4. PROSTATITIS
• May be ACUTE, caused by the same pathogens as
those implicated in UTI; lot of neutrophilic
infiltrates
• May be CHRONIC, usually abacterial -There is no
history, however, of recurrent urinary tract
infection. Expressed prostatic secretions contain
more than 10 leukocytes per high-power field,
but bacterial cultures are uniformly negative.
• Or from recurrent or persistent acute infections ;
lymphocytic infiltration
5.
6. GRANULOMATOUS PROSTATITIS
• Can non-TB or TB-related
• Nonspecific granulomatous prostatitis is
relatively common and represents a reaction
to secretions from ruptured prostatic ducts
and acini.
7.
8. Benign Prostatic Hyperplasia
(Nodular Hyperplasia)
• BPH is characterized by proliferation of both
stromal and epithelial elements, with
resultant enlargement of the gland and in
some cases, urinary obstruction.
• It is present in a significant number of men by
the age of 40, and its frequency rises
progressively with age, reaching 90% by the
eighth decade of life.
9. Etiopathogenesis:
– Androgen Related. Conversion of testosterone by enzyme
type 2 5∞-reductase to DHT (dihydrotestosterone). This
enzyme is located entirely on the stromal cell whereby the
stromal cell is responsible for androgen-dependent
prostatic growth.
– DHT binds to androgen receptors both present on the
stromal and epithelial cell; DHT serves as an indirect
mitogen on prostate (stromal) cells. DHT will induce
increase production of several growth factors which will
increase no. of stromal cells
– DHT does not increase cellular epithelial proliferation but
instead inhibits death of the epithelial cells
10. NOTES
• Testosterone (T) diffuses into the prostate epithelial and stromal cell.
T can interact directly with the androgen (steroid) receptors bound to
the promoter region of androgen regulated genes.
• In the stromal cell a majority of T is converted into
dihydrotestosterone (DHT)—a much more potent androgen—which
can act in an autocrine fashion in the stromal cell or in a paracrine
fashion by diffusing into epithelial cells in close proximity.
• DHT produced peripherally, primarily in the skin and liver, can diffuse
into the prostate from the circulation and act in a true endocrine
fashion.
• In some cases the basal cell in the prostate may serve as a DHT
production site, similar to the stromal cell. Autocrine and paracrine
growth factors may also be involved in androgen-dependent
processes within the prostate.
11.
12. Morphology
– BPH virtually always occurs in the inner, transitional zone
of the prostate.
– weighing between 60 and 100 g
– The nodules may appear solid or contain cystic spaces, the
latter corresponding to dilated glandular elements.
– The urethra is usually compressed by the hyperplastic
nodules, often to a narrow slit.
– Microscopically the hyperplastic nodules are composed of
variable proportions of proliferating glandular elements
and fibromuscular stroma. The hyperplastic glands are
lined by tall, columnar epithelial cells and a peripheral
layer of flattened basal cells
15. Nodular hyperplasia of the prostate.
Low-power photomicrograph demonstrates a well-demarcated nodule
at the right of the field with a portion of urethra seen to the left.
18. PIN
• Probable precursor lesion for prostatic carcinoma
• Divided into low grade (mild dyplasia/ grade I) and high grade
(moderate dysplasia/ grade 2 and severe dysplasia/ grade 3)
• High grade PIN is a marker for cancer
• Histologic features:
– on low power, the glands appear large and complex, but more
basophilic (blue) than the normal glands of BPH
– basal cells are present, if only focally
– high power shows prominent nucleoli, nuclear crowding and
pseudostratification (piling up of the nuclei)
– also: the papillary structures at low power turn out to be caused by
the cellular pile-up; in BPH, the papillary structures actuallly have
fibrovascular cores and therefore are true papillae.
•
28. LOW GRADE PIN HIGH GRADE PIN
Architecture Epithelial cell crowding and
stratification, with irregular
spacing.
More crowding &
stratification, 4 pattern-
tufting, cribriform,
micropappilary & flat.
Nuclei slightly enlarged with
variation in size
markedly enlarged
Chromatin Normal Increased density &
clumping
Nucleoli Rarely prominent Frequently large &
prominent, sometimes
multiple.
Basal cell layer Intact May show some
disruption.
Basement membrane Intact Intact
29. CARCINOMA OF THE PROSTATE-
ADENOCARCINOMA
• Adenocarcinoma of the prostate occurs mainly
in men older than 50 years of age.
• It is the most common form of cancer in men,
accounting for 25% of cancer in men in the
United States in 2009.
• It is almost always occur in peripheral zone of
the prostate.
