The Pathology of Prostate Cancer: From Population Studies to the Molecule
Moderators: Dr. John R. Srigley and Dr. Rodolfo Montironi
Section 5 -
Diagnosis Of Adenocarcinoma In Needle Biopsies
Professor of Pathology, Urology and Oncology
The Johns Hopkins Hospital
Recognition of Limited Cancer on Needle Biopsy
One of the more common problems seen with needle biopsy material is the underdiagnosis of carcinoma in
cases with a limited amount of tumor. At the edge of a tumor nodule, one commonly finds only scattered
glands of adenocarcinoma infiltrating between non-neoplastic glands. It is not uncommon, therefore, for
biopsies of adenocarcinoma of the prostate to yield several cores of tissue containing benign glands and
stroma with only a few neoplastic glands intercalated amongst benign glands.
In order to optimize the detection of prostate cancer, specimens should not be submitted in only 2
cassettes (left and right). The first problem is that when there are multiple cores in a given jar, the
histotechnologist in processing these needle biopsy specimens, cannot guarantee that the cores will all
remain in the same plane of section within the paraffin. This results in histological slides where they
may be missing gaps of prostate tissue that the pathologist will not see. This can be critical, as the
key focus within a prostate needle biopsy showing the only malignancy may be present in one of these gaps
of tissue. A second major concern with throwing multiple cores into one jar, is that the urologist
loses information as to where these cores are coming from. In 5%-10% of prostate needle biopsies, the
pathologist will render an "atypical, suspicious for carcinoma" diagnosis, necessitating a repeat
biopsy. We have demonstrated that the cancer is often near or adjacent to these atypical sites.
Consequently, if one knows the sextant region where the initial atypical site has come from, one can
focus the repeat biopsy by doing more repeat biopsies in this region and in the adjacent regions. It
makes no sense to know where the cores are coming from and have the specific information only to lose it
by throwing all the cores, for example from the left side, into one jar.
There is another reason why it is important to know the location of each core. Within the central
zone toward the base of the prostate around the ejaculatory duct, there is a close mimicker of high-grade
prostatic intraepithelial neoplasia (PIN). If pathologists know that the biopsy that they are looking at
comes from the base of the prostate, it is easier for the pathologist to recognize this central zone
histology as a mimicker of high-grade PIN, rather than over-diagnosing these lesions as high grade PIN.
Recognizing mimickers of high-grade PIN can prevent false positive biopsies and obviate the need for
unnecessary repeat needle biopsy. The final reason why it is important to separate cores into 6 distinct
jars depending on the sextant location is to help the pathologist identify tumor in the radical
prostatectomy specimen when the tumor is extremely focal. In approximately 5% of radical prostatectomy
specimens, it may be extremely difficult to identify prostate cancer. These cases represent very small
tumors that have been incidentally hit by needle biopsy. If the pathologist knows the approximate
location (i.e. sextant region) of the cancer on needle biopsy, the pathologist can then focus their hunt
in the radical prostatectomy for prostate cancer in these regions by performing cut-downs and flipping
paraffin blocks. I am aware of at least one urologist who has been sued when no cancer was found in the
radical prostatectomy, despite an accurate diagnosis of minute cancer of the prostate on needle biopsy.
Patients are naturally suspicious when they undergo a major surgical operation and no cancer is found.
Knowing the site of origin of the cancer on needle biopsy within the prostate can minimize the likelihood
that prostates will be signed out showing no evidence of residual carcinoma. Separating cores into 6
separate jars (one jar or block per each sextant site) is the optimal technique.
The importance of recognizing these cases of prostatic adenocarcinoma relates to the high
false-negative rate with core biopsy of the prostate. Approximately 19%-25% of sextant core biopsies
which are initially negative may show cancer on subsequent biopsy
Furthermore, a limited amount
of tumor on needle biopsy does not equate with a limited amount of cancer in the prostate. In a study of
non-palpable prostate cancer diagnosed by needle biopsy, we found that in cases where there was <3mm.
