ABSTRACT
Pancreatic cancer, most frequently as ductal adenocarcinoma (PDAC), is the third leading cause of cancer death. Clear-cell primary adenocarcinoma of the pancreas (CCCP) is a rare, aggressive, still poorly characterized subtype of PDAC. We report here a case of a 65-year-old male presenting with pancreatic neoplasia. A histochemical examination of the tumor showed large cells with clear and abundant intracytoplasmic vacuoles. The clear-cell foamy appearance was not related to the hyperproduction of mucins. Ultrastructural characterization with transmission electron microscopy revealed the massive presence of mitochondria in the clear-cell cytoplasm. The mitochondria showed disordered cristae and various degrees of loss of structural integrity. Immunohistochemistry staining for NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) proved specifically negative for the clear-cell tumor. Our ultrastructural and molecular data indicate that the clear-cell nature in CCCP is linked to the accumulation of disrupted mitochondria. We propose that this may impact on the origin and progression of this PDAC subtype.
Subject(s)
Mitochondria , Pancreatic Neoplasms , Humans , Male , Aged , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/ultrastructure , Pancreatic Neoplasms/metabolism , Mitochondria/ultrastructure , Mitochondria/metabolism , Mitochondria/pathology , Adenocarcinoma, Clear Cell/pathology , Adenocarcinoma, Clear Cell/ultrastructure , Adenocarcinoma, Clear Cell/metabolism , Microscopy, Electron, Transmission , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/ultrastructure , Carcinoma, Pancreatic Ductal/metabolism , ImmunohistochemistryABSTRACT
Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression.