Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma.
OBJECTIVE
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.
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. v.scagliotti@qmul.ac.uk.
Valeria
V
Scagliotti
Department of Health Sciences, Università degli Studi di Milano, Via A. Di Rudini, 8, 20142, Milan, Italy. laura.avagliano@unimi.it.
Laura
L
Avagliano
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. angelica.gualtieri@stud.unifi.it.
Angelica
A
Gualtieri
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. federica.graziola@fastwebnet.it.
Federica
F
Graziola
Department of Health Sciences, Università degli Studi di Milano, Via A. Di Rudini, 8, 20142, Milan, Italy. patridoi@libero.it.
Patrizia
P
Doi
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@gosh.nhs.uk.
Jane
J
Chalker
Radiology and Neuroradiology Department, Children's Hospital V. Buzzi, 20142, Milan, Italy. andrea.righini@icp.mi.it.
Andrea
A
Righini
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. m.korbonits@qmul.ac.uk.
Marta
M
Korbonits
Department of Health Sciences, Università degli Studi di Milano, Via A. Di Rudini, 8, 20142, Milan, Italy. gaetano.bulfamante@unimi.it.
Gaetano
G
Bulfamante
Developmental Biology and Cancer Programme, UCL Institute of Child Health, University College London, London, UK. thomas.jacques@gosh.nhs.uk.|Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, 30 Guilford Street, London, WC1N 1EH, UK. thomas.jacques@gosh.nhs.uk.
Thomas S
TS
Jacques
Department of Health Sciences, Università degli Studi di Milano, Via A. Di Rudini, 8, 20142, Milan, Italy. valentina.massa@unimi.it.
Valentina
V
Massa
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. c.gaston-massuet@qmul.ac.uk.
Carles
C
Gaston-Massuet
D001932:Brain Neoplasms / Q000175:diagnosis; D003397:Craniopharyngioma / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D010902:Pituitary Gland / Q000473:pathology; D010911:Pituitary Neoplasms / Q000175:diagnosis; D011247:Pregnancy
Congenital brain tumours; Craniopharyngioma; Genetics hypothalamic-pituitary axis; Pituitary gland; Pituitary tumours