of well or moderately differentiated cancer on one needle biopsy core, 21% of the radical prostatectomy
specimens contained a moderate or advanced amount of tumor . Only a limited amount of tumor on needle
biopsy seen in the setting of low serum PSA values may indicate limited tumor in the prostate . The
recognition of prostatic cancer in these cases with limited tumor rests on both the architectural
abnormalities resulting from the infiltrating neoplastic glands and the cytologic features of the
It is important when examining needle biopsy specimens to gain an appreciation of what the normal
non-neoplastic prostate looks like in that patient. Even with limited needle biopsy material one can see
if the patient's non-neoplastic prostate appears normal composed of tall eosinophilic cytoplasm, or is
atrophic consisting of small basophilic or less commonly pale glands. In order to identify limited
amounts of cancer on needle biopsy material, first there must be an appreciation of the patient's normal
non-neoplastic prostate and then look for glands which do not fit in with the normal prostate. By
scanning the non-neoplastic prostate one can also gain an appreciation for the amount of stroma that
separates the normal glands. The first step in recognizing limited amounts of tumor on needle biopsy
material is the identification of an abnormal architectural pattern. Abnormal patterns include: 1)
smaller glands than normal; 2) crowded glands; and 3) glands infiltrating between non-neoplastic glands,
and more definitively on both sides of benign glands.
After recognizing that there is an abnormal growth pattern on low magnification, one can proceed to
higher magnification. If there are some suspicious glands present, verification that these glands are
malignant requires evaluation of cytologic detail at higher magnification. It is often very helpful on
high magnification to compare the glands that one is considering as diagnosing as carcinoma to the
surrounding benign glands. In order to diagnose certain glands as carcinoma there should be some
differences between these glands and the surrounding benign glands.
In most needle biopsy specimens with a limited amount of tumor infiltrating amongst normal glands, the
tumor is of intermediate grade with atypical nuclear features. One of the most frequently seen features
of malignant glands on needle biopsy is their enlarged nuclei as compared to the surrounding benign
nuclei. In addition, small nucleoli can often be seen in the carcinoma as compared to the surrounding
benign glands which lack nucleoli. The finding of nucleoli may be helpful in diagnosing cancer of the
prostate, although not all malignant glands contain nucleoli. One must also take into account the
overall setting in which the nucleoli are seen. With intense chronic or acute inflammation, nucleoli may
result within benign reactive glands. Consequently, first an abnormal architectural pattern suspicious
for carcinoma must be present before assessing cytologic features such as nucleoli. Hyperchromatism is
another feature of prostate cancer nuclei. A feature that may be helpful in establishing the diagnosis
of carcinoma is the presence of mitoses, since they are rarely seen in hyperplastic glands.
Unfortunately, mitotic figures are uncommon in intermediate grade adenocarcinomas of the prostate. In a
recent study, only 11% of consult needle biopsies contained mitoses .
The majority of attention in assessing diagnostic criteria for prostate cancer has concentrated within
the nucleus. We have noted in prior works that in some carcinomas the cytoplasm is more amphophilic than
surrounding benign glands and may be helpful in diagnosing limited carcinoma. In a recent study of
needle biopsies seen in consultation, in 60% of the evaluable cases this diagnostic criterion was present
and helped to establish a diagnosis of carcinoma . Unfortunately, in 32% of the cases as a whole, one
could not utilize the criterion. In these cases, the H&E stain was not ideal and benign glands also
exhibited amphophilic cytoplasm. Because we find this feature to be helpful in a large number of cases,
one should tinker with one's H&E stains to insure that the cytoplasm of benign glands appears lightly
eosinophilic or clear. Straight luminal borders in larger glands with abundant cytoplasm also favor the
diagnosis of prostate cancer. Comparably sized benign glands with abundant cytoplasm tend to have
papillary infolding or luminal ruffling.
