From Pediatric to Adult Brain Cancer: Exploring Histone H3 Mutations in Australian Brain Cancer Patients.

Genetic histone variants have been implicated in cancer development and progression. Mutations affecting the histone 3 (H3) family, H3.1 (encoded by HIST1H3B and HIST1H3C) and H3.3 (encoded by H3F3A), are mainly associated with pediatric brain cancers. While considered poor prognostic brain cancer biomarkers in children, more recent studies have reported H3 alterations in adult brain cancer as well. Here, we established reliable droplet digital PCR based assays to detect three histone mutations (H3.3-K27M, H3.3-G34R, and H3.1-K27M) primarily linked to childhood brain cancer. We demonstrate the utility of our assays for sensitively detecting these mutations in cell-free DNA released from cultured diffuse intrinsic pontine glioma (DIPG) cells and in the cerebral spinal fluid of a pediatric patient with DIPG. We further screened tumor tissue DNA from 89 adult patients with glioma and 1 with diffuse hemispheric glioma from Southwestern Sydney, Australia, an ethnically diverse region, for these three mutations. No histone mutations were detected in adult glioma tissue, while H3.3-G34R presence was confirmed in the diffuse hemispheric glioma patient.

Somatostatin receptor expression and clinical outcome of multilineage pituitary tumours expressing PIT1 and SF1.

The application of transcription factor immunohistochemistry to pituitary neuroendocrine tumour (PitNET) assessment has allowed identification of tumours that do not conform to a single lineage. Multilineage pituitary transcription factor 1 (PIT1) and steroidogenic factor 1 (SF1) PitNETs are a rare and relatively newly described tumour subtype. These tumours express both transcription factors and may also express combinations of hormones corresponding to both lineages. Histological and clinical characteristics can vary, and overall clinical behaviour and prognosis is not known. We describe the clinical outcomes and somatostatin receptor status (SSTR) of a series of nine cases identified from our cohort of pituitary tumours at Westmead Hospital. Eight PitNETs (88.9%) expressed growth hormone and caused acromegaly at presentation. Of the seven macrotumours that caused acromegaly, one had cavernous sinus invasion. The Ki-67 labeling index score ranged from 0.6% to 3.6%. About 88% of tumours that secreted excess growth hormone exhibited strong immunostaining for SSTR 2 and all tumours displayed weak immunoreactivity for SSTR5. In 62.5% of patients with acromegaly, cure was achieved after surgical resection. Somatostatin receptor ligands resulted in clinical remission in cases where medical treatment was initiated. There was no new tumour recurrence or regrowth over an overall mean follow-up period of 62.5 months.

Successful stereoelectroencephalography re-evaluation in epilepsy patients after failed initial subdural grid evaluation.

OBJECTIVE: Epilepsy surgery success is dependent on accurate localization of the epileptogenic zone. Despite the use of invasive EEG using subdural grids and strips, surgical failures can occur. In this series, we explore the utility of a second evaluation with stereoelectroencephalography in patients whose initial invasive evaluation with subdural grid electrodes was unsuccessful in localizing seizure origin. METHODS: We conducted a retrospective review of patients who underwent subdural grid evaluation (SDE) at our center and identified patients who underwent a re-evaluation with stereoelectroencephalography (SEEG). RESULTS: We identified three patients who had both subdural and SEEG electrodes in the region of the identified epileptogenic zone in whom the initial SDE evaluation failed to make the patients seizure-free. Two of these patients underwent a second resection and became seizure-free. SIGNIFICANCE: Stereoelectroencephalography can be useful in the re-evaluation and re-operation of patients who previously had surgical failure using SDE.

Endovascular and microsurgical management of blister aneurysms: a multi-centre review.

