Despite the extensive investigations, the histogenesis has remained obscure and still hypothetical, because the results from different studies are conflicting. Although vimentin, AAT or NSE are positive in most cases, this phenotype in not specific and does not define a specific lineage [
59]. The electron microscopical (EM) studies would be a good tool in this context, however, the findings are incongruent. The presence of zymogen granules and the positive trypsin-stain would indicate an acinar character [
6,
60,
61], but other authors failed to detect them [
53,
62]. In the vast majority of studies, no neurosecretory granules were found [
53,
60,
62], only occasional studies claimed their presence in about 50% of the cells [
63]. The strong galectin-3 expression also differentiates it from the galectin-3-negative neuroendocrine tumors [
44]. The ductal origin is similarly very unlikely: ultrastructurally the tumors cells do not display ductal cell character [
61], K-ras mutation is not detectable [
22], the CK19 – which is a characteristically positive marker in conventional adenocarcinoma – is also absent [
64]. Based on both immunohistochemical and ultrastructural features,
Kallichandra et al. proposed that the centroacinar cells would be origin of SPN [
65,
66], although the CK7 is negative in this tumor, and among our cases only 1 out of 13 displayed just 10% positivity of the cells. The neural crest [
16] or the genital ridge/ovarian anlage attached to the pancreatic tissue [
48] have also been proposed. Because of the highly divergent immunohistochemical findings, it fails to reveal a definite phenotypic relationship with any clearly defined lineage [
48,
50], some authors suggest that SPN may originate from totipotent primordial cells that would further differentiate toward duct epithelial, acinar or endocrine patterns [
55,
66]. This would explain the different immune profiles behind the identical morphology. This hypothesis, however, does not lie on solid evidence, because the genes expressed during pancreatic organogenesis and determine the lineage developmental routes are not regularly identifiable in SPN. So, the histogenesis still remained enigmatic.