ADENOCARCINOMA OF THE PROSTATE

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ADENOCARCINOMA OF THE PROSTATE

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Title: ADENOCARCINOMA OF THE PROSTATE

1
ADENOCARCINOMA OF PROSTATE
DR Mohammad HosseinSANEI Department of
pathology Isfahan university of medical science
2

. Gross tumor may be identified by examination of
the posterior and posterolateral horseshoe-shaped
peripheral zone of the prostate looking for
asymmetry in size, color, and density of tissue
between right and left halves of the prostate

In more than 85 of prostates, gross tumor will
be identified
Submission of the prostate in this manner will
allow detection of more than 90 of positive
margins, extraprostatic extension, and seminal
vesicle invasion with, on average, a submission
of only 12 to 13 cassettes (see later for
description of lymph node examination

FIGURE 45-3. Gross photograph of benign prostatic
hyperplasia

5
adenocarcinoma

FIGURE 45-66. Gross appearance of adenocarcinoma
of the prostate. Note more solid, homogeneous,
graywhite appearance to carcinoma (left) as
compared with contralateral benign prostate with
a more spongy appearance.

6
Gleason system
7
Gleason system

is based on the glandular pattern of the tumor as
identified at relatively low magnification
cytologic features play no role in the grade of
the tumor

Both the primary (predominant) and the secondary
(second most prevalent) architectural patterns
are identified and assigned a grade from 1 to 5,
with 1 being the most differentiated and 5 being
undifferentiated

Because both the primary and secondary patterns
were considered influential in predicting
prognosis, a combined Gleason grade resulted,
obtained by the addition of the primary and
secondary grades.
If a tumor had only one histologic pattern, then
for uniformity, the primary and secondary scores
were given the same grade

The combined Gleason grades range from 2 (1 1
2), which represents tumors uniformly composed of
Gleason pattern 1 tumor, to 10 (5 5 10),
which represents totally undifferentiated tumors

11
The advantages of the Gleason grading system are

(a) it is easy to learn and apply because it is
based on low-magnification pattern recognition
and (b) it is less time consuming than the
grading systems that examine cytologic features.

Two older studies demonstrated good interobserver
and intraobserver reproducibility with the
Gleason system with agreements to within one
combined Gleason grade of more than 80 and 90,
respectively
However, more recent studies showed only moderate
interobserver reproducibility among academic and
private pathologists

As shown on Gleasons schematic diagram (Fig.
15), there is a continuum of differentiation
between the various Gleason patterns such that
the grade assigned at the extremes of a
particular Gleason pattern may be somewhat
subjective

Another reason for grading discrepancies is the
presence of more than two grades
Gleason's system and most of the other grading
systems were developed predominantly on needle
biopsy and TUR specimens, in which it is uncommon
for more than two grades to be represented.

In prostatectomy specimens, however, tumors with
multiple grades are not infrequent
If more than two grades exist in Gleason's
system, they should be commented on in a note.
The Gleason grade on biopsy material has been
shown to correlate fairly well with that of the
subsequent radical prostatectomy

Two large series comparing radical prostatectomy
specimens and their diagnostic biopsies showed a
correlation to within one combined Gleason grade
in approximately 73 of the cases
The tendency to undergrade needle-biopsy material
results from the minimal amount of tumor in the
needle biopsy and the consequent difficulty in
appreciating either the infiltrative nature of
the tumor or the variability in size and shape of
the neoplastic glands, features that are
characteristic of Gleason pattern 3

An unavoidable cause of discrepant grading
between the biopsy and subsequent prostatectomy
specimen is that due to sampling error by the
needle biopsy
Because in TUR material there is greater sampling
of the prostate and more tissue, the better to
appreciate the overall architecture of the tumor,
the grades assigned to TUR material tend to be
more accurate than those given on needle-biopsy
specimens.

The major weakness of the Gleason grading system
is that, although at both the low and high ends
of the Gleason system we have fairly accurate
predictive ability, the prognosis of the
remaining patients is uncertain

19
The positive lymph node rate for various Gleason
scores is reported as follows

2 to 4, less than 1
5 to 6, 2 to 3
7, 10
8 to 10, 20.