30. Prostatic carcinoma with lots of nucleoli. Presence
of nucleoli distinguishes this from BPH.
Etiology
• Androgens play an important role in prostate
cancer the growth and survival of the cancer cells
depend on the androgens
• The androgens bind to the androgen receptors
and induce the expression of pro-growth and pro-
survival genes.
31. Morphology
• Carcinoma of the Prostate
– Most carcinomas detected clinically are not visible grossly. More
advanced lesions appear as firm, gray-white lesions with ill-
defined margins that infiltrate the adjacent gland.
– On histologic examination, most lesions are moderately
differentiated adenocarcinomas that produce well-defined
glands.
– The glands typically are smaller than benign glands and are lined
by a single uniform layer of cuboidal or low columnar epithelium,
lacking the basal cell layer seen in benign glands.
– In further contrast with benign glands, malignant glands are
crowded together and characteristically lack branching and
papillary infolding. The cytoplasm of the tumor cells ranges from
pale-clear (as in benign glands) to a distinctive amphophilic (dark
purple) appearance. Nuclei are enlarged and often contain one or
more prominent nucleoli
32. Adenocarcinoma of the prostate.
Carcinomatous tissue is seen on the posterior aspect (lower left). Note the
solid whiter tissue of cancer, in contrast with the spongy appearance of the
benign peripheral zone on the contralateral side.
33.
34. Adenocarcinoma of the prostate demonstrating small
glands crowded in between larger benign glands
38. Gleason Grade
• Gleason grading assigns prostatic malignancy a rank from 1
to 5 based on level of dedifferentiation. 1 being best. 1 and 2
are rarely used any more so really a rank from 3-5
• Prostatic cancers are typically heterogenous therefore
receive the sum of their two most common architectural
patterns
– the first number is the most prevalent pattern
– the second number is the second most prevalent pattern (a
minimum of 10% of the cancer volume)
– Denoted the two numbers separately is the Gleason score, i.e. 4+3
– the sum of the two, e.g., 7 is the Gleason sum or grade and is an
excellent predictor of clinical behavior.
– Sometimes a tertiary grade will be mentioned (or used as the
secondary grade) if it is poorly differentiated.
39. • Grades 1-3 consist of small, simple round glands with a single cell
layer surrounded by stroma
– Grade 1: Glands in nodular pattern
– Grade 2: Glands in vaguely rounded configuration
– Grade 3: Glands infiltrating between normal glands
Grade 4: “Fused” glands (no stroma separating some of the glands) or multiple lumens in
a single gland.
Grade 5: No longer attempting to create glands; cells in sheets, clumps, rows, or
individual.
40. OTHERS CARCINOMA
Small Cell Carcinoma
• Small round blue cells in sheets, necrosis, high mitotic rate.
• “Molded” nuclei with inconspicuous nucleoli
• PSA and PAP stains are typically negative and serum PSA levels
may be only mildly elevated. Neuroendocrine stains positive
41. Endometroid Carcinoma
• Typically arises in area of urethra/prostatic utricle
• PSA and PAP positive
• Often grade 3 or 4 but 5 if has necrosis
42. Transitional Cell Carcinoma
• Typically involves large ducts
• More cytologic atypia than prostate cancer
• PSA negative
43. Squamous Cell Carcinoma
• more often in areas where Schistosomiasis is endemic
• Histologic features include keratin pearl formation, intercellular
desmosomes, etc.
44. Rhabdomyosarcoma
• Average age 7 years, rapid growth
• Sheets of small round blue cells with scattered strap cells (tadpole
cells) having cross-striations
45. PROSTATE IMMUNOHISTOLOGY
• Alpha-methylacyl-CoA-racemase (racemase) aka, P504S, is an
enzyme involved in beta-oxidation of branched chain fatty acids.
Moderate to strong staining is seen in prostate cancer and high-
grade PIN, but not in benign prostatic tissue.
• HMW cytokeratin antibody (34ß-E12) stains the cytoplasm of
basal cells of the prostate. Increasing grades of PIN are associated
with progressive disruption of the basal cell layer. Cancer cells
consistently fail to react with this antibody.
• p63 antibody stains the nucleus of basal cells. Basal cell cocktail
(34 ß-E12 and p63) increases the sensitivity of the basal cell
detection and reduces staining variability, thus rendering basal
cell immunostaining more consistent.
• PSA, PAP antibodies are useful in cases of unknown primary or
very de-differentiated tumors.
46. • HMW keratin and p63 stain basal cell layer of atrophic benign gland
• Racemase stains malignant cells