- 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.
- Histology:
- 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.