Donald F. Gleason in 1966 created a unique grading system
for prostatic carcinoma
1 (Figure
1). In 1974 and 1977, he
provided additional comments concerning the application
of the Gleason system
2-3. Since its first proposal, the
Gleason grading system has been accepted as one of the
most powerful prognostic indicators in prostate cancer
throughout the world.
Gleason grading depends solely on architectural patterns
of the tumor. The grade is defined as the sum of the two
most common grade patterns and reported as the Gleason
score. Synonyms for “Gleason score” are “combined
Gleason grade” and “Gleason sum”. Both the primary
(predominant) and the secondary (second most prevalent)
architectural patterns are identified and assigned a number
from 1 to 5, being 1 the most differentiated and 5 the least
differentiated. When a tumor has only one histologic pattern,
the primary and secondary patterns are given the same
number. Thus Gleason scores range from 2 (1+1=2), which
are the tumors uniformly composed of Gleason pattern 1,
to 10 (5+5=10), which represents totally undifferentiated
tumors. A tumor that shows predominant Gleason pattern
3 with a lesser quantity of Gleason pattern 5 has a Gleason
score of 8 (3+5=8), as does a tumor that is predominantly
Gleason pattern 5 with a lesser amount of Gleason pattern
3 (5+3=8).
Both primary and secondary Gleason patterns have to be
assigned even for the cancer focus that is minute on a needle
biopsy. When the pathologist signs out a case as “Gleason
grade 4” to mean that the tumor is high grade (i.e. Gleason
pattern 4), the urologist may interpret it as Gleason score of
4 (i.e. Gleason grade 2+2=4). By assigning both a primary
and secondary pattern even in cases with a limited amount
of cancer, the urologists will be prevented from confusion.
Value of Gleason Scoring
While the decision for the definitive therapy of prostatic
carcinoma is based on multiple factors including the clinical
stage, patient age, preoperative PSA, patients general health,
life expectancy, etc., the Gleason grade in needle biopsy is
another variable that can potentially help stratify patients
into different therapeutic modalities. Gleason score on
biopsy correlates with all of the important pathologic
parameters at radical prostatectomy (pathologic stage,
tumor volume, inked margin status, lymph node metastasis),
with prognosis after radical prostatectomy (recurrence and
survival), and with outcome following radiotherapy as well
as serum pre-op PSA levels and many molecular markers.
4-8. Gleason score 7 tumors behave significantly worse
than Gleason score 5-6 tumors and do better than Gleason
score 8-10 tumors. If one wants to combine Gleason
scores on biopsies into groups the following categorization
is reasonable: Gleason score 2-4 (well-differentiated);
Gleason score 5-6 (moderately differentiated); Gleason
score 7 (moderately-poorly differentiated); and Gleason
8-10 (poorly differentiated). However, one loses some
discrimination by combining Gleason scores. For example,
Gleason score 4+4=8 has a better prognosis than Gleason
score 5+5=10. Grade is one of the most influential factors
used to determine treatment for prostate cancer. Whereas
some younger men with limited amounts of Gleason score
5-6 on needle biopsy and low PSA values may be followed
expectantly (“watchful waiting”), almost all men with
Gleason score 7 tumor will be treated more definitively 9-10 . The presence of a Gleason pattern 4 (score ≥7) dictates,
in most cases, prompt intervention by at least one of the
many therapeutic modalities available for prostate cancer.
Based on 703 patients with clinically localized prostate
cancer, Partin et al. showed that combinations of 3 variables
(serum PSA, Gleason score and clinical stage) allowed for
construction of probability plots and nomograms, which
assist in the preoperative prediction of final pathologic
stage for patients with clinically localized prostate cancer
11. Clinicians use the grade as part of the nomograms
to predict tumor extent, post-radical prostatectomy
progression, and post-radiotherapy failure 12-16.
