Topic Update

Volume 8, Issue 2, July 2013

Prof. Paul KS Chan

Professor, Department of Microbiology, Prince of Wales Hospital The Chinese University of Hong Kong

Introduction

The family Papillomaviridae is comprised of a large group of viruses found in many mammalian species. Infection with papillomaviruses can be asymptomatic or results in the development of benign or malignant neoplasia. Cervical cancer is the most important consequence, in terms of disease burden, of human papillomavirus (HPV) infection. To date, the genomic sequences of more than 150 HPV types have been characterized. Of these, more than 40 types can infect the female genital tract, and at least 15 types are epidemiologically linked to cervical cancer. Over the last few years, there has been a vast increase in using HPV DNA detection as an adjunctive or primary tool in cervica l cancer screening programmes. Primary prevention of cervical cancers associated with the two most common types (HPV16 and HPV18) can now be achieved by vaccination. A thorough understanding on the epidemiology of cervical HPV infection is essential to maximize the clinical benefits and cost-effectiveness of HPV-based diagnostic tests and vaccines. In this review, some key epidemiological features of HPV infection in Hong Kong are presented to assist the formulation of strategies applicable to Hong Kong.

Prevalence of infection

“How common is cervical HPV infection?” This is always the first question to ask before any advice on vaccination can be made. Local studies on “well-women” self-referred for cervical screening showed that the prevalence of cervical HPV infection (defined as having an HPV DNA-positive cervical scrape sample) was around 8% among adult women aged 26-45 years. 1,2 The figure “1 in 12” is recommended for public education. While the studies reported a significant association between number of life-time sexual partners and smoking exposure, the prevalence among those without any recognizable risk factors is high enough to recommend vaccination in general for everyone.

Download Topic Update for Epidemiology of Cervical Human Papillomavirus Infection in Hong Kong: Implications on Preventative Strategy

Volume 8, Issue 1, January 2013

Bob Wilson MSc, FFS(RCPA), Kerri Prain, BSc, David Gillis, FRCPA FRACP FFS(RCPA) and Richard Wong GDM FRCPA FRACP FRCP.

Division of Immunology, Central Laboratory, HSSA-Pathology Queensland, Royal Brisbane and Women’s Hospitals, Herston, Brisbane, 4061, Australia.

Introduction

The spectrum of antibodies against intracellular, cell surface and synaptic neuronal antigens has expanded rapidly in recent years. The antigenic targets include ion channels, receptors involved in neurotransmission across synapses and proteins associated with them. There are now more than twenty anti-neuronal antibodies detected in association with neurological diseases. These antibodies may be associated with underlying malignancies and are commonly referred to as paraneoplastic antibodies (PNAs). Many PNAs have been correlated with neurological manifestations and fall into two groups: those that are cytotoxic for example anti-purkinje cell antibody-1 (PCA-1/Yo) and anti-neuronal nuclear antibody-1 (ANNA-1/Hu); and others that have functional activity, such as anti-N-Methyl-D-Aspartate receptor (NMDAR) and anti-Voltage-gated potassium channel (VGKC). Recently there has been a marked interest in both anti-NMDAR and anti-VGKC antibodies as the presence of these antibodies identify patients with treatable neurological disease.

Anti-NMDAR was initially described as a paraneoplastic antibody associated with ovarian teratoma, with a characteristic clinical picture of encephalitis with psychiatric features, cognitive dysfunction and seizures. 1 2 Although subsequent case series have confirmed that ovarian teratoma is a frequent association, it has become apparent that many patients who are positive for anti-NMDAR do not have evidence of an associated malignancy.

There is also some evidence supporting the need for rapid identification of anti-NMDAR. Patients who are diagnosed and treated with immuno-suppressive/immunomodulatory therapy within 40 days of disease onset, have been reported to have a better clinical outcome than those treated after 40 days.

