1. health and fitness
2. disease
3. cancer

MORPHOLOGICAL SPECTRUM OF PROSTATIC LESIONS –
A CLINICOPATHOLOGICAL STUDY
By
Dr. ANUSHREE C. N.
Dissertation Submitted to the Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka
in partial fulfillment of the requirements for the degree of
M. D. (PATHOLOGY)
Under the guidance of
Dr. KUSUMA V. M. D., D. C. P.
DEPARTMENT OF PATHOLOGY
KEMPEGOWDA INSTITUTE OF MEDICAL SCIENCES
BANGALORE.
2006
i
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation entitled “MORPHOLOGICAL
SPECTRUM OF PROSTATIC LESIONS - A CLINICOPATHOLOGICAL
STUDY” is a bonafide and genuine research work carried out by me under the guidance
of Dr. KUSUMA V. M. D., D. C. P, Professor, Department of Pathology, Kempegowda
Institute of Medical Sciences, Bangalore.
Date:
Signature of the Candidate
Place:
Name: Dr. ANUSHREE C. N.
ii
CERTIFICATE BY THE GUIDE
This is to certify that this dissertation entitled “MORPHOLOGICAL
SPECTRUM OF PROSTATIC LESIONS - A CLINICOPATHOLOGICAL
STUDY” is a bonafide work done by Dr. ANUSHREE C. N. in partial fulfillment of the
requirement for the degree of M. D. in Pathology.
Date:
Place:
Signature of the Guide
Dr. KUSUMA V. M. D., D. C. P
Professor
Department of Pathology
Kempegowda Institute of Medical Sciences
Bangalore – 560 004
iii
ENDORSEMENT BY THE HEAD OF THE
DEPARTMENT/PRINCIPAL/HEAD OF THE INSTITUTION
This is to certify that this dissertation entitled “MORPHOLOGICAL
SPECTRUM OF PROSTATIC LESIONS - A CLINICOPATHOLOGICAL
STUDY” is a bonafide work done by Dr. ANUSHREE C. N. under overall guidance of
Dr. KUSUMA V M. D., D. C. P, Professor, Department of Pathology, Kempegowda
Institute of Medical Sciences.
Seal and Signature of the HOD
Dr. GEETHAMANI V. M. D.
Seal and Signature of the Principal
Dr. M. K. SUDARSHAN M. D.
Professor and Head
Department of Pathology
Kempegowda Institute of Medical Sciences
Bangalore – 560 004.
Principal
Kempegowda Institute of Medical Sciences
Bangalore – 560 004.
Date:
Date:
Place:
Place:
iv
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.
Date:
Signature of the Candidate
Place:
Name: Dr. ANUSHREE C. N.
© Rajiv Gandhi University of Health Sciences, Karnataka
v
ACKNOWLEDGEMENT
Thanksgiving is a pleasant job but it is nonetheless difficult where one sincerely tries to
put it in words. These humble words of expression and gratitude cannot wholly convey my
feelings.
With a deep sense of gratitude, I owe my sincere thanks to my teacher and guide
Dr. KUSUMA V. M. D. D. C. P., Professor, Department of Pathology, Kempegowda Institute of
Medical Sciences, Bangalore for her able guidance, critical evaluation and constant
encouragement, which aided in the timely completion of this dissertation. I am extremely
thankful for her guidance and support rendered.
It is a great privilege and opportunity to express my heartfelt gratitude and reverence to
my teacher and mentor, Dr. GEETHAMANI M D., Professor and Head, Department of
Pathology, Kempegowda Institute of Medical Sciences, Bangalore for being the guiding force all
the way through this course.
I wish to profoundly thank my respected Professors of Pathology Dr. Suguna B. V. M. D.
and Dr. Padmavathi K. L. M. D., for their help and finely suggestion.
I
sincerely
thank
Associate
Professors
Dr.
Rangaswamy
M.D.,
DNB
and
Dr. Niveditha S. R. M. D., DNB, for their encouragement and support.
I sincerely thank Dr. Hemalatha M. M. D., Dr. Savithri R., D. C. P, DNB,
Dr. Preetha D. Prabhu D. C. P., Dr. Gayathri B. R. D. C. P., Dr. Venkatesh Prasad V.
D. C. P., Dr. Suja Ajoy Kumar M. D., DNB, for their encouragement and support.
I extend my heartfelt gratitude to Dr. M. K. SUDARSHAN M. D., Principal,
Kempegowda Institute of Medical Sciences, Bangalore for his beneficial support.
vi
I wish to record my sincere thanks to Dr. Madhusudhan H. R., Honorary Assistant
Professor, Department of Urology, Kempegowda Institute of Medical Sciences, Bangalore for his
cooperation towards the progress of this dissertation. I wish to thank Dr. Krishnamurthy former
Head, Department of Pathology, Kempegowda Institute of Medical Sciences, Bangalore and
Dr. Swarna B., Vydehi Institute of Medical Sciences, Bangalore for their kind support
I wish to thank my friend Dr. Sruthi Prasad, for her constant assistance, support and
encouragement. My thanks are also due to my other colleagues, technical staff for their help and
cooperation.
I express my sincere thanks to Shri. K. P. Suresh, Scientist (Statistics), for his assistance
extended to me in statistical analysis.
I would like to thank Dr. Babu and Mr. A. S. Madhukeshwara, who deserve the credit for
the presentation of this manuscript in the present.
I am extremely grateful to my Father Chikkanarasimhaiah T. G., B. A., LLB, my Mother
Leelavathi D. P., Sister, Brother-in-law and my Niece Krisha M., for encouragement, moral
support, friendly advice, which helped me, tide over occasional moments of distress. The
completion of this study would not have been possible without their constant encouragement and
help.
My heartfelt gratitude to all my patients who submitted themselves most gracefully and
wholeheartedly participated in this study.
Date:
Signature of the Candidate
Place:
Name:
vii
LIST OF ABBREVIATIONS USED
ASAP
→
Atypical small acinar proliferation
BCG
→
Bacille Calmette Guerin
CCCH
→
Clear Cell Cribriform Hyperplasia
DTH
→
Dihydrotestosterone
H&E
→
Haematoxylin and Eosin
HGPIN
→
High Grade Prostatic Intraepithelial Neoplasia
LGPIN
→
Low Grade Prostatic Intraepithelial Neoplasia
NH
→
Nodular Hyperplasia
PIN
→
Prostatic Intraepithelial Neoplasia
PSA
→
Prostate Specific Antigen
SCC
→
Squamous Cell Carcinoma
TCC
→
Transitional Cell Carcinoma
TRUS
→
Transrectal ultrasound
TURP
→
Transurethral Resection of Prostate
WHO
→
World Health Organization
viii
ABSTRACT
BACKGROUND AND OBJECTIVES
Study of prostatic lesions has gained more importance because, development of
prostatic hyperplasia is an almost universal phenomenon in aging men.
Inflammatory conditions needs correct diagnosis as it can be treated with
antibiotics Prostatic carcinoma is the second most common cause of death in men over
the age of 55 years.
METHODS
The study included prostatic tissue specimens received in the pathology
laboratory at Kempegowda Institute of Medical Sciences and Hospital, Bangalore from
December 2003 to December 2005. A total of 150 specimens were studied. They were
graded into benign, inflammatory conditions and malignant lesions. Gleason`s
microscopic grading was used to grade all the prostatic adenocarcinoma cases. Serum
PSA levels were correlated in all the cases.
RESULTS
There were 134 TURP, 12 needle biopsies and 4 prostatectomy specimens. Most
of the patients were in sixth and seventh decade. Lesions encountered were nodular
hyperplasia / prostatitis 90%, HGPIN 0.7% and 9.3% malignant.
ix
INTERPRETATION AND CONCLUSION
Nodular hyperplasia was the common lesion encountered. Associated lesions like
prostatitis BCH, CCCH, transitional metaplasia, granulomatous prostatitis, abscesses
were encountered.
Among the malignant lesions adenocarcinoma was the common lesion seen in
seventh decade and Gleason`s score 7 was the commonest. An interesting case of primary
squamous cell carcinoma was encountered. One of the case sent as metastatic TCC from
bladder was confirmed histologically.
Immunohistochemistry for LCA was done in one case, which showed artifactual
change of lymphocytes in stroma appearing as signet ring cells. These cells showed
positive membrane reaction.
Serum PSA levels were elevated in few cases of benign lesions due to associated
lesions like prostatitis, abscesses and granulomatous prostatitis. Many of the malignant
cases showed very high levels of PSA.
KEYWORDS
Abscess; Adenocarcinoma of prostate; Gleason`s score; Granulomatous
prostatitis; Leucocyte common antigen; Nodular hyperplasia; Prostate specific antigen;
Squamous cell carcinoma; Transitional cell carcinoma, Transurethral resection prostate.
x
TABLE OF CONTENTS
Page Nos.
1.
INTRODUCTION
1
2.
AIMS AND OBJECTIVES
3
3.
REVIEW OF LITERATURE
4
4.
METHODOLOGY
45
5.
RESULTS
47
6.
DISCUSSION
71
7.
CONCLUSION
83
8.
SUMMARY
86
9.
BIBLIOGRAPHY
88
10.
ANNEXURES
•
CASE PROFORMA
102
•
PROCEDURE FOR SPECIAL STAINS
103
•
MASTER CHART
105
•
KEY TO MASTER CHART
110
xi
LIST OF TABLES
Page Nos.
1.
Age incidence of the various prostatic lesions
47
2.
Clinical presentation of prostatic lesions
49
3.
Digital rectal examination findings
51
4.
Serum PSA levels in the cases studied
52
5.
Clinical Diagnoses in the cases studied
53
6.
Nature of prostatic tissue studied
54
7.
Microscopic findings in benign lesions studied
55
8.
Microscopic findings in malignant lesions studied
57
9.
Incidence of carcinoma with reference to Gleason’s score (maximum
Score 10)
59
10.
Final histopathological diagnosis in the cases studied
60
11.
Showing the incidence of prostatitis
72
12.
Incidence of PIN in cases of prostates with and without prostatic
carcinoma
75
13.
Incidence of HGPIN in prostates with carcinoma
75
14.
Age incidence of prostatic carcinoma in different studies
77
15.
Prevalence of prostatic carcinoma in different studies
78
16.
Comparative incidence of carcinoma with reference to Gleason’s
score
79
17.
Incidence of prostatic carcinoma mean age and mean Gleaso’s score
80
18.
Incidence of prostatic carcinoma, median age and Gleason’s score
80
xii
LIST OF GRAPHS
Page Nos.
1 a..
Age incidence of the various prostatic lesions
48
1 b.
Incidence of benign and malignant lesions
48
2
Clinical presentation of prostatic lesions
50
3
Digital rectal examination findings
51
4.
Serum PSA levels in the cases studied
52
5.
Clinical Diagnoses in the cases studied
53
6.
Nature of prostatic tissue studied
54
7.
Microscopic findings in benign lesions studied
56
8.
Microscopic findings in malignant lesions studied
58
9.
Incidence of carcinoma with reference to Gleason’s score
(maximum Score 10)
59
10.
Final histopathological diagnosis in the cases studied
60
xiii
LIST OF FIGURES
Page Nos.
1.
Gross appearance of nodular hyperplasia (a) Showing hyperplastic
lateral lobes (b) Cut section showing solid and cystic areas
61
2.
Nodular hyperplasia showing hyperplastic glandular and stromal
components (H & E, 100x)
61
3.
Basal cell hyperplasia, showing glands filled with small darkly staining
basal cells with peripheral palisading (H&E, 100x)
62
4.
Clear cell cribriform hyperplasia, showing glands composed of cells
with abundant clear cytoplasm (H&E, 100x)
62
5.
Transitional metaplasia in a case of nodular hyperplasia (H&E, 100x)
63
6.
Squamous metaplasia in a case of nodular hyperplasia (H&E, 100x)
63
7.
Prostatic abscess showing sheets of neutrophils in and around the acini
(H&E, 100x)
64
8.
Chronic prostatitis showing infiltration of lymphocytes, plasma cells
and histiocytes in the stroma (H&E, 100x)
64
9.
Granulomatous prostatitis showing well formed epithelioid granuloma
with a giant cell (H&E, 40x)
65
10
Low grade PIN showing epithelial crowing and stratification with
anisonucleosis (a) (H&E, 100X) (b) (H&E, 400X)
65
11.
Artifactual change of lymphocytes in the stroma appearing as signet
ring cells (H&E, 400x)
66
12.
Immunohistochemistry of leucocyte common antigen for the above case
showing membrane positivity (a) IHC, 40x, (b) IHC, 400x
66
13.
High grade PIN showing pronounced epithelial crowding, stratification,
nuclear enlargement with prominent nucleoli and intact basement
membrane a) (H&E, 100X), (b) (H&E, 400X)
67
Prostatic adenocarcinoma, Gleason’s score 3+4=7/10 (a) Pattern 3
showing closely packed single glands (b) pattern 4 showing fused
glandular pattern (H&E, 100x)
67
15.
Prostatic adenocarcinoma, Gleason’s score 4+4=8/10,
cribriform gland with irregular border (H&E, 100x)
68
16.
Gleason pattern 5 with central comedo necrosis (H&E, 100x)
14.
xiv
Showing
68
17.
Perineural Invasion showing tumour cells invading the perineurium
(H&E, 100X)
69
18.
Intraluminal acidic mucin in lumens of neoplastic glands in a case of
prostatic adenocarcinoma (Alcian blue pH 1, 100x)
69
19.
Primary squamous cell carcinoma of prostate (H&E, 100x) inset
showing the same (H&E, 400X)
70
20.
Transitional cell carcinoma of bladder metastatic to prostate (H&E,
100x)
70
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
Prostate gland occupies center stage in the lives of many elderly males. Because
of its location at bladder neck, enlargement of the gland leads to problems related to
urinary obstruction.1 Incidence of prostatic disease, Nodular Hyperplasia (NH) and
carcinoma increases with age. Recently there has been a significant advance in
understanding of various prostatic diseases.
Prostatitis, NH and tumors are the three important lesions to be studied in detail as
they are frequently encountered. Diagnosis of prostatitis is very necessary as they can be
successfully treated with antibiotics. NH describes a hyper plastic process of stromal and
epithelial elements of prostate. It is an extremely common problem in elderly men over
the age 50.1 Prostatic carcinoma is more common in India compared to other Asian
Countries.2 It is the 5th cause of cancer in men and 4th in cancer mortality in India. At
some time in their lives approximately one in 22 Indian males will be struck by prostatic
carcinoma and its incidence is increasing by 3.5% every year.3 Etiology of prostatic
carcinoma is largely unknown today rendering disease prevention difficult. Hereditary
factors have a role.4,5 The great differences in the incidence of clinically manifest
1
carcinoma indicate that the nutritional and environmental factors also may have an
influence on the development and progression of the disease.6 Diet rich in animal fats,
red meat and diet poor in fruits, vegetables are the likely culprit in prostatic carcinoma.7
Low levels of dietary selenium, vitamin E and vitamin D also play a role.8 Studies also
reveal that there is no definite role of sexual activity, smoking, height, weight and alcohol
consumption.9
Although nodular hyperplasia can almost be considered as an aging process, the
histological variations like different types of hyperplasias, low grade prostatic
intraepithelial neoplasia (LGPIN) and high grade prostatic intraepithelial neoplasia
(HGPIN) merits discussion.
Prostatic carcinoma also has to be given importance as its incidence is increasing
owing to the westernization in Asian countries including India. This study comprises
description of incidence of various lesions of prostate encountered at KIMS hospital,
associated clinical manifestations, morphological changes and also serum Prostatic
Specific Antigen (PSA) level correlations. It is all the more necessary to study prostatic
diseases in the present situation as their incidence keeps growing due to extended male
longevity past the 60s.3
2
AIMS AND OBJECTIVES
1.
To study the incidence of various morphologic types of prostatic lesions
encountered at KIMS, Bangalore.
2.
To study the age incidence, clinical manifestations and their correlation with
benign and malignant lesions.
3.
To correlate serum PSA levels with the morphologic types.
4.
To study the mimickers of prostatic carcinoma like basal cell hyperplasia, clear
cell cribriform hyperplasia and lobular atrophy.
5.
To study the incidence of prostatic intraepithelial neoplasia (PIN).
6.
To study the histochemical characters of PIN and prostatic adenocarcinoma.
3
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 lateral lobes, an
anterior lobe, posterior lobe and middle based on embryonic finding.10
PSA was first demonstrated is 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.10 PSA is secreted into seminal fluid in high concentration, in which it is
involved in liquefaction of semen coagulum. PSA was widely used as a clinical marker
for prostate cancer by 1988.10 Serum PSA levels increases proportionately with
advancing clinical stage.11 Studies have shown that serial increases in serum PSA,
increases the incidence of occult carcinoma.12 Several modifications in the estimation of
serum PSA are developed. These include
a)
PSA density: Which is the ratio between the serum PSA value and volume of
prostate gland.
b)
PSA velocity: The rate of change of PSA and the value that distinguishes between
men with and without prostatic carcinoma is 0.75ng/ml per year.
c)
The age specific reference ranges, which is 2.5ng/ml for men of 40-49 yrs of age,
3.5ng/ml for men of 50-59yrs of age, 4.5ng/ml for men of 60-69 yrs years of age
and 6.5ng/ml for men of 70-79yrs of age.
