I Ilyas, Sumera

Abstract Objectives Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied. Methods Transcriptome sequencing and immunohistochemistry were performed on a series of mucinous cystic neoplasms. Results Mucinous cystic neoplasm of the liver exhibited significantly increased RNA expression of ovarian stromal markers WT1, PR, and ER2 and sex cord stromal markers SF-1, inhibin-α, and calretinin compared with nonneoplastic liver. Immunohistochemistry confirmed the RNA-level data. Evidence for sex hormone biosynthesis was identified by significant overexpression of multiple estrogen biosynthetic enzymes. Expression of 17β-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt pathways and significant downregulation of T-helper 1 and T-helper 2 pathways. Conclusions Mucinous cystic neoplasm of the liver recapitulates ovarian stroma at the morphologic, DNA, RNA, and protein levels. These data support the concept that this tumor likely arises from ectopic primitive gonadal tissue and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.

Abstract Objectives: The accurate diagnosis of malignancy from small bile duct biopsy specimens is often challenging. This proof-of-concept study assessed the feasibility of a novel optical technology, spatial-domain low-coherence quantitative phase microscopy (SL-QPM), that assesses nanoscale structural alterations in epithelial nuclei for improving the diagnosis of malignancy in bile duct biopsy specimens. Methods: The SL-QPM analysis was performed on standard histology specimens of bile duct biopsy specimens from 45 patients. We analyzed normal cells with benign follow-up, histologically normal cells with pancreaticobiliary malignancy, and malignant epithelial cells. Results: The SL-QPM–derived nuclear nanomorphology marker can not only distinguish benign and malignant epithelial cells but can also detect features of malignancy in those cells normal by light microscopy with a discriminatory accuracy of 0.90. When combining pathology with SL-QPM, the sensitivity is improved to 88.5% from 65.4% of conventional pathology, while maintaining 100% specificity. Conclusions: SL-QPM–derived nuclear nanomorphology markers represent a novel approach for detecting malignancy from histologically normal-appearing epithelial cells, with potential as an adjunctive test in patients with negative or inconclusive pathologic diagnosis on bile duct biopsy specimens.