Download Volume 8, Issue 1, January 2013

Volume 7, Issue 2, July 2012

Dr. King Chung Lee

Consultant Pathologist, St. Paul’s Hospital

Honorary Consultant, Queen Elizabeth Hospital

Background

Virtual microscopy using whole slide scanning has become increasingly popular in quality assurance program, teaching of pathologists and undergraduates and reproducibility studies 1-2. This concept was first extended to electron microscope (EM) about a year ago 3. This is made possible by two discoveries. Firstly, a free software component capable of stitching sequential pictures into a virtual slide that can be read by another free software. Secondly, an EM function capable of capturing up to 500 images covering a specified area automatically. Because of the simplicity acceptable degree of user intervention during the process and unsurpassed advantages over the conventional method, it was quickly adopted in routine renal biopsy diagnostic EM service and become the only routine service virtual microscopy system in Hong Kong. For those who are interested, you can download a sample from http://kvisit.com/SsKKqAQ and view it by Aperio ImageScope software, which was available for free download from the Aperio website, http://www.aperio.com/download-imagescope-viewer.asp

Summary of implementation

In the last year, over 400 renal biopsy cases were handled in our EM laboratory and over 1000 virtual ultrathin sections were generated (average 2.7 sections per case). The average EM time used in capturing is about 50 minutes per section. The average computing time is 40 minutes per section. The virtual ultrathin sections were either directly interpreted by Pathologists or screened and annotated by our EM tec hnologist before passing to Pathologists.

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Volume 7, Issue 1, January 2012

Dr W. S. Wong

Associate Consultant, Department of Pathology, Queen Elizabeth Hospital

Dr. K.F. Wong Chief of Service, Department of Pathology, Queen Elizabeth Hospital

Introduction

Chronic lymphocytic leukaemia (CLL) is the commonest chronic lymphoproliferative disorder of mature B-cells and affects mainly elderly. It is characterized by the presence of≥5x109/L monoclonal and often CD5+CD23+B-lymphocytes in peripheral blood. Haematogists usually have no problem in reaching the diagnosisas the majority of the cases have classical morphological and immunophenotypic features; however, it is an extremely heterogeneous disease clinically with highly variable clinical course.

Some patients are asymptomatic and do not require treatment while others progress early and require aggressive treatment. A number of clinical and biological parameters as well as molecular biomarkers have been demonstrated to predict the clinical outcome of the disease [1]. Molecular diagnostics has greatly improved the understanding of pathogenesis of CLL by pointing to candidate genes, for example 17p13 deletion, a common genetic aberration seen in CLL, corresponds to a tumour suppressor gene TP53. Moreover, different genetic subgroups have been shown to be associated with different prognosis: poor survival in 17p or 11q deletions and better survival in trisomy 12, normal karyotype or 13q deletion with the best survival found in isolated 13q deletion [2]. Cytogenetic studies may also help in the diagnosis of problem cases with atypical morphology or immunophenotypic profiles.

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Volume 6, Issue 1, July 2011

Dr W. T. Poon

Associate Consultant, Department of Pathology, Princess Margaret Hospital

Introduction

Toxicology analysis involves detection, identification and measurement of foreign compounds and their metabolites in biological and other specimens. It plays a useful role in them a nagement of poisoned patients when the diagnosis is in doubt, the administration of antidotes or protective agents is contemplated, or the use of active elimination therapy is being considered. As the scope and complexity of clinical toxicology continues to increase, continuing effort is required for the laboratory to expand its diagnostic capability and coverage. Apart from patient care, identification of a lethal or emerging toxin also serves to provide useful information for toxico-vigilance of potential public health threats and helps to prevent further poisonings. Some common and important herbal poisonings that have occurred in Hong Kong would be discussed as examples.

Apart from poisoning diagnosis, laboratory test can be used to predict the risk of adverse event to drugs in individual patients. It is now feasible to identify the genetic basis for certain toxic side effects and drugs will then be prescribed only to those who are not genetically at risk. Theranostic is the term used to describe the process of diagnostic therapy for individual patients - to test them for possible reaction to taking a new medication and to tailor a treatment for them based on the test results. In Hong Kong, genotyping for human lymphocyte HLA-B*1502 is recommended prior to administering carbamazepine for patients in order to avoid the development of Stevens-Johnson syndrome. An increasing number of pharmacogenetic tests are now available for clinical application. The criteria required of a pharmacogenetic test to make it useful for local application would be discussed.

