147Archivio Italiano di Urologia e Andrologia 2016; 88, 2 CASE REPORT Lymphoepithelioma-like carcinoma of the bladder: A case report Konstantinos Stamatiou 1, Georgios Christopoulos 2, Aikaterini Tsavari 3, Kallirhoe Koulia 3, Kassiani Manoloudaki 3, Thivi Vassilakaki 3 1 Urology Department, Tzaneio Hospital Pireas, Greece; 2 Department of Internal Medicine, Tzaneio Hospital Pireas, Greece; 3 Pathology Department, Tzaneio Hospital Pireas, Greece. Lymphoepithelioma is a rare histological type of low differentiated carcinoma of the nasopharyngeal region characterized by marked infiltra- tion of lymphocytes in the area involved by tumor. However, carcinomas with this peculiar morphologic feature have been also described in various anatomic locations and they are generally designated «lymphoepithelioma-like carcinomas». Those of the urinary bladder are uncommon as they account of 0.4%-1.3% of all bladder carcinomas. They may coexist with the conventional urothelial carcinoma. Given their rari- ty, there is poor information regarding their behaviour. Here we present a new case of lymphoepithelioma-like carci- noma in the bladder and we discuss its characteristics and prognosis. KEY WORDS: Lymphoepithelioma-like carcinoma; Bladder; Prognosis. Submitted 24 April 2015; Accepted 21 May 2015 Summary No conflict of interest declared. according to the percentance of lymphoepithelioma com- ponent within the tumor. Therefore three types of LELC are described: pure (100%), predominant (> 50%), or focal (< 50%) (3). Their occurrence in the urinary system is very rare and in fact, the reported incidence of LELC in the bladder is between 0.4% and 1.3% of all bladder car- cinomas (4). CASE PRESENTATION A 67-year-old woman suffering from recurrent urinary tract infections presented with macroscopic hematuria for 2 months. Urinalysis was non diagnostic for infection while urine cytology analysis showed markedly atypical urothelial cells. The patient underwent cystoscopic examination, which revealed a large tumor with mixed - polypoid and solid- morphology, located in the right lat- eral wall, the trigon and the dome of the bladder. A com- puted tomography (CT) scan suggested locally advanced disease (Figure 1) however no lymph node involvement, non distant metastasis, and no hydronephrosis were shown. She refused surgical intervention; however, she subsequently agreed to receive treatment after an episode DOI: 10.4081/aiua.2016.2.147 INTRODUCTION Lymphoepithelioma also known as “class III nasopharyn- geal carcinoma” is a rare form of undifferentiated carci- noma of the nasopharyngeal region that is considered a variant of undifferentiated non-keratinizing squamous cell carcinoma. It is characterized by excess inflammato- ry infiltrate of lymphocytes which appears to be inti- mately admixed with the carcinomatous cells. The last are large with vesicular nuclei and prominent nucleoli that are arranged in a dense growth pattern. This tumor displays a strong association with the Epstein Barr virus infection and its incidence exhibits a remarkable geo- graphic variation (1, 2). Reason explaining the above peculiarity is practically unknown. Lymphoepithelioma-like carcinomas (LELC) arise out- side of the nasopharynx, but resemble a lymphoepithe- lioma both morphologically and histologically. They may be found in almost any organ containing epithelial tissue such as the lung, thymus, breast, colon, endometrium, prostate, and skin, as well as urinary bladder, trachea, esophagus, stomach, salivary glands, vulva (3). They may coexist with the conventional adenocarcinomas of the abovementioned organs and therefore they are classified Figure 1. Computed tomography (CT) scan suggested locally advanced disease. Stamatiou_Stesura Seveso 01/07/16 11:12 Pagina 147 Archivio Italiano di Urologia e Andrologia 2016; 88, 2 K. Stamatiou, G. Christopoulos, A. Tsavari, K. Koulia, K. Manoloudaki, T. Vassilakaki 148 of recurrent gross hematuria accompanied by acute drop in hematocrit levels. The patient underwent an extensive transurethral resection of the bladder tumor (TUR-BT) in a single session. Sections of the TUR-BT showed invasive carcinoma, composed of predominant LELC (50% of the specimen) with grade 3 urothelial carcinoma (Figures 2- 5). The patient was diagnosed with local invasive blad- der tumor, and she was suggested to undergo cystectomy with ileal conduit formation. However due to special concerns regarding effects of surgery on her able-bodied- ness she seeked organ-conserving approaches and she was referred to the oncological clinic. There she was advised that bladder-conserving approaches were not recommended because of the likely poor response to chemotherapy by the LELC elements, rendering thus radical cystectomy the standard of care. However, the woman continued to seek bladder preservation