical specimens per year.
• No. 5
6
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AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Special Article
prostate have been proposed.7,8 Both of these approaches
yielded accurate data concerning tumor grade, volume, and
extent in 90% of cases. Based on initial findings many pathologists (87%) submit additional tissue. Reasons for submitting
more tissue include uncertainty that the main tumor mass was
sampled or whether margins were involved. In such situations,
additional blocks sometimes resolve the uncertainty. 7
The status of the apex (the most distal portion of the prostate), bladder neck (or base), and lymph nodes are deemed
important for patient management and for prediction of likelihood of surgical cure. Whereas knowing the histologic status of
all lymph nodes is important for accurate pathologic staging,
the status of the apex and base does not affect tumor stage.
Reporting
Histologic
Findings
(26-40)
Assign Gleason grade(s)? 81% yes
Assign combined Gleason score? 73% yes
Grade by an alternative system? 35% yes
Report percent involvement of each lobe? 54% yes
Report whether apex is involved by tumor? 83% yes
Report whether seminal vesicles are involved by tumor? 99%
yes
Report whether tumor invades or extends beyond capsule?
100%
Report distance of tumor from the surgical margin? 61% yes
Assign a nuclear grade? 21% yes
Estimate the mitotic activity? 21% yes
Report presence and grade of dysplasia? 50% yes
Comment upon vascular invasion? 89% yes
Comment upon perineural invasion? 90% yes
Comment upon non-neoplastic changes? 81% yes
Report whether the cancer is multifocal? 90% yes
Tumor Grade. Assignment of a grade has been shown in
many studies to be of value in predicting patient longevity and
disease-free survival. The particular grading system used does
not matter, as long as it is applied consistently and reproducibly, and it is a system known to clinicians caring for the patient.
The Gleason system of grading is the most widely used grading
scheme in the United States.9 The combined Gleason score (see
Appendix) is the most important for patient management,
rather than the grades of the individual Gleason patterns.
Thirty-five percent of respondents use another grading system, either in place of, or as a supplement to, the Gleason
system. Other grading systems are based on different combinations of cytologic and histologic findings.10
Laterality. Fifty-four percent of institutions estimate percent
involvement of each lobe. However, there is no proven clinical
value in knowing whether tumor is unilateral or bilateral, or in
knowing tumor location other than in being able to provide
retrospective correlation with preoperative imaging studies.
Apex. The majority (83%) report the status of the apex. Involvement of the apex by tumor is sometimes used as an indication for adjuvant therapy.
Seminal Vesicles. Reporting the status of the seminal vesicles is conventional (99%) because such data are requisite for
pathologic staging. Distinction should be made between tumors that invade the fibroadipose tissue adjacent to the seminal vesicle from tumors invading the muscular wall of the seminal vesicle, because the latter has a significantly poorer
prognosis.3 Furthermore, the pattern of invasion into the wall
of the seminal vesicle may have prognostic significance." Syn-
chronous regional nodal metastasis are less frequent in cases
where invasion of the seminal vesicle occurred by direct extension along the ejaculatory duct, but are more likely when tumors invaded the seminal vesicle via periprostatic nerves.
Capsule/Surgical Margins. All responding pathologists report whether tumor extends beyond the capsule (100%), and a
majority report the distance of tumor from the surgical margins (61%). Identification of the capsule is problematic because
the surface of the prostate is comprised of bands of dense fibroconnective tissue. These bands extend from the looser connective tissue of the pelvis and merge with the fibromuscular
stroma of the prostate without histologically discrete boundaries.12 For the present discussion, the "capsule" is defined as
the most peripheral layer of dense connective tissue around the
prostate.
Extension of tumor into this most peripheral layer of connective tissue, termed by some investigators "invasion" of the
"capsule", is a common finding. When extension of tumor into
the capsule is of limited extent, there are no adverse prognostic
implications. In contrast, extension of tumor through the
dense capsular connective tissue into periprostatic fibroadipose
tissue, termed "penetration" through the capsule, is associated
with a worse prognosis.13,14 There is evidence that only extensive capsular penetration has prognostic power greater than
that associated with tumor volume and grade. Extensive capsular penetration is defined as a length of tumor penetrating the
capsule that is > .5 cm 2 . 15
Extension of tumor to the surgical margin is of less certain
prognostic value, although it is frequently observed. Tumors
may extend to any surgical margin. One study reported the
following frequencies with which a tumor has been found at
surgical margins in specimens that have a tumor-positive margin: apical, 66%; posterior, 49%; anterior, 38%; and bladder
neck, 13%.16 Extension to the margin of the fibroadipose tissue
of the neurovascular bundle should be distinguished from capsular penetration that does not extend to that soft tissue margin. The histologic nature of the margin indicates whether it is a
surgical margin, (ie, a ragged margin is probably surgical).17
Recent reports indicate that the presence of a tumor at a
surgical margin may be of significant prognostic importance.
