Mimics in Surgical Pathology
Dr. Sunil Lakani
Dr. Salam Al-Sam
Case 5 -
Sclerosing Adenosis of the Prostate
Hema Samaratunga FRCPA
Sullivan Nicolaides Pathology
Brisbane , Queensland , Australia
A 68-year-old male presented in July 2002 with an elevated PSA of 13.19 ng/ml (normal <4.5). His
serum PSA had been progressively increasing since 1997, when it was 4.5. He had some associated lower
urinary tract symptoms. Digital rectal examination (DRE) revealed a smooth prostate. On transrectal
ultrasound (TRUS), the transition zone was enlarged and the volume was estimated to be about 85 g. He
underwent a TRUS guided prostatic biopsy in August 2002, and this was reported as benign with chronic
prostatitis. He continued to have urinary symptoms and his PSA continued to climb and was up to 16.9 in
December 2004 when he underwent a repeat biopsy. This again showed no evidence of malignancy, but had
atrophy with acute inflammatory changes. He continued to have obstructive lower urinary tract symptoms
and presented for a TURP when 60 g of prostatic tissue was removed. This was reported as nodular
prostatic hypertrophy with Gleason score 3+4 = 7 prostatic adenocarcinoma involving
< 5% of the tissue. Post operatively, his urinary symptoms improved significantly and his PSA
reduced to 3.9. PSA was at about the same level when he was last seen in May 2005.
Case 5 - Figure 1
About 10 prostate chips displayed a small glandular proliferation. This formed expansile nodules,
many of which had a poorly demarcated margin. In some nodules, the margin appeared infiltrative,
extending in between collections of benign glands. Very small, very tightly crowded glands formed a
large part of the lesion. These were interspersed with larger glands of varying size and shape with some
branching, solid nests, cords and single cells. Some glands contained luminal blue mucin. The glandular
lining appeared to be a single cell layer with large cells containing abundant finely granular pale
eosinophilic cytoplasm. In comparison to those of typical benign glands, these glands had enlarged
nuclei with prominent nucleoli. Single cells and cords of cells had similar morphology, but some of
these were cuboidal to elongated cells with more eosinophilic cytoplasm. In some areas, a thin layer of
hyaline basement membrane material surrounded glands. The background stroma was cellular and partly
myxoid. Elsewhere in the gland, there was nodular prostatic hypertrophy.
Luminal secretion stained strongly positively with PAS + D and alcian blue. The stroma also showed
alcian blue positivity. Immunohistochemical staining revealed widespread strong reactivity for high
molecular weight cytokeratin showing an intact basal cell layer. Staining was seen in flattened cells in
a basal cell location around glands, in single cuboidal cells and some spindled cells.
Sclerosing adenosis of the prostate
Sclerosing adenosis of the prostate is a benign glandular proliferation first described in 1983, when
it was thought to represent an adenomatoid tumour. Prostatic acid phosphatase reactivity in
lesional cells was taken as evidence of prostatic origin of adenomatoid tumours and thought to confirm
the histogenetic heterogeneity of adenomatoid tumours. Since then, immunohistochemical confirmation of
presence of basal cells in the lesion has led to the recognition that this is a lesion analogous to
sclerosing adenosis of the breast. Due to its composition of small crowded glands, solid
nests and single cells and cytologic atypical features, it can closely mimic prostate cancer. In one
study, 10% of cases misdiagnosed as prostate cancer were cases of sclerosing adenosis.  In
spite of its worrisome features, it is benign with no malignant potential.  On follow up, no
cases have developed malignancy.
resence of widespread high molecular weight
cytokeratin positivity confirming presence of basal cells also supports the benign nature of the lesion,
as carcinoma usually lacks a basal cell layer. For these reasons, it is also not appropriate to use the
term "atypical" for these lesions as some have suggested.  It could lead to inappropriate
management, as there may be confusion with atypical small acinar proliferations, which need rebiopsy.
This lesion has also been labelled fibroepithelial nodules of the prostate,  and
pseudoadenomatoid tumour. 
