Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The evolution of pleomorphic xanthoastrocytoma: from genesis to molecular alterations and mimics

Laboratory Investigation volume 102, pages 670–681 (2022)Cite this article

Subjects

Abstract

Pleomorphic xanthoastrocytomas (PXAs) are rare tumors accounting for less than 1% of astrocytomas. They commonly occur in young patients and have relatively favorable prognosis. However, they are well known to have heterogenous morphology and biological behavior with the potential to recur and disseminate throughout the central nervous system, especially their anaplastic counterparts. Recent advances in the molecular characterization have discovered BRAFp.V600E mutations in conjunction with CDKN2A/B deletions and TERTp mutations to be the most frequent alterations in PXAs. These tumors can present a diagnostic challenge as they share overlapping histopathological, genomic as well as methylation profile with various other tumor types, particularly epithelioid glioblastomas (eGBs). This review provides the spectrum of evolution of PXAs from their genesis to recent molecular insights and attempts to review pathogenesis and relationship to other tumors that they mimic especially eGB. It is postulated based on evidence from literature that PXA and eGB are possibly related and not distinct entities, being two ends of a continuous spectrum of malignant progression (grade 2–grade 4) with anaplastic PXA (grade 3) lying in between. Future WHO classifications will have to possibly redefine these tumors using more confirmatory data from larger studies.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Imaging characteristics of a case of pleomorphic xanthoastrocytoma (PXA) and anaplastic-PXA.
Fig. 2: Imaging characteristics of a case of epitheloid glioblastoma.
Fig. 3: Histologic features of pleomorphic xanthoastrocytoma (PXA) and anaplastic PXA.
Fig. 4: Common molecular alteration seen in pleomorphic xanthoastrocytoma and anaplastic PXA.

References

  1. Kepes, J. J., Rubinstein, L. J. & Eng, L. F. Pleomorphic xanthoastrocytoma: a distinctive meningocerebral glioma of young subjects with relatively favorable prognosis. A study of 12 cases. Cancer 44, 1839–1852 (1979).

    CAS  PubMed  Article  Google Scholar 

  2. Weldon-Linne, C. M., Victor, T. A., Groothuis, D. R. & Vick, N. A. Pleomorphic xanthoastrocytoma. Ultrastructural and immunohistochemical study of a case with a rapidly fatal outcome following surgery. Cancer 52, 2055–2063 (1983).

    CAS  PubMed  Article  Google Scholar 

  3. Iwaki, T., Fukui, M., Kondo, A., Matsushima, T. & Takeshita, I. Epithelial properties of pleomorphic xanthoastrocytomas determined in ultrastructural and immunohistochemical studies. Acta Neuropathol. 74, 142–150 (1987).

    CAS  PubMed  Article  Google Scholar 

  4. Kepes, J. J., Rubinstein, L. J., Ansbacher, L. & Schreiber, D. J. Histopathological features of recurrent pleomorphic xanthoastrocytomas: further corroboration of the glial nature of this neoplasm. A study of 3 cases. Acta Neuropathol. 78, 585–593 (1989).

    CAS  PubMed  Article  Google Scholar 

  5. Kleihues, P., Burger, P. C. & Scheithauer, B. W. The new WHO classification of brain tumours. Brain Pathol. 3, 255–268 (1993).

    CAS  PubMed  Article  Google Scholar 

  6. Kleihues, P. et al. The WHO classification of tumors of the nervous system. J. Neuropathol. Exp. Neurol. 61, 215–225 (2002).

    PubMed  Article  Google Scholar 

  7. Louis, D. N. et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114, 97–109 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  8. Okazaki, T. et al. Primary anaplastic pleomorphic xanthoastrocytoma with widespread neuroaxis dissemination at diagnosis-a pediatric case report and review of the literature. J. Neurooncol. 94, 431–437 (2009).

    PubMed  Article  Google Scholar 

  9. Kyritsis, A. P. et al. Mutations of the p16 gene in gliomas. Oncogene 12, 63–67 (1996).

    CAS  PubMed  Google Scholar 

  10. Giannini, C. et al. Pleomorphic xanthoastrocytoma: what do we really know about it? Cancer 85, 2033–2045 (1999).

    CAS  PubMed  Article  Google Scholar 

  11. Giannini C., et al. Anaplastic pleomorphic xanthoastrocytoma. in WHO Classification of Tumours of the Central Nervous System (eds Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K.) 4th edn, 98–99 (IARC, 2016).

