An uncommon mimic of spontaneous subarachnoid haemorrhage.

We here presented a rare disease entity with a clinical presentation mimicking aneurysmal subarachnoid haemorrhage. A 43-year-old woman presented with a 1-week history of neck pain and dizziness. Computed tomography of brain showed communicating hydrocephalus and subarachnoid hyperintensity suspicious of previous subarachnoid haemorrhage. Investigations revealed no underlying vascular lesion and leptomeningeal biopsy showed diffuse melanocytosis. We go on to discuss the diagnostic features and clinical course of this entity.

Eyelid tumours and pseudotumours in Hong Kong: a ten-year experience.

OBJECTIVE: To describe the clinicopathological characteristics of patients with eyelid tumours in Hong Kong. DESIGN: Retrospective case series. SETTING: A tertiary eye centre in Hong Kong. PATIENTS: A computerised retrieval system was used to identify all patients who underwent eyelid mass excisions with histological reports, encountered in the period 2000 to 2009, in a tertiary eye centre. The demographics (age, gender), clinical features (laterality, tumour topography), and the pathological diagnosis of each patient were documented. Descriptive statistical tabulation and analyses were performed on the data. RESULTS: In all, 198 patients were identified; all were Chinese. Their mean age was 54 years for benign lesions and 68 years for malignant ones. Women were more commonly affected. Benign tumourous lesions occurred more commonly on the upper (n=91; 54%) than lower eyelid (n=79; 47%), whereas malignant lesions more often affected the lower (n=17, 61%) than upper (n=11, 39%) eyelid. The distribution of left and right eye involvement was similar (103 vs 101, respectively). In six patients, there were bilateral benign lesion. Regarding benign masses, 45 (27%) were intradermal neavi, 38 (22%) were squamous papillomas, 25 (15%) were seborrhoeic keratosis lesions, 14 (8%) were epidermoid cysts, and 7 (4%) were compound naevi. Regarding malignant eyelid tumours, the most common was basal cell carcinomas (n=12, 43%), 5 (18%) were squamous cell carcinomas, 3 (11%) were actinic keratosis lesions, and 2 (7%) each were sebaceous gland carcinomas and melanomas. CONCLUSION: Benign lesions constituted the majority of these eyelid tumours. Among the malignant lesions, basal cell carcinoma was the commonest type, with lower lid involvement in majority. Sebaceous gland carcinoma is not rare, which is in contrast to Caucasian populations. The relative frequencies of the most common malignant tumours in Hong Kong differed substantially from those reported in other Asian studies.

Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China.

The attribution of individual human papillomavirus (HPV) types to cervical neoplasia, especially intraepithelial lesions, varies ethnogeographically. Population-specific data are required for vaccine cost-effectiveness assessment and type replacement monitoring. HPV was detected from 2,790 Chinese women (444 invasive cervical cancers [ICC], 772 cervical intraepithelial neoplasia [CIN] grade 3, 805 CIN2 and 769 CIN1. The attribution of each HPV type found in multiple-type infections was approximated by the fractional contribution approach. Multiple-type infection was common and correlated inversely with lesion severity (54.7% for CIN1, 48.7% for CIN2, 46.2% for CIN3, 27.5% for ICC). Vaccine-covered high-risk types (HPV16/18) attributed to 59.5% of squamous cell carcinoma, 78.6% of adenocarcinoma, 35.9% of CIN3, 18.4% of CIN2 and 7.4% of CIN1. Distinct features compared to worldwide were a higher attribution of HPV52 and HPV58, and a much lower attribution of HPV45. Inclusion of HPV52 and HPV58 in future vaccines would provide the highest marginal increase in coverage with 11.7% for squamous cell carcinoma, 14.4% for CIN3, 22.6% for CIN2 and 17.7% for CIN1. The attribution of HPV types in southern China is different from elsewhere, which should be considered in prioritizing HPV types for vaccine and screening assay development.

Pseudoprogression of malignant glioma in Chinese patients receiving concomitant chemoradiotherapy.

