The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

Delayed symptomatic haemorrhage from the remnants of a thalamic arteriovenous malformation after previous angiographic cure with radiotherapy.

In 1995 a 16-year old girl was diagnosed with a large left thalamic AVM that was considered unsuitable for microsurgical resection and was treated with radiotherapy twice, which led to angiographic cure. She re-presented 19 years after initial treatment with a symptomatic acute thalamic haemorrhage. Her digital subtraction angiography was negative for arterio-venous shunting. MRI/MRA showed cystic change with adjacent contrast enhancement in the region of the previously irradiated arteriovenous malformation. The patient underwent an interhemispheric transcallosal resection of the left thalamic haemorrhagic lesion via a contralateral craniotomy. Intra-operatively there was a cystic cavity filled with blood products in association with thrombosed, calcified vessels as well as actively filling vessels. Histologically there were aggregated abnormal blood vessels with a dilated lumen and surrounded by brain parenchyma. Some of the vessel walls were thickened with fibrosis and some were arterialised with presence of elastin fibres. Potential mechanisms for the delayed haemorrhage are discussed.

Diagnostic utility and accuracy of rapid on-site evaluation of bronchoscopic brushings.

The aim of the study was to determine the accuracy of rapid on-site examinations, performed on transbronchial brushings of peripheral pulmonary lesions, in determining final bronchoscopic diagnosis. In addition to determining if rapid on-site examination impacts procedural outcomes. A prospective cohort study of consecutive patients with peripheral pulmonary lesions, which had been located by radial endobronchial ultrasound, was undertaken. Bronchoscopy was terminated if rapid on-site examination demonstrated diagnostic malignant material. Non-diagnostic rapid on-site examination resulted in further bronchoscopic sampling, including transbronchial lung biopsy and/or sampling from different locations. 128 peripheral pulmonary lesions were located by endobronchial ultrasound in 118 patients. The final bronchoscopic diagnoses included nonsmall cell lung cancer (n=76), carcinoid (n=3), and metastatic malignancy (n=3). Procedure times were significantly shorter for procedures when rapid on-site examinations demonstrated malignancy compared to those where rapid on-site examination was non-diagnostic (19±8 min versus 31±11 min, respectively; p<0.0001). In four procedures, initial negative rapid on-site examination results prompted redirection of sampling from alternate bronchial segments, resulting in positive diagnostic tissue being obtained. Positive and negative predictive value of rapid on-site examination for a malignant bronchoscopic diagnosis was 63 (97%) out of 65, and 43 (68%) out of 63, respectively. Rapid on-site examination of brushing specimens has a very high, positive, predictive value for bronchoscopic diagnosis of cancer and shortens the bronchoscopy procedure times. It has the potential to reduce complications, improve cost-effectiveness, and may improve diagnostic performance via live feedback.

Interobserver agreement in determining non-small cell lung cancer subtype in specimens acquired by EBUS-TBNA.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) may diagnose suspected lung cancer. Determination of non-small cell lung cancer (NSCLC) subtype may guide therapy in select patients. Small-volume biopsies may be subject to significant interobserver variability in subtype determination. Three pathologists independently reviewed specimens from 60 patients who underwent EBUS-TBNA for diagnosis/staging of suspected/known NSCLC. Smear, haematoxylin and eosin (H&E) and immunohistochemistry (IHC) specimens were reviewed without reference to other specimen types obtained from the same patient. Final diagnoses, and degree of confidence in the diagnosis, were recorded for each specimen. Almost perfect agreement was seen for distinguishing between small cell lung cancer and NSCLC for all specimen types. Agreement in determination of NSCLC subtype for smear, H&E and IHC specimens was slight (κ=0.095, 95% CI -0.164-0.355), fair (κ=0.278, 95% CI 0.075-0.481) and moderate (κ=0.564, 95% CI 0.338-0.740), respectively. Perfect agreement was seen when all three observers were confident of diagnoses made on IHC specimens. Interobserver agreement in interpretation of EBUS-TBNA specimens is moderate for determination of NSCLC subtype. Agreement is highest following examination of IHC specimens. Clinicians should be aware of the degree of pathologist confidence in the tissue diagnosis prior to commencement of subtype-specific therapy for NSCLC.

Outcomes of patients with maxillofacial osteosarcoma: a review of 15 cases.

