Lymphoepithelioma-like Carcinoma of the Bladder: Is the Prognosis Different from Conventional Bladder Carcinoma?


Recognition of other histological variants of urothelial carcinoma of the bladder is important because they may mimic benign lesions or have different clinical implications and associated prognoses, as well as treatment protocols. We report a case of lymphoepithelioma-like carcinoma (LELCA) in the bladder and discuss this rare entity with a review of other articles. Although we could not draw a conclusion on this particular disease, it is hoped that by adding cases with sufficient detail into literature, we will enable a more thorough and meaningful study where characteristics of the disease and the appropriate treatment regime could be facilitated.

KEYWORDS: Bladder; Lymphoepithelioma-like carcinoma; Cancer

CORRESPONDENCE: Eng Hong Goh, Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur, 56000, Malaysia ().

CITATION: UroToday Int J. 2012 Feb;5(1):art 84.



Lymphoepithelioma is a form of undifferentiated carcinoma that was identified primarily in the nasopharynx in Asian patients. In this location, it is in close pathogenetic relation to Epstein-Barr virus (EBV), although such an association has not been documented for lymphoepithelioma-like carcinoma (LELCA) of the urinary bladder. In addition to the bladder, LELCA has been documented in other organs, including salivary glands, the thymus, lungs, skin, the stomach, the uterine cervix, and breasts [1]. First reported by Zuckerberg et al. in 1991 [2], LELCA of the urinary bladder has gradually gained recognition worldwide, but it seems that there is still no unanimous agreement on its subtypes or its prognosis. Our case has given us an opportunity to review the various papers and make a discussion on this interesting disease.


A 71-year-old Chinese woman had repeatedly presented with a history of suprapubic pain, dysuria, and intermittent hematuria for the last 7 years. All of these episodes were treated as urinary tract infections by her general practitioner. However, after a severe bout at the end of 2009, she developed a fever, chills, and rigors, in addition to the usual urinary symptoms aforementioned. She was admitted to a private hospital in another district, and it was during this admission that she was found to have a growth at the posterior wall of her bladder. The initial transurethral resection of the bladder tumor (TURBT) revealed a histopathology finding of muscle-invasive, high-grade urothelial carcinoma, but the specimen was unavailable for another inspection at our institution due to logistics and costs. Her subsequent management at our hospital included a work-up computed tomography (CT) scan (Figure 1) and bone scans showing T4aN2M0 disease, with bladder growth infiltrating to the vagina and right vesicoureteric orifice. This resulted in right obstructive uropathy and regional lymphadenopathies. The patient refused any neoadjuvant therapy. She underwent an uneventful cystectomy, including removal of her anterior portion of the vagina, uterus, both fallopian tubes, and ovaries, as well as a lymphadenectomy to iliac level and ileal conduit creation in March 2010. The intraoperative frozen-section assessment at the ureteric margin needed repeating, as there was tremendous difficulty in identifying the malignant cellular margin in the first samples. The official histopathology result reported the presence of diffusely infiltrating and rather undifferentiated malignant cells arranged in sheets, and trabeculae with pleomorphic nuclei and prominent nucleoli. There was also a prominent lymphoid infiltrate associated with the tumor sheets and clumps. The malignant cells infiltrated into the underlying muscularis propria up to the perivesical soft tissue and into the posterior cervical region. Fortunately, the surgical margin was clear, and there was no evidence of lymphovascular invasion. However, a 1 cm, right obturator node, out of 27 lymph nodes, harbored the malignant cells similar to those seen in the bladder. The malignant tissues stained positively for cytokeratin, CD3, CD20, p53, and Ki67 (90% high), but negatively for CK20 (Figure 2 and Figure 3). A diagnosis of pure lymphoepithelioma-like carcinoma of the bladder was thus made. During her follow-up 14 months later, she was not given adjuvant therapy and was free of the disease, both clinically and radiologically.


There have been numerous studies on this particular disease. Given that it is an uncommon entity with an incidence of 0.4 to 1.3% of all bladder carcinomas [2], most studies are either case reports or a case series with a small number of patients. The largest study to date was performed by Williamson et al. who described 34 cases in the bladder in 2011 [3]. Other large case series included those by Tamas et al. [4] with 28 cases in 2007, Lopez-Beltran et al. [5], which reported 13 cases in 2000, Holmang et al. [6] with 9 cases in 1998, and Amin et al. with 11 cases in 1994 [1]. A report by Serrano et al. in 2008 compiled all cases of LELCA of the bladder by searching through PubMed in English literature. It produced very informative details and characteristics of the disease in the form of tables [7]. We actually attempted to compile all of these cases for the purpose of analysis, as well as comparison, with the large series of conventional, transitional-cell carcinoma, but the effort was hindered by inconsistency in classification and a lack of vital details.

