Cytopathological and immunocytochemical findings of pancreatic anaplastic carcinoma with ZEB1 expression by means of touch imprint cytology

Abstract

Pancreatic anaplastic carcinoma (PAC) is rare and has an aggressive clinical course. We report an autopsy case of PAC focusing on the cytopathological characteristics of the tumor and immunocytochemical staining for vimentin, E-cadherin, and zinc finger E-box binding homeobox 1 (ZEB1), which markers are associated with epithelial markers of epithelial-mesenchymal transition (EMT). A 50-year-old woman presented to our hospital with a chief complaint of jaundice. A pancreatic head tumor and multiple liver nodules were detected on abdominal computed tomography. Biliary cytology under endoscopic retrograde cholangiopancreatography suggested ductal adenocarcinoma. Three months after admission, she died of multiorgan failure. At autopsy, touch imprint cytology using squash preparation of the pancreatic tumor identified two different cell types; numerous isolated malignant cells with large and pleomorphic nuclei and a few clusters showing irregularly overlapped nuclei and irregular contours within the necrotic background. Immunocytochemically, isolated cells were positive for vimentin and ZEB1, and negative for E-cadherin. Conversely, clusters were negative for vimentin and ZEB1, and positive for E-cadherin. Histologically, the tumor was composed of sarcomatous cells with small foci of adenocarcinoma, which were consistent with a diagnosis of PAC. Immunohistochemical staining of the adenocarcinoma and sarcomatous cells corresponded to those of the clusters and isolated malignant cells, respectively. Immunostaining of these EMT markers is useful to distinguish sarcomatous cells from adenocarcinoma and can contribute to the accurate diagnosis of pancreatic tumors with EMT.

Undifferentiated Pancreatic Carcinoma With Osteoclast-Like Giant Cells: What Do We Know So Far?

“…As mentioned above, UC-OGC shares with pancreatic ductal adenocarcinoma the same genetic background and derives from ductal tumoral clones; however, molecular events determining the pleiomorphic phenotype of tumoral cells forming UC-OGC are currently unknown. Some authors suggest that such pleiomorphic phenotype similar to a mesenchymal phenotype is the result of epithelial-to-mesenchymal transition (EMT): Yonemasu et al report a loss of E-cadherin in seven undifferentiated carcinomas (46), Sano et al demonstrate a deregulation of the b-catenin pathway in anaplastic carcinoma (47) and, more recently, Naito et al highlight that these cells are negative for E-cadherin and strongly positive for vimentin and ZEB1 (48) which is a pivotal element of the EMT process (49). A recent report described, however, that EMT activation is more frequent in undifferentiated carcinoma than in UC-OGC (50).…”

Morphologic and Molecular Landscape of Pancreatic Cancer Variants as the Basis of New Therapeutic Strategies for Precision Oncology

“…Conversely to E-cadherin, a positive correlation between UDC and vimentin and zinc finger E-box binding homeobox 1 (ZEB1) is observed by IHC [94,95]. Indeed, vimentin is a marker of mesenchymal features, while ZEB1 represents a transcriptional repressor of epithelial-to-mesenchymal transition (EMT) induction [96,97].…”

ZEB1 expression is frequently detected in undifferentiated and de‐differentiated carcinomas, but is not specific among endometrial carcinomas

“…However, it remains unclear whether ZEB1 immunohistochemistry is applicable to other sites. Although ZEB1 expression was previously reported in pancreatic UC, 37 validation analyses of normal and tumour tissues in other organs are needed.…”