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A young girl with a history of de novo chromosome 22q11.2 deletion syndrome (22q11.2DS), developmental delay, postrepair ventriculoseptal defect, polycystic kidney disease and progressive scoliosis presented with deteriorating balance and increasingly frequent falls. No vomiting, seizures or headache were reported, and no acute changes were appreciated on non-focal neurological examination. Brain MRI showed an enhancing pineal mass with hypoenhancing and possible cystic components without reduced diffusivity, calcifications, haemorrhage or surrounding oedema (figure 1A,B). A spinal MRI additionally revealed T2-hyperintensity along the dorsal cervicomedullary junction and left inferior cerebellar peduncle with associated irregular dorsal curvilinear enhancement (figure 1C); this lesion was radiographically most consistent with low-grade brainstem glioma as opposed to a more aggressive embryonal tumour or high-grade glioma. An MRI 2 years prior as workup for developmental delay showed a normal-appearing pineal gland and incompletely visualised cervicomedullary lesion present in retrospect (not shown).
Following negative workup for germinoma, including serum and cerebrospinal fluid tumour markers, the enlarging pineal mass was biopsied to exclude pineoblastoma, which may be associated with 22q11.2DS.1–3 Neuropathological analysis showed a sheet-like population of bland polygonal cells with round-to-oval nuclei, fibrillar process formation and round anuclear zones, without lobular bands of fibrous tissue (figure 1D). Rare calcification and a peripheral abundance of Rosenthal fibres were observed, and focal fine granular melanin pigment was noted in the parenchymal cells. No mitotic figures or necrosis were detected, and no fibrous bands or septa were visible with trichrome staining. Immunostaining portrayed diffuses synaptophysin positivity, nuclear INI-1 retention, sparse (<1%) Ki67 +nuclei, few lymphocytes positive for leucocyte common antigen, scattered S100 +cells and sparse CAM5.2 positivity. The lesion stained immunonegative for epithelial membrane antigen, H3K27M and glial fibrillary acidic protein, and was considered histologically diagnostic of pineocytoma. Tumour microarray analysis identified the expected 2.59 Mb deletion at 22q11.21 but otherwise revealed no clinically significant abnormalities. Next-generation sequencing detected no known clinically significant variants but variants of uncertain significance in three known cancer genes, BCL6 (c.1649G>A), EGFR (c.2492G>A) and NSD1 (c.2746G>A). MRIs up to 6 months postbiopsy have portrayed minimal residual postoperative enhancement of the pineal region without tumour recurrence. The presumptive brainstem glioma (not biopsied) remains under stable observation without change from initial MRI; the patient will continue under surveillance neuroimaging.
Although 22q11.2DS may increase risk for particular malignancies,1–3 few reports have documented brain tumours in 22q11.2DS.1 4 5 The low population prevalence of brain tumours6 encourages suggestion that 22q11.2DS pathology facilitated the development of the tumours in our patient. Proposed explanations for how 22q11.2DS might increase malignancy risk aside from genomic instability include thymic hypoplasia and resultant immunodeficiency, thereby increasing susceptibility to oncogenic viruses, or deletion of the catechol-O-methyltransferase gene, which helps detoxify carcinogens.1 Although a prior report documenting a glioma in a paediatric patient with DiGeorge syndrome and two viral infections, one in the brain,5 suggestively supports an association with immunodeficiency, future research will be necessary to causally define pathways of brain tumorigenesis in 22q11.2DS. Nevertheless, this patient, the first to our knowledge of a pineocytoma in 22q11.2DS, expands our awareness of brain tumours in 22q11.2DS and reinforces the need for surveillance neuroimaging in this population.
Patients with 22q11.2DS are at increased risk for a variety of malignancies including those of the central nervous system.
Surveillance neuroimaging is necessary for patients with 22q11.2DS to adequately determine the epidemiology of central nervous system tumours in this population.
Our case report expands the spectrum of central nervous system tumours associated with 22q11.2DS.
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Contributors JWA was responsible for the design and writing of the case report. DM was responsible for the design and writing of the case report. ML was responsible for the design and writing of the case report. JRC was responsible for the design and writing of the case report.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.