PURPOSE: To assess clinical behavior, response to treatment, and factors affecting survival in maxillofacial osteosarcoma treated at a tertiary referral center. PATIENTS AND METHODS: Ethics-approved retrospective review of clinical and pathological records was undertaken for 15 patients managed by the Royal Melbourne Hospital Head and Neck Oncology Tumor Stream. RESULTS: Treatment was a combination of surgery and chemotherapy. Chemotherapy was given as adjuvant, neoadjuvant, or in combination. The overall 2-, 5-, and 15-year disease-free survival rates in this study were 92%, 74%, and 74%, respectively. Using Kaplan-Meier analysis with log rank tests, increasing T stage (P = .01) and positive margins (P = .003) were found to affect survival significantly. Neoadjuvant chemotherapy was not significantly associated with tumor necrosis or improved survival. CONCLUSIONS: Tumor size and adequacy of local control were found to be the most important predictors of outcome.

MR imaging characteristics of protoplasmic astrocytomas.

INTRODUCTION: Protoplasmic astrocytomas are a poorly recognized and uncommon subtype of astrocytoma. While usually categorized with other low-grade gliomas, there is literature to suggest that protoplasmic astrocytomas have differences in biology compared to other gliomas in this group. This paper presents the MR imaging characteristics of a series of eight protoplasmic astrocytomas. METHODS: We retrospectively reviewed MR images and histopathology of eight consecutive cases of histologically proven protoplasmic astrocytomas. RESULTS: Patients ranged from 17 to 51 years of age with a 5:3 male to female ratio. The tumors were located in the frontal or temporal lobes and tended to be large, well defined, and had a very high signal on T2 (close to cerebrospinal fluid). Generally, a large proportion of the tumor showed substantial signal suppression on T2 fluid-attenuated inversion recovery (FLAIR). Six of the eight lesions also demonstrated a partial or complete rim of reduced apparent diffusion coefficient (ADC) around the T2 FLAIR suppressing portion. CONCLUSIONS: The possibility that a primary cerebral neoplasm represents a protoplasmic astrocytoma should be considered in a patient with a large frontal or temporal tumor that has a very high signal on T2 with a large proportion of the tumor showing substantial T2 FLAIR suppression. A further clue is a partial or complete rim of reduced ADC.

Splenic angiosarcoma metastasis to the brain.

Angiosarcoma is a rare primary non-haematolymphoid malignant neoplasm of the spleen. This neoplastic process has a poor prognosis, with disease usually widespread by the time of presentation. In the literature there has been only six case reports of cerebral metastasis from splenic angiosarcomas. We report a 61-year-old woman who presented with a right occipital metastasis of a splenic angiosarcoma, 5 years after initial diagnosis, treated by stereotactic occipital craniotomy and resection of metastasis.

The evolution of cerebrovascular changes in Köhlmeier-Degos disease: An 11-year follow-up case report.

Köhlmeier-Degos disease is rare idiopathic vasculopathy, the exact pathogenesis of which remains unclear. Here, we review pertinent literatutre and present a case of a Köhlmeier-Degos disease with central nervous system involvement followed-up over 11 years with various neuroimaging modalities. Evolution of neurovascular and neuropathological changes over an extended time period has not been previously described.

Reliability of noncontrast-enhancing tumor as a biomarker of IDH1 mutation status in glioblastoma.

Isocitrate dehydrogenase 1 (IDH1) mutations in gliomas have been associated with a frontal lobe location and a greater proportion of noncontrast-enhancing tumour (nCET). The purpose of our study was to validate the utility of MRI imaging features in predicting IDH1 mutations in glioblastomas. Pre-operative MRIs of new glioblastoma patients, consisting of at least FLAIR and T1-weighted post-contrast sequences, were reviewed by a neuroradiologist based primarily on the VASARI feature set. IDH1 mutation testing was performed on all patients using immunohistochemistry. 153 patients met the inclusion criteria, of whom five had IDH1 mutations (3.3%). A frontal lobe location had equivalent frequency in both the IDH1-mutated and IDH1-wildtype cohorts (p=1.000). Three (60%) of the IDH1-mutated tumours had >33% nCET, compared to 21% of IDH1-wildtype (p=0.073). 12 tumours had a frontal lobe epicentre and >33% nCET, all being IDH1-wildtype. All five IDH1-mutated tumours had either a frontal lobe epicentre or >33% nCET, but none had both these features. Our results question the strength of the association between frontal lobe glioblastomas with substantial nCET and IDH1 mutations, as these features are also relatively frequent in IDH1-wildtype tumours, which are much more common. MRI is thus more useful for ruling out an IDH1 mutation rather than strongly suggesting its presence: if a particular glioblastoma does not have a frontal lobe epicentre and has less than 33% nCET, it can be predicted to be IDH1-wildtype with a high degree of confidence.