Blister aneurysms (BA) are high-risk cerebrovascular lesions accounting for 1% of intracranial aneurysms. The defective vessel wall and broad-based neck make this clinical entity difficult to treat, with high rates of re-rupture and mortality in patients presenting with acute subarachnoid haemorrhage. Blister aneurysms pose substantial challenges for both endovascular and microsurgical management. The objective of this study is to evaluate endovascular and microsurgical outcomes in intracranial blister aneurysm management across two tertiary hospitals. A review of two tertiary hospitals with a systematic imaging database search for term of "blister" in modalities from January 2010 to October 2022 was conducted. Operation reports were screened for the 5-year period since cerebral angiogram reports transitioned to surgical database. Identified reports were screened and reviewed for confirmed diagnosis by consultant neuroradiologist. A total of 21 cases of blister aneurysms managed at respective facilities were included. Sixteen cases (76%) were managed endovascularly. Four cases (19%) were managed surgically-2 with primary clipping, and 2 wrap and clipping. One case was managed conservatively (5%). Clinical outcomes were discharge disposition, aneurysm exclusion and post-operative complications. BAs have challenging considerations with high mortality and morbidity. Endovascular treatment offers a less invasive modality with lower rates of intraoperative rupture and morbidity. Mortality rates and patients discharged home were comparable. Commencement of dual anti-platelet therapy was safe in patients with flow diversion stents despite sub-arachnoid blood volume. Management of blister aneurysms is complex. Endovascular treatment shows promise for acute management but careful collaborative consideration of antithrombotic regime and requirement for further surgery should be considered.

Aneurysmal Bone Cyst of the Orbit With USP6 Gene Rearrangement.

PURPOSE: Aneurysmal bone cyst (ABC) of the orbit is a very rare tumor, occurring mostly in the pediatric population, and can result in sight threatening complications and disfigurement. This review discusses previously reported cases with a focus on evolving treatment options and molecular genetics. METHODS: We report the youngest case of an orbital ABC with a confirmed gene fusion: a 17-month-old girl, with confirmed FGFR-UPS6 (Fibroblast Growth Factor Receptor 1-ubiquitin specific peptidase 6/tre-2). A literature search for relevant publications on the topic was performed via Medline and PubMed, with the appropriate data extracted. RESULTS: Thirty-two cases of orbital aneurysmal bone cyst were identified in the literature. Presentations are varied and can include pain, proptosis, decreased vision, and extraocular motility disturbance. Typical imaging and histopathology findings are discussed, in particular the usefulness of identifying USP6 gene arrangements. Treatment modalities are reviewed including surgery, embolization, and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors. Recurrences can occur, usually within 2 years. CONCLUSIONS: Orbital ABC is a neoplasm that presents unique diagnostic and treatment challenges. Gene rearrangements can confirm primary ABC and rule out other underlying pathology. Disfigurement and sight threatening complications can occur due to both the disease process and with treatment. Outcomes may be improved with the use of systemic therapy.

Predictors of longitudinal seizure outcomes after epilepsy surgery in childhood.

There is a paucity of data on longitudinal seizure outcome of children undergoing epilepsy surgery. All children (n = 132) who underwent resective epilepsy surgery from January 1998 to December 2015 were identified. Relevant clinical, neurophysiological, imaging, surgical and seizure outcome data were extracted. Multivariable logistic regression analysis and Kaplan-Meier survival with Cox proportional hazard modelling were performed. The mean age at surgery was 7.8 years (range 0.2-17.9). 71% were seizure-free at a mean follow up of 5.3 ± 2.7 years. Of those who were seizure-free, 65 patients were able to completely wean off anti- seizure medications successfully. Using survival analysis, the probability of Engel Class I outcome at one year after surgery was 81% (95% confidence interval [CI] 87%-75%). This dropped to 73% at two years (95% CI 81%-65%), 58% at five years (95% CI 67.8%-48%), and 47% at ten years. Proportional hazard modelling showed that the presence of moderate to severe developmental disability (HR 6.5; p = 0.02) and lack of complete resection (HR 0.4; p = 0.02) maintain association as negative predictors of seizure-free outcome. Our study demonstrates favorable long-term seizure control following pediatric epilepsy surgery and highlights important predictors of seizure outcome guiding case selection and counseling of expectations prior to surgery.

FISH analysis of brain smears obtained at intraoperative diagnosis - An accurate and fast method to detect 1p/19q-codeletion in gliomas.

