1
18
Male reproductive system
Prostate and seminal vesicles
Testis
Testicular adnexa
Penis and scrotum
Prostate and seminal vesicles
Prostate
NORMAL ANATOMY
ECTOPIA
NODULAR HYPERPLASIA
INFARCT
PROSTATITIS
Abscess
Tuberculosis and BCG-induced granulomas
Other specific infections
Granulomatous prostatitis
Prostatitis with eosinophils
Other inflammations
CALCULI
TUMORLIKE CONDITIONS OF PROSTATE AND PROSTATIC
URETHRA
CARCINOMA
General features
Clinical features
Prostate
Normal anatomy
The prostate is a pear-shaped glandular organ that
weighs up to 20 g in the normal adult male and that
depends for its differentiation and subsequent growth on
androgenic hormones synthesized in the testis, acting
through a poorly understood mesenchymal–epithelial
interaction.10 Traditionally, it has been divided into anterior, middle, posterior, and two lateral lobes by drawing
divergent lines from the centrally located urethra. A division that correlates better with the physiologic and
pathologic features of the organ is into an inner (periurethral) and an outer (cortical) zone. The inner zone is the
primary site for nodular hyperplasia (and the rare carcinomas arising from large ducts), whereas the outer zone
Pathologic features
Adenocarcinoma of peripheral ducts and acini
“Minimal adenocarcinoma” and atypical small acinar
proliferation (ASAP)
Carcinoma of large (“primary”) ducts
HC & IHC features
MG features
Other microscopic types
Intraepithelial proliferative lesions
Cytology
Histologic examination
Microscopic differential diagnosis
Spread and metastases
Staging and grading
Treatment
Prognosis
OTHER TUMORS
Seminal vesicles and Cowper’s glands
is the site of predilection for the ordinary adenocarcinoma arising from peripheral ducts and acini.4,14 A
modification of this scheme divides the prostate into
peripheral, central, transitional, and periurethral gland
regions.17 According to this system, the transitional and
periurethral regions are the exclusive sites of origin of
nodular hyperplasia, whereas the peripheral zone is the
one most susceptible to prostatitis and carcinoma.
The prostate is enveloped by a fibromuscular layer
usually referred to as a capsule, but it has been pointed
out that this is not a well-defined anatomic structure
with constant features.3 It is more evident along the base
of the organ and less so along the anterior and apical surfaces.
The glandular component of the organ is composed of
acini and ducts, the latter subdivided into large (primary,
major, excretory) and peripheral (secondary, minor).
Both acini and ducts contain secretory cells, basal cells,
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2 Male reproductive system
and scattered neuroendocrine cells. The secretory cells,
which are located in the luminal side of the gland, contribute a wide variety of products to the seminal fluid.
They produce prostatic acid phosphatase (PAP) and
prostate-specific antigen (PSA), both of which can be
readily identified immunohistochemically and have
been proved of great diagnostic utility because of their
organ-related specificity. PSA is a glycoprotein that has
been identified as a kallikrein-like protease.1 Secretory
cells also coexpress various keratins and vimentin.1,16 The
keratins do not include high-molecular-weight types
such as 34βF12, a fact of diagnostic significance.
The normal prostatic secretion is a neutral mucosubstance (a feature of some diagnostic significance because
most adenocarcinomas secrete a mixture of acidic and
neutral mucins). However, on occasion one encounters
scattered columnar mucin-secreting cells in nonneoplastic prostatic epithelium, particularly in areas of
atrophy.1,12,20
The complex secretory mechanism of normal prostatic
glands is severely altered in neoplastic conditions, as
evidenced through morphologic, histochemical, and
immunohistochemical techniques.9
The basal cells form a thin continuous layer that separates the luminal secretory cells from the basement
membrane. They characteristically contain keratins 34
βE12, CK8.12, and 312 C8-1 and stain strongly for antikeratin antibody 903, a fact that has been exploited in the
differential diagnosis between well-differentiated carcinomas (in which basal cells are absent) and benign
conditions that simulate it (in which they are generally
present, although sometimes in a discontinuous fashion).
