Skip to main content
SpringerLink
Log in

Histopathology and Molecular Pathology of Craniopharyngioma in Adults

  • Chapter
  • First Online:
Adult Craniopharyngiomas

Abstract

Craniopharyngiomas are rare epithelial tumors of the sellar and parasellar region. They are biologically benign but may cause significant morbidities. The 2016 World Health Organization classification distinguishes two subtypes: adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP). These two subtypes are characterized by distinctive histopathological and molecular features. ACP occurs in both children and adults. It shows invasive borders and frequent regressive changes including calcifications, cholesterol deposition, old hemorrhages, and fibrosis. Histopathologically, ACP consists of epithelial clusters with an outer palisading epithelium, a stellate reticulum, and aggregates of “wet keratin.” ACP is characterized by an activation of the Wnt/β-catenin pathway due to mutations in exon 3 of the CTNNB1 gene. PCP is typically an adult tumor and is usually more circumscribed than ACP. PCP is composed of papillae covered by a regular non-keratinizing squamous epithelium. Molecularly, PCP is characterized by an activation of the MAPKinase pathway due to BRAF V600E mutation.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zacharia BE, Bruce SS, Goldstein H, Malone HR, Neugut AI, Bruce JN. Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program. Neuro-Oncology. 2012;14:1070–8.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Pascual JM, Rosdolsky M, Prieto R, Straubeta S, Winter E, Ulrich W. Jakob Erdheim (1874-1937): father of hypophyseal-duct tumors (craniopharyngiomas). Virchows Arch. 2015;467:459–69.

    Article  PubMed  Google Scholar 

  3. Bulsei R, Rushing EJ, Giangaspero F, Paulus W, Burger PC, Santagata S. Craniopharyngioma. In: Louis DN, Hiroko O, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: IARC; 2016. p. 324–8.

    Google Scholar 

  4. Holsken A, Sill M, Merkle J, Schweizer L, Buchfelder M, Flitsch J, Fahlbusch R, Metzler M, Kool M, Pfister SM, von Deimling A, Capper D, Jones DT, Buslei R. Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles. Acta Neuropathol Commun. 2016;4:20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Muller HL. Craniopharyngioma. Handb Clin Neurol. 2014;124:235–53.

    Article  PubMed  Google Scholar 

  6. Szeifert GT, Sipos L, Horvath M, Sarker MH, Major O, Salomvary B, Czirjak S, Balint K, Slowik F, Kolonics L, et al. Pathological characteristics of surgically removed craniopharyngiomas: analysis of 131 cases. Acta Neurochir. 1993;124:139–43.

    Article  CAS  PubMed  Google Scholar 

  7. Zada G, Lin N, Ojerholm E, Ramkissoon S, Laws ER. Craniopharyngioma and other cystic epithelial lesions of the sellar region: a review of clinical, imaging, and histopathological relationships. Neurosurg Focus. 2010;28:E4.

    Article  PubMed  Google Scholar 

  8. Larkin SJ, Ansorge O. Pathology and pathogenesis of craniopharyngiomas. Pituitary. 2013;16:9–17.

    Article  PubMed  Google Scholar 

  9. Kawamata T, Kubo O, Hori T. Histological findings at the boundary of craniopharyngiomas. Brain Tumor Pathol. 2005;22:75–8.

    Article  PubMed  Google Scholar 

  10. Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y, Sakamoto M, Hirohashi S. Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol. 2002;161:1997–2001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F, Hahnen E, Kreutzer J, Fahlbusch R. Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol. 2005;109:589–97.

    Article  CAS  PubMed  Google Scholar 

  12. Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, Lawrence MS, Rodriguez FJ, Bernardo LA, Schubert L, Sunkavalli A, Shillingford N, Calicchio ML, Lidov HG, Taha H, Martinez-Lage M, Santi M, Storm PB, Lee JY, Palmer JN, Adappa ND, Scott RM, Dunn IF, Laws ER Jr, Stewart C, Ligon KL, Hoang MP, Van Hummelen P, Hahn WC, Louis DN, Resnick AC, Kieran MW, Getz G, Santagata S. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. 2014;46:161–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goschzik T, Gessi M, Dreschmann V, Gebhardt U, Wang L, Yamaguchi S, Wheeler DA, Lauriola L, Lau CC, Muller HL, Pietsch T. Genomic alterations of adamantinomatous and papillary craniopharyngioma. J Neuropathol Exp Neurol. 2017;76:126–34.

