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Page 456 Julka et al. J Transl Genet Genom 2020;4:455-63 I http://dx.doi.org/10.20517/jtgg.2020.46

of clinical outcome but also demonstrate the rational selection of a regimen as a viable option for such a clinically
challenging disease.

Keywords: Adenoid cystic carcinoma, prostate cancer, chemotherapy, degarelix

INTRODUCTION
Prostate cancer is the most commonly diagnosed malignancy in men and the second leading cause of
[1,2]
cancer death in Western nations . The pathology of prostate cancer varies with classical adenocarcinoma
being the most common histological variant. Small-cell, colloid, mesenchymal and metastatic tumors are
[3-5]
the other histological variants . However, Adenoid cystic carcinoma (ACC) is an unusual histological
[6]
variant of prostatic carcinoma, that accounts for less than 0.01% cases . Here, we describe the clinical
features, morphological spectrum, immunohistochemical (IHC) findings and management option for this
unusual subtype of prostatic carcinoma.

Histological features and pathological findings of ACC
The prostatic epithelium in humans is composed of three major cell types including the secretory epithelial,
[7]
neuroendocrine and basal cells with the predominance of the secretory epithelial cells . These are tall
columnar cells containing secretory granules and enzymes that stain for acid phosphatase and prostate-
specific antigen (PSA), commonly referred to as glandular epithelium. The neuroendocrine cells that
express neuroendocrine markers are present in significant numbers, and the small, round basal cells with
little cytoplasm and large irregular nuclei are present in the normal prostate gland. These cells express
keratin (types 4, 5 and 6)and are referred to as pluripotent cells with stem cell-like functions .

[8]
ACC of the prostate is derived from basal cells (the stem cell compartment of the epithelium) instead of
[9]
epithelial cells of the ducts and acini . The tumor is whitish and comprised of ill-defined, infiltrative edges
with involvement of transition and peripheral zones . The tumor can have either a predominant basaloid
[10]
pattern or a cystically dilated acini with cells arranged in cribriform spaces surrounding a eosinophilic-
hyaline basement membrane. The nuclei may be hyperchromatic or micro-vacuolated with angulated
nuclear contours. Extensive perineural invasion, extraprostatic extension and desmoplastic or myxoid
alterations of the stroma have been described for the tumor .
[11]
IHC assessment of ACC exhibits high-molecular-weight keratin (clone 34βE12) and ytokeratin 14 in the
majority of cases. Staining for cytokeratin 7 tends to mark an adluminal cell population and basal cell
cytokeratin (34βE12) staining is more frequent in peripheral cells. Staining for cytokeratin 20, p63, and
S100 protein has been described in adenoid cystic carcinoma of the prostate with inconsistent results.
Scattered chromogranin-positive cells have been reported in these tumors, and the tumor cells are
consistently negative for synaptophysin. Elevated Bcl-2 protein and Ki-67 index establishes the extent of
proliferation in prostate basal cell lesions. Staining for PSA is usually negative, but some positive cases
have been reported, especially in association with concomitant proliferative acinar adenocarcinoma.
Additionally, tumor cells have been reported as negative for calponin, smooth muscle myosin heavy chain,
and usually smooth muscle actin.

[12]
Ho et al. sequenced the entire exome or genome in 60 ACC samples and found mutations in cheomatin
state regulators (SMARCA2, CREBBP, KDM6A), MYB-NFIB translocations and MYB-associated genes as
well as recurrent mutations in the FGF/IGF/PI3K pathway. These findings suggest that ACC carcinogenesis
is associated with aberrant epigenetic regulation. Although, ACC originates from the basal cells of prostatic
ducts and acini, very little is known about the natural history of the disease owing to the rarity of these