Under normal conditions these basal cells do not have
the phenotype of myoepithelial cells, in the sense that
they lack immunoreactivity for S-100 protein or smooth
muscle actin.13,18,21 However, they can be viewed as being
equivalent to the myoepithelial cells of the breast and
other glandular organs. Support for this interpretation
derives from the fact that they can undergo clearcut
myoepithelial metaplasia in conditions such as sclerosing adenosis (see p. XXXX). They do not express PSA or
PAP, but they have been shown to exhibit strong
immunoreactivity for androgen receptors focally.5,8 They
are thought to represent a multipotential population that
gives rise to all epithelial lineages present in the normal,
hyperplastic, and neoplastic prostate.7
The neuroendocrine cells express chromogranin A and
B, secretogranin II, and various peptide hormones such
as somatostatin, calcitonin, and bombesin11,19; they
coexpress PSA, suggesting a common origin with the
secretory cells.2 However, they are negative for androgen
receptors.6
The large prostatic ducts are lined by transitional
epithelium that is continuous and indistinguishable from
that lining the prostatic urethra. In contrast to bladder
epithelium, its surface does not display umbrella cells
but rather a single layer of columnar cells that are
immunoreactive for PSA and PAP. On occasion, this
epithelium undergoes squamous metaplastic changes;
these were very common at the time that estrogen therapy was widely employed for prostatic carcinoma.15
The prostatic stroma is notable because of its large
content of smooth muscle fibers, whose function is to
squeeze out the prostatic secretion when properly stimulated; it has been pointed out that the presence of this
muscular stroma duplicates the function of myoepithelial cells in other organs, such as breast, and makes the
presence of myoepithelial cells in the prostate superfluous. Prostatic stromal cells have been found to contain
androgen receptors.
Peripheral nerves are evenly distributed in the apex,
mid gland, and base22; they are of importance to pathologists because of the high frequency with which the loose
connective space that surrounds them (formerly thought
to represent perineural lymph vessels) is involved by
adenocarcinomas of this organ.
The prostatic lymph vessels drain into the pelvic
lymph nodes and from there into the retroperitoneal
chain.
Ectopia
Ectopia of prostatic tissue is a very rare event, save for
the benign urethral polyps discussed in Chapter 17B. It
has been described in the bladder, root of the penis, epididymis, testis, seminal vesicle, retrovesical space,
submucosa of the anal canal, pericolic fat/pararectal
space, and spleen.23
Nodular hyperplasia
Benign prostatic hypertrophy is the usual name applied to a
common benign disorder of the prostate that, when
extensive, results in varying degrees of urinary obstruction, sometimes requiring surgical intervention. The
term nodular hyperplasia, as proposed by Moore44 in his
classic study, is a more exact designation. The disease
represents a nodular enlargement of the gland caused by
hyperplasia of both glandular and stromal components.
This results in an increase in the weight of the organ well
beyond the 20 g regarded as normal for adult individuals. The clinical incidence of this disease is only 8%
during the fourth decade, but it reaches 50% in the fifth
decade and 75% in the eighth decade. It has been estimated that the process begins before the age of 30 and
that its doubling time progressively increases from 4.3
years in the early stage (third to fifth decade) to over 100
years in the late stage (patients beyond 70 years old).28
No predisposing or protecting factors (other than
castration) have been identified. As Badenoch26 put it,
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Nodular hyperplasia
nodular hyperplasia of the prostate occurs “in saints and
sinners, in fat men and thin, in parsons with large families and monks with none, in postmen and prime
ministers.” It has been established that prostatic nodular
hyperplasia occurs only in individuals with intact testes
and that it is an androgen-dependent disorder. Other
possible contributing factors have been proposed, such
as inflammation-induced release of platelet-derived
growth factor37 and human papilloma virus,42 but it is difficult to escape from the conclusion that the disease is
fundamentally the consequence of a hormonal imbalance which leads to an alteration of the delicate balance
that exists both in the epithelium and the stroma
between cell death and proliferation.29,41 Specifically, it
has been suggested that nodular hyperplasia may result
from an initial activation of mesenchymal clones with
embryonal functions that stimulate development of the
glandular component.24 In turn, this may result from
dihydrotestosterone accumulation within the gland,
resulting from decreased catabolism of the molecule and
enhanced intracellular binding.57 A peculiar immunohistochemical finding that may throw some light on this
issue is the demonstration that p27 protein (a negative
regulator of the cell cycle) is prominently expressed in
the epithelial and stromal cells of the normal prostate but
essentially negative in nodular hyperplasia.32
At autopsy the average weight of a prostate gland
affected by nodular hyperplasia is 33 g ± 16 g. Specimens
obtained surgically weigh 100 g on average, but on rare
occasions weights of over 800 g have been recorded.
