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Presented by George Netto, M.D. and prepared by Safia Salaria, M.B.B.S.
Case 3: A 73 year old male smoker presented with gross hematuria and symptoms of polyuria and dysuria.
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Week 499: Case 3
A 73 year old male smoker presented with gross hematuria and symptoms of polyuria and dysuria. On cystoscopy, an ulcerated 3.7 cm mass was present in the trigone region. A transurethral biopsy was obtained.images/1alex/101011case3image1.jpg
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images/1alex/101011case3image5.jpgCorrect
Answer: Lymphoepithelioma like carcinoma (LELC) of urinary bladder
Histology: The epithelial neoplasm is composed of a proliferation of “undifferentiated” highly atypical cells arranged in a syncitial pattern with indistinct cytoplasmic borders. Characteristic of lymphoepithelioma like carcinoma of bladder, the epithelial cells contain large vesicular nuclei with very prominent nucleoli. The latter is associated with a dense obscuring lymphoid infiltrate at times admixed with other inflammatory cells such as polymorphonuclear leukocytes and histiocytes. The lymphoid cells are smaller in size than the neoplastic epithetlial cells. Mitotic figures are easily identified in the latter population of cells. Frequently, the tumor extensively invades the muscularis propria. The surface urothelium may or may not show evidence of flat carcinoma in situ (CIS) or a non invasive papillary carcinoma component. Immunostains for cytokeratins AE1/AE3, CK903, CK7 and EMA could be of help in confirming the epithelial nature of the undifferentiated cells. The lymphoid infiltrate is usually composed of a mixture of B (LCA; CD20 and CD79a positive) and T cells (LCA and CD3 positive).Unlike their nasopharyngeal counterparts, EBV studies by immunohistochemistry (LMP1) and in situ hybridization (EBER) have been shown to be consisently negative in lymphoepithelial like carcinoma of bladder.
Discussion: Lymphoepithelial like variant of urothelial carcinoma is a rare type of urinary bladder carcinoma named for its resemblance to nasopharyngeal undifferentiated carcinoma or lymphoepithelioma. The pathogenesis and biological behavior of these tumors is controversial. The associated dense lymphoid host response could lead to a misdiagnosis of such lesions as malignant lymphoma especially on a small transurethral biopsy with extensive cautery artifact. Distinguishing bladder tumors with pure or predominant lymphoepithelial like carcinoma morphology from other undifferentiated and high grade urothelial carcinoma may have implications on patient management given the relatively higher chemotherapy response rates and the potentials for bladder salvage in this variant.
Recently, Williamson et al. reported the largest series of lymphoepithelioma like carcinoma of urinary tract. The study included 34 patients (male:female, 2.8:1), ranging in age from 54 to 84 years (mean, 70 years). Urothelial carcinoma in situ was identified in 50% of patients. Immunoexpression of high molecular weight keratin 34âE12, CK7 and p63 was documented in 75%, 57%, and 53% of tumors respectively. Expression of p53 was noted in a subset of tumors (61%). In situ hybridization for human papillomavirus and immunostaining for Epstein-Barr virus were again negative in all studied tumors. The authors also used UroVysion FISH to evaluate numerical chromosomal abnormalities and found similar alterations to those usually encountered in usual cases of invasive urothelial carcinoma. Outcome in five patients with pure or predominant lymphoepithelial like carcinoma who were treated with transurethral resection and adjuvant chemotherapy was favorable with all being alive without disease up to 5 years after treatment. The latter seems to support initial suggestion that pure or predominant lymphoepithelial like carcinoma may be treated with transurethral resection and chemotherapy. However, larger studies with long-term follow-up are needed to determine the best course of treatment in this variant.Reference(s):
– Williamson SR, Zhang S, Lopez-Beltran A, Shah RB, Montironi R, Tan PH, Wang M,
Baldridge LA, MacLennan GT, Cheng L. Lymphoepithelioma-like carcinoma of the
urinary bladder: clinicopathologic, immunohistochemical, and molecular features.
Am J Surg Pathol. 2011;35(4):474-83. PubMed PMID: 21383609.
– Cohen RJ, Stanley JC, Dawkins HJ. Lymphoepithelioma-like carcinoma of the
renal pelvis. Pathology. 1999;31(4):434-5. PubMed PMID: 10643022.
– Lopez-Beltran A, Luque RJ, Vicioso L, Anglada F, Requena MJ, Quintero A, Montironi R. Lymphoepithelioma-like carcinoma of the urinary bladder: a clinicopathologic study of 13 cases. Virchows Arch. 2001 Jun;438(6):552-7.
