Prostatic carcinoma
Core biopsies

Author: Kenneth Iczkowski, M.D. (see Authors page)

Revised: 8 August 2016, last major update May 2015

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Core biopsies [title] prostate
Cite this page: Core biopsies. website. Accessed May 27th, 2017.
Definition / general
  • Sextant (6) samples from selected portions of prostate via a spring-loaded 18 gauge biopsy has a false negative rate of 12% due to sampling error
  • Currently, up to 18 samples are now taken
  • However, as of 2014, Medicaid has limited the number of biopsy sites to 9 for full 88305 reimbursement, so some practices are capping the number of biopsies at 9 (AUA - New Codes for Prostate Pathology Services)
  • 25% of tumor bearing specimens contain only a small focus of carcinoma
  • Transrectal biopsies are more accurate than transperineal biopsies
  • Gleason score in biopsy correlates with that in prostatectomy (same: 58%, +/- 1 unit: 92%)
  • More errors occur with Gleason scores 5 or 6, which tend to underestimate the prostatectomy Gleason score (Am J Surg Pathol 1997;21:566)
  • Tumor seeding of needle tract is a rare complication of perineal needle biopsy, more likely with poorly differentiated carcinomas, less common with transrectal biopsy
  • Findings at 12 core transrectal ultrasound-guided prostate needle biopsy plus preoperative PSA predict advanced local disease at prostatectomy (Am J Clin Pathol 2012;137:739)

  • Core submission and processing:
    • Method of gross submission of prostate biopsies is crucial
    • Most laboratories submit up to 2 cores (a core being defined as at least 1 cm length) per cassette regardless of the number of cores per vial
      • If a vial contains a dozen cores or core fragments, submission of all the material in one cassette leads to almost uninterpretable slides because of specimen crossing over and fragmentation (Ann Diagn Pathol 2014;18:301, see Fig. 1 below)
      • Having no more than 2 full cores per cassette minimizes the tissue that falls out of the plane of section
    • However, some laboratories are able to submit 3 cores (from 3 different vials) in one cassette using differential inking to indicate sites of the cores
      • Great care must be taken with this approach, but the diagnostic yield can be comparable to 1 specimen per cassette (Ann Diagn Pathol 2013;17:357)
      • This has some advantages in reducing the number of slides for the pathologist to look at, and reduces processing costs and storage space
    • Three levels are recommended (Arch Pathol Lab Med 1998;122:833, Am J Clin Pathol 1997;107:26, Am J Surg Pathol 1999;23:257) for maximal detection of cancer
    • Additional levels may be useful if findings of atypical small acinar proliferation (ASAP), suspicious for but not diagnostic of malignancy (Am J Clin Pathol 1998;109:416)
    • Pathology review of core biopsies is recommended before radical prostatectomy is performed (Am J Surg Pathol 1996;20:851)
    • Biopsy is unsatisfactory if no prostatic glands or stroma are found; "stroma only" may indicate a stromal hyperplastic nodule and is satisfactory
    • Average of 23% of total length of a core is missed by a single histologic level
    • Preembedding cores using "stretch" method may yield more tumor/core, more cores with tumor, more cases with tumor, fewer atypical small acinar diagnoses, fewer cases with 3 mm or less of Gleason 6 or less cancer (Hum Pathol 2000;31:1102)
    • IN 2005, ISUP endorsed the concept that grading of prostate cancer on biopsy specimens and perhaps even in prostatectomy and TURP specimens begins at 3+3=6, with grades of 1 and 2 rarely if ever used (Am J Surg Pathol 2005;29:1228)

