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“SPECTRUM OF HISTOLOGICAL
LESIONS IN PROSTATIC SPECIMENS”
By
Dr. SUSHMA .T.A.
M.B.B.S.,
Dissertation submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore.
In Partial fulfillment
of the requirements for the degree of
DOCTOR OF MEDICINE
IN
PATHOLOGY
Under the guidance of
Dr. H. GURUBASAVARAJ
M.D.,
DEPARTMENT OF PATHOLOGY
J.J.M. MEDICAL COLLEGE
DAVANGERE – 577 004.
2008
i
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
DECLARATION BY THE CANDIDATE
I
hereby
declare
that
this
dissertation
entitled
“SPECTRUM
OF
HISTOLOGICAL LESIONS IN PROSTATIC SPECIMENS” is a bonafide and
genuine
research
work
carried
out
by
me
under
the
guidance of
Dr.H.GURUBASAVARAJ M.D., Professor, Department of Pathology, J.J.M .Medical
College, Davangere.
ii
CERTIFICATE BY THE GUIDE
This
is
to
certify
that
this
dissertation
entitled “SPECTRUM
OF
HISTOLOGICAL LESIONS IN PROSTATIC SPECIMENS” is a bonafide work
done by Dr. SUSHMA .T.A. in partial fulfillment of the requirement for the degree of
M.D. in PATHOLOGY.
iii
CERTIFICATE BY THE CO-GUIDE
This
is
to
certify
that
this
dissertation
entitled “SPECTRUM
OF
HISTOLOGICAL LESIONS IN PROSTATIC SPECIMENS” is a bonafide work
done by Dr. SUSHMA .T.A. in partial fulfillment of the requirement for the degree of
M.D. in PATHOLOGY.
iv
ENDORSEMENT BY THE HOD,
PRINCIPAL/HEAD OF THE INSTITUTION
This
is
to
certify
that
this
dissertation
entitled “SPECTRUM
OF
HISTOLOGICAL LESIONS IN PROSTATIC SPECIMENS” is a bonafide research
work done by Dr. SUSHMA .T.A. under the guidance of Dr. H. GURUBASAVARAJ
M.D., Professor, Department of Pathology, J.J.M. Medical College, Davangere.
v
COPYRIGHT
Declaration by the Candidate
I hereby declare that the Rajiv Gandhi University of Health Sciences, Karnataka
shall have the rights to preserve, use and disseminate this dissertation / thesis in print or
electronic format for academic / research purpose.
п›™ Rajiv Gandhi University of Health Sciences, Karnataka.
vi
ACKNOWLEDGEMENT
TRUE GRATITUDE IS DIFFICULT TO EXPRESS IN WORDS
I thank Almighty for having blessed me with the ability to accomplish this task.
With the deepest sense of gratitude, I take this opportunity to express
overwhelming
devotion
to
my
esteemed
and
learned
teacher
Dr.H.R.CHANDRASEKHAR M.D., Principal for his excellent guidance, encouragement
and constant inspiration during my post-graduate course.
I profusely thank my guide Dr. H. GURUBASAVARAJ M.D., Professor of
Pathology who with his able guidance and constant encouragement has been an
important part of my dissertation.
I owe Dr. HIREMATH S.S. M.D., Professor of Pathology who with his able
guidance, constructive criticism at each step gave me all the confidence and
determination to complete my dissertation.
I place on record my gratitude and sincere thanks to Dr. PRAKASH KUMAR
M.D., Professor and Head of Department of Pathology for his veritable advice and
suggestions during the course of the study.
I consider myself very fortunate to have Dr.P.K.BASAVARAJA M.D.,
Dr.KADAM SATYANARAYANA RAO
M.D., Dr.B.BASAVARAJU M.D.,
Dr.M.M.DODDIKOPPAD M.D., Dr.RAJASHEKAR
M.D., Dr.
SURESH
HANAGAWADI M.D., and Dr.SHASHIKALA P. M.D., Professor of Department of
Pathology, who have been a source of inspiration and helped me throughout my postgraduate training course.
I owe a special debt of gratitude to Dr.CHATURA K.R. M.D., Professor, for her
priceless suggestions and encouragement which helped to pursue this study to
completion.
My sincere thanks to Dr. ARUNA S.B. M.D., Dr.K.K.SURESH M.D.,
Dr.THIPPESWAMY M.T.R. M.D., Dr.JAYASHREE G. PAWAR M.D., Dr.JAGADISH
C.N. D.C.P., Dr.JAGADESHWARI K. D.C.P., Dr. KAVITHA U.G. M.D.,
Dr.DEEPTI.S. M.D., Dr. SUNIL KUMAR K.B. M.D., Dr.MALLIKARJUN M.D.,
Dr.SWARNA,M.D., and Dr.ANUSHREE M.D., for their willing guidance and help
throughout the course of this study.
I would like to thank Dr. GURUPADAPPA M.D., Director of Post-graduate studies for
allowing me to utilize the institutional facilities.
I acknowledge my gratitude to Dr. H.B. SHIVAKUMAR M.S., Mch., Urologist, for his
cooperation in providing the material required for the study.
vii
I would like to express my thanks to the technical staff comprising
Mr.Shankarappa, Mr. Puttappa, Mr.Yogesh, Mr. Nagaraj, Mr.Pranesh Rao,
Mr.Venkatesh, Smt.Bharathi and Mr. Mallikarjun for their skilled assistance and cooperation. I also thank Mr.Shivanandappa, Smt.Gowramma, Mr.Chandru, Mr.Ramesh
and Mr.Malatesh for their timely help.
I sincerely acknowledge the contribution and aid of my senior colleagues and
friends Dr. Ramaswamy, Dr. Kishan Prasad, Dr. Manjunath, Dr. Sridhar, Dr. Geetha,
Dr.Gayathri, Dr. Sheela, Dr. Prakash, Dr. Nidhinath and Dr.Manjula for their timely
help and co-operation and my junior colleagues Dr. Veena, Dr. Rajiv, Dr. Preethi, Dr.
Shahid,, Dr. Tushar, Dr. Kuladeep, Dr. Kasturi, Dr. Parneeth, Dr.Aravind, Dr.Rashmi
for their assistance.
I thank Mr. MAHESH P.S., Chief Librarian and all the staff members of Library
and Mr. SANGAM, Statistician for their co-operation and assistance during my study
period.
It is very difficult to express in words, gratitude to my parents Mrs. Mani T.R.,
and Mr. Ankegowda T.C. for their love, sacrifice and moral support, without whom I
would not have been, what I am today. The blessings and prayers of my parents-in-law
are also valuable during the course of my study.
I would like to express my special word of thanks to my husband Dr.Narendra.S
whose constant help and understanding demeanour formed an ideal matrix for
completing my work. For all the hardships undergone, the only solace comes from the
smile that I see on my beloved son Chandan’s face helping me tide over moments of
distress.
My special thanks to M/s. GUNDAL Compu-Center for their meticulous
computerized printing of this dissertation.
Above all, my sincere thanks to all the patients without whom this dissertation
would not have been possible.
viii
LIST OF ABBREVATIONS
AAH
Atypical Adenomatous Hyperplasia
AgNORs
Argyrophilic Nucleolar Organizer Regions
AR
Androgen Receptor
BCH
Basal Cell Hyperplasia
BPH
Benign Prostatic Hyperplasia
DRE
Digital Rectal Examination
DTH
Dihydrotestosterone
H&E
Haematoxylin And Eosin
HGPIN
High Grade Prostatic Intraepithelial Neoplasm
HMW-CK
High Molecular Weight Cytokeratin
IHC
Immunohistochemistry
LGPIN
Low Grade Prostatic Intraepithelial Neoplasm
NE
Neuroendocrine Tumors
NH
Nodular Hyperplasia
PAH
Post Atrophic Hyperplasia
PASd
Periodic Acid Schiff Diastase
PIN
Prostatic Intraepithelial Neoplasia
PSA
Prostate Specific Antigen
PAP
Prostatic Acid Phosphatase
SCC
Squamous Cell Carcinoma
STUMP
Stromal Tumor Of Unknown Malignant Potential
TURP
Transurethral Resection Of Prostate
VACURG
Veterans Administration Co-operative Urologic Research Group
WHO
World Health Organization
ix
ABSTRACT
Background:
Prostatic diseases are the most common urologic disease to affect elderly men.
Prostatic carcinoma is the second most common cause of cancer deaths in men and the
incidence is increasing significantly over recent years, due to early screening measures.
Objectives :
The objective of the study was to evaluate the various histological lesions in
prostatic specimens.
Methods:
198 prostatic lesions were studied using Hematoxylin and Eosin (H&E) and mean
AgNOR count was done.
Results :
Nodular hyperplasia was the commonest lesion encountered. Associated lesions
like prostatitis, basal cell hyperplasia, red infarcts, granulomatous prostatitis and abscess
were encountered. Among the adenocarcinoma prostate, Gleason score 8 was seen in
majority of cases.
Mean AgNOR counts of malignant lesions were significantly higher when
compared to benign lesions. Mean AgNOR count also increased with histological grade
of tumor.
Interpretation and Conclusion :
Mean AgNOR count combined with routine histopathology significantly
improves the analysis of prostate diseases.
Key words :
Nodular hyperplasia, granulomatous prostatitis, abscess, red infarcts, basal cell
hyperplasia, adenocarcinoma prostate, Gleason’s score, AgNOR.
x
TABLE OF CONTENTS
Page No.
1.
INTRODUCTION
01
2.
OBJECTIVES
02
3.
REVIEW OF LITERATURE
03
4.
METHODOLOGY
59
5.
RESULTS
62
6.
DISCUSSION
86
7.
CONCLUSION
100
8.
SUMMARY
101
9.
BIBLIOGRAPHY
104
10.
ANNEXURES
•
PROFORMA
120
•
MASTER CHART
125
xi
LIST OF TABLES
Tables
Sl.No.
Page No
1
Incidence of prostatic lesions
62
2
Age incidence of various prostatic lesions
64
3
Clinical presentations of prostatic lesions
66
4
Digital rectal examination findings
67
5
Microscopic findings in benign lesions
69
6
Prostatic intraepithelial neoplasia
70
7
Microscopic findings in carcinoma prostate
71
8
Incidence of carcinoma with reference to gleason’s score
73
9
Final histopathological diagnosis
74
10
Mean AgNOR count in prostatic lesions
75
11
Serum P S A levels in prostatic lesions
77
12
Histopathological diagnosis in different studies
87
13
Incidence of prostatitis
88
14
Incidence of PIN in cases of prostates with and
without prostatic carcinoma
90
15
Incidence of HGPIN in prostates with carcinoma
91
16
Prevalence of prosta tic carcinoma in different studies
93
17
Age incidence of prostatic carcinoma in different
studies
94
18
Incidence of prostatic carcinoma, mean age and mean
Gleason’s score
95
19
Incidence of Gleason’s score and prostatic carcinoma
95
20
Comparison of
lesions
99
mean AgNOR
xii
count in prostatic
LIST OF FIGURES
Sl.No.
List of Graphs
Page No.
1
Incidence of Prostatic lesions
2
Nature of prostatic specimens
62
63
3
Age incidence of various prostatic lesions
64
4
Clinical presentation of prostatic lesions
66
5
Digital rectal examination findings
67
6
Microscopic findings in benign lesions
69
7
Microscopic findings in carcinoma prostate
71
8
Incidence of carcinoma with reference to Gleason’s score
73
9
Mean AgNOR counts in benign and malignant lesions
76
10
Serum PSA levels in prostatic lesions
77
xiii
LIST OF PHOTOGRAPHS
Fig.
No.
Photographs
Page
No
1
Gross appearance of nodular hyperplasia
78
2
Nodular hyperplasia showing hyperplastic glandular and stromal
components (H&E, 100x)
78
3
Corpora amylacea inside the glandular lumen in case of NH (PASd
100x)
78
4
Prostatic abscess showing neutrophilic infiltration in and around the
acini (H&E, 100x)
79
5
Nodular hyperplasia showing foci of AAH (H&E 100x)
79
6
Transitional metaplasia in case of NH (H&E, 100x)
79
7
Squamous metaplasia with red infarct in case of NH (H&E, 100x)
79
8
BCH showing proliferation of basaloid cells in solid nests and
tubules (H&E, 100x)
80
9
BCH showing microcalcified deposit (H&E, 100x)
80
10
BCH showing clear cell change (H&E, 100x)
80
11
Non specific granulomatous prostatitis showing granulomas causing
destruction of the acini (H&E, 100x)
81
12
Granulomatous prostatitis showing well formed epithelioid
granuloma with langhan’s giant cell (H&E, 100x)
81
13
Acid fast bacilli positivity (Ziehl Neelsen, 1000 x)
81
14
LGPIN showing epithelial crowding, stratification and
ansisonucleosis (H&E, 100x)
82
15
HGPIN showing cribriform pattern of glands with luminal bridging
and adjacent area of infiltrating carcinoma (H&E, 100x)
82
16
Prostatic adenocarcinoma Gleason’s score 3+4=7 (H&E,100x)
83
17
Prostatic adenocarcinoma Gleason’s score 4+4=8 (H&E,100x)
83
xiv
18
Prostatic adenocarcinoma Gleason pattern 5 with central comedo
necrosis (H&E,100x)
83
19
Prostatic adenocarcinoma sho wing atypical mitosis and occasional
prominent nucleoli (H&E, 400x)
84
20
Prostatic adenocarcinoma showing perineural invasion of tumour
cells (H&E, 400x)
84
21
Intraluminal acidic mucin in lumen of neoplastic glands in
adenocarcinoma of prostate (Alcian blue pH-1, 100x)
84
22
NH showing one or two AgNOR dots per nucleus (AgNOR stain,
1000x)
85
23
Adenocarcinoma of the prostate showing numerous AgNOR dots
per nucleus (AgNOR stain, 1000x)
85
xv
INTRODUCTION
“When hair becomes gray and scanty, when specks of earthy matter begin to be
deposited in tunics of artery, and when a white zone is formed at the margin of the
cornea, at this same period the prostate gland usually, might perhaps say invariably
becomes increased in size”
-
Sir Benjamin Brodie
Prosta tic disease is responsible for significant morbidity and
mortality in men, throughout the world. Recently there is considerable
change in the understanding of many prostatic diseases.
Accurate
simultaneous
diagnosis
of
prostatic
disease
frequently
requires
data from clinical chemistry, imaging techniques and
surgical pathology laboratory. Even following detailed histopathologic
examination
of
biopsy
tissues,
taken
from
precisely
defined
microanatomic sites within the prostate, informed opinions as to the
d iagnostic or prognostic significance of particular morphologic features,
frequently remain controversial, to the extent that distinction of benign
from malignant neoplastic disease may not be possible.
The subject of prostatic disease is fraught with doubts , uncertainties
and apparent contradictions. This has prompted to take up this study.
1
OBJECTIVES
1. To evaluate the histological lesions of prostatic specimens.
2. To correlate the histological features of these lesions with the clinical
data.
2
REVIEW OF LITERATURE
Prostate was believed to be a lobular structure for many years. Prior
to 1906, when Home described the middle lobe, prostate was considered
to be composed of only 2 lateral lobes. Later the existence of 5 prostatic
lobes was proposed- 2 late ral lobes, an anterior lobe, posterior lobe and
middle lobe based on embryonic finding. 1
The term nodular hyperplasia (NH) was proposed by Moore in
1943.2 It is a classical age related disease present in 20% of men at age
40 years with progression to 70% by the age of 60 years. Of the many
species with prostate glands, only man, chimpanzee and dog are known to
develop benign prostatic hyperplasia (BPH).
It occurs in transition zone
of the prostate and is characterized by progressive histologic changes tha t
arise initially in the stromal compartment, which becomes enlarged and
altered in its cellular composition. NH is a multifactorial disease
involving environmental, endocrine and genetic factors. 3
The tissue resected for NH is quite heterogeneous and that the
nodules are composed of varying proportion of both epithelial and stromal
components. 4
The relative proportions of epithelium and stroma are
related to the development of symptomatic BPH. 5
release
of
platelet
derived
growth
factor
contributing factor in development of BPH. 6
3
Inflammation induced
(PDGF)
is
a
possible,
Prostatic intraepithelial neoplasia (PIN) was first described in
1960s by McNeal and more precisely characterized in 1986 by McNeal
and Bostwick as dysplasia. Currently, it is referred to as prostatic
intraepithelial neoplasia. 7
Atypical
localized
adenomatous
proliferation
of
hyperplasia
small
glands
(AAH)
that
of
can
prostate
be
is
the
mistaken
for
carcinoma.8
The
architectural
patterns
of
high
grade
PIN
(HGPIN)
was
described as tufting, micropapillary, cribriform and flat. The tufting
pattern being the most common. 9
Rare variants of HGPIN like signet
ring, small neuroendocrine, mucinous and inverted type were identified.
These types present in invasive carcinoma of prostate provides supp ort for
a close relationship between HGPIN and invasive carcinoma.1 0
The
histology of the central zone located at the base of the prostate adjacent to
seminal vesicle was studied and concluded to be a potential mimicker of
HGPIN. 1 1
Egan M. et al described prostatic adenocarcinoma with atrophic
features, a malignancy mimicking a benign process 1 2 . Levi et al studied
on pseudohyperplastic prostatic adenocarcinoma on needle biopsy and
simple prostatectomy. 1 3 Nelson et al emphasized on an unusual variant of
prostate carcinoma, characterized by abundant xanthomatous cytoplasm. 1 4
The diagnosis of mucinous adenocarcinoma of the prostate was made
when the mucinous component is composed of at least 25% of tumor
4
volume. 1 5 Tamas et al emphasized that when tumor is co mposed entirely
of Paneth cell- like neuroendocrine differentiation, it has a favorable
prognosis.1 6
Atypical
small
acinar
proliferation(ASAP),
suspicious
for
malignancy in prostatic needle biopsies was evaluated and concluded that
the
histologic
malignancy. 1 7
finding
of
ASAP
had
a
high
predictive
value
for
The significance of intraluminal crystalloids in benign
prostatic glands on needle biopsy showed no risk of having cancer on
repeat biopsy even if crystalloids were not present.1 8
Gleason’s unique ap proach to grading cancers was developed
following a detailed, prospective, case controlled and fully randomized
clinical study performed by the Veterans Administration Co- operative
Urological Research Group (VACURG). 1 9
Spires et al observed that with careful histological evaluation,
Gleason histologic grading in prostatic carcinoma identified in smaller
biopsy
cases
correlated
well
with
that
seen
at
prostatectomy. 2 0
Srigley et al updated the protocol on examination of specimens from
patients with carcinomas of the prostate gland. 2 1
Pathologic factors that influence prognosis of prostatic carcinoma
have been studied by many authors. They include grade, extent, cytology,
infiltration, inflammatory response and associated changes in prostate. 2 2
5
In prostate lesions, many studies have shown a significantly
increased proportion of proliferative cells in malignant lesions compared
to that of benign hyperplasia. Proliferative markers like Argyrophilic
nucleolar organizer regions (AgNORs) is of greater he lp for tumor
analysis.2 3
Crocker
and
his
colleagues
have
applied
the
AgNOR
techniques in diagnostic tumor pathology. 2 4 Deschenes et al compared
AgNOR counts in benign, atypical and
malignant prostatic lesions and
correlated them with nucleolar diameter.2 5 Ghazizadeh et al observed that
the mean AgNOR count significantly increased with increasing Gleason’s
grade and clinical stage of the tumor. 2 6 Lloyd et al emphasized AgNOR
count may be beneficial when used in combination with histological grade
and clinical stage. 2 7 Verma et al also has shown that AgNOR score is of
great help in distinguishing benign and malignant tumors as well as low
and high grade tumors in cytological specimens.2 3
Prostate specific antigen (PSA) was first demonstrated in prostatic
tissues, then in seminal plasma, purified from prostatic tissue and finally
measured in serum of men. PSA in serum was demonstrated to be a
clinically important assay for the monitoring of prostatic carcinoma.1
PSA is secreted into seminal fluid in high concentration, which is
involved in liquefaction of semen coagulum. PSA was widely used as a
clinical marker for prostate cancer by 1988. 1 Serum PSA levels increases
proportionately with advancing clinical stage. 2 8 Studies have shown that
6
serial
increase
in
serum
PSA,
increases
the
incidence
of
occult
carcinoma.2 9
Age specific, upper reference ranges for serum PSA for men is 2.5
ng/ml for 40- 49 years of age, 3.5 ng/ml for 50- 59 years, 4.5 ng/ml for 6069 years and 6.5 ng/ml for 70- 79 years.