The importance of molecular testing of gliomas is highlighted in the 2016 revised 4th edition of the WHO Classification of Tumours of the Central Nervous System, which applies an integrated diagnosis of histological and molecular features. In this classification system, oligodendrogliomas (ODG) are defined as IDH-mutant and 1p/19q-codeleted. Fluorescence in situ hybridization (FISH) analysis of formalin-fixed paraffin-embedded (FFPE) tissue is a standard method of determining 1p/19q-codeletion. However, it has several disadvantages, including requiring lengthy pretreatment, truncation artefact and lack of on-site access in many centers. In an effort to address these issues, we analysed FISH performed on smears obtained at intraoperative frozen section on 51 gliomas and compared this to FISH performed on subsequent FFPE sections. Four cases were excluded due to uninterpretable FISH results. Of the remaining 47 cases, 17 were concordant for 1p/19q-codeletion, 29 were concordant for lack of 1p/19q-codeletion, and 1 was discordant with 1p/19q-codeletion found on FFPE tissue but not on intraoperative smears. The discordant case was most likely due to sampling error, as the frozen section had not shown definite tumor. The FISH results on intraoperative smears were received within 24-48 h after the sample was collected, compared with 3-4 days for FFPE tissue. FISH on smears obtained at intraoperative frozen section is an accurate and fast method for determining 1p/19q-codeletion.

Successful epilepsy surgery for tuberous sclerosis complex evaluated by stereoelectroencephalography.

Evaluating the candidacy for epilepsy surgery in patients with tuberous sclerosis can be challenging, particularly when non-invasive investigations do not show a clear epileptogenic zone. Stereoencephalography may be useful in such cases. We present a case in which the primary epileptogenic tuber was successfully identified by stereoencephalography, which resulted in seizure freedom following epilepsy surgery. [Published with video sequences].

The varied semiology of seizures in the context of small anterior temporal encephaloceles.

Small encephaloceles of the anterior temporal pole have been increasingly recognised as an underlying epileptogenic substrate in patients with medically refractory epilepsy. The current report aims to expand on the current knowledge by emphasising that seizure semiology in such patients can vary significantly. Patients were selected from an epilepsy surgery database between 2012 and 2017. Of the 143 patients who underwent epilepsy surgery, six patients had a temporal encephalocele. Four of these patients had stereo-EEG implantation. Of the four patients studied, each had a seizure semiology discordant with an ictal focus in the temporal lobe. Intracranial EEG assessment demonstrated, irrespective of this semiology, seizures originated from the anterior temporal pole. Seizures were observed to rapidly propagate to the orbitofrontal cortex, insula, temporo-occipital junction, and posterior language regions. Engagement of the mesial temporal structures could occur early or late, however, a good surgical outcome was achieved following a focused lesionectomy in either situation. The major finding was that seizures arising from anterior temporal encephaloceles can have an extra-temporal semiology. The varied clinical semiology and the rapid propagation to seemingly distant cortical regions could be explained by the connectivity of the anterior temporal lobe.

Antemortem histopathology and imaging findings in a case of Marchiafava-Bignami disease.

Marchiafava-Bignami disease (MBD) is a rare condition often associated with chronic alcohol abuse. Clinical presentation is diverse. Characteristic magnetic resonance imaging (MRI) changes in the corpus callosum are the mainstay of radiological diagnosis. We present a case of a 54-year-old man with chronic alcoholism and peripherally enhancing lesion in the body of the corpus callosum on MRI Brain. Open biopsy of the lesion showed necrosis and demyelination. He was diagnosed with Marchiafava-Bignami disease based on clinical, radiology and histopathology findings. Our case represents the only case in the literature with antemortem histopathology findings describing MBD.

An alternative technique for pituitary tumour removal: Sequential endoscopic-microscopic pituitary procedure (SEMPP).

