Mixed pituitary adenoma/craniopharyngioma: Clinical, morphological, immunohistochemical and ultrastructural study of a case, review of the literature, and pathogenetic and nosological considerations

Mixed pituitary adenoma/craniopharyngiomasare very rare tumors. Their pathogenesis is still unclear and it is not known whether they are collision tumors derivedfrom independent stem cells or whether they originate from a single stem cell undergoing divergent differentiation. Thelatter hypothesis is supported by the close commixture between the two tumor components with transition areasthat has been previously described. However, ‘‘hybrid’’ cells with both pituitary adenoma and craniopharyngiomafeatures have never been described. In this paper we report a case of mixed pituitary adenoma/craniopharyngiomaobserved in a 75-year-old woman presenting with diplopia and slight increase of serum prolactin, who underwent endoscopic endonasal trans-sphenoidal tumor resection.Histologically, the tumor was composed of a typical pituitary silent subtype 2 ACTH cell adenoma admixed with islands of adamantinomatous craniopharyngioma. Electron microscopy showed that, in addition to distinct silent subtype 2 ACTH and craniopharyngioma cells, there were‘‘hybrid’’ cells, showing characteristics of both pituitary adenoma and craniopharyngioma, consisting of smalldense secretory granules, bundles of cytoplasmic filaments, and desmosomes. This ultrastructural finding was alsoconfirmed by the presence of cells showing nuclear p40 expression and chromogranin A immunoreactivity. Theclose commixture between the two components and the ultrastructural and immunohistochemical findings demonstrate a common histogenesis of the two components and support the classification of the neoplasm as a mixedtumor. The patient completely recovered and, 10 months after surgery, head MR confirmed the complete resection ofthe lesion.