title: Aggressive silent corticotroph adenoma progressing to pituitary carcinoma: the role of temozolomide therapy.
abstract: Temozolomide (TMZ) has recently been recommended as a novel approach in the management of aggressive pituitary tumors. Herein, we present the case of a 43-year-old man with a 20-year history of silent subtype 2 pituitary corticotroph adenoma. Nine surgical resections and radiotherapy had failed to provide a cure. Morphological evaluation of the tumor revealed a mildly pleomorphic adenoma, the cells of which showed low-level cell proliferative activity with Ki67, increased topoisomerase II alpha index and conclusive O-6-methylguanine-DNA methyltransferase (MGMT) as well as vascular endothelial growth factor (VEGF) immunoreactivity. Given its aggressive behavior and failure of conventional therapy, TMZ was administered. The treatment was continued even after MGMT immunopositivity was identified, but failed to decrease MGMT immunoexpression and exerted no morphologic effect. Examination of the lesion after TMZ therapy showed neither morphologic nor immunohistochemical alterations. In our case, TMZ administration, despite changing the TMZ dosing regimen to prompt a drug response, was incapable of depleting MGMT stores.
authors: Department of Laboratory Medicine, Peterborough Regional Health Centre, ON, Canada. omoshkin@prhc.on.ca
authors: Olga
authors: O
authors: Moshkin
authors: Luis V
authors: LV
authors: Syro
authors: Bernd W
authors: BW
authors: Scheithauer
authors: Leon D
authors: LD
authors: Ortiz
authors: Camilo E
authors: CE
authors: Fadul
authors: Humberto
authors: H
authors: Uribe
authors: Ricardo
authors: R
authors: Gonzalez
authors: Michael
authors: M
authors: Cusimano
authors: Eva
authors: E
authors: Horvath
authors: Fabio
authors: F
authors: Rotondo
authors: Kalman
authors: K
authors: Kovacs
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000473:pathology*; D000236:Adenoma / Q000188:drug therapy / Q000473:pathology*; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide