Histopathology of Benign Prostate Hyperplasia

1. Prostate
Nodular Hyperplasia,
Hormonal Hyperplasia,
Benign Prostate Hyperplasia,
Benign Enlargement of Prostate
BPH, BNH, BEP
Dr Mohammad Manzoor Mashwani

2. The prostate gland is an encapsulated (pseudo) organ situated
inferior to the neck of the bladder.
The normal prostate is composed of glands (tubuloacinar) and
stroma.
The glands are seen in cross section to be rounded to irregularly
branching.
These glands represent the terminal tubular portions of long
tubuloalveolar glands that radiate from the urethra.
The glands are lined by two cell layers: an outer low
cuboidal layer and an inner layer of tall columnar
mucin-secreting epithelium.
These cells project inward as papillary projections.

3. CORPORA AMYLACEA: concretions, stones
A characteristic fibromuscular stroma with smooth muscle
bundles, mixed with collagen and elastic fibers,
surrounds the prostatic glands and the prostatic
urethra.
Stroma accounts for about half of the volume of the
prostate.
As a male ages, there are more likely to be small concretions (Stones) within
the glandular lumina, called corpora amylacea, that represent laminated
concretions of prostatic secretions. Path.calcification
The glands are normally separated by stroma.
The prostate is surrounded by a thin layer of connective tissue that merges
with surrounding soft tissues, including nerves. There is no distinct capsule.
An acinus refers to any cluster of cells that resembles a many-lobed
"berry", such as a raspberry (acinus is Latin for "berry").
Amylaceameans STARCHY

4. The prostate gland in the normal adult weighs approximately
20gm (walnut size).
It surrounds the commencement of the male urethra
and is composed of 5lobes during embryonic development—
anterior, middle, posterior and two lateral lobes.
But at birth, the five lobes fuse to form 3 distinct lobes—two major
lateral lobes and a small median lobe.

5. Histology
The prostate is composed of tubular alveoli (acini) embedded in
fibromuscular tissue mass (Stroma).
The glandular epithelium forms infoldings (convolutions) and consists
of 2 layers—a basal layer (Outer) of low cuboidal cells and an inner layer
of mucus-secreting tall columnar cells.
The alveoli are separated by thick fibromuscular septa containing
abundant smooth muscle fibres.
alveolus. [al-ve´o-lus] (pl. alve´oli) (L.) a little hollow, pit or cavity, as the socket of a tooth, a
follicle of an acinous gland, or a pulmonary alveolus.
Alveolus means:
Hollow, pit or cavity.

6. Corpora amylacea or Prostatic concretion (Stones)
• Corpora amylacea are small hyaline masses of unknown
significance found in the prostate gland, neuroglia,
and pulmonary alveoli.
• They are derived from degenerated cells or thickened
secretions and occur more frequently with advancing age.
• While their significance is unknown, they can be used to
identify these organs microscopically.
• In the prostate, where they are also known as prostatic
concretions, they usually appear in benign glands;
however, their presence cannot be used to exclude cancer.
Amylacea is a Latinate biological word from the Greek amylon, which means 'starchy.
Corpora amylacea, which are calcium growths formed from the build-up of protein-
laced fluid over time. Calcification

7. laminated concretions of prostatic secretions.

8. Corpora amylacia or Prostatic concretion
Stones within the glandular Lumina

10. The prostate has numerous blood vessels and nerves.
In addition to nervous control, the prostate is an endocrine dependent organ.
Based on hormonal responsiveness, the prostate is
divided into 2 separate parts:
1. The inner periurethral female part
which is sensitive to oestrogen & androgen; and
2. Outer subcapsular true malepart
which is sensitive to androgen.

11. Disorders of Prostate
Prostate is involved in 3 important pathologic processes:
1. Prostatitis,
2. Nodular hyperplasia ( BPH or BNH, BEP)and
3. Carcinoma.
While benign nodular hyperplasia occurs in the
periurethral part (female part) distorting and compressing
the centrally located urethral lumen,
The prostatic carcinoma usually arises from the outer
subcapsular part (male part) in which case it does not
compress the urethra.

