Lymphoepithelioma-like carcinoma of the urinary bladder: A rare case report.

Bladder cancers are the second most common urogenital malignancy, its most common type being urothelial carcinoma. Lymphoepithelioma-like carcinoma (LELC) which is commonly described in the nasopharynx is a very rare presentation in the bladder. Diagnosis of this entity poses a histopathological challenge. Nonetheless, the correct diagnosis is important as it implies a different therapeutic approach with the potential bladder salvage treatment protocol. We here present a case of an 87-year-old man, who was diagnosed as LELC. To the best of our knowledge, this is the first case of LELC reported from India in English literature.

INTRODUCTION

Bladder cancer is the second most common malignancy of the urogenital tract in males in India, with an annual incidence of 2.8%.[1] Urothelial carcinoma is the most common type of bladder malignancy accounting for more than 90% cases.[23] Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated form of carcinoma consisting of poorly differentiated epithelial cells with dense lymphoid cell infiltration. LELC was initially described in the nasopharynx and was subsequently reported in multiple organ system including various sites in the head and neck, lung, cervix, stomach, skin, breast, etc.[4] Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is exceedingly rare with an incidence of 0.3–1.3% of all bladder malignancies. Since its initial description by Zukerberg et al. in 1991, no more than 93 cases has been described in English literature, with no published report from India, to the best of our knowledge.[56]

Diagnosis of this entity can be challenging owing to its resemblance with poorly differentiated urothelial carcinoma and lymphoma. Nonetheless, identification of LELCB is important for it is sensitive to radiotherapy and chemotherapy, irrespective of the stage, making it an ideal candidate for bladder salvage therapy.[56]

CASE REPORT

An 87-year-old man presented with episodic macroscopic hematuria for 1-week. He had a similar episode around 4 months back. There was no associated dysuria or any past history of urological problems. Physical examination, vitals, and basic laboratory workup were unremarkable.

Urine cytology revealed the presence of hematuria, pyuria, and cells with atypical morphology and the cytology was reported as suspicious for malignancy. Cystoscopy was performed which showed the presence of a 5 cm ×4 cm × 3 cm, solid looking tumor in the posterolateral surface of the bladder along with multiple small cauliflower like papillary tumor in the dome and the posterior wall. Computerized tomography (CT) of the lower abdomen revealed the growth [Figure 1] along with the presence of multiple enlarged inguinal lymph nodes. No evidence of distant metastasis was observed. Transurethral resection of the bladder tumor (TURBT) was done using 1.5% glycine irrigation and monopolar cautery and the sample obtained was sent for histopathological examination, with a clinical working diagnosis of lymphoma, owing to the unusual solid appearance of the tumor and presence of the regional lymph node enlargement. On histopathological examination, the tumor was predominantly composed of the lymphoepithelioma-like component which comprised more than 90% of the tumor [Figure 2]. The tumor showed the presence of a large pleomorphic cell with prominent nucleoli and ill-defined cytoplasmic outline, imparting a syncytial appearance [Figure 3]. These cells were seen infiltrating into the muscularis propria and was staged pT2b. There was heavy infiltration of lymphoid cell within the tumor. The papillary area seen on cystoscopy was consistent with urothelial carcinoma, but this component comprised no more than 5% of the tumor, and this component was not seen to infiltrate the muscle layer. Immunohistochemistry (IHC) showed the expression of CK7 in the tumor cells [Figure 4] and the cells were negative for CK20 [Figure 5]. Special stains performed for glycogen and mucin were negative. In situ hybridization for Epstein–Barr virus (EBV) was negative for EBV-encoded RNA. The lymphoid cells were CD45 positive on IHC [Figure 6]. The final histopathological diagnosis was the predominant type of LELC. The patient, following TURBT is further planned on systemic chemotherapy. Radiotherapy, if required will be given, and the patient will be kept under close follow-up.

Figure 1

Computerized tomography scan showing a solid growth arising from the left posterolateral wall of the urinary bladder

Figure 2

Microphotograph showing epithelial tumor cells intricately mixed with lymphoid cells (H and E, ×100)

Figure 3

Pleomorphic tumor cells with hyperchromatic nuclei and prominent nucleoli with a syncytial appearance. Lymphoid cells can be appreciated (H and E, ×200)

Figure 4

Immunohistochemistry showing intense cytoplasmic and membranous CK7 positivity in tumor cells (Immunohistochemistry, CK7, ×200)

Figure 5

Tumor cells are negative for CK20 immunostaining (Immunohistochemistry, CK20, ×200)

Figure 6

Lymphoid cells are CD45 (leukocyte common antigen) positive on immunohistochemistry. The epithelial cells have not taken up the stain (immunohistochemistry, CD45, ×200)

DISCUSSION

LELC is an uncommon form of bladder tumor seen mostly in elderly males with the mean age of 69 years at presentation, and most cases are in pT2–pT3 stage at the time of diagnosis.[2] LELC is a common malignancy in the nasopharynx, and it is associated invariably with EBV. However, this association is not seen in the bladder.[7] The exact pathogenesis of LELC remains elusive, but an abnormality in p53 regulation and stem cell origin for the carcinoma has been suggested.[89]

The most common presenting symptom is macroscopic hematuria, accompanied with urgency.[10] Amin et al. have provided a histopathological classification for LELC based on the proportion of lymphoepithelioma component as pure (100%), predominant (≥50%), or focal (<50%). The predominant and mixed pattern were usually associated with transitional cell urothelial carcinoma or with squamous or adenocarcinoma like differentiation.[11] Histologic differential diagnosis includes poorly differentiated urothelial carcinoma with lymphoid cell infiltration, lymphoma, and small cell carcinoma of the bladder. Furthermore, due to the presence of dense inflammatory background, and histiocytes mimicking the neoplastic cells, chronic cystitis should be excluded.[12] In the present case, the morphology of neoplastic cells with the presence of CK7 and the absence of CK20 expression and CD45 expression in the lymphoid cells with mixed B- and T-cell phenotype ruled out the above mentioned conditions.

Yoshino et al. performed a pooled analysis of all the 93 cases LELCB cases described in English literature. They found that 74% of the cases were described in a male with 83% cases belonging to the pure and predominant histological category. The majority of the cases (83%) were in pT2–pT3. Fifty-five percentage cases were treated by TUR and 48% cases received adjuvant therapy in the form of radiotherapy, systemic or intravesical chemotherapy. The overall cause-specific survival for LELCB was 83% and was 90% for the pure and predominant cases. The pure and predominant subtypes were more favorable than the focal subtype in prognosis, despite the presence of muscle infiltration. This might be related to the dense inflammatory infiltrate that results in a strong immune response against the tumor cells.[5]

Due to the scarcity of cases described, no clear cut treatment guideline exists for LELCB. It has been suggested that pure and predominant subtypes are sensitive to chemotherapy and may be best treated with bladder preservation. On the other hand, focal LELC has a more aggressive character and the best management suitable for this subtype would be multifocal therapies, including radical cystectomy, adjuvant systemic chemotherapy or external beam radiotherapy, as for advanced conventional urothelial carcinoma.[13]

CONCLUSION

As outlined in the article, experience with our patient suggests that the diagnosis of LELCB may be a histopathological challenge requiring experience and good knowledge about this entity. Due to the potential for a bladder salvage treatment for the pure and predominant subtype, histopathological information remains important in proper case selection and appropriate management of these cases.

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Conflicts of interest

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