Download Volume 6, Issue 1, July 2011

Volume 5, Issue 2, December 2010

WOO, Patrick CY

Professor, Department of Microbiology, The University of Hong Kong

Coronavirus study group, International Committee for Taxonomy of Viruses

Introduction

The Coronaviridae family is classified into two subfamilies, Coronavirinae and Torovirinae. Members of the Coronavirinae subfamily are in general referred to as coronaviruses. Phenotypically, coronaviruses are enveloped viruses of 120-160 nm in diameter. Under electronmicroscopy, coronaviruses have a crown-like appearance and the name “coronavirus” is derived from the Greek word κορώνα, which means crown. Genotypically, coronaviruses are positive-sense, single-stranded RNA viruses with genome sizes of about 30 kb, the largest genome size among all RNA viruses. Traditionally, coronaviruses were classified into three groups based on their antigenic relationships. Groups 1 and 2 are madeup of mammalian coronaviruses and group 3 aviancoronaviruses. Recently, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses (ICTV) has proposed three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, to replace these threetraditional groups of coronaviruses. Before 2003, there were less than 10 coronaviruses with complete genomes available, with only two human coronaviruses, namely human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43), which were discovered in the 1960s. The SARS epidemic in 2003 has boosted interest in coronavirus research globally; and most notably, in the discovery of novel coronaviruses and their genomics. In the past six years, our group has discovered 13 novel coronaviruses, including one novel human coronavirus [human coronavirus HKU1 (HCoV-HKU1)], SARS-related Rhinolophus batcoronavirus (SARSr-Rh-BatCoV), eight other bat coronaviruses and three avian coronaviruses, and has sequenced the genomes of nine of them(1-5). Others have also discovered additional coronaviruses, the most notable being human coronavirus NL63 (HCoV-NL63), discovered by a group in the Netherlands (6).

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Volume 5, Issue 1, June 2010

POON, WM

Senior Medical & Health Officer, Forensic Pathology Service, Department of Health

Introduction

Investigation of sudden death is the commonest challenge encountered by Forensic Pathologists. Most cases of sudden death are due to cardiovascular abnormalities evident at macroscopic and/or microscopic examination, such as coronary heart disease, myocarditis, cardiomyopathies, aortic dissection, etc. Unfortunately, a significant number of sudden death, estimated to be 1-5% (1), remains unexplained despite a thorough autopsy including toxicology, histology and other laboratory tests. This article attempts to look into some recent advances in the understanding of these “negative autopsies”. Issues related to “negative autopsies in infancy, which in itself merits another separate article, will not be covered in this article.”

Most of these cases of “negative autopsies” are believed to be caused by cardiac arrhythmias in “morphologically normal hearts” (2). Many of these “morphologically normal hearts”, however, are genetically abnormal with gene defects in ionchannels (i.e. channelopathies) in the myocytes leading to rhythm disturbances, ECG abnormalities and increased risk of sudden death. There is a growing list of inherited and congenital arrhythmia disorders caused by mutations in genes encoding defective ionic channels proteins governing the cell membrane transit of sodium, potassium and calcium ions including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). 

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Volume 4, Issue 3, December 2009

KHOO, Ui Soon

Clinical Associate Professor, Department of Pathology, The University of Hong Kong, Queen Mary Hospital

Background

Breast cancer is the leading female cancer in Hong Kong. Now at 52.1 per 100,000 (Hong Kong Cancer Registry, 2008) its incidence has been steadily rising over the last few decades, and is the highest reported in Asian regions. There are two major breast and ovarian susceptibility genes, BRCA1 and BRCA2. About 30-70% of patients with hereditary breast/ovarian cancer and about 5-10% of all breast and/or ovarian cancer cases harbor a germline mutation in these genes 1. The defective gene is inherited in autosomal dominance pattern. Individuals carrying a mutation in the BRCA1 or BRCA2 genes have a 85% lifetime risk of breast cancer, and a lifetime risk for ovarian, fallopian tube or primary peritoneal cancer that ranges from 35-60% for BRCA1 and 10-27% for BRCA2 2. 

