Mixed pituitary adenoma/craniopharyngioma: clinical, morphological, immunohistochemical and ultrastructural study of a case, review of the literature, and pathogenetic and nosological considerations Giovanna Finzi • Michele Cerati • Alessandro Marando • Cesare Zoia • Fabio Ferreli • Giustino Tomei • Paolo Castelnuovo • Stefano La Rosa • Carlo Capella Ó Springer Science+Business Media New York 2013 Abstract Mixed pituitary adenoma/craniopharyngiomas are very rare tumors. Their pathogenesis is still unclear and it is not known whether they are collision tumors derived from independent stem cells or whether they originate from a single stem cell undergoing divergent differentiation. The latter hypothesis is supported by the close commixture between the two tumor components with transition areas that has been previously described. However, ‘‘hybrid’’ cells with both pituitary adenoma and craniopharyngioma features have never been described. In this paper we report a case of mixed pituitary adenoma/craniopharyngioma observed 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 pitu- itary 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 small dense secretory granules, bundles of cytoplasmic filaments, and desmosomes. This ultrastructural finding was also confirmed by the presence of cells showing nuclear p40 expression and chromogranin A immunoreactivity. The close commixture between the two components and the ultrastructural and immunohistochemical findings demon- strate a common histogenesis of the two components and support the classification of the neoplasm as a mixed tumor. The patient completely recovered and, 10 months after surgery, head MR confirmed the complete resection of the lesion. Keywords Pituitary adenoma Á Craniopharyngioma Á Mixed tumor Á Electron microscopy Introduction Mixed neuroendocrine/non-neuroendocrine tumors are an emerging topic in surgical pathology with several diagnostic, clinicopathologic and therapeutic implications. Moreover, they are an intriguing entity because several pathogenetic features are not fully understood and need to be clarified [1]. The systematic application of immunohistochemical tech- niques to the study of tumors has led to the recognition that neoplasms composed of both neuroendocrine and non-neu- roendocrine components are not as rare as believed in the past. Such tumors have been well described and character- ized in the gastrointestinal tract and pancreas [2–5] and, during the last 20 years, different terms have been used to classify them, creating some confusion among clinicians and pathologists [1]. In the most recent WHO classification of tumors of the digestive system, they have been defined as mixed adenoneuroendocrine carcinomas (MANECs) that, G. Finzi Á M. Cerati Á S. La Rosa (&) Department of Pathology, Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy e-mail: stefano.larosa@ospedale.varese.it A. Marando Á C. Capella Department of Surgical and Morphologic Sciences, University of Insubria, Viale Borri 57, 21100 Varese, Italy C. Zoia Á G. Tomei Neurosurgical Clinic, University of Insubria, Viale Borri 57, 21100 Varese, Italy F. Ferreli Á P. Castelnuovo Department of Otorhinolaryngology, University of Insubria, Viale Borri 57, 21100 Varese, Italy 123 Pituitary DOI 10.1007/s11102-013-0465-5