20
Extent of Cancer on Biopsy

There are few data as to how the extent of cancer
on needle biopsy should be recorded
. Our own results show that only the number of
involved cores and bilaterality add to the
prediction of pathologic stage, beyond that
provided by biopsy grade and serum PSA values

21
Extent of Cancer on Biopsy

Nevertheless, it is the convention to provide
additional quantification when diagnosing cancer
on needle biopsy
We record the number of positive cores and the
percentage positivity of each core

22
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23
FIGURE 45-15. Gleason pattern 1 tumor composed of
a circumscribed nodule of uniform, single,
separate, closely packed glands
24
.
FIGURE 45-16. In Gleason pattern 2, although the tumor is still fairly circumscribed, at the edge of the tumor nodule, there can be minimal extension by neoplastic glands into the surrounding nonneoplastic prostate. The glands in pattern 2 are still single and separate, yet they are more loosely arranged and not quite so uniform as in pattern 1. FIGURE 45-16. In Gleason pattern 2, although the tumor is still fairly circumscribed, at the edge of the tumor nodule, there can be minimal extension by neoplastic glands into the surrounding nonneoplastic prostate. The glands in pattern 2 are still single and separate, yet they are more loosely arranged and not quite so uniform as in pattern 1.
25

FIGURE 45-17. Pattern 3 tumor infiltrates in and among the nonneoplastic prostate, with the glands having marked variation in size and shape. Many of the glands are smaller than those seen in pattern 1 or 2 tumors. Smoothly circumscribed cribriform nodules of tumor also are classified as pattern 3. FIGURE 45-17. Pattern 3 tumor infiltrates in and among the nonneoplastic prostate, with the glands having marked variation in size and shape. Many of the glands are smaller than those seen in pattern 1 or 2 tumors. Smoothly circumscribed cribriform nodules of tumor also are classified as pattern 3.
26

FIGURE 45-18. In Gleason pattern 4 tumor, the glands are no longer single and separate, as seen in patterns 1 through 3, and are composed of fused glands with ragged infiltrating edges. If one can mentally draw a circle around well-formed individual glands, then it is Gleason pattern 3. FIGURE 45-18. In Gleason pattern 4 tumor, the glands are no longer single and separate, as seen in patterns 1 through 3, and are composed of fused glands with ragged infiltrating edges. If one can mentally draw a circle around well-formed individual glands, then it is Gleason pattern 3.
27
.
FIGURE 45-19. The Gleason pattern 5 tumor shows no glandular differentiation with either solid masses of cells or individually infiltrating cells. FIGURE 45-19. The Gleason pattern 5 tumor shows no glandular differentiation with either solid masses of cells or individually infiltrating cells.
28
.
FIGURE 45-21. Adenocarcinoma of the prostate, Gleason grade 3 3 6 on needle biopsy. Note small glands infiltrating in and among larger benign glands. FIGURE 45-21. Adenocarcinoma of the prostate, Gleason grade 3 3 6 on needle biopsy. Note small glands infiltrating in and among larger benign glands.
29

FIGURE 45-22. Adenocarcinoma, Gleason grade 3 4 7. Note well-formed glands consistent with Gleason pattern 3 (lower right) compared with fused glands of Gleason pattern 4 (upper left). FIGURE 45-22. Adenocarcinoma, Gleason grade 3 4 7. Note well-formed glands consistent with Gleason pattern 3 (lower right) compared with fused glands of Gleason pattern 4 (upper left).
30

FIGURE 45-24. Adenocarcinoma of the prostate, Gleason grade 3 3 6. Infiltrative appearance among benign glands is diagnostic of cancer. FIGURE 45-24. Adenocarcinoma of the prostate, Gleason grade 3 3 6. Infiltrative appearance among benign glands is diagnostic of cancer.
31

FIGURE 45-20. Gleason pattern 5 with central
comedonecrosis.

32
Microscopic Diagnosis
33

The types of difficulty encountered in diagnosing
adenocarcinoma of the prostate depend on whether
we are evaluating needle-biopsy material or TUR
resection specimens
. In needle-biopsy material, there exists the
risk of overdiagnosing atrophic glands and
seminal vesicles as carcinoma, as well as
underdiagnosing adenocarcinoma because of the
limited amount of tumor present.

