Protocol for the Examination of TURP and Enucleation

Specimens From Patients With Carcinoma of the Prostate Gland

Version: 4.1.0.0
Protocol Posting Date: June 2021
The use of this protocol is recommended for clinical care purposes but is not required for accreditation
purposes.

This protocol may be used for the following procedures AND tumor types:
Procedure Description

TURP and enucleation Includes specimens designated transurethral resection of the prostate (TURP),
specimens and enucleation specimens (simple or subtotal prostatectomy)

Tumor Type Description

Carcinoma Includes all adenocarcinomas and histologic variants, neuroendocrine

carcinomas, and others

The following should NOT be reported using this protocol:

Procedure
Biopsy (consider Prostate Biopsy protocol)
Radical Prostatectomy (consider Prostate Radical Prostatectomy protocol)
Tumor Type
Lymphoma (consider the Hodgkin or non-Hodgkin Lymphoma protocols)
Sarcoma (consider the Soft Tissue protocol)

Authors
Gladell P. Paner, MD*; John R. Srigley, MD*; Jason Pettus, MD; Giovanna Angela Giannico, MD; Joseph
Sirintrapun, MD; Lara R. Harik, MD.

With guidance from the CAP Cancer and CAP Pathology Electronic Reporting Committees.
* Denotes primary author.

© 2021 College of American Pathologists (CAP). All rights reserved. For Terms of Use please visit www.cap.org/cancerprotocols . 1
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Accreditation Requirements
The use of this case summary is recommended for clinical care purposes but is not required for
accreditation purposes. The core and conditional data elements are routinely reported. Non-core data
elements are indicated with a plus sign (+) to allow for reporting information that may be of clinical value. 

Summary of Changes

v 4.1.0.0

 General Reformatting
 Histologic Grade Updated
 New Section - IDC Incorporated into Grade
 Cribriform Glands Question Updated
 Tumor Quantitation Added
 Revised Margins Section
 Atypical Intraductal Proliferation (AIP) to added Additional Findings
 Equivocal response added to Periprostatic Fat Invasion and Seminal Vesicle Invasion 

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Reporting Template

Protocol Posting Date: June 2021

Select a single response unless otherwise indicated.

CASE SUMMARY: (PROSTATE GLAND: Transurethral Prostatic Resection (TURP), Enucleation

Specimen (Simple or Subtotal Prostatectomy))
Standard(s): AJCC-UICC 8
This template is recommended for reporting TURP specimens, but is not required for accreditation purposes.

SPECIMEN

Procedure (Note A)
___ Transurethral resection of the prostate (TURP)
___ Enucleation (simple or subtotal prostatectomy)
___ Other (specify): _________________
___ Not specified

TUMOR

Histologic Type (Note B) (select all that apply)

___ Acinar adenocarcinoma
___ Ductal adenocarcinoma
___ Small-cell neuroendocrine carcinoma
___ Isolated intraductal carcinoma
___ Other histologic type not listed (specify): _________________
___ Cannot be determined (explain): _________________
+Histologic Type Comment: _________________

Histologic Grade (Note C)

Grade
___ Not applicable: _________________
___ Cannot be assessed: _________________
___ Grade group 1 (Gleason Score 3 + 3 = 6)
___ Grade group 2 (Gleason Score 3 + 4 = 7)
Percentage of Pattern 4
___ Less than or equal to 5%
___ 6 - 10%
___ 11 - 20%
___ 21 - 30%
___ 31 - 40%
___ Greater than 40%
___ Grade group 3 (Gleason Score 4 + 3 = 7)
Percentage of Pattern 4
___ Less than 61%
___ 61 - 70%
___ 71 - 80%
___ 81 - 90%
___ Greater than 90%
___ Grade group 4 (Gleason Score 4 + 4 = 8)

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___ Grade group 4 (Gleason Score 3 + 5 = 8)

