Anthony P Y Liu1, Megan M Kelsey2, Nelly Sabbaghian3, Sung-Hye Park4, Cheri L Deal5, Adam J Esbenshade6, Oswald Ploner7, Andrew Peet8,9, Heidi Traunecker10, Yomna H E Ahmed11, Margaret Zacharin12, Anatoly Tiulpakov13, Anastasia M Lapshina14, Andrew W Walter15, Pinaki Dutta16, Ashutosh Rai16, Márta Korbonits17, Leanne de Kock18, Kim E Nichols19, William D Foulkes3,20, John R Priest21. 1. Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 2. Department of Pediatrics, Section of Pediatric Endocrinology, Children's Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 3. Department of Medical Genetics, The Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada. 4. Department of Pathology, Seoul National University, College of Medicine, Seoul, Republic of Korea. 5. Endocrinology and Diabetes Service, CHU-Sainte Justine and Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada. 6. Department of Pediatrics, Monroe Carell Jr. Children's Hospital, Nashville, Tennessee, USA. 7. Diakonie-Klinikum, Stuttgart, Germany. 8. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. 9. Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK. 10. Noah's Ark Children's Hospital for Wales, Cardiff, UK. 11. Royal College of Surgeons in Ireland-Bahrain, Bahrain. 12. Department of Endocrinology and Diabetes, Royal Children's Hospital, Parkville, Melbourne, Victoria, Australia. 13. Department and Laboratory of Inherited Endocrine Disorders, Endocrinology Research Centre, Moscow, Russia. 14. Department of Fundamental Pathomorphology, Endocrinology Research Centre, Moscow, Russia. 15. duPont Hospital for Children, Wilmington, Delaware, USA. 16. Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 17. Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, UK. 18. Harry Perkins Institute of Medical Research, QEII Medical Centre and UWA Centre for Medical Research, the University of Western Australia, Perth, Australia. 19. Division of Cancer Predisposition, Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. 20. Department of Medical Genetics and Cancer Research Program, Research Institute McGill University Health Centre, Montreal, Quebec, Canada. 21. Minneapolis, Minnesota, USA.
Abstract
CONTEXT: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome. OBJECTIVE: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases. DESIGN AND SETTING: A multi-institutional case series is presented from tertiary pediatric oncology centers. PATIENTS: Patients included children with pituitary blastoma. INTERVENTIONS: Genetic testing, surgery, oncologic therapy, endocrine support are reported. OUTCOME MEASURES: Outcome measures included survival, long-term morbidities, and germline and tumor DICER1 genotypes. RESULTS: Seventeen pituitary blastoma cases were studied (10 girls and 7 boys); median age at diagnosis was 11 months (range, 2-24 months). Cushing syndrome was the most frequent presentation (n = 10). Cushingoid stigmata were absent in 7 children (2 with increased adrenocorticotropin [ACTH]; 5 with normal/unmeasured ACTH). Ophthalmoplegia and increased intracranial pressure were also observed. Surgical procedures included gross/near-total resection (n = 7), subtotal resection (n = 9), and biopsy (n = 1). Six children received adjuvant therapy. At a median follow-up of 6.7 years, 9 patients were alive; 8 patients died of the following causes: early medical/surgical complications (n = 3), sepsis (n = 1), catheter-related complication (n = 1), aneurysmal bleeding (n = 1), second brain tumor (n = 1), and progression (n = 1). Surgery was the only intervention for 5 of 9 survivors. Extent of resection, but neither Ki67 labeling index nor adjuvant therapy, was significantly associated with survival. Chronic complications included neuroendocrine (n = 8), visual (n = 4), and neurodevelopmental (n = 3) deficits. Sixteen pituitary blastomas were attributed to DICER1 abnormalities. CONCLUSIONS: Pituitary blastoma is a locally destructive tumor associated with high mortality. Surgical resection alone provides long-term disease control for some patients. Quality survival is possible with long-term neuroendocrine management.
CONTEXT: Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome. OBJECTIVE: This work aims to describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases. DESIGN AND SETTING: A multi-institutional case series is presented from tertiary pediatric oncology centers. PATIENTS: Patients included children with pituitary blastoma. INTERVENTIONS: Genetic testing, surgery, oncologic therapy, endocrine support are reported. OUTCOME MEASURES: Outcome measures included survival, long-term morbidities, and germline and tumor DICER1 genotypes. RESULTS: Seventeen pituitary blastoma cases were studied (10 girls and 7 boys); median age at diagnosis was 11 months (range, 2-24 months). Cushing syndrome was the most frequent presentation (n = 10). Cushingoid stigmata were absent in 7 children (2 with increased adrenocorticotropin [ACTH]; 5 with normal/unmeasured ACTH). Ophthalmoplegia and increased intracranial pressure were also observed. Surgical procedures included gross/near-total resection (n = 7), subtotal resection (n = 9), and biopsy (n = 1). Six children received adjuvant therapy. At a median follow-up of 6.7 years, 9 patients were alive; 8 patients died of the following causes: early medical/surgical complications (n = 3), sepsis (n = 1), catheter-related complication (n = 1), aneurysmal bleeding (n = 1), second brain tumor (n = 1), and progression (n = 1). Surgery was the only intervention for 5 of 9 survivors. Extent of resection, but neither Ki67 labeling index nor adjuvant therapy, was significantly associated with survival. Chronic complications included neuroendocrine (n = 8), visual (n = 4), and neurodevelopmental (n = 3) deficits. Sixteen pituitary blastomas were attributed to DICER1 abnormalities. CONCLUSIONS: Pituitary blastoma is a locally destructive tumor associated with high mortality. Surgical resection alone provides long-term disease control for some patients. Quality survival is possible with long-term neuroendocrine management.
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