In a multivariate analysis of more than 500 patients who underwent radical prostatectomy, Epstein and colleagues found
that margin positivity for tumors more strongly predicted disease progression than did capsular penetration. 3
Mitotic Count. Twenty-one percent of institutions report the
degree of mitotic activity. However, stratifying patients by mitotic activity of their tumors is of no apparent predictive value.
Although mitoses are rare in prostate cancers, the presence of
any mitoses is an unfavorable prognostic indicator in a univariate analysis.18 In a multivariate analyses, however, the extent
of mitotic activity does not provide prognostic power beyond
that provided by tumor grade and stage. Furthermore, finding
mitoses can be laborious for the pathologist because the proliferative rate of prostate cancers is low compared with other solid
tumors. In one series, the median S-phase fraction of tumor
cells was 1%.19
Dysplasia or Prostatic Intraepithelial Neoplasia. Half of the
respondents report prostatic intraepithelial neoplasia (PIN).
There is no clinical value in seeking and reporting PIN in the
radical prostatectomy specimen. Furthermore, there is poor
interobserver reproducibility in grading PIN. 20 The situation in
which identification of PIN leads to different management of
A.J.C.P. • November 1994
TRUE
Prostate Gland:
the patient is the finding of PIN in needle biopsy specimens.
High-grade PIN correlates imperfectly with the presence of invasive carcinoma. 2 '
Vascular/Perineural Invasion. The majority (89%-90%) of
respondents report vascular or perineural invasion. Although
the presence of angiolymphatic invasion may be of prognostic
value,22 it does not have prognostic power independent of
grade.23 Although finding perineural invasion in a needle
biopsy specimen is predictive of capsular penetration in the
radical prostatectomy specimen,24 perineural invasion in the
radical specimen appears not to be of independent prognostic
importance. Finding perineural tumors can also help support
the diagnosis of prostate cancer, although not all glands near
nerves are malignant.
Non-Neoplastic Changes. Most respondents report such
changes as hyperplasia, atrophy, metaplasia, infarct, and inflammation. Although these changes have no known clinical
relevance to tumor behavior, the reporting of such changes
when they are prominent can provide data for correlation with
clinical and radiologic findings.
Multifocality. Commented on by the majority (90%), multifocality is hard to confirm. Only by reconstructing prostates
from serial sections can multifocality be verified with certainty.
Making the distinction between unifocal and multifocal tumors is of no known clinical significance.
DNA Content of Tumor
Never perform analysis by flow cytometry? 57% yes
Occasionally perform analysis by flow cytometry? 30% yes
Frequently perform analysis by flow cytometry? 5% yes
Always perform analysis by flow cytometry? 3% yes
Never perform analysis by image cytometry? 67% yes
Occasionally perform analysis by image cytometry? 15% yes
Frequently perform analysis by image cytometry? 2% yes
Always perform analysis by image cytometry? 3% yes
Although the majority of respondents "never" analyze the
DNA content of tumor, by either flow or image cytometry, >
30% "occasionally" do. Most pathologists who analyze tumor
DNA content use flow cytometry, either directly or by referral
to another lab. Image cytometry yields DNA ploidy values similar to those obtained by flow cytometry.25
Whether knowledge of tumor cell DNA content provides
information of value in managing localized prostate cancer is
debatable. Currently, it is not generally accepted as providing
information important for patient care. The various studies of
prostate cancer DNA ploidy differ in a number of respects:
1. Whether the finding of aneuploidy/tetraploidy is of value26
or not.27
2. Whether an elevated S-phase fraction is of prognostic
value28 or not.29
3. The nature of the program used for histogram analysis.30
At a
mended
variable
ation of
recent consensus conference, the conferees recominclusion of tumor cell DNA content analysis as a
in randomized cancer therapy trials, and considertumor cell S-phase fraction as a possible variable.31
575
Practice Survey
Embed entire specimen if < 10 g? 94% yes
Base number of cassettes on total weight? 19% yes
Submit additional cassette for each 10 g tissue? 36% yes
Submit 10 cassettes regardless of weight? 10% yes
Weight. Virtually all pathologists use weight to determine
specimen mass. Weight is more efficiently and accurately obtained than other measurements of mass, such as number of
chips or total volume of tissue.
