The solid-pseudopapillary neoplasm of the pancreas is a rare but enigmatic entity occurring mainly in young women. Since the first description by V. Frantz in 1959 the terminology of this tumor has continuously changed but it has remained simply descriptive, because the exact histogenesis is still obscure. Although in majority of cases the survival is excellent, nevertheless, the expected prognosis is not exactly predictable. In this review the authors aim to summarize its clinico-pathological features, the expected biological behavior, the molecular alterations, the immune phenotype and discuss the putative histogenesis. From diagnostic point of view, the salient histological characteristic findings are analyzed that would help to differentiate it from other, look-alike pancreatic tumors, and suggestions are made about the desirable content of the histological report.

• Histogenesis
• Pancreas
• Review
• Solid-pseudopapillary neoplasm

• Immunohistochemistry
• Inmunohistoquímica
• Neoplasia sólida pseudopapilar del páncreas
• Pancreas
• Páncreas
• Solid pseudopapillary neoplasm

AIM: To construct a global “metabolic phenotype” of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.

METHODS: A systematic review of the literature was performed using OvidSP and PubMed databases using keywords “pancreatic cancer” and individual glycolytic and mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype.

RESULTS: Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated.

CONCLUSION: Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.

• Metabolism
• Pancreatic cancer
• Warburg effect
• Metabolic inhibitor
• Glycolysis
• Krebs cycle

• Animals
• Carcinoma, Pancreatic Ductal/enzymology
• Carcinoma, Pancreatic Ductal/genetics
• Carcinoma, Pancreatic Ductal/pathology
• Energy Metabolism/genetics
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Glucose/metabolism
• Humans
• Pancreatic Neoplasms/enzymology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Phenotype

• autofluorescence
• cancer stem cells
• epithelial cancer stem cells
• lipofuscin
• lipofuscin-like substances
• stem cells

A brief overview is here provided on lipofuscin and lipofuscin-like substances, with particular reference to their biological significance as well as to their cellular origin and pathophysiological role. Special emphasis is also placed on the mutual relationships between lipofuscin and lipofuscin-like lipopigments on one side, and cell autofluorescence on the other.

• Cadherins/metabolism
• Carcinoma, Papillary/diagnosis
• Carcinoma, Papillary/genetics
• Carcinoma, Papillary/metabolism
• Cell Nucleus/metabolism
• DNA Mutational Analysis
• Female
• Humans
• Mutation
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Young Adult
• beta Catenin/genetics
• beta Catenin/metabolism

• Biomarkers, Tumor/analysis
• Carcinoma, Pancreatic Ductal/chemistry
• Carcinoma, Pancreatic Ductal/pathology
• Carcinoma, Pancreatic Ductal/therapy
• Cystadenocarcinoma/chemistry
• Cystadenocarcinoma/pathology
• Cystadenocarcinoma/therapy
• Cystadenocarcinoma, Mucinous/chemistry
• Cystadenocarcinoma, Mucinous/pathology
• Cystadenocarcinoma, Mucinous/therapy
• Cystadenocarcinoma, Papillary/chemistry
• Cystadenocarcinoma, Papillary/pathology
• Cystadenocarcinoma, Papillary/therapy
• Cystadenocarcinoma, Serous/chemistry
• Cystadenocarcinoma, Serous/pathology
• Cystadenocarcinoma, Serous/therapy
• Humans
• Immunohistochemistry
• Pancreas, Exocrine/chemistry
• Pancreas, Exocrine/pathology
• Pancreatic Ducts/chemistry
• Pancreatic Ducts/pathology
• Pancreatic Neoplasms/chemistry
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/therapy
• Precancerous Conditions/chemistry
• Precancerous Conditions/pathology