After assessing nuclei and the cytoplasm, one should evaluate luminal contents. Two diagnostic
criteria are blue tinged mucinous secretions and pink acellular secretions. Whereas corpora amylacea are
prominent in benign glands and rarely seen in cancer, pink amorphous acellular secretions are seen in
approximately half of cancers and uncommonly seen in benign glands. This criterion must be used in
conjunction with other diagnostic features. One can, on occasion, see benign glands with these pink
acellular secretions yet lack any other features of malignancy. Blue intraluminal mucinous secretions,
although seen less frequently, appear to be more specific. We have only rarely seen blue secretions in
benign glands. The prevalence of these blue tinged secretions appears to be in part influenced by the
nature of ones hematoxylin and eosin stain. In some institutions referral material this feature appears
to be fairly prevalent whereas in other institutions, such as our own, it is rarely seen. One should
not, however, perform mucin stains to aid in the diagnosis of prostate cancer. Although initially
reports suggested that acid mucin could distinguish malignant from benign glands
shown that acid mucin may be present in mimickers of carcinomas such as adenosis as well as in atrophic
Prostatic crystalloids are intraluminal dense eosinophilic crystalline-like structures that appear in
various geometric shapes. Biopsy and TUR material reveal an incidence of 10-23% and in
cystoprostatectomy or autopsy specimens, the incidence of crystalloids in carcinomas reaches 60%
All studies have noted a relative increased incidence of crystalloids within low grade
adenocarcinomas. In a study of cancer on needle biopsy, we found a 25% incidence of crystalloids, and
also demonstrated an inverse correlation between the presence of crystalloids and Gleason grade . On
occasion, we noted crystalloids within entirely benign glands elsewhere in the case. In some instances
these benign glands were adjacent to carcinoma yet in other examples they were present in other areas of
the prostate. Studies have shown that when crystalloids are seen in benign glands on prostate needle
biopsy, patients are not at increased risk for cancer on subsequent biopsy
Perineural invasion, when present, is one of the few only diagnostic criteria that is diagnostic by
itself of prostatic adenocarcinoma. In a series of consecutive needle biopsies containing carcinoma, 20%
revealed perineural invasion . In order to use perineural invasion as a diagnostic criteria, the
glands in question should encircle the nerve. This is to distinguish perineural invasion by carcinoma
from perineural invasion that can sometimes be seen with benign glands . Occasionally, benign
prostatic glands may be seen adjacent to prostatic nerves, resulting in compression and indentation of
the nerves. Benign glands can even partially surround or be within a nerve. In these cases the lack of
circumferential growth of the glands around the nerve as well as the benign features of the gland should
prevent one from misdiagnosing adenocarcinoma of the prostate.
In addition to perineural invasion, there are two other features pathognomonic for prostate cancer.
Occasionally, intraluminal mucinous secretions are so extensive that they become focally organized. This
lesion, known as either mucinous fibroplasia or collagenous micronodules, is typified by very delicate
lose fibrous tissue with an ingrowth of fibroblasts . Glomerulations consist of glands with a
cribriform proliferation that is not transluminal. Rather, these cribriform formations are attached to
only one edge of the gland resulting in a structure superficially resembling a glomerulus
most cases with either perineural invasion, mucinous fibroplasia, or glomerulations, there is overt
carcinoma, but in some cases these features are the key to establishing a diagnosis of carcinoma.
Carcinomas Mimicking Benign Glands
Just as there are benign mimickers of prostate cancer, some cancers closely resemble benign prostate
glands in their architectural pattern and may not be recognized as malignant.
Pseudohyperplastic prostate cancer is characterized by the presence of larger glands with branching
and papillary infolding.
The recognition of cancer with this pattern is based on the
architectural pattern of numerous closely packed glands as well as nuclear features more typical of
carcinoma. A variant of pseudohyperplastic adenocarcinoma composed of markedly dilated glands with
abundant cytoplasm may be particularly difficult to recognize as malignant. This form of cancer can be
recognized by the appearance of numerous large glands that are almost back-to-back with straight even
luminal borders, and abundant cytoplasm. Comparably sized benign glands either have papillary infoldings
or are atrophic. The presence of cytologic atypia in some of these glands further distinguishes them
from benign glands. It is almost always helpful to verify pseudohyperplastic cancer with the use of
immunohistochemistry for high molecular weight cytokeratin. As with foamy gland cancer,
pseudohyperplastic cancer, despite its benign appearance, may be associated with intermediate grade
cancer and can exhibit aggressive behavior (ie. Extraprostatic extension).
Foamy gland cancer must be recognized as carcinoma by its abundant foamy cytoplasm, its architectural
pattern of crowded and/or infiltrative glands, and frequently present pink acellular secretions .
Although the cytoplasm has a xanthomatous appearance, it does not contain lipid, but rather empty
vacuoles . More typical features of adenocarcinoma such as nuclear enlargement and prominent
nucleoli are frequently absent, which makes this lesion difficult to recognize as carcinoma. Despite its
benign cytology, 96% of the cases when there is an associated non-foamy cancer it is Gleason score >4,
such that foamy gland carcinoma appears best classified as intermediate grade carcinoma. In foamy gland
carcinoma the cytoplasm is copious with nuclei occupying <10% of the cell height. Characteristically,
the nuclei in foamy gland carcinoma are small, round, and densely hyperchromatic. The nuclei in foamy
gland carcinoma are actually rounder than those of benign prostatic secretory cells.
