HISTOPATHOLOGICAL DIAGNOSIS OF UROTHELIAL CARCINOMA VARIANTS ON TRANSURETHRAL RESECTION SPECIMENS

The presentation "Histopathological Diagnosis of Urothelial Carcinoma Variants on Transurethral Resection Specimens" explores the classification and pathological features of urothelial carcinoma (UC) variants based on specimens from Târgu Mureș Emergency County Hospital (2004-2015). It highlights the importance of recognizing these histological subtypes due to their implications on prognosis and treatment. The study categorizes UC into six major variants (e.g., squamous differentiation, sarcomatoid, micropapillary, small-cell carcinoma) and discusses differential diagnoses, TNM staging, and prognostic factors. The findings emphasize the clinical relevance of proper histopathological evaluation in improving therapeutic strategies

1. HISTOPATHOLOGICAL DIAGNOSIS OF UROTHELIAL CARCINOMA VARIANTS ON TRANSURETHRAL RESECTION SPECIMENS Author: Cosma Catalin-Dumitru IV t h year student, General Medicine Coordinators: Professor Dr. Angela Borda Associate professor Dr. Andrada Loghin Coauthors: Victor Vacariu Muresan David

2. Background urothelial carcinoma (UC) is the most common tumor of the urinary bladder the majority are conventional UC an increasing number of histological variants of ( UC) have been described t he recognition of these histologic variants is important c an be confunded with tumors from other organs some may require a different therapeutic approach

3. Aim to present the UC variants diagnosed on the transurethral resection (TUR) specimens in our Pathology Department over a 12 year period .

4. Materials and methods Patients : all the patients with a TUR-V performed in the Department of Urology examined in the Department of Pathology , Tirgu Mures Emergency County Hospital between January 2004 and December 2015 C linicopathological data : a ge gender histopathological diagnosis (based on WHO classification 2004) p athological stage (TNM 2002, 2009)

5. WHO classification (2004) UC nested variant UC inverted papiloma -like variant UC micropapillary variant UC microchistic variant UC lymphoepithelioma -like variant variant UC plasmacytoid /lymphoma-like variant UC clear cell (glycogen-rich) variant UC lipoid cell varinat UC with syncytiotrophoblastic giant cells Sarcomatoid UC ( carcinosarcoma ) Small cell carcinoma UC with mixed differentiation Squamos differentiation Glandular differentiation Large cell undifferentiated carcinoma UC with unusual stromal reactions Pseudosarcomatous stroma Stromal osseous of cartilaginous metaplasia Osteoclast-type giant cells Prominent lymphoid infiltrate

6. Ta – non- invazive papillary carcinoma T1 - Tumor invades subepithelial connective tissue T2 - Tumor invades muscles T2a – Tumor invades superficial muscle T2b – Tumor invades deep muscle T3 –Tumor invades perivesical tissue T3a – microscopically T3b – macroscopically T4 –Tumor invades organs T4a- Invades prostrate , seminal vezicules , uterus or vagina T4b- Tumor invades pelvic wall or abdominal wall   Tx - Primary tumor cannot be assessed T0 - No evidence of primary tumor TNM Classification of Malignant Tumours (2002, 2009 )

7. UC with squamous differentiation 21% of urothelial carcinomas keratinisation and presence of intercellular bridges areas of conventional urothelial carcinoma are always present Differential diagnosis Invasive squamous cell carcinoma of the bladder

8. UC with glandular differentiation 6% of UC of the bladder presence of true glandular spaces within a UC pseudo glands are lined by cuboidal to tall columnar cells Differential diagnosis (clinical data, IHC) secondary spread from colorectal adenocarcinoma prostatic duct adenocarcinoma

9. Sarcomatoid UC evidence of epithelial and mesenchymal differentiation the sarcomatous component : high grade spindle cell neoplasm the epithelial component : invasive urothelial carcinoma Differential diagnosis (IHC) Primary bladder sarcoma

10. Micropapilary UC 1-6% of all invasive UC slender , delicate filiform papillary processes without fibrovascular cores tight cell clusters within empty lacunar spaces tumor cells : high nuclear to cytoplasmic ratio advaced stage with lymph node metastases Differential diagnosis (clinical data, IHC) Metastatic or secondary spread of micropapillary carcinoma of the ovary, colon, breast, lung

11. Large cell undifferentiated carcinoma extremely rare in the urinary tract sheets of large polygonal or round cells with moderate to abundant cytoplasm and distinct cell borders may contain epithelial tumor giant cell resembling giant cell carcinoma of the lung Differential diagnosis (IHC) L arge cell neuroendocrine carcinoma

12. Small cells UC 0,5-1 % of all invasive UC sheets and nests of small epithelial neuroendocrine cells (blue cells) high nuclear-to cytoplasmic ratio nuclear molding positivity for neuroendocrine markers ( synaptophysin , chromogranin, CD56) Differential diagnosis (clinical data, IHC) malignant lymphoma metastatic or secondary spread of small cell carcinoma of other primary site

13. Nested variant UC < 0,5 % of all invasive UC nests of infiltrative tumor cells infiltrating the lamina propria and deep muscularis propria irregular infiltrating border with lamina propria is characteristic tumor cells are deceptively benign looking degree of nuclear atypia increases with the depth of invasion Differential diagnosis von Brunn nests cystitis cystica , glandularis nephrogenic adenoma

14. Microcystic UC ~ 1 % of all invasive UC cysts and tubules within the lamina propria and muscularis propria often merging with conventional areas of urothelial carcinoma lining of cysts comprise neoplastic urothelial cells , which may be cytologically bland to more atypica l Differential diagnosis Florid cystitis cystica and glandularis Nephrogenic adenoma

15. Results 3227 TUR-V cases examined in the Department of Pathology between January 2004 and December 2015 male predominance (81 %) average age: 67 years-old ( ranging from 16 to 94 ) 147 cases : UC variants male predominance (92 %) a verage age: 71 years-old (raging from 54 to 82 )

16. Results UC variants identified squamous differentiation 63 glandular differentiation 47 micropapillary 15 sarcomatoid 14 small-cell 3 nested 2 microcystic 2 large cell undifferentiated carcinoma 1

17. Conclusion Recognizing the presence of histological variants of UC on TUR specimens is sometimes challenging because of limited tissue sample size. A correct diagnosis is essential, considering that these histological variants often indicates poor prognosis with increased risk not only for recurrence and progression, but also for lymph-node and distant metastasis.

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