These nomograms factoring preoperative variables such
as Gleason score, clinical stage, serum PSA and more
recently the extent of cancer on biopsy calculate the risk of
extraprostatic disease, seminal vesicle invasion, and lymph
node metastases. A man with a Gleason score 6 tumor may
be a candidate for interstitial radiotherapy (brachytherapy)
as a monotherapy. However, if this man had a Gleason
score 7 tumor, due to a greater probability of extra-prostatic
extension by the neoplasm, he would most likely be given
external beam radiotherapy with or without brachytherapy,
as radioactive seeds may not effectively treat extra-prostatic
disease. Gleason score 7 tumor can also be offered radical
prostatectomy as a treatment option. An accurate diagnosis
of Gleason scores 8 and above is also critical for patient
management. For a man with a Gleason score ≥ 8 cancer
on biopsy, surgery may not be preferable treatment choice,
depending on the extent of tumor and other clinical factors,
due to the higher probability of extraprostatic extension,
seminal vesicle or lymph node involvement. The patients
with Gleason score 8-10 may benefit more from radiation
to the prostate rather than radical prostatectomy.
Another use of the nomograms, which factor in the needle
biopsy grade, is to predict the likelihood of lymph node
metastases. In a man with a biopsy Gleason score of 6,
a normal digital rectal examination, and a serum PSA
value of less than 10 ng/ml, the risk of having lymph node
metastases is so low that some urologists might leave out
lymphadenectomy at the time of radical prostatectomy. On
the other hand, the presence of Gleason score 8-10 may
prompt intraoperative evaluation of pelvic lymph nodes
by frozen sectioning so that positive node(s) may abort a
prostatectomy while negative result at frozen section may
allow for the procedure to be completed. Thus, accurate
Gleason scoring is critical for correct patient management.
Gleason Patterns in Prostatic Adenocarcinoma
As described by Gleason, the grading of prostate carcinoma
has to be performed under low magnification (4x or 10x
objective) 3. One should not initially use the 20x or 40x
objectives to look for rare fused glands or a few individual
cells seen only at higher power which would lead to an
overdiagnosis of high Gleason patterns.
Gleason Pattern 1
Gleason pattern 1 tumor is a circumscribed nodule
composed of uniform, single, separate, closely packed glands
(Figure 2). Gland spacing usually does not exceed one
gland diameter. Gleason pattern 1 is so uncommon on any
prostate specimen that its existence is now questioned. A
Gleason score of 1+1=2 must be considered as an extremely
rare exception regardless of the type of specimen. The
Gleason system predated the use of immunohistochemistry.
It is likely that with immunostaining for basal cells many of
Gleason’s original 1+1=2 adenocarcinomas of the prostate
would today be regarded as adenosis (atypical adenomatous
hyperplasia).
Gleason Pattern 2
In Gleason pattern 2, the tumor is still fairly circumscribed,
however at the edge of the tumor nodule there can be
minimal extension by neoplastic glands into the surrounding
non-neoplastic prostate (Figure 3). The glands are more
loosely arranged and not quite as uniform in comparison
with Gleason pattern 1. The Gleason pattern 1 and Gleason
pattern 2 glands tend to be larger than intermediate grade
carcinomas. Contrary to the original Gleason system,
cribriform glands are not allowed in pattern 2. Typically,
both Gleason pattern 1 and pattern 2 carcinomas have
abundant pale eosinophilic cytoplasm.
Gleason Pattern 3
The vast majority of Gleason pattern 3 is composed of
single glands that show marked variation in size and shape
(Figure 4). The neoplastic gland size is usually smaller than
seen in Gleason pattern 1 or 2. Gleason pattern 3 tumor
infiltrates in between non-neoplastic prostate acini (Figure
5). A disagreement with the original Gleason classification
system is that “individual cells” are not allowed within
Gleason pattern 3. In contrast to Gleason pattern 4, the
glands in Gleason pattern 3 are distinct units so that one
can mentally draw a circle around well-formed individual
glands. Gleason grading as stated above has to be applied
at low power objective; the presence of a few poorly formed
glands at high power is still consistent with Gleason pattern
3.
