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An unuual tumor of the urinary bladder. (Pathologic Quiz Case).

A 74-year-old woman presented to our institution for recurrent hematuria and dysuria. She had no significant medical history. Cystoscopy showed a 1.1-cm ulcerated tumor located in the dome of the bladder. A transurethral resection was performed, and histologic examination revealed a poorly differentiated invasive carcinoma. The patient underwent a partial cystectomy.

Macroscopically, the resected specimen measured 4 x 2.5 cm. A central ulcerated tumor measuring 1.5 cm was observed. Light microscopic examination of hematoxylineosin-stained sections demonstrated nests, sheets, and cords of undifferentiated malignant cells arranged in syncytia (Figure 1). The tumor cells were large, polygonal, and had scanty ill-defined cytoplasm and large vesicular nuclei with prominent nucleoli (Figure 2). There were numerous mitoses. These atypical cells were intimately admixed with an intense lymphoid infiltrate, which consisted of mature lymphocytes, plasma cells, histiocytes, and rare neutrophils (Figure 1). The tumor cells invaded the superficial muscle.


Immunohistochemical studies on paraffin-embedded sections showed staining of the large atypical cells with antibodies against pancytokeratin and cytokeratin 7 (Figure 3). The sections were negative for cytokeratin 20, leukocyte common antigen, CD20, and CD3. The accompanying lymphoid infiltrate was variably positive for CD20 and CD3. Immunodetection for Epstein-Barr virus was negative with immunohistochemistry (latent membrane protein 1) and in situ hybridization (Epstein-Barr virus-encoded RNA 1).


What is your diagnosis?

Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is a rare and recently described entity; only 23 cases have been reported to date. (1) The first case was reported in 1991 by Zukerberg et al. (2) This tumor occurs in late adulthood (mean, 69 years) and more frequently in men (10:3 ratio). (3) Patients present with macroscopic hematuria and dysuria. The tumor is usually relatively small and is located in the dome, posterior wall, or trigone of the bladder.

Microscopically, the LELC pattern is defined by undifferentiated tumor cells arranged in syncytial sheets with ill-defined borders, prominent nucleoli, and numerous mitoses. These tumor cells are admixed with a lymphoid infiltrate mimicking a nasopharyngeal lymphoepithelioma. Lymphoepithelioma-like carcinoma tumor cells are immunoreactive to cytokeratin and epithelial membrane antigen and are negative for leukocyte common antigen, confirming their epithelial nature. These tumors are subdivided into pure LELC, predominate (>50% of the whole tumor) LELC, and focal (<50%) LELC patterns. (4) This case involved pure LELC.

There are several potential pitfalls when diagnosing a tumor with an LELC pattern. First, a malignant lymphoma must be excluded. Primary lymphoma of the urinary bladder is extremely rare. Polymorphism of the lymphoid background and immunohistochemical stains using keratin and leukocyte common antigen will help make the diagnosis.

Also, the intense lymphoid infiltrate of the LELC can mask the neoplastic cells and causes misdiagnosis of the lesion as florid chronic cystitis, especially on biopsy specimen. Thus, dense lymphoid infiltrate must be closely examined for neoplastic cells. Immunohistochemistry should be employed to demonstrate an epithelial component within the inflammation.

On biopsy specimens, which could be crushed or inadequately fixed, differential diagnosis of LELC includes small cell carcinoma of the bladder. Immunohistochemical stains show positivity for neuroendocrine markers (chromogranin A, synaptophysin).

Lastly, an undifferentiated transitional cell carcinoma with lymphoid reaction has to be distinguished from LELC with the typical cytologic features and syncytial pattern of the tumor cells.

The best reason to recognize LELC pattern is the favorable outcome of this histologic subtype, especially the pure or the predominate pattern. (1) Chemotherapy combined with transurethral resection has been proposed, allowing preservation of the bladder. (3) Unlike cases affecting the nasopharynx, salivary glands, lung, or thymus, no association with Epstein-Barr virus was found in LELC of the urinary bladder. (5)


(1.) Holman S, Borghede G, Johansson SL. Bladder carcinoma with lymphoepithelioma-like differentiation: a report of 9 cases. J Urol. 1998;159:779-782.

(2.) Zukerberg LR, Harris NL, Young RH. Carcinomas of the urinary bladder simulating malignant lymphoma: a report of five cases. Am J Surg Pathol. 1991; 15:569-576.

(3.) Grignon DJ. Neoplasms of the urinary bladder. In: Bostwick DG, Eble JN, eds. Urological Surgical Pathology. Mosby-Year Book Inc; 1997:241-242.

(4.) Amin MB, Ro JY, Lee KM, et al. Lymphoepithelioma-like carcinoma of the urinary bladder. Am J Surg Pathol. 1994;18:466-473.

(5.) Gulley ML, Amin MB, Nicholls FM, et al. Epstein-Barr virus is detected in undifferentiated nasopharyngeal carcinoma but not in lymphoepithelioma-like carcinoma of the urinary bladder. Hum Pathol. 1995;26:1207-1214.

Accepted for publication February 1, 2001.

From the Department of Pathology, Lille University Hospitals, Lille, France.

Reprints not available from the authors.
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Author:Augusto, David; Gosselin, Bernard; Leroy, Xavier
Publication:Archives of Pathology & Laboratory Medicine
Article Type:Brief Article
Geographic Code:1USA
Date:Oct 1, 2001
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