[1815] BRAF V600E Mutation Is Seen in 50% of Adult Pleomorphic Xanthoastrocytoma with Anaplastic Features but Does Not Predict Prognosis for Individual Patients

Yao X Schmidt, BK Kleinschmidt-DeMasters, Dara L Aisner, Kevin O Lillehei, Denise Damek. University of Colorado Denver SOM, Aurora, CO

Background: Pleomorphic xanthoastrocytoma with anaplastic features (PXA-A) is an uncommon tumor about which little is known regarding prognostic factors. Indeed, debate exists as to which histological features (number of mitoses, MIB-1 rate, necroses) best correlate with anaplasia in this tumor type. PXAs often have BRAF V600E mutation, although the actual percentage of + cases is variable. Dias-Santagata et al. found 60% of PXAs WHO grade II and 17% of PXA-As + for mutation, whereas Schindler et al. identified mutation in 63-69% of PXAs WHO grade II and 38% of adult PXA-As and 100% of pediatric PXA-As. It is unknown if the mutation has value for predicting individual patient outcome. In addition, virtually no information exists about immunohistochemistry for IDH-1 in PXA-A.
Design: Eleven cases of adult PXA-A were reviewed. Ten cases were assessed for the BRAF V600E mutation by PCR and ten for IDH-1 by IHC.
Results: Patients ranged in age from 18-68 years; 5/11 PXA-As affected temporal lobe and 2/11 tumors were cystic. 5/11 had gross total resection; all but 2 received external beam cranial irradiation; 10/11 received adjuvant chemotherapy (TMZ, BCNU). A dichotomy existed for survival: 4 survived less than 2 years. Long term survivors, in contrast, are alive at 7, 9.3, 10.9, and 11.4 years post diagnosis. Of these long term survivors, only 2 of 4 manifested BRAF V600E mutation. Interestingly, these two patients were amongst the youngest ages in the cohort, at 18 and 28 years. Another young patient (22 years) did possess the BRAF V600E mutation, but succumbed to his disease 1.7 years after diagnosis; he received only subtotal resection and was the single patient who refused post-operative chemo- or radiotherapy, underscoring the need for adjuvant treatment. Correlating with the series by Schindler et al. that suggest higher incidence of BRAF mutation in pediatric versus adult PXA-As, in our series, 3 of 4 patients over age 45 years were negative; a 68-year-old did show BRAF mutation; her survival after diagnosis was 1.9 years. Almost all patients were negative for IDH-1 immunoreactivity.
Conclusions: V600E BRAF mutation is seen in at least 50% of PXA-As in adults; mutational status has no positive or negative predictive value for individual patients in terms of survival. Positive mutation is not exclusive to younger-aged individuals. Negative IDH-1 by IHC is usually identified in PXA-As of adults.
Category: Neuropathology

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 276, Monday Morning

 

Close Window