Atrophic glands stand out at scanning
magnification because of their open lumina lined
by cells with a high nuclear-to-cytoplasmic
ratio, resulting in a very basophilic appearance
to the glands

35
The most useful criteria to establish a diagnosis
of atrophic adenocarcinoma are

(a) an infiltrative pattern of growth,
(b) the presence of macronucleoli
(c) increased nuclear size
(d) the presence of adjacent, nonatrophic cancer
An important feature, which may not necessarily
be readily identifiable in atrophic glands, is
the presence of a basal cell layer

FIGURE 45-30. Atrophic adenocarcinoma of the
prostate with very prominent nucleoli.

FIGURE 45-31. Atrophic adenocarcinoma of the
prostate (left) merging with more typical
adenocarcinoma of the prostate (right).

FIGURE 45-43. Needle biopsy showing glands with
partial atrophy.

FIGURE 45-41. Needle biopsy showing sclerotic
atrophy with an infiltrative appearance.

The use of keratin antibodies specific for
prostatic basal cells is helpful in identifying
basal cells in atrophic glands
Another potential source of overdiagnosing
prostatic adenocarcinoma is the presence of
seminal vesicles or seminal vesicletype
epithelium on needle biopsy

The presence of prominent lipofuscin granules
within seminal vesicle epithelium is an important
diagnostic aid
Despite their marked enlargement and often
bizarre shapes, these cells lack mitotic activity
and commonly appear degenerated in nature,
similar to what is seen with radiation atypia

FIGURE 45-44. Needle biopsy of seminal vesicles
showing multiple small glands arranged around
central lumen.

FIGURE 45-45. Scattered markedly atypical nuclei
with a degenerative appearance, characteristic of
seminal vesicle epithelium. Prominent lipofuscin
pigment noted.

Seminal vesicle-type epithelium is also PSAP (not
always PSA) negative and high-molecular-weight
cytokeratin can distinguish between the two
tissue types.
A more common problem with the evaluation of
needle-biopsy material from the prostate is not
the overdiagnosis of carcinoma, but rather the
underdiagnosis of carcinoma as a result of the
limited amount of tumor present

45
underdiagnosis of carcinoma

An unusual pattern of adenocarcinoma seen on
needle biopsy that may be underdiagnosed involves
cancers with voluminous xanthomatous cytoplasm in
which nuclei are small and often show no or
minimal atypia, termed foamy gland carcinoma
intraluminal pink homogeneous secretions are
often present

46
underdiagnosis of carcinoma

The identification of this type of cancer hinges
on recognizing that the cytoplasm is unique to
malignant glands, and the small, round nuclei are
more uniformly hyperchromatic and round without a
hint of a basal cell layer, as compared with
normal glands.

FIGURE 45-32. Adenocarcinoma of the prostate with
abundant xanthomatous cytoplasm, small nuclei,
and pink homogeneous intraluminal secretions.
Compare cytoplasm with more typical
adenocarcinoma (right).

FIGURE 45-55. Xanthoma of the prostate.

49
recognition of prostatic cancer

The recognition of prostatic cancer in these
cases rests on both the architectural
abnormalities resulting from the infiltrating
neoplastic glands and the cytologic features of
the neoplastic epithelium
Although the finding of prominent nucleoli in the
small glands is reassuring, it is not necessary
to diagnose carcinoma. Often, only significant
nuclear enlargement discriminates cancer from the
surrounding benign glands

50

FIGURE 45-25. Neoplastic glands composed of a single layer of cells with enlarged nuclei, some with prominent nucleoli. FIGURE 45-25. Neoplastic glands composed of a single layer of cells with enlarged nuclei, some with prominent nucleoli.
51

FIGURE 45-34. Low-grade adenocarcinoma showing
large back-to-back glands in which the luminal
surfaces have an even straight edge without
papillary infolding, and cells have abundant
cytoplasm. Stains for 34be12 were negative in
these glands

FIGURE 45-33. Pseudohyperplastic adenocarcinoma
where cancerous glands are relatively large and
have papillary infolding architecturally
resembling benign glands or high-grade prostatic
intraepithelial neoplasia (PIN). The glands show
prominent nucleoli, yet are too crowded to
represent high-grade PIN. Stains for high
molecular weight cytokeratin were also negative
in the entire focus, in support of the diagnosis
of cancer.