Several modifications in the estimation of serum PSA includes –
1.
PSA velocity - It is the rate of change of PSA and the value that
distinguished between men with and without prostatic carcinoma
is 0.75 ng/ml per year.
2.
PSA density – It reflects the PSA produced per gram of prostatic
tissue and the upper normal value is 0.15. 3 0
Prostatic acid phosphatase (PAP), a glycoprotein was previously
used for detection and monitoring of patients with prostatic carcinoma,
however its sensitivity is low and serum PSA has largely supp lanted
serum PAP.3 1
7
EMBRYOLOGY OF PROSTATE :
Prostate begins development from the mesenchyme, surrounding
the urogential sinus in the 3 r d month of gestation. Epithelial buds
invaginate from the posterior sinus on either side of verumontanum.
Concurrently, Wolffian ducts develop into seminal vesicles, epididymis,
vas
deferens
and
ejaculatory
ducts
that
are
stimulated
by
fetal
testosterone. By 4 t h month of gestation, basic structure of prostate is
complete.
In the fetal prostate, glandular buds begin as solid outgrowth of
cells; small lumina develop, lined by cuboidal or columnar cells. During
the perinatal period, active secretion is seen in the peripheral portion of
prostate along with squamous metaplasia of urethral epithelium, utricle
and central portion of prostate. All these effects are due to maternal
oestrogens. 3 2
ANATOMY :
By age of 20 years, prostate approximately weighs 20gms and has
the shape of an inverted cone, with the base at the bladder neck and apex
at the urogenital diaphragm. Posteriorly, the prostate and seminal vesicles
are separated from the rectum by a thin filmy layer of connective tissue
known as Denonvillier’s fascia.
At the apex, the skeletal muscle of the
urogenital diaphragm extends into the prostate predominantly in the
a nterior and anterolateral aspect. 3 3
8
The posterior part is divided into various zones, it is known as
McNeals models of the prostate.
The zones are :
1.
Anterior fibromuscular stroma
2.
Peripheral zone
3.
Central zone
4.
Transitional zone.
The anterior fibromuscular stroma occupies 1/3r d of the prostate and
consists of very few glands and smooth muscle tissue.
The peripheral zone constitutes 70% of the prostate. It is distal to
the central zone and corresponds to the horseshoe shaped structure
extending posteriorly, posterolaterally and laterally.
The central zone constitutes 25% of the prostate, forming a cone
shaped area that includes the entire base of the prostate and encompasses
the ejaculatory duct. Glands in the central zone are complex and large
with
papillary
infoldings.
Epithelial
bridges
(Roman
bridge)
and
cribriform pattern are also seen.
The central zone and peripheral zone together are now called the
outer prostate.
The ducts of the outer prostate are larger and branched,
and drain into prostatic sinuses. Outer prostate/zone has more predilection
for carcinoma.
The transitional zone is the smallest aspect of the prostate,
approximately 5% of the prostatic volume.
9
The transitional zone and
anterior fibromuscular stroma is together called inner prostate or inner
zone. It has a predilection for benign prostatic enlargement.
HISTOLOGY OF PROSTATE3 3 :
The epithelial cells of prostate are :a)
Transitional cells
b)
Secretory cells
c)
Basal cells
d)
Neuroendocrine cells.
The proximal portions of ducts, that are near to the urethra are lined
by transitional epithelium. In the distal portion, secretory columnar cells
with pale- clear cytoplasm and vesicular nuclei, line ducts and acini. These
cells are terminally differentiated and stain positively for PSA and PAP.
Basal cells lie beneath the secretory cells. The basal cells are cigar
shaped with ovoid nucleus and lighter chromatin. They are arranged
parallel to the basement membrane.
Basal cells are less differentiated
than secretory cells. They are identified by the im munohistochemical
reaction with antibodies to high molecular weight cytokeratin (HMW- CK).
Stroma is composed of smooth muscle cells and fibroblasts.
The neuroendocrine
cells
can be recognized on hematoxylin and
eosin (H&E) stained sections by their basally located nucleus, deeply
eosinophilic cytoplasm with fine cytoplasmic granules. Most of them
contain serotonin and less frequently calcitonin, somatostatin or human
chorionic gonadotrophin (HCG).
10
Corpora amylacea is inspissated secretions present within the
lumina of the glands. They are seen in approximately 25% of prostate
glands in men aged between 20- 40 years and very rarely in carcinomas.
They are round laminated hyaline eosinophilic structures that may be
calcified. 3 3
NEUROVASCULAR BUNDLES :
Neurovascular bundles furnish the nerve supply to the prostate.
The main nerves are located in the neurovascular bundles on the superior
– lateral borders of the prostate. 3 4
Benign glands are seen in close proximity to the nerves, mimicking
perineural invasio n by cancer. These glands indent the nerve on one side
rather than circumferential involvement as seen in cancer. 3 5
PATHOLOGY OF PROSTATE
BENIGN PROSTATIC HYPERPLASIA:
The term “Nodular Hyperplasia” proposed by Moore is a more
exact designation than the common name BPH. Disease represents a
nodular enlargement of gland caused by hyperplasia of both glandular and
stromal components.2
NH involves the overgrowth of the epithelium and fibromuscular
stroma in the transition zone and periurethral area. 3 6
11
EPIDEMIOLOGY :
Nodular hyperplasia is extremely common disease of the ageing
population. There is a rapid increase in prevalence of NH beginning in the
4 t h decade of life and culminating in nearly 100% prevalence by
9t h
decade.
in
The
age
–
specific
prevalence
is
remarkably
similar
populations throughout the world.3 6
RISK FACTORS :
Advanced
age
and
an
intact
androgen
supply
are
the
only
undisputed risk factors for NH. It does not occur in men castrated before
puberty. The risk is lower in patients with androgen resistance or
deficiencies.
Antiandrogens,
gonadotropin- releasing hormone (GnRH)
agonists and 5 О± - reductase inhibitors also reduce the symptoms. Most
epidemiological studies of environmental and life style risk factors have
yielded equivocal results, including studies of medical history, sexual
history, smoking, alcohol use, socio- economic status and occupational
exposure.3 6
PATHOGENESIS :
The development of NH includes 3 pathologic changes3 6 :
a. Nodule formation
b. Diffuse enlargement of transition zone and periurethral tissue
c. Enlargement of nodules.
12
The primary mediator of NH is dihydrotestosterone (DTH). This
androgen is the major intracellular metabolite of testosterone after its
conversion by 5 О± - reductase. Testosterone and DTH bind to nuclear
andro gen receptors in stromal and epithelial cells in prostate, although
DTH has 5 fold higher affinity. The nuclear androgen receptor content of
NH is greater than that of normal prostatic tissue.
CLINICAL FEATURES :
Symptoms are caused by interference with muscular sphincteric
function and by obstruction of urine flow through the prostatic urethra.
The
symptoms
include
urgency,
difficulty
in
starting
urination,
diminished stream size and force, increased frequency, a sensation of
incomplete bladder emptying a nd nocturia.3 6
GROSS APPEARANCE :
NH is characterized by variable sized nodules, which are soft to
firm, rubbery, yellow- gray in colour weighing between 40 and 400g (mean
60g) and bulge from the cut surface on transection.
•
If there is predominant epithelial hyperplasia, the abundant luminal
spaces create soft and grossly spongy nodules due to interspersed
cysts, from which oozes a pale white watery fluid.
•
If it is predominantly fibromuscular, there may be diffuse enlargement
or numerous trabeculations without a prominent nodularity.
•
Degenerative changes include calcifications and infarction. 3 6
13
MICROSCOPIC APPEARANCE :
NH
of
prostate
is
the
result
of
proliferation
of
the
mesenchymal – stromal and glandular – epithelial components in varying
proportions. Franks described the 5 histopathological subtypes.
♦
Stromal (fibrous or fibrovascular) nodules located in periurethral
submucosa are composed predominantly of loose mesenchyme and
prominent small round blood vessels.
♦
Fibromuscular nodule shows balanced distribution of fibres of the
fibroblastic and smooth muscle types.
♦
Muscular nodules are composed of smooth muscle cells arranged in
intermingled bundles.
♦
Fibroadenomatous
nodule
with
cytologically
benign
stroma
compressing prostatic glands into slit like spaces, resembling
intracanalicular fibroadenoma of breast.
♦
Fibromyoadenomatous nodule are almost always laterally situated
and tend to occur in periurethral zone near the proximal end of
verumontanum, consisting of all the element s.
The
glandular
component is made up of small and large acini, some of them
showing papillary infoldings and projections containing central
fibrovascular cores.
The stroma consists of smooth muscle and
fibrous tissue.3 7
14
In limited hyperplasia, transurethral resection of prostate (TURP)
specimens contains a higher percentage component of bladder neck and
anterior fibromuscular tissue. Larger specimens obtained from enucleation
shows nodules with predominant epithelial component. 3 3
VARIANTS OF HYPERPLAS IA :
1. Post- atrophic hyperplasia (PAH):
It arises in the peripheral zone of prostate as a cluster of small acini
with irregular luminal contours, usually surrounding and budding from
central dilated acini. The acini are lined by cuboidal cells with sma ll
nuclei and nucleoli, cytoplasm is scanty, clear and is often basophilic.
Basal cell layer is irregular and is invariably present. Dense stromal
sclerosis with shrunken smooth muscle cells is an useful diagnostic
finding.
Awareness of PAH is important as it displays small glandular
proliferative
lesions
causing
diagnostic
difficulties
with
adeno-
carcinoma.3 8 , 3 9
2. Basal cell hyperplasia (BCH) :
It is characterized by basal cell proliferation.
nests of uniform small cells.
It appears as solid,
It can be two or more cell layers thick
protruding into the lumen in a peripheral palisading manner with retention
of overlying secretory luminal epithelium. Basal cell proliferation shows
a wide spectrum of morphological features ranging from benign to
15
malignant
lesions.
BCH
occasionally
contains
calcified
laminated
structures. BCH with adenoid cystic pattern and cribriform pattern and
squamoid features are also described. 4 0 , 4 1
Basal cell adenoma :
Consists of large, round circumscribed nodule or
nodules that contain uniformly spaced aggregates of hyperplastic basal
cells varying from small solid nests to cystically dilated glands. 4 2
Atypical BCH refers to the BCH with prominent nucleoli and may
be accompanied by mitotic figures, mimicking cancer and HGPIN. 4 3
3. Cribriform hyperplasia :
It includes clear cell cribriform hyperplasia and occurs in transition
zone.
The cells comprising the cribriform glands have abundant clear
cytoplasm and the nucleus is small uniform with inconspicuous nucleoli.
These cells are surrounded by basal cell layer in many of the glands. 3 7 , 4 4
4. Sclerosing adenosis :
It is a pseudoneoplastic lesion, that can mimic prostate cancer. It is
usually an incidental finding in TURP specimens.
The lesion is partially well circumscr ibed with minimal infiltrative
margin at the periphery.
It is composed of well formed small glands
admixed with a dense cellular spindle cell stroma. The glands are
composed of cells with pale to clear cytoplasm and nucleus is small and
uniform with occasional prominent nucleoli. Basal cell layer is identified
16
in many of glands and shows striking myoepithelial cell differentiation on
immunohistochemistry (IHC). 4 5
Association of NH and prostate cancer :
NH and prostate cancer display a number of similarities, including a
parallel age – specific increase in prevalence, high incidence and
prevalence levels in advanced age and a requirement for androgens for
development and growth.
Cancer is found incidentally in a significant
number (10%) of TURP specimens . NH may be related to prostate cancer
arising in transition zone but NH is not a premalignant lesion or a
precursor of cancer. 4 6
Infarct :
In 20- 25% of prostate removed for NH, small infarcts ranging in
size from few millimeters to 5cm are detected. These patients are more
prone for acute urinary retention and gross hematuria which is due to
larger size of gland and not due to infarcts.
The mechanism of infarct is unknown, but may be related to the
presence of prostatic infection or trauma resulting fr om an indwelling
catheter, cystitis or prostatitis, all of which may result in thrombosis of
intraprostatic portion of urethral arteries.
Grossly, they are speckled, grayish yellow and often contain streaks
of blood. The peripheral margins are sharp and hemorrhagic.
17
Microscopically,
acute prostatic infarcts have a characteristic
zonation. Coagulative necrosis and recent hemorrhages are found in the
center of infarcts. Immediately adjacent to infarcts, there may be reactive
epithelial nests with prominent nucleoli and mitotic figures. Further away
there is mature squamous metaplasia showing reactive nuclear features.
Squamous islands may be cystic with intraluminal cellular debris but
rarely show keratinisation.
Infarct may cause serum elevation of PSA
levels, however removal of infarcted area return the levels to normal. 2
METAPLASIA IN PROSTATE :
Urothelial (Transitional cell) metaplasia :
When urothelium is present in the more peripheral prostatic acini
and ducts, it is referred to as “Urothelial metaplasia”. It is composed of
spindle shaped epithelial cells that are often oriented with their long axis
perpendicular to the lumen. Urothelial metaplasia may be seen throughout
the prostates in infants and neonates, and is also associated with infarcts
a nd chronic inflammation. 4 7
Mucous gland metaplasia :
It is found in 1% of prostates. It consists of tall mucin filled goblet
cells. The nuclei are tiny, dark and basal. They may occur in groups of
5- 10 cells or as scattered individual cells.
The cells are positive for
mucicarmine and alcian blue and is negative for PSA and PAP.
18
It is
found in normal and hyperplastic prostate with areas of atrophy. It is not
related to cancer or inflammation. 4 8
Squamous metaplasia :
It is common in areas adjacent to infarcts, following, antiandrogen
therapy and neonates. 4 7
Mesenchymal metaplasia :
One case of cartilaginous metaplasia in the prostate is reported.
Prostatic inflammation :
Acute and chronic prostatitis are common diseases in urologic
practice.
They
a re
usually
diagnosed
clinically
and
treated
with
antibiotics such that histologic examination of specimens removed for
symptomatic prostatitis is rare. It is associated with increased serum PSA
levels, which return to normal following treatment.
Acute bacterial prostatitis :
Acute bacterial prostatitis presents with sudden fever, chills and
irritative voiding symptoms. The prostate is swollen, tender and warm.
Microscopically, there are sheets of neutrophils in and around
prostatic ducts and acini with desquamated epithelium and cellular debris.
Stroma is edematous, hemorrhagic and contains variable numbers of
lymphocytes, plasma cells, macrophages and microabscesses are also
frequently
seen.
Diagnosis
is
by
contraindicate d.
19
urine
culture
and
biopsy
is
The bacteria responsible for acute prostatitis are Escherichia Coli
(E.coli) (80%), other enterobacteriaceae
such as pseudomonas, serratia,
klebsiella (10- 15%) and enterococci (5- 10%).3 6
Prostatic abscess :
A rare complication of acute prostatitis occurring most commonly
in immunocompromised patient.
Predisposing factors include urethral
instrumentation, diabetes, internal prosthesis, chronic renal failure and
indwelling catheters. Patient presents with prostatic enlargement, fever
and retention of ur ine. A fluctuant mass is occasionally palpated by rectal
examination. It is caused by aerobic and anaerobic bacteria. 2
Chronic prostatitis :
Chronic prostatitis presents with variable clinical features and
include frequency, urgency, dysuria, pain in perineum, lower back and
testis. Digital rectal examination (DRE) varies from normal to tender and
boggy. Microscopically characterized by aggregates of lymphocytes,
plasma cells and macrophages within the prostatic stroma. The epithelium
displays reactive a typia
with
occasional
prominent
nucleoli.
The
histologic findings in combination with the clinical manifestations are
characteristic of chronic prostatitis.
a. Chronic bacterial prostatitis :
Most cases are due to E.coli
infection. In patients with prosta tic calculi and relapsing urinary
20
tract infection, the stones serve as a nidus of infection with
bacteria embedded in the mineral matrix.
b. Chronic abacterial (idiopathic) prostatitis :
common
than
bacterial
prostatitis.
Cultures
This is more
of
expressed prostatic secretion yield negative results.
urine
and
This form
of prostatitis has a prolonged indolent course characterized by
relapses and remissions. 3 6
Non specific granulomatous prostatitis :
The most commonly diagnosed granulomatous process within the
prostate is nonspecific granulomatous prostatitis. The incidence of this
lesion is 0.5%.
The age incidence ranges from 18- 86 years with a mean
of 62 years. Common symptoms include irritative and obstructive voiding
symptoms, fever and chills.
The etiology of this lesion is thought to be a reaction to bacterial
toxins, cell debris, and secretions spilling into the stroma from blocked
ducts.
The earliest lesion consists of dilated ducts and acini filled with
neutrophils, foamy histiocytes, and desquamated epithelial cells. Rupture
of these ducts and acini result in a localized granulomatous and chronic
inflammatory reaction. Surrounding the ruptured acini are multinucleated
giant
cells,
eosinophils.
lymphocytes,
plasma
cells,
epithelioid
histiocytes
and
These dense nodules of inflammatory infiltrate obscure and
efface ductal and acinar elements.4 9
21
Granulomatous prostatitis :
It is a immune mediated process probably caused by blockage of
prostatic ducts and stasis of secretions.
Epithelium is destroyed and
cellular debris, bacterial toxins, prostatic secretions, sperm and semen
escape into stroma eliciting an intense localized inflammatory response.
Grossly the gland is firm to stony hard, cut section shows
obliteration of architecture with forma tion of yellow granular nodules.
Microscopically large nodular aggregate of histiocytes, epithelioid cells,
multinucleated giant cells and plasma cells are seen. 2
Classification of granulomatous prostatitis 4 7 :
♦
Idiopathic (non- specific)
o Typical nonspec ific granulomatous prostatitis
o Xanthoma – xanthogranulomatous prostatitis
♦
Infectious
o Bacterial
В§
Tuberculosis, Brucellosis, Syphilis
o Fungal
В§
Coccididiomycosis,
Cryptococcosis,
Blastomycosis,
Histoplasmosis, Paracoccidioidomycosis.
o Parasitic
В§
Schistosomiasis, Echinococcosis, Enterobiasis.
o Viral
В§
Herpes simplex virus.
♦
Malakoplakia
♦
Iatrogenic
o Post surgical
o After radiation therapy
22
o BCG associated
♦
Systemic diseases
o Sarcoidosis, Rheumatoid arthritis, Wegener’s granulomatosis,
Polyarteritis nodosa, Churg- Strauss syndrome.
Xanthoma : It is a rare form of idiopathic granulomatous prostatitis and
characterized by a localized collection of cholesterol laden histiocytes. It
is a solitary microscopic lesion in the peripheral zone or transition zone.
It closely mimics clear cell carcinoma 5 0 .
Post surgical granulomatous prostatitis :
They are frequent sequelae after transurethral resection or may
rarely develop following needle biopsy.
