Interpretation of Prostate Needle Biopsies
Case 8 -
Benign Mimics of Prostate Cancer and Unusual Cancer Morphologies which Mimic Benign Conditions
Rajal Shah and Ming Zhou
A 50 year-old male patient with family history of prostate cancer
and PSA of 4.5 ng/ml. The patient underwent 12 core extended biopsy.
Adenocarcinoma of the prostate, Gleason score of 3+3=6
with pseudohyperplastic and foamy features involving 60% of one core.
Prostate Carcinomas Mimicking as Benign Process
As there are many benign conditions, which can mimic cancer, some carcinomas may resemble benign
prostate process due to their bland cytology or architectural pattern. A careful correlation of several
morphological features along with adjunctive immunohistochemistry stains is necessary to arrive at the
Table 1 Prostate Carcinomas mimicking benign lesions
|Histological pattern of cancer ||Benign condition they may mimic|
|Foamy carcinoma ||Benign/Cowper's glands or Xanthoma cells|
|Atrophic carcinoma ||Atrophy|
|Pseudohyperplastic carcinoma ||Hyperplasia or HGPIN|
|Low grade Gleason score 2-5 carcinomas ||Adenosis|
1) Foamy gland carcinoma
Foamy gland carcinoma is relatively common differentiation seen in needle biopsies. Conventional
carcinoma component is usually present. When it is well differentiated it may mimic benign glands such
as cowper's glands or xanthomatous infiltrate when it is of higher grade, due to its relatively bland
Key histological features:
1) Architectural pattern of crowded and/or infiltrative glands lined by abundant foamy cytoplasm. Due
to abundant foamy cytoplasm nucleus to cytoplasm ratio is very low, simulating benign condition. The
cytoplasm has similar appearance to seen in xanthoma cells; however it does not contain lipid, but rather
2) More typical features of adenocarcinoma such as nuclear enlargement and prominent nucleoli are
usually not conspicuous. Nuclei in the foamy gland cancer are typically rounder than oval nuclei seen in
3) Basal cell markers are typically negative and useful to provide an objective support to the
diagnosis. AMACR may demonstrate low sensitivity (68-70%) for this type of cancer
Despite the bland cytology of the foamy gland carcinoma, biologically they appear to behave as an
intermediate to aggressive cancers . Many of the foamy cancers, when associated with
non-foamy cancer represent Gleason pattern 4. In a recent Gleason grading consensus conference it was
adopted that foamy gland cancer should be graded based on its underlying architecture rather than foamy
2) Atrophic cancer
Pure atrophic cancer unassociated with hormonal therapy is rare in needle biopsy. The diagnosis can
be challenging and one has to rely on several important architectural and cytological features.
Key histological features helpful to differentiate it from benign atrophy
1) A truly infiltrative process with small atrophic glands situated between larger benign glands
2) Usual concomitant presence of conventional adenocarcinoma of the prostate is typically present and
very helpful to facilitate its recognition.
3) Greater cytological atypia than seen in typical benign atrophic glands. The cytoplasm is
relatively scant but still more than typical atrophic glands giving them less basophilic appearance then
conventional atrophic glands.
4) Basal cell markers are typically negative and similar to foamy cancers AMACR may demonstrate low
sensitivity for this cancer .
Most atrophic cancers represent Gleason pattern 3 carcinomas.
3) Pseudohyperplastic cancer
Pseudohyperplastic cancer typically resemble to hyperpastic/PIN glands due to glands of large size,
complex undulating architecture and papillary infolding.
Key histological features helpful to separate them from hyperplasia or HGPIN
1) Architectural pattern of numerous closely packed glands with complex and undulating architecture
and frequent papillary infolding. This diagnosis should be made with extreme caution when the focus of
concern is small as the diagnosis of HGPIN cannot be excluded with certainty. Immunohistochemical
markers may not be very helpful in this circumstance.
2) Nuclear features are usually typical of conventional adenocarcinoma with enlarged nuclei and
3) The cytoplasm is amphophilic with frequent amorphous secretions and blue mucin.
4) The conventional basal cell markers provide an objective support to the diagnosis. AMACR has lower
sensitivity for this type of cancer than conventional adenocarcinoma .
Majority of pseudohyperplastic carcinomas represent Gleason 3 pattern.
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