It is unfortunate that we could not compare the 2 histological specimens of our patient, nor could we explain the differences, although there is a propensity of urothelial carcinoma for divergent variation and abundant variability in tumor morphology [3]. The histological pattern and the subclassification of LELCA of the bladder have been well described in many earlier papers [1,4,6]. Its importance lies in the fact that the prognosis of “pure” or “predominant” disease is considered better than the conventional carcinoma of the bladder, whereas the prognosis of the “focal” disease does not differ from the conventional type [1,2,5]. However, Tamas et al., who subclassified their cases into either “pure” or “mixed” types, did not share their findings. They observed that the outcomes similarly disregarded subclassification. The paper also claimed that LELCA, as a whole, shared similar outcomes with conventional urothelial carcinoma [4]. In regards to the differing opinions, many of these papers reported that the T stage of the disease and the N status—crucial prognostic factors—were tremendously unknown. The latest and largest series by Williamson et al. included the N status in almost all of their cases and reported a favorable prognosis in “pure” or “predominant” cases, but the number of patients involved was quite small; i.e., only 5 [3]. Determining the prognosis is vital, as the arguments have primarily concentrated on whether or not bladder preservation therapy is appropriate [3,4]. Taking into account our patient, with a 7-year history of symptoms, a final stage of T4aN1M0, and the absence of neoadjuvant or adjuvant therapy while remaining disease-free until the present moment, the notion that “pure” or “predominant” LELCA has a favorable prognosis is perhaps true. Is there another prognosis determinant in LELCA of the bladder? Thus far, attention has been paid to the morphological pattern of the tumor, but the molecular abnormalities have not been studied thoroughly yet [3].

In conclusion, it is our opinion that “pure” or “predominant” LELCA carries a positive outcome based on our experience, as well as that of others, although current limited data could not prove the evidence sufficiently. By pooling cases of LELCA of the bladder with adequate and comparable details in literature, a more precise understanding of this disease and a comparison with the conventional urothelial carcinoma can be facilitated. Venturing out of the avenue of morphological patterns may open up new insights into this particular disease.


  1. Amin MB, Ro JY, Lee KM, et al. Lymphoepithelioma-like carcinoma of the urinary bladder. Am J Surg Pathol. 1994;18:466-473.
  2. PubMed ; CrossRef
  3. Porcaro AB, Gilioli E, Migliorini F, Antoniolli SZ, Lannucci A, Comunale L. Primary lymphoepithelioma like carcinoma of the urinary bladder: Report of one case with review and update of the literature after a pooled analysis of 43 patients. Int Urol Nephrol. 2003;35:99-106.
  4. PubMed ; CrossRef
  5. Williamson SR, Zhang S, Lopez-Beltran A, et al. Lymphoepithelioma-like carcinoma of the urinary bladder: Clinicopathologic, immunohistochemical, and molecular features. Am J Surg Pathol. 2011;35:474-483.
  6. PubMed ; CrossRef
  7. Tamas EF, Nielsen ME, Schoenberg MP, Epstein JI. Lympoepithelioma-like carcinoma of the urinary tract: A clinicopathological study of 30 pure and mixed cases. Mod Pathol. 2007;20:828-834.
  8. PubMed ; CrossRef
  9. Lopez-Beltran A, Luque RJ, Vicioso L, et al. Lymphoepithelioma-like carcinoma of the urinary bladder: A clinicopathologic study of 13 cases. Virchows Arch. 2001;438:552-557.
  10. PubMed ; CrossRef
  11. Holmäng S, Borghede G, Johansson SL. Bladder carcinoma with lymphoepithelioma-like differentiation: A report of 9 cases. J Urol. 1998;159(3):779-782.
  12. PubMed ; CrossRef
  13. Serrano GB, Fúnez FA, López RG, et al. [Bladder lymphoepithelioma-like carcinoma. Bibliographic review and case report]. Arch Esp Urol. 2008;61(6):723-729.
  14. PubMed