It is composed of a central region of fibrinoid necrosis surrounded
by palisading epithelioid histiocytes. In contrast to infectious granulomas,
necrosis in post biopsy granulomas contain ghost- like structures of
vessels, acini and stroma.4 9
Malakoplakia :
This
is
a
granulomatous
disease
attributable
to
defective
intracellular lysosomal digestion of bacteria. Grossly, it is characterized
by discrete and confluent soft yellow brown plaques, with central
umbilication or ulceration and peripheral hyperemia. Microscopically, the
architecture is effaced by dense sheet – like aggregates of histiocytes
(Van- Hansemann cells) admixed with lymphocytes and plasma cells.
Intracellular and extracellular Michaelis – Gutmann bodies are seen.
23
These stain with periodic acid schiff (PAS) (polysaccharides), Alizarin
red- S (calcium), Prussian blue (iron) and Von Kossa (anionic component
of calcium ions).5 1
Prostatic calculi :
Prostatic calculi are found within the tissues or acini of the gland.
It is seen in about 7% of prostates with NH. Generally, they are multiple
and small with an average diameter of less than 5mm.
Microscopically,
calculi
are
composed
of
concentric
layers
resembling calcified corpora amylacea and are formed by consolidation
and calcification of corpora amylacea or by calcification of precipitated
prostatic secretions. 5 2
P R E-MALIGNANT LESIONS OF PROSTATE :
The two proposed histological premalignant lesions of prostate are
1)
Prostate intraepithelial neoplasia (PIN)
2)
Atypical adenomatous hyperplasia (AAH).
1) PROSTATIC INTRAEPITHELIAL NEOPLASIA:
Definition :
It is a neoplastic transformation of lining epithelium of prostatic
ducts and acini. The process is confined within the epithelium. 1 0
The term �PIN’ was introduced in 1987 by Bostwick and endorsed
by
consensus
at
1989
International
24
Conference
to
replace
other
synonymo us terms used in the literature including “intraductal dysplasia,
hyperplasia with malignant change, marked atypia and duct acinar
dysplasia”. This consensus group also agreed that PIN should be divided
into two grades (low grade and high grade) to replace the previous three
grade system. PIN - 1 is considered low grade and PIN - 2 and PIN - 3 a r e
considered high grade.5 3
PIN consists of dysplasia and proliferation of the normal luminal
cell layer lining the prostatic ducts and acini.
Prostatic intraepithelial neoplasia : Diagnostic criteria 3 6
Features
Low grade PIN
High grade PIN
1
Architecture
Epithelial cell
crowding and
stratification with
irregular spacing
Similar to low grade PIN;
more crowding and
stratification; and patterns
– tufting, micropapillary,
cribriform and flat
2
Cytology
a)
Nuclei
Enlarged with
marked size
variation
Enlarged
b)
Chromatin
Normal
Increased density and
clumping
c)
Nucleoli
Rarely prominent
Occasionally to frequently
large and prominent
3
Basal cell layer
Intact
May show some disruption
4
Basement
membrane
Intact
Intact
25
LGPIN :
There is proliferation and “piling up” of secretory cells lining
epithelium with irregular spacing. Some nuclei have small inconspicuous
nucleoli while a few contain more prominent nucleoli. The basal cell layer
is intact. It is
difficult to reproducibly distinguish low grade PIN from
normal and hyperplastic epithelium. 1 0
HGPIN :
It is characterized by a more uniform morphologic alteration.
Cytologically, the acini and ducts are lined by malignant cells with
variety of architectural complexity and patterns. The individual cells are
almost uniformly enlarged with increased nuclear/cytoplasmic ratio. Many
cells of HGPIN contain prominent nucleoli and show coarse clumping of
chromatin that is often present along nuclear membrane.
At low
magnification, glands with high grade PIN have a basophilic appearance
reflecting the expanded nuclear chromatin area.1 0
Architectural patterns of HGPIN 9 , 1 0 :
•
Tufting pattern : Nuclei become more piled up, resulting in undulating
mounds of cells.
•
Micropapillary pattern : Show columns of atypical epithelium that
typically lacks fibrovascular cores.
•
Cribriform pattern : Consists of complex architectural pattern such as
Roman bridge and cribriform forma tion.
26
•
Flat pattern : Shows nuclear atypia without significant architectural
changes.
In HGPIN, nuclei towards the center of the gland tend to have bland
cytology as compared to peripherally located nuclei. The grade of PIN is
assigned based on assessment of the nuclei located up against the
basement membrane.
Histologic variants :
Signet ring variant :
HGPIN with signet ring cells is exceedingly rare.
Histologically, cytoplasmic vacuoles displace and indent PIN cell nuclei.
The vacuoles are mucin – ne gative by histochemical staining.
Mucinous variant
: Mucinous HGPIN, a rare form exhibits solid
intraluminal masses of blue tinged mucin that fill and distend the PIN
glands, resulting in flat pattern of growth.
Foamy variant :
Microscopically, foamy PIN glands are large with
papillary infoldings lined by cells with bland nuclei and xanthomatous
cytoplasm.
Inverted variant : It is typified by polarization of enlarged secretory cell
nuclei toward the glandular lumen of high grade PIN glands with tufted or
micropapillary architectural patterns. 5 4
The frequency was estimated to
be less than 1% of all PIN cases.
Small cell neuroendocrine variant :
It is also rare variant in which small
neoplastic cells with rosette – like formations are seen in center of the
27
glands, which display peripheral, glandular type PIN cells.
The small
cells are chromagranin and synaptophysin positive and harbour dense core
membrane – bound neurosecretory granules at the ultrastructural level.
Evidence for the association of PIN a nd prostatic carcinoma 5 3 :
1.
2.
Histology : Similar cytoarchitectural features.
Location : Both are multifocal with predominant peripheral zone
distribution. 5 5
3.
Correlation with proliferative activity : Both have more than 3
times the proliferative activity of benign glands.
4.
Loss of the basal cell layer : PIN - III has loss of basal cell layer
similar to invasive carcinoma.
5.
Increased frequency of PIN, in the presence of carcinoma : Higher
grades of PIN are associated
with a statistically significant
increase in the frequency of invasive carcinoma.5 6
6.
Increased severity of PIN in the presence of carcinoma : Higher
grades of PIN are associated with a statistically significant increase
in the frequency of invasive carcinoma.
7.
Immunophenotype : Both are immunore active for cytokeratins 14,
15, 16 and 19 unlike
NH. Both show Ulex Europaeus – 1 lectin
binding unlike normal epithelial and nodular hyperplasia. Both
show loss of vimentin immunoreactivity.
8.
Age: Incidence and extent of both lesions increase with patient age.
28
PIN and Mucin :
The histochemical study of mucin in PIN by using Alcian blue at
pH- 1
and
pH- 2.5
and
Periodic
acid
schiff
diastase
(PASd)
has
demonstrated that there is progressive decrease in neutral mucin from
normal prostate to high grade PIN and progressive increase in acidic
mucin in areas of HGPIN and carcinoma.
Acidic mucin was absent in
LGPIN and normal prostatic tissue.5 7
Molecular pathology of PIN :
Peptide growth factors appear to control development of normal and
neoplastic prostatic epithelium by acting as autocrine or paracrine
mediators of epithelial – stromal interaction and growth.
Epidermal growth factor (EGF) is expressed weakly in benign
epithelium and PIN and may be upregulated in cancer, although results are
contradictory. C onversely, EGF receptor is downregulated in PIN and
cancer. Mitogen- activated protein (MAP) kinases are key elements of the
signaling
system
to
transduce
extracellular
messages
into
cellular
responses. Overexpression of three MAP kinases (JNK- 1, ERK - 1, and
p38/RK) and MKP- 1 mRNA has been found in all cases of HGPIN
compared with normal prostate.
The bcl- 2 gene suppresses apoptosis and increases the length of
survival of cells. Over expression of bcl- 2 is observed in PIN and cancer
compared with normal pro static tissue, thus interfering with apoptosis
29
resulting in accumulation of genetic abnormalities.
Mutations of the
suppressor gene p53 have been found in a minority of cases of early
prostate cancer. Calcium dependent cell –
Ecad herin
is
downregulated
in
prostate
cell adhesion molecule,
cancer.
Downregulation
of
epithelial cell adhesion molecules in PIN and cancer is accompanied by
upregulation of many of the enzymes for degradation of the extracellular
matrix, including matrix metalloproteinases and type IV collagenases.
Cell proliferation, Death and Differentiation in PIN 5 8 :
The progression from PIN to prostatic carcinoma is a complex
process
in
which
the
kinetic
organization
of
the
normal
prostate
epithelium is altered. Cell proliferation has been d etermined in the
prostatic tissue by evaluating the frequency and location of proliferating
cell nuclear antigen (PCNA).
Similar results were obtained with other
proliferation markers such as MIB- 1 a n d K i- 67 and with deoxyribonucleic acid (DNA) static cytometry as well as by analyses of mitoses and
AgNORs.
The basal cell layer of prostate ducts and acini, which contains cells
able to divide or dividing, includes the proliferative compartment. The
luminal layer, which is unable to proliferate because it contains postmitotic maturing and mature cells, is in the differentiated compartment.
PIN lesions show PCNA positive nuclei in all the cell layers, with
decreasing proportion towards the lumen. This indicates that cells able to
30
proliferate appear in all cell layers of PIN and prostatic carcinoma, thus
resulting in the expansion of the proliferative compartment.
The frequency of apoptotic bodies increase from normal prostate
through PIN to prostatic carcinoma. In PIN, apoptotic bodies are present
in all c ell layers, including the luminal, the frequency decreasing
progressively towards the lumen. The location of apoptotic bodies
basically corresponds to the extension of the proliferative compartment,
which may be the main site of apoptotic body production a nd/or
accumulation.
All studies of differentiation markers indicate that HGPIN is more
closely related to carcinoma than to benign epithelium. Many markers are
downregulated with increasing grades of PIN and cancers, including
markers of secretory diffe rentiation, such as PAP and PSA.
2) ATYPICAL ADENOMATOUS HYPERPLASIA:
It is one of the most common lesions that may be confused with
carcinoma.5 9 Other terms for AAH are adenosis, small gland hyperplasia,
atypical adenosis, and small acinar atypical hyp erplasia.
AAH at low magnification is composed of numerous crowded,
small,
pale- staining
glands
that
resemble
carcinoma.6 0
31
a
nodule
of
low
grade
Diagnostic criteria for AAH and difference between AAH and lowgrade adenocarcinoma 8 , 6 1 :
AAH
Low- grade carcinoma
At low magnification
o Lobular growth
o Infiltrative / Haphazard growth
o Small crowded glands admixed
with larger glands
o May be pure population of small
crowded glands
At high magnification
o Huge (≥3 µm) nucleoli absent
o Occasiona l huge nucleoli present
o Small glands share cytological
and nuclear features with
admixed benign glands
o Small glands differ from
surrounding benign glands
o Pale to clear cytoplasm
o May have amphophilic
cytoplasm
o Blue tinged mucinous secretion
rare
o Blue tinged mucinous secretions
common
o Corpora amylacea common
o Corpora amylacea rare
o Occasional glands with basal
cells
o Basal cells absent
o Basal cell - specific antikeratin
antibodies stain basal cells in
some glands.
o Small glands are not
immunoreactive to antikeratin
antibodies.
AAH has been proposed as a precursor of prostatic adenocarcinoma
in the transitional zone.
32
CARCINOMA OF THE PROSTATE :
Epidemiology :
Prostate cancer is one of the most common cancer occurring in men
after 5t h decade of life.
Age distribution :
The risk of prostate cancer rises very steeply with age. Incidence of
clinical disease is low until after age 50 and increases at approximately 910 t h power of age. World wide, about three- quarters of all cases occur in
men aged 65 or more.6 2
Time trends :
Time trends in prostate cancer incidence and mortality have been
greatly affected by the advent of screening for raised levels of PSA,
allowing increased detection of pre- clinical (asymptomatic) disease. The
largest increase in incidence, especially in younge r men are seen in high
risk countries, probably due to the effect of increasing detection
following TURP and more recently, due to use of PSA test.
PROPOSED RISK FACTORS FOR CARCINOMA PROSTATE :
1) Genetic factors :
Familial association is seen in minority of cases.
There is a 5- 11
fold increased risk among men with two or more affected first degree
relatives. A putative prostate cancer susceptibility gene has been
identified with genetic linkage to 1q24- 25 in such families. 6 3
33
2) Diet :
D i e t r i c h i n fat, cadmium, zinc, non vegetarian have a increased
risk of cancer. Vitamin D deficiency is also implicated in cancer
development.6 4
3) Environmental influences :
Increased risk in the workers exposed to chemicals in the rubber,
textile, chemical, drugs, fertilizers and atomic energy industries.6 4
4) Behavioral factors :
Both increased and reduced sexual activity levels have been
associated with prostate cancer, but the role of sexual activity in prostatic
carcinogenesis is uncertain. 6 4
5) Endocrine s ystem:
Male sex hormone play an important role in the development and
growth of prostate cancer. Testosterone diffuses into the gland where it is
converted by enzyme steroid 5- О± reductase type II to the metabolically
active form DHT.
DHT and testosteorne bind to the androgen receptor
(AR) and the receptor/ligand complex translocates to the nucleus for DNA
binding and transactivation of genes which have androgen – responsive
elements, including those controlling cell division. Polymorphism in the
genes regulating this process might be an explanation for higher risk of
prostate cancer. AR gene has a highly polymorphic region of CAG repeats
34
in exon 1, men with a lower number of AR CAG repeat lengths are at
higher risk of prostate cancer. 6 2 , 6 5
6) Role of viruses :
Herpes simplex virus type II, cytomegalovirus and RNA viruses. 6 4
7) Precursor lesions :
HGPIN is strongly associated with invasive carcinomas.
CLINICAL FEATURES :
Prostatic carcinoma has no specific presenting symptoms, and is
usually clinically
silent.
But
may
sometimes
present
with
urinary
obstructive symptoms. Cancer is often initially manifested in metastatic
sites such as cervical lymphnodes and bone.6 2
Distribution and frequency of cancer in different anatomical zones of
the prostate 3 .
Zone
Transition
Percentage of total
glandular tissue
5- 10
Frequency of
prostatic cancer (%)
20
Central
25
1- 5
Peripheral
70
70
CATEGORIES :
Prostatic carcinoma may be categorized into four groups. 6 6
a)
Latent carcinoma
b)
Incidental carcinoma
c)
Occult carcinoma
d)
Clinical carcinoma
35
Latent carcinoma :
Latent carcinoma is the one that is discovered by the pathologist on
postmortem examination of a patient, who has had no signs or symptoms
referable to prostatic disease.
They are seen in central and peripheral
zones and are well differentiated. The frequency ranges from 27- 73%.
Incidental carcinoma :
It is detected incidentally on routine histopathologic examination of
prostatic tissue removed for benign hyperplasia of the prostate. It is seen
in periurethral area and frequency ranges from 6- 20%.
Occult carcinoma :
Occult carcinoma is the carcinoma found in biopsy of bone or
lymphnode in a
patient who has had no symptoms of prostatic disease.
The prostatic origin is demonstrated by elevated levels of PSA and PAP in
the serum and confirmed by prostatic biopsy.
Clinical carcinoma :
It includes cases in which DRE reveals induration, irregularity of
the outline, or a nodule suspicious of carcinoma of the prostate.
36
WHO
HISTOLOGICAL
CLASSIFICATION
OF
TUMORS
OF
PROSTATE EPITHELIAL TUMORS:
1)
Glandular neoplasms
♦
Adenocarcinoma (acinar)
o Atrophic
o Pseudohyperplastic
o Foamy
o Colloid
o Signet ring
o Oncocytic
o Lymphoepithelioma – like
♦
Carcinoma with spindle cell differentiation (carcinosarcoma,
sarcomatoid carcinoma)
♦
Prostatic intraepithelial neoplasia (PIN)
♦
Prostatic intraepithelial neoplasia, grade III (PIN III)
♦
Ductal adenocarcinoma
o Cribriform
o Papillary
o Solid
2.
Urothelial tumors
♦
3.
Urothelial carcinoma
Squamous tumors
♦
Adenosquamous carcinoma
♦
Squamous cell carcinoma
37
4.
5.
6.
7.
Basal cell tumors
♦
Basal cell adenoma
♦
Basal cell carcinoma
Neuroendocrine (NE) tumors
♦
Endocrine differentiation within adenocarcinoma
♦
Carcinoid tumor
♦
Small cell carcinoma
♦
Paraganglioma
♦
Neuroblastoma
Prostatic stromal tumors
♦
Stromal tumor of unc ertain malignant potential (STUMP)
♦
Stromal sarcoma
Mesenchymal tumors
♦
Leiomyosarcoma
♦
Rhabdomyosarcoma
♦
Chondrosarcoma
♦
Angiosarcoma
♦
Malignant fibrous histiocytoma (MFH)
♦
Malignant peripheral nerve sheath tumor (MPNST)
♦
Hemangioma
♦
Chondroma
♦
Leiomyoma
♦
Gra nular cell tumor
♦
Hemangiopericytoma
38
♦
8.
9.
Solitary fibrous tumor
Hematolymphoid tumors
♦
Lymphoma
♦
Leukemia
Miscellaneous tumors
♦
Cystadenoma
♦
Nephroblastoma (Wilm’s tumor)
♦
Rhabdoid tumor
♦
Germ cell tumour
o Yolk Sac tumor
o Seminoma
o Embryonal carcinoma and terato ma
o Choriocarcinoma
10.
♦
Clear cell adenocarcinoma
♦
Melanoma
Metastatic tumors
METHODS TO OBTAIN PROSTATE TISSUE FOR DETECTION OF
PROSTATE NEOPLASIA6 2 :
1)
Needle Core biopsy :
The 18- gauge needles are widely used for core biopsy. Sextant
biopsies of pro state can be done with same needle with minimum
discomfort. Post biopsy infection is minimal. Needle biopsy involves
tissue only from peripheral zone.
39
2)
Transurethral resection of prostate
TURP specimen consists of tissue from the transitional zone,
urethra, periurethral area, bladder neck, and anterior fibro muscular
stroma.
Well- differentiated tumors found incidentally in the transitional
zone are detected in TURP specimens. Poorly differentiated tumors in the
TURP chips represent part of a larger tumor that has invaded the
transitional zone after arising in peripheral zone.
3)
Prostatic enucleation (Suprapubic prostatectomy)
In patients with massive BPH, this procedure is applied. The
specimen usually consists exclusively of transitional zone and periurethral
tissue with grossly visible nodules.
4)
Radical prostatectomy :
There are two main surgical approaches to radical prostatectomy.
i)
Retropubic prostatectomy allows staging, lymphnode biopsies
with frozen section evaluation prior to removal of prostate.
ii)
Perineal prostatectomy.
1) GLANDULAR NEOPLASMS :
A) ACINAR ADENOCARCINOMA 6 2 :
Gross features :
Carcinoma of prostate arise most commonly in posterior lobe and
thus it is readily palpable on DRE. Grossly evident cancers are firm,
solid, gr itty and range in colour from white- gray to yellow- orange which
40
contrasts with adjacent benign parenchyma. Anterior and apical tumors
are difficult to grossly identify because of admixed stromal and NH.
Histopathology :
Adenocarcinoma of prostate range from well
differentiated gland
forming cancers to poorly differentiated tumors where it is difficult to
identify as being of prostatic origin.
a) Architectural features :
Glands
are
crowded,
grow
in
a
haphazard
fashion,
oriented
perpendicular to each other and irregularly separated by bundles of
smooth muscle, indicative of an infiltrative process.
Small atypical
glands situated in between the larger benign glands also indicate their
infiltrative nature.