4
Studies have revealed that immunoreactive PSA exits in 2 forms, a major fraction
bound to α1 anti-chymotrypsin and a minor free fraction. The percentage of free PSA
(free PSA/total PSA x100) is lower in prostatic carcinoma than in NH. It helps in
discriminating benign and malignant lesion when total PSA level is in “gray zone” of 4 to
10ng/ml. In a study it was found that normal prostate had a higher percent of free PSA
(27.7%), than those with NH (20.1%), HGPIN (20.8%) and percentage was lowest in
prostatic carcinoma.13
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 supplanted serum PAP.14
Benign prostatic hyperplasia (BPH) was replaced by the term nodular hyperplasia
first proposed by Moore in 1943.15 The first study of natural history of NH was reported.
Later the first prospective studies on natural history of NH was described.
A
retrospective review of natural history of NH was studied.16 NH first develops in
periurethral zone of prostate.10 NH begins before the age of 30 (early phase), in the mid
phase (men between 51-70 yrs) the doubling time is 10yrs and increases to more than
100yrs in men beyond 70yrs.17 Basal cell proliferation in NH was described.18,19 The
histological, ultrastructural and immunohistochemical features of florid basal cell
hyperplasia was charecterised.20 Clear cell cribriform hyperplasia of prostate was
described in 10 patients with clinical diagnosis of NH.21 A rare variant of NH was
designated as sclerosing adenosis, analogous to that in breast.22
5
The tissue resected for NH is quite heterogeneous and that the nodules are
composed of varying proportion of both epithelial and stromal components.23 The relative
proportions of epithelium and stroma are related to development of symptomatic NH with
higher percentage of symptomatic NH.24 Inflammation induced release of platelet derived
growth factor (PDGF) is a possible, contributing factor in development of BPH.25
Atypical basal cell hyperplasia was described in 12 cases that were confused with
adenocarcinoma of prostate.26
The first case of prostatic infarct was reported and it occurs predominantly in
large prostates that exhibit NH.27 The clinical spectrum of granulomatous prostatitis was
documented and reported in 200 cases.28 A lesion called incidental lymphocytic prostatitis
was described.29 A prostate lesion called proliferative inflammatory atrophy was
proposed. These are focal atrophic lesions that are associated with chronic inflammation
and are adjacent to lesions of PIN, prostatic carcinoma or both.7 Intraductal dysplasia, a
potentially premalignant lesion of prostate was described along with reproducible
diagnostic criteria.30 It was replaced by term Prostatic Intraepithelial Neoplasia (PIN)
introduced in 1989.31,32 It is divided into two grades low grade PIN (LGPIN) and high
grade PIN (HGPIN). The prevailing theory, that prostatic carcinoma arose from atrophic
epithelium was challenged by postulating that carcinoma arose from active proliferative
epithelium.33 Atypical Adenomatous Hyperplasia (AAH) a premalignant lesion of the
prostate is the localized proliferation of small glands with in the prostate that can be
mistaken for carcinoma.34 A histochemical study of 27 well differentiated prostatic
carcinoma cases associated with PIN was done and it was found that lower neutral mucin
production by HGPIN was linked to higher proliferative activity of this lesion and also
6
found increased acidic mucin secretion by PIN and prostatic carcinoma.35 The four
architectural patterns of high grade PIN was described; tufting, micropapillary, cribriform
and flat, the tufting pattern being the most common.36 Rare forms of high grade PIN like
signet ring cell, small neuroendocrine and mucinous type were identified.37 These types
which are present in invasive carcinoma of prostate provides support for a close
relationship between HGPIN and invasive carcinoma. The histology of the central zone
located at the base of the prostate adjacent to seminal vesicle was studied and it was
concluded to be a potential mimicker of HGPIN.38
Prostatic carcinomas with endometrioid features are best classified and treated as
variants of prostatic duct carcinomas.39 A case of adenoid cystic carcinoma with negative
immunoperoxidase staining for both PSA as well as prostate specific acid phosphatase
was identified and suggested its origin from periurethral glands and metaplastic urethral
mucosa.40 For the diagnosis of mucinous adenocarcinoma of the prostate at least 25% of
tumor resected during a single procedure should contain lakes of extracellular mucin.41
Mucinous differentiation is common in prostatic adenocarcinoma although it seldom
involved more than 25% of volume of any cancer.42
Cribriform adenocarcinoma of prostate has been studied.43 The involvement of
prostate by Transitional Cell Carcinoma (TCC) in 43% cases of cystoprostatectomy
specimens removed for bladder cancer was reported.44 An unusual variant of prostatic
adenocarcinoma called foamy gland carcinoma characterized by abundant xanthomatous
cytoplasm was described in needle biopsy specimens.45
7
Prostatic adenocarcinoma with atrophic features was described.46 An unusual
pseudohyperplastic pattern of prostatic adenocarcinoma was described.47 Atypical small
acinar proliferation (ASAP) suspicious for malignancy in prostatic needle biopsies was
evaluated and concluded that the histologic finding of ASAP had a high predictive value
for malignancy.48 The significance of intraluminal crystalloids in benign prostate glands
on needle biopsy specimen was explored and then concluded that there is no significant
higher risk of having cancer on repeat biopsy if crystalloids were not present.49
The Gleason system of histopathologic grading is more reliable, reproducible and
an accurate prediction of surgical stage of disease.50,51 The international TNM
classification system for prostatic carcinoma has been revised and is most helpful for
comparisons between various groups of patients.52
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.53 The ratio of chips with cancer to the
number of chips in Transurethral Resection of Prostate (TURP) specimens was a reliable
predictor of stage of the disease.54 The percentage of TUR specimen involved and the
tumour volume with progression of prostatic carcinoma was correlated.55
8
Embryonic Development
The prostate first appears and starts its development from urogenital sinus during
the third month of fetal growth and its development is directed primarily by dihydro
testosterone, which is produced from metabolic conversion of fetal testosterone through
the action of enzyme 5 α reductase.
The prostate forms acini and collecting ducts by arborization that branches into
urethra and may be visualized as similar to a small tree with the growth occurring on tips
as ducts extend and branch during development.
At birth the majority of prostatic acini are lined by squamous epithelium and
metaplastic epithelial cells that have scattered secretory activity and lead to cyst
formation. Pubertal maturation period starting about age 11 or 12 yrs is characterized by
general development of pseudostratified epithelium with basal and secretory cells in all
parts of gland and increase in diameter of lumen of ducts. Formation of mature acini
starts at about 15-16 yrs. The prostate reaches its mature morphologic and functional
structure by age 18-20 yrs and retains this organization for approximately 10 yrs. Around
age 30 yrs initial signs of structural and functional disintegration occur and gland
gradually loses its functionally organized structure.
Thus, prostate is derived from a composite area of urogenital sinus requiring
androgen during organogenesis. It undergoes different phases of androgen responsivity
perinatally and during puberty.56
9
Anatomy and Histology
Prostate gland is an accessory gland of the male reproductive system. Normal
adult gland weighs 20 gms ± 6 gms and lies immediately below the base of bladder
surrounding the proximal part of urethra. The length of anterior aspect is between 3 and
4 cms and its width between 3.5 and 5cms.Prostate is composed of approximately
70% glandular elements and 30% fibromuscular stroma. Prostate contains a number of
individual glands composed of 30 to 50 lobules leading to 15-30 secretory ducts that open
into urethra. Prostate is composed of 3 distinct zones (a) peripheral zone comprising of
70% of prostate and common site of PIN and carcinoma, (b) central zone comprising
25% of prostate and surrounds ejaculatory ducts, (c) transition zone comprising 5% of
prostate and is the site for NH.57
The glands of prostate are tubuloalveolar and lined with cuboidal or columnar
epithelium. Scattered neuroendocrine cells of unknown function is found between the
secretory cells. Beneath the epithelial cells flattened basal cells line each acinus and are
believed to be stem cells for secretory epithelium. Each acinus is surrounded by a thin
layer of stromal smooth muscle and connective tissue.
Pathology of Prostate
Nodular Hyperplasia
NH involves overgrowth of epithelium and fibro muscular stroma of transition
zone and periurethral area. It results in varying degrees of urinary obstruction sometimes
requiring surgical intervention.
10
Epidemiology
NH is extremely common accounting for approximately 4,00,000 partial
prostatectomies annually, the most common form of surgery in American men. The age
specific prevalence is remarkably similar in populations through out the world. There is
rapid increase in prevalence of NH beginning in the 4th decade of life and culminating in
100% prevalence in 9th decade.57
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. Anti-androgens, gonadotropin releasing
hormone agonists and 5 alpha reductase inhibitors also reduce the symptoms. Most
epidemiologic 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.57
Pathogenesis
The development of NH includes 3 pathologic changes:
a)
Nodule formation
b)
Diffuse enlargement of transition zone and periurethral tissue
c)
Enlargement of nodules.
11
In men under 70 yrs of age diffuse enlargement predominates. In men over 70 yrs
of age, prostatic enlargement characteristic of NH is dominated by epithelial proliferation
and expansile growth of existing nodules probably as a result of androgenic and other
hormonal stimulation. The primary mediator of NH is dihydrotestosterone (DTH). This
androgen is the major intracellular metabolite of testosterone after its conversion by
5 alpha reductase. Testosterone and DTH bind to nuclear androgen receptors in stromal
and epithelial cells in prostate, although, DTH has a 5 fold higher affinity. The nuclear
androgen content of NH is greater than that of normal prostatic tissue.
Pathology
Grossly it is characterized by nodules of varying sizes, which are soft or firm,
rubbery and grayish white in colour weighing between 60 to 100 gms. The cut section is
nodular. Degenerative changes include calcification and infarction.57
Microscopy
The earliest change is stromal proliferation, which contains more smooth muscle
and less elastic tissue than normal stroma. The glands are dilated or even cystic often
contain an inspissated secretion corpora amylacea. Epithelium is flat or columnar
sometimes facing each other in same gland (functional polarization). The epithelium is
thrown in to numerous papillary buds and infoldings. The cells have pale cytoplasm and
regular central nuclei. Aggregates of lymphocytes are often found within the stroma. In
majority of instances, the nodules are adenofibromyomatous nodules, which contain all
elements. Small areas of hemorrhagic necrosis surrounded by reactive change in residual
12
epithelium at the margins (squamous metaplasia or transitional metaplasia) may be seen
within the nodules.57
Variants of hyperplasia
1)
Post-atrophic hyperplasia
This is characterized by benign proliferating luminal cells with scanty clear
cytoplasm in an atrophic background. The cells often show mild cytologic atypia and
luminal mucin may be identified.57
2)
Basal cell hyperplasia
This is characterized by proliferation of basal cells of more than two cells thick
and protrudes into the gland lumen, retaining the overlying secretory luminal epithelium.
The hyperplastic basal cells are usually larger than normal, are elongated (spindled) basal
cells and is often accompanied by nuclear enlargement.19
3)
Cribriform hyperplasia
This includes clear cell cribriform hyperplasia and consists of nodule composed
of glands arranged in distinctive cribriform pattern. The cells usually have pale-clear
cytoplasm and small uniform nuclei with inconspicuous nucleoli.21
4)
Sclerosing adenosis
It shows striking myoepithelial metaplasia of basal cell compartment as well as a
exuberant stroma composed of fibroblasts and loose ground substance.22
13
Associated benign lesions
1)
Atrophy
This is characterized by small-distorted glands with a flattened epithelium,
hyperchromatic nuclei and stromal fibrosis. It is idiopathic and its prevalence increases
with advancing age.
2)
Atypical basal cell Hyperplasia
This is basal cell hyperplasia in which nucleoli are prominent.26
3)
Basal cell adenoma
This 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)
Adenoid basal cell tumour
Consists of basaloid cell nests of varying sizes that infiltrate the stroma. The cell
nests are often large, round to angular. The peripheral basaloid cells have elongated
nuclei and often show palisading. There is prominent cell crowding.
5)
Atypical adenomatous hyperplasia (Adenosis)
This is localized and circumscribed proliferation of small glands within the
prostate that may be mistaken for carcinoma.
14
6)
Stromal Hyperplasia with atypia
This is characterized by stromal nodules that occur in setting of NH but show
increased cellularity and nuclear atypia. These appear as solid stromal nodules or as
atypical cells interspersed within benign glands. Stromal nuclei are large hyperchromatic,
rarely multinucleated or vacuolated and contain inconspicuous nucleoli. There are no
mitoses and necrosis. Stromal hyperplasia with atypia has no malignant potential and the
atypical cells are considered to be degenerative.
7)
Phyllodes Tumour
This is a rare neoplasm of adults. It is a fibroadenoma that shows increased
cellularity and cytologic atypia, reminiscent of phyllodes tumour of breast. The glandular
epithelium is distorted and lines slit like spaces surrounded by a variably cellular
proliferative stroma composed of fibroblasts and smooth muscle cells.58,59
Association of NH and prostate cancer
Both show a parallel increase in prevalence with increasing age according to the
results of autopsy studies, although cancer lags by 15-20 yrs. Both require androgens for
growth and development to occur and both may respond to androgen deprivation
treatment. Most cancers arise with in prostate together with NH. Cancer is found
incidentally in a significant number (10%) of TURP specimens. NH may be related to
prostate cancer arising in transition zone, perhaps in association with certain forms of
hyperplasia, but NH is not a pre-malignant lesion or a precursor of cancer.
15
Infarct
Infarct of prostate occurs predominantly in large prostates that exhibit nodular
hyperplasia. It is found to be present in 18% to 25% cases. The size and number of
infarcts are directly related to degree of prostatic hyperplasia. The mechanism of infarct
is unknown, but may be related to the presence of prostatic infection or trauma resulting
from an indwelling catheter, cystitis or prostatitis all of which may result in thrombosis of
intraprostatic portion of urethral arteries.57
Grossly, infarcts vary in size from a few millimeters up to five centimeters. They
are speckled grayish yellow and often contain streaks of blood. The peripheral margins
are sharp and hemorrhagic.
Microscopically, there are sharply outlined areas of ischemic coagulative necrosis
involving the glands and stroma. Prominent squamous metaplasia is often seen in the
ducts bordering a infarct. This metaplastic change is confined to the expanded ducts,
keratinizes only rarely, and does not extend to the surrounding prostatic tissue. Infarct
may cause serum elevation of PSA levels, removal of infarcted area return the levels to
normal.
Prostatic Inflammation
The spectrum of prostatitis encompasses a multitude of inflammatory diseases of
prostate. These varied forms of prostatitis show marked differences in treatment and
clinical outcome and therefore require accurate diagnosis. Patchy acute and chronic
inflammatory infiltrate is present in the prostate of most adult men and is considered a
16
normal finding. But when the inflammation is severe and extensive or clinically apparent
the term prostatitis is warranted. It is associated with increased serum PSA levels, which
return to normal levels following treatment.
1)
Acute Bacterial Prostatitis
Acute bacterial prostatitis presents with sudden fever, chills and irritative voiding
symptoms. The prostate is swollen, tender and warm. The bacteria responsible for acute
prostatitis are Escherichia Coli (80%) other enterobacteriacea such as pseudomonas,
serratia, klebsiella (10-15%) and enterococci (5-10%).60
Microscopically there are sheets of neutrophils in and around prostatic ducts and
acini with desquamated epithelium and cellular debris. Stroma is edematous and
hemorrhagic and contains variable numbers of lymphocytes, plasma cells and
macrophages. Microabscesses are frequently seen. Diagnosis is based on findings yielded
by urine culture and biopsy is contraindicated.
Prostatic Abscess
A rare complication of acute bacterial prostatitis occurring most commonly in
immunocompromised patients. Predisposing factors include urethral instrumentation and
use of indwelling catheters. Patients present with prostatic enlargement, fever and
retention of urine. A fluctuant mass is occasionally palpated by rectal examination.
Prostatic abscess can be caused by aerobic and anaerobic bacteria.
17
2)
Chronic Prostatitis
The spectrum includes chronic bacterial, chronic abacterial and granulomatous
prostatitis. Chronic prostatitis presents with variable clinical features and include
frequency, urgency, dysuria, pain in perineum, lower back and testis. Digital rectal
examination varies from normal to tender and boggy. Microscopically charecterised by
aggregates of lymphocytes, plasma cells and macrophages within the prostatic stroma.
The epithelium displays reactive atypia with occasional prominent nucleoli. The
histologic findings in combination with clinical manifestations are characteristic of
chronic prostatitis.
Bacterial and abacterial chronic prostatitis mimic each other clinically and
histologically but differentiated by presence or absence of bacteria on culture. Usually
gram-positive bacteria are found in cultures of prostatic fluid.
a)
Chronic bacterial prostatitis
Most cases are due to E.Coli infection. In patients with prostatic calculi, and relapsing
urinary tract infection (UTI), the stones serve as a nidus of infection, with bacteria
embedded in mineral matrix.
b)
Chronic abacterial (idiopathic) prostatitis
This is more common than bacterial prostatitis. Cultures of urine and expressed
prostatic secretion yield negative results. This form of prostatitis has a prolonged indolent
course characterized by relapses and remissions.
