Summary We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival ‘neuronal’ subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, lncRNA, and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma-in-situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

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Invasive ductal and lobular breast carcinomas often have different preferred metastasis sites and distinct histomorphologic characteristics. Their metastatic cytomorphologic cell features in body cavity fluids are generally readily recognized, but the single-cell/mesothelial-like pattern and its relationship to the primary tumor type have not been well studied, nor whether metastases have a propensity for certain body cavity sites on the basis of the primary tumor type. To further assess the tumor type and single-cell pattern of breast carcinoma metastases in pleural and peritoneal effusions, we retrospectively studied 853 pleural and peritoneal effusions and correlated the findings with the primary tumor type. When necessary, the single- cell/mesothelial-like pattern was documented immunohistochemically. Metastatic breast carcinomas represented 249 (50.8%) of 490 pleural and 51 (14.0%) of 363 peritoneal effusions. Most metastases in pleural and peritoneal effusions were ductal carcinomas (92.4% and 62.7%, respectively). Lobular carcinoma accounted for only 2 (0.8%) of 249 pleural and 11 (21.6%) of 51 peritoneal effusions. The single-cell/mesothelial-like cell pattern was found in all lobular carcinomas but also in 11 (6.0%) of 184 reviewed ductal carcinomas (nine pleural and two peritoneal). Awareness of these findings and the use of immunohistochemical analyses are necessary for accurately diagnosing metastatic breast carcinoma, especially lobular type.

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Cystic epithelial tumors arising from the prostate are rare, and their full histologic spectrum has yet to be defined. Herein, we present 8 examples of prostatic cystic tumors including 1 giant multilocular cystadenoma and 7 cystadenocarcinomas. We divided the cystadenocarcinomas into "giant multilocular" cystadenocarcinoma (3) and "microscopic" cystadenocarcinoma (4) because of their differing clinical presentations with clinically apparent cystic masses in the former. The cystadenoma was an 11 cm multilocular cystic pelvic tumor in a 55-year-old man who presented with lower urinary tract symptoms. The cystadenoma was lined predominantly by benign acinar cells and had a distinct basal cell layer. No recurrence occurred 3 months after resection. The 3 patients with giant multilocular cystadenocarcinomas were 62 to 82 years old, had large pelvic cystic masses (up to 16 cm), and 2 presented with obstructive urinary and lower intestinal tract symptoms. One giant multilocular cystadenocarcinoma had a markedly high cystic fluid prostate-specific antigen at >80,000 ng/mL. All 3 giant multilocular cystadenocarcinomas were ductal adenocarcinoma with exuberant intracystic papillary formations. One tumor was associated with a high-grade noncystic conventional (acinar) adenocarcinoma (Gleason score 9 [ISUP grade group 5]). Follow-up on the 3 giant multilocular cystadenocarcinoma cases (7 to 21 mo) showed multiple metastases in 1 patient but was attributed to the high-grade conventional adenocarcinoma component. In addition, we described 4 examples of microscopic cystadenocarcinomas that were small (≤1 cm) solitary or multiple cystic tumors identified on pathologic examination of the prostate. In 3 of 4 microscopic cystadenocarcinomas the lining was ductal adenocarcinoma with occasional to exuberant papillae and appeared similar to the smaller cysts in the giant multilocular cystadenocarcinomas. One of the 4 microscopic cystadenocarcinomas had an acinar adenocarcinoma lining with occasional papillae and was associated with a conventional adenocarcinoma. Follow-up of the 4 patients with microscopic cystadenocarcinoma (1 to 14 mo) showed no evidence of disease. Review of literature highlighted similarities between the findings in our cases and previously published prostatic cystadenocarcinomas, including the markedly high cystic fluid prostate-specific antigen level in giant multilocular cystadenocarcinomas and the typical ductal adenocarcinoma morphology with intracystic papillary pattern. In conclusion, cystic epithelial tumors of the prostate exhibit unique clinicopathologic features. Cystadenocarcinomas, whether the clinically apparent giant multilocular form or the incidentally identified microscopic type, represent a rare underrecognized pattern of prostatic adenocarcinoma mostly within the histologic spectrum of the ductal variant.