Undifferentiated prostatic carcinoma is composed of
solid sheets, cords of cells or isolated individual cells. These architectural
patterns are key components to the grading of prostate cancer.
b) Nuclear features :
Nuclear enlargement with prominent nucleoli is a frequent finding.
c) Cytoplasmic features :
Glands of adenocarcinoma tend to have a discrete crisp, sharp
luminal
border
without
undulations
or
ruffling
of
the
cytoplasm.
Neoplastic glands may have amphophilic cytoplasm. Prostate cancer of all
grades typically lacks lipofuscin compared to its presence in some benign
prostatic glands.
41
d) Intraluminal features :
Prostatic crystalloids are dense eosinophilic crystal- like structures
that appear in various geometric shapes – rectangle, hexagon, triangle or
rod- like, usually seen in low grade prostate cancer. Recently it was also
identified in areas of adenosis and in benign glands adjacent to
adenocarcioma.1 8 , 6 7 Intraluminal pink acellular dense secretions or blue
tinged mucinous secretions on H & E is seen in low grade cancer.
Corpora amylacea is rarely seen in prostate cancer.
e) Malignant specific features :
iii)
Perineural invasion – malignant glands should completely
encircle the nerve. 3 5
iv)
Mucinous fibroplasias (collagenous micronodules) – very
delicate loose fibrous tissue with an ingrowth of fibroblasts
sometimes reflecting organization of intraluminal mucin. 6 8
v)
Glomerulations – glands with cribriform proliferations that is
not transluminal.
Histologic variants :
1.
Atrophic variant : Consists of small atrophic glands exhibiting
marked cyto logic atypia.1 2
2.
Pseudohyperplastic variant : Neoplastic glands are closely packed
which are large with branching and papillary infolding along with
cytologic atypia. 1 3
42
3.
Foamy gland variant : Consists of glands with cells having
xanthomatous cytoplasm with a very low nuclear to cytoplasmic
ratio with dense pink amorphous intraluminal secretions. Nuclei are
small and densely hyperchromatic. 1 4
4.
Mucinous (colloid) carcinoma :
The diagnosis of mucinous
adenocarcinoma is made when at least 25% of tumor resected
contains lakes of extracellular mucin. They behave aggressively
than conventional adenocarcinoma.1 5
5.
Signet ring cell carcinoma : Signet ring carcinoma grows in solid
acinar pattern or single invasive cells and is composed of cells with
signet ring configuration resulting from intracellular accumulation
of mucin. 6 2
6.
Oncocytic variant : Consists of glands with large cells having
granular eosinophilic cytoplasm and round to ovoid hyperchromatic
nuclei. 6 2
7.
Lymphoepithelioma
like
variant
:
Undifferentiated
carcino m a ,
consisting of syncitial pattern of malignant cells associated with
heavy lymphocytic infiltrate. 6 2
8.
Sarcomatoid variant (carcinosarcoma) : Consists of both malignant
epithelial and malignant spindle cell and/or mesenchymal elements.
43
B) DUCTAL ADEN OCARCINOMA6 9 , 7 0 :
Composed of large glands lined by tall pseudostratified columnar
cells with abundant amphophilic cytoplasm.
prostate cancer.
more
frequently
It accounts for 0.2- 0.8% of
It may be located centrally around prostatic urethra or
located
peripherally
admixed
with
typical
acinar
adenocarcioma.
Various patterns may be seen and are intermingled :
1.
Papillary pattern, seen in both centrally or peripherally located
tumors.
2.
Cribriform pattern, formed by back to back large glands with
intragland ular bridging resulting in the formation of slit - like
lumens.
3.
Individual gland pattern, characterized by single glands.
4.
Solid pattern – Solid nests of tumor cells are separated by
incomplete fibrovascular core.
2) UROTHELIAL CARCINOMA :
Accounts for 0.7 – 2.8% of prostatic tumors in adults. It is usually
located within the proximal prostatic ducts.
Histologic types range from papillary urothelial neoplasm to high
grade lesions associated with in situ components.
44
Urothelial carcinoma fills and expa nd ducts, and often develops
central comedonecrosis. Stromal invasion is associated with a prominent
desmoplastic
stromal
response
with
tumor
cells
arranged
in
small
irregular nests, cords and single cells. Angiolymphatic invasion is often
seen. 7 1 , 7 2
3) SQUAMOUS TUMORS :
Tumors with squamous cell differentiation involving the prostate,
accounts for < 0.6% of all prostate cancers.
Adenosquamous carcinoma : It consists of both glandular (acinar) and
squamous cell carcinoma components and usually seen after radiation or
hormonal therapy for prostate cancer.
Squamous cell carcinoma : Pure squamous cell carcinoma (SCC) does
not contain glandular features and is identical to SCC of other origin.
Evidence of keratinisation and squamous differentiation are requir ed for
diagnosis. It is associated with poor prognosis.7 3 , 7 4
4) BASAL CELL TUMORS
♦
Basal cell adenoma
♦
Basal cell carcinoma – consists of large basaloid cell nests
with peripheral palisading and necrosis.7 5
45
5) NEUROENDOCRINE TUMORS(NE) :
NE differentia tion has 3 forms 7 6 , 7 7 –
a)
Focal
NE
differentiation
in
conventional
prostatic
adenocarcinoma. All prostatic carcinoma shows focal NE
differentiation. In 5- 10% of prostatic carcinomas there are
zones with large number of single or clustered NE cells
detected by chromogranin A immunostaining.
b)
Carcinoid tumor : (WHO - well differentiated NE tumor).
They show classic cytologic features of carcinoid tumor and
diffuse NE differentiation.
c)
Small cell NE carcinoma : (New WHO classification - poorly
differentiated NE carcinoma).
They are identical to small
cell carcinomas of the lung and misinterpreted as Gleason
pattern 5b prostatic adenocarcinoma.7 8
6) MESENCHYMAL TUMORS :
Both benign and malignant mesenchymal tumors arise in the
prostate. Sarcomas of the prosta te account for 0.1 – 0.2% of all malignant
prostatic tumors.
Specialised stromal tumors of the prostate encompass stromal
sarcoma and STUMP based on degree of stromal cellularity, presence of
mitotic figures, necrosis and stromal overgrowth. 7 9
46
Four distinct patterns of STUMP
i)
80
Degenerative atypia : Commonest pattern composed of stroma
ranging in cellularity from normal to mildly hypercellular, with
scattered cytologically atypical cells associated with benign
glands.
ii)
Hypercellular pattern : Moderately hypercellular stroma with no
cytologic atypia.
iii)
Myxoid pattern : Extensive overgrowth of cytologically bland,
mitotically
inactive
often
with
myxoid
stroma
resembling
stromal nodules of BPH.
iv)
Phyllodes type growth : Pattern reminiscent of benign phyllodes
t umor of the breast with a leaf- like pattern to the glands and
hypocellular fibrotic stroma.
HISTOCHEMISTRY OF THE PROSTATE8 1 :
Histochemistry, including IHC offers assistance in resolving the
unequivocal diagnosis of malignancy.
Various types of mucins and polysaccharides in prostatic carcinoma
can be demonstrated by alcian blue and PASd. Normal prostate gland
contains mucopolysacharides which are PASd positive.
Mucin expression is seen in both benign and malignant prostatic
epithelium. Most of the benign and normal prostatic glands show neutral
mucin whereas acidic mucin is seen in malignant glands.
47
Alcian blue – PAS staining techniques demonstrated that both latent
and clinical prostatic carcinomas contained acid mucins with sulfated
sialic acid residues; mostly seen in moderate to well differentiated
carcinomas and also in colloid carcinomas.
A non- sulphated acid mucin
is also found in colloid carcinomas and in carcinomas with extensive
mucin production.
Also there is similar level of acidic mucin expression in AAH and
adenocarcinoma, which cannot be used as an adjunctive study in
separating these two lesions but may be of value in separating them from
benign glands. 8 2
NUCLEOLAR ORGANIZER REGIONS :
Nucleolar organizer regions (NORs) are loops o f chromosomal DNA
encoding ribosomal RNA.
NORs
are located on the short arms of five
pairs of the acrocentric chromosomes 13,14,15,21 and 22 within, or
adjacent nucleoli. 2 4
Detectable by the argyrophilia of associated proteins, AgNOR
numbers
correlate
with
growth
fraction
and
have
diagnostic
and
prognostic utility in human tumors.
AgNORs are visualized as small black dots and counts are higher in
tumors and in premalignant lesions as compared with benign lesions and
the counts increase gradually with increasing grades and stages of the
tumors.2 5
48
GLEASON’S HISTOLOGIC GRADING SYSTEM OF PROSTATIC
CANCER :
Gleason grading system named after Donald F. Gleason was created
in 1966 and was later recommended by a WHO consensus conference.
Gleason grading system defines five histological patterns or grades with
decreasing differentiation.
In 2005, International Society of Urological
Pathology (ISUP) consensus conference on Gleason grading of prostatic
carcinoma gave the modified Gleason Grading System. 8 3
2005 ISUP MODIFIED GLEASON GRADING SYSTEM
83
:
Pattern
Description
1
Circumscribed nodule of closely packed but separate,
uniform, rounded to oval, medium sized acini (larger glands
than pattern 3).
2
Like pattern 1, fairly circumscribed, yet at the edge of the
tumor nodule there may be minimal infiltration.
Glands are more loosely arranged and not quite as uniform
as Gleason pattern 1.
3
Discrete glandular units
Typically smaller glands than seen in Gleason pattern 1 or 2
Infiltrates in and amongst non- neoplastic prostate acini.
Marked variation in size and shape.
Smoothly circumscribed small cribriform nodules of tumor
4
Fused microacinar glands
Ill- defined glands with poorly formed glandular lumina
Large cribriform glands
Cribriform glands with an irregular border
Hypernephromatoid
5
Essentially no glandular differentiation, composed of solid
sheets, cords, or single cells.
Comedocarcinoma with central necrosis
papillary, cribriform, or solid masses.
49
surrounded
by
WHO histopathological grading 6 2 :
GX
Grade cannot be assessed
G1
Well differentiated tumor (Gleason score 2- 4 )
G2
Moderately differentiated tumor (Gleason score 5- 6 )
G3- 4 Poorly differentiated tumor/undifferentiated (Gleason score 7- 10).
Gleason score :
Primary grade is assigned to the domina nt pattern and secondary to
the sub - dominant pattern. The two numeric grades are added to obtain the
combined Gleason score.
In tumors with one pattern, the number is
doubled.
2002
TNM
CLASSIFICATION
OF
CARCINOMAS
OF
THE
PROSTATE6 2 :
Clinical Primary Tumor (T)
Tx
Primary tumor cannot be assessed
To
No evidence of primary tumor
T1
Clinically inapparent tumor not palpable or visible by
imaging.
T1a
Tumor
incidental
histologic
finding
in
≤5%
of
tissue
histologic
finding
in
>5%
of
tissue
resected.
T1b
Tumor
incidental
resected.
T1c
Tumor identified by needle biopsy (eg: because of elevated
PSA).
50
T2
Tumor confined within the prostate.
T2a
Tumor involves ≤ ½ of one lobe.
T2b
Tumor involves > ВЅ of 1 lobe but not both lobes
T2c
Tumor involves both lob e s .
T3
Tumor extends through prostate capsule
T3a
Extracapsular extension (Unilateral or bilateral)
T3b
Tumor invades seminal vesicle (s)
T4
Tumor is fixed or invades adjacent structures other than
seminal vesicles, bladder neck, external sphincter, rectum,
levator muscles and pelvic wall.
Pathologic Primary Tumour (pT)8 7
pT2
Organ confined
pT2a
Tumor involves ≤ ½ of 1 lobe.
pT2b
Tumor involves > ВЅ of 1 lobe but not both lobes.
pT2c
Tumor involves both lobes.
pT3
Extraprostatic extension
pT3a
Extraprostatic extension
pT3b
Seminal vesicle invasion
pT4
Invasion of bladder, rectum
51
Regional lymphnodes (N)
Nx
Regional lymph nodes cannot be assessed
No
No regional lymph node metastasis
N1
Metastasis in regional lymph node or nodes.
Distant metastasis (M)
Mx
Distant metastasis cannot be assessed
Mo
No distant metastasis
M1
Distant metastasis
M1a
Involvement of non- regional lymphnodes
M1b
Involvement of bone(s)
M1c
Involvement of other distant sites
Stage grouping :
Stage- I
T1a
No
Mo
G1
Stage- II
T1a
No
Mo
G2,3- 4
T1b,c
No
Mo
Any G
T1,T2
No
Mo
Any G
Stage- III
T3
No
Mo
Any G
Stage- IV
T4
No
Mo
Any G
Any T
N1
Mo
Any G
Any T
Any N
M1
Any G
The ten year cancer- specific survival rate for all stages of ca ncer is
about 51% with an estimated cure rate of 32%.
52
Patients with a well differentiated tumors, Gleason total score 2- 4
have no clinically progressive cancer, where as one- third of patients with
high grade lesions Gleason total score 7- 10 will progress into locally
invasive or metastatic disease.
Patients with less than 5% cancer do not have progressive cancer
and do not require therapy, but patients with more than 5% cancer, about
one - third of the patients progress to clinically manifest disease. If the
tumor is unifocal, the chances of progressive cancer is less, but the
patient with more than 2 foci do progress to clinically manifest disease.
Even after 40 years after the inception of the Gleason grading
system it remains one of the most powerful pr ognostic predictors in
prostate cancer.8 3
TREATMENT :
Localized prostatic carcinomas are treated by radical prostatectomy,
external radiation therapy and deferred (expectant) treatment. For locally
advanced and metastatic tumor, hormonal manipulation like estrogens
anti- androgen can be used. 2
MOLECULAR BIOLOGY OF PROSTATE CANCER 6 2 :
Comparative genomic hybridization screening in DNA of prostate
cancer have shown most commonly chromosomal alterations in prostate
cancer.
They include losses at 1p, 6p, 8p, 10q, 13q, 16q and 18q and
gains at 1q, 2p, 7, 8q, 18q and xq. Several genes have been implicated in
53
the early development of prostate cancer.
S- transferase
(GST),
which
plays
a
The pi- class of Glutathione
caretaker
role
demonstrates
hypermethylation in high percentage of prostate cancer.
NKX3.1, a
homeobox gene located at 8p21 is also implicated in prostate cancer.
PTEN encodes a phosphatase, active against both proteins and
lipids is commonly altered in prostate cancer progression.
PTEN is
be lieved to regulate the phosphatidylinositol 3`- kinase/protein kinase B
(Pl3/Akt) signaling pathway and therefore mutation or alterations lead to
tumor progression.
Tumor suppressor gene p53 are inactivated in late stages in
advanced and metastatic prostatic tumors.
Another common somatic
genomic alteration in prostate and other cancers is telomere shortening.
Several studies have used c- DNA microarrays to characterize the gene
expression profiles of prostate cancer in comparison with benign prostate
d isease and normal prostate tissue which include a - methyl acyl COA
racemose (AMACR), heparin, KLF6 (Kruppel like factor- 6) and EZH2.
Androgen receptor plays a critical role in prostate development.
Withdrawal of androgens leads to rapid decline in prostate cancer growth
shortly to re- emerge, which ar e independent of androgen stimulation.
Mutation in androgen receptor leads to growth of prostate cancer with
significantly lower levels of androgen.
In addition high percentage of
polymorphic CAG repeats are due to mutations in amino – terminal
domain.
Shorter CAG repeat lengths have been associated with greater
54
risk of developing prostate cancer and prostate cancer progression in
African American men.
ANCILLARY STUDIES
A)
Immunohistochemistry 8 4 , 8 5 , 8 6 :
IHC is mainly used in two different clinical settings. Most often in
needle biopsies to distinguish low grade prostatic cancer from benign
mimics and in transurethral resection specimens or metastatic tumor
samples to establish the prostatic origin of a poorly differentiated
carcinoma.
Currently, prostate specific antigen is the most commonly used
biomarker for the diagnosis and the prediction of prognosis of prostate
cancer.
However, PSA is not a cancer specific marker, as it is present
in both benign and malignant prostatic epithelial cells. Serum PSA levels
are frequently elevated in benign conditions such as BPH and prostatitis
in addition to prostate cancer. Consequently patients with elevated serum
PSA must undergo a biopsy to confirm or exclude the presence of prostate
cancer.
34ОІ E12, a high molecular weight cytokeratin is a basal cell marker
identifical immunohistochemically.
However it is also immunoreactive
against squamous, urothelial, bronchial / pneumocyte, thymic, some
intestinal and ductal epithelium.
55
p63, a nuclear stain is co expressed with 34ОІ E12 in majority, of
normal prostate basal cells.
specific as 34ОІ E12
for
the
p63 immunostaining is as sensitive and
identification
of
prostatic
basal
cells
highlighting the nuclei of basal cells of benign glands with no staining
evide nt in malignant glands.
Antibodies against intermediate sized keratin filaments cytokeratin
5 and 6 (CK 5/6) are also excellent markers of prostatic basal cells. So,
there are atleast 3 separate useful immunostains for basal cells (34ОІ E12,
P63 and CK 5 /6), which are regarded as `negative markers’ for cancer.
The diagnosis of small foci of prostate cancer on needle biopsy
requires combination of multiple histological features and immuno
histochemical marker like use of AMACR (P504S).
AMACR displays
several attractive features for a prostate cancer marker, first with
significant levels of over expression. It is viewed as a “positive” marker
for cancer and stains positively in prostate cancer cells in paraffin
embedded tissue specimens.
AMACR
is
a
marker
with
high
specificity
for
prostate
adenocarcinoma. In contrast to carcinoma, most benign cases and benign
prostate tissue adjacent to carcinoma were negative for AMACR.
The
negative predictive value is 95%. Some benign prostatic conditions
mimicking
cancer
including
atrophy,
basal
cell
hyperplasia
and
inflammatory glands can be easily distinguished from prostate cancer by
their non- detectable AMACR.
56
AMACR is also present in different grades of prostate cancer. As a
result, there is considerable interest in the use of `cocktails’ of negative
and positive markers to evaluate atypical acinar foci.
Such cocktails
demonstrate the presence of basal cells in benign glands, the absence of
basal cells in malignant acini and the presence of positive cytoplasmic
staining for AMACR in the cells lining these acini.
B)
DNA ploidy analysis :
DNA content analysis of prostatic adenocarcinoma is done by flow
cytometry, static image analysis, and fluorescent insitu hybridization
(FISH).
C)
Cytogenetics and Allelic loss.
PROGNOSIS AND PREDICTIVE FACTORS :
The College of American Pathologists (CAP) have classified
prognostic factors into 3 categories. 8 7
Category -I : Factors proven to be of prognostic importance and useful in
clinical
patients
management,
which
include
–
Preoperative
PSA,
histologic grade (Gleason score), TNM stage grouping and surgical
margin status.
Category –II : Factors that are extensively studied biologically and
clinically, but where importance remains to be validated in statistically
robust studies.
These include tumor volume, histologic type and DNA.
57
Category -III : All other factors not sufficiently studied to demonstrate
their
prognostic
value.
These
include
–
perineural
invasion,
NE
differentiation, microvessel density, nuclear features other than ploidy,
proliferation markers and
a variety of molecular markers such as
oncogenes and tumor suppressor genes.
58
METHODOLOGY
The present study is a prospective study, undertaken in the
Department of Pathology, J.J.M. Medical Co llege, Davangere, during the
period of June 2005 to May 2007.
This study was conducted on 198
prostatic specimens referred to department of pathology.
Brief clinical data were noted from the case records, which included
the age, presenting symptoms, DRE findings, serum PSA levels and
clinical diagnosis.