    CAS  PubMed  Google Scholar 

  14. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36:1461–73.

    Article  CAS  PubMed  Google Scholar 

  15. Ghosh N, Hossain U, Mandal A, Sil PC. The Wnt signaling pathway: a potential therapeutic target against cancer. Ann N Y Acad Sci. 2019;1443:54–74.

    Article  PubMed  Google Scholar 

  16. Gao C, Wang Y, Broaddus R, Sun L, Xue F, Zhang W. Exon 3 mutations of CTNNB1 drive tumorigenesis: a review. Oncotarget. 2018;9:5492–508.

    PubMed  Google Scholar 

  17. Stamos JL, Weis WI. The beta-catenin destruction complex. Cold Spring Harb Perspect Biol. 2013;5:a007898.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. MacDonald BT, He X. Frizzled and LRP5/6 receptors for Wnt/beta-catenin signaling. Cold Spring Harb Perspect Biol. 2012;4:a007880.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Gomes CC, de Sousa SF, Gomez RS. Craniopharyngiomas and odontogenic tumors mimic normal odontogenesis and share genetic mutations, histopathologic features, and molecular pathways activation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019;127:231–6.

    Article  PubMed  Google Scholar 

  20. Muller C, Adroos N, Lockhat Z, Slavik T, Kruger H. Toothy craniopharyngioma: a literature review and case report of craniopharyngioma with extensive odontogenic differentiation and tooth formation. Childs Nerv Syst. 2011;27:323–6.

    Article  PubMed  Google Scholar 

  21. Dubois PM, Elamraoui A. Embryology of the pituitary gland. Trends Endocrinol Metab. 1995;6:1–7.

    Article  CAS  PubMed  Google Scholar 

  22. Khonsari RH, Seppala M, Pradel A, Dutel H, Clement G, Lebedev O, Ghafoor S, Rothova M, Tucker A, Maisey JG, Fan CM, Kawasaki M, Ohazama A, Tafforeau P, Franco B, Helms J, Haycraft CJ, David A, Janvier P, Cobourne MT, Sharpe PT. The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling. BMC Biol. 2013;11:27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Asa SL, Kovacs K, Bilbao JM. The pars tuberalis of the human pituitary. A histologic, immunohistochemical, ultrastructural and immunoelectron microscopic analysis. Virchows Arch A. 1983;399:49–59.

    Article  CAS  Google Scholar 

  24. Luse SA, Kernohan JW. Squamous-cell nests of the pituitary gland. Cancer. 1955;8:623–8.

    Article  CAS  PubMed  Google Scholar 

  25. Martinez-Barbera JP, Andoniadou CL. Paracrine role of stem cells in pituitary tumors: a focus on adamantinomatous craniopharyngioma. Stem Cells. 2016;34:268–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Apps JR, Martinez-Barbera JP. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology. Brain Pathol. 2017;27:364–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Som PM, Miletich I. Review of the embryology of the teeth. Neurographics. 2018;8:369–93.

    Article  Google Scholar 

  28. Apps JR, Carreno G, Gonzalez-Meljem JM, Haston S, Guiho R, Cooper JE, Manshaei S, Jani N, Holsken A, Pettorini B, Beynon RJ, Simpson DM, Fraser HC, Hong Y, Hallang S, Stone TJ, Virasami A, Donson AM, Jones D, Aquilina K, Spoudeas H, Joshi AR, Grundy R, Storer LCD, Korbonits M, Hilton DA, Tossell K, Thavaraj S, Ungless MA, Gil J, Buslei R, Hankinson T, Hargrave D, Goding C, Andoniadou CL, Brogan P, Jacques TS, Williams HJ, Martinez-Barbera JP. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathol. 2018;135:757–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Crotty TB, Scheithauer BW, Young WF Jr, Davis DH, Shaw EG, Miller GM, Burger PC. Papillary craniopharyngioma: a clinicopathological study of 48 cases. J Neurosurg. 1995;83:206–14.

    Article  CAS  PubMed  Google Scholar 

  30. Borrill R, Cheesman E, Stivaros S, Kamaly-Asl ID, Gnanalingham K, Kilday JP. Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature. Childs Nerv Syst. 2019;35:169–73.

    Article  CAS  PubMed  Google Scholar 

  31. La Corte E, Younus I, Pivari F, Selimi A, Ottenhausen M, Forbes JA, Pisapia DJ, Dobri GA, Anand VK, Schwartz TH. BRAF V600E mutant papillary craniopharyngiomas: a single-institutional case series. Pituitary. 2018;21:571–83.