  12. Dias-Santagata, D. et al. BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications. PLoS ONE 6, e17948 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Schindler, G. et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol. 121, 397–405 (2011).

    CAS  PubMed  Article  Google Scholar 

  14. Weber, R. G. et al. Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas. Oncogene 26, 1088–1097 (2007).

    CAS  PubMed  Article  Google Scholar 

  15. Lassaletta, A. et al. Therapeutic and prognostic implications of BRAF V600E in pediatric low-grade gliomas. J. Clin. Oncol. 35, 2934–2941 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Mistry, M. et al. BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. J. Clin. Oncol. 33, 1015–1022 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Vaubel, R. A. et al. Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation. Brain Pathol. 28, 172–182 (2018).

    CAS  PubMed  Article  Google Scholar 

  18. Giannini, C. et al. Pleomorphic xanthoastrocytoma. in The WHO Classification of Tumors of the Central Nervous System (eds Reifenberger, G. & Perry A.) 5th edn (IARC) (2007).

  19. Dono, A. et al. Predictors of outcome in pleomorphic xanthoastrocytoma. Neurooncol. Pract. 8, 222–229 (2020).

    PubMed  PubMed Central  Google Scholar 

  20. Ostrom, Q. T. et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010-2014. Neuro Oncol. 19, v1–v88 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  21. Ida, C. M. et al. Pleomorphic xanthoastrocytoma: natural history and long-term follow-up. Brain Pathol. 25, 575–586 (2015).

    CAS  PubMed  Article  Google Scholar 

  22. Dolecek, T. A., Propp, J. M., Stroup, N. E. & Kruchko, C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro Oncol. 14(Suppl 5), v1–v49 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  23. Fouladi, M. et al. Pleomorphic xanthoastrocytoma: favorable outcome after complete surgical resection. Neuro Oncol. 3, 184–192 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Gil-Gouveia, R. et al. Pleomorphic xanthoastrocytoma of the cerebellum: illustrated review. Acta Neurochir. 146, 1241–1244 (2004).

    CAS  PubMed  Article  Google Scholar 

  25. Nakamura, M., Chiba, K., Matsumoto, M., Ikeda, E. & Toyama, Y. Pleomorphic xanthoastrocytoma of the spinal cord. Case report. J. Neurosurg. Spine 5, 72–75 (2006).

    PubMed  Article  Google Scholar 

  26. Zarate, J. O. & Sampaolesi, R. Pleomorphic xanthoastrocytoma of the retina. Am. J. Surg. Pathol. 23, 79–81 (1999).

    CAS  PubMed  Article  Google Scholar 

  27. McNatt, S. A., Gonzalez-Gomez, I., Nelson, M. D. & McComb, J. G. Synchronous multicentric pleomorphic xanthoastrocytoma: case report. Neurosurgery 57, E191 (2005).

    PubMed  Article  Google Scholar 

  28. Lubansu, A. et al. Cerebral anaplastic pleomorphic xanthoastrocytoma with meningeal dissemination at first presentation. Childs Nerv. Syst. 20, 119–122 (2004).

    PubMed  Article  Google Scholar 

  29. Passone, E. et al. Non-anaplastic pleomorphic xanthoastrocytoma with neuroradiological evidences of leptomeningeal dissemination. Childs Nerv. Syst. 22, 614–618 (2006).

    PubMed  Article  Google Scholar 

  30. Davies, K. G., Maxwell, R. E., Seljeskog, E. & Sung, J. H. Pleomorphic xanthoastrocytoma-report of four cases, with MRI scan appearances and literature review. Br. J. Neurosurg. 8, 681–689 (1994).

    CAS  PubMed  Article  Google Scholar 

  31. Crespo-Rodríguez, A. M., Smirniotopoulos, J. G. & Rushing, E. J. MR and CT imaging of 24 pleomorphic xanthoastrocytomas (PXA) and a review of the literature. Neuroradiology 49, 307–315 (2007).

    PubMed  Article  Google Scholar 

  32. Osborn A. G., Blaser S. I. & Salzman K. L. (eds) Diagnostic Imaging: Brain 1st edn (Amirsys, 2004).

  33. Yu, S., He, L., Zhuang, X. & Luo, B. Pleomorphic xanthoastrocytoma: MR imaging findings in 19 patients. Acta Radiol. 52, 223–228 (2011).