Atrophic prostate cancers are rare and may be present on needle biopsy, usually unassociated with a
prior history of hormonal therapy
The diagnosis of carcinoma in these cases is made on: 1) a
truly infiltrative process with individual small atrophic glands situated between larger benign glands;
2) the concomitant presence of ordinary less atrophic carcinoma; and 3) greater cytologic atypia than is
seen in benign atrophy.
The importance of not underdiagnosing prostatic adenocarcinoma on needle biopsy relates back to the
relatively high false-negative rates with needle biopsy of prostatic carcinoma. In cases where the
needle biopsy material is strongly suspicious for carcinoma but the pathologist does not feel comfortable
in establishing the diagnosis, what usually transpires is that the needle biopsy is called atypical and a
repeat biopsy is recommended. However, because of the high false-negative rates with needle biopsy of
prostatic carcinoma, if the repeat biopsy or biopsies do not contain diagnostic material, it does not
negate the findings on the initial biopsy and does not exclude the presence of carcinoma within the
patient. Therefore, in those cases in which the initial histologic material is strongly suspicious for
carcinoma but the pathologist does not feel comfortable in establishing this diagnosis, and subsequent
biopsies do not show carcinoma, the material should be sent for consulting opinion rather than assuming
that the first biopsy was benign.
Most Common Mimickers of Prostate Cancer on Needle Biopsy
The diagnosis of carcinoma should not be based solely on any one of the features mentioned below but
can be more confidently made when several of the features are present. Although the features listed
below are more commonly seen in carcinoma, there are exceptions where benign glandular proliferations may
also show these features. The most common mimickers of prostate cancer on needle biopsy are atrophy
and nonspecific granulomatous prostatitis ,
and high grade PIN .
Atrophy is best diagnosed at medium to low magnification. Although the glands may appear
infiltrative, they appear invasive as a patch not as individual glands infiltrating in between and on
both sides of larger benign glands. At low power, atrophic glands have a very basophilic appearance.
This basophilic appearance is due to their scant cytoplasm and crowded nuclei such that at low
magnification one is merely seeing a nuclear outline of the gland. Longitudinal tangential sections of
atrophic glands results in cords of cells that can further mimic cancer. In some cases there may be
associated fibrosis, which gives the atrophic glands a more infiltrative appearance that has been termed
sclerotic atrophy. A characteristic finding in some cases is the presence of a centrally dilated
atrophic gland surrounding by fibrosis and clustered smaller glands, which has been termed "post-atrophic
hyperplasia (PAH)". Atrophy uniformly labels with high molecular weight keratin in contrast to negative
staining in adenocarcinoma. A variant of atrophy that may cause confusion with carcinoma is "partial
atrophy". Partial atrophy lacks the basophilic appearance of fully developed atrophy as the nuclei are
more spaced apart. The presence of crowded glands with pale cytoplasm may lead to an overdiagnosis of
low-grade adenocarcinoma. At higher power, however, the glands have benign features characterized by
undulating luminal surfaces with papillary infolding. Most carcinomas have more straight, even luminal
borders. In addition, the glands are partially atrophic with nuclei in areas reaching the full height of
the cytoplasm. The nuclear features in partial atrophy tend to be relatively benign without prominent
nucleoli. One should hesitate diagnosing cancer when the nuclei occupy almost the full cell height and
the cytoplasm has the same appearance as surrounding more obvious benign glands.
Adenosis (atypical adenomatous hyperplasia) is one of the closest mimickers of prostate adenocarcinoma
on needle biopsy as it is difficult to appreciate its characteristic lobular pattern. Probably the most
important differentiating feature of adenosis seen on H&E stain is that within a nodule of adenosis
there are elongated glands with papillary infolding and branching lumina typical of more benign glands,
yet in their nuclear and cytoplasmic features they look similar to the adjacent small glands suspicious
for carcinoma. At higher power, adenosis is typically composed of small glands with pale to clear
cytoplasm, as opposed to some carcinomas, which have more amphophilic cytoplasm. Occasional single cells
or poorly formed glands are not uncommon in a nodule of adenosis and probably represent tangential
sections of small glands. Usually, adenosis has bland appearing nuclei without nucleoli, yet fairly
prominent nucleoli may be present, which should not lead to the diagnosis of carcinoma. . Corpora
amylacea are commonly seen in adenosis, and are rare in carcinoma. Only 2% of cases of adenosis contain
blue intraluminal secretions visible on hematoxylin and eosin-stained sections, a feature common in
low-grade carcinomas. Foci of adenosis often contain crystalloids, sometimes in great number. As few as
10% of the glands in a nodule of adenosis may be labeled with antibodies to high molecular keratin,
although usually more than half of the glands will show some staining. The stain is also patchy within a
given gland, with sometimes only 1 to 2 basal cells identified. If some glands suspicious for adenosis
lack high molecular weight cytokeratin immunoreactivity, yet are otherwise indistinguishable from
adjacent glands which demonstrate basal cell keratin immunoreactivity, the absence of a basal cell layer
in some glands should not be used to diagnose the lesion as carcinoma.