Embedding Protocol. The proportion of transurethral specimen tissue to embed has been the subject of several recent
articles. This discussion has become important with the realization that some cancers of low volume have a significant risk of
recurrence/progression. Historically, stage A1 cancers, defined
as cancers found incidentally in a transurethral prostatectomy
(TURP) specimens and having a volume fraction of less than
approximately 5%, and a grade that was not high, were thought
to have little likelihood of decreasing patient longevity. There
has been controversy concerning the grade of tumor that is
acceptable for Al designation. Some investigators have excluded tumors with a combined Gleason score > 4. Others
have excluded only tumors with a combined Gleason score >
7.32 Follow-up of patients with stage Al prostate cancer has
revealed a significant, although small, risk of cancer-associated
death. 33 Furthermore, 25% of radical prostatectomy specimens
obtained for stage Al tumors have extensive tumors that are
comparable to stage B tumors in extent.34 Thus, finding Al
tumors now is considered important.
Some investigators have reported that all stage A2 tumors
and 90% of stage A1 cancers can be found by submitting either
5 blocks35 or 12 g of tissue.36 However, it is important to understand that all cancers cannot be identified using this reasoned
approach to sampling. To find virtually all cancers in TURP
specimens requires embedding all tissue.37 The extent of cancer
found in a specimen is proportional to the number of sections
that are submitted and examined. 6
Reporting
Findings
Report percent of currettings involved by cancer? 92% yes
Assign Gleason grade(s)? 82% yes
Assign combined Gleason score? 71% yes
Grade by an alternative system? 35% yes
Volume Fraction of Cancer. Knowledge of specimen volume
fraction that is cancer and the grade of the cancer are essential
for distinguishing stage Al tumors from stage A2 tumors (see
Appendix). The most efficient approach is to express volume
fraction as the percentage of chips that contain cancer. Morphometry, by planimetry, is a more accurate technique for determining volume fraction.35 However, the gain in precision is
minimal compared with the additional time and labor that is
involved in any morphometric analysis.
Grading. The majority of pathologists report tumor grade
using the Gleason system. A substantial minority (35%) use an
alternate grading system. The grading scheme used is of little
importance as long as it is familiar to the clinicians concerned
with the management of the individual patient.
TRANSURETHRAL PROSTATECTOMY
SPECIMENS
Specimen
Handling
Record specimen weight? 100% yes
Embed entire specimen regardless of weight? 11% yes
Histologic
NEEDLE BIOPSY PROSTATE SPECIMENS
Specimen
Handling
Report number and size of specimens? 97% yes
Comment on adequacy of specimen? 69% yes
Vol. 102 • N o . 5
576
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Special Article
BLADBER
RADICAL PROSTATECTOMY
CASE
GUIDE TO TAKING SECTIONS
NAME
Ink right BLACK, left BLUE or RED
POSTERIOR
#
WEIGHT
orams
Guide to block numbers:
Block 1 - Tumor in Methacarn Fixative
Right - odd numbers
Left - even numbers
ANTERIOR
ANTERIOR
POSTERIOR
POSTERIOR
ANTERIOR
OVERHEAD
VIEW
POSTERIOR
ANTERIOR
LEFT
RIBHT
BLADDER
21
P08TERIOR
NECK
OVERHEAD
VIEW
22
POSTERIOR
POSTERIOR
Identify location of biopsy specimens? 76% yes
Obtain at least 3 levels of each block? 84% yes
Obtain more levels based on clinical data? 45% yes
Nature of Specimens. More than 95% of responding pathologists report the number and size of the biopsy specimens.
Specimen Adequacy. Reporting the nature of tissue in a
biopsy specimen that lacks prostate parenchyma, such as seminal vesicle, fibroadipose tissue, or skeletal muscle, provides
more precise feedback to the clinician than does a report of
"inadequate".
Biopsy Specimen Location(s). Although the majority of pathologists report the location of the biopsy specimen, more
than 20% do not. Location of minimal cancer (ie, unilateral or
regional), is information used by the urologist in deciding on
the nature of the resection (ie, bilateral vs. unilateral nerve
sparing prostatectomy).
Levels of Sections. The majority of pathologists (84%) routinely obtain at least 3 levels of each block. This number of
levels seems to be a reasonable sampling strategy. Half of respondents obtain more levels "based on clinical information."