    Article  PubMed  Google Scholar 

  32. Larkin SJ, Preda V, Karavitaki N, Grossman A, Ansorge O. BRAF V600E mutations are characteristic for papillary craniopharyngioma and may coexist with CTNNB1-mutated adamantinomatous craniopharyngioma. Acta Neuropathol. 2014;127:927–9.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Marucci G, de Biase D, Zoli M, Faustini-Fustini M, Bacci A, Pasquini E, Visani M, Mazzatenta D, Frank G, Tallini G. 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. 2015;18:905–11.

    Article  CAS  PubMed  Google Scholar 

  34. Yoshimoto K, Hatae R, Suzuki SO, Hata N, Kuga D, Akagi Y, Amemiya T, Sangatsuda Y, Mukae N, Mizoguchi M, Iwaki T, Iihara K. High-resolution melting and immunohistochemical analysis efficiently detects mutually exclusive genetic alterations of adamantinomatous and papillary craniopharyngiomas. Neuropathology. 2018;38:3–10.

    Article  CAS  PubMed  Google Scholar 

  35. Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170:17–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yaeger R, Corcoran RB. Targeting alterations in the RAF-MEK pathway. Cancer Discov. 2019;9:329–41.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Haston S, Pozzi S, Carreno G, Manshaei S, Panousopoulos L, Gonzalez-Meljem JM, Apps JR, Virasami A, Thavaraj S, Gutteridge A, Forshew T, Marais R, Brandner S, Jacques TS, Andoniadou CL, Martinez-Barbera JP. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma. Development. 2017;144:2141–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Aylwin SJ, Bodi I, Beaney R. Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor. Pituitary. 2016;19:544–6.

    Article  PubMed  Google Scholar 

  39. Brastianos PK, Shankar GM, Gill CM, Taylor-Weiner A, Nayyar N, Panka DJ, Sullivan RJ, Frederick DT, Abedalthagafi M, Jones PS, Dunn IF, Nahed BV, Romero JM, Louis DN, Getz G, Cahill DP, Santagata S, Curry WT Jr, Barker FG. Dramatic response of BRAF V600E mutant papillary craniopharyngioma to targeted therapy. J Natl Cancer Inst. 2016;108:djv310.

    Article  PubMed  CAS  Google Scholar 

  40. Rostami E, Witt Nystrom P, Libard S, Wikstrom J, Casar-Borota O, Gudjonsson O. Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy. Acta Neurochir. 2017;159:2217–21.

    Article  PubMed  Google Scholar 

  41. Fujio S, Juratli TA, Arita K, Hirano H, Nagano Y, Takajo T, Yoshimoto K, Bihun IV, Kaplan AB, Nayyar N, Fink AL, Bertalan MS, Tummala SS, Curry WT Jr, Jones PS, Martinez-Lage M, Cahill DP, Barker FG, Brastianos PK. A clinical rule for preoperative prediction of BRAF mutation status in craniopharyngiomas. Neurosurgery. 2018;85(2):204–10.

    Article  Google Scholar 

  42. Okada T, Fujitsu K, Miyahara K, Ichikawa T, Takemoto Y, Niino H, Yagishita S, Shiina T. Ciliated craniopharyngioma--case report and pathological study. Acta Neurochir. 2010;152:303–6.

    Article  PubMed  Google Scholar 

  43. Schlaffer SM, Buchfelder M, Stoehr R, Buslei R, Holsken A. Rathke’s cleft cyst as origin of a pediatric papillary craniopharyngioma. Front Genet. 2018;9:49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Karavitaki N, Scheithauer BW, Watt J, Ansorge O, Moschopoulos M, Llaguno AV, Wass JA. Collision lesions of the sella: co-existence of craniopharyngioma with gonadotroph adenoma and of Rathke’s cleft cyst with corticotroph adenoma. Pituitary. 2008;11:317–23.

    Article  CAS  PubMed  Google Scholar 

  45. Chang KC, Jin YT, Chen RM, Su LJ. Mixed olfactory neuroblastoma and craniopharyngioma: an unusual pathological finding. Histopathology. 1997;30:378–82.