and pre- sented to our institution to discuss bladder-sparing options. Due to the limited experience regarding treat- ment of this particular tumor, the patient was further referred to the radiotherapy department. There she was advised to receive chemoradiation. Uncertainty regard- ing the outcome and additional consulting helped the patient to choose radical cystectomy. She did not receive adjuvant therapy. She is now under close observation with regular clinical and radiologic follow-up. DISCUSSION Given their rarity, there is poor information regarding LECCs behaviour. However, urinary bladder carcinomas with a lymphoepithelioma-like component often mani- fest in T2-T3 stages and in 10% to 15% of the reported cases the cancer has spread to distant organs at the time of the first diagnosis. On the other hand, since these tumors constitute less than 1.5% of all carcinomas encountered at this anatomic location, no large system- atically collected follow-up data exists and limited infor- mation regarding their biologic behaviour render treat- ment choice difficult (5). Figure 2. Lymphoepithelioma-like carcinoma of the bladder infiltrating tumours cells and nests in an inflamatory background (H-Ex20). Figure 3. The coexistent typical urothelial carcinoma in the same tumour (H-Ex20). Figure 4. Strong immunoreactivity against CKAE1-AE3 of tumours cells (x20). Figure 5. CKAE1-AE3 in typical urothelial carcinoma. Comparative study (x20). Stamatiou_Stesura Seveso 01/07/16 11:12 Pagina 148 Therefore, the fact that most LECCs are discovered in advanced stages (T2-T3) could be rather attributed to the lack of specific symptoms than to a presuming aggressive behaviour. In fact, evidence suggests that LELCs of the urinary tract may exhibit less malignant potential than the conven- tional urothelial carcinoma: it has been demonstrated that pure or predominant type responds better to chemotherapy than conventional urothelial carcinoma (6). In mixed cases of urinary bladder carcinomas and LELCs, the more the presence of lymphoepithelioma-like elements, the less the risk of death from the disease. More precisely, a 5-year survival rate of 59% was report- ed for the predominant type while that of the pure type achieves 62% (7). Favourable prognosis along with response to chemother- apy provides a potential to salvage bladder function in patients with locally advanced LELC. In a small number of patients with pure and predominant LELC treated with transurethral resection of bladder tumor (TUR) and chemotherapy only, no evidence of disease was achieved in a follow-up period between 2 to 18 years (8-10). In most of the reported cases, the platinum-based chemotherapies were performed in the treatment of both locally advanced and metastatic disease (9). However, as with other variants of bladder tumors, there are no clear guidelines for the treatment of LELC. Exactly because of the respectively favourable prognosis efforts should be given in the prompt diagnosis of this rare tumor, espe- cially when occurs in the pure type. The differential diagnosis includes chronic cystitis, malignant lymphoma, and poorly differentiated carcino- ma with a prominent stromal lymphocytic infiltrate (10). However, in our case lymphoplasmacytic infiltrate was not sufficiently dense as to obscure the epithelial com- ponent, while the presence of an epithelial malignancy was clearly apparent. In conclusion, more experience in the management of this rare tumour is needed in order to extract safe con- clusions on its prognosis and provide clear guideline for its treatment. REFERENCES 1. Wenig BM. Squamous cell carcinoma of the upper aerodigestive tract: precursors and problematic variants. Mod Pathol. 2002; 15:229-254. 2. Terada T. Epstein-Barr virus associated lymphoepithelial carcino- ma of the esophagus. Int J Clin Exp Med. 2013; 6:219-26. 3. Mayer EK, Beckley I, Winkler MH. Lymphoepithelioma-like car- cinoma of the urinary bladder—diagnostic and clinical implications. Nat Clin Pract Urol. 2007; 4:167-71. 4. Amin MB, Ro JY, Lee KM. et al. Lymphoepithelioma like carcino- ma of the urinary bladder. Am J Surg Pathol. 1994; 18:466-473. 5. Samaratunga H, Delahunt B. 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Virchows Arch 2001; 438:552-557. 149Archivio Italiano di Urologia e Andrologia 2016; 88, 2 Lymphoepithelioma-like carcinoma of the bladder Correspondence Konstantinos N. Stamatiou, MD (Corresponding Author) stamatiouk@gmail.com Urology Department, Tzaneio Hospital Afendouli 1 Ave 18536 Pireas, Attica, Greece Georgios Christopoulos, MD Department of Internal Medicine, Tzaneio Hospital, Pireas, Greece Aikaterini Tsavari, MD Kallirhoe Koulia, MD Kassiani Manoloudaki, MD Thivi Vassilakaki, MD Pathology Department, Tzaneio Hospital, Pireas, Greece Stamatiou_Stesura Seveso 01/07/16 11:12 Pagina 149