Most common cancer and 2nd leading cause of cancer-related death in men.
Common in elderly, incidence increases with age, 70% affected by 70 years.
~50% harbor TMPRSS2 and ETS gene fusion; TMPRSS2:ERG (~90%).
75-80% occurs in peripheral zone, 15-25% in transition zone.
Gross: solid yellow or gray-white areas, although often tumor is not grossly discernible.
Spectrum of architectures (that is why we have the unique Gleason grading system, see later).
Diagnosis of well-differentiated tumors (well formed glands or grade 3) is most difficult due to overlap with benign glands and lesions.
Diagnosed by architectural, nuclear, cytoplasmic, and intraluminal features; some may be seen in benign glands (except pathognomonic features listed below).
Malignant gland should lack basal cells!
Large nuclei with prominent nucleoli that can be multiple.
Cytoplasmic tincture different to adjacent benign glands.
Lumen may have blue mucin (image A), crystalloids (bright eosinophilic rhomboid to prismatic structures, seen in ~40% cancer) (image B) and amorphous eosinophilic secretions.
Pathognomonic features: glomerulation(looks like glomerulus), collagenous micronodules (mucinous fibroplasia) and circumferential perineural(image C) or intraneural invasion(benign glands can next to nerve).
Immunohistochemistry: NO basal cells (HMWK- and p63-) and over expresses AMACR, in contrast to benign glands (image D).
Metastasis often to bone (osteoblastic), lung and pelvic (obturator) lymph nodes.
PSA or PSAP immunostain helpful to confirm prostatic origin.