comparative pathology of trus biopsy, mapping biopsy and prostatectomy specimens

Comparative PathologyComparative Pathologyof TRUS Biopsy, Mapping Biopsyof TRUS Biopsy, Mapping Biopsy

and Prostatectomy Specimensand Prostatectomy Specimens

Francisco G. La Rosa, MDFrancisco G. La Rosa, MDFrancisco.LaRosa@ucdenver.eduFrancisco.LaRosa@ucdenver.edu

Associate Professor, Department of PathologyAssociate Professor, Department of Pathology

University of Colorado Denver, Aurora, ColoradoUniversity of Colorado Denver, Aurora, Colorado

Targeted Focal Therapy WorkshopTargeted Focal Therapy Workshop

August 16 – 17, 2012August 16 – 17, 2012

SAGITAL SECTION OF THE PROSTATE GLANDSAGITAL SECTION OF THE PROSTATE GLAND

SeminalVesicle

Central Zone

Bladder

Peri-urethralzone

Anterior ZoneFibro-muscular

PeripheralZone

TransitionZone

Urethra

CROSS SECTION OF THE PROSTATECROSS SECTION OF THE PROSTATE

FIBROMUSCULAR STROMAanterior

PERI-URETHRALSTROMA

EJACULATORY DUCTS

HISTORY OF PROSTATE BIOPSYHISTORY OF PROSTATE BIOPSY

- 1930, Ferguson: First described prostate biopsy.- 1930, Ferguson: First described prostate biopsy.Obtained cancer cells by aspirating prostate tissue with an Obtained cancer cells by aspirating prostate tissue with an 18-gauge needle transperineally.18-gauge needle transperineally. - 1937, Astraldi: First transrectal biopsy- 1937, Astraldi: First transrectal biopsy

- 1963, Takahashi & Ouchi: First TRUS biopsy- 1963, Takahashi & Ouchi: First TRUS biopsy - 1967, Watanabe: First clinical application of TRUS images- 1967, Watanabe: First clinical application of TRUS images

- 1980’s Transperineal biopsies- 1980’s Transperineal biopsies

The first sextant prostate needle biopsy scheme was developed by Hodge et al. in 1989 The sextant biopsy scheme consisted of biopsies of the prostate in the midline at the base, mid-gland, and apex. The midline sextant biopsies had a PCa detection rate of 20-30% . However, 25-50% of aggressive PCa remain undetected when using the midline sextant biopsies scheme.

J Urol 1989; 142: 71-74J Urol 2000; 163: 152-157J Urol 2000; 163: 163-166Urology 2003; 61: 1181-1186J Urol 1998; 159: 1260-1264

Stamey et al. in 1995 evaluated radical prostatectomy Stamey et al. in 1995 evaluated radical prostatectomy specimens and found that PCa had a higher likelihood of specimens and found that PCa had a higher likelihood of being found in the anterior horns of the peripheral zone being found in the anterior horns of the peripheral zone and suggested that laterally directed biopsies may provide and suggested that laterally directed biopsies may provide better detection.better detection.

Urology 1995; 45: 2-12Urology 1995; 45: 2-12

Multiple studies have found that directing prostate needle Multiple studies have found that directing prostate needle biopsies more laterally increases the PCa detection rates.biopsies more laterally increases the PCa detection rates.

J Urol 2000; 163: 152-157J Urol 2000; 163: 152-157J Urol 2000; 163: 163-166J Urol 2000; 163: 163-166Urology 2003; 61: 1181-1186Urology 2003; 61: 1181-1186

The current recommendation is an extended-biopsy The current recommendation is an extended-biopsy scheme with at least 8-12 cores including lateral scheme with at least 8-12 cores including lateral biopsies. Transition zone biopsies are not recommended biopsies. Transition zone biopsies are not recommended on initial evaluation.on initial evaluation.

Curr Opin Urol 2004; 14: 157-162Curr Opin Urol 2004; 14: 157-162

It is important to perform both the lateral modified fan-shaped biopsy and the midline sextant biopsies to improve overall PCa detections rates.