This lesion is most commonly found in the transition zone, therefore appearing predominantly in TURP
and radical prostatectomy specimens. The prevalence of sclerosing adenosis in a study by Sakamoto et al
was 2%. This was in a series of cases including TURPs, and open and radical
prostatectomies. Grignon et al  studied a series of radical prostatectomy specimens and also
found an incidence of 2%. Sclerosing adenosis may rarely be sampled on needle biopsy. With increasing
needle biopsy sampling of the transition zone, it is likely that this lesion will be seen more commonly
in needle biopsies. The lesion usually appears incidentally in TURP specimens in patients who present
with urinary obstructive symptoms and is usually seen in older patients. It is not known whether
sclerosing adenosis contributes to symptoms or elevation of PSA above that caused by BPH in these
Usually only one or two small foci of sclerosing adenosis are seen in each case. Rarely, the lesion
can be multifocal and many prostate chips can be involved. Lesional size can vary from a few millimetres
to more than 1 cm. Typically, these are circumscribed nodular lesions composed of variably sized and
shaped, often compressed glands. These are accompanied by epithelial cells in small clusters or singly
embedded in a cellular, often myxoid stroma. Larger branching glands are commonly interspersed with
tightly crowded small glands, many of which appear to be lined by a single cell layer. Sometimes, small
crowded glands are seen merging with or budding off of the larger glands. In rare cases, lesions can
appear poorly circumscribed with an infiltrative looking periphery. However, lesional glands are not
seen interspersed with normal benign glands. Glandular lumina are usually empty or contain pale
eosinophilic secretions. In some cases, luminal blue mucin and even crystalloids can be seen. Usually,
cytologic atypia is minimal or absent, but in some cases can be moderate. Nucleoli are often visible but
small. In rare cases, nucleoli can be enlarged and prominent. The secretory cells have pale granular of
vacuolated cytoplasm. Occasional vacuolated cells can resemble signet ring cells. Other cuboidal to
fusiform cells surrounding glands or merging with stroma tend to have more eosinophilic cytoplasm. In
some cases, these cells resemble flattened basal cells. A thickened basement membrane is sometimes
apparent around glands and cell clusters. Stroma is usually myxoid and contains some collagen and
spindled cells resembling fibroblasts.
High molecular weight cytokeratin is strongly positive in a basal cell location, within clusters of
epithelial cells and spindle cells merging with stroma. These cells are also positive for muscle
specific actin and S-100 stains confirming myoepithelial characteristics. PSA and PAP staining is seen
within glandular luminal cells and morphologically similar epithelial cells found singly and in small
The most crucial differential diagnosis is obviously with carcinoma. Features including a
pseudoinfiltrative appearance of the glandular proliferation in some cases, tightly crowded small glands
lined by an apparent single cell layer, presence of single cells, cellular and nuclear enlargement and
prominent nucleoli suggest a cancer diagnosis. Luminal blue mucin and crystalloids that are typically
found in carcinoma can also suggest a cancer diagnosed. Differentiating this lesion from carcinoma
necessitates recognition of the morphological appearances of the lesion. The cellular myxoid stroma of
this lesion usually alerts to the correct diagnosis. Prostate cancer typically has normal appearing
fibromuscular prostatic stroma and a stromal reaction is often not apparent. In contrast, sclerosing
adenosis usually lacks stromal smooth muscle. However, the myxoid stromal appearance of sclerosing
adenosis may not be striking in some cases causing diagnostic difficulty. Presence of hyaline
eosinophilic basement membrane in some cases, also suggests sclerosing adenosis. This lesion, with
poorly formed glands and single cells mimics Gleason score 7 or 8 carcinoma which typically does not form
well- circumscribed nodular lesions or present in limited foci unlike most cases of sclerosing adenosis.
Glandular structures found in this lesion are similar to those of adenosis with small glands budding off
from larger branching glands. Although, prominent nucleoli can be seen in some cases, macronucleoli as
seen in some carcinomatous glands are not seen in sclerosing adenosis.