Although most cases of nonspecific granulomatous prostatitis seen on needle biopsy do not
histologically resemble prostate cancer, 4% of cases can closely resemble cancer. These cases of
non-specific granulomatous prostatitis consists of sheets of epithelioid histiocytes some with prominent
nucleoli with abundant granular cytoplasm. The key feature to avoid a misdiagnosis of cancer is to
recognize the other inflammatory cells in nonspecific granulomatous prostatitis, such as scattered
neutrophils, lymphocytes, plasma cells, and eosinophils. Although it may be difficult to appreciate on
needle biopsy specimens, non-specific granulomatous prostatitis initially is localized around ruptured
ducts and acini. If there are difficulties in distinguishing non-specific granulomatous prostatitis from
poorly differentiated adenocarcinoma, immunohistochemistry can be utilized. These epithelioid cells will
be negative for PSA, PSAP, and pancytokeratin, and positive for various histiocytic markers.
The presence of associated clinical findings such as elevated serum PSA levels, abnormal transrectal
ultrasound findings, or abnormal rectal exam should not factor heavily into the diagnosis of
adenocarcinoma on needle biopsy. All of these tests have relatively low sensitivities and specificities
and the diagnosis of carcinoma should be rendered solely on histological grounds. For example in
non-specific granulomatous prostatitis the rectal exam can feel nodular like cancer, the serum PSA may be
as high as 30 ng/ml, and the ultrasound appearance can be hypoechoic identical to cancer.
Summary to Systematic Approach to Diagnosing Cancer
The approach of diagnosing adenocarcinoma of the prostate consists of making a mental balance sheet,
in one column features favoring a diagnosis of carcinoma and the other features favoring a benign
diagnosis. At the end of evaluating a case, if all the criteria line up on one side of the balance
sheet, even if there are limited number of suspicious glands, then one can reliably establish a diagnosis
of carcinoma. In cases where there are several features favoring a diagnosis of carcinoma yet other
favoring a benign diagnosis those cases should be signed out as being suspicious but not diagnostic for
cancer with recommendation for repeat biopsy.
ARCHITECTURAL FEATURES SUGGESTIVE OF CARCINOMA
- Finding of small glands infiltrating in between larger benign glands where otherwise one
would expect to see only stroma.
- The presence of glands infiltrating haphazardly in different directions within the stroma.
- The presence of back-to-back glands which do not merge in with surrounding more recognizably benign
- Areas of increased cellularity which are not as densely basophilic as collections of lymphocytes.
CYTOLOGIC FEATURES SUGGESTIVE OF CARCINOMA
- Nuclear enlargement with or without nucleoli when compared to surrounding more recognizably
- Nuclear hyperchromasia.
- Adjacent high grade PIN, as long as the small atypical glands are to numerous or far enough
away from the PIN so as not to represent outpouchings or tangential sections off of the PIN.
- Presence of mitoses.
- The presence of individual epithelial cells.
- Amphophilic cytoplasm in glands suspicious for carcinoma in contrast to surrounding benign
glands which have pale to clear cytoplasm.
- Relatively large glands which have a crisp even luminal surface without the ruffling and
undulations seen in comparably sized benign glands.
ADJUNCTIVE FINDINGS SEEN WITH CARCINOMA
- Presence of intraluminal blue-tinged mucinous secretions seen on H&E sections.
- The finding of numerous intraluminal prostatic crystalloids.
- The finding of pink amorphous intraluminal secretions.
FEATURES THAT ARE VIRTUALLY PATHOGNOMIC FOR PROSTATE CANCER
- Perineural invasion
- Mucinous fibroplasia (collagenous micronodules).
- Glomeruloid structures.
