Abstract A pituitary mass was removed by the trans- sphenoidal approach from a 63-year-old man with the clin- ical history and laboratory findings characteristic of Cush- ing’s disease with partial hypopituitarism. Histological, immunohistochemical, ultrastructural and immunoelec- tron microscopic investigation demonstrated a periodic acid-Schiff-positive, adrenocorticotropic hormone (ACTH)- immunoreactive, pituitary corticotroph adenoma with the formation of neural tissue resembling neuropil within the tumor. The neural elements showed immunopositivity for neurofilament protein and ACTH, but were immunonega- tive for other adenohypophysial hormones and for corti- cotropin-releasing hormone. Although the molecular mechanism accounting for neural transformation in this corticotroph adenoma remained obscure, based on the clinical, histological and morphological findings it ap- pears that formation of neural tissue most likely indicate a favorable prognosis. Keywords Corticotroph adenoma · Cushing’s disease · Neural transformation · Immunohistochemistry · Ultrastructure Introduction The concept of pituitary cell differentiation encompasses all processes leading to differently specialized cell types, beginning with the progressive divergence of developmen- tal pathways and ending with the successive programming and final formation of each particular cell type. Guidance and positional information are provided by external fac- tors, by cytoplasmic determinants such as mRNA for tran- scription and by cascades of paracrine signals [27]. In the pituitary the concept of irreversible differentiation is not concordant with the existence of transdifferentiation, i.e., the conversion of one hormonal cell type to another [13, 41, 43]. In addition to a shift in hormonal function and ap- propriate morphological changes, transformation may in- volve lineage infidelity, i.e., the emergence of pheno- type(s) inappropriate for the particular tissue. Several stud- ies revealed that cells of cancer of the lung, medullary carcinoma of thyroid and carcinomas of the pancreatic islets may undergo neural transformation, and formation of nerve cells from tumor cells was also documented in vitro as a result of nerve growth factor (NGF) exposure [1, 11, 21, 24, 29, 40]. In the pituitary, the majority of adenomas containing neural elements (neurons and neuropil) have been associ- ated with growth hormone (GH) production, elevated blood GH and insulin-like growth factor 1 (IGF-1) levels and clinical acromegaly [8, 14, 31, 33]. Rarely, pituitary ade- nomas containing neural elements have been accompa- nied by other endocrine abnormalities, such as amenor- rhea and galactorrhea or Cushing’s disease [3, 4, 19, 32, 35, 39]. Although the molecular basis of the neural trans- formation in pituitary adenomas remains an enigma, the present case broadens the morphological spectrum, adding a hitherto unreported type in a corticotroph ade- noma studied by histology, immunohistochemistry, elec- tron microscopy and immunoelectron microscopy. Sergio Vidal · Eva Horvath · Vivian Bonert · Hrayr Karnig Shahinian · Kalman Kovacs Neural transformation in a pituitary corticotroph adenoma Acta Neuropathol (2002) 104 : 435–440 DOI 10.1007/s00401-002-0561-5 Received: 31 October 2001 / Revised: 11 February 2002 / Accepted: 26 February 2002 / Published online: 29 May 2002 CASE REPORT S. Vidal · E. Horvath (✉) · K. Kovacs Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, 30 Bond Street, Toronto, Ontario M5B 1W8, Canada e-mail: kovacsk@smh.toronto.on.ca V. Bonert Pituitary Center, Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA H.K. Shahinian Division of Skull Base Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA S. Vidal Department of Anatomy, Laboratory of Histology, University of Santiago de Compostela, Lugo, Spain © Springer-Verlag 2002