Prostatic Intraepithelial Neoplasia

Prostatic intraepithelial neoplasia is a proliferation of atypical cells within pre-existing prostatic ducts and acini, with the basal cell layer preserved. Only the high grade form is clinically relevant. Low grade change is no longer reported.

High grade prostatic intraepithelial neoplasia is found in about 5 to 9% of needle biopsies, with a wider reported range of 1 to 20%.

It is regarded as a precursor lesion to some cancers, but isolated findings carry little added cancer risk with current sampling.

Pathophysiology. The lesion shows nuclear enlargement and prominent nucleoli in cells lining architecturally benign ducts. Basal cells are present, though patchy, which separates it from invasive cancer. Alpha-methylacyl-CoA racemase is often positive in both.

It is found in the peripheral zone and frequently near cancer. It appears at an earlier age than cancer, with a peak about 10 years before.

Cancer is found on repeat biopsy in about 20 to 30% of men with isolated lesions.

This is similar to the rate in men with a raised PSA and a first negative biopsy, and it is higher with multifocal disease (several cores), a rising PSA and limited initial sampling.

Intraductal carcinoma of the prostate is a different lesion. It is an invasive related, aggressive process, usually with high grade cancer.

No symptoms. The lesion does not cause a palpable abnormality and does not raise the PSA. It is found incidentally on biopsy or in a resection specimen. The clinical question is the indication for the biopsy, such as raised PSA, abnormal examination or suspicious MRI.

• Pathology: high grade prostatic intraepithelial neoplasia on needle biopsy, reported with the number of cores involved and any associated atypical glands. Immunostains for basal cells (p63, high-molecular-weight cytokeratin) show a patchy basal layer, and help exclude invasive cancer and intraductal carcinoma. Request a second uropathology opinion if unsure.
• PSA with age specific interpretation, and PSA density. Double the PSA for men taking a 5-alpha-reductase inhibitor for over 6 months.
• Multiparametric MRI with a suspicion score of 1 to 5, before any repeat biopsy.
• Adjunct tests when equivocal: prostate health index, kallikrein panel or urinary mRNA assays.
• Digital rectal examination.

Differential diagnosis.

• Prostatic adenocarcinoma
• Intraductal carcinoma of the prostate
• Atypical small acinar proliferation
• Partial atrophy and basal cell hyperplasia
• Atypical adenomatous hyperplasia
• Clear cell cribriform hyperplasia
• Urothelial carcinoma in situ involving prostatic ducts

• The lesion itself needs no treatment. Androgen deprivation, 5-alpha-reductase inhibitors, radiotherapy and surgery are not indicated, and chemoprevention is not advised.
• Isolated high grade lesion on an extensive biopsy (10 or more systematic cores or MRI-targeted sampling) with a normal MRI: no routine early repeat biopsy.
• Repeat biopsy within 12 months, using MRI-targeted and systematic cores, or sooner, for any of:
  • Limited initial sampling (under 10 cores) without MRI.
  • High grade lesion in several cores, or associated atypical glands.
  • A suspicious MRI lesion (score 3 to 5), a rising PSA, or an abnormal examination.
• Intraductal carcinoma on biopsy without invasive cancer: urgent MRI and repeat biopsy, then treatment by risk group.
• Finding in a transurethral resection or radical prostatectomy specimen: no further treatment.
• Lifestyle: weight control, exercise, and avoidance of smoking.

Monitoring. PSA and digital rectal examination every 12 months (every 6 months after a recent finding), with repeat MRI at 12 to 24 months or earlier when PSA rises or the examination changes. A rising PSA or new MRI lesion triggers repeat biopsy.

Referral and escalation. Refer to urology with uropathology review. Urgent referral for a rapidly rising PSA, a nodule, a high suspicion MRI lesion or intraductal carcinoma.