Glioblastomas with giant cell and sarcomatous features in patients with Turcot syndrome type 1: a clinicopathological study of 3 cases.
BACKGROUND
Turcot syndrome (TS) is a rare genetic disorder of DNA mismatch repair predisposing to glioblastoma (GBM) in the type 1 variant.


OBJECTIVE
We report the clinicopathological and genetic features of 3 gliomas in TS type 1 patients.


METHODS
Three cases were reviewed from our clinical and pathology files at Washington University with the diagnosis of TS 1 and GBM over the past 14 years. All 3 had classic features of GBM, but also demonstrated bizarre multinucleated giant cells and remarkably high mitotic indices. Sarcomatous regions were found in 2. Despite these features, the patients had prolonged survival times of 44, 55, and >29 months (ie, currently alive). Demographic and clinical courses were abstracted from retrospective chart review. Histopathology was reviewed from all cases and reticulin histochemistry was added to identify possible foci of sarcomatous differentiation.


RESULTS
All 3 had classic features of GBM, and Ki-67 labeling indices ranged from 18 to 45%. All 3 also showed strong nuclear p53 positivity. Two cases were negative for the isocitrate dehydrogenase 1 (IDH1) mutation, and O-Methylguanine methyltransferase promoter methylation was seen in one. Fluorescence in situ hybridization was done using 1p/1q, 19p/19q, centromere 7/epithelial growth factor receptor (EGFR), and PTEN/DMBT1 probes. Focal EGFR amplification was seen in one case, although other common alterations of either primary GBMs or gliomas with prolonged survival (1p/19q codeletion) were lacking.


CONCLUSIONS
We conclude that 1) the giant cell variant of GBM is overrepresented in TS; 2) gliosarcomas may also be encountered; and 3) survival is often favorable, despite histological anaplasia and exuberant proliferation.
Lusis
Eriks A
EA
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Travers
Sarah
S
Jost
Sarah C
SC
Perry
Arie
A
D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005260:Female; D015726:Giant Cells / Q000473:pathology*; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D018316:Gliosarcoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D055815:Young Adult