Several authors have reported advantages of the purely endoscopic (PE) approach over traditional purely microscopic (PM) techniques for many sinus and anterior skull base procedures. However, in pituitary surgery, the PE approach carries a number of limitations. Experienced microscopically-trained neurosurgeons are required to master the endoscopic technique which has a steep learning curve due to its one-handed nature and optically-distorted 2-dimensional view. We describe our novel technique, the sequential endoscopic and microscopic pituitary procedure (SEMPP) which does not require microscopically-trained neurosurgeons to alter their technique. We compare SEMPP with the PE approach in terms of outcome and safety. Retrospective chart review of consecutive SEMPP cases performed at our institution between January 2010 and December 2013 was conducted. Operative time, gross total resection rate, resolution of endocrine and visual dysfunction, hospital length of stay, cerebrospinal fluid (CSF) leak rate and revision rates were recorded. 32 patients were identified (50% female, mean age 53.0 years), and 33 SEMPP cases. Mean operating time was 132 min (range 90-200). 69% of patients experienced gross total resection. Most patients (81.3%) with preoperative visual deficit either experienced complete resolution or improved symptoms. The remainder experienced no change in vision. 12.5% (n = 4) of patients experienced intraoperative CSF leaks. All were repaired intraoperatively or with conservative management. Two patients (6.3%) experienced epistaxis managed with conservative measures. The SEMPP technique demonstrates comparable outcomes, complication rates and operative time to PE and PM techniques described in the literature.

A study of perfusion changes with Insula Epilepsy using SPECT.

PURPOSE: The non-invasive localisation of insular lobe epilepsy is a challenge. We aimed to determine if ictal SPECT is a reliable adjunctive test in insular cases and to explore its role in the tailoring of intracranial strategies. METHOD: From a dataset of patients who underwent SEEG between December 2012 and December 2016, we collected patients with focal insular onset epilepsy. We examined semiology, EEG, PET and SPECT hyperperfusion pattern with SISCOM. We also reviewed relevant literature. RESULTS: 5 patients were identified, 4 females, from a dataset of 51 patients. Median age of seizure onset was 8 years old (8 months to 10 years). All patients had an ictal SPECT during pre-surgical work-up: median injection time was 7 s (3-17 sec) from clinical onset, and median seizure duration was 42 s (11-85 sec). Insula cortex showed focal hyperaemia in four patients, all bilateral, with the greatest hyperperfusion contralateral to the ictal onset in two cases, using SISCOM threshold at 1.5 standard deviation. Other sites with hyperaemia included basal ganglia and middle temporal gyrus. The SEEG confirmed insular onset seizures in all the cases. All patients had epilepsy surgery and were seizure free at 21 to 50 months follow up. The results from the literature review showed frequent hyperperfusion in structures outside insula and frequently over the contralateral hemisphere. CONCLUSIONS: This study highlights the technical limitations of SPECT when attempting to assess seizures arising from the insula. Our findings and the literature show ictal SPECT can be localising but falsely lateralising in seizures arising from the insula.

Paediatric mild head injury: is routine admission to a tertiary trauma hospital necessary?

BACKGROUND: Previous studies have shown that children with isolated linear skull fractures have excellent clinical outcomes and low risk of surgery. We wish to identify other injury patterns within the spectrum of paediatric mild head injury, which need only conservative management. Children with low risk of evolving neurosurgical lesions could be safely managed in primary hospitals. METHODS: We retrospectively analysed all children with mild head injury (i.e. admission Glasgow coma score 13-15) and skull fracture or haematoma on a head computed tomography scan admitted to Westmead Children's Hospital, Sydney over the years 2009-2014. Data were collected regarding demographics, clinical findings, mechanism of injury, head computed tomography scan findings, neurosurgical intervention, outcome and length of admission. Wilcoxon paired test was used with P value <0.05 considered significant. RESULTS: Four hundred and ten children were analysed. Three hundred and eighty-one (93%) children were managed conservatively, 18 (4%) underwent evacuation of extradural haematoma (TBI surgery) and 11 (3%) needed fracture repair surgery. Two children evolved a surgical lesion 24 h post-admission. Only 17 of 214 children transferred from peripheral hospitals needed neurosurgery. Overall outcomes: zero deaths, one needed brain injury rehabilitation and 63 needed child protection unit intervention. Seventy-five percentage of children with non-surgical lesions were discharged within 2 days. Eighty-three percentage of road transfers were discharged within 3 days. CONCLUSIONS: Children with small intracranial haematomas and/or skull fractures who need no surgery only require brief inpatient symptomatic treatment and could be safely managed in primary hospitals. Improved tertiary hospital transfer guidelines with protocols to manage clinical deterioration could have cost benefit without risking patient safety.

