PATHOLOGY

Prostate Needle Biopsies Containing Prostatic Intraepithelial Neoplasia or Atypical Foci Suspicious For Carcinoma: Implications for Patient Care
Epstein JI, Herawi M
Department of Pathology, The Johns Hopkins University School of Medicine, The James Brady Urological Institute, The Johns Hospital, Baltimore, Maryland, USA
J Urol. 2006; 175 (3 Pt 1): 820-34

• Purpose: We identified information critical for patient treatment on prostate needle biopsies diagnosed with prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma.
• Materials and Methods: A search was performed using the MEDLINE database and referenced lists of relevant studies to obtain articles addressing the significance of finding PIN or atypical foci suspicious for carcinoma on needle biopsy.
• Results: There were certain results concerning PIN. 1) Low grade PIN should not be documented in pathology reports due to poor interobserver reproducibility and a relatively low risk of cancer following re-biopsy. 2) The expected incidence of HGPIN on needle biopsy is between 5% and 8%. 3) Although the diagnosis of HGPIN is subjective, interobserver reproducibility for its diagnosis is fairly high among urological pathologists, and yet only moderate among pathologists without special expertise in prostate pathology. 4) The median risk recorded in the literature for cancer following the diagnosis of HGPIN on needle biopsy is 24.1%, which is not much higher than the risk reported in the literature for repeat biopsy following a benign diagnosis. 5) The majority of publications that compared the risk of cancer in the same study following a needle biopsy diagnosis of HGPIN to the risk of cancer following a benign diagnosis on needle biopsy show no differences between the 2 groups. 6) Clinical and pathological parameters do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. 7) A major factor contributing to the decreased incidence of cancer following a diagnosis of HGPIN on needle biopsy in the contemporary era is related to increased needle biopsy core sampling, which detects many associated cancers on initial biopsy, such that re-biopsy, even with good sampling, does not detect many additional cancers. 8) It is recommended that men do not need routine repeat needle biopsy within the first year following the diagnosis of HGPIN, while further studies are needed to confirm whether routine repeat biopsies should be performed several years following a HGPIN diagnosis on needle biopsy. There were certain results concerning atypical glands suspicious for carcinoma. 1) An average of 5% of needle biopsy pathology reports are diagnosed as atypical glands suspicious for carcinoma. 2) Cases diagnosed as atypical have the highest likelihood of being changed upon expert review and urologists should consider sending such cases for consultation in an attempt to resolve the diagnosis as definitively benign or malignant before subjecting the patient to repeat biopsy. 3) Ancillary techniques using basal cell markers and AMACR (alpha-methyl-acyl-coenzyme A racemase) can decrease the number of atypical diagnoses, and yet one must use these techniques with caution since there are numerous false-positive and false-negative results. 4) The average risk of cancer following an atypical diagnosis is approximately 40%. 5) Clinical and pathological parameters do not help predict which men with an atypical diagnosis have cancer on repeat biopsy. 6) Repeat biopsy should include increased sampling of the initial atypical site, and adjacent ipsilateral and contralateral sites with routine sampling of all sextant sites. Therefore, it is critical for urologists to submit needle biopsy specimens in a manner in which the sextant location of each core can be determined. 7) All men with an atypical diagnosis need re-biopsy within 3 to 6 months.
• Conclusions: It is critical for urologists to distinguish between a diagnosis of HGPIN and that of atypical foci suspicious for cancer on needle biopsy. These 2 entities indicate different risks of carcinoma on re-biopsy and different recommendations for followup.
  
  
• Editorial Comment
  This is an excellent review of two important diagnoses on needle prostatic biopsies. Urologists should clearly distinguish these two pathologic conditions. High-grade prostatic intraepithelial neoplasia (high-grade PIN) is diagnosed whenever acinar cells show nucleomegaly and conspicuous nucleoli. This finding is indistinguishable from prostate cancer, however, in high-grade PIN, there is no acinar architectural disarrangement and, very important, basal cells are present. High-grade PIN corresponds to grade 2 or 3 prostatic intraepithelial neoplasia. Low-grade PIN corresponds to grade 1 and should not be reported by the pathologist due to poor interobserver reproducibility and a relatively low risk of cancer following re-biopsy. On the other hand, high-grade PIN is associated with a moderate risk of cancer following re-biopsy, however, due to an increased needle biopsy core sampling, which detects many associated cancers on initial biopsy, there is a decreased incidence of cancer following a diagnosis of high-grade PIN. Due to these facts, it is recommended that men do not need routine repeat needle biopsy within the first year following the diagnosis of high-grade PIN.
  Atypical foci suspicious for carcinoma are a completely different condition that urologists should not interpret as high-grade PIN, adenosis, or any other pathologic entity. It refers to a condition in which the pathologist is not able to make a diagnosis of adenocarcinoma with confidence. This happens in 3 main conditions: 1. the suspicious focus is very small; 2. the focus disappears in further sectioning of the paraffin block; and, 3. absence of cytologic criteria for the diagnosis of adenocarcinoma (1). Atypical focus suspicious for carcinoma was formerly known as ASAP (atypical small acinar proliferation). This term should not be used because may be erroneously interpreted by the urologist as a pathologic entity such as high-grade PIN, adenosis or any other one (2). Furthermore, not all suspicious foci for carcinoma show small acini; large acini may also be suspicious.
  Differently from high-grade PIN, atypical foci suspicious for carcinoma have a high risk of cancer on a repeat biopsy. All men with a pathology report “suspicious but not diagnostic for adenocarcinoma” need re-biopsy within 3 to 6 months. Repeat biopsy should include increasing sampling from the suspicious site. This is very important and emphasizes the need for properly identifying the cores from the different regions biopsied, which must be sent in separate containers to the pathology laboratory.

References
1. Iczkowski KA, MacLennan GT, Bostwick DG: Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases. Am J Surg Pathol. 1997; 21: 1489-95.
2. Amin M, Boccon-Gibod L, Egevad L, Epstein JI, Humphrey PA, Mikuz G, t al.: Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens. Scand J Urol Nephrol Suppl. 2005; 216: 20-33.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil