Topic Update

Pathology of Non-Alcoholic Fatty Liver Disease

"Non-alcoholic fatty liver disease1" by Nephron - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Non-alcoholic_fatty_liver_disease1.jpg#/media/File:Non-alcoholic_fatty_liver_disease1.jpg

Volume 10, Issue 1, January 2015

Dr. Anthony W.H. Chan

Associate Professor Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a serious global health problem and associated with over-nutrition and its related metabolic risk factors including central obesity, glucose intolerance, dyslipidaemia and hypertension. It is the most common metabolic liver disease worldwide and its prevalence in most Asian countries is similar to that in the States, Europe and Australia. About 10-45% of Asian population have NAFLD. With “westernized” sedentary lifestyle, the prevalence of NAFLD in general urban population in the mainland China is about 15%. NAFLD is even more prevalent in Hong Kong. Our recent study demonstrated that NAFLD is found in 27.3% of Hong Kong Chinese adults by using proton-magnetic resonance spectroscopy. We further realized that 13.5% of Hong Kong Chinese adults newly develop NAFLD in 3-5 years. Both prevalence and incidence of NAFLD in Hong Kong are alarmingly high. Accurate diagnosis of NAFLD is crucial to allow prompt management of patients to reduce morbidity and mortality. NAFLD is composed of a full spectrum of conditions from steatosis to steatohepatitis (NASH) and cirrhosis. Various non-invasive tests, based on clinical, laboratory and radiological tests, have been developed to assess the degree of steatosis and fibrosis in NAFLD. However, liver biopsy remains the gold standard for characterizing liver histology in patients with NAFLD, and is recommended in patients with NAFLD at high-risk of steatohepati tis and advanced fibrosis (bridging fibrosis and cirrhosis), and concurrent chronic liver disease of other aetiology. This article reviews pathological features of NAFLD and highlights some practical points for our daily diagnostic work.

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Molecular Classification and Genetic Alterations of Diffuse Large B-cell Lymphoma

"Glass ochem" by Purpy Pupple - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Glass_ochem.png#/media/File:Glass_ochem.png

Volume 9, Issue 2, July 2014

Dr CHOI Wai Lap

Department of Clinical Pathology Tuen Mun Hospital

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the commonest subtype of non-Hodgkin lymphoma, accounting for about 30% to 40% of newly diagnosed non-Hodgkin lymphoma worldwide and in Hong Kong. DLBCL is heterogeneous in clinical presentation, morphology, immunophenotype, cytogenetics and prognos is. In the WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues published in 2008, several specific clinicopathological entities of DLBCL have been recognized, while leaving the rest to DLBCL, not otherwise specified, which is by far the most prevalent entity among the large B-cell lymphomas. In the following discussion, the term DLBCL will be used interchangeably with DLBCL, not otherwise specified.

Gene expression profiling and molecular classification of DLBCL

Gene expression profiling (GEP) is the simultaneous measurement of the transcription levels of thousands of genes to their corresponding messenger RNAs (mRNAs). GEP can be achieved by various technologies including DNA microarray, serial analysis of gene expression (SAGE) and most recently next generation sequencing (RNA-Seq). Using DNA microarray technology on DLBCL, two distinct molecular subgroups were discovered based on the similarity of their gene expression pattern with a possible cell of origin (COO): the germinal centre B-cell-like (GCB-cell-like, or abbreviated as GCB) and the activated B-cell-like(ABC-like, or abbreviated as ABC). These molecular subgroups showed significantly different survival rates when treated with conventional cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapeutic regimen.

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Thyroid Dyshormonogenesis

Volume 9, Issue 1, January 2014

Dr YUEN Yuet Ping

Department of Chemical Pathology Prince of Wales Hospital

Introduction

Congenital hypothyroidism (CH) is an important preventable cause of mental retardation. To prevent irreversible brain damages caused by hypothyroidism, sufficient doses of thyroxine should be started within a few weeks after birth.(1) Since neonates with CH have no obvious or minimal clinical manifestations, biochemical screening in the newborn period has become the best public health strategy for early detection of affected neonates. In Hong Kong, a territory-wide screening programme for CH was started in 1984.(2) Cord blood samples are collected immediately after birth for measurement of thyroid stimulating hormone (TSH) by a single laboratory dedicated for newborn screening. The incidence of CH in Hong Kong was reported to be 1 in 2,404, which is comparable to that in other populations.

Causes of congenital hypothyroidism

The aetiologies of CH are summarized in Table 1.(7) Approximately 80-85% of CH are caused by thyroid dysgenesis, which is a group of congenital disorders of thyroid gland development or migration. Affected patients may have complete thyroid gland aplasia, hypoplasia or ectopic glands. The large majority of thyroid dysgenesis cases are sporadic and only about 5% has a genetic basis.(8,9) Thyroid dyshormonogenesis describes a group of inherited disorders which affect the biochemical pathway of thyroid hormone synthesis. These disorders collectively account for 10-15% of CH cases. Approximately 1/4 of patients with CH in Hong Kong have some forms of thyroid dyshormonogenesis.(10) Some neonates detected by newborn screening program have transient instead of permanent CH. Although this subgroup of patients does not require life- long thyroid hormone replacement, early identification and treatment in early years of life is equally important.(11) The time course of recovery of the hypothalamic-pituitary-thyroid axis in patients with transient CH depends on the underlying cause. Although most of the transient CH are due to acquired conditions such as iodine deficiency or maternal transfer of autoantibodies, a few genetic causes have been described.

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Epidemiology of Cervical Human Papillomavirus Infection in Hong Kong: Implications on Preventative Strategy

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.

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Laboratory Testing For Anti-NMDAR In Autoimmune Encephalitis: The HSSA- Pathology Queensland Experience

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.

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Virtual Electron Microscopy – update after one year of routine use

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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Chronic lymphocytic leukaemia – the role of conventional and molecular cytogenetics

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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Laboratory Role in Toxicology: From Diagnostic to Theranostic

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.

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Discovery of novel microbes: more and more coronaviruses after the SARS epidemic

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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Molecular Autopsy of Unexplained Sudden Death

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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