    PubMed  Article  Google Scholar 

  34. Yoshino, M. T. & Lucio, R. Pleomorphic xanthoastrocytoma. Am. J. Neuroradiol. 13, 1330–1332 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Bucciero, A. et al. Pleomorphic xanthoastrocytoma: clinical, imaging and pathological features of four cases. Clin. Neurol. Neurosurg. 99, 40–45 (1997).

    CAS  PubMed  Article  Google Scholar 

  36. Kepes, J. J., Kepes, M. & Slowik, F. Fibrous xanthomas and xanthosarcomas of the meninges and the brain. Acta Neuropathol. 23, 187–199 (1973).

    CAS  PubMed  Article  Google Scholar 

  37. Burger P. C. & Scheithauer B. W. Tumors of the Central Nervous System (American Registry of Pathology in collaboration with the Armed Forces Institute of Pathology, 2007).

  38. Perry A. & Brat D. J. Practical Surgical Neuropathology: a Diagnostic Approach (Elsevier, 2018).

  39. Primavera, J. et al. Clear cell pleomorphic xanthoastrocytoma: case report. Acta Neuropathol. 102, 404–408 (2001).

    CAS  PubMed  Article  Google Scholar 

  40. Xiong, J., Chu, S. G., Mao, Y. & Wang, Y. Pigmented pleomorphic xanthoastrocytoma: a rare variant and literature review. Neuropathology 31, 88–92 (2011).

    PubMed  Article  Google Scholar 

  41. Furuta, T. et al. Clinicopathological and genetic association between epithelioid glioblastoma and pleomorphic xanthoastrocytoma. Neuropathology 38, 218–227 (2018).

    CAS  PubMed  Article  Google Scholar 

  42. Alexandrescu, S. et al. Epithelioid glioblastomas and anaplastic epithelioid pleomorphic xanthoastrocytomas-same entity or first cousins? Brain Pathol. 26, 215–223 (2016).

    CAS  PubMed  Article  Google Scholar 

  43. Wang, J. et al. Evaluation of EZH2 expression, BRAF V600E mutation, and CDKN2A/B deletions in epithelioid glioblastoma and anaplastic pleomorphic xanthoastrocytoma. J. Neurooncol. 144, 137–146 (2019).

    CAS  PubMed  Article  Google Scholar 

  44. Hirose, T. et al. Pleomorphic xanthoastrocytoma: a comparative pathological study between conventional and anaplastic types. Histopathology 52, 183–193 (2008).

    CAS  PubMed  Article  Google Scholar 

  45. Giannini, C., Hebrink, D., Scheithauer, B. W., Dei Tos, A. P. & James, C. D. Analysis of p53 mutation and expression in pleomorphic xanthoastrocytoma. Neurogenetics 3, 159–162 (2001).

    CAS  PubMed  Article  Google Scholar 

  46. Paulus, W. et al. Molecular genetic alterations in pleomorphic xanthoastrocytoma. Acta Neuropathol. 91, 293–297 (1996).

    CAS  PubMed  Article  Google Scholar 

  47. Kaulich, K. et al. Genetic alterations commonly found in diffusely infiltrating cerebral gliomas are rare or absent in pleomorphic xanthoastrocytomas. J. Neuropathol. Exp. Neurol. 61, 1092–1099 (2002).

    CAS  PubMed  Article  Google Scholar 

  48. Vaubel, R. et al. Biology and grading of pleomorphic xanthoastrocytoma-what have we learned about it? Brain Pathol. 31, 20–32 (2021).

    CAS  PubMed  Article  Google Scholar 

  49. Nakajima, N. et al. BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions are frequent in epithelioid glioblastomas: a histological and molecular analysis focusing on intratumoral heterogeneity. Brain Pathol. 28, 663–673 (2018).

    CAS  PubMed  Article  Google Scholar 

  50. Phillips, J. J. et al. The genetic landscape of anaplastic pleomorphic xanthoastrocytoma. Brain Pathol. 29, 85–96 (2019).

