RET/PTC3 translocation in a rare hemorrhagic brain metastasis of papillary thyroid cancer post Chernobyl radiation affects vessels ultrastructure

Michela Relucenti; Pietro Familiari; Giorgia Iacopino; Placido Bruzzaniti; Selenia Miglietta; Maurizio Salvati; Xiaobo Li; Rui Chen; Giancarlo D'Andrea; Alessandro Frati; Cira Di Gioia; Angelina Pernazza; Carlo Della Rocca; Giuseppe Familiari; Antonio Santoro

Interdisciplinary Neurosurgery (Mar 2021)

RET/PTC3 translocation in a rare hemorrhagic brain metastasis of papillary thyroid cancer post Chernobyl radiation affects vessels ultrastructure

Michela Relucenti,
Pietro Familiari,
Giorgia Iacopino,
Placido Bruzzaniti,
Selenia Miglietta,
Maurizio Salvati,
Xiaobo Li,
Rui Chen,
Giancarlo D'Andrea,
Alessandro Frati,
Cira Di Gioia,
Angelina Pernazza,
Carlo Della Rocca,
Giuseppe Familiari,
Antonio Santoro

Affiliations

Michela Relucenti: Dept of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Section Human Anatomy, Sapienza University of Rome, Via Alfonso Borelli 50, 00161 Rome, Italy
Pietro Familiari: Dept of Human Neuroscience, Division of Neurosurgery, Sapienza University of Rome, Viale dell'Università 30, 00161 Rome, Italy; Corresponding author.
Giorgia Iacopino: Dept of Human Neuroscience, Division of Neurosurgery, Sapienza University of Rome, Viale dell'Università 30, 00161 Rome, Italy
Placido Bruzzaniti: Dept of Human Neuroscience, Division of Neurosurgery, Sapienza University of Rome, Viale dell'Università 30, 00161 Rome, Italy; Fabrizio Spaziani Hospital, Neurosurgery Division, Via Armando Fabi, 5, 03100 Frosinone, Italy
Selenia Miglietta: Dept of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Section Human Anatomy, Sapienza University of Rome, Via Alfonso Borelli 50, 00161 Rome, Italy
Maurizio Salvati: Dept of Human Neuroscience, Division of Neurosurgery, Sapienza University of Rome, Viale dell'Università 30, 00161 Rome, Italy
Xiaobo Li: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
Rui Chen: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
Giancarlo D'Andrea: Fabrizio Spaziani Hospital, Neurosurgery Division, Via Armando Fabi, 5, 03100 Frosinone, Italy
Alessandro Frati: Department of Neurosciences, Mental Health, and Sensory Organs, Sant'Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; Neuromed IRCCS, Via Atinense 18, 86077 Pozzilli, Italy
Cira Di Gioia: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Viale dell'Università 30, 00161 Rome, Italy
Angelina Pernazza: Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Corso della Repubblica 79, Latina, Italy
Carlo Della Rocca: Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Corso della Repubblica 79, Latina, Italy
Giuseppe Familiari: Dept of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Section Human Anatomy, Sapienza University of Rome, Via Alfonso Borelli 50, 00161 Rome, Italy
Antonio Santoro: Dept of Human Neuroscience, Division of Neurosurgery, Sapienza University of Rome, Viale dell'Università 30, 00161 Rome, Italy

Journal volume & issue: Vol. 23
p. 100889

Abstract

Read online

Background: Slow progression and good prognosis are the usual characteristics of papillary thyroid carcinoma (PTC). The presence of brain metastases (0.4–1.2%) is suggestive of a worse prognosis. RET/PTC rearrangements were particularly prevalent in PTCs developed after Chernobyl nuclear accident. Case description: A 50-year-old woman born in Slovakia, exposed to radiation resulting from the accident at the Chernobyl nuclear power plant, affected since 2017 by papillary thyroid cancer and in therapy at our hospital, experimented cerebral hemorrhagic metastasis. Biopsy analyses revealed a RET/PTC3 rearrangement, so our aim was to find possible morphological relation between hemorrhagic metastasis and RET/PTC3 translocation. Results: Immunohistochemical analysis showed diffuse and intense positivity for VEGF in endothelial cells of the neoplasm’ vascular network. Transmission electron microscopy images showed vessels with unorganized pattern and uneven diameters. In particular, metastasis endothelial cells (MECs) showed irregular shape and size, thickened cytoplasm and swelling of endoplasmic reticulum. MECs organized in irregular monolayers or multiple layers, surrounded by a thickened but unstructured extracellular matrix. Absence of strong junctional complexes among MECs resulted in a further weakened vessels wall. Conclusion: RET/PTC3 translocation causes VEGF overexpression via STAT3 signaling cascade and the increased amount of VEGF adds to the greater amount of VEGFRs expressed by MECs. Our ultrastructural investigation show that this condition creates a massive growth of altered vessels prone to bleeding. The clinical significance of our study consists in alert oncologist and surgeons on possible arising of hemorrhagic brain metastases in patients with PTC and RET/PTC3 translocation exposed to ionizing radiation as people living in areas caught up in Chernobyl or Fukushima disasters.

Published in Interdisciplinary Neurosurgery

ISSN: 2214-7519 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Surgery; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/interdisciplinary-neurosurgery/

About the journal

Abstract

Keywords