18
3)
Granulomatous prostatitis
It is a group of morphologically distinct chronic prostatitis caused by a wide
variety of inciting agents, including infections, tissue disruption after biopsy and
inflammation. It accounts for approximately 1% of benign inflammatory conditions of
prostate. Most of the patients have a history of UTI, it is probably caused by blockade of
prostatic ducts and stasis of secretions. Epithelium is destroyed and cellular debris,
bacterial toxins and prostatic secretions sperm, semen escape into stroma eliciting a
intense localized inflammatory response.
Grossly the gland is firm to stony hard. Cut section shows obliteration or
architecture with formation of yellow granular nodules. Microscopically large nodular
aggregate of histiocytes, epitheloid cells, lymphocytes and plasma cells are seen.
Caseation necrosis is absent.
a)
Idiopathic (non-specific) granulomatous prostatitis
This makes up the majority of cases. The granulomas are usually non-caseating and
associated with parenchymal loss, marked fibrosis and more number of eosinophils in
stroma.
Xanthoma: It is a rare form of idiopathic granulomatous prostatitis and is
characterized by a localized collection of cholesterol laden histiocytes.
19
b)
Infectious granulomatous prostatitis
Numerous microorganisms can induce granulomatous prostatitis, including
bacteria
(Mycobacterium
tuberculosis,
Brucellosis),
fungi
(Cryptococcus
and
Blastomycosis), parasite (Schistosoma haematobium) and virus (Herpes zoster).
c)
Iatrogenic granulomatous prostatitis: This can be caused by surgery, radiation
therapy and Bacille Calmette-Guerin (BCG) therapy for bladder cancer.16
i) Post-surgical Granulomatous Prostatitis
ii) Post-radiation granulomatous prostatitis
iii) BCG-Induced granulomatous prostatitis
Malakoplakia
This is a granulomatous disease attributable to defective intracellular lysosomal
digestion of bacteria. Patients present with obstructive symptoms including frequency,
urgency, dysuria, nocturia and fever. This occurs in men over 50 years of age with
systemic illnesses and other debilitating conditions. Digital rectal examination reveals
diffuse induration suggestive of prostatic carcinoma. E. coli is commonly isolated from
urine cultures.
Grossly, prostatic malakoplakia is characterized by discrete and confluent soft
yellow brown plaques, with central umbilication or ulceration and peripheral hyperemia.
Microscopically, the prostatic architecture is effaced by dense sheet-like
aggregates of histiocytes (Van-Hansemann cells) admixed with lymphocytes and plasma
20
cells. Intracellular and extracellular Michaelis-Gutmann bodies are seen, appearing as
sharply demarcated spherical structures with concentric “owl’s eyes” measuring 5 to
10 μm in diameter. These stain with Periodic acid Schiff (PAS) (polysaccharides),
Alizarin red-S (Calcium), Prussian blue (iron), and Von Kossa (anionic component of
calcium ions). Gram stain, acid-fast stain and fungal stains are negative.
d)
Systemic Granulomatous Disease
These include
i)
Allergic (eosinophilic) granulomatous prostatitis
ii)
Sarcoidosis
iii)
Rheumatoid Nodules
Prostatic inflammation and carcinogenesis: Chronic or recurrent inflammation
plays a role in development of carcinoma. Inflammatory cells elaborate numerous
microbicidal oxidant that cause cellular or genomic damage to prostate giving rise to cells
of PIN and carcinoma.7
Prostatic caliculi
Prostatic calculi are seen in about 7% of prostates with nodular hyperplasia. They
should be distinguished from those found in the prostatic urethra, which may have their
origin in the bladder, ureter or renal pelvis. The corpora amylacea seen in the glands with
nodular hyperplasia may act as the nucleus for stone formation as a result of improper
drainage, infection of the acini and calcium deposition. Blood clots, epithelial detritus,
and bacteria are also present in the stone nucleus. The main inorganic elements are
21
phosphated salts (calcium, magnesium, aminomagnesium, potassium), calcium carbonate
and calcium oxalate. Because of their extreme hardness, large prostatic calculi may be
mistaken for carcinoma on digital rectal examination. They are radio-opaque and can be
easily detected by radiographic examination.
PROSTATIC INTRAEPITHELIAL NEOPLASIA (PIN)
Definition: It is a neoplastic transformation of lining epithelium of prostatic ducts
and acini. The process is confined within the epithelium.61
The term prostatic intraepithelial neoplasia (PIN) was adopted by Bostwick and
Brawer (1989) to include all forms of atypical and malignant lesions of epithelial cells
confined to the lumens of duct/acinar system as well as similar lesions accompanied by
microinvasion. PIN is subdivided into 3 grades: PIN-I, II and III,described by Mc Neal
and Bostwick. The Bethesda workshop participants proposed a two-tier system
comprising low grade (PIN1) and high grade (PIN 2 and 3).31
PIN consists of dysplasia and proliferation of the normal luminal cell layer lining
the prostatic ducts and acini.
22
Diagnostic Criteria
McNeal and Bostwick (1986) described the diagnostic criteria for PIN.57
Features
Low
grade
(formerly PIN-I)
1. Architecture
Epithelial cell crowding,
Similar to low grade PIN; more
stratification with irregular
crowding and stratification
spacing
2. Cytology
PIN High
grade
(formerly PIN 2 and 3)
PIN
a. Nuclei
Enlarged with considerable Enlarged; some size and shape
size variation.
variation
b. Chromatin
Normal
Increased density and clumping
c. Nucleoli
Rarely prominent
Occasionally to frequently large
and prominent similar to invasive
carcinoma.
3. Basal cell layer
Intact
May show some disruption
4. Basement membrane Intact
Intact
LGPIN
The cells within ducts and acini are heaped up, crowded and irregularly spaced
and there is variation in nuclear size. Elongated hyperchromatic nuclei and nucleoli are
sometime seen but not prominent. Mc Neal summarizes that there is not a sharp line of
demarcation between LGPIN and mild degrees of deviation from normal histology.62
HGPIN
It exhibits features similar to LGPIN but cell crowding and stratification is more
pronounced and there is less variability in nuclear size but prominent nucleoli is
diagnostic. It displays four architectural patterns; tufting, micropapillary, cribrifom and
flat.
23
Evidence For The Association Of Prostatic Intraepithelial Neoplasia And Prostatic
Carcinoma
1.
Histology:
Similar cyto-architectural features.
2.
Location:
Both are multifocal with predominant peripheral zone distribution.
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.
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 immunoreactive for cytokeratins 14, 15, 16 and 19 unlike nodular
hyperplasia. Both show Ulex Europaeus-1 Lectin binding unlike normal
epithelium and nodular hyperplasia. Both show loss of vimentin immunoreactivity
24
unlike nodular hyperplasia. Both show loss of blood group A,B unlike normal
epithelium.
8.
Age:
Incidence and extent of both lesion increase with patient age.63
PIN and Mucin
The histochemical study of mucin in PIN by using Alcian blue at pH 1 and pH 2.5
and PASdiastase has demonstrated that there is progressive decrease in neutral mucin
from normal prostate to the 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.35
SPREAD OF PIN
PIN spreads through the prostatic ducts in 3 different patterns:
1)
Replacement of the normal luminal secretory epithelium by neoplastic cells, with
preservation of the basal cell layer and basement membrane.
2)
Pagetoid spread along the ducts, characterized by invasion of neoplastic cells
between the basal cell layer and luminal columnar secretory cell layer.
3)
Direct invasion through the duct/acinar wall with disruption of the basal cell layer
and basement membrane.63
25
CLINICAL IMPORTANCE OF PIN
PIN is obviously interesting on a number of grounds. The clinical importance of
recognizing PIN is based:
1.
On its association with prostate cancer.
2.
The association of PIN with serum prostate specific antigen levels:
PSA levels in PIN is intermediate between normal and carcinoma.
3.
PIN and Ultrasound
Transrectal ultrasound (TRUS) of the prostate in cases of PIN presents with
hypoechoic areas from which the ultrasound-guided biopsy of that area can be performed
and studied for the evidence of PIN and invasive carcinoma
4.
PIN and Repeat Biopsy:
Biopsy should be repeated at 3 months interval for first two years if the case is PIN
and then repeated yearly thereafter.
CLINICOPATHOLOGICAL EVALUATION OF PIN
On identification HGPIN on biopsy
1)
All the tissue should be processed and serially sectioned
2)
Basal cell specific anti-keratin monoclonal antibody (34βE12) stains should be
done.
3)
Transrectal ultrasound with biopsy should be done.
4)
Serum prostate specific antigen levels should be monitored.
26
5)
Repeat PSA, Trans rectal ultrasound guided biopsy at 3-month intervals for the
first two years and repeated yearly thereafter for life should be done.63
Carcinoma of the Prostate
Epidemiology
Prostatic carcinoma is the sixth most common malignancy in the world (in terms
of number of new cases). It represents 9.7% of cancers in men (15.3% in developed
countries and 4.3% in developing countries).64 It is the second most common cause of
cancer death in men. It is predominantly a disease of elderly men over 50 years.
The United States death rate for cancer of prostate is high compared to the other
countries. Rates for non-whites are about twice as high as whites in the United States.
Prostate cancer is extremely rare in orientals. The urban incidence rate is only slightly
higher than rural rate.
Aetiology
Little is known about the causes of prostatic cancer. The five main factors
implicated as aetiologic agents are:
a)
Age
b)
Race
c)
Endocrine system
d)
Environmental influences.
e)
Dietary and hereditary factors
27
Age
Risk of prostate cancer rises steeply with age. Incidence of clinical disease is low
until age fifty and then increases rapidly. The highest incidence is found in the age group
70-79 yrs as compared with 50-60 years of other epithelial cancers.57
Race
American blacks have higher incidence than whites. The prevalence rate among
Japanese, is in the range of 3-4% and for the Chinese in Hong Kong only one percent as
compared with the rate of 50-60 % among the whites in the United States.57
Endocrine System
Testosterone diffuses into gland where it is converted by enzyme steroid 5α
reductase type II to the more metabolically active form dihydrotestosterone (DHT). DHT
and testosterone bind to androgen receptor and receptor ligand complex translocates to
the nucleus for DNA binding and transactivation of genes which have androgen
responsive elements including those controlling cell division.
Environmental Influences
Environmental factors as occupational exposure or behavioral factors (sexual life)
do not seem to play a clear role. No relationship has been shown between prostatic
carcinoma and cigarette smoking, use of alcohol, weight, height, blood group or hair
distribution.9
28
Dietary and Hereditary Factors
Studies implicate strong association of prostate cancer with intake of animal
products especially red meat.7
There is 5-11 fold increased risk among men with two or more affected first
degree relatives.4,5
Location
Cancers detected on TURP are predominantly within the transition zone. 8% of
contemporary TURP specimens disclose carcinoma. When TURP is done without clinical
suspicion of carcinoma prostate cancer is incidentally detected in approximately 8-10%
of specimens.64
WHO Histological classification of tumors of prostate
Epithelial tumors
1)
Glandular neoplasms
•
Adenocarcinoma (acinar)
•
Atrophic
•
Psuedohyperplastic
•
Foamy
•
Colloid
•
Signet ring
•
Oncocytic
29
•
Lymphoepithelioma like carcinoma with spindle cell differentiation
(carcinosarcoma, sarcomatoid carcinoma)
2)
•
PIN
•
PIN Grade III (PIN III)
•
Ductal adenocarcinoma
•
Cribriform
•
Papillary
•
Solid
Urothelial tumors
•
3)
4)
5)
Urothelial carcinoma
Squamous tumors
•
Adenosquamous carcinoma
•
Squamous cell carcinoma
Basal cell tumors
•
Basal cell adenoma
•
Basal cell carcinoma
Neuroendocrine tumors
•
Endocrine differentiation with in adenocarcinoma
•
Carcinoid tumor
•
Small cell carcinoma
•
Paraganglioma
•
Neuroblastoma
30
6)
7)
8)
Prostatic stromal tumors
•
Stromal tumor of uncertain malignant potential
•
Stromal sarcoma
Mesenchymal tumors
•
Leiomyosarcoma
•
Rhabdomyosarcoma
•
Chondrosarcoma
•
Angiosarcoma
•
Malignant fibrous histiocytoma
•
Malignant peripheral nerve sheath tumor
•
Haemangioma
•
Chondroma
•
Leiomyoma
•
Granular cell tumor
•
Hemangiopericytoma
•
Solitary fibrous tumor
Hematolymphoid tumors
•
Lymphoma
•
Leukaemia
31
9)
10)
Miscellaneous tumors
•
Cystadenoma
•
Nephroblastoma (Wilm’s tumor)
•
Rhabdoid tumor
•
Germ cell tumors
•
Yolk sac tumor
•
Seminoma
•
Embryonal carcinoma and teratoma
•
Choriocarcinoma
•
Clear cell adenocarcinoma
•
Melanoma
Metastatic tumors
Acinar Adenocarcinoma
Gross Features
Carcinomas of prostate arise most commonly in posterior lobe and thus it is
readily palpable on rectal examination. The gland may be enlarged or of normal size,
nodular and firm in consistency. On transection the neoplastic tissue is gritty, dry, fibrous
and homogenously solid and often contains irregular, yellowish areas.1
Histopathological Examination
Adenocarcinoma of prostate range from well-differentiated gland forming cancers
to poorly differentiated tumors difficult to identify as being of prostatic origin.64
32
Architectural Features
Glands are crowded, grow in haphazard fashion, oriented perpendicular to each
other and irregularly separated by bundles of smooth muscle indicative of an infiltrative
process. Undifferentiated prostatic carcinoma is composed of solid sheets, cords of cells
or isolated individual cells.64
Nuclear Features
Nuclear enlargement with prominent nucleoli is characteristic.64
Cytoplasmic Features
Glands of adenocarcinoma tend to have discrete crisp, sharp luminal border
without undulations or ruffling of cytoplasm. In low-grade carcinoma the cells show pale
cytoplasm while neoplastic glands have amphophilic cytoplasm.64
Intraluminal Features
Prostatic crystalloids, are dense eosinophilic crystal like structures that appear in
various geometric shapes rectangle, hexagon, triangle and rod like.64
Extraprostatic Site Extension
a)
Perineural invasion- malignant gland should completely encircle the nerve.
b)
Mucinous fibroplasia (collagenous micro nodules)-very delicate loose fibrous
tissue, which are ingrowths of fibroblasts sometimes reflecting organization of
intraluminal mucin.
c)
Glomerulations-glands with a cribriform proliferation that is not transluminal.
33
Histologic Variants
1.
Atrophic variant
Consists of individual small atrophic glands exhibiting marked cytologic atypia
2.
Pseudohyperplastic variant
Consist of numerous closely packed glands, which are large with branching and
papillary infoldings.
3.
Foamy gland variant
Consists of glands with cells having abundant foamy cytoplasm with a very low
nuclear cytoplasmic ratio. Nuclei are small and densely hyperchromatic.
4.
Mucinous and signet ring variant
Mucinous tumor is accompanied by formation of large amounts of intracellular
and extra cellular mucin comprising 25% or more of the tumor. Microglandular,
cribriform, comedo, solid and hypernephroid patterns may be present. Signet ring
carcinoma grows in solid acinar fashion and is composed of cells with signet ring
configuration resulting from intracellular accumulation of mucin.
5.
Oncocytic variant
Consists of glands with large cells having granular eosinophilic cytoplasm and
round to ovoid hyperchromatic nuclei
6.
Lymphoepithelioma like variant
Undifferentiated carcinoma, consisting of synctial pattern of malignant cells
associated with heavy lymphocytic infiltrate.
34
7.
Sarcomatoid variant
Consisting of features of a carcinoma with sarcomatiod elements showing
differentiation towards cartilage bone, and/or skeletal muscle.64
PIN III
Incidence of HGPIN is uncommon with a rate of 2.3% to 2.8%.61 Four patterns of
HGPIN are noted.
1.
Flat-nuclear atypia with out significant architectural changes.
2.
Tufting-nuclei become more piled up resulting in undulating mounds of cells.
3.
Micropapillary-columns of atypical epithelium that typically lack fibrovascular
cores.
4.
Cribriform-more complex architectural patterns appear such as roman bridge.
Variants of PIN
Signet ring variant shows cytoplasmic vacuoles, which displace and indent nuclei.
Mucinous variant exhibiting solid intraluminal masses of blue tinged mucin that
fill and distend the glands resulting in flat pattern of growth.
Foamy variant were foamy PIN glands are large with papillary in-foldings lined
by cells with bland nuclei.65
Inverted variant consisting polarization of enlarged secretory cell nuclei toward
the glandular lumen with tufted or micropapillary patterns.
35
Small cell neuroendocrine variant consisting of small neoplastic cells with rosette
like formations are observed in center of glands.
Intraductal variant having overlapping features of cribriform HGPIN and
carcinoma.
Ductal adenocarcinoma
Composed of large glands lined by tall pseudostratified columnar cells with
abundant amphophilic cytoplasm. Accounts for 0.2-0.8 % of prostate cancer.66 The
patterns are:
a.
