PROSTATE CANCER PATHOLOGY

Prostate cancer pathology: adenocarcinoma
By far the most common (>95%) prostatic malignancy is adenocarcinoma carcinoma of the acinar or ductal epithelium. The basal cell layer is absent and the basement membrane is breached by the malignant cells which invade into the prostatic fibromuscular stroma. Macroscopically, they tend to be hard and white, though a soft mucin-producing variety exists. The prostatic urethra, ducts, or stroma may be invaded by transitional cell carcinoma of the bladder (see Fig. 7.6 and p.262). Prostatic sarcomas, most common of which is the rhabdomyosarcoma, are rare but may be seen in childhood. Secondary deposits (metastases) from other sites are rare.

Adenocarcinoma of the prostate
Most (75%) of adenocarcinomas occur in the peripheral zone of the prostate and most (85%) are multifocal. 20% appear to arise from the transition zones and 5% from the embryologically distinct central zone. The tumour spreads locally through the poorly formed prostatic capsule (this is absent at the apex and base of the gland) into surrounding tissue, at which time it is termed  locally advanced . Hence, the disease may involve the urethral sphincter, corpora of the penis, seminal vesicles, and trigone of the bladder including the distal ureters. Local spread is often along the course of autonomic nerves (perineural invasion). The most frequent sites of metastasis are lymph nodes and bone, although lung, liver, testis, and brain are not uncommon. Bone metastases are characteristically sclerotic, rarely lytic. The axial skeleton (spine and pelvis) are most commonly affected, followed by the proximal long bones, ribs, clavicles, and the skull.
Prostate cancer is a complex disease, exhibiting numerous genetic abnormalities, increasing with stage and grade. Frequent changes include:
- somatic loss of alleles on chromosomes 8, 16, and 18
- inactivation of tumour suppressor genes PTEN (chromosome 10q) and p53 (chromosome 17p)
- activation of c-myc and bcl-2 protooncogenes.

Prostate cancer pathology: possible premalignant lesions
Two histological lesions are currently regarded as either premalignant or perimalignant prostatic intraepithelial neoplasia and atypical small acinar proliferation.

Prostatic intraepithelial neoplasia (PIN)
PIN consists of architecturally benign prostatic acini and ducts lined by cytologically atypical cells. The basal cell layer is present, although the basement membrane may be fragmented. PIN was formerly known as ductal dysplasia or reported by pathologists as  suspicious for cancer . PIN was classified into low-grade (mild) and high-grade (moderate to severe) forms, based on the presence of prominent nucleoli. Subsequently, pathologists have agreed to report only high-grade PIN, since low-grade PIN reporting is very subjective and has no prognostic value. On the other hand, high-grade PIN is believed to be a precursor for intermediate or high-grade prostate cancer and its finding in sextant peripheral zone prostate biopsies carries a 30 - 40% prediction of prostate cancer at subsequent biopsy. However, with the widespread use of more extensive biopsy protocols, the significance of isolated high-grade PIN has become less clear.
High-grade PIN is reported in 5 - 10% of prostate needle biopsies. It does not appear to affect the serum PSA value. The site of the PIN is not indicative of the site of subsequently diagnosed cancer, nor is PIN always present in a prostate containing cancer. Currently, it is recommended that repeat systematic biopsies should be performed if isolated high-grade PIN is reported on needle biopsy or TURP.

Atypical small acinar proliferation (ASAP)
This is another histopathological prostatic lesion that pathologists report on needle biopsies as  suspicious for cancer . The acini are small, lined with cytologically abnormal epithelial cells. The columnar cells have prominent nuclei containing nucleoli, while the basal layer may be focally absent. The basement membrane is intact. As with PIN, studies have shown ASAP in needle biopsy predicts cancer at subsequent biopsy in over 40% of cases. Currently, it is recommended that repeat systematic biopsies should be performed if isolated ASAP is reported on needle biopsy or TURP.