A controversial area in the Gleason system is cribriform
Gleason pattern 3. This issue will be discussed below.
Gleason Pattern 4
Pattern 4 has become significantly expanded beyond
Gleason’s original description of tumors with clear
cytoplasm that resembled renal cell carcinoma. Gleason
pattern 4 today consists of large irregular cribriform glands
(Figure 6) or fused, ill-defined glands with poorly formed
glandular lumina (Figure 7). Glands are no longer single and
separate as seen in patterns 1 to 3. It must be remembered
that a tangential section of Gleason pattern 3 may produce
a minute cluster that gives false impression of ill-defined
glands with inconspicuous lumina, and thus may lead to
misdiagnosis as Gleason pattern 4. Very small, but still well
formed glands are within the spectrum of Gleason pattern
3.
Hypernephromatoid pattern is an uncommon variant of
Gleason pattern 4 (Figure 8). Here, tumor is composed of clear
cells and reminds renal cell carcinoma microscopically.
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Figure 4: Prostatic adenocarcinoma - Gleason pattern 3 (A: H&E, x200; B: H&E, x400). |
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Figure 5: Prostatic adenocarcinoma - Gleason pattern 3. Neoplastic acini infiltrating in-between benign prostatic glands (H&E, x100). |
Gleason Pattern 5
In Gleason pattern 5, tumor shows no glandular
differentiation. Instead it is composed of solid sheets, cords,
trabeculae or single cells (Figures 9,10). Cribriform or
solid nests of tumor with central comedonecrosis are also
classified under Gleason pattern 5. One must be stringent as
to the definition of comedonecrosis. Luminal eosinophilic
secretions may be misinterpreted as comedonecrosis. The
presence of intraluminal necrotic cells and/or karyorrhexis
is required especially in the setting of cribriform glands.
Tumors with comedonecrosis generally have high nuclear
grade often with brisk mitotic activity. Gleason stated that
“A small focus of disorganized cells did not change a pattern 3 or 4 tumor to pattern 5”.
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Figure 6: Large cribriform glands of Gleason pattern 4 prostatic adenocarcinoma (A: H&E, x100; B: H&E, x200). |
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Figure 7: Incompletely formed abortive glands in pattern 4 prostatic adenocarcinoma (H&E, x400). |
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Figure 8: Hypernephromatoid prostatic adenocarcinoma, a form of Gleason pattern 4 (H&E, x400). |
Modifications in Gleason System
Since the introduction of Gleason grading system, many
aspects of prostate cancer have changed, including the use of
PSA testing, transrectal ultrasound-guided prostate needle
biopsy with greater sampling, immunohistochemistry
for basal cells changing the classification of prostate
cancer, and discovery of new prostate cancer variants (ie
pseudohyperplastic, foamy gland, mucinous, ductal). These striking changes in prostate cancer created a need for revision of the Gleason grading system. Over the years several modifications have been proposed and certain aspects of the Gleason system are interpreted differently in surgical pathology practice today than its original description. A consensus conference of international experts in urologic pathology was recently convened to update the Gleason
grading system. 80 urological pathologists from around
the world gathered in a meeting at the United States and
Canadian Academy of Pathology convention in 2005 17.
They updated Gleason grading system based on data in
the literature (Figure 11). In areas where there was either a
lack of data or scant information as to the optimal method
of grading, the consensus was based on personal and
institutional experience with a large number of cases.
Below we list the major modifications to original Gleason
system, mainly in reference to ISUP-2005 consensus
conference outlines.
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Figure 9: Solid islands of tumor cells with no gland formation, Gleason pattern 5 (H&E, x200). |
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Figure 10: Gleason pattern 5. Neoplastic cells infiltrating in the stroma singly or in cords and trabeculae (H&E, x400). |
Recommendations of reporting of the Gleason score in needle biopsies
Gleason scores for each recognizable core have to reported
separately irrespective of whether the cores are individually
submitted (in individual container signifying specific
anatomic location, or submitted together (more than one
core, possibly sampling different areas of the prostate).