Papillary pattern, which can be seen in both centrally or peripherally, located
tumours.67
b.
Cribriform pattern, formed by back-to-back large glands with intraglandular
bridging resulting in formation of slit like lumens.68
c.
Individual gland characterized by single glands.
d.
Solid pattern, solid nests of tumor cells are separated by incomplete fibrovascular
core.
2.
Urothelial carcinoma
Accounts for 0.7-2.8% of prostatic tumor in adults. It consists of full range of
histologic types, papillary urothelial neoplasm, high-grade with in situ components.
Urothelial carcinoma fills and expands ducts and often develops central comedo
necrosis stromal invasion is associated with a prominent desmoplastic stromal response
36
with tumor cells arranged in small irregular nests cords and single cells. Angiolymphatic
invasion is often identified.66
3.
Squamous tumors
Adenosquamous.
Consists of both glandular (acinar) and squamous cell carcinoma components.
Occurs after radiation or hormonal therapy of adenocarcinoma.69
Squamous cell carcinoma
Tumors with squamous cell differentiation involving prostate, accounts for
<0.6% of all prostate tumors. Pure SCC does not contain glandular features and is
identical to SCC of other origin. Evidence of keratinization and squamous differentiation
are required for diagnosis.70
4.
Basal cell tumors
Basal cell adenoma.
Basal cell carcinoma.
Consisting of large basaloid cells with cell nests exhibiting peripheral palisading
and necrosis.71
5.
Neuroendocrine tumors
Neuroendocrine differentiation has three forms:
i)
Focal neuroendocrine differentiation in conventional prostatic adenocarcinoma –
All prostatic carcinoma show focal neuroendocrine differentiation. In 5-10% of
37
carcinomas there are zones with large number of single or clustered
neuroendocrine cells detected by chromogranin A immunostaining.
ii)
Carcinoid tumor (WHO well differentiated neuroendocrine tumor) – Classic
features of carcinoid tumour.
iii)
Small cell neuroendocrine carcinoma (new WHO classification poorly
differentiated neuroendocrine) identical to small cell carcinoma of lung.66
Mesenchymal Tumors
Sarcomas account for 0.1-0.2% of all malignant tumors.
Lesions are classified as prostatic stromal proliferation of uncertain malignant
potential (STUMP) and prostatic stromal sarcoma based on degree of stromal cellularity
presence of mitotic figures, necrosis and stromal overgrowth.66
Special Staining Methods
Various types of mucin and polysaccharides in prostatic cancer can be
demonstrated
by
Alcian
Blue,
PASd.
Normal
prostate
gland
contains
mucopolysaccharides or mucoprotiens, which are periodic acid schiff diastase positive.
But a shift from neutral to acidic mucin is seen in carcinoma. In occult or early
carcinoma, secretion in acinar lumina contains sulfomucin and in some cases shows
neutral mucin. In well-differentiated or moderately differentiated carcinomas, there is
abundant sialomucin or sulfomucin with a little neutral mucin. In undifferentiated
carcinomas, no secretions are generally detected.
38
Grading and staging
GLEASON`S
MICROSCOPIC
GRADING
SYSTEM
OF
PROSTATIC
CARCINOMA
Stage
Description
1
Single, separate, uniform glands in closely packed masses with a definite,
usually rounded, edge limiting the area of tumor.
2
Single, separate, slightly less uniform glands, loosely packed (separated by
small amounts of stroma), with less sharp edge.
3a
Single, separate, much more variable glands, may be closely packed but
usually irregularly separated; ragged, poorly defined edge.
3b
Like 3a, but very small glands or tiny cell clusters.
3c
Sharply and smoothly circumscribed rounded masses of papillary or loose
cribriform tumor (papillary intraductal tumor).
4a
Raggedly outlined, raggedly infiltrating, fused glandular tumor
4b
Like 4a, with large pale cells (hypernephroid).
5a
Sharply circumscribed, rounded masses of almost solid cribriform tumor,
usually with central necrosis (comedonecrosis).
5b
Ragged masses of anaplastic carcinoma with only enough gland formation
or vacuoles to identify it as adenocarcinoma.15
Primary grade is assigned to the dominant pattern and secondary to the
subdominant pattern. The two numeric grades are added to obtain the combined Gleason
grade or score. In tumors with one pattern the number is doubled. Gleason scores are
combined into groups : 2 to 4, representing well differentiated cancer, 5 to 6 representing
39
intermediate grade cancer, 7 representing moderate to poorly differentiated cancer and
8 to 10 representing high grade cancer.
The major system for staging is TNM system (primary tumor T, regional lymph
node N and Metastatic M)73
Primary tumor, clinical (T)
TNM
Description
Primary tumor, clinical (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 found incidental, histologic findings in 5% or less of tissue resected.
T1b
Tumor incidental histologic findings in more than 5% of tissue resected.
T1c
Tumor identified by needle biopsy (e.g. because of elevated PSA)
T2
Palpable tumor confined within the prostate.
T2a
T2b
Tumor involves one lobe.
Tumor involves both lobes
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 or pelvic wall
40
Primary tumor, pathologic (pT)
pT2
Organ confined
pT2a
Unilateral
pT2b
Bilateral
pT3
Extraprostatic extension
pT3a
Extraprostatic extension
pt3b
Seminal vesicle invasion
pT4
Invasion of bladder, rectum
N
Regional lymph nodes
Nx
Regional lymph nodes cannot be assessed.
No
No regional lymph node metastasis.
N1
Metastasis regional lymph node or nodes.
M
Distant metastatis
Mx
Distant metastasis cannot be assessed.
Mo
No distant metastasis.
M1
Distant metastasis.
M1a
Involvement of non-regional lymph nodes.
M1b
Involvement of bone(s).
M1c
Involvement of other distant sites.
None
None.
The ten year cancer-specific survival rate for all stages of cancer is about 51%
with an estimated cure rate of 32%.
41
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 yrs after the inception of the Gleason grading system it remains one
of the most powerful prognostic predictors in prostate cancer.72
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 androgens can be used.15
42
Prognosis
According to college of American Pathologists (1999) prognostic parameters are
divided into:
A)
Proven to be of prognostic importance and useful in clinical patient management
1. Preoperative serum PSA level
2. TNM stage grouping
3. Histologic grade as Gleason score
4. Surgical margin status
B)
C)
Extensively studied but whose importance remains to be validated :
1)
Tumor volume
2)
Histologic type
3)
DNA ploidy
Not sufficiently studied to demonstrate their prognostic value:
1)
Perineural invasion
2)
Neuroendocrine differentiation
3)
Microvessel density
4)
Nuclear roundness
5)
Chromatin texture
6)
Other karyometric factors
7)
Proliferation markers
8)
PSA derivates
9)
Other factors (oncogenes, tumor suppressor genes, apoptosis genes)
43
Immunohistochemical features
The two immunocytochemical markers for prostatic epithelium are Prostate
specific antigen (PSA) and Prostatic acid phosphatase (PAP).
Prostate specific membrane antigen (PSMA) a membrane bound glycoprotein is
expressed in all types of prostatic adenocarcinoma.
P504 S is an ∝-methyl COA racemase is highly sensitive in adenocarcinoma.
Prostatic cancer cells are immunoreactive for androgen and progesterone receptors.
Prostatic carcinoma cells are also positive for low molecular weight cytokeratins, Leu 7,
Epithelial membrane antigen, carcinoembryonic antigen, B 72.3, cathepsin D,
glycoprotein A-80, PTH-related protein and gastric acid proteinase gastricin.15
There are atleast 3 separate useful immunostains for basal cells 34βE12,P63 and
CK 5/6 all of which are negative markers for cancer (that is when they stain positively the
abnormal acinar focus is negative for cancer).74
Molecular Genetic features
Mutation in P53 gene occurs in 40% of prostatic carcinoma. It is a tumor
suppressor gene and exerts important regulatory control on apoptosis.
Alteration of Rb gene occur in significant number of cases. P27 an inhibitor of
cyclin and cyclin dependant kinases show decreased expression and aneuploidy of
prostate cancer increases. Expression of several anti-apoptotic members of the bcl–2.
gene family (including bcl2, bcl-x and mcl-1) increases during progression of prostatic
carcinoma.15
44
METHODOLOGY
The present study included prostatic tissue specimen received in the pathology
laboratory at Kempegowda Institute of Medical Sciences, Bangalore during the period
from December 2003 to December 2005. Brief clinical data were noted from the case
records, which included the age presenting symptoms, digital rectal examination findings,
serum PSA levels and clinical diagnosis.
The specimens thus obtained were fixed in 10% formalin after detailed and
careful examination. In case of TURP, approximately 5gm of tissue was processed in one
cassette and embedded. The entire tissue was processed in case of TURP and needle
biopsy and in cases of prostatectomy representative bits were processed. Then sections
4 to 6 microns thick were prepared. These were stained routinely with hematoxylin and
eosin.
Other special stains like Alcian blue pH 1, periodic acid schiff (PAS) and Ziehl
Neelson were performed wherever necessary. The procedure followed for tissue
processing and staining technique are those given in “Cellular Pathology technique” by
CFA Culling.75
All the lesions were graded into non-neoplastic and neoplastic lesions. The cases
of prostatic adenocarcinoma were graded using Gleason microscopic grading.
The clinical and histological data so obtained were analyzed and compared with
another similar studies.
45
STATISTICAL METHODS
Chi-square and Fisher exact test have been used to test the proportions in
association of lesions with Age, Clinical symptoms and Serum PSA values
1.
χ
2.
Chi-Square Test
2
∑ (Oi − Ei)
=
Ei
2
, Where Oi is observed frequency and Ei is Expected frequency
Fisher Exact Test
Class 1
Class 2
Total
Sample 1
a
b
a+b
Sample 2
c
d
c+d
a+c
b+d
n
Total
Fisher Exact Test statistic=
∑p=
(a + b)!(c + d )!(a + c)!(b + d )!
1
n!
∑ a!b!c!d!
Statistical software
The statistical software namely SPSS 11.0 and Systat 8.0 were used for the
analysis of the data and Microsoft word and Excel have been used to generate graphs,
tables etc.
46
RESULTS
The present study was carried out from December 2003 to December 2005, at the
Kempegowda institute of Medical Sciences, Bangalore.
Table 1
Age incidence of the various prostatic lesions
Age (yrs)
Benign
n (%)
Malignant
n(%)
30 – 39
-
-
40 – 49
4(2.94%)
-
4(2.67%)
P>0.05
50 – 59
19(13.97%)
1(7.14%)
20(13.33%)
0.694
60 – 69
55(40.44%)
6(42.86%)
61(40.67%)
0.861
70 – 79
49(36.03%)
7(50.00%)
56(37.33%)
0.303
80 – 89
9(6.62%)
-
9(6.00%)
P>0.05
Total
136(100.00%)
14(100.00%)
150(100.00%)
-
Inference
Total
n(%)
p value
-
Malignant cases are more commonly seen in the age group of
70-79 years with p=0.303 and benign cases are more common in the
age group of 40-59 years with p=0.470.
Benign lesions were common in the age group of 60-69 yrs while malignant
lesions were common in the age group 70-79yrs. However, when benign and malignant
lesions were compared, benign cases commonly occurred in the age of 40-59 yrs and
malignant lesions peaked in 70-79 yrs.
47
Graph 1 a
Age incidence of the various prostatic lesions
Benign
Malignant
Total
50
45
40
Percentages
35
30
25
20
15
10
5
0
30-39
40-49
50-59
60-69
70-79
80-89
Age in years
Graph 1b
Incidence of benign and malignant lesions
Malignant
9.33%
Benign
90.67%
48
Table 2
Clinical presentation of prostatic lesions
(Figures in parenthesis are percentages)
Benign Malignant
Total
p value
(n=136)
(n=14)
(n=150)
1.Frequency
50
5
55
0.323
(36.5)
(38.5)
(36.67)
2.Nocturia
10
2
12
0.278
(7.3)
(15.4)
(8.00)
3.Urgency
7
7
P>0.05
(5.1)
(4.67)
4.Difficulty in voiding
39
3
42
P>0.05
(28.5)
(23.1)
(28.00)
5.Straining
3
3
P>0.05
(2.2)
(20.00)
6.Poor stream
15
15
0.364
(10.9)
(10.00)
7.Hesitancy
2
2
P>0.05
(1.5)
(1.33)
8.Incomplete voiding
19
5
24
0.036*
(13.9)
(38.5)
(16.00)
9.Hematuria
1
2
3
0.020*
(0.7)
(15.4)
(2.00)
10.Acute retention
31
2
33
0.734
(22.6)
(15.4)
(22.00)
11.Dysuria
21
5
26
0.050*
(15.3)
(38.5)
(17.33)
Inference
Incomplete voiding, hematuria, dysuria are
significantly associated with the malignant lesions
with p≤0.05, poor stream is positively associated
with benign lesions with p=0.364.
* Significance at 5%
Clinical symptoms
Frequency was the most common symptom in benign lesions followed by difficulty in
voiding, acute retention and dysuria. Malignant lesions had common symptoms of
dysuria, incomplete voiding and frequency. However when both lesions were compared
poor stream was positively associated with benign lesions and incomplete voiding,
hematuria and dysuria were significantly associated with malignant lesions.
49
Graph 2
Clinical presentation of prostatic lesions
Benign
40
Malignant
1.Frequency
2.Nocturia
3.Urgency
4.Difficulty in voidi
5.Straining
6.Poor stream
7.Hesitancy
8.Incomplete voidin
9.Hematuria
10.Acute retention
11.Dysuria
35
Percentage
30
25
20
15
10
5
0
1
2
3
4
5
6
50
7
8
9
10
11
Table 3
Digital rectal examination findings
Digital rectal examination findings
Nodularity
137
Hard nodule
13
Graph 3
Digital rectal examination findings
13
Nodularity
Hard nodule
137
Clinically digital rectal examination findings showed nodularity in 137 cases and
presence of hard nodule in 13 cases.
51
Table 4
Serum PSA levels in the cases studied
PSA values (ng/ml)
Benign
Malignant
0-4
75
2
4.1-8
25
0
8.1-12
11
3
12.1-15
1
1
16.1-20
5
0
>20.1
19
8
Total
136
14
Inference
PSA values with >20.1 are
8.21 times more likely to be
malignant with p=0.001
Graph 4
Serum PSA levels in the cases studied
80
70
No.of cases
60
50
40
Malignant
30
Benign
20
10
0
0-4
4.1-8 8.1-12 12.115
15.1- >20.1
20
PSA Value (ng/ml)
52
Table 5
Clinical Diagnoses in the cases studied
Clinical diagnosis
No. of cases
BPH
132(88%)
Carcinoma prostate 17(11.3%)
Metastatic TCC
1(0.5%)
Total
150
Graph 5
Clinical Diagnoses In the cases Studied
BPH
CA prostate
Metastatic ca
17
1
132
Clinically 132 cases were diagnosed as benign prostatic hyperplasia with 17 cases
of prostatic carcinoma and one case of metastatic TCC from bladder.
53
Table 6
Nature of prostatic tissue studied
Nature of Tissue
No. of Cases
TURP chips
134 (89.3%)
Needle Biopsy
12 ( 8.0%)
Total Prostatectomy
4 (2.6%)
Total
150
Graph 6
Nature of prostatic tissue studied
140
120
No.of cases
100
80
60
40
20
0
1
2
3
1) TURP
2) Needle Biopsy
3) Prostatectomy
54
Table 7
Microscopic findings in benign lesions studied
Microscopic findings
No. of cases
1) Adenofibromyomatous hyperplasia
80
2) Basal cell Hyperplasia
5
3) Clear cell Hyperplasia
2
4) Squamous Metaplasia
5
5) Transitional Metaplasia
13
6) Prostatitis
24
7) Abscesses
2
Prostatic intraepithelial neoplasia
Lesions
No. of cases
LGPIN with BPH
12
HGPIN with BPH
1
HGPIN with carcinoma 6
55
Graph 7
Microscopic findings in benign lesions studied
80
70
No.of cases
60
50
40
30
20
10
0
1
2
3
4
5
6
7
Microscopic Findings
1) Adenofibromyomatous 5) Transitional metaplasia
2) Basal cell hyperplasia
6) Prostatitis
3) Clear cell hyperplasia
7) Abscesses
4) Squamous metaplasia
56
Table 8
Microscopic findings in malignant lesions studied
Microscopic Findings
No. of cases
1) Acinar Pattern
8
2) Trabeculae
4
3) Cords/strands
4
4) Cribriform
6
5) Nests
2
6) Sheets
5
7) Clear Cells
1
8) Perinueral Infiltration
3
9) Metastatic Tumour (TCC High Grade)
1
10) Primary SCC
1
Adjacent Prostatic Tissue
a) Adenofibromyomatous
hyperplasia
b) Inflammation
c) HGPIN
10
3
6
The commonest pattern in case of adenocarcinoma was the acinar pattern
followed by cribriform and sheets. The adjacent tissue in these cases showed
adenofibromyomatous hyperplasia in 10 cases, HGPIN in 6 cases and inflammation in
3 cases.
