Novel Ultrastructural Insights into the Clear-Cell Carcinoma of the Pancreas: A Case Report

Author:

Giansante Valentina1,Di Angelo Luca1,Calabrese Chiara1,De Sanctis Paolo1,Regi Paolo2ORCID,Martelli Filippo Maria2,Stati Gianmarco1ORCID,Lattanzio Rossano34ORCID,Alberti Saverio5ORCID,Guerra Emanuela14ORCID,Di Pietro Roberta16ORCID

Affiliation:

1. Department of Medicine and Aging Sciences, Section of Biomorphology, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy

2. “P. Pederzoli” Hospital, Via Monte Baldo, 24, 37019 Peschiera del Garda, Italy

3. Department of Innovative Technologies in Medicine & Dentistry, “G. d’Annunzio” University of Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy

4. Laboratory of Cancer Pathology, Center for Advanced Studies and Technology (CAST), “G. d’ Annunzio” University of Chieti-Pescara, Via L. Polacchi, 11, 66100 Chieti, Italy

5. Unit of Medical Genetics, Department of Biomedical Sciences—BIOMORF, University of Messina, Via Consolare Valeria, 98125 Messina, Italy

6. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA

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.

Funder

PhD grant in Translational Medicine awarded

Italian Ministry of University and Research (MUR) funds

Publisher

MDPI AG

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