Skip to main content

Advertisement

SpringerLink
Log in

Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination

  • Case Report
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

Dissemination of histologically benign hemangioblastoma is rare; approximately 30 cases have previously been reported, and all cases occurred several months to years after surgical resection. Herein, we report a case of hemangioblastoma in which leptomeningeal dissemination occurred 2 years after hypofractionated radiation therapy (39 Gy/13 fractions). The tumor was treated primarily with radiation without surgical resection. Biopsy of the disseminated lesion confirmed histological diagnosis as histologically benign hemangioblastoma. Ki67 index was not remarkably elevated for hemangioblastomas. In addition, the methylation class determined by the methylation profiling classifier developed by the German Cancer Research Center (DKFZ)/University Hospital Heidelberg/German Consortium for Translational Cancer Research was consistent with that of common hemangioblastomas. However, genetic analyses showed significant gains and losses throughout the whole genome, indicating that highly aberrant copy number profiles may be the key to elucidating this rare but life-threatening clinical entity. Accumulation of more detailed case reports based on the comparison of specimens obtained before and after surgery or radiation is necessary to better understand the pathophysiology of the dissemination phenotype of hemangioblastoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HIF:

Hypoxia-inducible factor

MLPA:

Multiplex ligation-dependent probe amplification

VHL:

Von Hippel–Lindau

References

  1. Conway JE, Chou D, Clatterbuck RE et al (2001) Hemangioblastomas of the central nervous system in von Hippel–Lindau syndrome and sporadic disease. Neurosurgery 48:55–62 ((discussion 62–3))

    CAS  PubMed  Google Scholar 

  2. Weil RJ, Vortmeyer AO, Zhuang Z et al (2002) Clinical and molecular analysis of disseminated hemangioblastomatosis of the central nervous system in patients without von Hippel–Lindau disease. Report of four cases. J Neurosurg 96:775–787

    Article  CAS  Google Scholar 

  3. Choyke PL, Glenn GM, Walther MM et al (1995) von Hippel–Lindau disease: genetic, clinical, and imaging features. Radiology 194:629–642

    Article  CAS  Google Scholar 

  4. Filling-Katz MR, Choyke PL, Oldfield E et al (1991) Central nervous system involvement in Von Hippel–Lindau disease. Neurology 41:41–46

    Article  CAS  Google Scholar 

  5. de La Monte SM, Horowitz SA (1989) Hemangioblastomas: clinical and histopathological factors correlated with recurrence. Neurosurgery 25:695–698

    Article  Google Scholar 

  6. Neumann HP, Eggert HR, Weigel K et al (1989) Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel–Lindau syndrome. J Neurosurg 70:24–30

    Article  CAS  Google Scholar 

  7. Latif F, Tory K, Gnarra J et al (1993) Identification of the von Hippel–Lindau disease tumor suppressor gene. Science 260:1317–1320

    Article  CAS  Google Scholar 

  8. Kanno H, Kondo K, Ito S et al (1994) Somatic mutations of the von Hippel–Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas. Cancer Res 54:4845–4847

    CAS  PubMed  Google Scholar 

  9. Maxwell PH, Wiesener MS, Chang GW et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275

    Article  CAS  Google Scholar 

  10. Iliopoulos O, Levy AP, Jiang C et al (1996) Negative regulation of hypoxia-inducible genes by the von Hippel–Lindau protein. Proc Natl Acad Sci USA 93:10595–10599

    Article  CAS  Google Scholar 

  11. Cheng J, Liu W, Zhang S et al (2017) Clinical features and surgical outcomes in patients with cerebellopontine angle hemangioblastomas: retrospective series of 23 cases. World Neurosurg 103:248–256

    Article  Google Scholar 

  12. Fukuda M, Takao T, Hiraishi T et al (2014) Clinical factors predicting outcomes after surgical resection for sporadic cerebellar hemangioblastomas. World Neurosurg 82:815–821

    Article  Google Scholar 

  13. Liao C-C, Huang Y-H (2014) Clinical features and surgical outcomes of sporadic cerebellar hemangioblastomas. Clin Neurol Neurosurg 125:160–165

    Article  Google Scholar 

  14. Akimoto J, Fukuhara H, Suda T et al (2014) Disseminated cerebellar hemangioblastoma in two patients without von Hippel–Lindau disease. Surg Neurol Int 5:145

    Article  Google Scholar 

  15. Bains SJ, Niehusmann PF, Meling TR et al (2019) Disseminated central nervous system hemangioblastoma in a patient with no clinical or genetic evidence of von Hippel–Lindau disease—a case report and literature review. Acta Neurochir 161:343–349

    Article  Google Scholar 

  16. Bakshi R, Mechtler LL, Patel MJ et al (1997) Spinal leptomeningeal hemangioblastomatosis in von Hippel–Lindau disease: magnetic resonance and pathological findings. J Neuroimaging 7:242–244

    Article  CAS  Google Scholar 

  17. Chung S-Y, Jeun S-S, Park J-H (2014) Disseminated Hemangioblastoma of the central nervous system without Von Hippel–Lindau disease. Brain Tumor Res Treat 2:96–101

    Article  Google Scholar 

  18. Courcoutsakis NA, Prassopoulos PK, Patronas NJ (2009) Aggressive leptomeningeal hemangioblastomatosis of the central nervous system in a patient with von Hippel–Lindau disease. AJNR Am J Neuroradiol 30:758–760

    Article  CAS  Google Scholar 

  19. Hande AM, Nagpal RD (1996) Cerebellar haemangioblastoma with extensive dissemination. Br J Neurosurg 10:507–511

    Article  CAS  Google Scholar 

  20. Hanse MCJ, Vincent A, van den Bent MJ (2007) Hemangioblastomatosis in a patient with von Hippel–Lindau disease. J Neurooncol 82:163–164

    Article  CAS  Google Scholar 

  21. Kato M, Ohe N, Okumura A et al (2005) Hemangioblastomatosis of the central nervous system without von Hippel–Lindau disease: a case report. J Neurooncol 72:267–270

    Article  Google Scholar 

  22. Kim H-R, Suh Y-L, Kim J-W, Lee J-I (2009) Disseminated hemangioblastomatosis of the central nervous system without von Hippel–Lindau disease: a case report. J Korean Med Sci 24:755–759

    Article  Google Scholar 

  23. Koo H-W, Park JE, Cha J et al (2016) Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature. Acta Neurochir 158:1169–1178

    Article  Google Scholar 

  24. Lightfoot NJ, Lucas PG, Finnis NDM (2007) Disseminated haemangioblastoma without evidence of the von Hippel–Lindau syndrome or haemangioblastomatosis—a case report and clinico-pathological correlation. Clin Neurol Neurosurg 109:305–310

    Article  Google Scholar 

  25. Mohan J, Brownell B, Oppenheimer DR (1976) Malignant spread of haemangioblastoma: report on two cases. J Neurol Neurosurg Psychiatr 39:515–525

    Article  CAS  Google Scholar 

  26. Ohba H, Yamaguchi S, Magaki T et al (2017) A case of holocord leptomeningeal dissemination from cerebellar hemangioblastoma without von Hippel–Lindau disease. Hiroshima J Med Sci 66:7–10

    PubMed  Google Scholar 

  27. Reyes-Botero G, Gállego Pérez-Larraya J, Sanson M (2012) Sporadic CNS hemangioblastomatosis, response to sunitinib and secondary polycythemia. J Neurooncol 107:439–440

    Article  Google Scholar 

  28. Reyns N, Assaker R, Louis E, Lejeune J-P (2003) Leptomeningeal hemangioblastomatosis in a case of von Hippel–Lindau disease: case report. Neurosurgery 52:1212–1215 ((discussion 1215–6))

    PubMed  Google Scholar 

  29. Rogers LR, LoRusso P, Nadler P et al (2011) Erlotinib therapy for central nervous system hemangioblastomatosis associated with von Hippel–Lindau disease: a case report. J Neurooncol 101:307–310

    Article  Google Scholar 

  30. Tohyama T, Kubo O, Kusano R et al (1990) A case of hemangioblastoma with subarachnoid dissemination. No Shinkei Geka 18:83–88

    CAS  PubMed  Google Scholar 

  31. Zhang Q, Ma L, Li W-Y et al (2011) Von Hippel–Lindau disease manifesting disseminated leptomeningeal hemangioblastomatosis: surgery or medication? Acta Neurochir 153:48–52

    Article  Google Scholar 

  32. Takayanagi S, Mukasa A, Tanaka S et al (2017) Differences in genetic and epigenetic alterations between von Hippel–Lindau disease-related and sporadic hemangioblastomas of the central nervous system. Neuro-Oncology 19:1228–1236

    Article  CAS  Google Scholar 

  33. Capper D, Jones DTW, Sill M et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474

    Article  CAS  Google Scholar 

  34. Jung S-M, Kuo T-T (2005) Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma. Mod Pathol 18:788–794

    Article  CAS  Google Scholar 

  35. Brown DF, Gazdar AF, White CL et al (1997) Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas. J Neuropathol Exp Neurol 56:1349–1355

    Article  CAS  Google Scholar 

  36. Bi WL, Greenwald NF, Abedalthagafi M et al (2017) Genomic landscape of high-grade meningiomas. NPJ Genom Med 2:iv1

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Reiko Matsuura for assisting with genetic reserch.

Funding

None.

Author information

Author notes

  1. Soichi Oya and Shunsaku Takayanagi have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan

    Soichi Oya, Masahiro Indo & Toru Matsui

  2. Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan

    Shunsaku Takayanagi, Hirokazu Takami & Nobuhito Saito

  3. Department of Pathology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Takahisa Yamashita

Authors
  1. Soichi Oya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunsaku Takayanagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirokazu Takami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masahiro Indo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takahisa Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nobuhito Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toru Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Soichi Oya.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oya, S., Takayanagi, S., Takami, H. et al. Masked malignant phenotype with a benign appearance: beat-up copy number profile may be the key for hemangioblastoma dissemination. Brain Tumor Pathol 38, 71–77 (2021). https://doi.org/10.1007/s10014-020-00387-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-020-00387-7

Keywords

Search

Navigation