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BRAF V600E mutant papillary craniopharyngiomas: a single-institutional case series

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Abstract

Purpose

To describe the clinical, radiographic and surgical outcomes in a cohort of patients with BRAF V600E mutant papillary craniopharyngiomas.

Methods

A retrospective review was performed to identify all patients with a histological diagnosis of CP operated upon at a single institution between 2005 and 2017. All cases with adequate material were sequenced to confirm the presence of BRAF V600E mutation.

Results

Sixteen patients were included in the present study. Approach was endoscopic endonasal (EEA) in 14 and transcranial (TCA) in 2. All patients were adult with an average age of 50 years (24–88). Radiographic review demonstrated that the majority (93.7%) were suprasellar and twelve (75%) had third ventricular involvement. No tumor showed evidence of calcifications and 68.7% were mixed solid-cystic. All patients had some evidence of hypopituitarism and 62.5% had hypothalamic disturbances. GTR was achieved in 11/14 (78.6%) EEA and 0/2 (0%) TCA (p < 0.05). The mean length of stay was 17.5 days in the TCA group and 7.6 days in the EEA group (p < 0.05). There were no CSF leaks. Post-operatively, eleven (68.7%) developed new DI or new hypopituitarism. Nine increased their BMI with a mean increase of 12.3%, whereas six patients lost weight with a mean decrease of 5.3%.

Conclusions

BRAF V600E mutant papillary tumors represent a clearly distinct clinical-pathological entity of craniopharyngiomas. These are generally non-calcified suprasellar tumors that occur in adults. These distinct characteristics may someday lead to upfront chemotherapy. When surgery is necessary, EEA may be preferred over TCA.

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Abbreviations

BMI:

Body mass index

CDG:

Clavien–Dindo grading

CP:

Craniopharyngioma

CT:

Computed tomography

EEA:

Extended endonasal approach

EOR:

Extent of resection

GTR:

Gross-total resection

MR:

Magnetic resonance

NGS:

Next generation sequencing

NS:

Not significant

NTR:

Near-total resection

PCR:

Polymerase chain reaction

STR:

Sub-total resection

SWI:

Susceptibility weighted imaging

TCA:

Trans-cranial approach.

References

  1. Brastianos PK, Taylor-Weiner A, Manley PE et al (2014) Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. https://doi.org/10.1038/ng.2868

    Article  PubMed  PubMed Central  Google Scholar 

  2. Buslei R, Nolde M, Hofmann B et al (2005) Common mutations of b-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol 109:589–597. https://doi.org/10.1007/s00401-005-1004-x

    Article  CAS  PubMed  Google Scholar 

  3. Hölsken A, Sill M, Merkle J et al (2016) Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles. Acta Neuropathol Commun 4:20. https://doi.org/10.1186/s40478-016-0287-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Malgulwar PB, Nambirajan A, Pathak P et al (2017) Study of β-catenin and BRAF alterations in adamantinomatous and papillary craniopharyngiomas: mutation analysis with immunohistochemical correlation in 54 cases. J Neurooncol 133:487–495. https://doi.org/10.1007/s11060-017-2465-1

    Article  CAS  PubMed  Google Scholar 

  5. Louis DN, Ohgaki H, Wiestler ODCW (2016) WHO classification of tumors of the central nervous system (Revised 4th edition). IARC, Lyon

    Google Scholar 

  6. Müller HL (2014) Craniopharyngioma. Endocr Rev 35:513–543. https://doi.org/10.1210/er.2013-1115

    Article  CAS  PubMed  Google Scholar 

  7. Adamson TE, Wiestler OD, Kleihues P, Yaşargil MG (1990) Correlation of clinical and pathological features in surgically treated craniopharyngiomas. J Neurosurg 73:12–17. https://doi.org/10.3171/jns.1990.73.1.0012

    Article  CAS  PubMed  Google Scholar 

  8. Crotty TB, Scheithauer BW, Young WF et al (1995) Papillary craniopharyngioma: a clinicopathological study of 48 cases. J Neurosurg 83:206–214. https://doi.org/10.3171/jns.1995.83.2.0206

    Article  CAS  PubMed  Google Scholar 

  9. Brastianos PK, Santagata S (2016) BRAF V600E mutations in papillary craniopharyngioma. Eur J Endocrinol 174:R139–R144

    Article  CAS  PubMed  Google Scholar 

  10. Larkin SJ, Preda V, Karavitaki N et al (2014) BRAF V600E mutations are characteristic for papillary craniopharyngioma and may coexist with CTNNB1-mutated adamantinomatous craniopharyngioma. Acta Neuropathol 127:927–929. https://doi.org/10.1007/s00401-014-1270-6

    Article  PubMed  PubMed Central  Google Scholar 

  11. Schweizer L, Capper D, Hölsken A et al (2015) BRAF V600E analysis for the differentiation of papillary craniopharyngiomas and Rathke’s cleft cysts. Neuropathol Appl Neurobiol 41:733–742. https://doi.org/10.1111/nan.12201

    Article  CAS  PubMed  Google Scholar 

  12. Brastianos PK, Shankar GM, Gill CM et al (2016) Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djv310

    Article  PubMed  Google Scholar 

  13. Aylwin SJB, Bodi I, Beaney R (2016) Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor. Pituitary 19:544–546. https://doi.org/10.1007/s11102-015-0663-4

    Article  PubMed  Google Scholar 

  14. Roque A, Odia Y (2017) BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol 6:95–99. https://doi.org/10.2217/cns-2016-0034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rostami E, Witt Nyström P, Libard S et al (2017) Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy. Acta Neurochir. https://doi.org/10.1007/s00701-017-3311-0

    Article  PubMed  Google Scholar 

  16. Himes BT, Ruff MW, Van Gompel JJ et al (2018) Recurrent papillary craniopharyngioma with BRAF V600E mutation treated with dabrafenib: case report. J Neurosurg. https://doi.org/10.3171/2017.11.JNS172373

    Article  PubMed  Google Scholar 

  17. Clavien PA, Barkun J, de Oliveira ML et al (2009) The Clavien–Dindo classification of surgical complications. Ann Surg 250:187–196. https://doi.org/10.1097/SLA.0b013e3181b13ca2

    Article  PubMed  Google Scholar 

  18. Laufer I, Anand VK, Schwartz TH (2007) Endoscopic, endonasal extended transsphenoidal, transplanum transtuberculum approach for resection of suprasellar lesions. J Neurosurg 106:400–406. https://doi.org/10.3171/jns.2007.106.3.400

    Article  PubMed  Google Scholar 

  19. Yaşargil MG, Curcic M, Kis M et al (1990) Total removal of craniopharyngiomas. Approaches and long-term results in 144 patients. J Neurosurg 73:3–11. https://doi.org/10.3171/jns.1990.73.1.0003

    Article  PubMed  Google Scholar 

  20. Kassam AB, Gardner PA, Snyderman CH et al (2008) Evolution of the endonasal approach for craniopharyngiomas expanded endonasal approach, a fully endoscopic transnasal approach for the resection of midline suprasellar craniopharyngiomas: a new classification based on the infundibulum. J Neurosurg 108:715–728. https://doi.org/10.3171/JNS/2008/108/4/0715

    Article  PubMed  Google Scholar 

  21. Samii M, Tatagiba M (1997) Surgical management of craniopharyngiomas: a review. Neurol Med Chir (Tokyo) 37:141–149. https://doi.org/10.2176/nmc.37.141

    Article  CAS  Google Scholar 

  22. Pascual JM, González-Llanos F, Barrios L, Roda JM (2004) Intraventricular craniopharyngiomas: topographical classification and surgical approach selection based on an extensive overview. Acta Neurochir 146:785–802. https://doi.org/10.1007/s00701-004-0295-3

    Article  CAS  PubMed  Google Scholar 

  23. Marucci G, de Biase D, Zoli M et al (2015) Targeted BRAF and CTNNB1 next-generation sequencing allows proper classification of nonadenomatous lesions of the sellar region in samples with limiting amounts of lesional cells. Pituitary 18:905–911. https://doi.org/10.1007/s11102-015-0669-y

    Article  CAS  PubMed  Google Scholar 

  24. Haston S, Pozzi S, Carreno G et al (2017) MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development 144:2141–2152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wan PTC, Garnett MJ, Roe SM et al (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116:855–867. https://doi.org/10.1016/S0092-8674(04)00215-6

    Article  CAS  PubMed  Google Scholar 

  26. Omay SB, Chen Y-N, Almeida JP et al (2017) Do craniopharyngioma molecular signatures correlate with clinical characteristics? J Neurosurg. https://doi.org/10.3171/2017.1.JNS162232

    Article  PubMed  Google Scholar 

  27. Kim JH, Paulus W, Heim S (2015) BRAF V600E mutation is a useful marker for differentiating Rathke’s cleft cyst with squamous metaplasia from papillary craniopharyngioma. J Neurooncol 123:189–191. https://doi.org/10.1007/s11060-015-1757-6

    Article  PubMed  Google Scholar 

  28. Capper D, Preusser M, Habel A et al (2011) Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol 122:11–19. https://doi.org/10.1007/s00401-011-0841-z

    Article  CAS  PubMed  Google Scholar 

  29. Jones RT, Abedalthagafi MS, Brahmandam M et al (2015) Cross-reactivity of the BRAF VE1 antibody with epitopes in axonemal dyneins leads to staining of cilia. Mod Pathol 28:596–606. https://doi.org/10.1038/modpathol.2014.150