___ Grade group 4 (Gleason Score 5 + 3 = 8)
___ Grade group 5 (Gleason Score 4 + 5 = 9)
___ Grade group 5 (Gleason Score 5 + 4 = 9)
___ Grade group 5 (Gleason Score 5 + 5 = 10)

+If Gleason Score is Greater Than 7 Specify Percentage of Pattern 4: _________________ %

+If Gleason Score is Greater Than 7 Specify Percentage of Pattern 5: _________________ %

Intraductal Carcinoma (IDC) (Note D)

___ Not identified
___ Present
IDC Incorporated into Grade
___ Yes
___ No
___ Cannot be determined (explain): _________________

Cribriform Glands (applicable to Gleason score 7 or 8 cancer only)

___ Not applicable
___ Not identified
___ Present
___ Cannot be determined (explain): _________________

Treatment Effect (select all that apply)

___ No known presurgical therapy
___ Not identified
___ Radiation therapy effect present: _________________
___ Hormonal therapy effect present: _________________
___ Other therapy effect(s) present (specify): _________________
___ Cannot be determined: _________________

TUMOR QUANTITATION (Note E)

Tumor Quantitation
___ For TURP Specimens
Estimated Percentage of Prostate Involved by Tumor
___ Less than 1%
___ 1 - 5%
___ 6 - 10%
___ 11 - 20%
___ 21 - 30%
___ 31 - 40%
___ 41 - 50%
___ 51 - 60%
___ 61 - 70%
___ 71 - 80%
___ 81 - 90%
___ Greater than 90%
___ Cannot be determined (explain): _________________
+Number of Positive Chips: _________________

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+Total Number of Chips: _________________

___ For Enucleation and Other Specimens

Greatest Dimension of Dominant Nodule in Millimeters (mm) (if present): _____________ mm

+Additional Dimension of Dominant Nodule in Millimeters (mm): ____ x ____ mm

Estimated Percentage of Prostatic Tissue Involved by Tumor: _________________ %

Periprostatic Fat Invasion (report if identified in specimen)

___ Not identified
___ Present
___ Equivocal (explain): _________________
___ Cannot be determined (explain): _________________

Seminal Vesicle Invasion (report if identified in specimen)

___ Not identified
___ Present
___ Equivocal (explain): _________________
___ Cannot be determined (explain): _________________

+Lymphovascular Invasion
___ Not identified
___ Present
___ Cannot be determined: _________________

+Perineural Invasion (Note F)

___ Not identified
___ Present

ADDITIONAL FINDINGS

+Additional Findings (select all that apply)

___ None identified
___ Atypical intraductal proliferation (AIP)
___ High-grade prostatic intraepithelial neoplasia (PIN)
___ Atypical adenomatous hyperplasia (adenosis)
___ Nodular prostatic hyperplasia
___ Inflammation (specify type): _________________
___ Other (specify): _________________

COMMENTS

Comment(s): _________________

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Explanatory Notes

A. Submission of Tissue for Microscopic Evaluation in Transurethral Resection

Transurethral resection specimens that weigh 12 grams or less should be submitted in their entirety. 1 For
specimens that weigh more than 12 g, the initial 12 g are submitted, and 1 cassette may be submitted for
every additional 5 g of remaining tissue.2

In general, random chips are submitted; however, if some chips are firmer or have a yellow or orange-
yellow appearance, they should be submitted preferentially.

If an unsuspected carcinoma is found in tissue submitted, and it involves 5% or less of the tissue
examined, the remaining tissue may be submitted for microscopic examination, especially in younger
patients.3 Involvement in 5% or less of the tissue is considered as T1a, whereas involvement in greater
than 5% is considered as T1b.4
 

References
1. Humphrey PA, Walther PJ. Adenocarcinoma of the prostate, I: sampling considerations. Am J
Clin Pathol. 1993;99:746-759.
2. Trpkov K, Thompson J, Kulaga A, Yilmaz A. How much tissue sampling is required when minimal
prostate carcinoma is identified on transurethral resection? Arch Path Lab Med.
2008;132(8):1313-1316.
3. Paner GP, Magi-Galluzzi C, Amin MB, Srigley JR: Adenocarcinoma of the prostate. In: Amin MB,
Grignon DJ, Srigley JR, Eble JN,eds. Urological Pathology. Philadelphia, PA: Lippincott William &
Wilkins; 2014:559-673.
4. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York, NY:
Springer; 2017.