Thus, we recommend performing midline sextant biopsies , modified fan-shaped biopsy , and transition zone biopsies based on prostate volume, as follows:

- 8 biopsies for ≤15 cc- 14 for those >15 cc but ≤50 cc- 14-20 for those >50 cc

1.Werahera PN, Sullivan K, La Rosa FG, Kim FJ, Lucia MS, O’Donnell C, Sidhu RS, Sullivan HT, Schulte B, Crawford ED. Optimization of Prostate Cancer Diagnosis by Increasing the Number of Core Biopsies Based on Gland Volume. . Int J Clin Exp Pathol (in press)

TRUS BiopsiesTRUS Biopsies

TRANS RECTAL ULTRASOUND (TRUS)TRANS RECTAL ULTRASOUND (TRUS)GUIDED BIOPSY PROCEDUREGUIDED BIOPSY PROCEDURE

Bad HistologyBad Histology

Good HistologyGood Histology

Peripheral ZonePeripheral Zone

Central ZoneCentral Zone

Central ZoneCentral Zone

40X40X Seminal VesiclesSeminal Vesicles

Mapping BiopsiesMapping Biopsies

Mapping Grid and its relationship with the ProstateMapping Grid and its relationship with the Prostate

Grid Alignment in perineal areaGrid Alignment in perineal areaand Rectal Location of Ultrasound Probeand Rectal Location of Ultrasound Probe

Pathology Report of Mapping BiopsiesPathology Report of Mapping Biopsies

3D Reconstruction of Prostate3D Reconstruction of ProstateWith Location of Cancer LesionsWith Location of Cancer Lesions

Watch Video “Mapping Biopsy procedure”Watch Video “Mapping Biopsy procedure”

http://3dprostate.com/videos/mapping-biopsy.html

Whole Mount Prostatectomy SpecimensWhole Mount Prostatectomy Specimens

http://3dprostate.com/videos/gross-prostate.html

Prostate Cancer: GrossProstate Cancer: Gross

3-Dimensional Reconstruction of whole-mounted prostatectomy specimens

3-Dimensional Reconstruction of whole-mounted prostatectomy specimens

Venn-diagram representation of activity of Venn-diagram representation of activity of patients between positive results from patients between positive results from transperineal mapping biopsies (TPMB) and transperineal mapping biopsies (TPMB) and three-dimensional whole-mounted radical three-dimensional whole-mounted radical prostatectomies (3D-WMRP).prostatectomies (3D-WMRP).

(+) indicates presence of prostatic cancer(+) indicates presence of prostatic cancer(-) indicates no cancer (-) indicates no cancer

- TPMB with a 5-mm grid is an important staging tool that more - TPMB with a 5-mm grid is an important staging tool that more closely reflects true PCa disease state as found at RP as 10-12-core closely reflects true PCa disease state as found at RP as 10-12-core TRUSB and other more limited protocols. TRUSB and other more limited protocols. - TPMB can detect or rule out more aggressive disease, identifying TPMB can detect or rule out more aggressive disease, identifying with more accuracy the size and GS of PCa lesions, ensuring that with more accuracy the size and GS of PCa lesions, ensuring that patients are not mistakenly under-treated or unnecessarily over-patients are not mistakenly under-treated or unnecessarily over-treated, minimizing treatment-related morbidity. treated, minimizing treatment-related morbidity.

Case 1Case 1

58-year-old man, PSA 4.2 ng/mL, 58-year-old man, PSA 4.2 ng/mL,

TRUS guided biopsiesTRUS guided biopsies

Prostate, right:Prostate, right:

- Prostatic adenocarcinoma, Gleason grade 3 + 3 (score = 6)- Prostatic adenocarcinoma, Gleason grade 3 + 3 (score = 6)involving <5% of 1 of 12 biopsy core fragments involving <5% of 1 of 12 biopsy core fragments -No evidence of perineural or extra-capsular invasionNo evidence of perineural or extra-capsular invasion

Prostate, left, fine needle core biopsies (B):Prostate, left, fine needle core biopsies (B):- Prostatic adenocarcinoma, Gleason grade 3 + 3 (score = 6)- Prostatic adenocarcinoma, Gleason grade 3 + 3 (score = 6)involving <5% of 2 of 10 biopsy core fragmentsinvolving <5% of 2 of 10 biopsy core fragments- No evidence of perineural or extra-capsular invasion- No evidence of perineural or extra-capsular invasion