Assigning a global (composite) score is optional and left to
the pathologist.
When there are multiple cores per container, they often
fragment. If tissue fragmentation makes grading of individual
cores difficult, the effort should be exerted to identify and
provide information on the core with the highest Gleason
score. When the cores are extremely fragmented, it becomes
impossible or potentially misleading to give a Gleason score
on small tissue pieces. In these cases where one cannot be
sure if the tumor fragments belong to one intact core, only
an overall score for that container must be given.
Gleason score 3 - 4 adenocarcinoma in needle biopsy - an extremely rare diagnosis
A Gleason score 3 or 4 should be made “rarely, if ever”
on needle biopsy. Such a diagnosis is usually incorrect
because: 1) There is poor interobserver reproducibility
even amongst urologic pathology experts; 2) The radical
prostatectomy show a higher Gleason grade in almost all
cases at resection; and 3) a diagnosis of Gleason score 3-4 may potentially misguide clinicians and lead patients to
under-treatment or counseling as to having indolent tumor
18-19. The major microscopic limitation for rendering
a diagnosis of Gleason score 4 on needle biopsy is that the
entire edge of the lesion cannot be visualized to determine
if it is completely circumscribed. Consequently, majority
of the lesions that appear to be very low grade on needle
biopsies are diagnosed by urological pathologists as Gleason
score 2+3=5 or 3+2=5.
Low grade prostate cancers (Gleason score 3-4
adenocarcinomas) do exist and may be diagnosed on
TURP (transurethral resection of prostate). However they
are rarely seen on needle biopsy because well differentiated
cancers are predominantly located anteriorly in the prostate
within the transition zone and they tend to be small.
Tertiary pattern in needle biopsies
The typical scenario with tertiary patterns on biopsy
is related to a tumor with patterns 3, 4, and 5 in various
proportions. As being different than radical prostatectomy,
these tumors on needle biopsy should not be graded simply
by summing the primary and secondary pattern with a note
relating to the tertiary pattern. The tables and nomograms
clinicians use, incorporate the Gleason score with no regard
to a tertiary pattern mentioned in a note. When the worst
Gleason grade is the tertiary pattern, it should influence
the final Gleason score and must replace the secondary
grade in the Gleason score calculation formula. Example:
a case with primary Gleason pattern 3, secondary pattern
4, and tertiary pattern 5 should be assigned a Gleason score
of 8 (3+5=8) (the primary pattern + the highest grade =
score). The rationale is that the presence of both Gleason
patterns 4 or 5 on needle biopsy most likely indicates an
overall high grade tumor, and that its limited extent reflects
a sampling issue. In cases where three patterns consist of
grades 2, 3, and 4, one should ignore the pattern 2 and the
biopsy would be called Gleason score 3+4=7 or Gleason
score 4+3=7, depending on whether pattern 3 or pattern 4
is more prevalent.
Tertiary pattern in radical prostatectomies
In the radical prostatectomy, the approach to the tertiary
pattern is not the same with that applied on needle biopsy,
since the entire nodule will be available for examination.
The consensus conference has recommended that
pathologists assign the Gleason score based on the primary
and secondary patterns with a comment as to the tertiary
pattern.
A difference between tertiary patterns on needle biopsy and
prostatectomy exists for the definition of “tertiary” patterns.
“Tertiary” on needle biopsy means simply the presence
of a tumor grade pattern that is the third most common.
On the other hand, the definition of tertiary pattern in
terms of its extent is controversial in radical prostatectomy
specimens. The authors of this article describe the tertiary
pattern on radical prostatectomy as “the presence of a third
component of a Gleason pattern higher than the primary
and secondary grades, where the tertiary component is
visually estimated to be <5% of the whole tumor”. When
the 3rd most common component is the highest grade and
occupies >5% of the tumor, we record it as the secondary
pattern. The prognosis of a tumor with a large amount of
tertiary high grade carcinoma is not analogous to cases
where the tertiary component is much more limited.