    CAS  PubMed  Article  Google Scholar 

  51. Korshunov, A. et al. Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis. Brain Pathol. 28, 656–662 (2018).

    CAS  PubMed  Article  Google Scholar 

  52. Zou, H. et al. Molecular features of pleomorphic xanthoastrocytoma. Hum. Pathol. 86, 38–48 (2019).

    CAS  PubMed  Article  Google Scholar 

  53. Koelsche, C. et al. Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. Acta Neuropathol. 126, 907–915 (2013).

    CAS  PubMed  Article  Google Scholar 

  54. Pratt, D. et al. BRAF activating mutations involving the β3-αC loop in V600E-negative anaplastic pleomorphic xanthoastrocytoma. Acta Neuropathol. Commun. 6, 24 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  55. Hsiao, S. J. et al. A novel, potentially targetable TMEM106B-BRAF fusion in pleomorphic xanthoastrocytoma. Cold Spring Harb. Mol. Case Stud. 3, a001396 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  56. Zhang, J. St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project. et al. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet. 45, 602–612 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  57. Bettegowda, C. et al. Exomic sequencing of four rare central nervous system tumor types. Oncotarget 4, 572–583 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  58. Phillips, J. J. et al. Activating NRF1-BRAF and ATG7-RAF1 fusions in anaplastic pleomorphic xanthoastrocytoma without BRAF p.V600E mutation. Acta Neuropathol. 132, 757–760 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  59. Lim, S. et al. Prognostic factors and therapeutic outcomes in 22 patients with pleomorphic xanthoastrocytoma. J. Korean Neurosurg. Soc. 53, 281–287 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  60. Korshunov, A. & Golanov, A. Pleomorphic xanthoastrocytomas: immunohistochemistry, grading and clinico-pathologic correlations. An analysis of 34 cases from a single Institute. J. Neurooncol. 52, 63–72 (2001).

    CAS  PubMed  Article  Google Scholar 

  61. Perkins, S. M., Mitra, N., Fei, W. & Shinohara, E. T. Patterns of care and outcomes of patients with pleomorphic xanthoastrocytoma: a SEER analysis. J. Neurooncol. 110, 99–104 (2012).

    PubMed  Article  Google Scholar 

  62. Ng, W. H., Lim, T. & Yeo, T. T. Pleomorphic xanthoastrocytoma in elderly patients may portend a poor prognosis. J. Clin. Neurosci. 15, 476–478 (2008).

    PubMed  Article  Google Scholar 

  63. Reis, G. F. et al. CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas. J. Neuropathol. Exp. Neurol. 74, 442–452 (2015).

    CAS  PubMed  Article  Google Scholar 

  64. Pahapill, P. A., Ramsay, D. A. & Del Maestro, R. F. Pleomorphic xanthoastrocytoma: case report and analysis of the literature concerning the efficacy of resection and the significance of necrosis. Neurosurgery 38, 822–829 (1996).

    CAS  PubMed  Article  Google Scholar 

  65. Byun, J., Hong, S. H., Kim, Y.-H., Kim, J. H. & Kim, C. J. Peritumoral edema affects the prognosis in adult pleomorphic xanthoastrocytoma: retrospective analysis of 25 patients. World Neurosurg. 114, e457–e467 (2018).

    PubMed  Article  Google Scholar 

  66. Macaulay, R. J., Jay, V., Hoffman, H. J. & Becker, L. E. Increased mitotic activity as a negative prognostic indicator in pleomorphic xanthoastrocytoma: case report. J. Neurosurg. 79, 761–768 (1993).

    CAS  PubMed  Article  Google Scholar 

  67. Koga, T. et al. Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation. Neuro Oncol. 11, 446–451 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  68. van Roost, D., Kristof, R., Zentner, J., Wolf, H. K. & Schramm, J. Clinical, radiological, and therapeutic features of pleomorphic xanthoastrocytoma: report of three patients and review of the literature. J. Neurol. Neurosurg. Psychiatry 60, 690–692 (1996).

    PubMed  PubMed Central  Article  Google Scholar 

  69. Khalafallah, A., Rakovec, M. & Mukherjee, D. Association between adjuvant radiation therapy and overall survival in pleomorphic xanthoastrocytoma. Clin. Neurol. Neurosurg. 196, 106042 (2020).

    PubMed  Article  Google Scholar 

  70. Hosona, J. et al. Role of a promoter mutation in TERT in malignant transformation of pleomorphic xanthoastrocytoma. World Neurosurg. 126, 624–630 (2019).

    Article  Google Scholar 

  71. Saikali, S. et al. Multicentric pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1: case report and review of the literature. J. Neurosurg. 102, 376–381 (2005).