B. Histologic Type
This protocol applies only to invasive adenocarcinomas of the prostate gland. 1 Carcinomas other than
adenocarcinoma are exceptionally uncommon, accounting for less than 1% of prostatic tumors. The
protocol does not apply to pure squamous cell carcinoma, basal cell carcinoma, urothelial carcinoma,
small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma. If these rare subtypes of
carcinoma, however, are mixed with acinar type adenocarcinoma, the protocol may be used.

Some adenocarcinoma variants have percentage cut-offs to render their diagnosis. Since examination of
the entire tumor may not be amenable in TURP, a descriptive approach in their diagnosis should also be
considered (e.g. adenocarcinoma with mucinous features, adenocarcinoma with signet ring-like cell
features).  

References
1. Humphrey P, Amin MB, Berney D, Billis A, et al. Acinar adenocarcinoma. In: Moch H, Humphrey
PA, Ulbright T, Reuter VE, eds. Pathology and Genetics: Tumors of the Urinary System and Male
Genital Organs. 4th edition. WHO Classification of Tumors. Zurich, Switzerland: WHO Press;
2015:3-28.

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C. Histologic Grade

Gleason Score
The Gleason grading system is recommended for use in all prostatic specimens containing
adenocarcinoma, with the exception of those showing treatment effects, usually in the setting of androgen
deprivation and radiation therapy.1,2,3,4,5,6,7,8,9 Readers are referred to the recommendations of three ISUP
consensus conferences and the GUPS position paper dealing with the contemporary usage of the
Gleason system (also see Figure 1).4,5,6,7

The Gleason score is the sum of the primary (most predominant in terms of surface area of involvement)
Gleason grade and the secondary (second most predominant) Gleason grade. Where no secondary
Gleason grade exists, the primary Gleason grade is doubled to determine a Gleason score. The primary
and secondary grades should be reported in addition to the Gleason score, that is, Gleason score 7(3+4)
or 7(3+4). In TURP or enucleation specimens, Gleason score is the sum of the primary (most
predominant) Gleason grade and highest Gleason grade.

Figure 1. 2015 modified ISUP Gleason schematic diagram.5

In TURP specimens, with a minor secondary component (less than 5% of tumor) and where the
secondary component is of higher grade, the latter should be reported. For instance, a case showing
more than 95% Gleason pattern 3 and less than 5% Gleason pattern 4 should be reported as Gleason
score 7(3+4). Conversely, if a minor secondary pattern is of lower grade, it need not be reported. For
instance, where there is greater than 95% Gleason pattern 4 and less than 5% Gleason pattern 3, the
score should be reported as Gleason score 8(4+4). 

In TURP specimens where more than 2 patterns are present, and the worst grade is neither the
predominant nor the secondary grade, the predominant and highest grade should be chosen to arrive at a
score (eg, 75% pattern 3, 20-25% pattern 4, less than 5% pattern 5 is scored as 3+5=8). 

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Another recommendation is that the percentage of pattern 4 should be reported in all Gleason score
7(3+4, 4+3) cases.6,7,10,11,12 This measurement further stratifies Gleason score 7 and allows identification of
cases with limited pattern 4 (e.g., <10%) or extensive pattern 4 (e.g., >80%). 