Grossly, variously sized nodules with a gray to yellow
color and a granular appearance are seen projecting
above the cut surface (Fig. 18.1).
A cross section of an entire gland with early involvement clearly shows that nodular hyperplasia usually
begins in the “inner” gland, i.e., the portions around the
urethra and specifically where the ejaculatory ducts
enter the urethra, which are also referred to as the periurethral and transitional zones. This fact supports the
interpretation that this portion of the gland reacts differently to hormonal stimuli than the outer portion. In most
instances the nodules congregate on both sides of the
urethra, resulting in so-called lateral lobe hyperplasia. In
others the disease results in a midline dorsal nodule at the
bladder neck protruding into the bladder lumen. With
increased growth, the periphery of the organ is pushed
aside and compressed. In only about 5% will a focal
lesion of nodular hyperplasia be found in the peripheral
zone of the organ.40,46,47,55
Microscopically, the earliest change is a stromal proliferation about small sinusoidal spaces in the periurethral
regions and, to a lesser degree, in the periductal and
intralobular areas (Fig. 18.2). This stromal proliferation
(which in the periductal areas may have a concentric or
an eccentric quality) contains more smooth muscle and
less elastic tissue than the normal stroma. This is
Fig. 18.1 Gross appearance of nodular hyperplasia in material
obtained from suprapubic prostatectomy. Note the multinodular
appearance and the admixture of solid and microcystic areas.
Fig. 18.2 Whole mount of nodular hyperplasia of prostate,
showing nodular configuration and cystic changes.
followed by hyperplasia of the glandular component,
so in the well-developed disease the nodules are composed of varying proportions of both elements.49 These
proportions are somewhat different in patients with
symptomatic and those with asymptomatic nodular
hyperplasia.52 The glands are dilated or even cystic and
often contain an inspissated secretion of glycoproteic
nature (corpora amylacea), which is sometimes calcified.53 The epithelium ranges from flat to columnar,
sometimes facing each other in the same gland (“functional polarization”); the cytoplasm is pale, and the
nuclei are regular and centrally located (Fig. 18.3). The
nucleoli are inconspicuous. Papillary infoldings are common. A continuous basal cell layer is seen immediately
above a well-developed basement membrane.
Small clusters of lymphocytes are common in the
interstitium and around the ducts. They are probably the
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4 Male reproductive system
ing their secretion or their conversion to their tissue
active form or at relaxing the stromal muscle
cells.33,36,38,45,47,48 Among these, the drug most widely used is
finasteride, which works by inhibiting 5-α reductase, the
enzyme that converts testosterone to the potent androgen dihydrotestosterone. The morphologic changes
induced by this compound in the prostate are relatively
minor and nonspecific. They include focal atrophy,
increase in the stromal–epithelial ratio, squamous metaplasia, and transitional metaplasia.35,43
Infarct
Fig. 18.3 Nodular hyperplasia of prostate, with cystic dilatation of
the glands. Characteristically, the epithelium is tall on one side and
flattened on the other.
result rather than the cause of the hyperplasia54; a diagnosis of chronic prostatitis is not warranted because of
their mere presence.