Following inclusion and exclusion criteria are adopted in this study
Inclusion criteria :
All types of prostatic specimens including TURP and prostatectomy
are considered in this study.
Exclusion crite ria :
Inadequate biopsies and poorly preserved prostatic specimens are
excluded.
All the prostatic specimens were subjected to a careful and detailed
gross examination. 10% formalin fixed and paraffin embedded tissue
sections from these specimens were used for microscopic study. 4- 6Вµ
thick sections being prepared and stained routinely with H&E.
59
H&E
stains were studied and classified into various benign and malignant
lesions.
Different types of carcinoma were analysed under light microscope.
Histologic grade for each type of adenocarcinoma using the VACURG,
Gleason grading system and Gleason’s histologic scores were noted.
Associated prostatic tissue changes like tumor invasion, PIN and other
prostatic lesions were also analysed.
AgNOR staining metho d of Smith and Crocker was done for every
case and mean AgNOR count calculated. In all specimens, 100 nuclei of
each lesions were examined using a x100 oil immersion objective and a
x10 ocular. Lesional nuclei were taken at random for the counting
procedure. Careful focusing allowed the nucleolar organizer regions
(NOR) to be visualized as black dots arranged both in clusters and clumps
and as individual “satellites” within the cell nucleus. To assess the
reproducibility of the counting procedure, all counts were repeated.
Other special stains like Alcian blue pH- 1, PASd, and Ziehl Neelsen
were performed wherever necessary.
All the specimens were subjected to a detailed study with special
reference to the features mentioned in the proforma and the stain ing of the
histological sections was done using standard procedures mentioned in the
annexures.
60
Statistical analysis :
Results are presented as Mean В± SD and range for quantitative data
and number and percentages for qualitative data.
Group- wise comp arisons were made either by student t- test or
Mann- Whitney test whichever was appropriate.
P value of 0.05 or less was considered for statistical significance.
61
RESULTS
The present study deals with evaluation of various histological lesions
in prostatic specimens. During the period of present study, 198 prostatic
specimens were analysed in the Department of Pathology, J.J.M. Medical
College, Davangere.
These prostatic specimens obtained, constituted 1.48% of 13,357 total
specimens received in the department during the same period.
Prostatic lesions :
Out of 198 prostatic specimens received, 179 cases were benign lesions
and prostatic malignancy was diagnosed in 19 cases. Incidence of benign
lesions was 90.4% and malignant lesions 9.6% in this study.
TABLE -1 : INCIDENCE OF PROSTATIC LESIONS
Gross
Benign lesions
TURP
SPP
Total
136
43
179 (90.4%)
Malignant
lesions
11
8
19 (9.6%)
GRAPH-1 : INCIDENCE OF BENIGN AND MALIGNANT LESIONS
9.6%
90.4%
Benign
Malignant
62
Total
147
51
198 (100%)
Nature of prostatic biopsies :
Among the benign lesions, TURP was done in 136 cases and suprapubic
prostatectomy (SPP) in 43 cases.
Malignant lesions were diagnosed in 11
TURP and 8 suprapubic prostatectomy specimens. So, TURP constituted
74.2% and SPP in 25.8% of the total specimens.
GRAPH-2 : NATURE OF PROSTATIC SPECIMENS
136
140
NO.OF CASES
120
100
80
60
43
40
11
20
8
0
Benign lesions
Malignant lesions
GROSS
TURP
SPP
Age :
Among 179 benign lesions, majority of the benign cases belonged to
the age group of 61- 70 years. Youngest case was 45 years and oldest was 89
years. The mean age group В±SD for benign lesions is 66.4В±8.6 years.
63
Among 19 malignant le sions, majority of the cases were seen in age
group of 71- 80 years. Youngest person was 53 years and oldest person was
82 years old in this category. The mean age group В±SD for malignant lesions
is 70.2В±8.7 years. When age groups of benign and malignant lesions were
compared, P=0.07, which is not significant.
TABLE -2 : AGE INCIDENCE OF VARIOUS PROSTATIC LESIONS
Age (years)
Benign lesions
41- 50
51- 60
61- 70
71- 80
81- 90
Total
8 (4.l7%)
44 (24.6%)
78 (43.8%)
43 (24.0%)
6 (3.43%)
179 (100%)
Malignant
lesions
3 (15.8%)
7 (36.8%)
8 (42.1%)
1 (5.3%)
19(100%)
Total
8 (4.0%)
47 (23.7%)
85 (42.9%)
51 (25.8%)
7 (3.6%)
198 (100%)
GRAPH-3 : AGE INCIDENCE OF VARIOUS PROSTATIC LESIONS
43.8
45
40
42.1
36.8
PERCENTAGE
35
30
24.6
25
20
24
15.8
15
10
5
0
4.5
3.4
5.3
0
41-50
51-60
61-70
71-80
81-90
AGE IN YEARS
Benign lesions
Malignant lesions
64
Clinical features :
The most common clinical symptom of benign lesions was frequency in
92 patients, followed by hesitancy and nocturia in 88 and 77 patients
respectively. Malignant lesions had common symptoms of hesitancy in 13
patients followed by nocturia and frequency in 11 and 9 patients respectively.
However when both lesions were compared, he maturia was significantly
associated with malignant lesions with p<0.05.
TABLE -3 : CLINICAL PRESENTATIONS OF PROSTATIC LESIONS
Symptom
Benign
lesions
(n=179)
Malignant
lesions
(n=19)
Total
(n=198)
P-value
92(51.4%)
9 (47.4%)
101(51.0%)
0.74
Nocturia
77 (43%)
11(57.9%)
88(44.4%)
0.22
Urgency
41(22.9%)
1(5.3%)
42(21.2%)
0.07
Hesitancy
88(49.2%)
13(68.4%)
101(51%)
0.11
Poor stream
63(35.2%)
5(26.3%)
68(34.3%)
0.44
Dribbling
38(21.2%)
4(21.1%)
42(21.2%)
0.99
Retention
75(41.9%)
7(36.8%)
82(41.4%)
0.67
Hematuria
1(0.6%)
5(26.3%)
6(3.0%)
P<0.05*
Fever & Chills
5(2.8%)
0
5(2.5%)
0.46
9(5%)
1(5.3%)
10(5.1%)
0.96
Frequency
Intermittent Stream
P<0.05, significant.
65
GRAPH-4 : CLINICAL PRESENTATION OF PROSTATIC
LESIONS
Intermittent Stream
Fever & Chills
5
0
5.3
2.8
26.3
Hematuria
0.6
36.8
Retention
41.9
21.1
21.2
Dribbling
26.3
Poor stream
35.2
68.4
Hesitancy
49.2
5.3
Urgency
22.9
57.9
Nocturia
43
47.4
Frequency
51.4
0
10
20
30
40
50
60
PERCENTAGE
Benign lesions
66
Malignant lesions
70
80
Digital rectal examination :
Out of 179 benign cases, 172 cases were firm whereas 7 cases were
hard in consistency. Out of 19 malignant cases, 13 cases were hard to feel
and 6 cases were firm in consistency. When both benign and malignant cases
were compared, hard nodule was significantly associated with malignant
cases.
TABLE -4 : DIGITAL RECTAL EXAMINATION FINDINGS
DRE
Benign lesions
Malignant
lesions
Total
Firm
172(96.1%)
6(31.6%)
178(89.9%)
Hard
7(3.9%)
13(68.4%)
20(10.1%)
Total
179(100%)
19(100%)
198(100%)
P<0.001, Highly significant
PERCENTAGE
GRAPH-5 : DIGITAL RECTAL EXAMINATION FINDINGS
100
90
80
70
60
50
40
30
20
10
0
96.1
68.4
31.6
3.9
Firm
Hard
Benign lesions
67
Malignant lesions
Microscopic features in benign lesions :
In the present study, 179 prostatic specimens were showing NH. The
lesions were composed of varying proportions of epithelium and stroma.
Corpora amylacea was
seen in majority of cases. 34 cases were showing
chronic inflammatory cell infiltrate composed of admixture of lymphocytes
and plasma cells. 1 case showed aggregate of neutrophils in and around the
acini.
5 cases were showing NH associated with BCH characterized by basal
cell proliferation. 4 cases of NH were showing a red infarct with squamous
metaplasia.
The lesions were composed of areas of ischemic haemorrhagic
necrosis accompanied by reactive changes in the residual epithelium, whereas
transitional cell metaplasia was seen in 1 case.
4 cases
were showing granulomatous prostatitis with scattered/
confluent epithelioid cell granulomas. Of these, 2 cases composed of
necrotizing granulomas with caseation in the centre. Acid - fast bacilli was
demonstrated by Ziehl- Neelsen staining technique in 1 case. Other 3 cases
were negative for acid fast bacilli.
3 cases were showing NH associated with foci of AAH (adenosis)
which were characterized
by localized well circumscribed proliferation of
small glands admixed with larger glands.
nucleolar prominence.
68
All the gland s showed occasional
TABLE – 5 : MICROSCOPIC FINDINGS IN BENIGN LESIONS
Microscopic findings
No.of cases
1. Adenofibromyomatous hyperplasia (NH)
179
2. Basal cell hyperplasia
05
3. Red infarct with squamous metaplasia
04
4. Transitional metaplasia
01
5. Chronic prostatitis
34
6. Abscess
01
7. Granulomatous prostatitis
04
8. Atypical adenomatous hyperplasia
03
GRAPH-6 : MICROSCOPIC FINDINGS IN BENIGN LESIONS
1
1 4 3
34
4
5
179
1
2
3
4
5
69
6
7
8
Prostatic intraepithelial neoplasia :
NH was associated with low grade PIN in 1 case, which showed
features of epithelial crowding and stratification. The nuclei were enlarged
with anisonucleosis and nuclear chromatin was apparently normal.
High grade PIN was associated with carcinoma in 1 case which showed
cribriform pattern of glands with luminal bridging and a sieve like pattern.
Adjacent area showed small glands infiltrating the stroma.
TABLE – 6 : PROSTATIC INTRAEPITH ELIAL NEOPLASIA
Lesions
No.of cases
LGPIN with NH
1
HGPIN with carcinoma
1
Microscopic features in carcinoma prostate:
19 cases of prostatic carcinoma were identified in the present study. All
of them were adenocarcinomas involving the prostate. All of them showed
one or more of the different growth patterns and were categorized depending
on the predominant growth pattern.
In this study, commonest pattern seen was a discrete glandular/ acinar
pattern in 11 cases, followed by arrangement of tumor cells in cords and
sheets in 8 cases each.
Fused glandular pattern was seen in 7 cases.
Cribriform and nested pattern was seen in 3 cases each. Cribriform pattern
with central necrosis was seen in 2 cases. Perineural invasion was seen in 2
cases.
70
Tumor cells arranged in glands, sheets, cords, had nuclear enlargement,
hyperchromasia with prominent nucleoli at places. These cells were separated
by smooth muscle bundles indicative of infiltrative process.
TABLE -7 : MICROSCOPIC FINDINGS IN CARCINOMA PROSTATE
Microscopic findings
No.of cases
1. Discrete glands
11
2. Fused glands
07
3. Cribriform pattern
03
4. Cords
08
5. Sheets
08
6. Nests
03
7. Cribriform gla nds with central necrosis
02
8. Perineural invasion
02
GRAPH-7 : MICROSCOPIC FINDINGS IN CARCINOMA PROSTATE
2
2
3
11
8
7
8
3
71
1
2
3
4
5
6
7
8
Adjacent prostatic tissue:
No.of cases
Nodular hyperplasia
12
Inflammation
02
HGPIN
01
The adjacent tissue in these cases showed NH in 12 cases, inflammation
in 2 cases and HGPIN in 1 case.
Gleason’s score :
All of these 19 malignant cases were graded using Gleason’s scoring
system. Primary grade is assigned to dominant pattern and secondary grade to
the subdominant pattern.
The two numeric grades are added to obta in the
combined Gleason’s score. In tumors with one pattern of arrangement, the
number is doubled.
Gleason score of 8 was the commonest pattern seen in 9 cases (47.4%).
Gleason score of 7 and 9 was seen in 4 cases (21%) each. Gleason score of 10
was see n in 2 cases (10.6%). The earlier patterns of Gleason’s score were not
seen in the study.
72
TABLE -8 : INCIDENCE OF CARCINOMA WITH REFERENCE TO
GLEASON’S SCORE
Gleason’s score
No.of cases
%
7
4
21
8
9
47.4
9
4
21
10
2
10.6
Total
19
100%
GRAPH-8 : INCIDENCE OF CARCINOMA WITH
REFERENCE TO GLEASON'S SCORE
50
47.4
45
40
PERCENTAGE
35
30
25
21
21
20
15
10.6
10
5
0
7
8
9
GLEASON'S SCORE
73
10
TABLE -9 : FINAL HISTOPATHOLOGICAL DIAGNOSIS
Final histopathological diagnosis
No.of
cases
%
a) Without prostatitis
126
63.64
b) With prostatitis
35
17.69
c) Granulomatous prostatitis
04
2.02
2. Basal cell hyperplasia
05
2.53
3. Red infarct with squamous metaplasia
04
2.02
4. NH with transitional metaplasia
01
0.5
5. Atypical adenomatous hyperplasia
03
1.5
6. PIN - LGPIN
01
0.5
7. Adenocarcinoma
19
9.6
1) NH
Among the 198 cases studied, 126 cases were NH without prostatitis
and 35 cases were with prostatitis, together constituting 81.33% of total cases.
Malignant cases (19) constituted 9.6% of total cases of which 1 case was
associated with HGPIN.
Mean AgNOR count :
The mean AgNOR counts were higher in cases of malignant lesions as
compared with benign lesions.
Occasionally, there was a fine background
precipitate of silver granules in some tissue sections which could be easily
differentiated by its random distribution and smaller size.
74
The mean AgNOR counts were : granulomatous prostatitis 1.40В±0.1,
metaplasias 1.45В±0.2, NH with or without prostatitis 1.60В±0.2,
AAH
2.20В±0.1, PIN 2.3В±0.0 and prostatic adenocarcinoma 5.49В±0.7. The pooled
mean AgNOR count
for the benign prostatic lesions was 1.60В±0.2 which was
significantly lower than that of the prostatic adenocarcinomas (P<0.001)
which was highly significant.
TABLE -10 : MEAN AgNOR COUNT IN PROSTATIC LESIONS
Mean AgNOR В±SD
1. Granulomatous prostatitis
1.40В±0.1
2. Metaplasias
1.45В±0.2
3. NH with or without prostatitis
1.60В±0.2
4. AAH
2.20В±0.1
5. PIN
2.30В±0
6. Carcinoma (Gleason score - 7)
4.7В±0.1
7. Carcinoma (Gleason score 8- 10)
5.7В±0.9
Mean AgNOR count in benign and malignant lesions :
Range
Mean AgNOR В± SD
Benign lesions
1.22 to 2.3
1.60 В± 0.2
Malignant lesions
4.52 to 7.4
5.49 В± 0.7
Mann – Whitney test was used to assess the statistical differences
between AgNOR counts of benign and malignant lesions with t=53.9, Z=7.23
and P<0.001 which was considered highly significant.
75
Graph-9 : Mean AgNOR Counts in Benign & Malignant Lesions
Mean AgNOR (per 100 Nuclei)
6
5
4
3
2
1
0
Gr.Pr.
Metp
NH+Prost
AAH
Benign
PIN
CA(GL SCR- CA(GL SCR:
7)
8-10)
Malignant
Serum PSA values :
Total serum PSA levels were done in only 65 cases of which 60 cases
were benign and 5 cases were malignant.
Serum PSA values over 10ng/ml
were seen in 10 benign (16.6%) cases and 5 malignant (60%) cases. However
when both PSA values were comp ared, P=0.02 which was highly significant.
76
TABLE -11 : SERUM PSA LEVELS IN PROSTATIC LESIONS
PSA values
(ng/ml)
Benign lesions
Malignant
lesions
Total
0 – 4.0
29 (48.33%)
1 (20%)
30 (46.15%)
4.1 – 10.0
21 (35%)
1 (20%)
22 (33.84%)
10.1 – 20.0
6 (10%)
0
6 (9.23%)
> 20+
4 (6.66%)
3 (60%)
7 (10.76%)
Total
60 (100%)
5 (100%)
65 (100%)
GRAPH-10 : SERUM PSA LEVELS IN PROSTATIC
LESIONS
70
60
60
48.33
PERCENTAGE
50
35
40
30
20
20
20
10
6.66
10
0
0
0-4.0
4.1-10.0
10.1-20.0
>20+
PSA VALUES (ng/ml)
Benign lesions
Malignant lesions
77
78
79
80
81
82
83
84
85
DISCUSSION
Prostatism is a common malady in the geriatric age group. BPH and
carcinoma of the prostate are increasingly frequent with advancing age.
Prostatic
specimens
pathology workload.8 8
thus
constitute
a
good
percentage
of
surgical
The various histological appearances of BPH and
prostatic adenocarcinoma
are well known and have been described and
illustrated ext ensively in the literature. 5 9 This study was undertaken to
evaluate the various histological lesions in the prostatic specimens.
In this study, 198 prostatic lesions were analysed.
These formed
1.48% of the total surgical specimens received during the study period.
Histopathological diagnosis :
The present study showed that majority, 90.4% of cases were benign
lesions, of which NH alone constituted 63.64% cases, followed by 9.6% of
cases of adenocarcinoma.
In a study, Mittal et al showed 92.98% of
followed by 7.02% of malignant cases.8 8
86
cases of benign lesions
TABLE – 12 : HISTOPATHOLOGICAL DIAGNOSIS IN DIFFERENT
STUDIES
Histopathological
Diagnosis
Mittal BV et
al (1989) 7 8
Elizabeth et al
(2005)8 9
Present study
(2007)
103 (55.67%)
1029 (88.5%)
126 (63.64%)
30 (16.24%)
-
35 (17.69%)
Granulomatous prostatits
3 (1.62%)
-
4 (2.02%)
Basal cell hyperplasia
10 (5.4%)
-
5 (2.53%)
19 (10.27%)
-
5 (2.52%)
Atypical adenomatous
hyperplasia
4 (2.16%)
-
3(1.51%)
Atrophy
3 (1.62%)
-
-
-
7 (0.6%)
1 (0.5%)
13(7.02%)
127 (10.9%)
19 (9.6%)
185
1163
198
Nodular hyperplasia
Prostatitis
Metaplasias
PIN
Carcinoma
Total no.of prostatic
specimens
Hyperplasias :
In the present study, the incidence of benign lesions was 90.4%.
NH associated with other lesio ns was seen in 191 cases where hyperplasia
of both epithelial and stromal (fibromuscular) components were seen.
includes those cases in which NH occurred together with any of
lesions
like
carcinoma,
PIN,
atypical
hyperplasia,
It
other
metaplasias,
granu lomatous prostatitis or basal cell hyperplasia. NH alone was noted in
63.64% of cases, out of which 43.8% of cases were encountered in the 6 t h
87
and 7t h decade. The decline in the number of cases beyond the age of 80
years may reflect the average life span of people in our country.
In the present study, 5 cases showed NH along with basal cell
hyperplasia in the age group of 55- 77 years with usual symptoms of
frequency and nocturia.
It is characterised by small uniform darkly
staining basal cell forming solid nests, tubules and cords with peripheral
palisading appearance.
2 cases showed clear cell change in BCH and
calcified deposit was seen in 1 case.
In a study by Cleary et al, all the patients were above the age of 60
years and all had NH, in additio n to basal cell hyperplasia. 4 0
The
present
study
showed
4
cases
of
squamous
metaplasia
associated with red infarct in addition to NH and 1 case of transitional
metaplasia along with NH, together accounting for 2.52% of total cases
studied. However study by Mittal et al showed metaplastic epithelium in
11.35% of cases.8 8
Prostatitis :
In the present study, out of 198 cases, 39 cases had prostatitis.
TABLE – 13 : INCIDENCE OF PROSTATITIS
Chronic prostatitis
34 (17.18%)
Abscess
01 (0.51%)
Granulomatous prostatitis
04 (2.02%)
Total
39 (19.71%)
88
In a study by Stillwell et al, 25 cases of prostatic abscess showed
sheets of neutrophils in and around the acini. 9 0
In cases of chronic non- specific prostatitis, lymphocytes, plasma
cells and macrophages were seen.
Bostwick in his study has reported
more cases of chronic abacterial as compared to bacterial prostatitis.3 6
In the present study, 4 cases of granulomatous prostatitis (2.02%)
were noted, out of which 2 cases showed evidence of caseation with
granulo mas. Ziehl Neelsen stain for AFB was positive in 1 case. Mittal et
al, showed granulomatous inflammation in 1.6% of his cases. 8 8
In a study of 200 cases of granulomatous prostatitis, non- specific
granulomatous prostatitis was seen in 138 cases (69%), 49 cases were post
biopsy granulomas (24.5%), 7 cases were due to tuberculosis (3.5%) and 6
cases were systemic granulomatous disease (3%). 9 1
Atypical adenomatous hyperplasia :
In the present study, AAH was seen in 3 cases (1.50%).
These
lesions seen in TURP specimens, were small, multifocal and associated
with NH. All these cases were in the age group of 68- 74 years.
The reported incidence of AAH ranges from 2.2% to 19.6% in the
literature in TURP specimens.4 5
PIN :
In the present study, 2 cases showed PIN. 1 case of LGPIN was
associated with NH and 1 case showed HGPIN which was associated with
89
prostatic carcinoma.
LGPIN was characterized by epithelial crowding,
stratification and anisonucleosis.
HGPIN was characterised by pronounced epithelial crowding,
nuclear enlargement, hyperchromasia and luminal bridging giving a
cribriform appearance.
Prominent nucleoli was also seen. Adjacent area
showed small glands infiltrating the stroma.
In our study, PIN was seen in the age group of 60- 68 years.
A
similar peak age group was seen in a study by McNeal on premalignant
lesions of the prostate. 5 6
TABLE-14 : INCIDENCE OF PIN IN CASES OF PROSTATES WITH
AND WITHOUT PROSTATIC CARCINOMA
Authors
No.of
prostates
examined
PIN
without
carcinoma
(%)
PIN with
carcinoma
(%)
McNeal & Bostwick et al (1986) 9 2
200
43
82
Kovi et al (1988) 9 3
429
46
59.3
1077
47
61.4
198
0.5
0.5
Horninger W. et al (2001)9 4
Present study (2007)
Brawer showed, the incidence of PIN was higher in organs with
carcinoma than in those without . According to this study, PIN was found
in 73% of prostates with carcinoma and 32% of prostates without
carcinoma.5 5
90
TABLE-15: INCIDENCE OF HGPIN IN PROSTATES WITH
CARCINOMA
Authors
Incidence of HGPIN in prostatic
adenocarcinoma (%)
McNeal & Bostwick e t al (1986) 9 2
33
Kovi et al (1988) 9 3
33
Troncoso et al (1988) 9 2
72
Quinn et al (1990)9 5
100
Horninger W. et al (2001)9 4
61.4
Present study (2007)
0.5
The incidence of HGPIN is relatively low in cases of prostatic
carcinoma in our study because most of the specimens were TURP which
does
not
have
enough
material
compared
specimen studied in other studies. 9 6
to
radical
prostatectomy
It is also suggested that transition
zone might not be associated with HGPIN. 5 5 Moreover the incidence of
isolated HGPIN is uncommon in TURP specimens (prevalence 2.3%)9 7 .
It is common in peripheral zone as compared to transition zone.7
The incidence of PIN varies considerably in different studies
probably because histological diagnosis of LGPIN shows subjective
variatio n and many studies do not report LGPIN.7
91
Prostatic carcinoma :
In the present study, the prevalence of carcinoma prostate was
9.6%.
This is rather low compared to most reported series and there is
wide variation in the incidence rate of prostate cancer in different parts of
the world.8 8
The prevalence rate of 9.6% observed in present study is
comparable with study by Murali et al, which showed a prevalence rate of
8.56%.
The increased incidence of prostatic carcinoma in developed
countries is attrib uted to the extent of diagnosis of latent cancers by
screening of asymptomatic individuals and also to the risk of the disease
associated in these countries. 6 2
Direct comparison of total rates of prostatic carcinoma in different
series may be misleading. There is a great discrepancy between the high
frequency of prostatic carcinoma revealed at autopsy and the occurrence
of
carcinoma
manifested
which
has
been
clinically
suspected.
In
clinically
carcinoma, the tumor is generally larger than in the latent
one, but the histological features are essentially the same. 8 8
92
TABLE-16 :
PREVALENCE OF PROSTATIC CARCINOMA IN
DIFFERENT STUDIES
Authors
No.of
prostates
examined
No.of
carcinoma
Prevalence
(%)
Newman et al (1982)9 2
500
71
14.0
Murali et al (1985)9 8
222
19
8.56
Moore et al (1986) 9 2
143
31
22
Murphy et al (1986)9 2
386
66
17
Yamabe et al – Japan (1986)9 2
191
24
13
Yamabe et al – Netherlands
(1986)9 2
452
57
13
Eble and Tejada (1986)9 2
700
132
19
Rohr et al (1987) 9 2
457
65
14
Mittal et al (1989) 8 8
185
13
7.02
Present study (2007)
198
19
9.6
In the present study, peak incidence of prostatic carcinoma was
seen in age group of 71- 80 years, a decade earlier than PIN which
occurred between age group of 60- 68 years; which was similar to that
found in the literature.
Many recent studies show a higher incidence of prostatic carcinoma
in the age group of 61- 70 years.
93
TABLE-17 : AGE INCIDENCE OF PROSTATIC CARCINOMA IN
DIFFERENT STUDIES
Authors
51- 60
yrs
61- 70
yrs
71- 80
yrs
81- 90
yrs
Total (%)
Rich (19 34) 9 2
7
8
12
0
27 (9%)
Moore (1935) 9 2
9
18
13
7
47(20%)
Baron & Angrist (1945)9 2
20
26
25
6
54(61%)
Andrews (1949)9 2
2
7
7
-
16(16%)
Edwards et al (1953) 9 2
3
10
12
3
28(19%)
Franks (1954)9 2
38
53
70
17
178(20%)
Scott et al (1961)9 2
-
-
36
26
62(39%)
Holund (1980)9 2
2
7
24
13
46(23%)
Mittal et al (1989) 8 8
1
6
5
1
13(7.02%)
Present study (2007)
3
7
8
1
19(9.6%)
In the present study, 19 cases of adenocarcinoma prostate were seen
accounting for 9.6% of the cases. Out of which 2 cases showed perine ural
invasion. These changes have been well documented in literature. 9 9
All these 19 malignant cases were graded using Gleason’s scoring
system. Majority of our cases showed moderate to poor differentiation.
Gleason score of 8 was the commonest pattern seen in 47.4%
of
cases. Gleason score of 7 & 9 was the next commonest pattern seen in
21% of cases each. In present study, low grade adenocarcinoma was not
detected probably as these lesions were asymptomatic.
94
In a study by Bob Djavan et al, the inc idence of carcinoma was
22%.
Mean age of patient was 67 years
and mean Gleason score was
6. 1 0 0
TABLE – 18 : INCIDENCE OF PROSTATIC CARCINOMA, MEAN
AGE AND MEAN GLEASON’S SCORE
Authors
Incidence
of prostate
cancer
Mean age
(years)
Mean score
22%
67
6
Babaian Richard et al (2001) 1 0 1
24.5%
62
6
Present study (2007)
9.6%
70
8
Bob Djavan et al (2007) 1 0 0
TABLE – 19 : INCIDENCE
PROSTATIC CARCINOMA
Authors
OF
GLEASON’S
Gleason
score
No.of
patients
6
12
7
1
8
1
9
0
10
0
7
4
8
9
9
4
10
2
Babaian Richard et al (2001) 1 0 1
Present study
95
SCORE
AND
Incidence
of cancer
24.5%
9.6%
Serum PSA values :
Normal levels of PSA are usually <4ng/ml but they vary according
to the age of the patient. PSA levels <4 ng/ml of 60 years or less and
levels <6.5 ng/ml in mean age of 60- 80 years are normal. PSA is elevated
by any change that destroys the normal architecture of the prostate which
allows diffusion of protease into the microvascular circulation. 1 0 2
NH is a common cause of serum PSA elevation and accounts for 6070% of cases. Studies of patients with histologically confirmed NH have
shown that 21- 86% have elevated serum PSA levels.
The degree of
elevation is modest (4.1 – 10 ng/ml).3 1
In the present study, only 65 cases had serum PSA levels estimated.
This is bec ause the specimens were received from both Government and
Private Hospitals
where there is no such feasible laboratory services
available. It is also observed that, not all the cases of surgical resection of
the prostate, serum PSA level estimation was requested.
Out of 65 cases, 60 cases were benign. A total of 21 cases showed
modest elevation of PSA levels and 10 cases showed elevation more than
10 ng/ml in benign cases. This is because, these cases of NH was
associated
with
prostatitis,
abscess,
infarcts
and
granulomatous
prostatitis.
According to a study on chronic prostatitis, serum PSA was high in
99% of cases. Prostatic manipulations including cystoscopy, needle
96
biopsy causes marked elevation of serum PSA levels.
Whereas digital
rectal examinatio n, prostatic massage and ultrasonography have minimal
effects on serum PSA levels in most patients. 1 0 3 Acute urinary retention
also elevates the serum PSA values. 1 0 4
Serum PSA levels were frequently elevated in patients with PIN
ranging from 0.3 to 22.3 ng/ml (mean 4.0). 1 0 5
In the present study, 3 cases of prostatic carcinoma showed PSA
levels > 20ng/ml, however 2 cases had PSA levels =10ng/ml.
This is
attributed to study in which prostate cancers detected at lower PSA levels
are more likely to have a small volume and are of low grade. 1 0 6
AgNOR count :
AgNOR in normal cells are usually tightly aggregated within one or
two nucleoli, making individual AgNORs
indiscernible.
An increase in
the mean AgNOR count of a cell population could be result of
a)
Cell proliferation causing nucleolar disaggregation and making
individual AgNOR detection easier.
b)
Defect of nucleolar association resulting in AgNOR dispersion.
c)
Increase in ploidy, resulting in a real increase of AgNOR
bearing chromosomes.
d)
Increase in transcriptional activity. 2 5
Theoretically, neoplastic cell populations could show any or all of
the above defects and therefore demonstrate increased AgNOR counts.
97
In prostate lesions many studies have shown a significantly
increased proportion of proliferating cells in malignant lesions compared
to that of benign hyperplasia, the greatest proliferative indices are noted
in high grade carcinomas.
Thus, AgNOR numbers increase with more
aggressive, higher grade prostate lesions. 2 5
In present study, mean AgNOR co unts progressively increased from
NH to AAH, PIN and carcinomas.
Furthermore, the mean AgNOR counts
of carcinomas were significantly different from those in benign conditions
and no overlap in count was seen between these conditions.
Although only 3 cases of AAH were studied to allow firm
conclusions regarding its benign or malignant nature, mean AgNOR
counts in AAH (2.2 В± 0.1) were slightly greater than that of NH (1.6 В±
0.2).
In the present study, mean AgNOR counts of intermediate grade
tumor (Gleason score- 7) was 4.7В±0.1 and high grade tumor (Gleason score
8- 10) was 5.7В±0.9 which correlated with conventional histological grade.
The counts were higher in high grade tumor compared to low count in
intermediate grade tumor.
Similar observations were seen in different
studies. 2 5 , 2 6
98
TABLE – 20 : COMPARISON OF MEAN AgNOR COUNT IN
PROSTATIC LESIONS
Authors
NH
Granulomatous
prostatitis
Metaplasia
AAH
PIN
Carcinoma
G- I
G- I I
G- I I I
Deschenes et al
(1990)2 5
4.51
-
-
5.64
7.35
-
8.87
10.45
Ghazizadeh et
al (1991) 2 6
1.56
1.35
1.23
2.2
-
2.96
4.42
5.89
Verma et al
(2006)2 3
2.93
-
-
-
-
4.98
7.26
10.98
Present study
(2007)
1.6
1.4
1.45
2.2
2.3
-
4.7
5.7
99
CONCLUSION
Prostatic nodular hyperplasia and adenocarcinoma are common
diseases that account for considerable morbidity and mortality in the
aging population.
Predisposing and protecting factors for these lesions,
need to be identified. Interpretation of prostatic biopsies has been, and
continues to be a challenge to the pathologist.
The cause of concern is
that majority of carcinomas are of higher grade tumors.
Mean AgNOR
counts of malignant lesions are significantly higher when compared to
benign lesions and correlated with histologic grade of tumor. Combined
staging, grading and follow- up study are required to obtain best predictive
values. Another obstacle is several forms of therapy may significantly
alter the normal and diseased prostatic tissue, making the assessment
difficult.
Further, immunohistochemistry and molecular genetic analysis
are suggested. Screening protocols and awareness programs need to be
instituted.
100
SUMMARY
A prospective study to evaluate the various histological lesions in
prostatic specimens was undertaken during the period from June 2005 to
May 2007. The follo wing are the salient observations noted in this study.
1.
Prostatic specimens constituted 1.48% of the total number of
surgical specimens received during the same period.
2.
Out of 198 cases studied, commonest pathology encountered was
benign lesion constituting 90.4% and malignant lesions were 9.6%.
3.
Majority
of
specimens
were
TURP
(74.2%)
followed
by
prostatectomy (25.8%) specimens.
4.
Benign lesions were common in age group of 61- 70 years with
commonest symptoms of frequency, hesitancy and nocturia.
5.
Digital re ctal examination finding showed firm nodule in 178 cases
and hard consistency in 20 cases.
6.
In benign cases, serum PSA was normal in 48.33% cases. Modest
elevation (4.1 – 10ng/ml) was seen in 35% cases and marked
elevation (>10ng/ml) in 16.66% cases. In ma lignant cases, modest
elevation was seen in 20% cases and marked elevation in 60% cases.
7.
Out of 179 cases of benign lesions, 126 cases (63.64%) were
diagnosed as nodular hyperplasia without prostatitis, 35 cases
(17.69%) were diagnosed as nodular hyperpla sia with prostatitis,
101
basal cell hyperplasia in 5 cases (2.53%), graulomatous prostatitis
and red infarct with squamous metaplasia in 4 (2.02%) cases each
and transitional metaplasia in 1 (0.5%) case. Atypical adenomatous
hyperplasia was seen in 3 (1.50%) cases.
8.
Low grade PIN was seen associated with NH in 1 case (0.5%) and
High grade PIN was seen adjacent to adenocarcinoma in 1 case
(0.5%).
9.
Clinical diagnosis of prostatic carcinoma was made in 21 cases, out
of which 13 cases correlated histologically.
10.
I ncidence of carcinoma was 9.6% and peak age group affected was
between 71- 80 years with commonest symptoms of hesitancy,
nocturia and frequency. Hematuria was significantly associated with
malignant lesions.
11.
Histologically,
all
the
malignant
adenocarcinoma of prostate.
lesions
encountered
were
The commonest pattern seen were
acinar followed by arrangement of tumor cells in cords, sheets and
cribriform pattern. In 2 cases perineural invasion was seen.
12.
Gleason’s score of
8 was seen in majority of the cases (47.4%).
Gleason score of 7 and 9 was seen in 21% cases each.
13.
In carcinoma of prostate there is a shift from neutral mucin to
acidic mucin as demonstrated by Alcian blue at pH- 1.
102
14.
Mean AgNOR count in benign and malignant lesions were 1.6В±0.2
and 5.49В±0.7 respectively.
15.
Mean AgNOR count of intermediate and high grade tumors were
4.7В±0.1 and 5.7В± 0.9 respectively, correlating with the histological
grade of tumor.
Prostatic carcinoma shows heterogeneity of differentiation, nuclear
anaplasia, cytoplasm, functional differentiation and DNA content. There
is a need for research on all aspects of this disease.
The ultimate
conquest of prostatic carcinoma will require substantial advances in our
understanding of the cause of this tumor, further development and
refine ment
of
diagnostic
techniques
and
the
development
therapeutic modalities for the treatment of systemic disease.
103
of
new
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cancer. Br J Urol 1988;62:584- 589.
105.
Alexander EE, Qian J, Wollan PC. Prostatic intraepithelial neopalsia
does not raise serum prostate specific antigen. Urol 1996;47:693- 698.
118
106.
Thompson MI, Pauler KD, Goodman JP, Tangen MC, Lucia SM, Parnes
LH, et al.
Prevalence of prostate cancer among men with a prostate
specific antigen level = 4.0 ng per ml. N.Engl J Med 2004;350:
2239- 2246.
119
PROFORMA
J.J.M. MEDICAL COLLEGE,
DEPARTMENT OF PATHOLOGY, DAVANGERE.
Guide : Dr. H.GURUBASAVARAJ
Student: Dr. SUSHMA .T.A.
Co-Guide: Dr. HIREMATH .S.S.
TOPIC : “SPECTRUM OF HISTOLOGICAL LESIONS IN PROSTATIC SPECIMENS”
Name :
Age :
Occupation :
Marital Status:
Address :
Hospital : CGH/BH/ESI/PVT
Ward No:
IP No. :
S.E.S :
Religion:
PRESENTING COMPLAINTS :
SYMPTOMS :
1. Frequency of micturation:
2. Urgency :
3. Nocturia :
4. Retention of urine:
5. Incontinence of urine
6. Obstructive symptoms like hesitancy, poor flow,
dribbling, intermittent stream :
Date
Case No
Biopsy No
DOA
DOD
:
:
:
:
:
7. Hematuria :
8. Painful ejaculation:
9. Discharge from urethra:
10. Fever with chills :
11. Symptoms of uremia:
Past history : H/o similar complaints / prostatic biopsy
:
H/o DM/HTN/UTI/ Gonorrhoea/Syphilis
:
Family history :
Personal history :
Yes/No
Yes/No
GENERAL EXAMINATION :
DIGITAL RECTAL EXAMINATION :
SYSTEMIC EXAMINATION :
CLINICAL DIAGNOSIS :
INVESTIGATIONS :
1. Blood :
Hb%
TC:
2. Urine:
Albumin:
3. Biochemical: Urea:
4. Cystoscopy :
5. X-ray :
6. Ultrasonography :
DC:
Sugar:
Sugar:
ESR:
Micro:
Blood group:
Culture:
PSA :
Treatment and advice :
HISTOPATHOLOGICAL EXAMINATION :
Type of biopsy : TURP /Needle biopsy/ Prostatectomy – Suprapubic / Perineal /Radical
120
GROSS EXAMINATION :
Size :
Weight :
Surface:
Consistency:
MICROSCOPY :
1.
Capsule
2.
Colour:
Cut surface :
Architectural pattern of glands
a. Gland size
b. Gland shape
c. Gland arrangement
3.
Intraluminal secretions
4.
Cell arrangement
Double layer / Single layer / Tufting/ Micropapillary / Cribriform/ Flat/ Papillary
Basal cell hyperplasia / Cribriform hyperplasia
Basal cell layer / Basement membrane
5.
Nuclear features :
Normal, evenly distributed chromatin / Anisonucleosis / Nucleomegaly /
Vesicular / Hyperchromatic / Nucleoli / Mitotic figures.
6.