    Article  CAS  PubMed  Google Scholar 

  30. Sartoretti-Schefer S, Wichmann W, Aguzzi A, Valavanis A (1997) MR differentiation of adamantinous and squamous-papillary craniopharyngiomas. Am J Neuroradiol. 18:77–87

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee IH, Zan E, Bell WR et al (2016) Craniopharyngiomas: radiological differentiation of two types. J Korean Neurosurg Soc. https://doi.org/10.3340/jkns.2016.59.5.466

    Article  PubMed  PubMed Central  Google Scholar 

  32. Yue Q, Yu Y, Shi Z et al (2017) Prediction of BRAF mutation status of craniopharyngioma using magnetic resonance imaging features. J Neurosurg. https://doi.org/10.3171/2017.4.JNS163113

    Article  PubMed  Google Scholar 

  33. Prieto R, Pascual JM, Rosdolsky M et al (2016) Craniopharyngioma adherence: a comprehensive topographical categorization and outcome-related risk stratification model based on the methodical examination of 500 tumors. Neurosurg Focus. https://doi.org/10.3171/2016.9.FOCUS16304

    Article  PubMed  Google Scholar 

  34. Sato K, Oka H, Utsuki S et al (2006) Ciliated craniopharyngioma may arise from Rathke cleft cyst. Clin Neuropathol 25:25–28

    CAS  PubMed  Google Scholar 

  35. Zoli M, Sambati L, Milanese L et al (2016) Postoperative outcome of body core temperature rhythm and sleep-wake cycle in third ventricle craniopharyngiomas. Neurosurg Focus. https://doi.org/10.3171/2016.9.FOCUS16317

    Article  PubMed  Google Scholar 

  36. Cavallo LM, Frank G, Cappabianca P et al (2014) The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg. https://doi.org/10.3171/2014.3.JNS131521

    Article  PubMed  Google Scholar 

  37. Moussazadeh N, Prabhu V, Bander ED et al (2016) Endoscopic endonasal versus open transcranial resection of craniopharyngiomas: a case-matched single-institution analysis. Neurosurg Focus 41:E7. https://doi.org/10.3171/2016.9.FOCUS16299

    Article  PubMed  Google Scholar 

  38. Ottenhausen M, Rumalla K, La Corte E et al (2017) Treatment strategies for craniopharyngiomas. J Neurosurg Sci. https://doi.org/10.23736/S0390-5616.17.04171-6

    Article  PubMed  Google Scholar 

  39. Mortini P, Losa M, Pozzobon G et al (2011) Neurosurgical treatment of craniopharyngioma in adults and children: early and long-term results in a large case series. J Neurosurg 114:1350–1359. https://doi.org/10.3171/2010.11.JNS10670

    Article  PubMed  Google Scholar 

  40. Younus I, Forbes JA, Ordóñez-Rubiano EG et al (2018) Radiation therapy rather than prior surgery reduces extent of resection during endonasal endoscopic reoperation for craniopharyngioma. Acta Neurochir (Wien). https://doi.org/10.1007/s00701-018-3567-z

    Article  Google Scholar 

  41. Dhandapani S, Singh H, Negm HM et al (2016) Endonasal endoscopic reoperation for residual or recurrent craniopharyngiomas. J Neurosurg. https://doi.org/10.3171/2016.1.JNS152238

    Article  PubMed  Google Scholar 

  42. Flaherty K, Puzanov I, Kim K et al (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363:809–819. https://doi.org/10.1056/NEJMoa1002011.Inhibition

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Weill Cornell Medical College, New York-Presbyterian Hospital, 525 East 68th St., Box #99, New York, NY, 10065, USA

    Emanuele La Corte, Iyan Younus, Francesca Pivari, Adelina Selimi, Malte Ottenhausen, Jonathan A. Forbes, Georgiana A. Dobri & Theodore H. Schwartz

  2. Department of Pathology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA

    David J. Pisapia

  3. Department of Neuroscience, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA

    Theodore H. Schwartz

  4. Department of Otolaryngology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA

    Vijay K. Anand & Theodore H. Schwartz

  5. Department of Health Sciences, University of Milan, Milan, Italy

    Emanuele La Corte & Francesca Pivari

  6. Department of Neurosurgery, Foundation IRCCS Neurological Institute “Carlo Besta”, Milan, Italy

    Emanuele La Corte

  7. Department of Medicine, University of Perugia, Perugia, Italy

    Adelina Selimi

  8. Department of Neurosurgery, University Mainz, Mainz, Germany

    Malte Ottenhausen

Authors
  1. Emanuele La Corte
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  2. Iyan Younus
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  6. Jonathan A. Forbes
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  10. Theodore H. Schwartz
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Correspondence to Theodore H. Schwartz.

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La Corte, E., Younus, I., Pivari, F. et al. BRAF V600E mutant papillary craniopharyngiomas: a single-institutional case series. Pituitary 21, 571–583 (2018). https://doi.org/10.1007/s11102-018-0909-z

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