CLASSIFICATION OF UROTHELIAL TUMOURS.pptx

PPT on Classification of urothelial tumours as per WHO classification

1. CLASSIFICATION OF UROTHELIAL TUMOURS Presented by: Dr. Abir Kumar Baruah , PGT 3 Moderator: Dr. Sarat Das, Associate Professor Department of Pathology, Jorhat Medical College

2. THE UROTHELIUM

3. Muscularis Mucosa Muscularis Propria Adjacent to urothelium Distant from urothelium Haphazardly arranged, individual fascicles or rounded bundles separated by intervening stroma Arranged into inner, middle circular and outer longitudinal layers Inconspicuous in trigone , hyperplastic (>3 layers) in dome Best individualized in neck region Smoothelin : Focal or absent Smoothelin : Strong and diffuse

4. Urothelial Neoplastic Entities

5. Two types: Non-invasive papillary tumours Flat Non-invasive urothelial carcinoma (Carcinoma in situ) Precursor Lesions

6. Histopathological feature Papilloma PNLMP LG-PC HG-PC Papillae Delicate Delicate, occasionally fused Fused, branching and delicate Fused, branching and delicate Organization of cells Identical to normal Poorly identical to normal, any thickness, cohesive Any thickness, predominantly ordered, minimal loss of polarity Any thickness, predominantly disordered, frequent loss of polarity. Nuclear size Identical to normal Maybe uniformly enlarged Enlarged with variation in size Enlarged with variation in size Nuclear shape Identical to normal Elongated, round to oval, uniform Round to oval, slight variation Moderate to marked pleomorphism Nuclear Chromatin Fine Fine Mild variation Moderate to marked variation, hyperchromatic Nucleoli Absent Absent to inconspicuous Usually inconspicuous Multiple, prominent Mitosis Absent Rare, basal Occasional, at any level Frequent Umbrella cells Uniformly present Present Usually present May be absent Non-invasive papillary tumours

7. Cytologically malignant cells within a flat urothelium May range from full thickness cytologic atypia to scattered malignant cells in an otherwise normal urothelium ( pagetoid spread ) Lack of cohesiveness : shedding of malignant cells into the urine FLAT NON-INVASIVE UROTHELIAL CARCINOMA (CIS)

8. Nested Microcystic Micropapillary Lymphoepithelioma -like Plasmacytoid / signet-ring cell/ diffuse Sarcomatoid Giant cell Poorly differentiated Lipid rich Clear cell Invasive Urothelial Carcinoma

9. WHO (1973) WHO/ISUP (1998) WHO (2016) WHO (2022) CLASSIFICATION SYSTEMS OF UROTHELIAL TUMOURS

10. Papilloma Grade 1 transitional cell carcinoma Grade 2 transitional cell carcinoma Grade 3 transitional carcinoma WHO (1973)

11. Flat lesions with atypia Reactive (inflammatory) atypia Atypia of unknown significance Dysplasia Carcinoma in situ Papillary Neoplasms Urothelial Papilloma Urothelial Neoplasm of Low Malignant Potential Papillary Urothelial Carcinoma, low grade Papillary Urothelial Carcinoma, high grade Invasive Neoplasms WHO 2004/ISUP 1998

12. WHO (2016)

13. WHO (2022)

14. Precursor lesions Urothelial dysplasia Preneoplastic lesion with cytologic changes that fall short of those of CIS The 2022 WHO classification elected not to dedicate a separate section for urothelial dysplasia (only a reference is made to it in the section of urothelial CIS ). What’s new in the WHO classification 5 th edition (2022)

15. Precursor lesions Urothelial papillary proliferation of undetermined malignant potential In the current WHO edition, these lesions are no longer recognized as a unique entity and are considered either early noninvasive low-grade papillary carcinomas or shoulder extensions of such tumors. What’s new in the WHO classification 5 th edition (2022)

16. Noninvasive urothelial papillary neoplasms 4-tier grade maintained R eporting of papillary tumors as high grade when high grade fraction represent 5% of the tumor [87]. Tumors with <5 % high-grade fraction are to be reported as ‘‘ low-grade tumors with <5% high-grade component ’’ Inverted histological patterns recognized What’s new in the WHO classification 5 th edition (2022)

17. Invasive urothelial carcinoma The 2022 classification emphasizes the importance of reporting the different components of conventional urothelial carcinoma , histologic subtypes, and/or divergent differentiation in every tumor. It also calls for a consistent attempt to quantify such elements, given potential management implications. R are lowgrade invasive urothelial carcinomas (lacking marked nuclear atypia ) are recognized in the 2022 WHO classification. What’s new in the WHO classification 5 th edition (2022)

18. Invasive urothelial carcinoma The term ‘‘signet ring’’ is dropped from plasmacytoid subtype and a qualifier ‘‘ glycogen rich ’’ is added to clear cell urothelial carcinoma subtype to further assure its distinction from clear cell adenocarcinoma tumors of Mullerian divergent differentiation . Large nested urothelial carcinoma: medium to large nests rounded circumscribed borders to occasional stromal-tumor interfaces with more irregular ragged appearances. What’s new in the WHO classification 5 th edition (2022)

19. Invasive urothelial carcinoma Tubular and microcystic urothelial carcinomas: Composed of bland cells arranged in tubular or microcystic structures Urothelial carcinoma with divergent differentiation What’s new in the WHO classification 5 th edition (2022)

20. Urine cytology The fifth edition fully endorses the adoption of the Paris System for Reporting Cytology (TPS ). Recognizes limitations What’s new in the WHO classification 5 th edition (2022)

21. Genomic advances and diagnostic molecular pathology in urothelial carcinoma The WHO 2022 highlights the potential impact of the novel molecular taxonomy on the diagnosis and future management of urinary tract cancers. What’s new in the WHO classification 5 th edition (2022)

22. Genomic advances and diagnostic molecular pathology in urothelial carcinoma 3 subtypes: Luminal, basal-squamous, neuronal Luminal-papillary: FGFR alterations, papillary histology, lower risk for progression Luminal-infiltrated: High expression of EMT, myofibroblast markers and moderate levels of CD274 and CTLA4 immune markers. Luminal subtype shows high expression of luminal markers ( uroplakin , GATA3, FOXA1) and KRT20

23. Genomic advances and diagnostic molecular pathology in urothelial carcinoma Basal-squamous subtype: higher incidence in women, frequent presence of squamous histology, high expression of basal and stem-like markers (CD44, KRT5, KRT6A, and KRT14), high expression of CD274 (PD-L1) and CTLA4. Neuronal subtype is associated with worst clinical prognosis

24. Thank You