膀胱原发性透明细胞腺癌5例的临床病理、免疫表型和分子遗传学特征OA

Objective To investigate the clinicopathological features,immunophenotype,molecular genetic al⁃terations,and prognosis of primary clear cell adenocarcinoma(CCA)of the bladder.Methods Five cases of primary bladder CCA diagnosed at Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,were retrospectively analyzed.Clinical data were collected,histomorphological features and immunomarker expression were evaluated by HE staining and immunohistochemistry,and next-generation sequencing(NGS)was per⁃formed in three cases to characterize the mutational profile,tumor mutational burden(TMB),and microsatellite sta⁃tus.Results All five patients were women,with a mean age of 64 years.The tumors were predominantly located in the bladder trigone and posterior wall.Histologically,the tumors showed tubular,papillary,microcystic,or solid growth patterns and contained hobnail cells with clear or eosinophilic cytoplasm.The tumor cells were diffusely posi⁃tive for CK7,PAX8,HNF1β,Napsin A,and CA125,whereas GATA3 was focally positive in four cases.All cases showed a wild-type p53 expression pattern and retained mismatch repair protein expression.NGS revealed heteroge⁃neous alterations involving PIK3CA,KRAS,FANCA,NSD1,and the TERT promoter.All three sequenced tumors were microsatellite stable and had low-to-intermediate TMB.One patient with high-risk features,including advanced stage and high-grade morphology,had a poor outcome;the tumor also showed reduced expression of the differentiation markers HNF1β and Napsin A and a complex mutational profile that included KRAS and NSD1 alterations.Conclu⁃sion Primary bladder CCA has distinctive morphological and immunophenotypic features.The molecular findings,in⁃cluding alterations in the TERT promoter,PIK3CA,and KRAS,may provide a basis for future targeted therapeutic strategies.