Microvascular decompression for elderly patients with trigeminal neuralgia.

Microvascular decompression (MVD) has been demonstrated to be an excellent surgical treatment approach in younger patients with trigeminal neuralgia (TN). However, it is not clear whether there are additional morbidity and mortality risks for MVD in the elderly population. We performed a systematic literature review using six electronic databases for studies that compared outcomes for MVD for TN in elderly (cut-off ⩾60, 65, 70years) versus younger populations. Outcomes examined included success rate, deaths, strokes, thromboembolism, meningitis, cranial nerve deficits and cerebrospinal fluid leaks. There were 1524 patients in the elderly cohort and 3488 patients in the younger cohort. There was no significant difference in success rates in elderly versus younger patients (87.5% versus 84.8%; P=0.47). However, recurrence rates were lower in the elderly (11.9% versus 15.6%; P=0.03). The number of deaths in the elderly cohort was higher (0.9% versus 0.1%; P=0.003). Rates of stroke (2.5% versus 1%) and thromboembolism (1.1% versus 0%) were also higher for elderly TN patients. No differences were found for rates of meningitis, cranial nerve deficits or cerebrospinal fluid leak. MVD remains an effective and reasonable strategy in the elderly population. There is evidence to suggest that rates of complications such as death, stroke, and thromboembolism may be significantly higher in the elderly population. The presented results may be useful in the decision-making process for MVD in elderly patients with TN.

The vestibular schwannoma surgery learning curve mapped by the cumulative summation test for learning curve.

OBJECTIVE: To demonstrate and quantify the learning curve for microsurgical excision of vestibular schwannoma in a newly formed neurootologic team by using the cumulative summation test for learning curve (LC-CUSUM). To secondarily identify the factors influencing postoperative facial nerve outcome. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Between 1999 and 2011, 153 consecutive cases of vestibular schwannoma excision. INTERVENTION: One-hundred and fifty-three patients underwent excision of vestibular schwannoma. MAIN OUTCOME MEASURES: Facial nerve outcomes were assessed using the House-Brackmann (HB) facial nerve grading system. Postoperative facial nerve outcomes at 12 months were analyzed using the LC-CUSUM method with HB Grades I to III being defined as successful outcomes. The factors that influence postoperative facial nerve outcome were analyzed. RESULTS: The constructed learning curve shows a gradual improvement in facial nerve outcomes. The learning curve crossed the derived LC-CUSUM barrier at the 56th procedure, indicating that sufficient evidence had accumulated to demonstrate that the surgeon had achieved optimal outcomes at this point. Tumor size (p = 0.008) and surgical approach (p = 0.005) were 2 additional significant factors influencing postoperative facial nerve outcome. CONCLUSION: The learning curve is evident in this series of microsurgical excisions of vestibular schwannoma. A newly formed team needs to perform at least 56 cases to gain sufficient experience to accomplish optimal results. Position along the learning curve, tumor size, and familiarity with a preferred surgical approach are the factors, which dominated facial nerve outcome. We recommend the use of LC-CUSUM test for learning curve analysis.

Paediatric germ cell tumours of the central nervous system: Results and experience from a tertiary-referral paediatric institution in Australia.