    PubMed  Article  Google Scholar 

  72. Mallick, S., Benson, R., Melgandi, W., Giridhar, P. & Rath, G. K. Grade II pleomorphic xanthoastrocytoma: a meta-analysis of data from previously reported 167 cases. J. Clin. Neurosci. 54, 57–62 (2018).

    PubMed  Article  Google Scholar 

  73. Thomas, A. et al. RARE-30. Anaplastic pleomorphic xanthoastrocytoma with leptomeningeal dissemination responsive to BRAF inhibition and bevacizumab. Neuro Oncol. 19, vi216 (2017). Suppl. 6.

    PubMed Central  Article  Google Scholar 

  74. Brown, N. F., Carter, T. & Mulholland, P. Dabrafenib in BRAFV600-mutated anaplastic pleomorphic xanthoastrocytoma. CNS Oncol. 6, 5–9 (2017).

    CAS  PubMed  Article  Google Scholar 

  75. Hyman, D. M. et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N. Engl. J. Med. 373, 726–736 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. Kaley, T. et al. BRAF inhibition in BRAFV600-mutant gliomas: results from the VE-BASKET Study. J. Clin. Oncol. 36, 3477–3484 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. Lukas, R. V. & Merrell, R. T. BRAF inhibition with concomitant tumor treating fields for a multiply progressive pleomorphic xanthoastrocytoma. CNS Oncol. 7, CNS10 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. Louis, D. N. et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 131, 803–820 (2016).

    PubMed  Article  Google Scholar 

  79. Tanaka, S. et al. Epithelioid glioblastoma arising from pleomorphic xanthoastrocytoma with the BRAF V600E mutation. Brain Tumor Pathol. 31, 172–176 (2014).

    PubMed  Article  Google Scholar 

  80. Matsumura, N. et al. Concurrent TERT promoter and BRAF V600E mutation in epithelioid glioblastoma and concomitant low-grade astrocytoma. Neuropathology 37, 58–63 (2017).

    CAS  PubMed  Article  Google Scholar 

  81. Broniscer, A. et al. Clinical, radiological, histological and molecular characteristics of paediatric epithelioid glioblastoma. Neuropathol. Appl. Neurobiol. 40, 327–336 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. Kleinschmidt-DeMasters, B. K. et al. Epithelioid versus rhabdoid glioblastomas are distinguished by monosomy 22 and immunohistochemical expression of INI-1 but not claudin 6. Am. J. Surg. Pathol. 34, 341–354 (2010).

    PubMed  Article  Google Scholar 

  83. Nobusawa, S. et al. Intratumoral heterogeneity of genomic imbalance in a case of epithelioid glioblastoma with BRAF V600E mutation. Brain Pathol. 24, 239–246 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. Khanna, G. et al. Immunohistochemical and molecular genetic study on epithelioid glioblastoma: series of seven cases with review of literature. Pathol. Res. Pract. 214, 679–685 (2018).

    CAS  PubMed  Article  Google Scholar 

  85. Kordek, R. et al. Pleomorphic xanthoastrocytoma with a gangliomatous component: an immunohistochemical and ultrastructural study. Acta Neuropathol. 89, 194–197 (1995).

    CAS  PubMed  Article  Google Scholar 

  86. Perry, A. et al. Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature. Am. J. Surg. Pathol. 21, 763–771 (1997).

    CAS  PubMed  Article  Google Scholar 

  87. Margetts, J. C. & Kalyan-Raman, U. P. Giant celled glioblastoma of brain: a clinico-pathological and radiological study of ten cases (including immunohistochemistry and ultrastructure). Cancer 63, 524–531 (1989).

    CAS  PubMed  Article  Google Scholar 

  88. Kozak, K. R. & Moody, J. S. Giant cell glioblastoma: a glioblastoma subtype with distinct epidemiology and superior prognosis. Neuro Oncol. 11, 833–841 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  89. Meyer-Puttlitz, B. et al. Molecular genetic analysis of giant cell glioblastomas. Am. J. Pathol. 151, 853–857 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Ogawa, K. et al. Giant cell glioblastoma is a distinctive subtype of glioma characterized by vulnerability to DNA damage. Brain Tumor Pathol. 37, 5–13 (2020).

    CAS  PubMed  Article  Google Scholar 

  91. Nesvick, C. L. et al. Atypical teratoid rhabdoid tumor: molecular insights and translation to novel therapeutics. J. Neurooncol. 150, 47–56 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  92. Ho, B. et al. Molecular subgrouping of atypical teratoid/rhabdoid tumors-a reinvestigation and current consensus. Neuro Oncol. 22, 613–624 (2020).