57
Graph 8
Microscopic findings in malignant lesions studied
8
7
No. of cases
6
5
4
3
2
1
0
1
2
3
4
5
6
7
8
9
10
Microscopic findings
1) Acinar pattern 6) Sheets
2) Trabeculae
7) Clear cells
3) Cords/Strands 8) Perineural Infiltration
4) Cribriform
9) Metastatic TCC
5) Nests
10) Primary SCC
58
Table 9
Incidence of carcinoma with reference to Gleason’s score (maximum Score 10)
Gleason`s Score No. of Cases
2
-
3
-
4
-
5
-
6
-
7
7 (58.3%)
8
3 (25%)
9
2 (16.7%)
10
-
Total
12 (100%)
Graph 9
Incidence of carcinoma with reference to Gleason’s score (maximum Score10)
16.7
0
25
58.3
59
2
3
4
5
6
7
8
9
10
Table 10
Final histopathological diagnosis in the cases studied
1) NH
a) Without Prostatitis
98(65.3%)
b) With Prostatitis
25(16.6%)
2) PIN a) LGPIN
12(8.0%)
b) HGPIN
1 (0.7)
3) Adenocarcinoma
12(8%)
4) Metastatic TCC (from Urinary Bladder)
1(0.7%)
5) Squamous Cell Carcinoma
1(0.7%)
Graph 10
Final histopathological diagnosis in the cases studied
90
80
No.of cases
70
60
50
40
30
20
10
0
1
2
3
4
Diagnosis
60
5
61
62
63
64
65
66
67
68
69
70
DISCUSSION
Enlargement of prostate is an age related process and incidence increases with
increasing age beginning in the forties. The incidence of NH increases from an average of
23 to 88% by the ninth decade.77
Hyperplasias
Gross:
1.
TURP specimens consisted of multiple gray white soft tissue bits. The weight
ranged from 2-30 grams.
2.
Needle biopsy consisted of 3-4 linear soft tissue bits measuring 1-1.5 cm in length
having thickness of 2-4 μm.
3.
Prostatectomy specimens showed hyperplastic lateral lobes. The cut section was
nodular with solid and cystic areas (Fig. 1).
Most patients over the age of 50yrs will have histological evidence of BPH and
many will suffer symptoms from urethral compression. Data indicate that on microscopic
examination both epithelium and stroma are involved in varying degrees and
predominant pattern is fibroadenomatous hyperplasia.
In the present study adenofibromyomatous hyperplasia was seen in 136 cases
where hyperplasia of both epithelial and stromal components was seen. According to
study by Bostwick et al. NH is composed of varying proportion of epithelium and stroma.
The most common nodules reported in their study was adenofibromyomatous nodules
which contained all elements.57 (Fig. 2)
71
In the present study 5 cases showed basal cell hyperplasia in the age group of 6575yrs with usual symptom of difficulty in voiding. It is characterized by nodular growth
of nests, tubules and cords filled with proliferating small, darkly staining basal cells.
Most of the nests of BCH show vertical palisading of basal cells towards the periphery
(Fig 3). According to a study, it occurs in the same age group as NH (range 63-80yrs,
mean 74yrs) and usual presenting symptom is urinary obstruction.19
In the present study 2 cases showed features of clear cell cribriform hyperplasia
(CCCH) in the age group of 55-75yrs. Ayala et al. reported ten cases of CCCH. It is
composed of glands with abundant clear cytoplasm and a nodular growth pattern78
(Fig 4). Their ages ranged from 62-87yrs with a mean age of 72yrs.19
The present study showed 13 cases of transitional metaplasia (Fig. 5) and 5 cases
squamous metaplasia (Fig. 6) in addition to NH.
PROSTATITIS
In the present study out of 150 cases, 26 cases had prostatitis. These included
Table 11
Showing the incidence of prostatitis
Chronic non specific prostatitis
20 (80%)
Abscesses
2 (8%)
Granulomatous prostatitis
3 (12%)
72
In the study by Granados et al. 25 cases of prostatic abscess were studied which
showed sheets of neutrophils in and around the acini79 (Fig. 7).
In cases of chronic non-specific prostatitis lymphocytes, plasma cells,
macrophages were seen. Bostwick in his study has reported more cases of chronic
abacterial as compared to bacterial prostatitis.57 (Fig 8).
In the present study 3 cases of non-specific granulomatous prostatitis were noted,
out of which one of the case showed well formed epitheloid granulomas with giant cell.
There was no evidence of caseation and special stain for AFB was negative (Fig 9).
Out of 25 cases of prostatitis urine culture was done in ten cases of which E. Coli
was seen in 6 cases, 2 cases showed growth of Klebsiella and one case each of
Enterococci and pseudomonas.
In a study by Still well 200 cases of granulomatous prostatitis were reported
amongst which 138 were of non specific granulomatous prostatitis (69%) and 49 cases
were of post biopsy granulomas (3.5%) and 6 cases were of systemic granulomatous
disease (3%).28
IHC was done for Leucocyte Common Antigen (LCA) in a case to distinguish
distorted lymphocytes in the stroma, (artifactual) which were appearing as signet ring
cells. The cells showed positive membrane reaction73 (Fig. 11 and 12).
73
PIN
In the present study out of 150 specimens examined 19 cases showed PIN,
12 cases LGPIN which was associated with NH and 7 cases showed HGPIN out of which
1 was associated with NH and the rest 6 were associated with prostatic carcinoma.
LGPIN was characterized by epithelial crowding and stratification with anisonucleosis
but no prominent nucleoli was observed (Fig. 10).
HGPIN was characterized by pronounced epithelial crowding and stratification
nuclear enlargement hyperchromasia with prominent nucleoli. None of these lesions
showed disruption of basal cell layer and basement membrane (Fig. 13).
In our study PIN was seen most commonly in the age group of 70 –79 yrs. In the
study by McNeal and Bostwick frequency of PIN was highest in the age group
60 –69yrs.28 In the study by Lee et al, the mean age of PIN was 65 yrs.
In our study out of 19 cases of PIN, 13 cases were associated with BPH out of
which 12 were LGPIN and 1 was HGPIN. Out of 12 case of adenocarcinoma 6 showed
HGPIN in the adjacent prostatic tissue.
74
Table 12
Incidence of PIN in cases of prostates with and without prostatic carcinoma
No. of
prostates
examined
PIN without
carcinoma
(% PIN)
PIN with
carcinoma
(%PIN)
McNeal and Bostwick (1986)80
200
43
82
Horinger W (2001) 81
1077
4.7
61.4
Kovi (1988)82
429
46
59.2
Present study
150
9.4
46.1
Studies
Brawer concluded in his study that PIN occurred more commonly in prostates
with invasive carcinoma than in without. According to his study PIN was found in 73%
of prostates with carcinoma and 32% of prostates without carcinoma.31
Table 13
Incidence of HGPIN in prostates with carcinoma
Incidence of HGPIN
in prostatic adenocarcinoma(%)
Authors
McNeal and Bostwick (1986)80
Kovi et al (1988)
33
82
Troncoso et al (1989)
33
80
72
83
Quinn et al (1990)
W. Horinger (2001)81
100
61.4
Present study
50
The incidence of PIN varies considerably in different studies probably because
histological diagnosis of LGPIN shows subjective variation and many studies do not
report LGPIN.62
75
The incidence of HGPIN is relatively low in cases of prostatic carcinoma because
most of the specimens were TURP which does not have enough material compared to
radical prostatectomy which was studied in other studies.33 It has also been suggested that
transition zone carcinoma might not be associated with HGPIN.31 Moreover incidence of
isolated HGPIN is uncommon in TURP specimens (prevalence 2.3%).84 This is because
the site of HGPIN is common in the peripheral zone as compared to transition zone.
Prostatic Carcinoma
In the present study peak incidence of both PIN and prostatic carcinoma was seen
in age group of 70-79 yrs. It has been observed that PIN occur at least a decade earlier
compared to prostatic carcinoma. But in present study no such age difference was noted.
Many recent studies show a higher incidence of prostatic carcinoma in the age group of
61-70 yrs. However in studies of Moore and Baron the peak incidence was seen in age
group of 51-60 yrs. This may indicate change in trend of prostatic carcinoma.
76
Table 14
Age incidence of prostatic carcinoma in different studies
Sl.
No.
Authors
21-30
31-40
41-50
51-60
61-70
71-80
81-90
Total
1
Rich (1934)80
-
-
-
7
8
12
0
27
2
Moore (1935) 80
-
-
9
18
13
7
-
47
3
Baron and Angrist
(1941)80
-
-
20
26
25
6
-
77
4
Andrews (1949)80
-
-
2
7
7
-
-
16
5
Edward
(1953) 80
-
-
3
10
12
3
-
28
6
Franks (1954)80
-
-
38
53
70
17
-
178
7
Scott et al (1961) 80
-
-
-
-
36
26
-
62
8
Holund (1980)80
-
-
2
7
24
13
-
46
9
Present study
-
-
-
3
6
4
0
13
et
al
Commonest of prostatic carcinoma is adenocarcinoma. Among 14 cases of
prostatic carcinomas encountered 12 (85.1%) are adenocarcinoma (Fig. 14. 15. 16)and
one was primary squamous cell carcinoma (Fig. 19) and one case was metastasis from
transitional cell carcinoma of bladder (Fig. 20).
There is wide variation in the incidence rate of prostate cancer in different parts of
the world. The age adjusted incidence rates in Bangalore is 5.2 per 100000.85 The
prevalence rate of 9.3% observed in present study is comparable with study by
Muruli et al86, which showed a prevalence rate of 8.5%. The increased incidence of
prostatic carcinoma in industrialized world is partly due to increased number of cases
diagnosed by screening and case finding by serum PSA testing.12
77
Table 15
Prevalence of prostatic carcinoma in different studies
Sl.
No.
Authors
No. of prostatic
specimens
No. of prostatic
carcinoma
Prevalence
1
Newman et al (1982)80
500
71
14.20
2
Muruli et al (1985)80
222
19
8.56
3
Moore et al (1986)80
143
31
21.68
4
Murphy et al (1986)80
386
66
17.10
5
Yamabe et al (1986) (Japan)80
191
24
12.57
6
Yamabe
et
(Netherlands)80
452
57
12.61
7
Eble and Tejada (1986) 80
700
132
18.56
8
Rohr (1987)80
457
65
14.22
9
Present study
150
12
9.3
al
(1996)
Histochemical stains for mucin in the present study demonstrated neutral mucin in
all LGPIN cases and in these cases acidic mucin was absent. All cases of carcinoma
showed positivity for acidic mucin.35 (Fig.18)
Present study showed 90% BPH/Prostatitis, 0.7% HGPIN and 9.3% prostatic
carcinoma. W. Horinger et al in his study reported 73.1% BPH/Prostatitis, 4.7% HGPIN
and 22.2% prostatic carcinoma.81
Present study showed 90.7% of BPH and 9.3% prostatic carcinoma. Anna Pacelli
and David G. Bostwick reported incidence of 81.7% of BPH and18.3%
adenocarcinoma87.
78
In the present study all cases of adenocarcinoma were showing basement
membrane disruption, with 3 cases showing perineural invasion (Fig. 17). These
pathological changes have been well documented in literature,88
Carter HB and Partin AW reported the distribution of Gleason score in 703 men
with clinically localized prostatic carcinoma.89
Table 16
Comparative incidence of carcinoma with reference to Gleason’s score
Studies
Gleason score No.of patients(%)
Carter HB and Partin AW
2-4
64(9)
5
168(24)
6
303(43)
7
130(19)
8-10
38(5)
Total
703(100)
2
0
3
0
4
0
5
0
6
1(8.3)
7
6(50)
8
3(25)
9
2(6.7)
Total
12(100)
Present study
79
In the present study low grade adenocarcinoma was not detected probably
because these lesions are usually asymptomatic
Bob Djavan et al reported 22% incidence of carcinoma. Mean age of patients was
67 yrs and mean Gleasons score was 6.90
Table 17
Incidence of prostatic carcinoma mean age and mean Gleason’s score
Studies
Incidence of prostate cancer Mean age Mean score
Bob Djavan
22%
67
6
Present study
9.3%
73
7
Richard Babajan et al studied 151 men between September 1998 and September
1999 at university of Texas M.D Anderson cancer center. Cancer was detected in 24.5%
of men biopsied. Mean age of all 151 men was 62yrs (range 43-74 ). Gleason score was
6 in 12 patients 7 in 1 and 8 in 1.91
Table 18
Incidence of prostatic carcinoma, median age and Gleason’s score
Studies
Richard J Babian et al
Present study
Incidence of prostatic
carcinoma
Median
age
24.5%
62
8%
70
80
Gleason
score
6-12 patients
7-1 patient
8-1 patient
7-7 patients
8-3 patients
9-2 patients
Serum PSA Levels
NH is a common cause of serum PSA elevation and accounts for 60-70% 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 (4.1-10ng/ml).92 In the
present study 36 cases had modest elevation of PSA levels and remaining 25 cases the
degree of elevation was severe with 19 cases having levels more than 20.1 ng/ml. This is
because these cases of NH was associated with prostatitis, abscesses and granulomatous
prostatitis. According to a study in chronic prostatitis serum PSA was high in 99% of the
cases. Also prostatic manipulations including cystoscopy, needle biopsy and TURP are
known to elevate serum PSA levels. In a small percentage of men digital rectal
examination (9%), prostatic massage (6%) and trans rectal ultrasound scanning (11%)
result in elevation of serum PSA levels.93Acute urinary retention also elevates the
PSA values.94
Serum levels of PSA were frequently elevated in patients with PIN ranging
from0.3 to 22.3 mg/ml (mean 4.0).95 In the present study, they showed normal levels
(< 4 ng/ml)
In the present study, 12 case of prostatic carcinoma had high levels of PSA
(>12ng/ml), however 2 cases had PSA levels below 4ng/ml this can be attributed to study
in which it was reported that prostate cancers detected at lower PSA levels are more
likely to have a small volume (less than 0.5ml) and are of low grade.96
81
LIMITATIONS OF STUDY
1.
In the cases of needle biopsy the tissue obtained was from the transition zone and
not from the peripheral zone, hence diagnosis of malignancy may be missed
inspite of strong clinical suspicion of malignancy.
2.
Immunohistochemistry was done in one case. Due to lack of facilities and
financial constraints it was not done in all the suspected cases.
SCOPE FOR IMPROVEMENT
The correct diagnosis of mimickers of adenocarcinoma should be made in order to
prevent radical prostatectomy, which has high rate of morbidity in elderly males. Since
serum PSA was increased in few benign and most of the malignant cases, newer
modalities of measuring PSA like PSA density, PSA velocity, age specific reference rates
should be adopted to distinguish between benign and malignant lesions.
Diagnosis of HGPIN should be included since it is a precursor of
adenocarcinoma.
Most of the cases of prostatic adenocarcinoma encountered were of high grade.
Since low-grade lesions are usually asymptomatic, awareness of serum PSA level
estimation, digital rectal examination should be brought among elderly males who are
prone for malignancy. Male individuals with a positive family history for prostatic
carcinoma must undergo relevant screening test.
82
CONCLUSION
1.
Out of 150 prostatic specimens studied benign lesions were common, which
accounted for 90.7% and malignant lesions accounted for 9.3%.
2.
Benign lesions were common in the age group of 60-69yrs, with common
symptoms of frequency, difficulty in voiding and acute retention.
3.
Prostatitis was commonly encountered in the age group of 60-69yrs.
4.
Among 136 cases of benign lesions, 111 cases (81.7%) were diagnosed as nodular
hyperplasia without prostatitis and 25 cases (18.3%) were diagnosed as nodular
hyperplasia with prostatitis.
5.
Histologically varied patterns of hyperplasia were noted in 25 cases of 98 nodular
hyperplasia without prostatitis.
Basal cell hyperplasia in 5 cases (5.1%), clear cell cribriform hyperplasia in
2 cases (2%), transitional metaplasia in 13 cases (13.2%) and squamous
metaplasia in 5 cases (5.1%).
6.
PIN accounted for 8.6% (13 cases) with a peak incidence in age group of
70-79 years. LGPIN accounted for 8% (12 cases) and HGPIN accounted for 0.6%
(1 case).
83
LGPIN were reported in view of complete description of histologic variants.
Incidence of isolated HGPIN was low because most of the specimens studied included
TURP, which is from transition zone, and HGPIN is common in peripheral zone.
However HGPIN was noted in adjacent prostatic tissue in 6 cases (50%) of prostatic
adenocarcinoma out of 12 cases of adenocarcinoma.
7.
Malignant lesions showed a peak incidence in the age group of 60-69 years with a
common symptoms of frequency, incomplete voiding and dysuria.
8.
In benign lesions serum PSA was normal in 75 cases (55.1%). Modest elevation
[4.1-10 ng/ml] was seen in 36 cases (26.4%) and marked elevation [>10 ng/ml] in
25 cases (18.3%) due to associated conditions like chronic prostatitis,
granulomatous prostatitis and abscesses. In malignant prostatic lesion
8 cases ( 57.1%) showed marked elevation in serum PSA levels (>20 ng/ml).
9.
Among the malignant lesions, commonest lesion was prostatic adenocarcinoma
(85.8%).