The yield from obtaining more than 3 levels is unknown. Information that might lead a pathologist to obtain more levels includes both clinical information, such as a previous focus of
low-grade cancer in a given area of the prostate, and pathologic
information, such as previously diagnosed high-grade PIN.
Reporting
Histologic
FIG. I. The figure is a schematic of
one method of completely sampling
and sectioning the prostate. The right
and left lobes are inked with black
and blue ink, respectively. The apex
and bladder neck margins are analyzed by submitting sagittal sections
of the respective en-face coronal sections. Sequential, 3 mm to 4 mm
thick sections parallel to the section
of the apex are taken from the distal
aspect of the specimen to the base of
the seminal vesicles. These sections
are submitted as quadrants following
a systematic numbering scheme (ie,
anterior and right are of lower number than posterior and left, and right
is always an odd number).
Findings
Estimate percentage of tissue containing cancer? 55% yes
Assign Gleason grade(s)? 76% yes
Assign combined Gleason score? 60% yes
Grade by an alternative system? 37% yes
Extent of Carcinoma. Approximately 50% of respondents
report the area fraction that is cancer. In small cancers that are
not of high grade and that are restricted to only one biopsy
specimen, the extent of cancer in the biopsy specimen may
correlate with concurrent tumor extent in the subsequent radical prostatectomy specimen.38 Whether reporting extent of tumor in a biopsy specimen will become generally accepted and
expected diagnostic information currently is unknown.
Grading. As with TURP specimens, most pathologists grade
tumors in needle biopsy specimens. The grade of tumor in a
biopsy specimen may be important for patient management.
Some tumors that have a combined Gleason score of S: 7 have
spread beyond the prostate at the time of resection.3 One relevant observation is that the Gleason score in a biopsy specimen
tends to be lower than that in the subsequent prostatectomy
specimen.39
ITEMS NOT A D D R E S S E D IN THE SURVEY
Some respondents commented on aspects of handling prostate specimens that had not been surveyed in the questionnaire. The following items are of potential clinical and pathologic importance:
Zonal Distribution of Tumor in Radical Prostatectomy Specimen. Some pathologists report the distribution of tumors in the
three zones of the prostate (central, transitional, and peripheral), because origin of a tumor by zone may be of prognostic
significance.38 In practice, it is impossible to identify these
zones with certainty, particularly in the presence of a tumor. 40
Volume of a Tumor in Radical Prostatectomy Specimen.
There is evidence that the volume of a tumor is of prognostic
value. In one series, no tumors with a volume < 4 cc had nodal
A.J.C.P. • November 1994
TRUE
Prostate Gland:
metastases.41 A consensus for a standard method of volume
determination has not yet evolved. Volume is most precisely
determined by a morphometric method, using either planimetry41 or point counting based on overlaid grids.42 However,
the time and labor involved in these approaches will probably
not lead to their wide acceptance. More efficient but less accurate is visual estimation of area fraction that is tumorous. An
estimate of tumor volume can be calculated from the area fraction that is cancer and the weight of the prostate gland.
Analysis of Tumor DNA Content in TURP and Needle
Biopsy Specimens. Some pathologists analyze tumor cell DNA
content in biopsy specimens. There is evidence that DNA
ploidy can predict disease course, survival, and hormonal responsiveness to tumor, particularly in lieu of knowledge of the
pathologic stage.31
Map of Tumor Distribution in Radical Prostatectomy Specimen. Some respondents include a map of tumor distribution in
radical prostatectomy specimens with their reports. Ways to
illustrate tumor distribution include tracing the tumor on either sketches of sections of the prostate gland or upon photocopies of the glass slides (Fig. 1).
Margins ofVas Deferens and Ejaculatory Duct. Some pathologists routinely submit margins of these structures. There is
little documentation of the value of these analyses.
Effects of Therapy on Prostate. Nonsurgical treatments of
prostate carcinoma can significantly affect the histology of
both benign and cancerous prostate tissue. The effects of radiation therapy include a decrease in the ratio of glands to stroma,
atrophy, squamous metaplasia, and vascular changes.43 The
histologic changes associated with androgen deprivation are
similar: a decrease in gland density and size, compression of
gland lumina, increased periglandular fibrous tissue, squamous
metaplasia, and basal cell hyperplasia.44,45 The effect of these
regimens on tumor cytology and grade is variable. In neither
situation can a grade that has prognostic value be determined.