FEATURES THAT SHOULD MAKE ONE HESITATE IN DIAGNOSING CARCINOMA
- Presence of acute and chronic inflammation where nuclei may be enlarged with reactive
nucleoli and often have an atrophic cytoplasm.
- The presence of a densely cellular lesion suggestive of high-grade prostate carcinoma yet
confounded by the presence of acute or chronic inflammation, which may represent non-specific
- The presence of epithelioid cells suggestive of high-grade prostate cancer centered on
ruptured and intact glandular spaces, which may represent non-specific granulomatous prostatitis.
- The presence of either fully or partially atrophic glands despite having an infiltrative
- The presence of small glands with minimal atypia merging in with similar glands which appear more
recognizably benign, which may represent adenosis.
- High grade PIN with only a few adjacent atypical glands, where one cannot rule out tangential sections or
outpouchings off of the PIN.
Use of Immunohistochemistry as an Adjunct in the Diagnosis of Limited Adenocarcinoma of the Prostate Cancer
There are cases which some pathologists may not feel comfortable diagnosing as adenocarcinoma based on
the architectural pattern of small glands infiltrating in between larger benign glands if there is a lack
of cytologic atypia. In these cases where there are a large number of atypical glands present for
evaluation, the use of antibodies that label basal cells of the prostate may resolve the diagnosis. The
most commonly used antibody used to label basal cells has been high molecular weight cytokeratin
More recently, antibodies to P63, which is a nuclear stain, has also been shown to label basal cells of
One study that compared high molecular weight cytokeratin and P63 have showed P63
to be slightly superior . In some cases, there will be faint staining of cancer glands with
antibodies to high molecular weight cytokeratin; this staining is nonspecific if it is not seen in a
basal cell distribution and is still supportive of a malignant diagnosis. More rarely, one can see
occasional cancer cells that are strongly positive for antibodies to high molecular weight cytokeratin,
yet as long as these cells are not in a basal cell distribution, these cells represent aberrant
expression of the antigen in cancer. The use of high molecular weight cytokeratin when presented with
only a few atypical glands is not as diagnostic, since benign glands may not show uniform positivity with
this marker. Negative staining for high molecular weight cytokeratin is most diagnostic when more than a
few glands are present for evaluation and the morphologic features are very suspicious for carcinoma.
Rather than used to establish a diagnosis of cancer, we use the high molecular weight cytokeratin stain
to help verify a suspicious focus as cancer. If we favor although are not sure that a focus is benign
and the stain is negative, we will diagnose it as atypical rather than as cancer.
AMACR, a cytoplasmic protein also known as P504S, has recently been recognized as a tumor marker for
several cancers and although its role in prostatic carcinogenesis is unclear, several recent studies have
shown that AMACR expression is significantly up-regulated in prostate cancer
immunohistochemistry, the majority of prostate cancers (80%-100%) are positive for AMACR although a high
proportion of high grade prostatic intraepithelial neoplasia (PIN), some foci of adenosis, and also some
entirely benign glands have also been reported positive for this marker. As negative staining for basal
cell markers especially in a small focus of atypical glands is not necessarily diagnostic of prostate
cancer, positive staining for AMACR can increase the level of confidence in establishing a definitive
malignant diagnosis. Although ours and previous findings confirm that AMACR is an excellent marker for
the detection and diagnosis of prostate adenocarcinoma, caution should be applied in interpreting the
immunohistochemical results. Different sensitivity and specificity have been reported among different
groups. These are likely the result of the use of different antibodies, different tissue fixation, or
other subtle differences in tissue preparation and methods of immunohistochemical staining. Negative
AMACR staining in small suspicious glands is not necessarily sufficient for a benign diagnosis. In
addition, we have demonstrated that pseudohyperplastic adenocarcinoma and atrophic adenocarcinoma of the
prostate, variants of prostate cancer that are particularly difficult to diagnose, are less frequently
(62%-77%) positive for AMACR.
In general, the use of immunohistochemistry for prostate-specific antigen (PSA) and
prostate-specific acid phosphatase (PSAP) is not helpful in distinguishing benign versus malignant
glandular lesions of the prostate since both conditions are positive. One of the few instances in which
immunohistochemistry for PSAP and PSA is useful is when one sees crushed cellular material suspicious for
cancer in and around a nerve or diffusely infiltrating the stroma as individual cells. In these cases
the identification of the atypical cells as being of prostatic epithelial origin by their
immunoreactivity with PSA or PSAP can establish a diagnosis of carcinoma of the prostate.
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