12. BPH, BNH, BEP
Non-neoplastic tumour-like enlargement of the prostate,
commonly termed benign nodular hyperplasia (BNH) or
benign enlargement of prostate (BEP), is a very common
condition in men and considered by some as normal ageing
process.
It becomes increasingly more frequent above the age of
50 years and its incidence approaches 75-80% in men
above 80 years.
However, symptomatic BEP producing urinary tract obstruction and
requiring surgical treatment occurs in 5-10% of cases only.
DHT: Dihydroxytestosterone, the ultimate mediator of prostatic growth

13. ETIOLOGY. The cause of BEP has not been fully established.
However, a few etiologic factors such as
 endocrinologic,
 racial,
 inflammation &
 arteriosclerosis have been implicated but
endocrinebasis for hyperplasia has been more fully
investigated and considered a strong possibility in its genesis.
It has been found that both sexes elaborate androgen and
oestrogen, though the level of androgen is high in
males and that of oestrogen is high in females.

14. With advancing age, there is decline in the level of
androgen and a corresponding rise of
oestrogen in the males.
The periurethral inner prostate which is primarily
involved in BEP is responsive to the rising level of
oestrogen,
whereas the outer prostate which is mainly involved
in the carcinoma is responsive to androgen.

15. Dihydroxy-testosterone (DHT)
A plausible hypothesis suggested is that there is
synergistic stimulation of the prostate by both
hormones—the oestrogen acting to sensitise the prostatic tissue to the
growth promoting effect of dihydroxy-testosterone derived from
plasma testosterone.
Dihydroxytestosterone (DHT), the ultimate mediator of
prostatic growth, is synthesized in the prostate by the
action of enzyme 5alpha- reductase, type 2.
Plausible: apparently reasonable & valid
DHT

16. MORPHOLOGIC FEATURES.
Grossly, the enlarged prostate is nodular, smooth and firm and weighs 2-4
times its normal weight i.e. may weigh up to 40-80 gm (Normal weight 20 g)
even up to 300 gms.
The appearance on cut section varies depending upon
whether the hyperplasia is predominantly of the
glandularor
fibromuscular tissue

17. 1.In primarily glandular BEP the tissue is
yellow-pink,
soft,
honey-combed, and
milky fluid exudes,
2.whereas in mainly fibromuscular BEP the cut
surface is
 firm,
 homogeneous and
 does not exude milky fluid.

18. The hyperplastic nodule forms a mass mainly in
the inner periurethral prostatic gland (female part) so that the
surrounding prostatic tissue forms a false capsule
which enables the surgeon to enucleate the nodular
masses.
The left-over peripheral prostatic tissue may
sometimes undergo recurrent nodular enlargement
or may develop carcinoma later.

19. This is the gross appearance of nodular prostatic hyperplasia
(benign prostatic hyperplasia, or BPH). The normal prostate is
3 to 4 cm in cross section, by comparison.

20. Microcystic areas

23. NODULARITY

24. Microscopy
Histologically, in every case, there is hyperplasia of all
three tissue elements in varying proportions— glandular,
fibrous and muscular :
Glandular hyperplasia predominates in most cases and
is identified by exaggerated intra-acinar papillary infoldings with delicate
fibrovascular cores.
The lining epithelium is two-layered:
1. the inner tall columnar mucussecreting with poorly-defined borders, and
2. the outer cuboidal to flattened epithelium with basal nuclei.

25. Fibromuscular hyperplasia when present as dominant
component appears as aggregates of spindle cells
forming an appearance akin (similar) to fibromyoma
(fibroid) of the uterus.
In addition to glandular and/or fibromuscular
hyperplasia, other histologic features frequently
found include:
 foci of lymphocytic aggregates,
 small areas of infarction,
 corpora amylacea and
 foci of squamous metaplasia.
Nodularity,
Aggregation of small to large to
cystically
dilated glands.