Cytoplasm
Scant/ Clear / Eosinophilic / Amphophilic
7.
Metaplasia
Squamous / Transitional
8.
Stroma
Inflammatory cells
Extra-prostatic extension
9.
AGNOR count
Histopathological diagnosis :
Gleason score :
Special stains :
• Alcian blue
• PAS
• Ziehl Neelsen Stain
DISCUSSION :
121
PROCEDURE FOR SPECIAL STAINS
Periodic Acid-Schiff with Diastase Predigestion:
1. Bring sections to water
2. Treat with diastase (saliva) for 30 minutes
3. Wash in running tap water for 10 min.
4. Oxidise for 5 min in 1% aqueous periodic acid.
5. Wash in running water for 5 minutes, and rinse in distilled water
6. Treat with schiff reagent for 15 minutes.
7. Wash for 10 minutes in running water.
8. Counterstain with haematoxylin.
9. Dehydrate, clear and mount in synthetic resin.
Result :
PAS positive substances
-
Bright red
Nuclei
-
Blue
Other tissue constituents
-
Yellow.
ALCIAN BLUE (pH-1 )
1. Bring sections to water
2. Stain in 1% Alcian blue 8 GX in 0.1 N hydrochloric acid for 30
minutes.
3. Rinse briefly in 0.1 H Hcl.
4. Blot dry with fine filter paper to prevent the staining which
sometimes occurs after dilution with water (which will change the
pH) in washing.
122
5. Dehydrate in alcohol, clear in xylene and mount in resinous
mountant.
Result :
Sulphated mucosubstances stain blue.
SOUTHGATE’S MUCICARMINE METHOD :
1. Bring sections to water
2. Stain nuclei with hematoxylin
3. Differentiate in acid alcohol and blue in tap water
4. Stain for 3 0 minutes in mucicarmine solution
5. Rinse in distilled water, dehydrate, clear and mount in canada
balsam or synthetic resin.
Result :
Mucin : Red,
Nuclei : Blue
ZIEHL-NEELSEN STAINING METHOD FOR AFB (Tubercle bacilli)
1. Bring the sections to water
2. Treat the sections with strong carbolfuchsin
3. Heat the underside of the slide till it fumes
4. The sections are subsequently treated with coconut oil to prevent
shrinkage for 10 min.
5. Decolorize with 20% sulfuric acid solution.
6. Counterstain
with
Loeffler’s
methylene
blue solution for 2- 5
minutes.
7. Rinse in water, dehydrate clear and mount in a resinous mountant.
Results :
AFB
:
Red
Nuclei
Other tissue constituents : Pale blue.
123
:
Blue
AgNOR STAINING MEHTOD OF SMITH AND CROCKER :
1. Dewax with xylene for 5 minutes.
2. Hydrate with distilled deionised water through ethanol water
solutions.
3. At room temperature (22В°C), treat sections with freshly prepared
working solution made up of one volume of 2g/100ml gelatin in 1%
formic acid solution and two volumes of 50% aqueous silver nitrate
solution for 30- 35 minutes in dark.
4. Wash
with
deionised
distilled
water
and
hydrated
through
increasing concentrations of ethanol solutions.
5. Clear and mount with DPX.
Results :
NOR – Black dots arranged in clumps, clusters and satellites within
the cell nucleus.
COUNTING PROCEDURE :
100 randomly chosen nuclei were studied and mean AgNOR count
per nucleus in each case was noted.
124
MASTER CHART
Clinical
investigation
Hematuria
Serum PSA
ng/ml
G.Hyp
FMH
BCH
SQ. METP
TR. METP
Inflammatory
infiltrate
PIN
Others
65
2712/05
+
-
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 8
+
+
+
-
-
-
-
-
-
-
1.8
NH
Madeggowda
80
2756/05
+
-
-
+
-
-
+
-
-
-
Hard
9.46
?Ca
TURP, 15
+
+
-
-
-
-
-
-
Cords,sheets
5+5=10
7.1
Poor diff.adeno ca.
3
Malthesh Rao
66
2796/05
+
-
-
-
-
+
-
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
Acute
-
-
-
-
1.9
NH+acute prostatitis
4
Gundappa
63
2894/05
-
-
-
+
+
+
-
-
-
-
Firm
0.76
BPH
TURP, 5
+
+
-
-
-
-
-
-
-
-
1.8
NH
5
M.B. Krishnappa
74
2993/05
+
-
-
+
-
+
-
-
-
+
Firm
8.02
BPH
TURP, 8
+
+
-
-
-
-
-
-
-
1.5
NH
6
Abdul Jilani Sab
65
3040/05
+
-
-
+
-
-
-
+
-
-
Hard
-
?Ca
TURP, 15
+
+
-
-
-
-
-
-
3+5=8
5.2
Poor diff.adeno Ca
7
Rangappa
65
3047/05
-
+
-
+
-
-
-
-
-
-
Hard
-
?Ca
SPP, 40
+
+
-
-
-
Chronic
-
-
3+5=8
5.1
Poor diff.adeno Ca
8
Halageri
60
3125/05
+
-
-
+
-
+
-
-
-
+
Firm
0.69
BPH
TURP, 12
+
+
-
-
-
Chronic
-
-
Glands cords,
sheets
Glands cords,
sheets
-
-
1.8
NH+Chr.Prostatitis
9
Rama Reddy
72
3144/05
+
-
-
+
+
-
-
-
-
-
Firm
7.62
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.6
NH
10 Veeranna
73
3166/05
+
-
+
-
-
-
-
-
-
-
Firm
41.37
?Ca
TURP, 7
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH+Chr.Prostatitis
11 Telga Naik
70
3176/05
-
-
-
+
-
-
+
+
-
-
Hard
-
?Ca
SPP, 30
+
+
-
-
-
-
-
PNI
Glands cords
3+5=8
5.4
Poor diff.adeno Ca
12 Ajjappa
67
3474/05
+
-
-
+
-
-
-
-
-
-
Firm
10.24
BPH
TURP, 10
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH+Chr.Prostatitis
13 Bheemappa
60
3491/05
-
-
-
+
+
+
-
-
-
-
Firm
16.24
BPH
TURP, 8
+
+
-
-
-
-
-
-
-
-
1.6
NH
14 Naseem Khatulla
68
3492/05
+
+
-
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 11
+
+
-
-
-
-
-
-
-
-
1.6
NH
15 Mallurappa
65
3502/05
+
+
-
-
-
+
-
-
-
-
Firm
-
BPH
SPP, 22
+
+
-
-
-
Chronic
-
-
-
-
1.8
NH+Chr.Prostatitis
16 Thippeswamy
71
3519/05
+
-
+
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 11
+
+
-
-
-
-
-
-
-
-
1.2
NH
17 Karibasappa
58
3587/05
-
-
+
-
-
+
+
-
-
-
Firm
0.71
BPH
TURP, 9
+
+
-
-
-
-
-
-
-
-
1.7
NH
18 Rahul Sab
60
3658/05
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.8
NH
19 Nagappa
75
3756/05
+
-
-
+
-
+
+
-
-
-
Firm
-
BPH
SPP, 25
+
+
-
-
-
-
-
-
-
-
1.8
NH
20 Asum Sab
70
3806/05
-
+
-
-
+
-
-
-
-
-
Firm
8.89
BPH
TURP, 10
+
+
-
-
-
Chronic
-
-
-
-
2
NH+Chr.Prostatitis
21 Sharanappa
64
3894/05
-
-
+
-
-
+
+
-
-
-
Firm
-
BPH
TURP, 8
+
+
-
-
-
Chronic
-
NCG
-
-
1.4
NH+non sp gran Prostatitis
22 Nanjappa
55
3953/05
+
+
-
-
-
-
-
-
-
-
Firm
1.1
BPH
TURP, 11
+
+
+
-
-
-
-
-
-
-
1.7
NH
23 Sarvadati
54
3983/05
-
+
-
+
-
-
-
-
-
-
Firm
3.38
BPH
TURP, 9
+
+
-
-
-
-
-
-
-
-
1.8
NH
24 Chamanasab
54
4031/05
+
+
-
+
-
-
-
-
-
-
Firm
5.52
BPH
TURP, 10
+
+
-
+
-
-
-
Red infarct
-
-
1.8
NH+red infarct sq.metp
25 Fakkiravh
55
4046/05
-
+
-
+
+
+
-
-
-
-
Firm
2.52
BPH
TURP, 7
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH+Chr.Prostatitis
26 Hanumanthappa
61
4093/05
-
+
-
+
-
+
-
-
-
-
Hard
1.3
?Ca
SPP, 20
-
-
-
-
-
-
-
-
Glands,cribriform
3+5=8
5.4
Mod diff. Adeno ca
27 Yellappa
76
4100/05
+
+
-
-
-
-
+
-
-
-
Firm
1.33
BPH
TURP, 9
+
+
-
-
-
Chronic
-
-
-
-
1.8
NH+Chr.Prostatitis
28 Hanumanthappa
70
4209/05
+
-
-
+
-
+
-
-
-
-
Firm
3.47
BPH
TURP, 15
+
+
-
-
-
-
-
Focal cr.gl
-
-
2.2
AAH
29 Shivalingappa
75
4270/05
+
+
-
+
-
-
-
-
-
-
Firm
3.74
BPH
TURP, 9
+
+
-
-
-
Chronic
-
-
-
-
1.5
NH+Chr.Prostatitis
30 Bheemappa
72
4377/05
-
-
-
+
+
+
+
-
-
-
Hard
-
?Ca
SPP, 30
+
+
-
-
-
Chronic
-
-
-
-
1.4
NH+Chr.Prostatitis
31 Boraiah
75
4433/05
+
-
-
-
-
-
+
-
-
-
Firm
10.86
BPH
TURP, 15
+
+
-
-
-
Chronic
-
-
-
-
1.4
NH+Chr.Prostatitis
32 Maheshwarappa
53
4553/05
-
-
+
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.5
NH
33 Rudrappa
68
4622/05
+
+
-
+
-
-
-
-
-
-
Firm
5.1
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.5
NH
Gross
(gm)
GL.SCR
Dribbling
Retention
Siddappa
2
Biopsy
No.
CA
Poor
stream
1
Name
Age
(yrs)
DRE
Urgency
Hesitancy
Clinical
diagnosis
Sl.
No.
Fever +
chills
Intermittent
stream
Nocturia
Microscopy
Frequency
Presenting complaints
Mean
AGNOR
count
Final diagnosis
Clinical
investigation
Biopsy
No.
Urgency
Hesitancy
Poor
stream
Dribbling
Retention
Hematuria
DRE
Serum PSA
ng/ml
Clinical
diagnosis
G.Hyp
FMH
BCH
SQ. METP
TR. METP
Inflammatory
infiltrate
PIN
Others
34 Shekarappa
80
4662/05
-
-
-
+
+
+
-
-
-
-
Hard
-
?Ca
TURP, 12
-
-
-
-
-
-
-
-
35 Bhavanappa
62
4756/05
+
-
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 11
+
+
-
-
-
-
-
-
Discrete & fused
glands
-
36 Channabasappa
50
4757/05
-
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 16
+
+
-
-
-
-
-
-
37 Chikkappa
60
4850/05
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
38 Marappa
65
4854/05
-
+
+
+
-
-
+
-
-
-
Firm
-
BPH
SPP, 30
+
+
-
-
-
-
-
39 Fazulla
65
5068/05
-
-
-
+
+
-
+
-
-
-
Firm
-
BPH
TURP, 13
+
+
-
-
-
Chronic
40 Bhavanappa
85
5105/05
-
-
-
+
+
-
+
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
41 Revanasiddappa
65
5158/05
-
-
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
42 Hanumanthappa
71
5161/05
+
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 11
+
+
-
-
-
43 Neelakntappa
64
5185/05
+
+
-
+
-
-
-
-
-
-
Firm
0.53
BPH
TURP, 18
+
+
-
-
44 Hamza Husain
65
5218/05
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
45 Adiveppa
70
5232/05
+
+
+
-
-
-
+
-
+
-
Firm
-
BPH
TURP, 18
+
+
46 Bheerappa
79
5381/05
-
-
+
+
+
-
-
-
-
-
Firm
2.7
BPH
TURP, 13
+
+
Gross
(gm)
Mean
AGNOR
count
Final diagnosis
3+4=7
4.8
Mod diff.adeno Ca
-
1.6
NH
-
-
1.4
NH+non sp gran Prostatitis
-
-
-
1.5
NH
-
-
-
1.8
NH
-
-
-
-
1.5
NH+Chr.Prostatitis
-
-
-
-
-
1.5
NH
Chronic
-
-
-
-
1.7
NH
-
-
-
-
-
1.8
NH
-
-
-
-
-
-
1.7
NH
-
-
-
-
-
-
-
1.7
NH
-
-
-
Chronic
-
-
-
-
1.7
NH+Chr.Prostatitis
-
-
-
-
-
-
-
-
1.5
NH
GL.SCR
Name
CA
Sl.
No.
Fever +
chills
Intermittent
stream
Age
(yrs)
Nocturia
Microscopy
Frequency
Presenting complaints
47 Ramanna
53
5426/05
-
+
-
+
+
-
-
-
-
+
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
Fused glands,
cords, sheets
4+5=9
5.9
Poor diff adeno Ca
48 Ramappa
55
5437/05
-
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.5
NH
49 Gangappa
70
5454/05
-
-
-
-
+
-
+
-
-
-
Firm
-
BPH
TURP, 14
+
+
-
-
-
-
-
-
-
-
1.6
NH
50 Eshwarappa
76
5457/05
-
-
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.8
NH
51 Gurushanthappa
55
5474/05
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 16
+
+
-
-
-
-
-
-
-
-
1.5
NH
52 Siddappa
68
5476/05
-
+
-
-
+
+
+
-
-
-
Firm
-
BPH
TURP, 11
+
+
-
-
-
-
-
-
-
-
1.5
NH
53 Gururaj
69
5478/05
-
-
+
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 13
+
+
-
-
-
-
LG PIN
-
-
-
2.3
NH+LG PIN
54 Jaganath Shetty
61
5481/05
-
-
-
-
+
+
-
-
-
+
Firm
-
BPH
TURP, 17
+
+
-
-
-
Chronic
-
-
-
-
1.7
NH+Chr.Prostatitis
55 Bhaktavathsala
61
5482/05
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 16
+
+
-
-
-
-
-
-
-
-
1.8
NH
56 Channabasappa
80
5543/05
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
TURP, 13
+
+
-
-
-
-
-
-
-
-
1.31
NH
57 Ramachandrappa
70
5641/05
+
-
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.5
NH
58 Mahadevappa
60
5737/05
-
-
-
+
+
-
-
-
-
+
Firm
-
BPH
SPP, 35
+
+
-
-
-
Chronic
-
-
-
-
1.5
NH+Chr.Prostatitis
59 Krishnamurthy
74
6014/05
-
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
Focal cr.gl
-
-
2.1
AAH
60 Siddappa
60
6106/05
+
+
-
-
-
-
+
-
+
-
Firm
-
BPH
SPP, 30
+
+
-
-
-
-
-
-
-
-
1.6
NH
61 Sonnurappa
45
6107/05
+
-
-
-
-
+
+
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.8
NH
Poor diff adeno Ca
62 Narayan Rao
74
6272/05
+
+
-
-
-
-
+
-
-
-
Firm
20.09
BPH
TURP, 18
+
+
-
-
-
-
-
-
Fused glands,
nests, cribriform
4+4=8
5.3
63 Shivalingappa
75
6357/05
-
+
+
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 17
+
+
+
-
-
-
-
-
-
-
1.6
NH
64 Godusab
66
6490/05
+
-
-
-
-
+
+
-
-
-
Hard
-
?Ca
SPP, 35
+
+
-
-
-
-
-
-
Fused glands
4+4=8
5.2
Poor diff adeno Ca
65 Yellappa Rao
70
6631/05
+
+
-
-
+
-
-
-
-
-
Firm
-
BPH
NH+non
TURP, 15
+ +sp gran Prostatitis
-
-
-
-
-
1.7
NH
66 Balaji Reddy
69
6764/05
-
+
-
-
+
-
-
-
-
-
Firm
1.2
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.6
NH
67 Ramappa
80
6776/05
+
-
-
-
+
-
+
-
-
-
Firm
-
BPH
SPP, 28
-
-
-
-
-
-
-
-
-
-
1.6
NH
Clinical
investigation
Serum PSA
ng/ml
G.Hyp
FMH
BCH
SQ. METP
TR. METP
Inflammatory
infiltrate
PIN
Others
CA
GL.SCR
+
-
-
+
-
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
Chronic
-
-
-
-
1.4
NH+Chr.Prostatitis
+
-
-
-
-
-
-
-
-
Firm
4
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.4
NH
70 Honnappa
85
158/06
+
+
+
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.3
NH
71 Sharanappa
67
176/06
+
+
-
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.3
NH
72 Ramappa
65
177/06
-
-
-
-
+
-
+
-
-
-
Hard
-
?Ca
SPP, 40
+
+
-
-
-
Chronic
-
-
-
-
1.5
NH+Chr.Prostatitis
73 Veruppanna
61
186/06
+
+
-
+
-
-
-
-
-
-
Firm
4.1
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.3
NH
74 Bhandappa
78
193/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.5
NH
75 Siddappa
80
196/06
+
+
-
+
-
-
-
-
-
-
Hard
-
?Ca
TURP, 20
+
+
-
-
-
Chronic
-
-
-
-
1.3
NH
76 M.S. Gowda
62
212/06
+
+
-
-
+
-
-
-
-
-
Firm
8.0
BPH
TURP, 22
+
+
-
-
-
-
-
-
-
-
1.3
NH
77 Annegundi
65
221/06
+
-
-
-
-
-
+
-
+
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
Chronic
-
-
-
-
1.4
NH+Chr.Prostatitis
78 Shivappa
77
240/06
+
-
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 18
+
+
+
-
-
-
-
-
-
-
1.5
NH
79 Parameshappa
70
262/06
-
-
+
+
-
-
-
-
-
-
Firm
-
BPH
SPP, 30
+
+
-
-
-
-
-
-
-
-
1.6
NH
80 Dayanand
67
268/06
-
+
+
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.5
NH
81 Honnegowda
80
274/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 17
+
+
-
-
-
Chronic
-
-
-
-
1.5
NH+Chr.Prostatitis
82 Hanumanthappa
65
290/06
+
+
-
-
+
+
-
-
-
-
Firm
2.26
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.6
NH
83 Hariharappa
64
411/06
-
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
Chronic
-
-
-
-
1.5
NH+Chr.Prostatitis
84 Shivarudrachari
74
423/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 22
+
+
-
-
-
Chronic
-
-
-
-
1.5
NH+Chr.Prostatitis
85 Verupakshappa
66
492/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
Chronic
-
-
-
-
1.48
NH+Chr.Prostatitis
86 Govinda Reddy
60
572/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.5
NH
87 Nagappa
68
663/06
+
-
-
-
+
-
+
-
-
-
Firm
-
BPH
SPP, 30
+
+
-
-
-
Chronic
-
-
-
-
1.7
NH+Chr.Prostatitis
88 Balakrishna
54
666/06
-
+
-
+
+
-
-
-
-
-
Firm
4.1
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.6
NH
89 Eranna
80
884/06
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
Chronic
-
-
-
-
1.8
NH+Chr.Prostatitis
90 Basavegowda
66
975/06
-
-
-
+
+
-
+
-
-
-
Firm
-
BPH
TURP, 22
+
+
-
-
-
-
-
-
-
-
1.6
NH
91 Shivappa
65
1172/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 16
+
+
-
-
-
-
-
-
-
-
1.6
NH
92 Mudalgiriappa
73
1264/06
+
+
-
+
-
-
-
-
+
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.5
NH
93 Chaman Sab
68
1351/06
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
SPP, 29
+
+
-
-
-
-
-
-
-
-
1.5
NH
94 Arude Mallaiah
65
1413/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.6
NH
95 Odda Mallaiah
70
1414/06
-
+
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 25
+
+
-
-
-
-
-
-
-
-
1.7
NH
96 Mahalingappa
60
1577/06
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.9
NH
97 Shivappa
70
1785/06
+
+
-
-
-
-
+
-
-
-
Firm
334.4
BPH
TURP, 18
-
-
-
-
-
-
-
-
Sheets
5+5=10
7.4
Poor diff adeno Ca
98 Thimmappa
80
1789/06
+
-
+
-
-
-
-
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
-
-
-
-
-
1.8
NH
99 Ramanna
70
1796/06
+
-
+
-
-
-
-
-
-
-
Firm
-
BPH
SPP, 20
+
+
-
-
-
-
-
-
-
-
2.1
NH
100 Ningappa
65
1870/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 18
+
+
-
-
-
-
-
-
-
-
1.9
NH
DRE
+
+
Biopsy
No.