Many morphologic variations of this basic theme
exist, some of them resulting from the overgrowth of one
component over the other and others from the emergence of distinctive patterns. Interestingly, many of the
latter bear a notable resemblance to lesions of the breast
(another organ characterized by a hormonally driven
mesenchymal–epithelial interaction) and have been
named accordingly. They include sclerosing adenosis
(see p. XXXX), fibroadenoma-like and phyllodes tumorlike hyperplasia25,39 (adenomatoid tumor31), leiomyomalike and fibromyxoid nodules, and the presence of
bizarre cells in the stroma.34,58
It should be pointed out that there is little relation
between a diagnosis of nodular hyperplasia made on a
biopsy specimen and either the weight of the gland or
the score system used to measure urinary obstructive
symptoms.55a
The conventional treatment for nodular hyperplasia is
surgical.30 The involved area may be excised by various
techniques, of which transurethral resection (TUR) and
suprapubic prostatectomy are the most common.27,56 It
should be realized that these procedures remove only the
newly formed nodules. The compressed peripheral portions of the gland remain; these expand by stromal
growth to surround the prostatic urethra and may be the
source of recurrent hyperplasia.44 Not surprisingly, the
chance of a patient undergoing a second operation for
this disorder is substantially higher after a TUR than an
open prostatectomy.50 Adenocarcinoma can also develop
in the residual gland many years after surgery.51 Medical
alternatives to surgery include various medications
aimed at blocking the actions of androgens by prevent-
Infarct of the prostate occurs predominantly in large
prostates that exhibit nodular hyperplasia.61 Its reported
incidence is probably related to the thoroughness of the
microscopic examination. In carefully studied glands, it
has been found to be present in 18% to 25% of the cases.62
It has been traditionally reported in TUR specimens, but
it can also be recognized in prostatic needle biopsies.61
The size and number of the infarcts are directly related to
the degree of prostatic hyperplasia. True infarcts occurring on a vascular basis should be distinguished from
necrotic changes involving a gland or group of glands
but sparing the stroma, a change sometimes seen in
nodular 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 the
intraprostatic portion of the urethral arteries.59
Grossly, prostatic infarcts vary in size from a few millimeters up to 5 cm. They are speckled, grayish yellow,
and often contain streaks of blood. The peripheral margins are usually sharp and hemorrhagic and may
impinge on the urethra (Fig. 18.4). Microscopically, the
infarcts are of ischemic type, with sharply outlined areas
of coagulative necrosis involving glands and stroma.
Prominent squamous metaplasia may develop in the
ducts at the periphery of the infarct, a change that should
not be confused with squamous cell carcinoma (Fig.
18.5). This metaplastic change is confined to the
expanded ducts, keratinizes only rarely, and does not
extend to the surrounding prostatic tissue.63 It should be
remembered that true squamous cell carcinomas of the
prostate are exceptionally rare (see p. XXXX).
Most prostatic infarcts are clinically silent. Occasionally,
they cause acute urinary retention because of the
accompanying edema.60 Since they are often adjacent to
the urethra, gross hematuria can also occur. Diffuse oozing
of blood from the overlying mucosa may be seen cystoscopically. They may cause serum elevation of PAP and
PSA.64 Removal of the infarcted area promptly returns
these levels to normal; if it does not, further workup is
indicated.
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Prostatitis
bacteria are the most common pathogens found in cultures from prostatic fluid.66,68
Microscopically, prostatitis usually appears as a localized process involving a small number of ducts or acini.
The lumina are distended and filled with secretion mixed
with inflammatory cells, among which neutrophils predominate. The stromal component, on the other hand, is
mainly mononuclear and is composed of a mixture of
lymphocytes, plasma cells, and histiocytes. In the presence of a monotonous infiltration of mature lymphocytes
throughout the organ, the alternative diagnosis of
involvement by chronic lymphocytic leukemia should be
considered.
Prostatitis is often accompanied by elevation of serum
PSA, which should return quickly to normal following
successful antibiotic treatment.67,70
Fig. 18.4 A, Gross appearance of infarct of prostate. The lesion has
a bright red color and bulges on the cut surface. Nodular
hyperplasia is also present.
Abscess
In the past, the majority of prostatic abscesses resulted
from gonorrhea. At present, most have an obstructive etiology and are the manifestation of secondary infection of
the prostate from an infected pool of residual urine.73
Escherichia coli is the organism usually responsible. In one
series,74 36% presented with acute urinary retention and
31% with perineal or suprapubic pain. Prostatic fluctuation on digital rectal examination is the most
characteristic sign, transrectal ultrasound is the most reliable diagnostic method, and transurethral drainage
under antibiotic coverage is the treatment of choice.71,72
Tuberculosis and BCG-induced granulomas
Fig. 18.5 Prominent metaplastic changes at the edge of a prostatic
infarct. These are sometimes overdiagnosed as carcinoma.
Prostatitis
Acute prostatitis is rarely seen in surgical specimens.
Chronic prostatitis is more common, but it is important to
distinguish the true infectious processes of this organ
from the inconsequential mononuclear infiltrates often
seen accompanying nodular hyperplasia (see p. XXXX).
