Calcifying pseudoneoplasm of neuroaxis (CAPNON) is a rare lesion of the central nervous system with uncertain histogenesis. We further explored phenotypic spectrum of the entity with respect to possible histogenesis. We collected 5 cases of CAPNONs, performed a detailed morphological assessment, and performed an extensive immunohistochemical analysis (EMA, progesterone receptors, MUC4, SSTR2A, cytokeratin AE1/3, cytokeratin 18, GFAP, neurofilaments, desmin, nestin, synaptophysin, S100 protein, SOX10, CD56, Podoplanin, SATB2, ERG, CD45, and CD163) to elucidate the histogenesis. Furthermore, we performed NGS analysis of one case. The clinical course was benign in all cases. All lesions showed extensively calcified matrix in multilobular arrangement, with a palisade of osteoblast-like cells. Characteristic fibrohyaline matrix was notable in 4/5 cases, while one case was myxoid with rod-like calcifications. Metaplastic lamellar bone was present in 4/5 cases and psammoma bodies were present in 2/5 cases. In 4/5 cases, areas of entrapped glial tissue were present. Expression of EMA was focally present in 3/5 cases, SSTR2A and nestin in 2/5 cases, and progesterone receptor in 2/5 cases in rare cells. We did not observe concomitant expression of EMA, SSTR2A, and progesterone receptor in the same cellular subsets. In one case, NGS showed multiple chromosomal alterations and missense mutation in PIK3CA, attributable to the admixed meningothelial population compatible with meningioma. In another case, biphasic proliferation with myoepithelial phenotype was present. The lesions showed no lineage-specific immunoprofile. Additional pathology was identified in two cases, furthermore suggestive of a possible reactive origin of the lesion.

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

Department of Neurosurgery Hospital Na Homolce Roentgenova 37 Prague 150 00 Czech Republic

Department of Neurosurgery The Regional Hospital Pardubice Kyjevská 44 Pardubice 530 03 Czech Republic

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

Department of Neurosurgery University Hospital Ostrava 17 listopadu 1790 5 Ostrava Poruba 708 00 Czech Republic

Department of Pathology Hospital Na Homolce Roentgenova 37 Prague 150 00 Czech Republic

Department of Pathology The Regional Hospital Pardubice Kyjevská 44 Pardubice 530 03 Czech Republic

Department of Pathology University Hospital Ostrava 17 listopadu 1790 5 Ostrava Poruba 708 00 Czech Republic

Faculty of Medicine University of Ostrava Syllabova 19 Ostrava jih 703 00 Czech Republic

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

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