Diagnosis of sclerosing adenosis on needle biopsy can be problematic as the entire lesion is not
sampled and a nodular appearance may be difficult to appreciate.  At least one edge of the
lesion can be seen and this may be partially circumscribed. However, the margin can look infiltrative
causing concern. Glands that are compressed due to cellular stroma can appear infiltrative and if the
nodularity of the lesion is not appreciated in the needle biopsy, misdiagnosis can occur. The
distinctive myxoid appearing cellular stroma if present, and the double cell population of pale/ clear
cells and eosinophilic cells are features that help in the correct diagnosis. Usually, immunostaining is
not necessary for diagnosis. However, in difficult cases, positive staining for high molecular weight
cytokeratin, S-100 protein and muscle specific actin is useful as carcinoma is negative for these
Other differential diagnostic considerations include adenosis, nephrogenic adenoma (metaplasia),
adenomatoid tumour, mesonephric hyperplasia and verumontanum mucosal gland hyperplasia. Presence of a
relatively circumscribed glandular proliferation composed of small crowded glands interspersed with
larger branching glands, cellular and nuclear enlargement and sometimes prominent nucleoli are also
features seen in adenosis. However, in adenosis, there is no stromal sclerosis.
Nephrogenic adenoma or metaplasia is another proliferative lesion of the prostate that can
superficially mimic sclerosing adenosis and prostate cancer. These lesions are composed of small round
to oval, sometime cystic or solid tubules. These lesions involve the prostatic parenchyma, but often
involve the lamina propria of the prostatic urethra and can have a papillary component. Tubules are
lined by a single layer of cuboidal, flattened or hobnailed cells with clear or eosinophilic cytoplasm.
Similar to sclerosing adenosis, some cases display prominent nucleoli. Unlike sclerosing adenosis, these
lesions have oedematous and vascularized stroma and stromal hypercellularity and myxoid stroma are not
features. Unlike sclerosing adenosis, these lesions are negative for PSA and PAP, but some cases display
focal reactivity for high molecular weight keratin. These lesions can be racemase positive and high
molecular weight cytokeratin negative. For this reason it can be mistaken carcinoma, unless the
diagnosis is made on H&E stains and PSA negativity is demonstrated. 
There is a superficial resemblance to adenomatoid tumour in some cases. However, the glandular
component is clearly prostatic epithelial with numerous PSA and PAP positive cells and not mesothelial as
in adenomatoid tumour. Mesonephric remnant hyperplasia is also characterised by a proliferation of
single layered tubules. However, in contrast to sclerosing adenosis, they have a lobular arrangement and
eosinophilic colloid-like material. Verumontanum mucosal gland hyperplasia is characterised by a small
glandular proliferation with "back-to-back" microacini lined by bland cuboidal columnar cells with
underlying basal cells. This lesion occurs near the verumontanum and adjacent prostatic urethra. No
crystalloids or intra-luminal mucin is seen but intra-luminal corpora amylacea are numerous.
The initiating event and pathogenesis of sclerosing adenosis is uncertain. It is thought to involve
mesenchymal induction of epithelial cell proliferation, possibly as a result of tissue
injury.  sclerosing adenosis has been noted within hyperplastic nodules and in association
with basal cell hyperplasia  with which it shares some histochemical and immunohistochemical
features. Normal basal cells of the prostate do not show myoepithelial differentiation, unlike
sclerosing adenosis in which basal cells display ultrastructural and immunohistochemical evidence of
Basal cell myoepithelial characteristics have also been
shown in basal cell hyperplasia.
Since this lesion has many features of adenosis, it has
also been suggested that sclerosing adenosis represents a focus at adenosis that for some reason has
undergone stromal sclerosis.
In conclusion, sclerosing adenosis is a benign glandular proliferation involving an interplay of
transformed basal cells with myoepithelial characteristics, secretory epithelial cells and cellular
myxoid stroma with fibroblasts. Knowledge of the morphological spectrum of this lesion should prevent
misdiagnosis as cancer.
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