    CAS  PubMed  Article  Google Scholar 

  93. Uner, M., Saglam, A., Meydan, B. C., Aslan, K. & Soylemezoglu, F. Atypical teratoid rhabdoid tumor arising in a pleomorphic xanthoastrocytoma: a rare entity. Clinic Neuropathol. 36, 227–232 (2017).

    Article  Google Scholar 

  94. Zacher, A. et al. Molecular diagnostics of gliomas using next generation sequencing of a glioma-tailored gene panel. Brain Pathol. 27, 146–159 (2017).

    CAS  PubMed  Article  Google Scholar 

  95. Gupta, K., Kalra, I., Salunke, P. & Vasishta, R. K. Lipidized glioblastoma: a rare differentiation pattern. Neuropathology 31, 93–97 (2011).

    PubMed  Article  Google Scholar 

  96. Arita, H. et al. A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathol. Commun. 4, 79 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  97. Ceccarelli, M. et al. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell 164, 550–563 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  98. Reinhardt, A. et al. Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathol. 136, 273–291 (2018).

    CAS  PubMed  Article  Google Scholar 

  99. Aldape K. D. & Rosenblum M. K. Astroblastoma. in WHO Classification of Tumours of the Central Nervous System (Louis, D. N., Ohgaki, H., Wiestler, O. D. & Cavenee, W. K.) 121–122 (International Agency for Research on Cancer, 2016).

  100. Lehman, N. L. et al. Genomic analysis demonstrates that histologically-defined astroblastomas are molecularly heterogeneous and that tumors with MN1 rearrangement exhibit the most favorable prognosis. Acta Neuropathol. Commun. 7, 42 (2019).

    PubMed  PubMed Central  Article  Google Scholar 

  101. Lehman, N. L. et al. Morphological and molecular features of astroblastoma, including BRAFV600E mutations, suggest an ontological relationship to other corticalbased gliomas of children and young adults. Neuro-Oncology 19, 31–42 (2017).

    CAS  PubMed  Article  Google Scholar 

  102. Boisseau, W. et al. Molecular profiling reclassifies adult astroblastoma into known and clinically distinct tumor entities with frequent mitogen-activated protein kinase pathway alterations. Oncologist 24, 1584–1592 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  103. Wood, M. D. et al. Multimodal molecular analysis of astroblastoma enables reclassifcation of most cases into more specifc molecular entities. Brain Pathol. 28, 192–202 (2018).

    CAS  PubMed  Article  Google Scholar 

  104. Sturm, D. et al. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164, 1060–1072 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  105. Capper, D. et al. DNA methylation-based classification of central nervous system tumours. Nature 555, 469–474 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. Fukuoka, K. et al. Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas. Neuro Oncol. 22, 1474–1483 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. Korshunov, A. et al. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol. 129, 669–678 (2015).

    CAS  PubMed  Article  Google Scholar 

  108. Mackay, A. et al. Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma. Cancer Cell 32, 520–537 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  109. Huillard, E. et al. Cooperative interactions of BRAFV600E kinase and CDKN2A locus deficiency in pediatric malignant astrocytoma as a basis for rational therapy. Proc. Natl Acad. Sci. USA 109, 8710–8715 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge Dr. Tejpal Gupta, Professor and Officer in charge, Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India, for his inputs and edits in the treatment section of this review.

Author information

Authors and Affiliations

  1. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

    Swati Mahajan, Iman Dandapath, Mehar C. Sharma, Vaishali Suri & Chitra Sarkar

  2. Department of Neuroimaging & Interventional Neuroradiology, All India Institute of Medical Sciences, New Delhi, India

    Ajay Garg

Authors
  1. Swati Mahajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iman Dandapath
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ajay Garg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehar C. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vaishali Suri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chitra Sarkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SM and CS: conceptualization, data curation, writing and editing. VS, ID and MCS: data curation.

Corresponding authors

Correspondence to Vaishali Suri or Chitra Sarkar.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mahajan, S., Dandapath, I., Garg, A. et al. The evolution of pleomorphic xanthoastrocytoma: from genesis to molecular alterations and mimics. Lab Invest 102, 670–681 (2022). https://doi.org/10.1038/s41374-021-00708-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41374-021-00708-0

Search

Advanced search

Quick links