Radical prostatectomy Radical prostatectomy

(after fixation)(after fixation) LengthLength (apex to base) (apex to base): 3.8 cm: 3.8 cm WidthWidth (left to right) (left to right): 5.2 cm: 5.2 cm HeightHeight (anterior to posterior) (anterior to posterior): 4.0 cm: 4.0 cm Volume: 50.0 mLVolume: 50.0 mL Weight: 50.5 gWeight: 50.5 g

Serial whole-mount sections from apex to base of entire prostate Serial whole-mount sections from apex to base of entire prostate and seminal vesicles submitted in (A1-A9), seminal vesicle complex and seminal vesicles submitted in (A1-A9), seminal vesicle complex in A10, A11, right seminal vesicle in A12, A13, left seminal vesicle in in A10, A11, right seminal vesicle in A12, A13, left seminal vesicle in A14, A15. A14, A15.

Prostate and seminal vesicles, radical prostatectomy:Prostate and seminal vesicles, radical prostatectomy:- Prostatic adenocarcinoma, overall Gleason Grade 4 + 5 (score = 9) - Prostatic adenocarcinoma, overall Gleason Grade 4 + 5 (score = 9) with secondary foci of Gleason grade 3 + 3 (score = 6), multifocal with secondary foci of Gleason grade 3 + 3 (score = 6), multifocal and bilateral, involving <5% of prostate (see comments)and bilateral, involving <5% of prostate (see comments)- Suspicious but not definitive for lymphovascular invasion- Suspicious but not definitive for lymphovascular invasion- Perineural invasion, multifocal- Perineural invasion, multifocal- No evidence of extracapsular extension- No evidence of extracapsular extension- Seminal vesicles with no evidence of malignancy - Seminal vesicles with no evidence of malignancy

Second Opinion Second Opinion ProcessProcess

Urology Clinic

PatientPatient(outside diagnostic material)(outside diagnostic material)

Uropathology(2(2ndnd opinion) opinion)

Clinical Decision for Therapy

Radiology(second opinion)(second opinion)

UROLOGIC CANCERSECOND OPINION CONFERENCE

Pathology Pathology slidesslides

returnedreturned

UROLOGIC CANCER SECOND OPINION CONFERENCE

The Value of 2The Value of 2ndnd Opinion Pathology Opinion Pathology Diagnosis of Prostate BiopsiesDiagnosis of Prostate Biopsies

Outside pathology reportOutside pathology reportversusversus

22ndnd Opinion in-house Opinion in-houseversusversus

Whole-Mount Radical ProstatectomyWhole-Mount Radical Prostatectomy

Second opinion of prostate Second opinion of prostate biopsiesbiopsies

Most critical histopathological features:Most critical histopathological features:

- Gleason Score Gleason Score (sum of primary plus secondary grades)

- Extracapsular extensionExtracapsular extension- Perineural invasion (multifocal)Perineural invasion (multifocal)- Identification of HG PIN, ASAP, acute inflammationIdentification of HG PIN, ASAP, acute inflammation

# of Cases Discrepancies

820 156 (19 %)

DIAGNOSIS DISCREPANCIESDIAGNOSIS DISCREPANCIESWITH OUTSIDE CASESWITH OUTSIDE CASES

2008 – 20102008 – 2010

(Source: Quality Improvement database, Department of Pathology, (Source: Quality Improvement database, Department of Pathology, UCD)UCD)

We found a significant disagreement We found a significant disagreement between outside and in-house primary and between outside and in-house primary and

secondary Gleason gradessecondary Gleason grades

(McNemar statistic 6.250, p=0.012)(McNemar statistic 6.250, p=0.012)

Barqawi AB, Turcanu R, Gamito EJ, Lucia SM, O'Donnell CI, Crawford ED, La Rosa DD, La Rosa FG. Barqawi AB, Turcanu R, Gamito EJ, Lucia SM, O'Donnell CI, Crawford ED, La Rosa DD, La Rosa FG. The value of second-opinion pathology diagnoses on prostate biopsies from patients referred for The value of second-opinion pathology diagnoses on prostate biopsies from patients referred for management of prostate cancer. Int J Clin Exp Pathol. 2011 Jun 20;4(5):468-75.management of prostate cancer. Int J Clin Exp Pathol. 2011 Jun 20;4(5):468-75.