Although identifying carcinoma in a prostate gland that has
been subjected to hormonal therapy, such as androgen blockade, can be difficult, the diagnosis can be reliably made by
different pathologists after a relatively brief training experi-
Acknowledgment. The survey on which this report is based was organized and conducted by the American Society of Clinical Pathologists,
under the direction and sponsorship of the Practice Review Committee
of the Council on Anatomic Pathology.
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PATHOLOGY
Article
Appendix. Staging Systems. 4 7 , 4 8 Staging of patients with
prostate cancer is based upon clinically characterized features
of the cancers. When resected tumors are pathologically
staged, the stage category is indicated as pathologic
by the prefix "p".
Whitmore
(modified)*
Occult (clinically inapparent-not palpable nor
visible by imaging studies)
<5% of specimen
>5% of specimen, or of high grade
Diagnosed in biopsy that was obtained
due to increased serum PSA
Palpable, organ confined (invasion not
beyond capsule)
<1.5 cm,, or < half of one lobe
>1.5 cm, or more than half of one lobe,
but not both lobes
Tumor involves both lobes
Palpable, local extension beyond the prostate
Unilateral extracapsular extension
Bilateral extracapsular extension
Tumor involving one seminal vesicle
Tumor involving both seminal vesicles
Tumor invades adjacent, structure, other
than seminal vesicle
Al
A2
UICC
AJC-f
Tla
Tib
Tlct
Bl
T2a
B2
T2b
T2c
CI
C2
T3a
T3b
T3
T3c
C3
T4
Status of lymph nodes
No nodal metastases
Tumor in a single node, <2 cm greatest
dimension
Tumor in a single node, between 2 and 5
cm diameter
Multiple nodes involved with tumor, or
tumor size within a node >5 cm
NO
Nl
N2
N
* Modified by Jewelt and Prout.
t Endorsed by American Cancer Society. American Joint Comission on Cancer, College of
American Pathologists. FIGO. and UICC.
t Prostate specific antigen.
Stage
Grouping
Assignment of stage to a specific t u m o r is based u p o n both
the features of the primary t u m o r (the " T " category) and upon
the extent of spread of the t u m o r , which is reflected in the
status of the lymph nodes ( " N " ) a n d the presence of distant
metastases ( " M " ) .
Stage 0 T l a
Stage I T l a
Tlb-lc
Stage II T2
Stage IIIT3
Stage IVT4
Any T
Any T
Further
NO
NO
NO
NO
NO
NO
N1-N3
Any N
Commentary
M0
M0
M0
M0
M0
M0
M0
Ml
upon
Low-grade, well differentiated
Grade other than low-grade
Any grade
Any grade
Any grade
Any grade
Any grade
Any grade
the Definition
of Stage
Al:
Distinction between t u m o r stages A1 and A2 is based principally u p o n the area fraction that is t u m o r . Different thresholds
A.J.CP. • November 1994
TRUE
Prostate Gland: Practice Survey
of tumor fraction have been used to distinguish tumors of stage
Al from tumors of stage A2:
a. Less than 3 chips contain tumor (49)
b. Less than 5 chips contain tumor (50)
c. Less than 5% of the chips contain tumor (51)
d. Tumor is confined to one quadrant (52)
Although some investigators rely solely upon the percentage
of tumor in a specimen for distinguishing stage Al tumors
from stage A2 tumors, other investigators exclude from stage
A1 category those tumors that are of higher grade. There is no
unanimity of opinion for this threshold grade (32). Examples of
grades above which a tumor has been excluded from the stage
Al category include:
Tumors with a Mayo grade 3.
Tumors with a combined Gleason score of ^ 7.
Tumors with a combined Gleason score of Si 4-5.
Gleason Grading System9
Tumors are evaluated with respect to how closely the histology of tumor resembles normal, on a scale of 1 (most "nor-
579
mal") to 5. A grade is assigned to both the most abundant
histologic pattern, the "primary pattern", and to the next most
abundant pattern, the "secondary" pattern. The sum of these
two values is the "combined Gleason score". The individual
values of the two patterns do not appear to be clinically important, although there is recent evidence that the absolute volume
of high-grade tumor in a radical prostatectomy specimen may
be of prognostic value.38
Alternative Method for Fixing Radical Prostatectomy
Specimens
Use a relatively large bore needle ie. 12 gauge, attached to a
50 mL syringe and inject buffered formaldehyde under "firm"
pressure through only a small number of puncture sites in each
lobe. Distribute fixative throughout each lobe. The needle
tracts will not be seen histologically. And, when the prostate
gland is subsequently immersed overnight in fixative and processed the second day, the histology should be excellent.