Virchows Archiv

, Volume 472, Issue 3, pp 451–460 | Cite as

Digital versus light microscopy assessment of surgical margin status after radical prostatectomy

  • Metka Volavšek
  • Ana Blanca
  • Rodolfo Montironi
  • Liang Cheng
  • Maria R. Raspollini
  • Nuno Vau
  • Jorge Fonseca
  • Francesco Pierconti
  • Antonio Lopez-Beltran
Original Article


Positive surgical margin (PSM) extension reported as focal or non-focal/extensive is an important pathologic prognostic parameter after radical prostatectomy. Likewise, there is limited or no agreement on how to measure and what the best cut-off points to be used in practice are. We hypothesized that digital microscopy (DM) would potentially provide a more objective way to measure PSM and better define its clinical significance. To further our knowledge, we have evaluated PSM status in 107 laparoscopic radical prostatectomies using digital and conventional light microscopy (LM). DM evaluation detected three additional PSM cases, but no differences were seen (LM vs DM; p = 0.220). Mean linear measurement correlated to biochemical recurrence (BR) (LM, p = 0.002; DM, p = 0.001). ROC analysis identified a cut-off point to assess linear measurement by LM (3.5 mm) or DM (3.2 mm), but only digital measurement was significant for BR-free survival. Our study also evaluated a cut-off ≤ 3 mm that was associated to BR using LM (p = 0.023) or DM (p = 0.001). Finally, the number of paraffin blocks bearing PSM correlated with BR (p < 0.001) status with either LM or DM. In conclusion, DM produces similar data than LM but shows more accurate measurements. Reporting of PSM with score of ≤ 3 vs. > 3 mm linear extent using LM (3.2 mm if digital microscopy is applied) might represent an important prognostic feature after radical prostatectomy. Alternatively, reporting the number of blocks with PSM 1 vs. 2 or more might also provide important prognostic data in practice.