A retrospective analysis was conducted on consecutive patients with intracranial germ cell tumours diagnosed and treated from 1 January 1997 to 31 December 2007 to assess and determine demographic factors and treatment outcomes of children with these tumours treated in a major paediatric referral hospital in Australia. In this study, intracranial germ cell tumours represented 4.8% of paediatric brain tumours seen. Of the 21 patients identified, 15 (71.4%) were diagnosed with pure germinoma and six (28.6%) with non-germinomatous germ cell tumours (NGGCT) or mixed tumours. One patient received chemotherapy alone, two patients were treated with radiation alone and the remaining 18 received a combination of chemotherapy and radiotherapy. A total of 33 neurosurgical operations were performed with 15 biopsies via open, endoscopic or transphenoidal means; nine open resections; and nine procedures for hydrocephalus comprising seven third ventriculostomies and two ventriculoperitoneal shunts. For patients with pure germinomas, the 5-year disease-free rate (DFS) was 93.3%, and overall survival (OS) rate was 100% compared to NGGCT or mixed tumours (DFS 50%; OS 50%) (DFS p=0.019, OS p=0.004). The data presented show that pure germinomas carry a favourable prognosis. The data also support that treatment with induction chemotherapy followed by dose-attenuated radiotherapy is an effective alternative with results comparable to historical controls treated with craniospinal irradiation. Although chemoradiotherapy has become the mainstay of treatment in intracranial germ cell tumours, surgery remains integral to the management of this condition. Surgery remains important in establishing the histological diagnosis, as well as in the treatment of hydrocephalus. Furthermore, debulking procedures may be advocated in NGGCT as they are often resistant to chemotherapy.

Histiocytic sarcoma of the brain.

Histiocytic sarcoma is a rare malignant neoplasm of the lympho-hematopoietic system that usually occurs in the skin, lymph nodes and intestinal tract. We present a 36-year-old woman with a rare histiocytic sarcoma with isolated central nervous system (CNS) involvement of multifocal circumscribed lesions. Biopsy of the brain lesions showed diffuse proliferation of pleomorphic histiocytes that were immunopositive for CD45, CD68 and CD163. Various cytokeratins and markers of lymphoma, melanoma, germ cell tumours and primary CNS tumours were negative. Examination of bone marrow trephine and a whole-body positron emission tomography scan showed no evidence of involvement of any other organ systems, thus establishing the primary nature of the lesion. The neoplastic cells uniquely showed eosinophilic globules within the cytoplasm, which were positive for CD68. These globules were shown by electron microscopy to be collections of lysosomes. A thorough discussion of the differential diagnosis and literature review is included.

Primary nerve repair following resection of a neurenteric cyst of the oculomotor nerve.

Neurenteric cysts are rare congenital lesions of endodermal origin occurring in the spinal canal and infrequently in the posterior cranial fossa. The authors report the case of a 3-year-old child who presented with a recurrent third cranial nerve palsy. Magnetic resonance imaging showed a large cystic mass lesion in the ambient cistern on the right side, with compression of the anterolateral aspect of the brainstem. The patient underwent a craniotomy, complete excision, and a primary third cranial nerve repair. While there have been 3 reported cases of neurenteric cysts arising from the oculomotor nerve, this is the first documented case with a primary nerve repair.

Diagnostic pitfall in the diagnosis of mesenchymal chondrosarcoma arising in the central nervous system.

Mesenchymal chondrosarcoma is a rare aggressive neoplasm typically affecting the bones of young adults. It may also arise in somatic soft tissue, the CNS and other organs. It has a characteristic biphasic histological pattern composed of highly undifferentiated small round cells and islands of well-differentiated hyaline cartilage. We report a case of mesenchymal chondrosarcoma arising from the right tentorium cerebelli in a 21-year-old woman with symptoms relating to mass effect. Histological examination demonstrated a purely small round cell appearance in a specimen obtained during partial resection at an outside institution, leading to an erroneous diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (PNET). The diagnosis of mesenchymal chondrosarcoma was made only after tissue obtained during a definitive complete macroscopic removal involving the regional tentorium cerebelli, transverse and sigmoid dural venous sinuses which showed a prominent cartilaginous component. We discuss the features of mesenchymal chondrosarcoma arising in the CNS, the important differential diagnoses of small round-cell tumors within the CNS, and the differentiating features of mesenchymal chondrosarcoma from Ewing sarcoma/PNET, medulloblastoma, hemangiopericytoma, monophasic synovial sarcoma and atypical teratoid/rhabdoid tumour.

A multicenter study of primary brain tumor incidence in Australia (2000-2008).

There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8-12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries.