Bladder & urothelial tract

• Inverted urothelial papilloma
• Inverted papilloma of the urinary bladder
• Brunnian adenoma (Hum Pathol 1978;9:229)

• Rare; < 1% of all urothelial neoplasms of the bladder
• Broad age range (8 - 88 years), commonly 50 - 60 years (Urol Oncol 2013;31:1584, Urol Case Rep 2020;35:101543)
• More common in men; M:F = 5.8:1 (Urol Oncol 2013;31:1584)

• Urinary bladder: bladder neck (most common, 41%), trigone, lateral wall, posterior wall, some tumors multifocal (Urol Oncol 2013;31:1584)
• Upper urinary tract and urethra

• HRAS mutation (10 of 11 tumors) and KRAS (1 of 11 tumors) (J Pathol 2019;248:260)

• Hematuria, dysuria, irritative voiding symptoms, lower urinary tract obstructive symptoms (Cancer 2006;107:2622)
• Flank pain in upper urinary tract lesions (Oncol Lett 2012;4:71)

• Tumor mass on computerized tomography (CT) scan and magnetic resonance imaging (MRI)
• Sessile or pedunculated mass with smooth contour on cystoscopy
• Histopathological exam (see Microscopic (histologic) description) (Mod Pathol 2015;28:612)

• CT scan with contrast: filling defect
• MRI: polypoid lesion with nonpapillary surface and thin stalk (AJR Am J Roentgenol 2015;205:311)

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• Low recurrence rate (< 2%) (Urol Oncol 2013;31:1584)

• Complete transurethral resection (Cancer 2006;107:2622)

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• Raised, sessile, pedunculated or polypoid mass with smooth contour
• Single or multiple (1.3 - 4.4%) (J Urol 1996;155:1391)
• Size ranges from 1 to 50 mm (mean of 12.8 mm), measured up to 8 cm (BJU Int 2011;107:532)

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• Sharply circumscribed, endophytic proliferation of thin and complex anastomosing cords, islands and trabeculae of cytologically bland urothelial cells with virtually no nuclear atypia (Mod Pathol 2015;28:612)
• Invaginating trabeculae composed of 5 - 10 layers of urothelial cells with central streaming and peripheral palisading cells, embedded in lamina propria
• Surface is lined by the normal urothelium with no or minimal exophytic papillary component
• Urothelial cells with vacuolation and foamy xanthomatous cytoplasmic changes may be seen (Hum Pathol 2006;37:1577)
• Mild degenerative cytologic atypia may be seen
• Mitotic figures are absent or extremely rare

Contributed by Y. Albert Yeh, M.D., Ph.D., Daniel Athanazio, M.D., Ph.D. and Debra Zynger, M.D.

A 74 year old man presented to the urology clinic with hematuria and dysuria. Cystoscopic examination showed a polypoid mass with smooth surface in the bladder neck. A transurethral bladder tumor resection was performed. An image of the histopathological examination is shown above. What is the diagnosis?

1. Florid cystitis cystica proliferation
2. Florid von Brunn nest proliferation
3. Inverted high grade papillary urothelial carcinoma
4. Inverted urothelial papilloma
5. Paraganglioma

D. Inverted urothelial papilloma. This image shows an inverted urothelial papilloma characterized by invaginating growth of anastomosing trabeculae with central streaming of bland urothelial cells. Answers B and A are incorrect because florid von Brunn nests and cystitis cystica are composed of large nests of urothelial cells arranged in a lobular pattern with regular spacing. There is no trabecular formation. Answer C is incorrect because inverted high grade papillary urothelial carcinoma is composed of irregular and complex anastomosing cords and trabeculae with disorganized, pleomorphic and hyperchromatic urothelial cells. Answer E is incorrect because no zellballen pattern of cells is seen.

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Reference: Inverted urothelial papilloma

A 68 year old man presented to the urology clinic with lower urinary tract obstructive symptoms. Cystoscopic examination showed a polypoid mass with smooth contour in the posterior wall of the bladder. A transurethral bladder tumor resection was performed. An image of the histopathological examination showed an endophytic growth with tumor cells stained positive for immunomarkers GATA3 and p63. A histopathological image is shown above. What is the diagnosis?

1. Carcinoid tumor
2. Inverted high grade papillary urothelial carcinoma
3. Inverted low grade papillary urothelial carcinoma
4. Inverted urothelial papilloma
5. Leiomyoma

D. Inverted urothelial papilloma. The tumor is composed of trabeculae of urothelial cells (positive for GATA3 and p63) with central streaming and peripheral palisading of cells. Answer E is incorrect because is incorrect because leiomyoma is negative for GATA3 and has very focal and weak cytoplasmic staining for p63. Answers B and C are incorrect because the urothelial cells in both inverted low grade and high grade papillary urothelial carcinoma show marked dispolarity of cells with moderate to severe nuclear pleomorphism and hyperchromasia. Answer A is incorrect because carcinoid tumor cells do not have fine and coarse chromatin. Neuroendocrine cells are stained negative for GATA3, although p63 may be weakly or focally positive.

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Reference: Inverted urothelial papilloma