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Urothelial carcinoma-invasive

Lymphoepithelioma-like carcinoma

Reviewers: Nat Pernick, M.D., PathologyOutlines.com, Inc. (see Reviewers page)
Revised: 27 June 2011, last major update June 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.


● Rare bladder tumor resembling undifferentiated nasopharyngeal carcinoma (lymphoepithelioma), but EBV negative


● Also called lymphoepithelial carcinoma, but most authors prefer adding “-like” since it is EBV negative, in contrast to the nasopharyngeal tumor


● Incidence: 0.4%-1.3% of all bladder carcinomas
● Adults, mean age 67-69 years, range 52-84 years
● 75% males

Clinical features

● Rare (< 50 cases described), first reported in 1991 in bladder
● Patients present with hematuria
● Not associated with Epstein Barr virus infection in bladder (Hum Pathol 1995;26:1207)
● Outcome may be similar to urothelial carcinoma when treated by cystectomy (Mod Pathol 2007;20:828)
● May have similar pathogenesis as high-grade invasive urothelial carcinoma (Am J Surg Pathol 2011;35:474)

Case reports

● 65 year old man with hematuria (Ann Saudi Med. 2009;29:478)
● 71 year old man with primary tumor of ureter (Ann Diagn Pathol. 2010;14:209)
● 74 year old woman (Arch Pathol Lab Med. 2001;125:1383)


● Cystectomy (partial cystectomy not recommended since tumor may be multifocal with coexisting urothelial carcinoma)

Gross description

● Relatively small tumor in dome, posterior wall or trigone

Micro description

● A subtype of urothelial carcinoma resembling lymphoepithelioma of nasopharynx, but EBV negative
● Lymphoepithelioma-like component should be >50% for diagnosis
● Undifferentiated tumor cells in syncytial sheets with minimal cytoplasm, prominent nucleoli, numerous mitoses and lymphocytes (Am J Surg Pathol. 1994;18:466)
● Usually muscle invasive
● Often co-existing urothelial carcinoma and urothelial carcinoma in situ
● May have markedly pleomorphic epithelial component (Int J Clin Exp Pathol. 2009;2:194)
● Chronic inflammation may obscure tumor cells
● Non-neoplastic cells are a mixture of polyclonal B and T lymphocytes, histiocytes, eosinophils and plasma cells
● Report the percentage of lymphoepithelioma-like areas (important for treatment)

Micro images


Sheets and nests of high grade tumor cells in a syncytial pattern with prominent lymphocytes

Cords of cells

Rare glandular features

Focal clear cell features

Marked nuclear pleomorphism

Muscularis propria invasion

At low magnification, the malignant epithelial elements are intimately intermixed with lymphoid tissue. (Courtesy of Dr. George Reichel, Lubbock, TX.)

At higher magnification, the anaplastic epithelial cells are conspicuous. These cells reacted positively with antibodies to cytokeratins.

Overlying carcinoma in situ

Overlying adenocarcinoma in situ

Fig 1/2: H&E; Fig 3: keratin




CD3 (T cells)/CD20 (B cells)

Cytology description

● Single cells or mixed with inflammatory cells
● Large tumor cells with high nuclear to cytoplasmic ratio, vesicular chromatin, prominent nucleoli (Diagn Cytopathol 2008;36:600)

Positive stains

Undifferentiated cells
● Cytokeratin (AE1/AE3, CK7) and EMA; often p53

● B and T cell markers

Negative stains

● CD45/LCA (for epithelial cells), EBV
● Usually CK20

Differential diagnosis

Florid chronic cystitis: no malignant epithelial component although it may be hard to find
Large cell undifferentiated carcinoma: distinct cell borders, no prominent lymphocytic component
Lymphoma: no malignant epithelial component
Small cell carcinoma: molding or crush artifact, no prominent nucleoli and usually no prominent lymphocytic component

End of Bladder > Urothelial carcinoma-invasive > Lymphoepithelioma-like carcinoma

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