Fever +
chills
Intermittent
stream
Hematuria
3/06
6/06
Age
(yrs)
Dribbling
Retention
60
73
Name
Urgency
68 Thippamma
69 Narasimha Rao
Sl.
No.
Nocturia
Clinical
diagnosis
Frequency
Poor
stream
Microscopy
Hesitancy
Presenting complaints
Gross
(gm)
Mean
AGNOR
count
Final diagnosis
101 Kasim Sab
60
1879/06
-
-
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 11
+
+
-
-
-
-
-
-
-
-
1.8
NH
102 Kader Sab
65
1934/06
+
-
+
-
-
-
+
-
+
-
Firm
-
BPH
SPP, 29
+
+
-
-
-
Chronic
-
-
-
-
1.9
NH+Chr.Prostatitis
Inflammatory
infiltrate
TR. METP
SQ. METP
Fever +
chills
Intermittent
stream
Mean
AGNOR
count
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.6
NH
-
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.9
NH
GL.SCR
+
-
CA
-
-
Others
-
-
PIN
-
+
BCH
-
+
FMH
-
-
Gross
(gm)
G.Hyp
+
DRE
1942/06
1995/06
Age
(yrs)
Poor
stream
65
68
Name
Urgency
103 Devendrappa
104 Channabasappa
Sl.
No.
Nocturia
Dribbling
Hematuria
Microscopy
Clinical
diagnosis
Retention
Frequency
Hesitancy
Biopsy
No.
Serum PSA
ng/ml
Clinical
investigation
Presenting complaints
Final diagnosis
105 Chidanandiah
62
1996/06
-
-
+
-
+
-
-
-
-
-
Firm
-
BPH
TURP, 16
+
+
-
-
-
-
-
-
-
-
1.2
NH
106 Neelappa
75
2054/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
Sheets,glands
5+3=8
5.6
Poor diff adeno Ca
107 Medahari
54
2113/06
-
-
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 22
+
+
-
-
-
-
-
-
-
-
1.7
NH
108 Mohantati
56
2115/06
-
-
-
-
+
-
+
-
-
-
Hard
-
?Ca
TURP, 16
+
+
-
-
-
Chronic
-
-
-
-
1.7
NH+Chr.Prostatitis
NH
109 Hanumanthappa
82
2166/06
-
-
-
-
+
+
-
-
-
-
Firm
-
BPH
TURP, 26
+
+
-
-
-
-
-
-
-
-
1.8
110 Siddappa
68
2197/06
+
-
+
-
-
-
-
+
-
-
Firm
4.68
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.5
NH
111 Ramanagowda
78
2208/06
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.6
NH
112 Rudramuniappa
62
2242/06
+
+
+
-
-
-
-
-
-
-
Hard
8.8
?Ca
SPP, 35
+
+
-
-
-
Chronic
-
-
-
-
1.7
NH+Chr.Prostatitis
113 Shivanna
50
2326/06
+
+
-
-
+
+
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
Chronic
-
-
-
-
1.3
NH+Chr.Prostatitis
114 Mahadevappa
80
2424/06
-
-
-
-
+
+
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.7
NH
115 Siddabasappa
48
2445/06
-
-
-
+
+
-
+
-
-
-
Firm
15.8
BPH
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.7
NH
116 Eralingappa
70
2665/06
+
-
-
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 30
+
+
-
+
-
Chronic
-
Red infarct
-
-
1.4
NH+ red infarct+sq.metp
3+4=7
4.8
Mod diff.adeno Ca
-
1.3
NH+red infarct+sq.metp
117 Honnappa
70
2684/06
-
-
-
+
+
+
-
-
-
-
Hard
-
?Ca
TURP, 20
-
-
-
-
-
-
-
-
Discrete & fused
glands
118 Doddahanumanthappa
70
2740/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
+
-
Chronic
-
Red infarct
-
119 Basavarajappa
82
2819/06
-
-
+
+
-
-
+
-
-
-
Firm
2.33
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.3
NH
120 Mohd. Sahulsab
65
2852/06
+
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 35
+
+
-
-
-
-
-
-
-
-
1.9
NH
121 Mohd. Anif
89
2921/06
-
+
+
-
-
-
+
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.4
NH
4+5=9
5.8
Poor diff adeno Ca
5+4=9
6.1
Poor diff adeno Ca
-
1.5
NH
-
1.4
NH
122 Butappa
79
2994/06
-
+
-
-
-
-
+
-
-
-
Hard
-
?Ca
SPP, 30
+
+
-
-
-
-
-
PNI
123 Puttappa
82
3063/06
+
+
+
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 15
+
+
-
-
-
-
-
-
124 Keshar Katie
70
3065/06
-
-
-
-
-
+
+
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
fused
glands,cords
cribriform, nests,
fused glands
-
125 Kotrappa
55
3066/06
-
-
+
+
-
-
+
-
-
-
Firm
27.5
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
126 Yellappa
75
3160/06
+
-
+
-
-
-
+
-
-
-
Firm
5.06
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.6
NH
127 Ganeshappa
70
3161/06
-
-
+
-
-
-
+
-
-
-
Firm
20.63
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.4
NH
128 Neelakantha Rao
68
3208/06
-
-
+
+
-
-
+
-
-
-
Firm
-
BPH
TURP, 8
+
+
-
-
-
-
-
-
-
-
1.2
NH
129 Maheshwarappa
55
3210/06
-
-
+
+
-
-
+
-
-
-
Firm
-
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.3
NH
130 Benakappa
76
3226/06
-
-
-
-
-
+
+
-
-
+
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.5
NH
131 Thimmamma
70
3281/06
+
+
-
+
-
-
-
-
-
-
Firm
6.38
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.6
NH
132 Siddappa
50
3393/06
+
-
-
-
-
-
+
-
-
+
Firm
0.73
BPH
TURP, 8
+
+
-
-
-
-
-
-
-
-
1.7
NH
133 Hanumanthappa
60
3434/06
+
-
-
+
-
-
+
-
-
-
Firm
4.11
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.8
NH
134 Malleshappa
70
3435/06
+
+
-
+
-
+
-
-
-
-
Firm
0.49
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.8
NH
135 Manohar
80
3436/06
+
-
-
+
-
+
-
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.5
NH
136 Bomanna
75
3479/06
+
-
+
+
-
-
-
-
-
-
Firm
3.71
BPH
TURP, 15
+
+
-
-
+
-
-
-
-
-
1.5
NH
GL.SCR
CA
Others
PIN
Inflammatory
infiltrate
TR. METP
BCH
SQ. METP
Gross
(gm)
FMH
Microscopy
Clinical
diagnosis
G.Hyp
Serum PSA
ng/ml
Fever +
chills
Intermittent
stream
Hematuria
Dribbling
Retention
Poor
stream
Urgency
Biopsy
No.
Hesitancy
Age
(yrs)
Nocturia
Name
Frequency
Sl.
No.
DRE
Clinical
investigation
Presenting complaints
Mean
AGNOR
count
Final diagnosis
137 Basavaraja
55
3501/06
-
-
+
+
-
-
+
-
-
-
Firm
5
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.4
NH
138 Nagappa
75
3530/06
-
-
+
+
-
-
+
-
-
-
Firm
6.95
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.5
NH
139 Umpathy
70
3534/06
+
+
-
+
-
-
-
-
-
-
Firm
4.04
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.2
NH
140 Umpathy
78
3540/06
-
-
+
-
+
-
+
-
-
-
Firm
-
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.4
NH
141 Danappa
59
3550/06
+
-
-
-
-
+
-
-
-
+
Firm
-
BPH
TURP, 8
+
+
-
-
-
-
-
-
-
-
1.8
NH
142 Erappa
60
3603/06
+
-
-
+
-
+
+
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.9
NH
143 Julanaik
55
3658/06
+
+
-
+
-
-
-
+
-
-
Hard
-
?Ca
SPP, 40
+
+
-
-
-
Chronic
-
-
Sheets, discrete
glands
5+3=8
5.2
Poor diff adeno Ca
144 Venkataswamy
75
3702/06
-
-
+
-
-
+
+
-
-
-
Hard
-
?Ca
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.4
NH
145 Shekarappa
68
3728/06
-
+
-
-
-
+
+
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.8
NH
146 Vishweshwarappa
62
3787/06
+
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.2
NH
147 Nagendrappa
60
3799/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
-
-
-
-
-
1.6
NH
148 Gurushanthappa
62
3923/06
+
+
-
+
-
-
-
-
-
-
Firm
-
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.5
NH
149 Narayan Rao
56
3925/06
+
-
-
-
-
-
+
-
-
+
Firm
0.69
BPH
TURP, 12
+
+
-
-
-
-
-
-
-
-
1.6
NH
150 Marudrappa
75
4023/06
+
+
-
-
+
-
-
-
-
-
Firm
3.65
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.8
NH
151 Hanumanthappa
50
4029/06
-
-
+
+
-
-
+
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
-
-
-
-
-
1.8
NH
NH
152 Hanumappa
65
4034/06
-
-
+
-
-
-
+
-
-
+
Firm
2.55
BPH
TURP, 10
+
+
-
-
-
-
-
-
-
-
1.5
153 Kubergowda
76
4093/06
+
-
-
+
-
-
+
-
-
-
Hard
13.07
?Ca
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.9
NH
154 Ramachandrappa
54
4098/06
-
-
+
+
+
-
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
1.8
NH
155 Thippanna
60
4137/06
+
-
-
+
-
-
+
-
-
-
Firm
-
BPH
SPP, 35
-
-
-
-
-
-
HGPIN
-
3+4=7
4.7
Mod diff.adeno Ca
156 Hanumanthappa
70
4138/06
+
+
-
+
-
-
-
-
-
-
Firm
-
BPH
SPP, 30
+
+
-
-
-
Chronic
-
-
Small acini,
cribriform
-
-
1.5
NH
157 Channabasappa
75
4240/06
+
-
+
+
-
-
-
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
-
-
-
-
-
1.7
NH
158 Doddahanumanthappa
70
4285/06
+
-
-
-
-
-
+
-
-
-
Firm
133.59
BPH
SPP, 30
+
+
-
-
-
-
-
-
-
-
1.6
NH
159 Ningappa
70
4331/06
-
+
-
+
-
-
-
-
-
-
Firm
6.29
BPH
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.2
NH
160 Narayan Rao
58
4368/06
-
-
-
+
-
-
-
-
-
-
Firm
1.52
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.5
NH
161 Thimmappaji
60
4485/06
-
+
-
+
-
-
+
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.8
NH
162 Zaluddin
80
4512/06
-
-
+
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
Chronic
-
-
-
-
1.8
NH
163 Pakkerrappa
60
4595/06
-
-
-
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 30
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH
164 Verupakshappa
56
4930/06
-
-
-
+
+
-
-
-
-
-
Firm
1.57
BPH
TURP, 40
+
+
-
-
-
-
-
-
-
-
1.5
NH
165 Ramanna
76
5058/06
-
+
-
+
-
-
-
-
-
-
Firm
16.13
BPH
TURP, 40
+
+
-
+
-
Chronic
-
-
-
-
1.3
NH+red infarct+sq.metp
166 Ramachandrappa
75
5097/06
-
+
-
+
-
-
-
+
-
-
Hard
-
?Ca
TURP, 10
+
+
-
-
-
-
-
-
Cribriform, nests,
cords
4+5=9
5.6
Poor diff adeno Ca
167 Srinivas Gowda
60
5184/06
+
-
+
-
-
-
-
-
-
-
Firm
1.82
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.4
NH
168 M.K. Rajshekhar
51
5207/06
+
-
+
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 15
+
-
-
-
-
-
-
-
-
-
1.3
NH
169 Chennappa
65
5221/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH+Chr.Prostatitis
170 Thimmappa
65
5250/06
-
+
-
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 25
+
+
-
-
-
Chronic
-
-
-
-
1.4
NH+Chr.Prostatitis
Mean
AGNOR
count
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.9
NH
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.7
NH
GL.SCR
BPH
6.79
CA
0.89
Firm
Others
Firm
-
PIN
-
-
Inflammatory
infiltrate
-
-
TR. METP
-
+
BCH
+
-
SQ. METP
-
+
FMH
-
+
Gross
(gm)
G.Hyp
-
-
DRE
-
-
Hematuria
+
-
Dribbling
+
Biopsy
No.
Retention
5266/06
5346/06
Age
(yrs)
Poor
stream
86
65
Name
Urgency
171 Muniyappa
172 Eshwarappa
Sl.
No.
Hesitancy
Nocturia
Fever +
chills
Intermittent
stream
Microscopy
Clinical
diagnosis
Frequency
Serum PSA
ng/ml
Clinical
investigation
Presenting complaints
Final diagnosis
173 Durgappa
60
5391/06
-
-
-
+
+
-
-
-
-
-
Firm
1.09
BPH
TURP, 15
+
+
-
-
-
-
-
-
-
-
1.8
NH
174 Veerappa
65
5806/06
+
+
-
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 35
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH+Chr.Prostatitis
175 Thirthananda
63
5943/06
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.6
NH
176 Rangappa
60
51/07
+
-
-
-
+
-
+
-
-
-
Firm
-
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.5
NH
NH+Chr.Prostatitis
177 Shivalingappa
58
97/07
-
+
-
-
-
-
+
-
-
-
Firm
0.06
BPH
SPP, 38
+
+
-
-
-
Chronic
-
-
-
-
1.8
178 Laxmana Naik
70
101/07
+
+
-
-
-
-
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.7
NH
179 Muthappa
60
341/07
+
-
-
-
+
+
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.6
NH
180 Nagappa
76
389/07
+
-
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 28
+
+
-
-
-
-
-
-
-
-
1.8
NH
181 Kariappa
68
392/07
+
-
-
+
+
-
-
-
-
-
Firm
4.0
BPH
TURP, 15
+
+
-
-
-
-
-
Focal cr.gl
-
-
2.3
AAH
182 Ramappa
50
704/07
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.6
NH
183 Abdul Salam
68
757/07
-
+
-
+
-
+
-
-
-
-
Firm
1.99
BPH
TURP, 18
+
+
-
-
-
-
-
-
-
-
1.4
NH
184 Kenchappa
60
833/07
+
-
-
-
-
+
-
-
-
-
Firm
-
BPH
TURP, 20
+
+
-
-
-
-
-
-
-
-
1.5
NH
185 Yuvarajappa
55
854/07
+
-
+
-
-
-
-
-
-
-
Firm
-
BPH
SPP, 25
+
+
-
-
-
Chronic
-
-
-
-
1.6
NH+Chr.Prostatitis
NH+TB gran.prostatitis
186 Gurumurthy
75
1416/07
+
-
+
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 40
+
+
-
-
-
Chronic
-
CG
-
-
1.5
187 Ganganaik
60
1525/07
-
-
-
+
+
+
-
-
-
-
Firm
-
BPH
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.3
NH
188 Rudrappa
65
1649/07
-
-
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.5
NH
189 Ganisab
65
1651/07
+
+
-
-
-
-
-
-
-
-
Firm
-
BPH
TURP, 25
+
+
-
-
-
-
-
-
-
-
1.6
NH
190 Basappa
52
1670/07
+
-
-
-
-
-
+
-
-
-
Firm
4.92
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.5
NH
191 Gangappa
78
1683/07
+
+
-
-
+
-
-
-
-
-
Hard
155.96
?Ca
TURP, 30
-
-
-
-
-
-
-
-
Discrete glands,
cords, sheets
3+5=8
5.3
Poor diff adeno Ca
192 Ningappa
71
1757/07
-
-
-
+
+
-
-
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
Chronic
-
-
-
-
1.8
NH+Chr.Prostatitis
193 Boraiah
65
1819/07
+
+
-
-
+
-
-
-
-
-
Firm
-
BPH
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.7
NH
194 Ramappa
75
1883/07
+
-
-
-
-
-
+
-
-
-
Firm
6.18
BPH
SPP, 40
+
+
-
-
-
-
-
-
-
-
1.8
NH+Chr.Prostatitis
195 Appa Rao
70
1979/07
-
+
-
+
+
-
-
-
-
-
Firm
-
BPH
TURP, 30
+
+
-
-
-
-
-
-
-
-
1.6
NH
196 Eshwarappa
65
2052/07
-
-
-
+
+
+
-
-
-
-
Firm
0.7
BPH
TURP, 25
+
+
-
-
-
-
-
-
-
-
1.6
NH
197 Kariappa
75
2171/07
-
-
-
+
-
-
-
+
-
-
Hard
-
?Ca
TURP, 25
-
-
-
-
-
-
-
-
Discrete & fused
glands
3+4=7
4.5
Mod diff.adeno Ca
198 Kottayappa
48
2780/07
-
-
-
-
-
-
+
-
-
-
Firm
-
BPH
SPP, 40
+
+
-
-
-
-
-
NCG
-
-
1.3
NH+non sp gran Prostatitis
KEY TO MASTER CHART
AAH
AgNOR
:
:
BCH
CA
CG
DRE
FMH
Focal cr.gl
G.Hyp
Gl.SCR
HG PIN
:
:
:
:
:
:
:
:
:
LG PIN
:
Mod diff. adeno Ca
:
NCG
NH
NH+ Chr Prostatitis
NH+ non sp.gran
:
:
:
:
NH+ red infarct sq met
:
NH+ TB gran prostatitis
:
PIN
PNI
Poor diff. adeno Ca
PSA
SPP
SQ.METP
TR.METP
TURP
Well diff. adeno Ca
:
:
:
:
:
:
:
:
:
Atypical Adenomatous Hyperplasia
Argyrophilic Nucleolar Organizer
Region
Basal Cell Hyperplasia
Carcinoma
Caseating Granulomas
Digital Rectal Examination
Fibromuscular Hyperplasia
Focal Crowding Of Glands
Glandular Hyperplasia
Gleason Score
High Grade Prostatic Intraepithelial
Neoplasia
Low- Grade Prostatic Intraepithelial
Neoplasia
Moderately Differentiated
Adenocarcinoma
Noncaseating Granulomas
Nodular Hyperplasia
NH With Chronic Prostatitis
Nodular Hyperplasia With Non Specific
Granulomatous Prostatitis
Nodular Hyperplasia With Red Infarct
And Squamous Metaplasia
Nodular Hyperplasia With Tubercular
Granulomatous Prostatitis
Prostatic Intraepithelial Neoplasia
Perineural Invasion
Poorly Differentiated Adenocarcinoma
Prostate Specific Antigen
Suprapubic Prostatectomy
Squamous Metaplasia
Transitional Metaplasia
Transurethral Resection Of Prostate
Well Differentiated Adenocarcinoma
131
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