Intraparenchymal infratentorial ependymoma.

Ependymomas are glial series tumours that can occur throughout the neural axis, usually in close proximity to the ventricles or central canal. While the fourth ventricle is a common location for ependymoma, we present a rare case of an entirely intraparenchymal infratentorial tumour, remote from the ventricular surface, and discuss the imaging characteristics that may suggest the diagnosis. The histological features, which remain identical despite the varied morphology of intraventricular versus intraparenchymal tumours, are also considered.

Four cases of spinal epidural angiolipoma.

Spinal angiolipomas are uncommon benign tumours composed of mature fatty tissue and abnormal vascular elements, most commonly found within the posterior spinal epidural space. Most tumours are located within the mid-thoracic spine; in contrast thoracolumbar junction and purely lumbar angiolipomas are rare. We report a case series of four spinal angiolipomas, including a thoracolumbar junction and a purely lumbar tumour.

Pilomyxoid astrocytoma in the adult cerebellum.

Pilomyxoid astrocytoma (PMA) is a recently recognised World Health Organization (WHO) Grade II tumour that was previously characterised as a subtype of the WHO Grade I pilocytic astrocytoma (PA). PMA has a histological appearance distinct from PA and a poorer prognosis due to its greater propensity for local recurrence and cerebrospinal dissemination. Although originally considered a paediatric tumour involving mainly the hypothalamic and chiasmatic region, reports of the lesion occurring in the adult population and other areas of the neuroaxis are emerging. We review the literature on PMA within the adult population and present the first case of PMA in the cerebellum of an adult female.

Magnetic resonance imaging features of gemistocytic astrocytoma.

INTRODUCTION: Gemistocytic astrocytoma is the second most common subtype of World Health Organization grade 2 astrocytoma, but has a worse prognosis than other grade 2 lesions. We aim to describe the MR imaging features of histopathologically proven gemistocytic tumours. METHODS: Ethics approval was obtained from both institutions. Patient consent was not required for this retrospective study. We reviewed MR imaging findings of 16 consecutive cases of histopathologically proven gemistocytic astrocytoma and anaplastic astrocytoma with gemistocytic features. RESULTS: Average patient age was 48 years, with a 3:1 male to female ratio. Based on our series, the typical appearance of a gemistocytic astrocytoma is a large, heterogeneous mass most commonly supratentorial and lobar. Regions of cyst formation, partial signal suppression on FLAIR images and contrast enhancement are all common features. Additionally, contrary to previous literature that describes gemistocytic astrocytoma as a purely supratentorial lesion, we present two cases of gemistocytic astrocytoma involving the brainstem. CONCLUSIONS: The possibility of gemistocytic astrocytoma should be considered in patients presenting with large heterogeneous tumours that have regions of cyst formation, partial FLAIR suppression and contrast enhancement. This may be especially useful in reconciling a lesion with high-grade MR imaging features with low-grade histopathology. An infratentorial location does not preclude the diagnosis of gemistocytic astrocytoma.

Current challenges and novel treatment strategies in double hit lymphomas.

High-grade B-cell lymphomas with recurrent chromosomal break points have been termed 'double hit lymphoma' (DHL). The most commonly seen DHL is diffuse large B-cell lymphoma (DLBCL) with t(14;18) and t(8;14) or t(8;22) resulting in overexpression of BCL2 and MYC, respectively. The increased proliferation due to MYC overexpression, without the ability for an apoptotic brake as a result of BCL2 overexpression, results in 'the perfect storm of oncogenesis'. Thus this disease presents a number of diagnostic and therapeutic challenges for the hematologist. The first and foremost challenge is to recognize the DHL. As different morphological entities can be affected it is incumbent on pathologists and clinicians to maintain a high index of suspicion especially in disease that appears unusually aggressive or refractory to therapy. Diagnosis by fluorescence in situ hybridization (FISH) is a sensitive and specific method for detection of the disease but is time-consuming and expensive. While detection by immunohistochemistry (IHC) is sensitive and correlates with survival, standardized methods for this are not widely agreed upon. The second and equally important challenge in DHL is optimizing clinical outcome in a group of patients for whom the prognosis is widely regarded as poor. While improvements have been achieved by dose escalating standard chemotherapeutic regimens, many patients continue to do badly. Furthermore as a disease of aging many patients are unsuitable for dose-intensive chemotherapy regimens. There are now multiple novel targeted agents in various stages of clinical development that offer hope for better outcomes without undue toxicity. Among the most exciting of these developments include specific inhibitors of both BCL2 and MYC.