In-house pathologists detected significant In-house pathologists detected significant features not reported by outside features not reported by outside

pathologists:pathologists:

i.e. the presence of adipose tissue invasion which is highly i.e. the presence of adipose tissue invasion which is highly suspicious for extraprostatic extension by tumorsuspicious for extraprostatic extension by tumor

Barqawi AB, Turcanu R, Gamito EJ, Lucia SM, O'Donnell CI, Crawford ED, La Rosa DD, La Rosa FG. Barqawi AB, Turcanu R, Gamito EJ, Lucia SM, O'Donnell CI, Crawford ED, La Rosa DD, La Rosa FG. The value of second-opinion pathology diagnoses on prostate biopsies from patients referred for The value of second-opinion pathology diagnoses on prostate biopsies from patients referred for management of prostate cancer. Int J Clin Exp Pathol. 2011 Jun 20;4(5):468-75.management of prostate cancer. Int J Clin Exp Pathol. 2011 Jun 20;4(5):468-75.

REPORTING ACUTE INFLAMMATION and BPHREPORTING ACUTE INFLAMMATION and BPH

RELEVANCE:RELEVANCE:

- Explains increased PSA values in patients negative for PCaExplains increased PSA values in patients negative for PCa

- It can help in determining the need for quick repeat biopsiesIt can help in determining the need for quick repeat biopsies

Schatteman PHF, Hoekx L, Wyndaele JJ, Jeuris W, van Marck E. Inflammation in Prostate Schatteman PHF, Hoekx L, Wyndaele JJ, Jeuris W, van Marck E. Inflammation in Prostate Biopsies of Men without Prostatic Malignancy or Clinical Prostatitis. Eur Urol 2000;37:404-412Biopsies of Men without Prostatic Malignancy or Clinical Prostatitis. Eur Urol 2000;37:404-412

We strongly recommend that a re-evaluation We strongly recommend that a re-evaluation by in-house urologic pathologists should be by in-house urologic pathologists should be performed on all outside specimens before performed on all outside specimens before patients are admitted for treatment in any patients are admitted for treatment in any

institution.institution.

Barqawi AB, Turcanu R, Gamito EJ, Lucia SM, O'Donnell CI, Crawford ED, La Rosa DD, La Rosa FG. Barqawi AB, Turcanu R, Gamito EJ, Lucia SM, O'Donnell CI, Crawford ED, La Rosa DD, La Rosa FG. The value of second-opinion pathology diagnoses on prostate biopsies from patients referred for The value of second-opinion pathology diagnoses on prostate biopsies from patients referred for management of prostate cancer. Int J Clin Exp Pathol. 2011 Jun 20;4(5):468-75.management of prostate cancer. Int J Clin Exp Pathol. 2011 Jun 20;4(5):468-75.

Paul AranguaPaul AranguaAl Barqawi, MDAl Barqawi, MD

E. David Crawford, MDE. David Crawford, MDThomas Flaig, MDThomas Flaig, MDEduard Gamito (+)Eduard Gamito (+)

Mark GallenMark GallenMichael GlodeMichael Glode

Kenneth Iczkowski, MDKenneth Iczkowski, MDClifford Jones, DDClifford Jones, DD

Francisco G. La Rosa, MDFrancisco G. La Rosa, MDM. Scott Lucia, MDM. Scott Lucia, MDColin I. O’DonnellColin I. O’DonnellNayana Patel,, MDNayana Patel,, MD

Susan SullivanSusan SullivanKathleen TorkkoKathleen Torkko

Ruslan Turcanu, MDRuslan Turcanu, MD

Departments of Pathology, Surgery, Radiology &Departments of Pathology, Surgery, Radiology &Division of Medical OncologyDivision of Medical Oncology

University of Colorado Denver Anschutz Medical CampusUniversity of Colorado Denver Anschutz Medical CampusSchool of MedicineSchool of MedicineAurora, CO 80045Aurora, CO 80045

Urology TeamUrology Team