). Intraluminal pink acellular dense secretions
or blue-tinged mucinous secretions seen in small
suggestive glands may be additional features that
help to differentiate malignant from benign
glands, given their greater frequency in
malignancy
). If the architectural or cytologic features or
both are diagnostic of cancer, searching for a
basal cell layer tends to confound rather than to
help.

54
.
FIGURE 45-27. Adenocarcinoma of the prostate with blue-tinged mucinous secretions seen on hematoxylin and eosinstained section. FIGURE 45-27. Adenocarcinoma of the prostate with blue-tinged mucinous secretions seen on hematoxylin and eosinstained section.
55
.
FIGURE 45-28. Adenocarcinoma with small glands with enlarged nuclei, crystalloids, and mitotic figure. Adjacent benign prostate glands contain lipofuscin pigment. FIGURE 45-28. Adenocarcinoma with small glands with enlarged nuclei, crystalloids, and mitotic figure. Adjacent benign prostate glands contain lipofuscin pigment.
56
.
FIGURE 45-35. Adenocarcinoma of the prostate with perineural invasion. Occasionally glands with perineural invasion will show papillary infolding, mimicking a benign gland. FIGURE 45-35. Adenocarcinoma of the prostate with perineural invasion. Occasionally glands with perineural invasion will show papillary infolding, mimicking a benign gland.
57
FIGURE 45-38. Perineural indentation by benign
prostate gland
58
.
FIGURE 45-37. Glomerulations with adenocarcinoma showing cribriform formation that is not transluminal, resembling glomeruli. FIGURE 45-37. Glomerulations with adenocarcinoma showing cribriform formation that is not transluminal, resembling glomeruli.
59

FIGURE 45-49. Basal cellspecific cytokeratin
(34BE12) immunostaining demonstrates a patchy
basal cell layer surrounding some of the glands
within a nodule of adenosis.

60

FIGURE 45-49. Basal cellspecific cytokeratin (34BE12) immunostaining demonstrates no basal cell in small gland consist with adenocarcinom. FIGURE 45-49. Basal cellspecific cytokeratin (34BE12) immunostaining demonstrates no basal cell in small gland consist with adenocarcinom.
61

Also, basal cells in benign glands tend to stain
uniformly and intensely, in contrast to the
patchy staining in adenosis
Adenosis tends to be located centrally within the
gland, such that it is most commonly seen in TUR
resection specimens

In TUR resection specimens, we usually have an
entire nodule of adenosis to evaluate it would
be highly unlikely for the entire focus to show
no immunoreactivity with basal cellspecific
cytokeratin
. Consequently, the lack of basal cellspecific
cytokeratin staining in a nodule of glands in
which we are deciding between adenosis and
low-grade adenocarcinoma is highly supportive of
the diagnosis of adenocarcinoma

FIGURE 45-52. Sclerosing adenosis showing glands
of adenosis (left) merging with cytologically
similar cords and spindle cells (right).

FIGURE 45-94. Basal cell hyperplasia
characterized by glandular structures with
multiple cell layers.

FIGURE 45-95. Basal cell hyperplasia with
prominent nucleoli and mitotic figures.

Table 2. Helpful features in the needle-biopsy
diagnosis of adenocarcinoma on HE-stained
sections
Features diagnostic of adenocarcinoma
Perineural invasion
Mucinous fibroplasia (collagenous micronodules)
Glomerulations
Features favoring the diagnosis of cancer
(diagnosis based on a constellation of features)
Architecture
Small glands in between larger benign glands
Crowded glands that stand out from adjacent
benign glands
Cytology
Prominent nucleoli
Nuclear enlargement
Hyperchromatic nuclei
Amphophilic cytoplasm
Mitotic figures
Luminal contents
Blue mucinous secretions

PROSTATIC INTRAEPITHELIAL NEOPLASIA as

68
Roman bridge

FIGURE 45-64. Central zone with Roman bridge and
cribriform formation. Note lack of nuclear atypia.