OBJECTIVES: To investigate the frequency of pseudoprogression of glioblastoma in Chinese patients receiving concomitant chemoradiotherapy and investigate its association with pseudoprogression and tumour molecular marker O(6)-methylguanine-DNA methyltransferase promoter methylation status. DESIGN: Case series with internal comparisons. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients with glioblastoma treated with concomitant chemoradiotherapy during April 2005 to June 2010 were reviewed. Magnetic resonance imaging brain scans, pre- and post-concomitant chemoradiotherapy and 3-monthly thereafter were reviewed by an independent neuroradiologist according to Macdonald's criteria. Relevant patient information (clinical condition, performance score, development of new neurological deficits, use of steroids, and survival) was retrieved. For each patient, O(6)-methylguanine-DNA methyltransferase methylation status was investigated with genomic DNA from formalin-fixed or paraffin-embedded sections of tumour tissues by methylation-specific polymerase chain reaction. RESULTS: During the study period, 28 primary glioblastoma patients underwent concomitant chemoradiotherapy. The mean age of the patients was 48 (range, 16-71) years. Thirteen patients (13/28, 46%) developed early radiological progression of the tumour after completion of concomitant chemoradiotherapy, of whom five (39%) were subsequently found to have had pseudoprogression. Patients with pseudoprogression showed a trend towards longer survival (22 months in pseudoprogression vs 17 months in all others vs 11 months in those with genuine progression). Among the 27 patients tested for O(6)-methylguanine-DNA methyltransferase promoter status, 12 (44%) were methylated. Two (2/12, 17%) in the methylated group had pseudoprogression, while three (3/15, 20%) in the unmethylated group had pseudoprogression. CONCLUSIONS: Nearly half of all patients (46%) developed early radiological progression (within 3 months of completing concomitant chemoradiotherapy). Moreover, about one in three of such patients had pseudoprogression. Pseudoprogression is an important clinical condition to be aware of to prevent premature termination of an effective treatment.

PRAME immunostain expression in sebaceous lesions, cutaneous carcinomas and adnexal structures.

The use of immunostain for PRAME antigen is well established for cutaneous melanolocytic lesions. However, its staining in other cutaneous structures and lesions is under reported. This study assessed PRAME staining in a large cohort of normal skin tissue, sebaceous lesions, and cutaneous carcinomas to better delineate patterns of PRAME immunoreactivity. PRAME immunostaining was performed on sections of sebaceous lesions and tissue microarrays of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Normal cutaneous adnexal structures were assessed on the sections of sebaceous lesions. For sebaceous lesions and non-lesional sebaceous glands, PRAME immunostaining was assessed for mature, germinative and sebocytes independently. A total of 193 sebaceous lesions, 64 BCCs and 35 SCCs were stained for PRAME immunostain. Staining pattern was predominantly cytoplasmic in normal apocrine glands, germinative sebocytes of sebaceous glands, and hair germs (p<0.001). Lesional sebocytes did not show different staining compared to normal sebaceous glands (p>0.05). Rare nuclear staining was observed in the normal epidermis (0.6%) and junctional melanocytes (4.1%). BCC, SCC and sebaceous carcinoma all showed low levels of PRAME immunoreactivity with variable proportions of cases demonstrating nuclear staining (BCC 59.4%, SCC 37.1%, sebaceous carcinoma 5.3%). PRAME immunostaining is positive in germinative sebocytes, various cutaneous structures and carcinomas. Nuclear staining, identical to melanoma, was observed in normal epidermis, junctional melanocytes, BCCs, SCCs, and sebaceous carcinomas. The pattern of PRAME staining in the skin must be recognised to avoid pitfalls in interpretating PRAME immunostain.

Association of molecular marker O(6)Methylguanine DNA methyltransferase and concomitant chemoradiotherapy with survival in Southern Chinese glioblastoma patients.

OBJECTIVES: (1) To compare the survival of concomitant chemotherapy and radiotherapy with radiotherapy alone in Chinese patients with primary glioblastoma. (2) To determine the methylation status of O(6)Methylguanine DNA methyltransferase in Chinese primary glioblastoma, and to assess the prognostic value of O(6)Methylguanine DNA methyltransferase methylation status in such patients. DESIGN: Retrospective correlative analysis. SETTING: University teaching hospital, Hong Kong. PATIENTS: Patients diagnosed with histologically proven primary glioblastoma in the period of March 2005 to June 2007 were recruited. Genomic DNA was isolated from formalin-fixed and paraffin-embedded sections of glioblastoma tissues. Methylation-specific polymerase chain reaction for O(6)Methylguanine DNA methyltransferase was performed. Patients' information at presentation was collected (age, performance status, steroid use, extent of resection, complications, radiotherapy data, use of chemotherapy). Primary outcome was measured by overall survival while secondary outcome was measured by progression-free survival. Overall and progression-free survivals were estimated by the Kaplan-Meier technique. Outcomes were assessed for groups with and without concomitant chemoradiotherapy and for groups with and without O(6)Methylguanine DNA methyltransferase methylation. RESULTS: A total of 35 glioblastoma patients were recruited; 27 were male and 8 female. Their mean age was 50 years. In all, 17 received concomitant chemoradiotherapy, and 18 received radiotherapy only. Their median overall survival was 12 (range, 7-17) months and the median progression-free survival was 5 (range, 3-6) months. In the radiotherapy alone group, the median progression-free survival and overall survival was 4 (range, 3-5) months and 6 (range, 2-10) months, respectively. In the concomitant radiochemotherapy group, the median progression-free survival and overall survival was 6 (range, 2-10) months and 13 (range, 8-18) months, respectively. Fifteen (43%) of the tumour samples showed methylation of O(6)Methylguanine DNA methyltransferase. There was a trend towards overall longer survival in the group with methylated tumours compared to those with unmethylated tumours; respective values for median survival (ranges) were 17 (13-21) versus 10 (6-14) months (P=0.105). CONCLUSIONS: Our single-centre results indicated that Chinese glioblastoma patients who had received concomitant chemoradiotherapy showed a trend towards longer overall survival compared to those receiving radiotherapy alone. Approximately 43% of our Chinese glioblastoma samples showed methylation of O(6)Methylguanine DNA methyltransferase. O(6)Methylguanine DNA methyltransferase methylation may be a significant prognostic factor in Chinese glioblastoma patients.