When a tumor has a sizeable (>5%) amount of high grade
tumor, it is reasonable to consider that this highest grade
component should be factored into the Gleason score itself
and not counted as only a tertiary component. However,
this definition is not universally accepted.
The consensus conference recommends that one should
assign a separate Gleason score to each dominant tumor
nodule; the dominant nodule with the highest stage and
highest grade is designated as the “index tumor”.
Reporting secondary patterns of higher grade when present to a limited extent in needle biopsies
Whatever the quantity of a high grade pattern detected on
a needle biopsy, it should be included within the Gleason
score. Example: A needle biopsy which is involved by
cancer with 98% Gleason pattern 3 and 2% Gleason pattern
4 would be diagnosed as Gleason score 3+4=7. The rationale
for this is: even a small amount of high grade tumor sampled
on needle biopsy will most likely indicate a more significant
amount of high grade tumor within the prostate.
Reporting secondary patterns of lower grade when present to a limited extent in needle biopsies
In the setting of high grade cancer, lower grade patterns
must be ignored if they occupy less than 5% of the tumor
area. Example: A biopsy core, 100% involved by cancer,
with 98% Gleason pattern 4 and 2% Gleason pattern 3
would be diagnosed as Gleason score 4+4=8. The same 5%
cut off rule for excluding lower grade cancer also applies for
prostatic carcinomas detected in transurethral resections.
Percent pattern 4-5
The value of information regarding the percentage pattern
4/5 both on biopsy or TURP is controversial. Percent pattern
4/5 has been found only very predictive for prognosis in
radical prostatectomy specimens at the extremes of the
percentages 20. Classifying tumors based on the percent
pattern 4-5 is not more predictive than Gleason score 2-4,
5-6, 3+4, 4+3, or 8-10. Consequently, percent pattern 4-5
is not required or recommended as a method of Gleason
grading. It remains optional if one wants to include this
information in addition to the routine Gleason score.
Cribriform carcinoma behaves more like Gleason pattern 4 than Gleason 3
The cribriform pattern described in Gleason’s original
schema as pattern 2 and 3 would today be considered higher
grade. Many of the cases in 1966 diagnosed as cribriform
prostate carcinoma would probably be referred to as
cribriform high grade prostatic intraepithelial neoplasia
today, if labeled with basal cell markers 21. Most cancer
in prostate with cribriform architecture is Gleason pattern 4
rather than 3 by consensus conference criteria.
Urological pathologists require extremely stringent criteria
for the diagnosis of cribriform pattern 3. They have to be
rounded, well circumscribed glands within the same size
range of normal glands. Even slight irregularities of the outer
border of cribriform glands typically results in upgrading
as pattern 4. Some experts additionally require for pattern
3 uniformly spaced lumina and that the cellular bridges
within the cribriform glands are of uniform thickness and
no thicker than the width of the luminal spaces. Thus,
only rare cribriform lesions can satisfy diagnostic criteria
for cribriform pattern 3 while the vast majority will be
designated as Gleason pattern 4.
The authors of this review believe that Gleason cribriform
pattern 3 carcinoma should almost never be diagnosed. This
is based on: 1) the rarity of even candidates for cribriform
Gleason pattern 3; 2) within these rare candidates, the
lack of interobserver reproducibility amongst experts on
assessing the diagnostic criteria proposed to distinguish
cribriform Gleason pattern 4 from Gleason pattern 3;
3) candidate cribriform pattern 3 cancers almost always
occur in association with typical Gleason pattern 4 cancer
elsewhere in the case; and 4) conceptually, one would
expect the change in grade from pattern 3 to pattern 4 to be
reflected in a distinct architectural paradigm shift, rather
than merely a subjective continuum of differences in size,
shape and contour of cribriform glands. Diagnosing all
cribriform prostate cancer as Gleason pattern 4 will remove
any elements of subjectivity in the assessment of cribriform
prostate cancer glands, by this way general pathologists’
grading of these lesions will now better correlate with
genitourinary pathologists, and genitourinary pathologists
will better agree with each other.