  • Use of second opinion:
    • Second opinion is advisable for patients whose diagnosis was made at an outside hospital (Int J Clin Exp Pathol 2011;4:468), and this is standard practice at NCI designated comprehensive cancer centers
    • Second opinion produces Gleason scores on biopsy that are significantly more predictive of radical prostatectomy findings than the outside diagnoses
    • The most important finding missed by outside pathologists is extraprostatic extension (EPE), which elevates the tumor stage from T2 to T3a (see Fig. 3 below)
      • In a cohort of 65 cases, 11 patients had EPE
      • In 5 of those 11 patients, the outside pathologists failed to comment on the presence of the EPE (Int J Clin Exp Pathol 2011;4:468)
    • Another finding that is easily missed is grade 5 prostate cancer (Urology 2012;79:178, see Fig. 4 below)
      • If there are single cells or clusters of cells without even the tiniest lumen formation, a component of Gleason grade 5 cancer should be diagnosed
      • It often forms the secondary part of the Gleason score, that is, 3+5 or 4+5
      • Gleason grade 5 cancer, however, may itself mimic inflammatory cells (see Fig. 5 below)
    • Intraductal prostate carcinoma (IDC) should be recognized
      • It consists of a cribriform to solid, large, often dilated gland space, bounded by basal cells, that contains cells with marked nuclear enlargement and atypia which exceeds the atypia in high grade prostatic intraepithelial neoplasia (see Fig. 6 below)
      • IDC almost always occurs with invasive carcinoma, and the invasive component is almost always high grade
      • However, IDC should be mentioned, whether isolated or associated with invasive carcinoma
    • Note that intra-observer agreement, even among expert urologic pathologists, is only mediocre, and there are certain findings that interfere with consensus (Ann Diagn Pathol 2014;18:333)
  • Photoessay of general principles: Ann Diagn Pathol 2014;18:301
  • Minimal cancer on biopsy is defined as <1 mm, but there is usually pathologically significant tumor at prostatectomy
  • Common morphologic features are nucleomegaly (96%), infiltrative growth pattern (88%), intraluminal secretions (78%), prominent nucleoli (64%), associated high grade PIN (40%), amphophilic cytoplasm (36%), hyperchromatic nuclei (30%), intraluminal crystalloids (22%)
  • Uncommon features are perineural invasion (2%), collagenous micronodules (2%), mitotic figures (2%) (Mod Pathol 1998;11:543)
  • Collagenous micronodules are nodular masses of paucicellular, eosinophilic, fibrillar stroma which impinge on acinar lumens (Arch Pathol Lab Med 1995;119:444)
  • Glomerulations are rounded epithelial tufts within glands reminiscent of renal glomeruli; are present in 5% of radical prostatectomy specimens (5-20% of each tumor) and 3% of needle biopsies with cancer (5-10% of each cancer); they are not observed in benign lesions (Hum Pathol 1998;29:543)
  • Reporting of prostate cancer should include: the fraction of biopsy cores or fragments that are involved by cancer, and either the percent of each involved core on the slide, or the length in millimeters of each involved core on the slide; for example:
    • Prostatic adenocarcinoma, Gleason 3+4 (score = 7) within 20% and 40% of two out of three core fragments, tumor lengths 3 mm and 5 mm
  • Perineural invasion and extraprostatic extension should be mentioned in the line diagnosis if present
    • If absent throughout the tumor, a comment at the conclusion of the line diagnoses should mention the absence of these findings
    • Caution should be taken with perineural invasion, as perineural impingement by benign acini can mimic invasion by cancer (see Fig. 2 below)
Prognostic factors
  • The fraction of cores involved by cancer should be stated
    • It is recommended to report the either the percentage or the length (millimeters) of each individual core involved by cancer (Am J Surg Pathol 2005;29:1228) since these strongly predict prostatectomy findings
    • Many laboratories and pathologists report both the percentage and the length, for example:
      • "Prostatic adenocarcinoma, Gleason 3+4 (score of 7) involving 20% and 30% of 2 out of 2 cores, tumor lengths 3 mm and 4 mm"
  • Each separately submitted vial gets its own line diagnosis
  • Whether perineural invasion and extraprostatic extension are present or absent can be stated as a comment at the end of the list of line diagnoses
Microscopic (histologic) description
  • Features suggestive of malignancy in a core are (malignant vs. benign specimens): prominent nucleoli (94% vs. 25%), marginated nucleoli (88% vs. 7%), multiple nucleoli (64% vs. 0%), blue-tinged mucinous secretions (52% vs. 0%), intraluminal crystalloids (41% vs. 1%), intraluminal amorphous eosinophilic material (87% vs. 2%), collagenous micronodules (2% vs. 0%), glomerulations (15% vs. 0%), perineural invasion (22% vs. 0%), retraction clefting (39% vs. 7%), and invasion of fat (1% vs. 0%) (Arch Pathol Lab Med 2002;126:554)
Microscopic (histologic) images

Images hosted on other servers:

Images courtesy of Dr. Kenneth Iczkowski:

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Too many cores or core fragments, Fig. 1

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Impingement of a
benign prostate
acinus by a nerve
twig, Fig. 2

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Extension of prostate cancer, Fig. 3

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Grade 5 prostate cancer, Fig. 4 & 5

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Intraductal carcinoma, Fig. 6

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Atypical small acinar proliferation,
Fig. 7

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Prostate basal cell cocktail plus P504S, Fig. 8

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Atypical adenomatous hyperplasia,
Fig. 9

Positive stains
  • Immunostains should be reserved for equivocal cases where conventional pathology is inconclusive (Int Urol Nephrol 2010;42:325)
  • Sensitive and specific for prostate carcinoma on needle biopsies, but not all ASAP cases can be resolved by immunostain cocktail (see Figs. 7 & 8 above)
  • Intervening levels 2 and 4 are often reserved for immunostains; 1, 3, and 5 are used for hematoxylin-eosin
  • One can also destain / restain needle biopsies and put original sections on coated slides (Hum Pathol 2000;31:1155)
  • Recommended to use cocktail with 34βE12 and p63 (Am J Surg Pathol 2003;27:365)
  • Recommended to use a combination of P504S and 34βE12 to diagnose limited prostatic adenocarcinoma (Am J Surg Pathol 2002;26:1169)
  • P504S stains some hyperplastic nodules and benign glands adjacent to transition zone carcinomas (Hum Pathol 2003;34:228)
  • P504S/p63 can be used as a single color cocktail to distinguish prostatic cancer involvement in seminal vesicles versus cancer mimickers because of the architectural complexity of the seminal vesicles and ejaculatory ducts (Arch Pathol Lab Med 2010;134:983)
Negative stains
  • High molecular weight cytokeratin (34βE12) and p63 detect basal cells, which are lacking in adenocarcinoma
  • Positive staining can identify benign mimickers of cancer including benign crowded glands, adenosis and atrophy, and occasionally differentiate high grade PIN vs. cancer
  • Diagnosis of prostatic adenocarcinoma with positive 34βE12 basal cell staining should be made with extreme caution, only if unequivocal cancer on H&E; when present, is usually patchy, may indicate outpouchings of high grade PIN (Am J Surg Pathol 2002;26:1151)
  • Note: A negative high molecular weight keratin is only diagnostic of adenocarcinoma if there is a high (90%) H&E suspicion of carcinoma, one must also see staining of obviously benign glands as internal control
  • Negative staining with P504S in suspicious foci does not necessarily indicate a benign diagnosis (Am J Surg Pathol 2002;26:1169)
Differential diagnosis