10.
A rare neoplasm of the primary squamous cell carcinoma of prostate was
encountered.
11.
Gleason’s microscopic grading was adopted for grading prostatic adenocarcinoma
in which the commonest Gleason score was score 7 (58.3%), followed by score
8 (25%) and score 9 (16.7%). Low-grade lesions were not encountered probably
because these lesions are usually asymptomatic
84
12.
Acidic mucin was demonstrated in the lumens, in all cases of prostatic adeno
carcinoma demonstrated by Alcian Blue pH1.
13.
In this study we did not encounter any case of infarct, calculi, malakoplakia, lowgrade adenocarcinoma and other rare variants of malignant neoplasms.
85
SUMMARY
1)
Total of 150 prostatic specimens were included in this study, received in the
Department of Pathology at Kempegowda Institute of Medical Sciences,
Bangalore from December 2003 - December 2005.
2)
Most of the specimens received were TURP 134 (89.3%), followed by needle
biopsy 12 (8%) and total prostatectomy 4 (2.6%).
3)
The cases were studied in relation to age, common presenting symptoms and was
correlated with serum PSA levels.
4)
Benign lesions were seen after the age of 50 years.
Benign lesions included Nodular hyperplasia without prostatitis (81.7%) and
nodular hyperplasia with prostatitis (18.3%).
5)
13 cases (8.6%) of cases showed PIN of these 8% (12 cases) were LGPIN, which
was reported in view of complete description of histologic variants. 1 case (0.6%)
of HGPIN, was noted.
6)
Out of 98 cases (70.6%) of NH, histologically varied patterns of hyperplasia were
noted in 25 cases with basal cell hyperplasia in 5 cases (5.1%), CCH in 2 cases
(2.0%), Transitional metaplasia in 13 cases (13.2%) and squamous metaplasia in
5 cases (5.1%).
7)
Out of 25 cases of prostatitis (16.6%), 20 cases (80%) had chronic non-specific
prostatitis and 2 cases of prostatic abscesses (8%) and 3 cases (12%) of
granulomatous prostatitis.
86
8)
Clinical diagnosis of prostatic carcinoma was done in 17 cases, out of which 8
cases correlated histologically and one case sent as metastatic transitional cell
carcinoma was confirmed to be the same.
9)
In benign cases serum PSA was normal in 75 cases (55.1%). Modest elevation
[4.1-10 ng/ml] was seen in 36 cases (26.4%) and marked elevation [>10 ng/ml]
seen in 25 cases (18.3%).
10)
Digital rectal examination finding showed nodularity in 137 cases and hard
nodule in 13 cases.
11)
Both PIN and malignancy showed peak in the age group of 60-79 years
12)
In the malignant lesion, prostatic adenocarcinoma was the commonest (85.8%),
followed by one case of primary squamous cell carcinoma (7.1%) and one case of
metastatic transitional cell carcinoma (7.1%).
13)
The commonest pattern encountered in prostatic adenocarcinoma is acinar pattern
followed by cribriform, sheets, trabeculae, cords, strands and clear cells.
14)
Gleason’s microscopic grading was adopted to grade prostatic adenocarcinoma
cases and score 7 (58.3%) was the commonest.
15)
All 12 cases of prostatic adenocarcinoma showed basement membrane disruption
with 3 cases showing perineural invasion and 3 cases showing inflammation.
16)
All cases of adenocarcinoma showed acidic mucin in the lumens as demonstrated
by Alcian blue pH1 and all the cases of LGPIN showed negativity for Alcian Blue
and positive PASd.
87
BIBLIOGRAPHY
1.
Epstein IJ. The lower urinary tract and male genital system. Kumar, Abbas and
Fausto (editors). Robbins and Cotran Pathologic basis of disease. 7th ed, Saunders:
2004; 1023-1058.
2.
Krishna V. Textbook of Pathology. Orient Longman 2004; 889-905.
3.
Cover story. Health Screen, 2004 Aug; 10-16.
4.
Carter SB, Bova GS, Beaty HT, Steinberg DG, Childs B, Isaacs BW et al.
Hereditary Prostate Cancer: Epidemiologic and clinical features. J Urol 1993;
150:797-802.
5.
Woolf MC. An Investigation of the familial aspects of carcinoma of the prostate.
Cancer 1960; 13: 739-744.
6.
Carter BH, Pianta Dosi S, Isaacs TJ. Clinical evidence for and implications of the
Multistep Development of Prostate Cancer. J Urol 1990; 143: 742-746.
7.
Nelson GW, De Marzo MA, Isaacs BW. Prostate Cancer. NEJM 2003; 349:
366-381.
8.
Mazhar D, Waxman J. Prostate Cancer. Postgrad Med J 2002; 78 (924): 590-608.
9.
Reiter ER, Dekernion BJ. Epidemiology, etiology and prevention of prostate
cancer. Walsh, Retik, Vaughan, Wein. Campbell`s Urology. 8th ed, W. B.
Saunder’s Company: Philadelphia: 2002; 3003-3060.
88
10.
Partin AW, Rodriguez R. The Molecular biology, Endocrinology and Physiology
of Prostate and Seminal vesicles. Walsh, Retik, Vaughen, Wein. Campbell`s
Urology. 8th ed, W. B. Saunder`s Company, Philadelphia: 2002; 1237-1250.
11.
Easthem JA, Scardino PT. Radical Prostatectomy. Walsh, Retik, Vaughen, Wein.
Campbell`s Urology. 8th ed, W. B. Saunder’s Company, Philadelphia: 2002;
3080-3107.
12.
Haggman JM, Macoska AJ, Wojno JK, Osterling JE. The relationship between
prostatic intraepithelial neoplasia and prostate cancer: Critical Issues. J Urol 1997;
158: 12-22.
13.
Ramos GC, Carvahal FG, Mager ED, Haberer B, Catalona JW. The effect of
high-grade prostatic intraepithelial neoplasia on serum total and percentage of free
prostate specific antigen levels. J Urol 1999; 162: 1587-1590.
14.
Lowe FE, Trauzzi SJ. Prostatic acid phosphatase. Its limited clinical utility. In:
Osterling (ed): Urol Clin North Am 1993; 20 (4): 589-595.
15.
Juan Rosai. Male reproductive system. Juan Rosai (editor). Juan Rosai and
Ackerman`s Surgical Pathology. 9th ed, Missouri: Mosby: 2004; 1361-1412.
16.
Mc. Conell JD. Epidemiology, Etiology, Pathophysiology and Natural history of
Benign
Prostatic
Hyperplasia.
Walsh,
Retik,
Vaughan,
Wein.
Campbell`s Urology. 8th ed, W. B. Saunder’s Company: Philadelphia: 2002;
1297-1337.
89
17.
Berry JS, Coffey SD, Walsh CP and Ewing LL. The Development of Human
Benign Prostatic Hyperplasia With Age. J Urol 1984; 132: 474-479.
18.
Dermer BG. Basal Cell Proliferation in Benign Prostatic Hyperplasia. Cancer
1978; 41: 1857-1862.
19.
Clearly RK, Choi YH, Ayala GA. Basal cell hyperplasia of the prostate. Am J
Clin Pathol 1983; 80: 850-854.
20.
Yang JX, Tretiakova SM, Senguptha E, Gong C, Jiang Z. Florid basal cell
hyperplasia of prostate: A histological, ultrastructural, immunohistochemical
analysis. Hum Pathol 2003; 341 (5): 462-470.
21.
Ayala GA, Sriley RJ, Ro YJ, Abdul-Karim WF, Johnson ED. Clear cell
cribriform hyperplasia of prostate. Am J Surg Pathol 1986; 10(10): 665-671.
22.
Grignon JD, Ro YJ, Srigley RJ, Troncoso P, Raymond K, Ayala GA. Sclerosing
adenosis of the prostate gland. Am J Surg Path 1992; 16 (4): 383-391.
23.
Price H, Mc Neal EJ, Stamey AT. Evolving patterns of tissue composition in
benign prostatic hyperplasia as a function of specimen size. Hum Pathol 1990; 21:
578-585.
24.
Shapiro E, Becich JM, Hartanto V, Lepor H. The relative proportion of stromal
and epithelial hyperplasia is related to development of symptomatic benign
prostate hyperplasia. J Urol 1992; 147: 1293-1297.
90
25.
Gleason EP, Jones AJ, Regan SJ, Salvas BD, Eble NJ, Lamp WW et al. Platelet
derived Growth factor (PGDF), Androgens and Inflammation: Possible etiologic
factors in development of prostatic hyperplasia. J Urol 1993; 149: 1586-1592.
26.
Epstien IJ, Armas AO. Atypical Basal Cell hyperplasia of the prostate. Am J Surg
Pathol 1992; 16 (12): 1205-1214.
27.
Abeshouse BS: Infarct of the prostate. J Urol 1993; 30: 27-112.
28.
Stillwell JT, Engen ED Farrow MG. The clinical spectrum of granulomatous
prostatitis: A report of 200 cases. J Urol 1987; 138: 320-323.
29.
Blumenfield W, Tucci S, Narayan P. Incidental Lymphocytic Prostatitis. Am J
Surg Pathol 1992; 16 (10): 975-981.
30.
Mc Neal EJ, Bostwick GD. Intraductal dysplasia: A premalignant lesion of the
prostate. Hum Pathol 1986; 17: 64-71.
31.
Brawer KM. Prostatic Intraepithelial Neoplasia: A premalignant lesion. Hum
Pathology 1992; 23: 242-248.
32.
Bostwick GD, Brawer KM. Prostatic Intraepithelial Neoplasia and Early Invasion
In Prostate Cancer. Cancer 1987; 59: 788-794.
33.
Mc Neal EJ. Morphogenesis of prostatic carcinoma. Cancer 1965; 18: 1659-1666.
91
34.
Bostwick GD, Srigley J, Grignon D, Maksem J, Humphery P, Vander Kwast HT
et al. Atypical adenomatous hyperplasia of prostate: Morphologic criteria for its
distinction from well-differentiated carcinoma. Hum Pathol 1993; 24 (8):
819-832.
35.
Sentinelli S. Mucins in prostatic intraepithelial neoplasia and prostatic Carcinoma.
Histopathol 1993; 22: 271-274.
36.
Montironi R, Mazzuchelli R, Algaba F, Beltran LA. Morphological identification
of patterns of prostatic intraepithelial neoplasia and their importance. J Clin
Pathol 2000; 53: 655-665.
37.
Reyes OA, Swanson EP, Carbone MJ, Humphery AP. Unusual histologic types of
High Grade Prostatic intraepithelial Neoplasia. Am J Surg Pathol 1997; 21 (10):
1215-1222.
38.
Srodon M, Epstein IJ. Central Zone histology of prostate: A mimicker of highgrade prostatic intraepithelial Neoplasia. Hum Pathol 2002; 33: 518-523.
39.
Epstein IJ, Woodruff MJ. Adenocarcinoma of prostate with endometrioid
features. Cancer 1986; 57: 111-119.
40.
Kuhajda PF, Mann BR. Adenoid cystic carcinoma of the prostate. A case report
with immunoperoxidase staining for prostate-specific acid Phosphatase and
prostate specific Antigen. Am J Clin Pathol. 1984; 81: 257-260.
92
41.
Epstein IJ, Lieberman HP. Mucinous adenocarcinoma of the prostate gland. Am J
Surg Pathol 1985; 9 (4): 299-308.
42.
Mc Neal EJ, Alroy J, Villers A, Redwine AE, Freiha SF, Stamey AT. Mucinous
differentiation in prostatic adenocarcinoma. Hum Pathol 1991; 22: 979-988.
43.
Mc Neal EJ, Reese HJ, Redwine AE, Freiha SF, Stamey AT. Cribriform
adenocarcinoma of the prostate cancer 1986; 58: 1714-1719.
44.
Wood PD, Montie EJ, Pontes EJ, Medendrop VS, Levin SH. Transitional Cell
Carcinoma of the prostate in cystoprostatectomy specimens removed for bladder
Cancer. J Urol 1989; 141: 346-349.
45.
Nelson SR, Epstein IJ. Prostatic Carcinoma with abundant xanthomatous
cytoplasm. Am J Surg Pathol 1996; 20 (4): 419-426.
46.
Mathew Egan AJ, Beltran LA, Bostwick GD. Prostatic adenocarcinoma with
atrophic features: Malignancy mimicking a benign process. Am J Surg Pathol
1997; 21 (8): 931-935.
47.
Humphrey AP, Kaleem Z, Swanson EP, Vollmer TR. Psuedohyperplastic
Prostatic Adenocarcinoma. Am J Surg Pathol 1998; 22 (10): 1239-1246.
48.
Iczkowski AK, Maclennan TG, Bostwick GD. Atypical Small Acinar
Proliferation suspicious for malignancy in prostate needle biopsies. Am J Surg
Pathol 1997; 21 (12): 1489-1495.
93
49.
Henneberry MJ, Kahane H, Humphery AP, Keetch WD, Epstien IJ. The
significance of intraluminal crystalloids in Benign Prostatic glands on needle
biopsy. Am J Surg Pathol 1997; 21 (6): 725-728.
50.
Kramer AS, Spahr J, Brendler BC, Glenn FJ, Paulson FD. Experience with
Gleason`s histopathologic grading in prostatic cancer. J Urol 1980; 124: 223-225.
51.
Thomas R, Lewis WR, Sarma DP, Coker GB, Rao MK, Roberts JA. Aid to
accurate clinical staging: Histopathologic grading in prostatic cancer. J Urol 1982;
128: 726-728.
52.
Murphy PG, Gaeta JF, Pickren J, Wajsman Z. Current status of classification and
staging of prostate cancer. Cancer 1980; 45: 1889-1895.
53.
Cantrell BB, Deklerk PD, Eggleston CJ, Boitnott KJ, Walsh CP. Pathological
factors that influence prognosis in stage A prostatic cancer: The influence of
extent versus grade. J Urol 1981; 516-520.
54.
Humphrey P, Vollmer TR. The ratio of prostate chips with cancer: A new
measure of tumor extent and its relationship to grade and prognosis. Hum Pathol
1988; 19: 411-418.
55.
Epstein IJ, Oesterling EJ, Walsh CP. Tumour volume versus percentage of
specimen involved by tumor correlated with progression in stage A prostatic
cancer. J Urol 1988; 139: 980-984.
94
56.
Aumuller G, Groos S, Renneberg H, Lutzkonrad, Aumuller M. Embryology and
postnatal development of prostate. Christopher S. Foster, David G. Bostwick
(editors). Pathology of the prostate volume 34 in the series of major problems of
pathology. W. B. Saunders Company, Philadelphia: 1998; 1- 19.
57.
Bostwick GD, Amin BM. Prostate and seminal vesicle. Damjanov I, Linder J.
Anderson`s Pathology. 10th ed, St. Louis: Mosby, 1996: 2197-2230.
58.
Attah BE, NKPosong EO. Phyllodes type of atypical prostatic hyperplasia. J Urol
1976; 115: 762-764.
59.
Beltran LA, Gaeta JF, Huben R, Croghan GA. Malignant phyllodes tumour of
prostate. Urol 1990; 35 (2): 164-167.
60.
Naber GK, Weidner W. Chronic prostatitis: An infectious disease? J
Antimicrobial Chemotherapy 2000; 46: 157-161.
61.
Sakr
AW,
Montironi
R,
Epstein
IJ,
Rubin
MA,
De
Marzo
AM,
Humphrey PA et al. Prostatic intraepithelial Neoplasia. John N. Eble, Guido
Sauter, Jonathan I. Epstein and Isabell A. Sesterhemn (editors). Pathology and
Genetics Tumors of urinary system and male genital organs- World Health
Organization Classification of Tumors; Lyon, France: IARC Press, 2004:
193-198.
95
62.
Epstein IJ, Yang JX. Prostatic intra epithelial neoplasia and its mimickers.
Prostate biopsy interpretation series. 3rd
ed, Lippincott Williams and Wilkin:
2002; 33-64.
63.
Bostwick GD, Sakr W. Prostatic intraepithelial neoplasia. Christopher S. Foster,
David G. Bostwick (editors). Pathology of the prostate. Volume 34 in the series of
major problems of pathology. W. B. Saunders Company, Philadelphia: 1998;
95- 114.
64.
Epstein IJ, Alagaba F, Allsbrook WC Jr., Bastacky S, Gibod BL, DeMarzo AM
et al. Acinar adenocarcinoma. John N. Eble, Guido Sauter ,Jonathan I. Epstein
and Isabell A. Sesterhemn (editors). Pathology and Genetics Tumors of urinary
system and male genital organs - World Health Organization Classification of
Tumors; Lyon, France: IARC Press, 2004; 162-192.
65.
Berman MD, Yang J, Epstein IJ. Foamy Gland High Grade prostatic
intraepithelial neoplasia. Am J Surg Pathol 2000; 24 (1): 140-144.
66.
Yang JX, Cheng L, Helpap B, Samaratunga H. Ductal Adenocarcinoma. John N.
Eble, Guido Sauter, Jonathan I. Epstein and Isabell A. Sesterhemn (editors).
Pathology and Genetics Tumors of urinary system and male genital organs World Health Organization Classification of Tumors; Lyon, France: IARC Press,
2004; 199-214.
