Analysis of plasmacytoid urothelial carcinoma of the urinary bladder
Plasmacytoid urothelial carcinoma is a rare histologic subtype of bladder cancer that is associated with aggressive clinical behavior. The authors conducted a study in which they analyzed the clinicopathologic and molecular features of plasmacytoid urothelial carcinoma in 52 patients from a single institution. The patients included 44 men and eight women and were a mean age of 64 years (range, 41–91 years). All bladder cancers were high-grade urothelial carcinoma, and plasmacytoid component accounted for a mean of 47 percent of bladder tumors (range, 5–100 percent). Distinct gene mutations were found in most plasmacytoid urothelial carcinomas (n=49). The most common mutations were TP53 (n=30), TERT (n=20), and CDH1 (n=18). Copy number analysis was performed in 34 patients, and 13 of them showed copy number variations. HER2 expression was analyzed in 18 patients by immunohistochemistry, and three of them showed HER2 overexpression, which was confirmed by FISH. Thirty-two patients died of disease in a median of 15 months (range, 1–45 months). No individual gene mutations were significantly associated with clinical outcome, but mutations in the mammalian target of rapamycin (mTOR) pathway, including PICK3CA and PIK3R1 mutations, were associated with significantly shorter survival (p<.05). The authors concluded that plasmacytoid urothelial carcinoma is an aggressive histologic subtype that demonstrates frequent somatic gene mutations and copy number variations, which may underlie its oncogenesis and progression. Gene mutations of the mTOR pathway are associated with poor outcome in a subset of patients with plasmacytoid urothelial carcinoma.
Zheng L, Chen H, Zhao J, et al. Plasmacytoid urothelial carcinoma of the urinary bladder—a clinicopathological and molecular analysis of 52 cases. Hum Pathol. 2024;148. doi.org/10.1016/j.humpath.2024.04.012
Correspondence: Dr. Charles C. Guo at ccguo@mdanderson.org
Insights into malignant mitral valve degenerative disease from a sudden cardiac death cohort
Mitral valve prolapse is an accepted cause of sudden cardiac death in most autopsy series. Diagnosis at autopsy relies on subjective assessment, not on established objective pathological criteria. The authors conducted a study to establish objective measurements for helping pathologists deal with sudden cardiac death. They diagnosed 120 cases of mitral valve prolapse in 8,108 (1.5 percent) instances of sudden cardiac death. The authors analyzed prolapsing mitral valves in 27 cases and compared them to normal mitral valves in 54 age- and sex-matched subjects with morphologically normal hearts. Age at death was 39 ± 16 years (59 females and 61 males). History of mild mitral valve disease was present in 19 (16 percent) cases. Eleven (nine percent) deaths were associated with exertion. Left ventricular hypertrophy was present in nine (15 percent) females and 10 (16 percent) males. Anterior and posterior mitral valve leaflets showed thickening and ballooning in all subjects. Mitral valve prolapse showed highly significantly increased annular circumference, elongation and thickening of both leaflets, and increased mitral annular disjunction (all P < .001). Left ventricular fibrosis was present in 108 (90 percent) subjects and may explain lethal arrhythmia. In this ventricular fibrosis group, interstitial fibrosis in the posterolateral wall and papillary muscle was found in 88 (81 percent) subjects and coexisting replacement fibrosis in 40 (37 percent). To the authors’ knowledge, this is the largest series of mitral valve prolapse cases associated with sudden cardiac death highlighting a young cohort with equal representation of males and females. The authors concluded that their quantitative measurements should serve as a reference for pathologists assessing postmortem hearts for mitral valve prolapse in future studies.
Westaby J, Bicalho L, Zullo E, et al. Insights into malignant mitral valve degenerative disease from a sudden cardiac death cohort highlighting significant measurement differences from normal. Histopathology. 2024;84(6):960–966.
Correspondence: Dr. Mary Sheppard at msheppar@sgul.ac.uk