BRCA mutation carriers tend to develop breast cancer at a young age, may have bilateral breast cancer or have a personal history of both breast and ovarian cancer. There is also an increased risk for prostate and pancreatic cancer as well as male breast cancer in BRCA2 mutation carriers. Other features of increased likelihood of hereditary susceptibility include the presence of two or more individuals in the family with breast cancer, the presence of both breast and ovarian cancer in the family, breast cancer in one or more male family members, and one of more members with two primary cancers. To estimate the probability of heritable genetic mutation in a family, one has to take into account the age of onset of breast cancer, the number of affected relatives, biological relationships of affected relatives, the ratio of affected to unaffected relatives as well as the presence/absence of associated malignancies and ethnic background.

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Volume 4, Issue 2, August 2009

Dr Jason C. C. So

Associate Professor, Division of Haematology, Department of Pathology, The University of Hong Kong, Queen Mary Hospital

Introduction

Globin gene disorders as a whole are the commonest group of monogenic disease in the world. In Southern China and Southeast Asia, alpha and beta thalassaemias, as well as specific types of haemoglobin (Hb) variants such as Hb E, are prevalent. Most people who have inherited these mutated globin genes are asymptomatic carriers. The number of severely affected patients is relatively small in developed regions where comprehensive antenatal screening and prenatal diagnosis programmes are in place. This is not the situation in less developed countries where the clinical, economical and social load of globin gene disorders is still heavily felt.

Phenotypic Diagnosis of Globin Gene Disorders 

The clinical and haematological manifestations of different forms of thalassaemias are well known. The approach to phenotypic diagnosis is largely standardised among haematology laboratories. Complete blood counting reveals the degree of anaemia. A low mean corpuscular volume (MCV) of red cells serves as an important screening parameter for further testing. Quantitation of HbA2 and F is performed for diagnosis of beta thalassaemia, delta-beta thalassaemia and hereditary persistence of foetal haemoglobin (HPFH). Demonstration of excess beta globin chains (Hb H) indicates alpha thalassaemia. When a Hb variant is suspected, its electrophoretic  mobility is assessed and compared with knownvariants. The advent of technological advances, including sophisticated blood cell analysers, automated high performance liquid chromatography (HPLC), capillary electrophoresis and antibody-based assays has made the analysis of Hb quicker, more accurate and precise. In most cases, the diagnosis of thalassaemias and common Hb variants is straight forward.

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Volume 4, Issue 1, April 2009

TAI, Morris

Associate Consultant, Department of Pathology and Clinical Biochemistry, Queen Mary Hospital

Introduction

The prevalence of diabetes mellitus (DM) has been increasing in recent years and DM is now a global epidemic. Haemoglobin A1c (HbA1c) plays an important role in the management of DM as the vast majority of outcome  studies on diabetic complications are based on it. The most famous of such studies, which demonstrated the relationship of HbA1c to diabetic complications, are the Diabetes Control and Complications Trial (DCCT) & the United Kingdom Prospective Diabetes Study (UKPDS). HbA1c is formed via a posttranslational nonenzymatic attachment of glucose to haemoglobin in an irreversible fashion. In strict chemical terms, the molecular structure of HbA1c is β-N-(1-deoxy)-fructosyl-haemoglobin and it serves as an indicator of glycaemic control over the preceding 2- to 3- month period.

There are a great number of analytical methods used in the measurement of HbA1c. More than 20 methods were in clinical use as reported in the year 2004. The heterogeneity of methodology eventually generated concerns about comparability and usability of HbA1c, especially when patients’ data were to be compared with study results. The call for test standardization was therefore critical. Various standardization programmes have been carried out since the 1990s. The National Glycohaemoglobin Standardization Program (NGSP) and the International Federation of Clinical Chemistry (IFCC) are the two mostimportant international standardization programmes while local ones such as Japan Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC) and Mono-S have been adopted in Japan and Sweden respectively.

Download Volume 4, Issue 1, April 2009