67.
Kuhajda PF, Gipson T, Mendelson G. Papillary adenocarcinomas of the prostate.
Cancer 1984; 54: 1328-1332.
96
68.
Rubin AM, Taille de LA, Bagiella E, Olmon AC, Toole MOK. Cribriform
carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia. Am J
Surg Pathol 1998; 22(7): 840-848.
69.
Saito R, Davis KB, Ollapally PE. Adenosquamous carcinoma of the prostate.
Hum Pathol 1984; 15: 87-89.
70.
Bostwick GD, Eble NJ. Variants of prostatic carcinoma. David G. Bostwick
(editor). Pathology of the prostate contemporary issues in surgical pathology.
Churchill Livingstone Anc, 1990; 37-61.
71.
Montironi R, Mazzuchelli R, Stramazzotti D, Scarpelli M, Beltran LA,
Bostwick GD. Basal cell hyperplasia and basal cell carcinoma of the prostate:
A comprehensive review and discussion of a case with c-erbB-2 expression.
J Clin Pathology 2005; 58: 290-296.
72.
Epstein IJ, Allsbrook CW, Amin BM, Egevad LL and the ISUP Grading
Committee.
The 2005 International Society of Urological Pathology (ISUP)
Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg
Pathol 2005; 29 (9): 1228-1242.
73.
Ro YJ, Amin BM, Sahin AA, Ayala GA. Tumors and tumorous conditions of
male genital and urinary tract. Christopher DM Fletcher (editor). Diagnostic
Histopathology of tumors .2nd ed,. New York: Churchill Livingstone, 2003;
733-782.
97
74.
Fleshman LR, MacLennan TG. Immunohistochemical markers in diagnosis of
prostate cancer. J Urol 2005; 173 (5): 1759.
75.
Dodson RA, Foster SC. The role of immunohistochemistry in problematic
prostate biopsy. Massimo Pignatelli and James C. E. Underwood (editors). Recent
advances in Histopathology 21. The Royal Society of Medicine Press Limited,
2005; 105-137.
76.
Culling CFA, Allison RT, WT. Barr (editors). In Cellular Pathology technique;
4th edition: London; Butterworth and Co., 1985.
77.
Walsh PC. Benign Prostatic Hyperplasia. Campbell`s Urology. Walsh, Gittes
Perlmutter, Stemey, WB Saunders Company, Philadelphia, 5th ed 1986;
1248-1265.
78.
Helpap B. Benign Prostatic Hyperplasia. Christopher S. Foster, David G.
Bostwick (editors). Pathology of the prostate Volume 34, In the series of major
problems of pathology. W. B. Saunders Company, Philadelphia: 1998; 66-95.
79.
Grandos AE, Riley G, Salvador J, Vincente J. Prostatic Abscess: Diagnosis and
Treatment. J Urol 1992; 148: 80-82.
80.
Bostwick GD, Srigley RJ. Premalignant lesions. David G. Bostwick (editor).
Pathology of the prostate contemporary issues in surgical pathology. Churchill
Livingstone Anc; 1990; 37-61.
98
81.
Horninger W, Volgger H, Rogatsch H, Strohmeyer D, Steiner H, Hobisch A et al.
Predictive value of total and percent free prostate specific antigen in high grade
prostatic intraepithelial neoplasia lesions: Results of tyrol prostate specific
Antigen Screening Project. J Urol 2001; 165: 1143-1145.
82.
Kovi J, Mostofi KF, Heshmat YM, Enterline PJ. Large Acinar Atypical
hyperplasia and carcinoma of the prostate. Cancer 1988; 61: 555-561.
83.
Quinn DB, Cho RK, Epstein IJ. Relationship of severe dysplasia to stage B
Adenocarcinoma of prostate. Cancer 1990; 65: 2328-2337.
84.
Gaudin PB, Wojno KJ, Sesterhenn IA,et al: High Grade PIN in TURP specimen
[Abstract]. Modern Pathology 8:76A, 1995.
85.
National Cancer Registry Programme. Cancer incidence and leading sites of
cancer in population based registries. Indian Council of Medical Research
Development of an Atlas of cancer in India. Bangalore, 2004; 11-18.
86.
Murali VP et al. Occult malignancy in benign prostatic hyperplasia. I J Urol 1(2):
1985; 96-98.
87.
Pacelli A, Bostwick GD. Clinical significance of high-grade prostatic
intraepithelial neoplasia in transurethral resection specimen. Urol 1997; 50:
355-359.
99
88.
Montie EJ, Wood PD, Pontes EJ, Boyelt MJ, Levin SH. Adenocarcinoma of
prostate in cystoprostatectomy specimens removed for bladder cancer. Cancer
1989; 63: 381-385.
89.
Carter HB, Partin AW. Diagnosis and staging of prostate cancer. Walsh, Retik,
Vaughan, Wein. Campbell’s Urology. 8th ed,
W. B. Saunder’s Company,
Philadelphia; 2002: 3055-3080.
90.
Djavan B, Ravery V, Zlotta A, Piotr Dobronski, Dobrovits M, Fakheri M et al.
Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3, and 4:
When should we stop? J Urol 2001; 166: 1679-1683.
91.
Babain JR, Johnston AD, Naccarto W, Ayala A, Bhadkamkar AV and Fritsche
AH. The incidence of prostate cancer in a screening population with serum
prostate specific antigen between 2.5 and 4.0 NG./ML.: Relation to biopsy
strategy. J Urol 2001; 165: 757-760.
92.
Humphery AP, Vollmer TR. Relationship between serum prostate antigen and
histopathologic appearances of prostate carcinoma, Volume 34 in the series of
Major problems of pathology. Christopher S. Foster, David G. Bostwick W.B.
Saunders Company Philadelphia, 1998; 253-281.
93.
Yuan JJ, Coplen DE, Petron JA et al : Effects of rectal examination, prostatic
massage, ultrasonography and needle biopsy on serum prostate specific antigen
levels. Journal of Urology 1992; 147:810-814.
100
94.
Armitage TG, Cooper EH, Newling DW et al. The value of measurement of
serum prostate specific antigen in patients with benign prostatic hyperplasia and
untreated prostate cancer. Br J Urol 1988; 62: 584-589.
95.
Alexander EE, Qian J, Wollan PC et al. Prostatic Intraepithelial neoplasia does
not raise serum prostate specific antigen. Urology 1996; 47: 693-698.
96.
Thompson MI,
Pauler
KD,
Goodman JP,
Tangen MC,
Scott Lucia M,
Parnes LH et al. Prevalence of prostate cancer among men with prostate specific
Antigen level ≤4.0 ng per milliliter. NEJM 2004; 350 (22): 2239-2246.
101
PROFORMA
Name:
Laboratory Number:
Age:
IP/OP Number:
Chief complaints:
Past History:
Personal History:
Family History:
General Physical Examination:
Systemic Examination:
Digital Rectal Examination:
Clinical Diagnosis:
Investigations:
Preoperative total PSA :
Type of surgical procedure done:
Histopathological Examination:
Gross:
Microscopy:
Final Diagnosis:
102
PROCEDURE FOR SPECIAL STAINS
Periodic Acid-Schiff with Diastase Predigestion
1)
Bring sections to water.
2)
Treat with diastase (saliva) for 30 minutes.
3)
Washed in running tap water for 10 minutes.
4)
Oxidize for 5 minutes 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.
RESULTS
PAS positive substances
Bright red
Nuclei
Blue
Other tissue constituents
Yellow
103
ALCIAN BLUE (pH1)
1)
Bring sections to water.
2)
Stain in 1% Alcian blue 8 GX in 0.1 N hydrochloric acid for 30 minutes. Rinse
briefly in 0.1 N HCL.
3)
Blot dry with fine filter paper to prevent the staining which sometimes occurs
after dilution with water (which will change the pH) in washing.
4)
Dehydrate in alcohol, clear in xylene and mount in resinous mountant.
Results
Acid sulphated mucosubstances stain blue.
Ziehl-Neelson staining method for AFB (Tubercle Bacilli)
1)
Bring the sections to water
2)
Treat the sections with strong carbol fuchsin
3)
Heat the underside of the slide till it fumes
4)
The sections are subsequently treated with coconut oil to prevent shrinkage for
10 minutes.
5)
Decolorize with 20% sulfuric acid solution
6)
Counter stain 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
Blue
Other tissue constituents
Pale blue
104
KEY TO MASTER CHART
Presenting complaints
Diff voiding
→
difficulty in voiding
Incmp voiding
→
incomplete voiding
Clinical investigations
USG
→
Ultrasound findings
DRE
→
Digital rectal examination
PSA
→
Prostate specific antigen
TURP
→
Transurethral resection prostate
G. Hyp
→
Glandular hyperplasia
FMH
→
Fibromuscular hyperplasia
TR MT
→
Transitional Metaplasia
CC METP
→
Clear cell cribriform hyperplasia
SQ METP
→
Squamous metaplasia
MONO
→
Mononuclear cells
BCH
→
Basal cell hyperplasia
PIN
→
Prostatic intraepithelial neoplasia
C/S
→
Urine culture and sensitivity
CA
→
Carcinoma
GL SCR
→
Gleason score
Microscopy
110
Final
→
Final histopathological diagnosis
NH
→
Nodular hyperplasia
LGPIN
→
Low-grade prostatic intraepithelial neoplasia
HGPIN
→
High-grade prostatic intraepithelial neoplasia
SCC
→
Squamous cell carcinoma
TCC
→
Transitional cell carcinoma
111
1
Anadigowda
75
1466/03
2
ThammeGowda
55
1504/03
3
KempeGowda
70
1535/03
4
Chikkachandraiah
55
1569/03
3M
5
Shivappa
70
1651/03
1M
6
Mariyappa
75
1875/03
7
Huchaiah
67
1984/03
8
Hombalaiah
65
1987/03
USG
DRE
dysuria
acute retention
Clinical investigation
haemturia
incmp voiding
hesitancy
strain
diff voiding
Lab No.
frequency
Age
(Yrs)
urgency
Name
No.
nocturia
Sl.
poor stream
Presenting complaints
1D 15D
G.Hyp FMH
TR
CC
MT METP
+
+
hard nodule 38
?Ca
TURP, 10cc
+
+
1D 3M
nodularity
2.1
BPH
TURP, 5cc
+
+
2D
nodularity
3
BPH
TURP, 4cc
+
+
+
+
2D 2D
2Y
nodularity
2.3
BPH
TURP, 5cc
+
+
nodularity
2.72
BPH
TURP 10cc
+
+
nodularity
32
?Ca
TURP, 8cc
+
+
nodularity
230
?Ca
TURP, 10cc
+
+
9
Kencharangaiah
75
2126/03
1M
nodularity
1.46
BPH
TURP, 5cc
+
+
10
Mudalappa
77
2127/03
1M
nodularity
4.2
BPH
TURP, 10cc
+
+
11
Muddegowda
65
2219/03
nodularity
4.32
BPH
TURP, 10cc
+
+
12
Thimme gowda
65
2220/03
nodularity
7.6
BPH
TURP, 5cc
+
+
13
Channakeshava
53
42/04
nodularity
3.2
BPH
TURP, 5cc
+
+
14
Honappa
65
65/04
2D
nodularity
5.8
BPH
TURP, 10cc
+
+
15
Nanjundegowda
69
69/04
1D
nodularity
3.23
BPH
TURP, 7cc
+
+
16
Doddachari
54
223/04
nodularity
16.45
BPH
TURP, 10cc
+
+
17
Kempaiah
73
225/04
1D
nodularity
3.2
BPH
TURP 5cc
+
+
18
Doddavenkatappa
62
289.04
2D
nodularity
3.2
BPH
TURP, 5cc
+
+
19
Singaraiah
70
400/04
nodularity
0.49
BPH
TURP, 6cc
+
+
20
Narayanappa
71
455/04
21
Kenchegowda
75
460/04
22
Basavaiah
76
479/04
4D
23
Shenoy
62
526/04
2M
24
Srinivas
57
527/04
1M
25
Munireddy
45
55/04
1.5 Y
26
Nanjappa
82
559/04
3M
nodularity
2.1
27
Krishoji rao
85
569/04
15D
nodularity
9.86
28
Krishoji rao
85
601/04
2D 15D
Prostate
nodularity
enlarged
9.86
BPH
1M
2D
7D
20D
1M
1Wk
4D
1D
1D
GL
SCR
GROSS
TURP,10cc
1M
3.2
Microscopy
BPH
5M
nodularity
PSA
(ng/ml)
clinical diagnosis
MASTER CHART
PIN
Others
CA
nests,comedo,cords,cribr
9
iform, perinural invasion
+
prostatitis
+
cribriform,trabeculae,
8
sheets,inflam, HGPIN
small
acinar,sheets,trabeculae, 7
inflam, HGPIN
+
+
+
Prostatitis, C/S- E. coli
+
Perineural invasion small
acinar,sheets,cords,trabe 8
culae
nodularity
5.24
BPH
TURP, 10cc
+
+
nodularity
2.1
BPH TURP, 30cc
+
+
nodularity
8.26
BPH TURP, 7cc
+
+
+
nodularity
3.2
BPH
TURP, 5cc
+
+
+
nodularity
0.21
BPH
TURP, 4cc
+
+
nodularity
2.1
BPH
TURP, 3cc
+
+
BPH
TURP, 5cc
+
+
BPH
Needlebiopsy
+
+
TURP, 6cc
+
+
109
SQ METP MONO BCH
+
+
+
+
prostatitis, C/SPseudomonas
MASTER CHART
Final
NH
Adenocarcinoma High-grade
NH with prostatitis
NH
NH
NH
Adenocarcinoma High-grade
Adenocarcinoma High-grade
NH
NH
NH
NH
NH
NH
NH
NH with prostatitis
NH
NH
Adenocarcinoma High-grade
NH
NH
NH
NH
NH
NH
NH
NH with prostatitis
NH
109
29
Pandu rangaiah
60
619/04
30
Muniyappa
40
630/04
31
Siddalingaiah
70
730/04
1M
32
Neelakantaiah
60
764/04
1M
33
Doddaappaiah
85
778/04
34
Aravind
65
793/04
35
Rangappa
60
868/04
36
Metayappa
60
893/04
37
Kadrinaganna
82
996/04
3M
38
Krishnaswamy
65
1019/04
5M
39
Narasaiah
65
1021/04
1M
40
Nanjaiah
70
1045/04
41
Dharmaiah
70
1103/04
42
Basavaraju
58
1111/04
43
Ramanna
70
1159/04
44
Narasimhamurthy
70
1242/04
45
Cheluvarangaiah
65
USG
1M
1D
3M
1D
2D
1M
2M
8D
1D
2M 3D
2M
1243/04
2M
5.46
BPH
TURP, 2cc
+
+
BPH
TURP, 4 cc
+
+
nodularity
5.2
BPH
TURP, 6cc
+
+
280
?Ca
Needle biopsy
nodularity
1
BPH
TURP, 40 cc
+
+
nodularity
15.22
BPH
TURP, 20 cc
+
+
nodularity
12
BPH
TURP, 3 cc
+
+
plus
nodularity
1.13
BPH
TURP, 10 cc
+
+
nodularity
3.8
BPH
TURP, 5 cc
+
+
nodularity
3
BPH
TURP, 5 cc
+
+
nodularity
1.2
BPH
TURP, 5 cc
+
+
nodularity
4.17
BPH
TURP, 20 cc
+
+
nodularity
0.9
BPH
TURP, 8 cc
+
+
nodularity
2.4
BPH
TURP, 8 cc
+
+
7.26
BPH
TURP, 20 cc
+
+
3
BPH
TURP, 20 cc
+
+
4.2
BPH
TURP, 10 cc
+
+
+
nodularity
1M
Prostate
nodularity
enlarged
6D 6D
G.Hyp FMH
2.1
1Y
46
Kalappa
70
1308/04
47
Vishakantegowda
75
1309/04
48
Vishakantegowda
75
1404/04
49
Janaki Ram
76
1437/04
50
Madaiah
61
1495/04
2M
1M
51
Chota sab
60
1586/04
2M
2M
52
Marilinge Gowda
75
1617/04
hard nodule 21
?Ca
Needle biopsy
+
+
53
Balakrishna
50
1654/04
1D
nodularity
6
BPH
TURP, 5 cc
+
+
54
ThammeGowda
80
1665/04
3D
Prostate
nodularity
enlarged
16
BPH
+
+
55
Siddiahashetru
60
1812/04
1 Yr
nodularity
32
BPH
Needle biopsy
+
+
56
Krishnappa
72
1895/04
5M
nodularity
0.3
BPH
TURP, 20 cc
+
+
57
Siddiahashetru
60
1905/04
1 Yr
nodularity
32
BPH
TURP, 10 cc
+
+
58
Nanjaiah
70
2006/04
6M
nodularity
25.12
BPH
TURP, 12 cc
+
+
59
Narasappa
60
2007/04
1Y
nodularity
1.65
BPH
TURP, 5cc
+
+
5Y
hard nodule 20.9
?Ca
Needle biopsy
15D
15 D
hard nodule 24.8
?Ca
Needle biopsy
+
15D
15 D
hard nodule 24.8
?Ca
+
+
nodularity
BPH
TURP, 10 cc
+
+
5 Yr
2M
1D
1 Yr
1Y
1M 6M
5.2
GL
SCR
GROSS
nodularity
Prostate
nodularity
enlarged
1D
PSA
(ng/ml)
Microscopy
nodularity
Prostate
enlarged
5D
3M
DRE
dysuria
acute retention
Clinical investigation
haemturia
incmp voiding
hesitancy
strain
diff voiding
Lab No.