Prostate cancer Radical prostatectomy Surgical margin status Digital microscopy Digital pathology Biochemical recurrence 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Têtu B, Evans A (2014) Canadian licensure for the use of digital pathology for routine diagnoses one more step toward a new era of pathology practice without borders. Arch Pathol Lab Med 138(3):302–304. CrossRefPubMedGoogle Scholar
  2. 2.
    Evans AJ, Salama ME, Henricks WH, Pantanowitz L (2017) Implementation of whole slide imaging for clinical purposes issues to consider from the perspective of early adopters. Arch Pathol Lab Med 141(7):944–959. CrossRefPubMedGoogle Scholar
  3. 3.
    Pantanowitz L, Sinard JH, Henricks WH, Fatheree LA, Carter AB, Cintis L, Beckwith BA, Evans AJ, Otis CN, Lal A, Parwani AV (2013) Validating whole slide imaging for diagnostic purposes in pathology. Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med 137(12):1710–1722. CrossRefPubMedGoogle Scholar
  4. 4.
    Goacher E, Randell R, Williams B, Treanor D (2017) The diagnostic concordance of whole slide imaging and light microscopy. A systematic review. Arch Pathol Lab Med 141(1):151–161. CrossRefPubMedGoogle Scholar
  5. 5.
    Montironi R, Cheng L, Lopez-Beltran A, Marina Scarpelli (2016) Quantitative image analysis on histologic virtual slides for prostate pathology diagnosis, response to chemopreventive agents, and prognosis. Eur Urol Focus doi:
  6. 6.
    Tan PH, Cheng L, Srigley JR, Griffiths D, Humphrey PA, van der Kwast TH, Montironi R, Wheeler TM, Delahunt B, Egevad L, Epstein JI, and the ISUP Prostate Cancer Group. International Society of Urological Pathology (ISUP) (2011) Consenus conference on handling and staging of radical prostatectomy specimens. Working group 5: surgical margins. Modern Pathol 24(1):48–57. CrossRefGoogle Scholar
  7. 7.
    Pierorazio PM, Walsh PC, Partin AW, Epstein JI (2013) Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int 111(5):753–760. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Epstein JI, Lars E, Amin MB, Delahunt B, Srigley JR, Peter H, the Grading Committee (2016) 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 40:244–252. PubMedGoogle Scholar
  9. 9.
    Epstein JI, Amin MB, Reuter VE, Humphrey PA (2017) Contemporary Gleason grading of prostatic carcinoma: an update with discussion on practical issues to implement the 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 41(4):e1–e7. CrossRefPubMedGoogle Scholar
  10. 10.
    Humphrey PA, Amin MB, Berney DM, Billis A, Cao D, Cheng L, Delahunt B, Egevad L, Epstein JI, Fine SW, Grignon DJ, Christiansen G, Lopez-Beltran A, Magi-Galluzzi C, Netto GJ, Rubin MA, Samaratunga H, Srigley JR, True LD, Tsuzuki T, Van der Kwast T (2016) Acinar adenocarcinoma. In: Moch H, Humphrey PA, Ullbright TM, Reuter V (eds) WHO classification of tumours of the urinary system and male genital organs, 4th edn. IARC, Lyon, pp 138–162Google Scholar
  11. 11.
    Buyyounouski MK, Choyke PL, Kattan MW, McKenney JK, Srigley JR, Barocas DA, Brimo F, Brookland RK, Epstein JI, Fine SW, Halabi S, Hamstra DA, Mason MD, Oh WK, Pettaway CA, Sartor O, Schymura MJ, Touijer KA, Zelefsky MJ, Sandler HM, Amin MB, Lin DW (2017) Prostate. In: Amin MA (ed) AJCC cancer staging manual, 8th edn. American Joint Committee on Cancer, Chicago, Springer, pp 715–726. Google Scholar
  12. 12.
    Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Trasher JB, Thompson I (2007) Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association prostate guidelines for localized prostate cancer update panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 177(2):540–545. CrossRefPubMedGoogle Scholar
  13. 13.
    Mann MJ, DeCastro GJ, Desai M, Benson MC, McKiernan JM (2008) Predictive significance of surgical margin status after prostatectomy for prostate cancer during PSA era. Urology 72(6):1203–1207. Epub 2008 Jul 31CrossRefPubMedGoogle Scholar
  14. 14.
    Yossepowitch O, Briganti A, Eastham JA, Epstein J, Graefen M, Montironi R, Touijer K (2014) Positive surgical margins after radical prostatectomy: a systematic review and contemporary update. Eur Urol 65(2):303–313. CrossRefPubMedGoogle Scholar
  15. 15.
    Ahyai SA, Zacharias M, Isbarn H, Steuber T, Eichelberg C, Köllermann J, Fisch M, Karakiewicz PI, Huland H, Graefen M, Chun FKH (2010) Prognostic significance of a positive surgical margin in pathologically organ-confined prostate cancer. BJU Int 106(4):478–483. CrossRefPubMedGoogle Scholar