It is now recognized that Gleason pattern 4 has four basic architectures in cribriform, fused, poorly-formed
and glomeruloid glands.12,13,14 Among these architectures, cribriform has been shown to be an
independent predictor of poorer outcome particularly in Gleason score 7 tumors and its presence is now
recommended to be reported in Gleason pattern 4 cancer. There are recent attempts to standardize the
definition of cribriform pattern.15 

The presence treatment effects to cancer should be reported and is important especially if Gleason
grading is rendered not applicable.3,4 It should be recognized that in post-treatment settings, grading may
still be applied for prostate cancers lacking treatment effects particularly in new onset (de novo) cancers.

Grade Group
It is recognized that contemporary Gleason scores can be grouped into five prognostic categories, Grade
groups 1-5.16 This grade grouping has also been subsequently validated by other independent studies in
surgical cohorts showing significant correlation with outcome. 17,18 The new grade grouping has been
endorsed by ISUP, GUPS and in the 2016 WHO classification. The grade group is also referred to as
ISUP grade or WHO grade in other publications. 1,5,6,7 The grade group should be reported in parallel with
the Gleason score.

Table: Grade Groups

Grade Group   Gleason Score Definition
  Less than or
1 Only individual discrete well-formed glands
equal to 6
  Predominantly well-formed glands with lesser
2 3+4=7
component of poorly formed/fused/cribriform glands
  Predominantly poorly formed/fused/cribriform glands
3 4+3=7
with lesser component (#) of well-formed glands
  4+4=8 Only poorly formed/fused/cribriform glands
  Predominantly well-formed glands and lesser
3+5=8
4 component (##) lacking glands (or with necrosis)
  Predominantly lacking glands (or with necrosis) and
5+3=8
lesser component (##) of well-formed glands
  Lack gland formation (or with necrosis) with or without
5 9-10
poorly formed/fused/cribriform glands (#)
#
For cases with greater than 95% poorly formed/fused/cribriform glands on a core or at radical prostatectomy, the component of less
than 5% well-formed glands is not factored into the grade; should therefore be graded as grade group 4.
##
Poorly formed/fused/cribriform glands can be a more minor component.

References
1. Humphrey P, Amin MB, Berney D, Billis A, et al. Acinar adenocarcinoma. In: Moch H, Humphrey
PA, Ulbright T, Reuter VE, eds. Pathology and Genetics: Tumors of the Urinary System and Male
Genital Organs. 4th edition. WHO Classification of Tumors. Zurich, Switzerland: WHO Press;
2015:3-28.
2. Gleason DR, Mellinger GT, the Veterans Administration Cooperative Urological Research Group.
Prediction of prognosis for prostate adenocarcinoma by combined histological grading and clinical
staging. J Urol. 1974;111:58-64.

