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Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma

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Abstract

Purpose

Adamantinomatous craniopharyngiomas (aCPs) are complex epithelial neoplasms that arise from the progenitors of the pituitary gland. Although benign, these tumours can be locally aggressive invading vital neighbouring structures such as the hypothalamus, the cranial and optic nerves. Congenital forms of aCPs diagnosed during foetal development are very rare. The purpose of this article is to present with a histopathological and molecular characterisation of congenital craniopharyngioma.

Methods

Here we report a case of in utero diagnosed aCP, detected at 21 weeks of gestation by ultrasound, visualised by MRI at 22 weeks and histologically diagnosed at 23 weeks. We provide with histopathological characterisation of rare form of congenital aCPs.

Results

Detailed examination of the tumour reveals the classical histological hallmarks of aCPs with the presence of stellate reticulum, palisading epithelium, wet keratin and calcification deposits. The tumour demonstrated complete absence of all pituitary hormones and the absence of the neuroendocrine marker, synaptophysin. Immunohistochemistry against β-catenin revealed occasional cells with nuclear-β-catenin localisation and the presence of pituitary progenitors positive for SOX9 and SOX2. Targeted Sanger sequencing revealed no genetic variants in oncogenes CTNNB1 and BRAF, previously associated with CP.

Conclusions

In this article, we provide with in-depth molecular and histological characterisation of in utero aCP due to an unknown driving mutation that could represent a sub-cohort of congenital aCPs.

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Acknowledgments

We are very grateful to Dr Evelien Gevers for critically reading the manuscript and to Daniela Graziani for technical assistance with sequencing experiments. VS, AG, CGM are sponsored by the Early Career Research (ERC) fellowship program from Barts and The London Medical School (supported by the Medical College of Saint Bartholomew’s Hospital Trust); Barts and The London Charity (BTLC, Grants 417/2081 and 417/2238) Queen Mary University of London; Action Medical Research (Grant GN2272). FG was a recipient of Society for Endocrinology Summer Studentship.

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    Authors and Affiliations

    1. Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

      Valeria Scagliotti, Angelica Gualtieri, Federica Graziola, Marta Korbonits & Carles Gaston-Massuet

    2. Department of Health Sciences, Università degli Studi di Milano, Via A. Di Rudini, 8, 20142, Milan, Italy

      Laura Avagliano, Patrizia Doi, Gaetano Bulfamante & Valentina Massa

    3. Haematology, Cellular and Molecular Diagnostic Service, Camelia Botnar Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK

      Jane Chalker

    4. Radiology and Neuroradiology Department, Children’s Hospital V. Buzzi, 20142, Milan, Italy

      Andrea Righini

    5. Developmental Biology and Cancer Programme, UCL Institute of Child Health, University College London, London, UK

      Thomas S. Jacques

    6. Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, 30 Guilford Street, London, WC1N 1EH, UK

      Thomas S. Jacques

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    1. Valeria Scagliotti
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    2. Laura Avagliano
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    Correspondence to Carles Gaston-Massuet.

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    Valeria Scagliotti and Laura Avagliano have contributed equally to this work.

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    Scagliotti, V., Avagliano, L., Gualtieri, A. et al. Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma. Pituitary 19, 50–56 (2016). https://doi.org/10.1007/s11102-015-0682-1

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