Non-Cancerous Findings on Prostate Biopsy

Men with an elevated PSA often undergo prostate biopsy to look for prostate cancer.  Many times, the prostate biopsy does not demonstrate cancer but gives another diagnosis including:

• High-grade prostatic intraepithelial neoplasia (HGPIN)
• Proliferative Inflammatory Atrophy (PIA)
• Acute or Chronic Inflammation
• Atypia, or Atypical small acinar proliferation (ASAP)

None of these diagnoses are cancerous, however valuable information can be gained by each diagnosis, in some cases implications regarding the future risk of cancer.  Here we review the implications of benign diagnoses on prostate biopsy.

High-grade prostatic intraepithelial neoplasia (HGPIN)

HGPIN currently is the only recognized premalignant precursor to prostatic adenocarcinoma.  Under the microscope, HGPIN appears much like prostate cancer with atypical cells containing prominent nucleoli.  However, the main histologic difference between prostate cancer and HGPIN is that HGPIN has a preserved basal cell layer in the glandular architecture.  Morphologic and molecular data also support HGPIN as a precursor to prostatic carcinoma.[1,2]  Morphologically,  prostate cancer is observed budding off areas of HGPIN.[1,2]  Molecularly, HGPIN and prostate cancer share a number of molecular genetic and chromosomal abnormalities that support a common evolution.[3]

HGPIN appears in prostate biopsies in 5-8% of men and concomitantly with prostate cancer at radical prostatectomy in up to 80% of cases.[4,5]  HGPIN can be seen as early as the 3rd decade of life, preceding the age of prostate cancer diagnosis by at least 10 years.  However, the risk of detecting subsequent prostate cancer is the range of 22-24% - which is not clinically or statistically different from the risk of finding prostate cancer after a previous negative biopsy in men with an elevated PSA.[4,6]  The amount of HGPIN found may influence the detection of subsequent prostate cancer.  In men with 3 or greater cores of HGPIN, the risk of prostate cancer is significantly higher.[7-11]  Therefore, men with 1-2 cores of HGPIN should be followed with routine PSA and digital rectal examination with repeat biopsy within 3 years or as indicated sooner; and men with 3 or more cores of HGPIN undergo repeat biopsy within 12-18 months of the initial diagnosis.

Proliferative Inflammatory Atrophy (PIA) and Inflammation

Occasionally prostate biopsies will demonstrate inflammatory cells and PIA.  Atrophy occurs in the setting of inflammation and has been suggested relate to prostate cancer as early as the 1950's.[12,13]  PIA contains atrophic epithelial cells that appear to be regenerating in response to cellular damage.  The cellular damage is mediated by inflammatory cell infiltrates.[14]  PIA will occasionally merge directly with HGPIN and morphological transitions between PIA, HGPIN and prostate cancer have been described.[15,16]  However, other than its relationship to HGPIN and cancer, no association between PIA on biopsy on subsequent prostate cancer is noted.

Atypical small acinar proliferation (ASAP)

ASAP or atypia does not have specific histologic, morphologic or molecular features that align it with prostate cancer like HGPIN.  Rather, ASAP is a diagnosis of exclusion for glands within the prostate that do not meet criteria for prostate cancer but appear suspicious for the diagnosis.  The incidence of ASAP on initial prostate biopsy is 2-3%.  However, different from HGPIN, the risk of subsequent prostate cancer on repeat biopsy is as high as 60%.[17-21]  Therefore men with ASAP should undergo repeat biopsy within 6-12 months due to the high likelihood of harboring undetected prostate cancer.

Summary

• HGPIN is a premalignant prostate cancer lesion.  It is present in 5-8% of biopsies.
• If 1-2 cores of HGPIN, repeat PSA and DRE annually, consider repeat biopsy within 3 years or sooner if clinically indicated.
• If 3 or mores cores of HGPIN are found at biopsy, a repeat biopsy should be performed within 12-18 months.
• PIA is found with inflammation and in the spectrum of HGPIN and prostate cancer.  There is no evidence that inflammation or PIA on biopsy is indicative of prostate cancer on subsequent biopsy.
• ASAP or atypia is found in 2-3% of prostate biopsies and highly correlated with prostate cancer on subsequent biopsy; men with ASAP should be biopsied within 6-12 months of an initial diagnosis. 

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