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3. Paner GP, Magi-Galluzzi C, Amin MB, Srigley JR: Adenocarcinoma of the prostate. In: Amin MB,
Grignon DJ, Srigley JR, Eble JN, eds. Urological Pathology. Philadelphia, PA: Lippincott William
& Wilkins; 2014:559-673.
4. Epstein JI, Allsbrook Jr WC, Amin MB, Egevad L, ISUP Grading Committee. The 2005
International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading
of Prostatic Carcinoma. Am J Surg Pathol. 2005;29:1228-1242.
5. Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA; and the Grading
Committee The 2014 International Society of Urological Pathology (ISUP) Consensus
Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and
proposal for a new grading system. Am J Surg Pathol. 2016; 40: 244-252.
6. Epstein JI, Amin MB, Fine SW, et al. The 2019 Genitourinary Pathology Society (GUPS) White
Paper on Contemporary Grading of Prostate Cancer. Arch Path Lab Med 2021;145:461-493.
7. van Leenders GJLH, van der Kwast TH, Grignon DJ, et al. The 2019 International Society of
Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma. Am J
Surg Pathol 2020;44:e87-e99.
8. Epstein JI, Amin MB, Reuter VE, et al. Contemporary Gleason grading of prostate carcinoma. An
update with discussion on practical issues to implement the International Society of Urological
Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg
Pathol. 2017;41:e1-e7.
9. Paner GP, Gandhi J, Choy B, et al. Essential updates in grading, morphotyping, reporting and
staging of prostate carcinoma for general surgical pathologists. Arch Pathol Lab Med.
2019;140:55-564.
10. Sauter G, Steurer S, Clauditz TS, et al. Clinical Utility of Quantitative Gleason Grading in Prostate
Biopsies and Prostatectomy Specimens. Eur Urol. 2016;69:592-598.
11. Cole AI, Morgan TM, Spratt DE, et al. Prognostic value of percent Gleason grade 4 at prostate
biopsy in predicting prostatectomy pathology and recurrence. J Urol 2016;196:405-411.
12. Choy B, Pearce SM, Anderson BB, et al. Prognostic significance of percentages and architectural
types of contemporary Gleason pattern 4 prostate cancer in radical prostatectomy. Am J Surg
Pathol. 2016;40:1400-6.
13. Iczkowski KA, Torkko KC, Kotnis GR, et al. Digital quantification of five high-grade prostate
cancer patterns, including the cribriform pattern, and their association with adverse outcome. Am
J Clin Pathol 2011;136:98-107.
14. Kweldam CF, Wildhagen MF, Steyerberg EW, et al. Cribriform growth is highly predictive for
postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer. Mod
Pathol 2015;28:457-464.
15. van der Kwast TH, van Leenders GJ, Berney DM, et al. ISUP consensus definition of cribriform
prostate cancer. Am J Surg Pathol 2021. Online ahead of print.
16. Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic Gleason grade grouping: data based
on the modified Gleason scoring system. BJU Int. 2013;111:753-760.
17. Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A contemporary prostate cancer grading system: a
validated alternative to the Gleason score. Eur Urol. 2016;69:428-435.
18. Berney DM, Beltran L, Fisher G, et al. Validation of a contemporary prostate cancer grading
system using prostate cancer death as outcome. Br J Cancer. 2016;114(10):1078-1083.

D. Intraductal Carcinoma (IDC)

Intraductal carcinoma (IDC) has independent prognostic significance and its reporting is
recommended.1,2,3,4,5 Intraductal carcinoma is uncommon in TURP specimens and when present it is
usually found within an invasive tumor. It is important to distinguish IDC from high-grade prostatic
intraepithelial neoplasia (PIN) and atypical intraductal proliferation (AIP). 

Both ISUP and GUPS recommend that Gleason scores or grade groups should not be assigned to pure
IDC.6,7,8 However, grading invasive cancer with concomitant IDC is controversial. ISUP recommends
incorporating IDC in determining the grade while GUPS recommends not to include IDC in determining

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the grade. It is recommended to specify which of these two approaches is applied when grading invasive
cancer with concomitant IDC.

Distinction between IDC and invasive cribriform or comedonecrosis patterns should be based on
morphological examination. In the approach where IDC is not incorporated in grading,
immunohistochemistry for basal cells can be used if the results will change the grade. 7

References
1. Guo CC and Epstein JI. Intraductal carcinoma of the prostate on needle biopsy: Histologic
features and clinical significance. Mod Pathol. 2006;19(12):1528-1535.
2. Cohen RJ, Wheeler TM, Bonkhoff H and Rubin MA. A proposal on the identification, histologic
reporting, and implications of intraductal prostatic carcinoma. Arch Pathol Lab Med.
2007;131(7):1103-1109.
3. Zhou M. Intraductal carcinoma of the prostate: the whole story. Pathology. 2013;45(6):533-539.
4. Montironi R, Zhou M, Magi-Galluzzi C, Epstein JI. Features and prognostic significance of
intraductal carcinoma of the prostate. Eur Urol Oncol. 2018;1:21-28.
5. Varma M. Intraductal carcinoma of the prostate: A guide for practicing pathologist. Adv Anat
Pathol. 2021. Online ahead of print.
6. Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA; and the Grading
Committee The 2014 International Society of Urological Pathology (ISUP) Consensus
Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and
proposal for a new grading system. Am J Surg Pathol. 2016; 40: 244-252.
7. Epstein JI, Amin MB, Fine SW, et al. The 2019 Genitourinary Pathology Society (GUPS) White
Paper on Contemporary Grading of Prostate Cancer. Arch Path Lab Med 2021;145:461-493.
8. van Leenders GJLH, van der Kwast TH, Girgnon DJ, et al. The 2019 International Society of
Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma. Am J
Surg Pathol 2020;44:e87-e99.

