General
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• Primary urothelial carcinoma arising in vagina with no evidence of direct extension or metastasis from lower urinary tract or urinary bladder, or implantation by irrigation fluid of transurethral resection or transfer of urine

Terminology
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• Primary vaginal urothelial carcinoma

Epidemiology
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• Extremely rare (Int J Clin Oncol 2010;15:626)

Pathophysiology
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• Pathogenesis is unclear but direct extension or metastasis from bladder urothelial carcinoma needs to be ruled out
• Both vagina and urinary bladder are embryologically derived from urogenital sinus
• May derive from common vaginal stem cell line containing an immature cell with pluripotent capacity during development (Int J Clin Oncol 2010;15:626)
• May originate from urothelial / transitional cell metaplasia of vaginal squamous epithelium (Int J Gynaecol Obstet 2011;115:292)

Clinical features
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• Vaginal bleeding

Diagnosis
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• Based on clinical history and histomorphological features
• Can be both non-invasive and invasive (Int J Clin Oncol 2010;15:626)

Case reports
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• 62 year old and 76 year old women with papillary tumors (Scand J Urol Nephrol 1997;31:107, Pathol Res Pract 1990;186:358)
• Low grade tumor (Histopathology 1994;24:581)
• With pagetoid spread pattern (Hum Pathol 1998;29:299)

Micro description
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• Histology resembles conventional urothelial carcinoma / transitional cell carcinoma
• Tumor cells have papillary architecture with a fibrovascular core
• Low grade to high grade cytological atypia can be seen
• Can be both non-invasive without infiltration of lamina propria or invasive with infiltration into stroma (Int J Gynaecol Obstet 2011;115:292)

Micro images
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Neoplastic cells in sheets and trabeculae

Cells arranged around central vascular core

Cytology description
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• Specimen is usually highly cellular with tumor cells arranged singly and in loose three dimensional clusters, with overlapping nuclei
• Tumor cells are large and polygonal with well defined cell borders, high nuclear to cytoplasmic ratio, granular basophilic cytoplasm, coarse chromatin and conspicous nucleoli
• Scattered keratinized single cells with atypical hyperchromatic nuclei can also be present
• Shares many morphologic features with primary squamous cell carcinoma of vagina, including focal keratinization (Diagn Cytopathol 2012;40:168)

Positive stains
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• p63, cytokeratin 7, cytokeratin 20, and 34βE12 (Int J Gynaecol Obstet 2011;115:292)

Negative stains
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• p16, HPV (Int J Gynaecol Obstet 2011;115:292)

Differential diagnosis
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• Metastasis from urinary bladder or urinary tract
• Primary vaginal squamous cell carcinoma

Additional references
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• Urology 1989;33:477, Br J Urol 1991;67:102, Br J Urol 1991;67:660, Eur J Gynaecol Oncol 1999;20:233

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