Gleason grading of carcinoma with glomerulations on needle
biopsy remains controversial 22. Glomerulations are
dilated glands containing intraluminal cribriform structures
with a single point of attachment, resembling a renal
glomerulus (Figure 12). On a biopsy, they are considered
pathognomonic for invasive prostate carcinoma. Some
urological pathologists do not assign a grade to glomeruloid
patterns and rather just grade the surrounding tumor.
According to some experts for the rare case where the entire
tumor is composed of glomeruloid glands, a grade of 3+3=6
is assigned as long as the glomeruloid structures are small.
Larger glomeruloid structures are uniformly accepted by
urological pathologists as Gleason pattern 4. Other experts
in the field feel that all glomeruloid structures should be
assigned a Gleason pattern 4. In a recent study by TL Lotan
and JI Epstein on 45 prostate needle biopsies containing
carcinoma with glomeruloid features, glomerulations have
been found overwhelmingly associated with Gleason pattern
4 or higher grade carcinoma, both on the same core, as well
as on additional cores in the same case 23. Authors have
observed transitions between small glomerulations, large
glomeruloid structures, and cribriform pattern 4 cancer
in several cases. This data suggests that glomerulations
represent an early stage of cribriform pattern 4 cancer and
until follow-up data is available, are best graded as Gleason
pattern 4.
Grading after therapy (radiation or androgen deprivation)
Tumors showing treatment effect of radiotherapy or
hormone depletion are atrophic and shrunken; glands
are closely packed and artificially appear to be fused or
in cords; or single vacuolated histiocyte like tumor cells
are prevalent. These features give deceptive impression of
Gleason pattern 4 or 5 to the tumor 24. At this time of
the clinical course of the disease, the biologic potency or
tumor viability is more critical than the histologic grade of
the tumor, which was presumably assigned at the time of
primary diagnosis. Gleason system is applied only to the
tumor or a part of tumor if it does not reflect prominent
therapy related secondary changes.
Grading histologic variants and variations of prostate cancer
It is obvious that the original Gleason system can not
answer how to grade newly described variants and patterns
of prostatic adenocarcinoma. Although being not a formal
approach, the Gleason system principles can be extrapolated
and employed in the grading of histologic variants of
prostate cancer to fill in this defect. The outcome of patients
with these variants appears to correlate with the proposed
Gleason system application; although the experience with
many of the variants is limited.
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Figure 12: Prostatic adenocarcinoma with glands forming glomeruloid structures (Immunohistochemistry, anti-34bE12 Ab, x 400). |
approach, the Gleason system principles can be extrapolated
and employed in the grading of histologic variants of
prostate cancer to fill in this defect. The outcome of patients
with these variants appears to correlate with the proposed
Gleason system application; although the experience with
many of the variants is limited.
Vacuoles: Clear vacuoles may occur in adenocarcinomas of
the prostate (Figure 13) and these should be distinguished
from true signet-ring carcinomas containing mucin.
Gleason’s original scheme describes vacuoles under pattern
5 as signet cells. In fact, vacuoles are typically seen within
Gleason pattern 4 cancer. Nevertheless they may also be
observed within Gleason pattern 5 and even Gleason pattern
3 tumors. Tumors should be graded, as if the vacuoles were
not present, by taking only the underlying architectural
pattern into consideration.
Foamy Gland Carcinoma: Similar to way of handling cancers
with vacuoles, the foamy cytoplasm must be disregarded
and grading should be based on the architectural features
of the tumor 25-26. Most foamy gland carcinomas are
Gleason score 3+3=6 (Figure 14). But higher grade foamy
gland carcinomas do exist and should be graded accordingly
in the view of the pattern.
