Clinical Outcomes and Complications of Pituitary Blastoma

Abstract

Context Pituitary blastoma is a rare, dysontogenetic hypophyseal tumor of infancy first described in 2008, strongly suggestive of DICER1 syndrome. Objective To describe genetic alterations, clinical courses, outcomes, and complications in all known pituitary blastoma cases. Design and Setting: Multi-institutional case series from tertiary pediatric oncology centers. Patients Children with pituitary blastoma. Interventions Genetic testing, surgery, oncologic therapy, endocrine support. Outcome Measures Survival, long-term morbidities, germline and tumor DICER1 genotypes. Results Seventeen pituitary blastoma cases were studied (10 female and 7 male); median age at diagnosis was 11 months (range 2–24). Cushing syndrome was the most frequent presentation (n=10). Cushingoid stigmata were absent in seven children (two with raised ACTH; five 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, nine patients were alive; eight patients died of 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 five of nine survivors. Extent of resection, but neither Ki67 labelling 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.

Clinical outcomes and complications of pituitary blastoma

“…We subsequently studied DNA from tumor and germline DNA from the parents and two siblings. The patient and siblings inherited a splice-site DICER1 variant from the father; splicing studies revealed that the variant creates an out-of-frame nucleotide sequence predicted to result in a truncated protein, which may be subject to nonsense-mediated decay (30). Despite poor-quality tumor DNA, an RNase IIIb hotspot mutation was weakly, but reproducibly, detected.…”

“…DICER1 genotyping has been previously reported for 14 cases (3,4,17,18). Sequencing of DICER1 was performed on Case 17 by using the custom-design Access Array (Fluidigm), and an exon trapping assay was used to validate the functional consequence of a newly identified splice-site variant (4, 29,30). In two cases, no molecular information was available, but one of the cases showed strong clinical evidence of DICER1 syndrome (4).…”

“…Since the reports by Sahakitrungruang et al (1 case) and de Kock et al (13 cases), three additional cases of pituitary blastoma have been thoroughly investigated (1)(2)(3)(4)(16)(17)(18)(20)(21)(22)(23)(24)(25)(26)(27)(28). In 2010, Salunke et al reported a 2-month-old female with Cushingoid stigmata since birth, ophthalmoplegia, hemiparesis, and a pituitary tumor diagnosed as a "congenital immature teratoma" (Case 17; Table 1) (30,31); the pathology on review was consistent with pituitary blastoma (16). We subsequently studied DNA from tumor and germline DNA from the parents and two siblings.…”

“…In a 2015 abstract, Gresh et al reported pituitary blastoma in a 22-month-old male with headaches and vomiting (17). A DICER1 hotspot mutation was found in the tumor tissue, with loss of heterozygosity (LOH) suggested; a germline pathogenic variant could not be identified in DNA extracted from peripheral blood lymphocytes (Case 16; Table 1) (30,31). In a 2017 abstract, Kalinin et al reported pituitary blastoma in a 10-month-old male with Cushing disease and a past medical history of cystic lung dysplasia; the primary investigators documented somatic hotspot and inherited germline DICER1 pathogenic variants (Case 15; Table 1) (18,30,31).…”

Genetics of Acromegaly and Gigantism

“…Biochemically, serum GH and IGF-1 levels were not elevated. Clinically, patients did not present increased growth velocity or tall stature [ 188 ].…”