Clinicopathological characteristics of circumscribed high-grade astrocytomas with an unusual combination of BRAF V600E, ATRX , and CDKN2A/B alternations

We report four cases of high-grade astrocytoma with aBRAF V600E mutation,ATRX inactivation, andCDKN2A/B homozygous deletion. Children to young adults aged 3 –46 presented with a well demarcated contrast-enhancing mass in the supratentorial area. Pathological examination revealed packed growth of short spindle to round polygonal cells including some pleomorphic cells. The tumors had less ability to infiltrate into the adjacent brain parenchyma and pres ented a circumscribed growth pattern. Mitosis was readily found, accompanied by focal necrosis and/or microvascular proliferation. Tumors were histologically similar in part to pleomorphic xanthoastrocytoma (PXA) or anaplastic PXA, but did not fit criteria for either neoplasm. ABRAF V600E mutation and homozygous deletion ofCDKN2A/B were observed, which is similar to the genetic features of PXA or epithelioid glioblastoma, but the additional loss of ATRX nuclear immunoreactivity and absence ofTERT promoter mutation were unusual findings, indicating a novel genetic profile. Despite their malignant histological features, all patients had a favorable clinical course and remained alive for 6  months to 28 years under standard medical treatment for malignant glioma. In summary, high grade astrocytomas withBRAF V600E,ATRX, andCDKN2A/B alternations had unique clinicopathological features and may be a novel subset of high grade glioma.
Source: Brain Tumor Pathology - Category: Neurology Source Type: research