The latter phenomenon is sometimes dignified by terms
such as “chronic nonbacterial prostatitis” or “lymphocytic prostatitis.”65,69 In bacterial prostatitis, the route of
infection remains uncertain in most cases. Some cases
follow gonococcal or nongonococcal urethritis, and
others result from periurethral infection associated
with indwelling urethral catheterization. Gram-positive
The prostate is the organ most commonly involved in
tuberculosis of the male genital system. Of 105 autopsy
cases included in the classic study by Auerbach,75 the
prostate was involved in 100, and in 35 of the 105, it was
the sole site in the system. In most cases, the infection is
the result of hematogenous spread from the lungs (or,
less often, from the skeletal system), but it may also
result from direct invasion from the urethra.77
Early tuberculous lesions in the prostate are seldom
detected on palpation. It is only when the disease is
advanced that enlargement occurs and fluctuant, tender
zones may be felt. Grossly, the lesions are usually bilateral. Confluent caseous zones occur with liquefaction
and cavitation, until finally the prostate becomes an
enlarged mass with multiple cavities. It may perforate
into the urethra and extend into the urinary bladder.76
With still further spread, sinus tracts may form into the
rectum, perineum, and peritoneal cavity. Healing with
calcification may supervene, a change detectable by radiographic examination. In the late stages, the prostate
becomes shrunken, fibrotic, and hard, to the point that it
may simulate carcinoma on palpation.
Microscopically, the initial lesion is in the stroma but
quickly spreads to the acini. Well-developed lesions
show confluent foci of caseation with incomplete fibrous
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6 Male reproductive system
encapsulation. There is little tendency for the formation
of typical tubercles.
Patients treated with intravesical bacillus Calmette–
Guerin (BCG) for bladder carcinoma may develop granulomas in the prostate similar to those seen more often in
the bladder itself (see Chapter 17).76 These granulomas
may be of noncaseating or caseating type.78 They may be
located along the periurethral or transitional zone or
involve the gland diffusely. Stains for acid-fast organisms are usually negative, although occasionally a few
organisms are visualized.
Other specific infections
The prostate can be involved by blastomycosis,81 coccidioidomycosis,83,86 actinomycosis,84 cryptococcosis,80,87,89,90
histoplasmosis,94 aspergillosis,82 and candidiasis.88,93
Many of these infections occur in the setting of immunosuppression resulting from AIDS or other disorders.80,89,94
Chlamydia trachomatis91 and Trichomonas vaginalis85 have
been identified in the prostate gland, but their possible
role as etiologic agents of prostatitis remains to be determined. The Chlamydia organism can be detected in tissue
by immunohistochemical and in situ hybridization techniques.79,92
Granulomatous prostatitis
The term (granulomatous prostatitis, sometimes preceded
by qualifiers such as nonspecific or idiopathic, is applied to
a rare prostatic disorder thought to represent an initially
immune-mediated process accompanied by a reaction
to the prostatic secretions released from obstructed
ducts.96,100 Most cases occur in glands affected by nodular
hyperplasia in patients over 50 years of age. The clinical
triad of high fever, symptoms of prostatitis, and a hard
prostate on palpation is present in one fifth of cases and
Fig. 18.6 Granulomatous prostatitis. The inflammatory infiltrate,
which contains scattered multinucleated cells, is characteristically
centered on a prostatic acinus.
should suggest the diagnosis.97 A preoperative diagnosis
of carcinoma is made in about 30% of cases because of
the firmness of the lesion, caused by the dense fibrosis.
Grossly, the gland is firm to stony hard. The cut surface shows obliteration of the architecture, with formation of yellow granular nodules. Microscopically, large
nodular aggregates of histiocytes, epithelioid cells, lymphocytes, and plasma cells are seen. Characteristically,
these granuloma-like formations are centered in the lobules (Fig. 18.6). A tubercle-like reaction with multinucleated giant cells, as well as collections of neutrophils,
eosinophils, and detritus within the ducts, also may be
seen. Microorganisms and caseation necrosis are absent.
The microscopic changes can simulate carcinoma in needle biopsy specimens.98 Immunohistochemical studies
have shown a concentration of T cells in and around
damaged ducts and glands95 and strong reactivity for
lysozyme in the histiocytes.99
Prostatitis with eosinophils
Most cases of prostatitis associated with an eosinophilic
infiltrate, sometimes intense, belong to one of the following categories101,111:
1 (Nonspecific) granulomatous prostatitis similar in all
regards to the type described previously but for the
presence of eosinophils diffusely admixed with the
other inflammatory components.
2 Eosinophilic prostatitis (allergic prostatitis, allergic
granuloma of prostate), characterized by small stellate necrobiotic nodules surrounded by palisading
epithelioid histiocytes and eosinophils, resembling
rheumatoid nodules.106,109 Vasculitis may be found.