Multicentric hemispheric ganglioglioma in a 20-year-old adult.

Gangliogliomas are rare primary central nervous system tumours that characteristically contain both neuronal and glial neoplastic components. They usually present as solitary, slow growing tumours that are frequently associated with pharmacologically refractory epilepsy. Multicentric variants of the tumour are exceedingly rare. We report a 20-year-old patient with multiple gangliogliomas located in the right frontal, temporal and occipital lobes. He presented with headache, fatigue and occasional nausea and vomiting. MRI revealed three large, distinct tumours with striking cyst formation. Stereotactic craniotomy and excision of the temporal and occipital tumours confirmed ganglioglioma. The coincidence of three distinct gangliogliomas involving the right frontal, temporal and occipital lobes has not been reported to our knowledge.

Atypical and malignant meningiomas: Considerations for treatment and efficacy of radiotherapy.

The purpose of this study was to add to the current body of literature which is aimed at establishing the role of postoperative adjuvant radiotherapy (RT) in the treatment of atypical and malignant meningiomas. Meningiomas are the most frequently reported primary intracranial tumours, accounting for more than 35%. The majority of meningiomas are benign, with atypical and malignant tumours accounting for only 6-18%. Utilising a prospective multi-institutional database, we retrospectively reviewed 67 patients with documented World Health Organisation (WHO) Grade II/III meningiomas, diagnosed between 1989 and 2012 and resected at two major Australian hospitals. Nine patients were excluded and the remaining 58 were analysed. The patient demographics, tumour characteristics, surgical details and adjuvant therapy were retrieved. Kaplan-Meier curves were used to compare the survival of patients treated with RT versus surgery alone. The 3 year progression free survival (PFS) and overall survival (OS) were 44 and 76% for the entire cohort, respectively. Of the patients who had gross total resections, 42% had 3 years PFS and 77% had 3 years OS, which was not significantly different from those with subtotal resection. The overall median survival was 11.0 years, 12.2 for atypical and 1.6 for malignant meningiomas. The patients with malignant meningiomas were 14 times as likely to receive RT as the patients with atypical meningiomas. The patients who received RT had a 3 year PFS of 63% compared to 40% in those who did not receive radiation. The 3 year OS was 31% higher for females than males. Histopathological progression was noted in 17% of our cohort. This study reinforces a number of important factors that should be considered when treating patients presenting with WHO Grade II and III meningiomas, including sex, potential for grade progression, and the lack of evidence for adjuvant RT and the timing thereof.

Paraneoplastic cerebellar degeneration associated with squamous cell carcinoma of the lung.

We report a 78-year-old man who presented with rapidly progressive cerebellar ataxia, dysarthria and vertigo. MRI of the brain showed no evidence of infiltrative pathology in the posterior fossa. Cerebrospinal fluid analysis revealed an elevated protein and pleocytosis. He was subsequently diagnosed with squamous cell carcinoma of the lung on bronchoscopy. Paraneoplastic cerebellar degeneration (PCD) was diagnosed. To our knowledge, there are only two previously reported patients with PCD associated with squamous cell carcinoma of the lung.

Intracranial neuroenteric cysts: a concise review including an illustrative patient.

Neuroenteric cysts (NC) are rare, benign lesions lined by mucin-secreting cuboidal or columnar epithelium of an intestinal or respiratory type. They are regarded as ectopic endodermal cysts, and tend to be found in the spine rather than an intracranial location. Advances in neuroimaging have led to an increased frequency of diagnosis of NC, especially as an incidental finding, although such cysts may be confused radiologically with other lesions such as epidermoid and arachnoid cysts. We undertook a PubMed search of the literature using the search terms "neuroenteric cyst" and its many pseudonyms, including "endodermal cyst", "enterogenous cyst", "neurenteric cyst", "epithelial cyst", "intestinome", "teratomatous cyst", "gastrocytoma", and also "enterogenic", "foregut", "respiratory", and "bronchogenic cyst". Only reports in English and those containing histopathologically-confirmed NC were considered for this review. In total, 140 patients with intracranial NC were found, including the patient reported in the present review. This review describes the classification, epidemiology, embryology, clinical presentation, radiology, histopathology, and surgical treatment of NC, and includes an illustrative patient.