frequency
Age
(Yrs)
urgency
Name
No.
nocturia
Sl.
poor stream
Presenting complaints
clinical diagnosis
MASTER CHART
nodularity
1.2
BPH
TURP, 10 cc
+
+
1.2
BPH
TURP, 10 cc
+
+
109
SQ METP MONO BCH
PIN
+
Others
CA
prostatitis
LG PIN
plus
small acinar,cords,sheets 7
LG PIN
+
+
+
prostatitis, C/Senterococcus
+
+
Prostate
nodularity
enlarged
TURP, 25 cc
TR
CC
MT METP
C/S-Klebsiella
+
prostatitis
LG PIN
small acinar, cords,
sheets,
7
MASTER CHART
Final
NH
NH with prostatitis
NH with LGPIN
Adenocarcinoma High-grade
NH,
LGPIN
NH
NH
NH
NH
NH
NH
NH
NH
NH with
prostatitis
NH
NH
NH
Adenocarcinoma:
High grade
NH
NH with
prostatitis
NH
NH
NH
NH
NH
NH with LGPIN
NH
NH
NH
NH
NH
109
USG
DRE
dysuria
acute retention
Clinical investigation
haemturia
incmp voiding
hesitancy
strain
diff voiding
Lab No.
frequency
Age
(Yrs)
urgency
Name
No.
nocturia
Sl.
poor stream
Presenting complaints
PSA
(ng/ml)
clinical diagnosis
MASTER CHART
Microscopy
G.Hyp FMH
60
Subania
69
2075/04
15D
15D
nodularity
1.14
BPH
TURP, 5 cc
+
+
61
Hanumaiah
54
2079/04
3M
15D
nodularity
3.67
BPH
TURP, 10 cc
+
+
Prostate
nodularity
enlarged
9.47
BPH
TURP, 20cc
+
+
6.32
BPH
TURP, 10 cc
+
+
0.8
BPH
TURP, 10 cc
+
+
4
BPH
TURP, 5 cc
+
+
3
BPH
TURP, 8 cc
+
+
nodularity
2.6
BPH
TURP, 20 cc
+
+
nodularity
0.4
BPH
TURP, 10 cc
+
+
nodularity
0.6
BPH
TURP, 6 cc
+
+
nodularity
5
BPH
TURP, 4 cc
+
+
3M
62
Shivanna gowda
69
2115/04
63
Siddegowda
52
2131/04
64
Veerabhadraiah
50
2142/04
65
Nanjunde gowda
45
2275/04
2M
66
Muniyappa
48
2513/04
3M
67
Rangaswamy
70
2525/04
2M
68
Singari gowda
52
2562/04
69
Shivanne gowda
50
2703/04
70
Needasiddya
55
2704/04
71
Abdulbasheer
68
2754/04
1M
nodularity
21.72
BPH
TURP, 8 cc
+
+
72
Md. Hussain
72
2769/04
20D
nodularity
2.8
BPH
TURP, 20 cc
+
+
73
Linge Gowda
60
2815/04
1M
nodularity
4.8
BPH
TURP, 15 cc
+
+
74
Somaiah
78
2832/04
nodularity
3
BPH
TURP, 1 cc
+
+
75
Manchaiah
71
2866/04
5D
nodularity
2.5
BPH
TURP, 15 cc
+
+
76
Huchegowda
65
2886/04
3M
3M
nodularity
4
BPH
TURP, 2 cc
+
+
77
Nanjappa
72
2887/04
6M
1M
hard nodule 12
?Ca
TURP, 5 cc
+
+
78
Kenchaiah
63
2892/04
4M
nodularity
3.2
BPH
TURP, 2 cc
+
+
79
Somasiddaiah
65
2893/04
nodularity
2.2
BPH
TURP, 5 cc
+
+
80
Puttaiah
53
2894/04
nodularity
11
BPH
TURP, 5 cc
+
+
81
Appaji
71
2950/04
82
Krishna
61
2986/04
83
Byrappa
75
2989/04
84
Chikkajalappa
65
3014/04
85
Doddamuthappa
70
3017/04
86
Paramashivaiah
66
3113/04
87
Basavaraj
70
3116/04
88
Lingappa
70
19/05
1M
3M
1M
nodularity
Prostate
nodularity
enlarged
nodularity
Prostate
nodularity
enlarged
2Y
1M
1M
1M
1M
4M
6M 2M
10D
1D 2M
6D
2M 1M
1D
1M
25D
nodularity
1
BPH
TURP, 5 cc
+
+
1Y
nodularity
6.35
BPH
TURP, 10 cc
+
+
2M
nodularity
8.4
BPH
TURP, 5 cc
+
+
nodularity
0.8
BPH
Prostatectomy
+
+
nodularity
3.2
BPH
TURP, 8 cc
+
+
nodularity
29.3
?Ca
Needle biopsy
+
+
hard nodule 13.3
?Ca
TURP, 4 cc
+
+
nodularity
BPH
TURP, 6 cc
+
+
1M
2M
1M
1Y
6M
6.6
GL
SCR
GROSS
109
TR
CC
MT METP
SQ METP MONO BCH
PIN
Others
CA
LG PIN
granulomatous
AFB-ve
LGPIN
+
Prostatitis, C/S- Klebsiella
LG PIN
granulomatous, AFB - Ve
LG PIN
LG PIN
+
Prostatitis, C/S-Klebsiella
small acinar,cribriform,
7
HGPIN
MASTER CHART
Final
NH
NH with LGPIN
NH with
granulomatous
prostatitis
NH
NH
NH
NH with LGPIN
NH
NH
NH
NH
NH with prostatitis
NH
NH
NH
NH with LGPIN
NH
SCC
NH
NH
NH with
granulomatous
prostatitis
NH
NH
NH with LGPIN
NH
NH with
LGPIN
NH with prostatitis
Adenocarcinma HighGrade
NH
109
89
Venkatappa
60
34/05
90
Poornashivaiah
61
38/05
3M
1M
1D
USG
DRE
dysuria
acute retention
Clinical investigation
haemturia
incmp voiding
hesitancy
strain
diff voiding
Lab No.
frequency
Age
(Yrs)
urgency
Name
No.
nocturia
Sl.
poor stream
Presenting complaints
PSA
(ng/ml)
clinical diagnosis
MASTER CHART
Microscopy
GL
SCR
GROSS
G.Hyp FMH
nodularity
2.4
BPH
TURP, 10 cc
+
+
nodularity
29.3
BPH
TURP, 20 cc
+
+
109
TR
CC
MT METP
SQ METP MONO BCH
PIN
Others
CA
MASTER CHART
Final
NH
NH
109
MASTER CHART
Honnappa
65
65/05
92
Muddachinnaiah
65
86/05
93
Gopalakrishnashetty
85
99/05
94
Channappa
65
140/05
95
Narayanappa
70
152/05
96
Mustafa
62
176/05
97
Ranganathaiah
60
187/05
98
Kenchappa
70
303/05
99
Lakshmagowda
78
326/05
100 Raghavan
69
332/05
101 Jayaramanna
65
357/05
1Y
104 Thammaiah
70
447/05
6M
105 Mukanna
80
480/05
106 Doddachantappa
64
483/05
107 Lakshmegowda
70
498/05
108 Hanumanthaiah
65
536/05
109 Holegowda
78
616/05
110 Marigowda
62
662/05
3M
111 Laxmaiah
60
938/05
1Y
112 Thammegowda
65
1082/05
113 Kariyanna
60
1198/05
114 Madigappa
75
1222/05
115 Mohammad
52
1467/05
118 Venkatappa
60
1549/05
119 Arvind
60
1572/05
120 Venkateshappa
55
1600/05
+
+
TURP, 10 cc
+
+
nodularity
2.2
BPH
TURP, 10 cc
+
+
nodularity
2.86
BPH
TURP, 10 cc
+
+
nodularity
1.8
BPH
TURP, 10 cc
+
+
?Ca
Needle biopsy
dysuria
acute retention
haemturia
TURP, 10 cc
BPH
3.2
BPH
TURP, 15 cc
+
+
BPH
TURP, 20 cc
+
+
6M
nodularity
20.2
BPH
Needle biopsy
+
+
nodularity
4
BPH
TURP, 15 cc
+
+
nodularity
2.8
BPH
TURP, 20 cc
+
+
6M
1D
6M
1Wk
15D
1D 10D
3M
1D 1M
2M
1D
2D
6M
5D
20D
GL
SCR
SQ METP MONO BCH
PIN
Others
+
Prostatitis
+
prostatitis, C/S-E-coli
+
Prostatis
CA
+
nodularity
8.83
BPH
TURP, 20 cc
+
+
nodularity
2
BPH
TURP, 10 cc
+
+
nodularity
16.8
BPH
Prostatectomy
+
+
nodularity
1.07
BPH
TURP, 10 cc
+
+
nodularity
3.08
BPH
Prostatectomy
+
+
nodularity
2.27
BPH
TURP, 25 cc
+
+
hard nodule 12
?Ca
TURP, 15 cc
+
+
TCC bladder
hard nodule 87.98
?Ca
Needle biopsy
+
+
small
acinar,trabeculae,cribrifo 8
rm
4
BPH
TURP, 10 cc
+
+
8
BPH
TURP, 20 cc
+
+
hard nodule 96.48
?Ca
TURP, 30 cc
nodularity
2.09
BPH
TURP, 20 cc
+
+
nodularity
22.71
BPH
TURP, 30 cc
+
+
nodularity
8
BPH
TURP, 30 cc
+
+
Prostate
nodularity
enlarged
nodularity
20M
TR
CC
MT METP
+
2.7
1Y
1M
BPH
4.75
nodularity
15D
6M
0.6
nodularity
nodularity
3M 3M
1M
nodularity
DRE
G.Hyp FMH
3M
3M
2M
Microscopy
GROSS
PSA
(ng/ml)
hard nodule 38.98
1Y
6M
378/05
1520/05
incmp voiding
1D
380/05
1531/05
hesitancy
15D
60
78
strain
1Y
70
72
1M
1D
103 Ningaiah
117 Chinappa
USG
1D
3M
102 Puttaswamaiah
116 Dodda kamaiah
Clinical investigation
clinical diagnosis
91
diff voiding
Lab No.
frequency
Age
(Yrs)
urgency
Name
No.
nocturia
Sl.
poor stream
Presenting complaints
+
+
cribriform,cords,clear
cells
+
+
Prostatitis
+
Prostatitis
+
nodularity
3.6
BPH
TURP, 10 cc
+
+
LGPIN
nodularity
10
BPH
TURP, 30cc
+
+
LGPIN
nodularity
4
BPH
TURP, 8cc
+
+
hard nodule 12
?Ca
TURP, 20cc
+
+
nodularity
BPH
TURP,4 cc
+
+
6.2
109
7
trabeculae,cribriform,infl
7
am
+
prostatitis, C/S- E. Coli
LGPIN
MASTER CHART
Final
NH
NH
NH with
prostatitis
NH
NH
Fibro myo
hyperplasia
NH with
prostatitis
NH
NH
NH
NH
NH
NH with prostatitis
NH
NH
NH
NH
TCC bladder
Adenocarcinoma high
Grade
NH
NH
Adenocarcinoma high
Grade
NH with prostatitis
NH with prostatitis
NH
NH with LGPIN
NH with LGPIN
Adenocarcinoma
High Grade
NH with prostatitis
NH with LGPIN
109
MASTER CHART
72
1716/05
122 Siddappa
70
1840/05
123 Ramappa
56
1868/05
124 Thimmarayappa
55
1870/05
125 Chikkanna
60
1923/05
126 Chunche gowda
70
1941/05
127 Puttaswamy
70
1968/05
128 Kempanna
70
2051/05
129 Kalamaregowda
75
2107/05
130 Narayanaswamy
55
2121/05
131 Ramaiah
60
2251/05
132 Rehaman
65
2228/05
133 Inayathulla
60
2304/05
134 Venkatappa
76
2339/05
USG
1M
2D
1Y
1D 1W
20D
1M
4M
2M
20D
1D
2M
1M
2M
80
2352/05
60
2408/05
137 Jayanna
50
2438/05
138 Sabja baig
60
2510/05
139 Channegowda
65
2528/05
140 Hanumanthaiah
70
2592/05
141 Hombegowda
65
2593/05
142 Vasudevareddy
70
2602/05
2M
143 Thimmappa
72
2603/05
3M
144 Abdulwahab
60
2769/05
145 Naidu
75
2770/05
146 Rangaiah
60
2879/05
12.3
BPH
TURP, 6 cc
+
+
nodularity
47.25
BPH
TURP, 10 cc
+
+
nodularity
4
BPH
TURP, 5cc
+
+
nodularity
5.75
BPH
TURP, 5cc
+
+
nodularity
1.7
BPH
TURP, 20 cc
+
+
nodularity
15.25
BPH
TURP, 25 cc
+
+
nodularity
0.6
BPH
TURP, 20cc
+
+
nodularity
25.32
BPH
TURP, 15 cc
+
+
nodularity
1
BPH
TURP, 1 cc
+
+
prostatitis, C/S-E-coli
+
+
Prostatitis
+
prostatitis
+
TURP, 6 cc
+
+
2M
nodularity
12
?Ca
Needle biopsy
+
+
nodularity
2.6
BPH
TURP, 12 cc
+
+
6M
nodularity
3.2
BPH
TURP, 4cc
+
+
nodularity
38.35
BPH
TURP, 15 cc
+
+
nodularity
4
BPH
TURP, 15 cc
+
+
15D
nodularity
2.6
BPH
TURP, 15 cc
+
+
15D
nodularity
3
BPH
TURP, 4 cc
+
+
nodularity
3.8
BPH
TURP, 3 cc
+
+
nodularity
0.8
BPH
TURP, 15 cc
+
+
nodularity
8
BPH
TURP, 20 cc
+
+
nodularity
27.6
BPH
TURP, 8 cc
+
+
Granulomatous,HGPIN
nodularity
21.61
BPH
TURP, 15 cc
+
+
prostatitis
nodularity
1
BPH
TURP, 12 cc
+
+
1M
2D
3M
147 Chikkaboraiah
75
2899/05
2M
148 Ningegowda
75
2924/05
1M
149 Chikkappa
62
2977/05
1M
+
Prostatitis
+
+
Abscess
nodularity
18.02
BPH
Prostatectomy
+
+
+
nodularity
6.97
BPH
TURP, 2 cc
+
+
+
nodularity
1.89
BPH
TURP, 2 cc
+
+
109
7
perineural
invasion small
acinar,nests
9
+
BPH
15D
small acinar,inflamm
HGPIN
abscess
+
3
1M
CA
LGPIN
nodularity
2D
3M
nodularity
Others
1M
2M
2M
+
PIN
+
1D 15D
1M
+
+
GL
SCR
SQ METP MONO BCH
Needle biopsy
2M
1M
+
TURP, 3 cc
TR
CC
MT METP
?Ca
4M
6M
TURP, 30 cc
BPH
G.Hyp FMH
hard nodule 51
1M
136 Ramu
BPH
68.3
PSA
(ng/ml)
1M
3M
135 Lingappa
10
nodularity
DRE
Prostate
nodularity
enlarged
2D
Microscopy
GROSS
dysuria
acute retention
haemturia
incmp voiding
hesitancy
strain
Clinical investigation
clinical diagnosis
121 Chikapa
diff voiding
Lab No.
urgency
Age
(Yrs)
nocturia
Name
No.
frequency
Sl.
poor stream
Presenting complaints
MASTER CHART
Final
NH with LGPIN
Adenocarcinoma
High Grade
NH with prostatic
abscess
NH with prostatitis
NH
NH
NH
NH with prostatitis
NH
NH
NH
NH with prostatitis
NH with prostatitis
Adenocarcinoma high
Grade
NH
NH
NH with prostatits
NH
NH
NH
NH
NH
NH with abscess
NH with
granulomatous
prostatitis
NH with prostatitis
NH
NH
NH
NH
109
MASTER CHART
62
2980/05
2M
1M
USG
DRE
dysuria
acute retention
haemturia
incmp voiding
hesitancy
strain
diff voiding
urgency
Lab No.
Clinical investigation
nodularity
PSA
(ng/ml)
30
Microscopy
clinical diagnosis
150 Muthegowda
Age
(Yrs)
nocturia
Name
No.
frequency
Sl.
poor stream
Presenting complaints
GROSS
BPH
TURP, 25 cc
G.Hyp FMH
109
+
+
TR
CC
MT METP
GL
SCR
SQ METP MONO BCH
+
PIN
Others
prostatitis, C/S-E. coli
CA
MASTER CHART
Final
NH with prostatitis
109