The 2021 WHO Classification of Tumors of the Central Nervous System: a summary.

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading.

cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT-NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles-relating to classification categories, approaches to classification, nomenclature, and grading-that the group hopes will also inform the future classification of CNS neoplasms.

Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts.

Human placentation displays many similarities with tumourigenesis, including rapid cell division, migration and invasion, overlapping gene expression profiles and escape from immune detection. Recent data have identified promoter methylation in the Ras association factor and adenomatous polyposis coli tumour suppressor genes as part of this process. However, the extent of tumour-associated methylation in the placenta remains unclear. Using whole genome methylation data as a starting point, we have examined this phenomenon in placental tissue. We found no evidence for methylation of the majority of common tumour suppressor genes in term placentas, but identified methylation in several genes previously described in some human tumours. Notably, promoter methylation of four independent negative regulators of Wnt signalling has now been identified in human placental tissue and purified trophoblasts. Methylation is present in baboon, but not in mouse placentas. This supports a role for elevated Wnt signalling in primate trophoblast invasiveness and placentation. Examination of invasive choriocarcinoma cell lines revealed altered methylation patterns consistent with a role of methylation change in gestational trophoblastic disease. This distinct pattern of tumour-associated methylation implicates a coordinated series of epigenetic silencing events, similar to those associated with some tumours, in the distinct features of normal human placental invasion and function.

Vermal hemorrhage with fourth ventricle extension due to ruptured posterior inferior cerebellar artery aneurysm.

Distal posterior inferior cerebellar artery (PICA) aneurysm located at the choroidal branch is uncommon. We report a ruptured distal PICA aneurysm in a 50-year-old man who presented with sudden onset of coma. The management and clinical significance are highlighted.

On tests of rate ratio under standard inverse sampling.

Inverse sampling suggests one continues to sample subjects until a pre-specified number of rare events of interest is observed. It is generally considered to be more appropriate than the usual binomial sampling when the subjects come sequentially, when the response probability is rare, and when maximum likelihood estimators of some epidemiological measures are undefined under binomial sampling. Reliable but conservative exact conditional procedure for the ratio of the response probabilities of subject without the attribute of interest has been studied. However, such a procedure is inapplicable to the risk ratio (i.e., ratio of the response probabilities of subject with the attribute of interest). In this paper, we investigate various test statistics (namely Wald-type, score and likelihood ratio test statistics) for testing non-unity risk ratio under standard inverse sampling scheme, which suggests one continue to sample until the predetermined number of index subjects with the attributes of interest is observed. Both asymptotic and numerical approximate unconditional methods are considered for P-value calculation. Performance of these test procedures are evaluated under different settings by means of Monte Carlo simulation. In general, the Wald-type test statistic is preferable for its satisfactory and stable performance with approximate unconditional procedures. The methodologies are illustrated with a real example from a heart disease study.

Hemangioblastoma of filum terminale associated with arteriovenous shunting.

BACKGROUND: Spinal arteriovenous shunt typically presents in middle age or in the elderly with a strong male predilection. The clinical presentation is usually progressive neurological deficits such as paraparesis or incontinence due to cord edema, although back pain is also a common presentation. Progress of neurological deficit is typically stopped by occlusion of the shunt (surgically or endovascularly), but the return of loss of function may be found in less than half of these patients. In contrast, spinal hemangioblastomas usually occur in adults, and the most common presentation is pain with radiculopathy. Location in the filum terminale is very rare. CASE DESCRIPTION: After a review of the medical literature, we identified 7 cases of hemangioblastomas arising from the filum terminale (Am J Neuroradiol. 2005;26:936-945; Acta Neurochir [Wien]. 2000;142:1059-1062; J Neurosurg Sci. 2001;45:58-62; J Clin Neurosci. 2006;13:285-288; Neurosurgery. 1999;44:220-223; Clin Neurol Neurosurg. 1985;87:55-59). We report an additional case of a filum terminale hemangioblastoma occurring in a 64-year-old man with 1 month exacerbation of chronic low back pain. Preoperatively, it was misdiagnosed as filum terminale arteriovenous fistula. CONCLUSION: Even with modern imaging, preoperative diagnosis can still be difficult.

Specific epitopes of the structural and hypothetical proteins elicit variable humoral responses in SARS patients.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an infectious disease which was caused by a novel coronavirus (SARS-CoV). SARS has caused an outbreak in the world during 2003 and 2004, with 8098 individuals being infected and a death toll of 774 in 28 regions around the world. Specific humoral responses to viral infection remain unclear. OBJECTIVE: To analyse the antigenicity of the SARS-CoV genome and identify potential antigenic epitopes in the structural proteins. METHODS: Potential antigenic epitopes were identified in the structural proteins (nucleocapsid, membrane, spike, and small envelope proteins) and hypothetical proteins (SARS3a, 3b, 6, 7a, and 9b) that are specific for SARS-CoV. A peptide chip platform was created and the profiles of antibodies to these epitopes were investigated in 59 different SARS patients' sera obtained 6-103 days after the onset of the illness. Serial sera from five additional patients were also studied. RESULTS: Epitopes at the N-terminus of the membrane protein and the C-terminus of nucleocapsid protein elicited strong antibody responses. Epitopes on the spike protein were only moderately immunogenic but the effects were persistent. Antibodies were also detected for some putative proteins, noticeably the C-termini of SARS3a and SARS6. CONCLUSIONS: Important epitopes of the SARS-CoV genome that may serve as potential markers for the viral infection are identified. These specific antigenic sites may also be important for vaccine development against this new fatal infectious disease.

Apolipoprotein E epsilon4 allele is associated with the volume of white matter changes in patients with lacunar infarcts.

The relationship between the apolipoprotein E (APOE) exon 4 polymorphism and white matter changes (WMC) in elderly subjects or patients with Alzheimer's disease is controversial. To investigate this polymorphism in relation to WMC in patients with lacunar infarcts, we prospectively observed 67 patients with acute lacunar infarct and 134 age- and sex-matched controls. Genotypes were determined using a nested polymerase chain reaction. WMC were measured quantitatively and were divided into two groups, severe and mild, with the mean volume of WMC as the cut point. Twenty-two patients (33%) had severe WMC. There was a significant difference in the distribution of APOE epsilon2, epsilon3, and epsilon4 alleles between severe and mild WMC groups (P = 0.002). The frequency of epsilon4 alleles was higher in patients with severe WMC than in those with mild WMC (25% vs. 7%, P = 0.003). These results suggest that APOE epsilon4 may exacerbate WMC in patients with lacunar infarcts. Further studies are required to confirm this finding.

Migration of bone marrow stem cells in ischaemic brain.

Stem cell therapy has been demonstrated to be effective in the management of haematological malignancy and solid cancer, but its role in neurodegenerative conditions remains uncertain. We hypothesize that: (1) ventricular delivery of bone marrow stem cells improves functional outcome in experimental ischaemia of the mouse brain; and (2) this improved outcome is due to migration of bone marrow stem cells to areas of ischaemia. Twelve mice with transient cerebral hemisphere ischaemia were randomly allocated to receive bone marrow stem cells or saline. The six animals that underwent cell therapy were found to perform better and committed fewer errors in the water maze system compared with the six control mice. Migration of these bone marrow stem cells was evident within the ventricular cerebro-spinal fluid (CSF) system and the brain parenchyma. This could also occur in clusters of cells. Preferential migration of these cells took place in lesioned areas.

Surgical treatment of a neonate with refractory seizures secondary to congenital giant cell astrocytoma: case report and literature review.

Congenital brain tumours are rare. They account for 0.5% to 1.9% of intracranial tumours in childhood and have an incidence of 0.34 per million live births. Most congenital brain tumours are neuro-ectodermal tumours and medulloblastomas; giant cell astrocytoma and other tuberous sclerosis-related tumours are rare. We report on a neonate who developed seizures that were refractory to medical treatment. Imaging studies revealed a right frontal calcified tumour. Surgical resection was performed successfully and pathology revealed the tumour to be a giant cell astrocytoma. The child was seizure-free afterwards.