    Article  CAS  PubMed  Google Scholar 

  46. Moshkin O, Scheithauer BW, Syro LV, Velasquez A, Horvath E, Kovacs K. Collision tumors of the sella: craniopharyngioma and silent pituitary adenoma subtype 3: case report. Endocr Pathol. 2009;20:50–5.

    Article  PubMed  Google Scholar 

  47. Kristopaitis T, Thomas C, Petruzzelli GJ, Lee JM. Malignant craniopharyngioma. Arch Pathol Lab Med. 2000;124:1356–60.

    CAS  PubMed  Google Scholar 

  48. Ishida M, Hotta M, Tsukamura A, Taga T, Kato H, Ohta S, Takeuchi Y, Nakasu S, Okabe H. Malignant transformation in craniopharyngioma after radiation therapy: a case report and review of the literature. Clin Neuropathol. 2010;29:2–8.

    Article  CAS  PubMed  Google Scholar 

  49. Nomura S, Aihara Y, Amano K, Eguchi S, Chiba K, Komori T, Kawamata T. A rare case of malignant craniopharyngioma reactive to adjunctive stereotactic radiotherapy and chemotherapy: case report and literature review. World Neurosurg. 2018;117:332–8.

    Article  PubMed  Google Scholar 

  50. Schweizer L, Capper D, Holsken A, Fahlbusch R, Flitsch J, Buchfelder M, Herold-Mende C, von Deimling A, Buslei R. BRAF V600E analysis for the differentiation of papillary craniopharyngiomas and Rathke’s cleft cysts. Neuropathol Appl Neurobiol. 2015;41:733–42.

    Article  CAS  PubMed  Google Scholar 

  51. Paulus W, Honegger J, Keyvani K, Fahlbusch R. Xanthogranuloma of the sellar region: a clinicopathological entity different from adamantinomatous craniopharyngioma. Acta Neuropathol. 1999;97:377–82.

    Article  CAS  PubMed  Google Scholar 

  52. Kleinschmidt-DeMasters BK, Lillehei KO, Hankinson TC. Review of xanthomatous lesions of the sella. Brain Pathol. 2017;27:377–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fujio S, Takajo T, Kinoshita Y, Hanaya R, Arimura H, Sugata J, Sugata S, Bohara M, Hiraki T, Yoshimoto K, Arita K. Sellar xanthogranuloma: a quest based on nine cases assessed with anterior pituitary provocation test. World Neurosurg. 2019;130:e150–9.

    Article  PubMed  Google Scholar 

  54. Hofmann BM, Kreutzer J, Saeger W, Buchfelder M, Blumcke I, Fahlbusch R, Buslei R. Nuclear beta-catenin accumulation as reliable marker for the differentiation between cystic craniopharyngiomas and rathke cleft cysts: a clinico-pathologic approach. Am J Surg Pathol. 2006;30:1595–603.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de Pathologie et de Neuropathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France

    Alexandre Vasiljevic

  2. Faculté de Médecine Lyon Est, Université Lyon 1, Lyon, France

    Alexandre Vasiljevic

  3. INSERM U1052, CNRS UMR5286, Cancer Research Centre of Lyon, Lyon, France

    Alexandre Vasiljevic

  4. Department of Pathological Cytology and Anatomy, Foch Hospital, Suresnes, France

    Chiara Villa

  5. INSERM U1016, CNRS UMR8104, Paris Descartes University, Cochin Institute, Paris, France

    Chiara Villa

  6. Department of Endocrinology, University of Liège, CHU de Liège, Liège, Belgium

    Chiara Villa

Authors
  1. Alexandre Vasiljevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chiara Villa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandre Vasiljevic .

Editor information

Editors and Affiliations

  1. Skull Base and Pituitary Neurosurgical Department, Hôpital Pierre Wertheimer “Groupement Hospitalier Est” Hospices Civils de Lyon“Claude Bernard” Lyon 1 University, Lyon, France

    Emmanuel Jouanneau

  2. Endocrinology Department, Reference Center for Rare Pituitary Diseases HYPO“Groupement Hospitalier Est” Hospices Civils de Lyon“Claude Bernard” Lyon 1 University, Lyon, France

    Gérald Raverot

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Vasiljevic, A., Villa, C. (2020). Histopathology and Molecular Pathology of Craniopharyngioma in Adults. In: Jouanneau, E., Raverot, G. (eds) Adult Craniopharyngiomas. Springer, Cham. https://doi.org/10.1007/978-3-030-41176-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-41176-3_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-41175-6

  • Online ISBN: 978-3-030-41176-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation