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

  • Chiaki MurakamiEmail author
  • Yuka Yoshida
  • Tatsuya Yamazaki
  • Ayako Yamazaki
  • Satoshi Nakata
  • Yohei Hokama
  • Shogo Ishiuchi
  • Jiro Akimoto
  • Yukiko Shishido-Hara
  • Yuhei Yoshimoto
  • Nozomi Matsumura
  • Sumihito Nobusawa
  • Hayato Ikota
  • Hideaki Yokoo
Original Article


We report four cases of high-grade astrocytoma with a BRAF V600E mutation, ATRX inactivation, and CDKN2A/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 presented 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. A BRAF V600E mutation and homozygous deletion of CDKN2A/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 of TERT 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 with BRAF V600E, ATRX, and CDKN2A/B alternations had unique clinicopathological features and may be a novel subset of high grade glioma.


High-grade astrocytoma Circumscribed astrocytoma BRAF V600E ATRX CDKN2A/B 



We thank Ms. Machiko Yokota (Gunma University) for her excellent technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10014_2019_344_MOESM1_ESM.xlsx (11 kb)
Supplementary file1 (XLSX 10 kb)


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Copyright information

© The Japan Society of Brain Tumor Pathology 2019

Authors and Affiliations

  • Chiaki Murakami
    • 1
    Email author
  • Yuka Yoshida
    • 1
  • Tatsuya Yamazaki
    • 1
  • Ayako Yamazaki
    • 1
  • Satoshi Nakata
    • 2
  • Yohei Hokama
    • 3
  • Shogo Ishiuchi
    • 3
  • Jiro Akimoto
    • 4
  • Yukiko Shishido-Hara
    • 5
  • Yuhei Yoshimoto
    • 2
  • Nozomi Matsumura
    • 1
  • Sumihito Nobusawa
    • 1
  • Hayato Ikota
    • 1
  • Hideaki Yokoo
    • 1
  1. 1.Department of Human PathologyGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of NeurosurgeryGunma University Graduate School of MedicineMaebashiJapan
  3. 3.Department of NeurosurgeryUniversity of the Ryukyus Graduate School of MedicineOkinawaJapan
  4. 4.Department of NeurosurgeryTokyo Medical UniversityTokyoJapan
  5. 5.Department of PathologyTokyo Medical UniversityTokyoJapan

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