– Amin MB, Ro JY, Lee KM, Ordonez NG, Dinney CP, Gulley ML, Ayala AG. Lymphoepithelioma-like carcinoma of the urinary bladder. Am J Surg Pathol. 1994 May;18(5):466-73.Incorrect
Answer: Lymphoepithelioma like carcinoma (LELC) of urinary bladder
Histology: The epithelial neoplasm is composed of a proliferation of “undifferentiated” highly atypical cells arranged in a syncitial pattern with indistinct cytoplasmic borders. Characteristic of lymphoepithelioma like carcinoma of bladder, the epithelial cells contain large vesicular nuclei with very prominent nucleoli. The latter is associated with a dense obscuring lymphoid infiltrate at times admixed with other inflammatory cells such as polymorphonuclear leukocytes and histiocytes. The lymphoid cells are smaller in size than the neoplastic epithetlial cells. Mitotic figures are easily identified in the latter population of cells. Frequently, the tumor extensively invades the muscularis propria. The surface urothelium may or may not show evidence of flat carcinoma in situ (CIS) or a non invasive papillary carcinoma component. Immunostains for cytokeratins AE1/AE3, CK903, CK7 and EMA could be of help in confirming the epithelial nature of the undifferentiated cells. The lymphoid infiltrate is usually composed of a mixture of B (LCA; CD20 and CD79a positive) and T cells (LCA and CD3 positive).Unlike their nasopharyngeal counterparts, EBV studies by immunohistochemistry (LMP1) and in situ hybridization (EBER) have been shown to be consisently negative in lymphoepithelial like carcinoma of bladder.
Discussion: Lymphoepithelial like variant of urothelial carcinoma is a rare type of urinary bladder carcinoma named for its resemblance to nasopharyngeal undifferentiated carcinoma or lymphoepithelioma. The pathogenesis and biological behavior of these tumors is controversial. The associated dense lymphoid host response could lead to a misdiagnosis of such lesions as malignant lymphoma especially on a small transurethral biopsy with extensive cautery artifact. Distinguishing bladder tumors with pure or predominant lymphoepithelial like carcinoma morphology from other undifferentiated and high grade urothelial carcinoma may have implications on patient management given the relatively higher chemotherapy response rates and the potentials for bladder salvage in this variant.
Recently, Williamson et al. reported the largest series of lymphoepithelioma like carcinoma of urinary tract. The study included 34 patients (male:female, 2.8:1), ranging in age from 54 to 84 years (mean, 70 years). Urothelial carcinoma in situ was identified in 50% of patients. Immunoexpression of high molecular weight keratin 34âE12, CK7 and p63 was documented in 75%, 57%, and 53% of tumors respectively. Expression of p53 was noted in a subset of tumors (61%). In situ hybridization for human papillomavirus and immunostaining for Epstein-Barr virus were again negative in all studied tumors. The authors also used UroVysion FISH to evaluate numerical chromosomal abnormalities and found similar alterations to those usually encountered in usual cases of invasive urothelial carcinoma. Outcome in five patients with pure or predominant lymphoepithelial like carcinoma who were treated with transurethral resection and adjuvant chemotherapy was favorable with all being alive without disease up to 5 years after treatment. The latter seems to support initial suggestion that pure or predominant lymphoepithelial like carcinoma may be treated with transurethral resection and chemotherapy. However, larger studies with long-term follow-up are needed to determine the best course of treatment in this variant.Reference(s):
– Williamson SR, Zhang S, Lopez-Beltran A, Shah RB, Montironi R, Tan PH, Wang M,
Baldridge LA, MacLennan GT, Cheng L. Lymphoepithelioma-like carcinoma of the
urinary bladder: clinicopathologic, immunohistochemical, and molecular features.
Am J Surg Pathol. 2011;35(4):474-83. PubMed PMID: 21383609.
– Cohen RJ, Stanley JC, Dawkins HJ. Lymphoepithelioma-like carcinoma of the
renal pelvis. Pathology. 1999;31(4):434-5. PubMed PMID: 10643022.
– Lopez-Beltran A, Luque RJ, Vicioso L, Anglada F, Requena MJ, Quintero A, Montironi R. Lymphoepithelioma-like carcinoma of the urinary bladder: a clinicopathologic study of 13 cases. Virchows Arch. 2001 Jun;438(6):552-7.
– Amin MB, Ro JY, Lee KM, Ordonez NG, Dinney CP, Gulley ML, Ayala AG. Lymphoepithelioma-like carcinoma of the urinary bladder. Am J Surg Pathol. 1994 May;18(5):466-73.
