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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Pleomorphic lymphoepithelioma-like carcinoma of the urinary bladder
Oluwole Fadare1, Idris L Renshaw, Christopher Rubin
1Department of Pathology, Wilford Hall Medical Center, Lackland AFB, TX, USA.
Abstract:
Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is often mixed with conventional transitional cell carcinoma and/or other histotypes. The pathologist's determination of the morphologic purity of a given LELC at the biopsy stage is a clinically relevant endeavour, because there is some anecdotal evidence suggesting that pure or predominant LELC may be comparatively chemosensitive and have a favorable prognostic profile, which may potentially offer the possibility of effective therapy without bladder resection. The precise degree of cellular pleomorphism that is allowed in a pure LELC is unclear. We describe herein an otherwise conventional and pure LELC that showed, in a localized area that constituted approximately 25% of the overall tumor volume, a two to six fold variation in nuclear size, including multinucleated tumor cells. These pleomorphic areas were set in the same lymphoplasmacytic infiltrate as their conventional counterparts, and similarly displayed cellular syncytia. We performed a detailed immunophenotypic comparison between the conventional areas and the pleomorphic areas. No significant differences were found between the 2 areas in overall lymphoplasmacytic or histiocytic density, lymphocytic CD4/CD8 ratio, and lymphoplasmacytic kappa/lambda ratio. Similarly, both displayed similar qualitative and quantitative staining indices for p53, Ki67, cytokeratin AE1/AE3 and p16(INKa). Scattered cells were cytoplasmically beta-catenin positive exclusively in the pleomorphic areas; however these cells were not notably larger than the cells in the conventional areas. Both components were immunohistochemically negative for HMB-45, CD1a, the estrogen receptor, Epstein-Barr virus, CD117, D2-40, CD56, cytokeratin 20 and chromogranin. Clinicopathologic analysis of a series of cases is required to establish if there is any significance to nuclear pleomorphism in LELC. However, the phenotypic similarity between the 2 areas in this case, the intimate admixture of the pleomorphic cells with the lymphoplasmacytic infiltrate, and their syncytial pattern of growth, all suggest that pure LELC may display marked nuclear pleomorphism, and that this finding may not, in of itself, be a valid basis for removing a case from the "pure" group.
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