Updates in Urologic Pathology WHO Made Those Changes?! Peyman Tavassoli Pathology Department BC Cancer Agency
World Health Organization Available in Feb 2016 Frame work for reporting Major contributing group: International Society of Urologic Pathologists (ISUP) Last Update in 2004
Bladder Cancer
Molecular Pathways in Urothelial Carcinoma 80% Low Grade FGFR3 / H-RAS mutation 20% HIGH Grade p53 / MDM2 RB mutation / alteration RAS-MAPK Cell cycle / DNA repair / Apoptosis Proliferation
Molecular Pathways in Urothelial Carcinoma 80% Low Grade 20% HIGH Grade FGFR3 / H-RAS mutation Recurrence p53 / MDM2 RB mutation / alteration RAS-MAPK Cell cycle / DNA repair / Apoptosis Proliferation
Non-invasive Lesions:
Urothelial dysplasia Flat urothelial lesion with cytologic and architectural atypia that falls short of the diagnosis of CIS
Urothelial dysplasia Felt to be a preneoplastic lesion Clinical significance still uncertain Generally seen in patients with prior history of cancer Rarely seen de novo
Normal Dysplasia CIS Carcinoma in situ
Invasive urothelial carcinomas
Plasmacytoid/ Signet Ring/ Diffuse Variant Nested Variant With squamous differentiation Amin et al. Mod Path 2015. Micropapillary Variant
Incipient Lesions or Formes Frustes Most frequently seen during surveillance cystoscopy Microscopically: Blunted, incomplete or abortive papillae +/-thickened urothelium Cytologic atypia (mild to severe)
Amin et al. Mod Path 2015.
Incipient Lesions or Formes Frustes If patient has prior diagnosis of papillary neoplasia and Low grade cytologic atypia: Early, non-invasive low grade papillary urothelial carcinoma High grade cytologic atypia: Early, non-invasive high grade papillary urothelial carcinoma
Incipient Lesions or Formes Frustes If patient has No prior diagnosis of papillary neoplasia and Low grade cytologic atypia: Urothelial dysplasia with early papillary formation High grade cytologic atypia: Urothelial carcinoma in situ with early papillary formation
Prostate Cancer
IntraductalCarcinoma 2004 Definition: Not recognized
IntraductalCarcinoma 2004 Definition: Not recognized 2016 Definition: Intra-acinar and/or intraductal proliferation of neoplastic cells exhibiting much greater cytological and/or architectural atypia than HGPIN and typically associated with high grade, high stage prostate cancer
IntraductalCarcinoma Independent predictor of poor outcome PTEN loss frequently seen Rarely seen in isolation or with only Gleason 6 cancer - Merits definitive therapy, or at least immediate repeat biopsy
Modified Gleason Grading System ISUP modifications in 2014 Primarily codified what was in practice already Gleason pattern 3 Gleason pattern 4 Gleason pattern 5
Modified Gleason Grading System ISUP modifications in 2014 Primarily codified what was in practice already Gleason pattern 3 2016 System: Gleason Score + Grade grouping: Grade group 1: Gleason score less than 6 Grade group 2: Gleason score 3+4=7 Grade group 3: Gleason score 4+3=7 Grade group 4: Gleason score 4+4; 5+3; 3+5=8 Grade group 5: Gleason score 4+5; 5+4=9 Gleason pattern 4 Gleason pattern 5
Biochemical Recurrence Free Survival Kaplan Meier analysis of Gleason score at RP pathological analysis Pierorazio P, et al, BJU Int. 2013 May
Grade Groups: Based on Gleason score Primarily help clinician and patient recognize that Gleason 6 is the best possible tumor to have and is not an intermediate grade cancer Highlights clinically significant difference in Gleason 7 disease (3+4=7 vs 4+3=7) Grade group 1: Gleason score less than 6 Grade group 2: Gleason score 3+4=7 Grade group 3: Gleason score 4+3=7 Grade group 4: Gleason score 4+4; 5+3; 3+5=8 Grade group 5: Gleason score 4+5; 5+4=9
Gleason 3+3=6 (Grade Group 1)
Gleason 3+4=7 (Grade Group 2)
Gleason 4+3=7 (Grade Group 3)
Gleason 4+4=8 (Grade Group 4)
Gleason 4+5=9 (Grade Group 5)
Reporting Gleason pattern 4 Estimating volume (%) of Gleason pattern 4 is recommended for Gleason 3+4=7 tumors Helps to select active surveillance candidates
Current Method of Reporting Cancer in Prostate Biopsies in Weill Cornell Medicine A. Prostate, left apex, biopsy: - Prostatic adenocarcinoma, Grade Group 2 (Gleason score 3+4=7), involving 30% and 10% (5 mm, 2 mm) of 2/2 cores. - Gleason pattern 4 constitutes 10% of the tumor volume.
Current Method of Reporting Cancer in Prostate Biopsies in Sloan Kettering A. Prostate, left apex, biopsy: - Prostatic adenocarcinoma - Grade Group 2 - Gleason score 3+4=7-2/2 cores, 30% (5 mm) and 10% (2 mm) - Gleason pattern 4: 10%
Renal Tumors
Papillary adenoma 2004 Definition: Unencapsulated, low grade papillary neoplasm <5 mm in size
Papillary adenoma 2004 Definition: Unencapsulated, low grade papillary neoplasm <5 mm in size 2016 Definition: Unencapsulated, low grade papillary neoplasm <1.5 cm in size
Papillary adenoma 2004 Definition: Unencapsulated, low grade papillary neoplasm <5 mm in size 2016 Definition: Unencapsulated, low grade papillary neoplasm <1.5 cm in size Based on data from MSKCC, Mayo Clinic, et al. Unencapsulated, low grade tumors with papillary and/or tubular architecture that are <1.5 cm have no metastatic potential
Multilocular Cystic Renal Cell Carcinoma 2004 Definition: Tumor composed of cysts lined by low grade clear cells and no expansile solid nodules
Multilocular Cystic Renal Cell Carcinoma 2004 Definition: Tumor composed of cysts lined by low grade clear cells and no expansile solid nodules 2016 Definition: Same
Multilocular Cystic Renal Cell Carcinoma 2004 Definition: Tumor composed of cysts lined by low grade clear cells and no expansile solid nodules 2016 Definition: Same 2016 Name: Multilocular cystic renal neoplasm of low malignant potential
Multilocular Cystic Renal Neoplasm of Low Malignant Potential Related to clear cell renal cell carcinoma (ccrcc) VHL mutation and 3p deletion rates similar BUT No recurrence or metastasis in >200 reported patients with >5 years follow-up Avoids label of carcinoma
New RCC Entities Poor Prognosis: Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated RCC Good Prognosis: Succinate dehydrogenase-deficient RCC Tubulocystic RCC Acquired cystic disease-associated RCC Clear cell papillary RCC (1-4% of all tumors)
Clear Cell Papillary RCC Tubulocystic RCC Acquired Cystic Disease-Associated RCC
New Grading System 2004 System: Fuhrman nuclear grade
New Grading System 2004 System: Fuhrman nuclear grade 2016 System: WHO/ISUP nucleolar grade
New Grading System WHO/ISUP nucleolar system more reproducible and provides better outcome prediction Reflects what was already being practiced Like Fuhrman, validated ONLY for clear cell and papillary RCCs
1 2 3 4
Testicular Tumors
Intratubular Germ Cell Neoplasia- Unclassified (ITGCN, IGCN-U) 2004 Definition: Intratubular proliferation of gonocyte-like germ cells with clear cytoplasm; large, angulated, hyperchromatic nuclei; and prominent nucleoli
Intratubular Germ Cell Neoplasia- Unclassified (ITGCN, IGCN-U) 2004 Definition: Intratubular proliferation of gonocyte-like germ cells with clear cytoplasm; large, angulated, hyperchromatic nuclei; and prominent nucleoli 2016 Definition: Same
Intratubular Germ Cell Neoplasia- Unclassified (ITGCN, IGCN-U) 2004 Definition: Intratubular proliferation of gonocyte-like germ cells with clear cytoplasm; large, angulated, hyperchromatic nuclei; and prominent nucleoli 2016 Definition: Same Germ Cell Neoplasia In Situ GCNIS
Spermatocytic Seminoma 2004 Definition: Germ cell tumor resembling spermatogenic cells, most commonly spermatogoniaor early primary spermatocytes
Spermatocytic Seminoma 2004 Definition: Germ cell tumor resembling spermatogenic cells, most commonly spermatogoniaor early primary spermatocytes 2016 Definition: Same
Spermatocytic Seminoma 2004 Definition: Germ cell tumor resembling spermatogenic cells, most commonly spermatogoniaor early primary spermatocytes 2016 Definition: Same 2016 Name: Spermatocytic Tumor
Spermatocytic Tumor Completely different biology from seminoma: No malignant potential (unless sarcoma component) No association with GCNIS Does not occur outside the testis Does not occur in pre-pubertal men No association with crytporchidism