  16. 16.
    Weldon VE, Tawl FR, Neuwirth H, Cohen R (1995) Patterns of positive specimen margins and detectable prostate specific antigen after radical perineal prostatectomy. J Urol 153(5):1565–1569. CrossRefPubMedGoogle Scholar
  17. 17.
    Babaian RJ, Troncoso P, Bhadkamkar VA, Johnston DA (2001) Analysis of clinicopathologic factors predicting outcome after radical prostatectomy. Cancer 91(8):1414–1422.<1414::AID-CNCR1147>3.0.CO;2-G CrossRefPubMedGoogle Scholar
  18. 18.
    Sherwin JC, Mirmilstein G, Pedersen J, Lawrentschuk N, Bolton D, Mills J (2010) Tumor volume in radical prostatectomy specimens assessed by digital image analysis software correlates with other prognostic factors. J Urol 183(5):1808–1815. CrossRefPubMedGoogle Scholar
  19. 19.
    Kamat AM, Babaian K, Cheung MR, Naya Y, Huang SH, Kuban D, Babaian RJ (2003) Identification of factors predicting response to adjuvant radiation therapy in patients with positive margins after radical prostatectomy. J Urol 170(5):1860–1863. CrossRefPubMedGoogle Scholar
  20. 20.
    Evans AJ, Henry PC, Van der Kwast TH, Tkachuk DC, Watson K, Lockwood GA, Fleshner NE, Cheung C, Belanger EC, Amin MB, Liliane B-G, Bostwick DG, Egevad L, Epstein JI, Grignon DJ, Jones EC, Montironi R, Moussa M, Sweet J, Trpkov K, Wheeler T, Srigley JR (2008) Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. Am J Surg Pathol 32(10):1503–1512. CrossRefPubMedGoogle Scholar
  21. 21.
    Epstein JI, Carmichael MJ, Pizov G, Walsh PC (1993) Influence of capsular penetration on progression following radical prostatectomy: a study of 196 cases with long-term follow up. J Urol 150(1):135–141. CrossRefPubMedGoogle Scholar
  22. 22.
    Chan SM, Garcia FJ, Moussa M, Gabril MY (2011) The clinical significance of in-depth pathological assessment of extraprostatic extension and margin status in radical prostatectomies for prostate cancer. Prostate Cancer Prostatic Dis 14(4):307–312. CrossRefPubMedGoogle Scholar
  23. 23.
    Sengupta S, Christensen CM, Zincke H, Slezak JM, Leibovich BC, Bergstralh EJ, Myers RP, Blute MJ (1996) Detectable prostate specific antigen between 60 and 120 days following radical prostatectomy for prostate cancer: natural history and prognostic significance. J Urol 176(2):559–563. CrossRefGoogle Scholar
  24. 24.
    Uchio EM, Aslan M, Wells CK, Calderone J, Concato J (2010) Impact of biochemical recurrence in prostate cancer among US veterans. Arch Intern Med 170: 1390–1395Google Scholar
  25. 25.
    Rodriguez-Urrego PA, Cronin AM, Al-Ahmadie HA, Gopalan A, Tickoo SK, Reuter VE, Fine SW (2011) Interobserver and intraobserver reproducibility in digital and routine microscopic assessment of prostate needle biopsies. Hum Pathol 42(1):68–74. CrossRefPubMedGoogle Scholar
  26. 26.
    Emerson RE, Koch MO, Jones TD, Daggy JK, Juliar BE, Cheng L (2005) The influence of extent of surgical margin positivity on prostate specific antigen recurrence. J Clin Pathol 58(10):1028–1032. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Metka Volavšek
    • 1
  • Ana Blanca
    • 2
  • Rodolfo Montironi
    • 3
  • Liang Cheng
    • 4
    • 5
  • Maria R. Raspollini
    • 6
  • Nuno Vau
    • 7
  • Jorge Fonseca
    • 8
  • Francesco Pierconti
    • 9
  • Antonio Lopez-Beltran
    • 10
    • 11
  1. 1.Institute of Pathology, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
  2. 2.Maimonides Biomedical Research Institute of Cordoba, SpainCordobaSpain
  3. 3.Institute of Pathological Anatomy and Histopathology, School of MedicinePolytechnic University of the Marche Region (Ancona), United HospitalsAnconaItaly
  4. 4.Department of Pathology and Laboratory Medicine, School of MedicineIndiana UniversityIndianapolisUSA
  5. 5.Department of Urology, School of MedicineIndiana UniversityIndianapolisUSA
  6. 6.Histopathology and Molecular DiagnosticsUniversity Hospital CareggiFlorenceItaly
  7. 7.Urologic Oncology, Champalimaud Clinical CenterLisbonPortugal
  8. 8.Urology Clinic, Champalimaud Clinical CenterLisbonPortugal
  9. 9.Division of Anatomic Pathology and HistologyCatholic University of the Sacred Heart, “Agostino Gemelli” School of MedicineRomeItaly
  10. 10.Department of Pathology, Unit of Anatomical Pathology, Department of Surgery, Faculty of MedicineCordobaSpain
  11. 11.Champalimaud Clinical CenterLisbonPortugal

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