E. Quantitation of Tumor
Studies have shown that prostate cancer volume is a prognostic factor, although the data on its
independent prognostic significance is conflicting. 1,2,3,4,5   The designation of the percentage of cancer
tissue in transurethral samples is important. When prostate cancer is discovered incidentally (ie,
discovered in specimens submitted for clinically benign disease, usually benign prostatic hyperplasia
[BPH]), the percentage involvement is used to determine the clinical T1 substage, with less than or equal
to 5% involvement being T1a and greater than 5% being T1b. 6 In TURP and enucleations specimens, the
percentage of tissue involved by tumor can also be quantified by simple visual inspection.

References
1. Stamey T, McNeal J, Yemoto C, et al. Biological determinants of cancer progression in men with
prostate cancer. JAMA 1999;281:1395-1400.
2. Salomon L, Levrel O, Anastasiadis A, et al. Prognostic significance of tumor volume after radical
prostatectomy: a multivariate analysis of pathological prognostic factors. Eur Urol 2003;43:39-44.
3. Epstein JI. Prognostic significance of tumor volume in radical prostatectomy and needle biopsy. J
Urol. 2011;187:790-7.
4. Paner GP, Magi-Galluzzi C, Amin MB, Srigley JR: Adenocarcinoma of the prostate. In: Amin MB,
Grignon DJ, Srigley JR, Eble JN,eds. Urological Pathology. Philadelphia, PA: Lippincott William &
Wilkins; 2014:559-673. 
5. Ito Y, Vertosick EA, Sjoberg DD, et al. In organ-confined prostate cancer, tumor quantitation not
found to aid in prediction of biochemical recurrence. Am J Surg Pathol 2019;43:1061-1065.  

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6. Amin MB, Edge SB, Greene FL, et al. eds. AJCC Cancer Staging Manual. 8th ed. New York, NY:
Springer; 2017. 

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F. Perineural Invasion
Perineural invasion (PNI) in needle core biopsies has been associated with extraprostatic extension in
some correlative radical prostatectomy studies. However, the significance of this finding as a predictor of
stage and outcome is questionable in multivariate analysis. 1,2,3,4,5 Presence of perineural invasion may
also be reported in TURP specimens.

References
1. O’Malley KJ, Pound CR, Walsh PC, Epstein JI, Partin AW.  Influence of biopsy perineural
invasion on long-term biochemical disease-free survival after radical prostatectomy. Urology.
2002;59:85-90.
2. Bismar TA, Lewis JS, JR, Vollmer RT, Humphrey PA. Multiple measures of carcinoma extent
versus perineural invasion in prostate needle biopsy tissue in prediction of pathologic stage in a
screening population. Am J Surg Pathol. 2003;27:432-440.
3. Harnden P, Shelley MD, Clements H, et al. The prognostic significance of perineural invasion in
prostatic carcinoma biopsies: a systematic review.  Cancer. 2007;109:13-24.
4. Loeb S, Epstein J, Humphreys E, et al. Does perineural invasion on prostate biopsy predict
adverse prostatectomy outcomes? BJU Int 2010;105:1510–1513.
5. Paner GP, Magi-Galluzzi C, Amin MB, Srigley JR: Adenocarcinoma of the prostate. In: Amin MB,
Grignon DJ, Srigley JR, Eble JN,eds. Urological Pathology. Philadelphia, PA: Lippincott William &
Wilkins; 2014:559-673.

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