26. Enlarged Glands
Hyperplastic cystic glands

28. Nodular hyperplasia of the prostate. There is hyperplasia of fibromuscular elements.
There are areas of intra-acinar papillary infoldings (convolutions) lined by two layers of
epithelium with basal polarity of nuclei.
Hyperplastic cystic glands

30. Female Part

31. RightLeft
1. Loss of Convolutions
2. Loss of fibromuscular sling
3. Back to back microacini - No stroma
4. Perineural invasion
5. Small & close-packed glands
6. Rare corpora amylacea
7. Single-layered epithelium
8. In 95% of cases, prostatic carcinoma is
located in the peripheral zone,
especially in the posterior lobe.

32. 1. Loss of Convolutions
2. Loss of fibromuscular sling
3. Back to back microacini
4. Perineural invasion

33. 1. Loss of Convolutions
2. Loss of fibromuscular sling
3. Back to back microacini
4. Perineural invasion

34. CLINICAL FEATURES
Clinically, the symptomatic cases develop symptoms due to
complications such as urethral obstruction and secondary
effects on the bladder (e.g.
hypertrophy, cystitis), ureter (e.g. hydroureter) and kidneys(e.g.
hydronephrosis). The presenting features include
 frequency,
 nocturia,
 difficulty in micturition,
 pain,
 hematuria and
 sometimes, the patients present with acute retention of urine
requiring immediate catheterisation.

35. CARCINOMA OF PROSTATE
Cancer of the prostate is the second most common
form of cancer in males, followed in frequency by
lung cancer.
It is a disease of men above the age of 50 years and
its prevalence increases with increasing age so that
more than 50% of men 80 years old have
asymptomatic (latent) carcinoma of the prostate.
Many a times, carcinoma of the prostate is small
and detected as microscopic foci in a prostate
removed for BEP or found incidentally at autopsy.

36. Types
1. Latent carcinoma. This is found unexpectedly as a small
focus of carcinoma in the prostate during autopsy studies in
men dying of other causes. Its incidence in autopsies has been
variously reported as 25-35%.
2. Incidental carcinoma. About 15-20% of prostatectomies
done for BEP reveal incidental carcinoma of the prostate.
3. Occult carcinoma. This is the type in which the patient
has no symptoms of prostatic carcinoma but shows evidence
of metastases on clinical examination and investigations.
4. Clinical carcinoma. Clinical prostatic carcinoma is the
type detected by rectal examination and other investigations
and confirmed by pathologic examination of biopsy of the
prostate.

37. Etiology
• 1. Endocrinologic factors: Androgens
2. Racial & geographic influences: It is uncommon in
Japanese and Chinese, while the prevalence is high in Americans.
3. Environmental influences: High dietary fat, and exposure to polycyclic
aromatic hydrocarbons.
Flavonoids, antioxidants and selenium may reduce the risk.
4. Nodular hyperplasia (BPH) ?
5. Heredity: 2-fold higher frequency in first-degree relatives.

38. HISTOGENESIS
Histogenesis of prostatic adenocarcinoma has been
documented as a multistep process arising from
premalignant stage of prostatic intraepithelial neoplasia
(PIN).
PIN refers to multiple foci of cytologically atypical luminal
cells overlying diminished number of basal cells in
prostatic ducts and is a forerunner of invasive prostatic
carcinoma.
Based on cytologic atypia, PIN may be low grade to high
grade.
PIN of high-grade progresses to prostatic
adenocarcinoma.

39. MORPHOLOGIC FEATURES
Grossly, the prostate may be enlarged, normal in size
or smaller than normal.
In 95% of cases, prostatic carcinoma is located in the
peripheral zone, especially in the posterior lobe.
Outer subcapsular true malepart
The malignant prostate is firm and fibrous.
Cut section is homogeneous and contains irregular
yellowish areas.

40. Microscopy
Microscopically, 4 histologic types are described—
1. Adenocarcinoma 96%,
2. transitional cell carcinoma,
3. squamouscell carcinoma and
4. undifferentiated carcinoma.
However, adenocarcinoma is the most common type
found in 96% of cases and is the one generally
referred to as carcinoma of the prostate.
The other three histologic types are rare and resemble in
morphology with similar malignant tumours
elsewhere in the body.

41. Adenocarcinoma of the Prostate
The histologic characteristics of adenocarcinoma of the
prostate are as under :
1. Architectural disturbance.
 In contrast to convoluted appearance of the glands seen in
normal and hyperplastic prostate, there is loss of intra-acinar
papillary Convolutions (infoldings).
 The groups of acini are either closely packed in back-to-back
arrangement without intervening stroma or
 are haphazardly distributed.
1. Architectural disturbance
2. Stroma
3. Gland pattern
4. Tumor cells
5. Invasion

42. The histologic characteristics of adenocarcinoma
of the prostate
2. Stroma. Normally, fibromuscular sling surrounds
the acini, whereas malignant acini have little or no
stroma between them.
The tumour cells may penetrate and replace the
fibromuscular stroma.

43. The histologic characteristics of adenocarcinoma of the prostate
3. Gland pattern.
Well-differentiated :Most frequently, the glands in
well differentiated prostatic adenocarcinoma are
small or medium-sized, lined by a single layer of
cuboidal or low columnar cells.
Moderately-differentiated tumours have cribriform
or fenestrated glandular appearance.
Poorly differentiated tumours have little or no
glandular arrangement but instead show solid or
trabecular pattern.
Trabeculae: Rod-shaped structures of fibrous tissues that divide an organ into parts (as in
the penis) or stabilize the structure of an organ (as in the spleen).

44. The histologic characteristics of adenocarcinoma of the prostate
4. Tumour cells. In many cases, the individual tumour cells in
prostatic carcinoma do not show usual morphologic features of
malignancy.
The tumour cells may be clear, dark and eosinophilic cells.
 Clear cells have foamy cytoplasm,
 dark cells have homogeneous basophilic cytoplasm,
and
 eosinophilic cells have granular cytoplasm.
The cells may show varying degree of anaplasia and
nuclear atypia but is generally slight.

45. The histologic characteristics of adenocarcinoma of the prostate
5. Invasion. One of the important diagnostic features
of malignancy in prostate is the early and frequent
occurrence of invasion of intra-prostatic perineural
spaces.
Lymphatic and vascular invasion may be present but are
difficult to detect.
Invasion of
Intra-prostatic
Perineural Spaces

46. Carcinoma of the prostate. The field shows microacini of small
malignant cells infiltrating the prostatic stroma. Single layer epithelium.
1. Loss of Convolutions
2. Loss of fibromuscular sling
3. Back to back microacini
4. Perineural invasion

47. Carcinoma of the prostate. The field shows microacini of small malignant cells infiltrating the prostatic
stroma. Inset in the photomicrograph shows perineural invasion by prostatic adenocarcinoma.

48. Gleason’s microscopic grading system
Gleason’s microscopic grading system which is
based on two features:
i) Degree of glandular differentiation (Grade).
ii) Growth pattern of the tumour in relation to the stroma.
Gleason’s
Grading

49. Tumor markers: PAP & PSA
1. Prostatic acid phosphatase (PAP) is secreted by
prostatic epithelium.
Elevation of serum level of PAP is found in cases of
prostatic cancer which have extended beyond the
capsule or have metastasised.
PAP can also be demonstrated in the normal prostatic
tissues.
1. Prostatic acid phosphatase (PAP)
2. Prostate-specific antigen (PSA)

50. Tumor Markers
2. Prostate-specific antigen (PSA) can be detected by
 immunohistochemical method in the malignant
prostatic epithelium
 as well as estimated in the serum.
 A reading between 4 and 10 (normal 0-4 ng/ml) is highly suspicious (10% risk) but
 value above 10 is diagnostic of prostatic carcinoma.
Normal: 0-4 ng/ml

51. PSA assay
 PSA assay is useful in deciding whether the
metastasis originated from the prostate or
not.
 PSA assay is also helpful in distinguishing high-
grade prostatic cancer from urothelial
carcinoma, colonic carcinoma, lymphoma and
prostatitis.
PSA level is generally higher in low-grade
tumours than in high-grade tumours.
Normal: 0-4 ng/ml