Ductal Adenocarcinoma: Ductal adenocarcinomas of the
prostate most commonly are composed of either papillary
fronds or cribriform structures 27 (Figure 15). Less
frequently, there exists a pattern consisting of individual
glands lined by tall pseudostratified columnar cells
resembling high grade prostatic intraepithelial neoplasia
(PIN-like ductal adenocarcinoma) (Figure 16). Ductal
adenocarcinomas are recognized as being aggressive tumors
with most studies showing comparable behavior to acinar
cancer with a Gleason score 4+4=8. Ductal adenocarcinomas
should be graded as Gleason score 4+4=8, while retaining
the diagnostic term of ductal adenocarcinoma to denote
their unique clinical and pathological findings. This can be
achieved by diagnosing such a tumor as “Prostatic ductal
adenocarcinoma (Gleason score 4+4=8)”. In cases with
mixed ductal and acinar patterns, the ductal patterns should
be assigned Gleason pattern 4. The exception appears to
be for PIN-like ductal adenocarcinomas, which have a
prognosis more similar to Gleason score 6 28.
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Figure 13: Prostatic adenocarcinoma with vacuolated cells (H&E, x 400). |
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Figure 14: Prostatic adenocarcinoma “foamy gland” variant (H&E, x 400). |
Colloid (Mucinous) Carcinoma: The majority of cases
with colloid carcinoma consist of irregular cribriform
glands floating within a mucinous matrix which would
be scored Gleason score 4+4=8 29-30 (Figure 17).
However, uncommonly one may see individual round
discrete glands floating within mucinous pools. There is
no consensus in these cases whether such cases should
be diagnosed as Gleason score 4+4=8 or Gleason score
3+3=6. Some urological pathologists consider by definition
all colloid carcinomas as Gleason score 8, while others
ignore the extracellular mucin and grade the tumor based
on the underlying architectural pattern. Given the lack
of consensus, either method is acceptable for practicing
pathologists until future data indicates which method is
correct.
Small Cell Carcinoma: Small cell carcinoma of the prostate
has unique histological, immunohistochemical, and clinical
features (Figure 18). Comparable to its more common
pulmonary counterpart, chemotherapy is the mainstay of
therapy for prostatic small cell carcinomas in contrast to
hormonal therapy for Gleason pattern 5 prostatic acinar
carcinoma, such that small cell carcinoma should not be
assigned a Gleason grade.
Adenocarcinoma with Focal Mucin Extravasation:
Adenocarcinomas of the prostate with focal mucinous
extravasation (Figure 19) should not be by default graded
as Gleason score 4+4=8. Rather, one should ignore focal
mucinous extravasation and grade the tumor based on
the underlying architecture of the glands. The distinction
between focal mucinous extravasation and colloid
carcinoma is the presence in colloid carcinoma of epithelial
elements floating within the mucinous matrix as opposed to
mucinous extravasation where there is only focal acellular
mucin adjacent to cancer.
Mucinous Fibroplasia (Collagenous Micronodules): The
delicate ingrowth of fibrous tissue seen with mucinous
fibroplasia can result in glands appearing to be fused
resembling cribriform structures although the underlying
architecture is often that of individual discrete rounded
glands invested by loose collagen 31-32 (Figure 20).
One should try to subtract away the mucinous fibroplasia
and grade the tumor based on the underlying glandular
architecture. The majority of these cases would accordingly
be graded as Gleason score 3+3=6.
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Figure 16: PIN-like ductal prostate adenocarcinoma (A: H&E, x100; B: Immunohistochemistry, triple stain, anti-34bE12+antip63+anti-AMACR Ab’s, x100). |
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Figure 18: Small cell carcinoma accompanying conventional prostatic adenocarcinoma (A: H&E, x400; B: H&E, x400). |
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Figure 19: Prostatic adenocarcinoma with mucin extravasation in some glands (H&E, x400). |
Pseudohyperplastic Adenocarcinoma: These cancers should
be graded as Gleason score 3+3=6 with pseudohyperplastic
features 33-34 (Figure 21). This is in large part based on
the recognition that they are most often accompanied by
more ordinary Gleason score 3+3=6 adenocarcinoma.
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Figure 21: Pseudohyperplastic type prostatic adenocarcinoma (H&E, x100). |
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