Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.

4th Department of Internal Medicine Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Sokolska 581 500 05 Hradec Kralove Czech Republic

AeskuLab Patologie k s Prague Czech Republic

Department of Histology and Embryology Faculty of Medicine in Hradec Králové Charles University Hradec Kralove Simkova 870 500 03 Hradec Kralove Czech Republic

Department of Medical Biology and Genetics Faculty of Medicine in Hradec Králové Charles University Hradec Kralove Czech Republic

Department of Neurosurgery and Neurooncology 1st Faculty of Medicine Charles University Military University Hospital Prague Prague Czech Republic

Department of Neurosurgery Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Sokolska 581 500 05 Hradec Kralove Czech Republic

Department of Neurosurgery Faculty of Medicine Comenius University and University Hospital Bratislava Bratislava Slovakia

Department of Neurosurgery Masaryk Hospital J E Purkyne University Ustı nad Labem Czech Republic

Department of Neurosurgery The Pardubice Region Hospital a s Kyjevska 44 53203 Pardubice Czech Republic

Department of Neurosurgery University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Pathology Military University Hospital Prague Prague Czech Republic

Department of Pathology University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Radiology Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Sokolska 581 500 05 Hradec Kralove Czech Republic

The Faculty of Medicine in Pilsen Department of Neurosurgery University Hospital in Pilsen Charles University Prague Prague Czech Republic

The Fingerland Department of Pathology Charles University Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové Sokolska 581 500 05 Hradec Kralove Czech Republic

Unilabs sro Bratislava Polianky 7 84101 Bratislava Slovak Republic

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