Patients often have a history of allergy and asthma
and usually exhibit peripheral eosinophilia; in some
cases, systemic vasculitis is present. Elevation of
serum PSA levels may occur in this disorder.105
3 Iatrogenic granulomas, a morphologically similar
condition in patients lacking these systemic symptoms that develops after a surgical procedure to the
area, usually a TUR but sometimes a prostatic needle
biopsy.101,102,104,107 The interval between the surgical procedure and the appearance of the prostatitis ranges
from less than 1 month to several years; eosinophils
are more numerous when this interval is shorter. The
granulomas may represent a reaction to collagen
altered as a result of the surgery or to the metal deposition from the instruments themselves.103 Some of
these granulomas are elongated and tortuous,
whereas others are wedge shaped, with their base facing the cauterized tissue.101,108
4 A parasitic infestation resulting from metazoa.110
Other inflammations
Malakoplakia can involve the prostate, usually in association with bladder disease115,116 (see Chapter 17). As in
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Tumorlike conditions of prostate and prostatic urethra
the latter site, it should be viewed as a peculiar form of
tissue reaction to bacterial infection. The infiltrate is
usually located around prostatic ducts and has a mixed
composition. A similar condition but lacking Michaelis–
Guttmann bodies has been described as nodular histiocytic prostatitis.114
Malakoplakia may simulate sonographically prostatic
carcinoma.112 It can also be seen in prostates having carcinoma in other portions of the gland.117
Vasculitis of either necrotizing, fibrinoid, or granulomatous type can involve the prostate as an isolated
event.118,119
Hair granuloma, described exceptionally in TUR
specimens, is thought to result from hair from the perineal area being introduced into the prostate by an earlier
perineal prostatic needle biopsy.113
Fig. 18.7 Low-power appearance of a postoperative spindle cell
nodule. The surface is ulcerated and covered by granulation tissue.
Calculi
Prostatic calculi are seen in about 7% of prostates with
nodular hyperplasia.120 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 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 phosphated salts (calcium,
magnesium, aminomagnesium, potassium), calcium carbonate, and calcium oxalate.
Because of their extreme hardness, large prostatic calculi may be erroneously diagnosed as carcinoma on
palpation. They are radiopaque and easily detectable in
plain x-rays. If they are extremely large and numerous, a
prostatectomy may be required.
Tumorlike conditions of prostate and
prostatic urethra
Postoperative spindle cell nodules resembling sarcomas can develop as a result of an exuberant stromal
reaction after a TUR procedure, the interval ranging from
a few weeks to several months.131,138 They present as friable reddish nodules in the prostatic bed and may be the
source of postoperative bleeding. The superficial portion
looks like granulation tissue, but the deep areas simulate
sarcoma (particularly leiomyosarcoma) because of their
extreme cellularity and high mitotic activity (Figs 18.7
and 18.8). Intersecting fascicles of spindle cells with
extravasated red blood cells between are seen, resulting
in a picture vaguely reminiscent of Kaposi’s sarcoma.
The proliferating cells, which in all likelihood are myofibroblastic, show immunohistochemically a strong and
Fig. 18.8 Postoperative spindle cell nodule. The lesion is
hypercellular, relatively monomorphic, and accompanied by high
mitotic activity.
unexpected reactivity for keratin. They also express keratin and (inconstantly) actin and are EMA negative (Fig.
18.9). The temporal relationship of these changes with a
surgical procedure and their benign evolution support a
reactive pathogenesis.138
Inflammatory pseudotumor (pseudosarcomatous
fibromyxoid tumor), similar to that more commonly seen
in the bladder (see Chapter 17B), is sometimes seen in the
prostate. Microscopically there is a proliferation of spindle cells of myoid (myofibroblastic) appearance in a
well-vascularized and myxoid background.139 As with its
more common bladder counterpart, there is some question as to whether it should be regarded as a reactive
pseudoneoplastic condition (as its original name
implies) or as a low-grade neoplasm (as the alternative
name inflammatory myofibroblastic tumor suggests).
Urethral polyps composed of tall columnar cells of
prostatic origin are a common source of hematuria in
young adults124 (Fig. 18.10). They may have a villous configuration (“villous polyps”) and tend to be found in the
verumontanum but also along most of the posterior and
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8 Male reproductive system
Fig. 18.9 Immunoreactivity for low-molecular-weight keratin (Cam
5.2) in the proliferating cells of a postoperative spindle cell
nodule. This finding should not lead to a diagnosis of sarcomatoid
carcinoma.
Melanosis of the prostate refers to the presence of
melanin-containing elongated cells in the prostatic
stroma. The microscopic appearance is analogous to that
of blue nevus.127,133 The pigmented spindle cells are
immunoreactive for S-100 protein,134 and melanosomes
can be demonstrated ultrastructurally.140 This condition
should be distinguished from lipofuscin pigmentation of
the prostatic epithelium, which is equivalent to that more
often seen in the seminal vesicle.121,129
Extramedullary hematopoiesis rarely involves the
prostate in patients with myelofibrosis; the atypical
megakaryocytes present in it should not be confused
with malignant cells.132
Other tumorlike conditions of the prostate (such as
basal cell hyperplasia and sclerosing adenosis) are discussed in connection with the differential diagnosis of
prostatic carcinoma (see p. XXXX).
Carcinoma
General features
Fig. 18.10 Urethral polyp composed of well-differentiated
prostatic glands. This is a common cause of hematuria in young
males.
lateral surfaces of the prostatic urethra.122,137,140 They have
traditionally been thought to arise from ectopic prostatic
tissue located in the prostatic urethra but are more
likely of hyperplastic–metaplastic nature.123 They stain
intensely for both PAP and PSA.143 Most are cured by
transurethral fulguration, but instances of local recurrence have been described. Rarely, prostatic urethral
polyps have an adenomatoid “nephrogenic” configuration,125,135,143,144 and occasionally they may be the site of
carcinoma.142 Truly ectopic prostatic tissue has been seen
in urachal remnants, bladder trigone, root of the penis,
and pericolic fat.128
Other congenital and acquired non-neoplastic abnormalities of the prostatic utricle (verumontanum) include
hyperplasia and hypertrophy, inflammation, cysts, and
squamous metaplasia.126,136 The latter change, which was
common at the time that estrogen therapy for prostatic
carcinoma was popular, may result in obstructive symptoms.130
Carcinoma of the prostate is the most common internal
malignancy among men in the United States and is
responsible for 10% of cancer deaths in this population.
Each year in New York State more than 11,000 men are
diagnosed with prostatic cancer, and more than 2300 die
from it. Prostate cancer is the leading cause of new cancer
in men and is second only to lung cancer as a leading
cause of cancer-related deaths in men. Rates among black
males are one and a half those of white males.150 The ageadjusted incidence is on the increase in most countries.
Hormonal factors appear to play a role in the development of prostatic carcinoma. The disease does not occur
in eunuchs castrated before puberty, and its incidence is
low in patients with hyperestrogenism resulting from
liver cirrhosis. It has been estimated that 5% to 10% of
prostatic carcinomas have a genetic link. If a man’s
brother or father had prostatic carcinoma, his own risk of
developing the disease is two to three times greater than
average. There is no demonstrable correlation with diet,
venereal disease, sexual habits, smoking, or occupational
exposure.146 There is no convincing evidence that patients
with nodular hyperplasia (or those who have had a
transurethral resection for it) are at an increased risk for
the development of prostatic carcinoma, although the
two conditions often coexist.145,147,148
Almost 75% of the men diagnosed with prostatic cancer are age 65 or older, but the tumors can be seen in
younger adults and even in children and adolescents.149
Their frequency increases with age, a fact well substantiated by careful observations at autopsy. The frequency
with which incidental carcinoma is found at post
mortem examination varies between 15% and 70%146 and
is directly related to the age of the patient and the thoroughness of the sampling.
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Carcinoma
Clinical features
Skillful rectal examination remains a practical and efficient method for the detection of prostatic carcinoma155,158,161; however, pathologic confirmation is always
necessary because early carcinomas cannot be distinguished with assurance from foci of nodular hyperplasia, granulomatous prostatitis, tuberculosis, infarct, or
lithiasis.159 Transrectal ultrasonography can detect carcinomas (which appear as hypoechoic lesions) as small as
5 mm in diameter157; however, it will miss up to 30% of
the prostatic tumors that are isoechoic and has not
proved an efficient tool for screening.160
PSA is secreted by all but the most undifferentiated
prostatic tumors.165 Gram for gram, the average prostatic
carcinoma produces ten times or more the amount of
PSA produced by normal tissue, and this is reflected in
the circulatory levels of this marker. Serum determination of PSA has all but replaced the time-honored
determination of PAP.154,164 The test has a high sensitivity
and specificity, is rapid and inexpensive, and is minimally invasive.152,153,162 Mild serum elevations of PSA can
be seen with nodular hyperplasia, but levels above 4 call
for serial determination, with the performance of a
biopsy if they continue to rise. Almost half of patients
with prostatic carcinomas have levels over 10 mg/ml.
Elevations of serum PSA also occur in prostatitis, prostatic infarct, and major trauma to the prostate, such as
needle biopsy or TUR, but these elevations should be
transitory and resolve with proper treatment.
The combination of digital rectal examination, transrectal ultrasonography, and serum PSA represents a
powerful diagnostic triad for the detection of early
prostatic carcinoma.151,156 It is not clear whether measurement of the PSA density (PSA level as a function of
prostatic volume) will provide a more specific test for
carcinoma.163
Adenocarcinoma of peripheral ducts and acini
It is often emphasized that most prostatic carcinomas
arise in the posterior lobe. Although this statement is
basically correct, it is somewhat ambiguous because of
the various definitions regarding the boundaries of this
lobe.204 More important than this is the fact that most prostatic carcinomas arise in the peripheral zone, whether
posteriorly, laterally, or anteriorly, with sparing of the
periurethral region except for the late stages of the disease173,200 (Fig. 18.11).
Grossly, the tumor may be difficult to see but usually
can be identified as a gray or yellowish, poorly delineated, firm area (Fig. 18.12).199 Early detection efforts are
resulting in the identification of increasingly smaller
tumors. As a matter of fact, residual carcinoma may be
Fig. 18.11 Whole mount of radical prostatectomy specimen
showing involvement by an extremely small prostatic carcinoma
located at the periphery of the organ and accompanied by
perineurial invasion, the latter better seen in the inset.
Pathologic features
Prostatic carcinomas can be divided into two major categories: (1)adenocarcinoma of peripheral (“secondary”)
ducts and acini, and (2) carcinoma of large (“primary”)
ducts. This morphologic distinction has traditionally
been based on the belief of a different site of origin for the
two tumors. However (and as in the breast before), this
histogenetic approach has been challenged by the observation that the two patterns are often seen together, and
the alternative proposal has been advanced that it is the
site of the growth rather than the origin that governs the
tumor architecture.166 Be that as it may, the majority of the
tumors belong to the first category, and most studies
dealing with grading, staging, prognosis, and therapy of
prostatic carcinoma refer exclusively to them.
It should be pointed out that these two major tumor
types may coexist in the same prostate, and that there are
rare tumors with combined features in the same neoplasm.166a
Fig. 18.12 Gross appearance of prostatic adenocarcinoma. The tumor
appears as an irregularly shaped, yellowish mass with punctate foci
of necrosis in a gland that is also involved by nodular hyperplasia.
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9
NINTH EDITION
ROSAI AND ACKERMAN’S
Surgical Pathology
Announcing a new edition of this classic authoritative reference work of surgical
pathology written by one of the foremost names in the field. Offering a comprehensive and practical guide to all aspects of diagnosis and interpretation, this
new edition is now for the first time produced in full color throughout and is
lavishly illustrated with thousands of high quality color photomicrographs.
Building on the strengths of the previous editions, Dr Rosai has thoroughly
revised and updated the ninth edition to help the surgical pathologist in practice and in training keep pace with the latest tools and techniques in
interpretation and diagnosis.
Largely written by a single author, (with the assistance of six internationally
renowned experts) Rosai and Ackerman’s Surgical Pathology provides a unique
consistency and uniformity of style. Dr Rosai provides hundreds of diagnostic
pearls which are the product of decades of experience.
Virtually all of the photomicrographs are now in full color and provide true to
life images of what is actually seen under the microscope.
All of the major tumor types have been handled systematically for easy reference: General and Clinical features, Gross features, Microscopic features etc
Coverage of immunohistochemistry and genetic molecular features has been
greatly expanded and rewritten to complement the gross and microscopic examination.
The chapter on Special Techniques includes a comprehensive catalog of immunohistochemical markers which is like a book within a book.
Finally, this new edition contains a CD-ROM which has all of the thousands of
illustrations from the text and a slide making package so that this material can
be reused in lectures and as a teaching aid.
ISBN 0-323-01342-2