OMPRN Pathology Matters Meeting 2017

Transcription

1 OMPRN Pathology Matters Meeting 2017 Pathology of Aggressive Prostate Cancer Intraductal Carcinoma and Cribriform Carcinoma Dr. Michelle Downes, Staff Urologic Pathologist Sunnybrook Health Sciences Centre, Toronto Assistant professor, LMP, University of Toronto

2 Overview Prostate Cancer What is intraductal carcinoma? The case for cribriform pattern invasive carcinoma Clinical evidence for its prognostic impact Molecular underpinnings

3 Prostate Cancer Original Gleason schematic 2014 modified ISUP Gleason schematic Main change is the Gleason grade 3 and 4 groups SEER Data US ISUP Grade Groups GS 6 GS 7 (3+4) GS 7 (4+3) GS 8 GS 9-10

4 Gleason 4 patterns

5 What is intraductal carcinoma? Distension of antecedent prostate ducts and glands by neoplastic cells / lumen spanning

6 Intraductal carcinoma is NOT High grade PIN No distension, not lumen spanning Ductal adenocarcinoma (aka endometrioid carcinoma) Variant of invasive carcinoma

7 Intraductal Carcinoma - Prostatecomy Intraductal Carcinoma ~ 20% of radical prostatectomies Associated with Tumour volume Stage Gleason score + Surgical margins Independent prognostic factor 1. Cohen R, Chan W, Edgar S, et al. Prediction of pathologic stage and clinical outcome in prostate cancer; an improved pre- operative sequential model incorporating biopsy determined intraductal carcinoma. Br J Urol 1998;81: Rubin MA, de La Taille A, Bagiella E, Olsson CA, O Toole KM. Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications. Am J Surg Pathol 1998;22: Wilcox G, Soh S, Chakraborty S, Scardino P, Wheeler T. Patterns of high grade prostatic intra-epithelial neoplasia associated with clinically aggressive prostate cancer. Hum Pathol 1998;29: Cohen RJ, McNeal JE, Baillie T. Patterns of differentiation and proliferation in intraductal carcinoma of the prostate: significance for cancer progression. Prostate 2000;43:11 9. McNeal JE, Yemoto CE. Spread of adenocarcinoma within prostatic ducts and acini: morphologic and clinical correlations. Am J Surg Pathol 1996;20:

8 Intraductal Carcinoma A Rediscovery in Biopsies Intraductal carcinoma either isolated or with Gleason score 6 prostate cancer in biopsy is associated with advanced stage cancer and risk of metastatic disease

9 The Case For Cribriform Pattern Carcinoma Prognostic role for cribriform pattern invasive carcinoma: Presence of cribriform carcinoma in a GS 7 (3 + 4) biopsy is associated with non-organ confined prostate cancer (1) Intraductal carcinoma has frequently a cribriform architecture Intraductal carcinoma is often associated with cribriform invasive carcinoma (2) Cribriform carcinoma in prostatectomy is an independent predictor of biochemical recurrence (2), metastatic disease and death (3) References: 1) Keefe DT, Schieda N, El Hallani S, Breau RH, Morash C, Robertson SJ, Mai KT, Belanger EC, Flood TA. Cribriform morphology predicts upstaging after radical prostatectomy in patients with Gleason score = 7 prostate cancer at transrectal ultrasound (TRUS)-guided needle biopsy. Virchows Arch 467: ) Trudel D, Downes MR, Sykes J, Kron KJ, Trachtenberg J, van der Kwast TH. Prognostic impact of intraductal carcinoma and large cribriform carcinoma architecture after prostatectomy in a contemporary cohort. Eur J Cancer 2014;50(9): ) Kweldam CF, Wildhagen MF, Steyerberg EW, Bangma CH, van der Kwast TH, van Leenders GJ. Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer. Mod Pathol 2015;2 8:

10 Large Cribriform Intraductal Carcinoma

11 Nested Case-Control GS 7 Prostatectomy Series Metastatic Disease / Survival as Outcome Parameter Study design: 52 cases (with metastasis, disease-specific mortality or both) and 109 controls, matched for age, PSA level and pt stage. Overall prevalence of G4 sub-patterns: Fused: 75% Ill-defined: 64% Cribriform 48% Glomeruloid 25% Cases: 81% cribriform Controls: 38% cribriform Kweldam C et al. Mod Pathol. 2015;28(3):

12 Molecular-Genetic Features of IDC PGA higher in IDC+ than in IDC- prostate cancers IDC is feature of BRCA2 carrierassociated prostate cancers Increased genomic instability Chua et al. A prostate cancer Nimbosus : Genomic instability and SChLAP1 dysregulation underpin aggression of intraductal and cribriform subpathologies. Eur Urol, online Nat. Commun. 8, doi: /ncomms13671 (2017).

13 Molecular Underpinnings

14 Conclusions: Intraductal / cribriform invasive carcinoma can be combined to provide a novel independent histopathological prognosticator on prostate biopsies. Intraductal / cribriform invasive carcinomas are distinct at molecular-genetic level (genetically unstable, SChLAP1) and a feature of BRCA2-associated prostate cancer. Intraductal / cribriform carcinoma in Gleason 6 and 7 (3+4) cancer can be used as a determinant of clinically significant prostate cancer Routine reporting of intraductal / cribriform invasive carcinoma on biopsies is recommended as it may lead to imaging and therapy intensification

15 Thank You! Acknowledgement: Dr Theo van der Kwast, University Health Network, Toronto