69

FIGURE 45-56. Low-grade prostatic intraepithelial neoplasia with slight enlargement of nuclei and stratification, yet no prominent nucleoli. FIGURE 45-56. Low-grade prostatic intraepithelial neoplasia with slight enlargement of nuclei and stratification, yet no prominent nucleoli.
70

FIGURE 45-61. High-grade prostatic
intraepithelial neoplasia (PIN) (left) with only
a few atypical small glands. We cannot
distinguish between PIN and adjacent infiltrating
carcinoma versus outpouchings or tangential
sections off of high-grade PIN.

71

FIGURE 45-57. Low magnification of high-grade prostatic intraepithelial neoplasia, showing glands with a normal architectural pattern yet a basophilic appearance. FIGURE 45-57. Low magnification of high-grade prostatic intraepithelial neoplasia, showing glands with a normal architectural pattern yet a basophilic appearance.
72
.
FIGURE 45-58. Basophilia of gland with high-grade prostatic intraepithelial neoplasia (PIN) owing to nuclear stratification and high nuclear-to-cytoplasmic ratio with large nuclei and prominent nucleoli. Note in left portion of field within a single gland, the abrupt transition between benign-appearing nuclei and PIN nuclei. FIGURE 45-58. Basophilia of gland with high-grade prostatic intraepithelial neoplasia (PIN) owing to nuclear stratification and high nuclear-to-cytoplasmic ratio with large nuclei and prominent nucleoli. Note in left portion of field within a single gland, the abrupt transition between benign-appearing nuclei and PIN nuclei.
73

FIGURE 45-59. Prominent tall papillary tufts within high-grade prostatic intraepithelial neoplasia (PIN). Nuclei appear more benign toward the luminal surface of the papillary projections. Note large nuclei with frequent nucleoli, diagnostic of high-grade PIN, toward the edge of the gland up against the basement membrane. FIGURE 45-59. Prominent tall papillary tufts within high-grade prostatic intraepithelial neoplasia (PIN). Nuclei appear more benign toward the luminal surface of the papillary projections. Note large nuclei with frequent nucleoli, diagnostic of high-grade PIN, toward the edge of the gland up against the basement membrane.
74

FIGURE 45-60. High-grade prostatic intraepithelial neoplasia with cribriform pattern. FIGURE 45-60. High-grade prostatic intraepithelial neoplasia with cribriform pattern.
75

FIGURE 45-71. Adenocarcinoma of the prostate
invading the seminal vesicles.

FIGURE 45-80. Adenocarcinoma after hormone
therapy, showing tumor cells with pyknotic nuclei
and foamy cytoplasm resembling histiocytes.

FIGURE 45-81. Benign prostate glands showing
radiation effect.

FIGURE 45-82. Mucinous adenocarcinoma of the
prostate with glands of adenocarcinoma floating
within mucin.

FIGURE 45-83. Adenocarcinoma of the prostate with
signet ring celllike features.

FIGURE 45-84. Adenocarcinoma of the prostate with
fine, eosinophilic cytoplasmic granules
corresponding to neuroendocrine differentiation.
Immunostaining revealed strong positivity with
human chorionic gonadotropin.

FIGURE 45-85. Small cell carcinoma of the
prostate admixed with ordinary adenocarcinoma of
the prostate (right).

FIGURE 45-86. Papillary prostatic duct
adenocarcinoma showing tall pseudostratified
columnar epithelium with dark cytoplasm.

FIGURE 45-87. Cribriform pattern of prostatic
duct adenocarcinoma.

FIGURE 45-88. Adenosquamous carcinoma.

FIGURE 45-89. Infiltrating transitional cell
carcinoma in the prostate. Cells are more
pleomorphic than is poorly differentiated
prostate adenocarcinoma.

FIGURE 45-90. Intraductal transitional cell
carcinoma with rounded malignant urothelial
nests. Associated stromal invasion characterized
by cords and single cells of infiltrating
transitional cell carcinoma.