Trainee Presentation Session 2020

Venue: Pao Yue Kong Auditorium, Hong Kong Academy of Medicine Jockey Club Building

Time: 28 Nov 2020 13:45 - 18:00

Detail schedule in pdf

Introduction

Dr. YAU Tsz Wai Derek

13:45 - 13:55

Platform Oral Presentation

13:55 - 15:55

Dr. FUNG Ka Kin Ben

Risk Factors and Antibiotic Susceptibility to Cephalosporin/Beta-Lactamse Inhibitor Combinations for Multidrug Resistant Pseudomonas aeruginosa

Dr. LEE Lok Hang Alfred

Diagnostic Stewardship Program for Urine Culture - the Impact on Antimicrobial Prescription in a Multi-Centre Cohort

Dr. LI Jing Xi Joshua

Cytomorphological Parameters in Correlation of Growth Pattern and Prediction of Grading of Ductal Carcinoma-in-situ of the Breast by Fine-Needle Aspiration

Dr. LIAO Jiawei Gary

"Pauci-Hemosiderotic" Fibrolipomatous Tumor: A Mimicker of Various Lipomatous Lesions

Dr. YUEN Ka Wan Karen

Thyroid Adenoma of Probable Ultimobranchial Body Origin: A Case Report

Dr.YEUNG Chun Fai Maximus

Importance of Alternative Promoter Usages in Cancers Revealed by Pan-Cancer Transcriptome Analysis

Dr. LING Tsz Ki Jacky

NT-proBNP for the Diagnosis and Monitoring in the First Local Case of Kawasaki-Like Multisystem Inflammatory Syndrome (MIS) Associated with COVID-19 Infection

Dr. HO Man Kit Mark

Collagenofibrotic Glomerulopathy: A Case Report

Poster Presentation

15:55 - 17:25

Dr. CHOW Kin Yi CHristina

Evaluation of BioFire FilmArray Respiratory Panel for Detection of Viruses

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Dr. NG King Man Kevin

Molecular Detection of Mycoplasma genitalium in Endocervical Swabs and Associated Macrolide and Fluoroquinolone Resistance in Hong Kong

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Dr. LI Xiu Ling Vivian

Data Review on a New Flow Cytometry Panel for the Diagnosis of Low Grade B-Cell Lymphoproliferative Disease

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break

Dr. KWOK Lok Ming Angie

Adenofibromatous Solitary Fibrous Tumor: a New Morphologic Variant Occurring in the Sinonasal Tract

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Dr. LUI Yin Wing

Dr. Cytology May be the First Clue to a Perforated Oesophagus: Stay Vigilant Even When it is 'Negative for Malignant Cells'

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Dr. HAU Man Nga

Oncocytic Variant of Secretory Carcinoma: Expanding the Morphological Spectrum of Secretory Carcinoma in Salivary Gland - a Case Report

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Dr. FONG Tsun Nestor

An Autopsy Case Report of Intravascular Large B-Cell Lymphoma with Initial Neurologic Presentation

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Dr. SO Yik Ka

Myxoid Spindle Cell Sarcoma with LMNA-NTRK Fusion: Expanding the Morphologic Spectrum of NTRK- Rearranged Tumors

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Dr. TSSNG Cheuk Ho Jason

Glomus Tumor of Sella Turcica with Synaptophysin Expression Mimicking Pituitary Adenoma

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Dr. NG Ka Man Joanna

Trichoblastic Carcinosarcoma Arising from the Vagina: A Case Report with Comprehensive Immunophenotypic Analysis

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Dr. CHAN Cheong Kin Ronald

Digitized Library of Pathology Specimens

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Dr. LAI Shun Wun Billy

The Clinical Significance of Neuroendocrine Features in Invasive Breast Carcinomas

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Dr. CHAN Angela Zaneta

Case Report: Malignant Sinonasal Solitary Fibrous Tumour with BCOR Immunoexpression

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Dr. WONG Wing Fung Wilson

A Rare Case of Constitutional Mismatch Repair Deficiency Syndrome in a 2-year-old Girl with Medulloblastoma and Signs of Neurofibromatosis Type 1

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Dr. CHANG Lik Chun John

A Sarcoma with MXD4-NUTM1 gene fusion - a Case Report

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Dr. CHEUNG Ka Chun Kevin

A Case Report on Monomorphic Epitheliotropic Intestinal T- Cell Lymphoma (MEITL)

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Judges Meeting and Words from Judges

17:25 - 17:40

Prize and Certificates Presentation

17:40 - 18:00

Results of College Exam 2020 (Council Meeting 16 October 2020)

 

Fellowship Assessment:

 

EXAM NO.	RESULT
E20221	FAIL

 

Membership Examination:

 

EXAM NO.	RESULT
E20117	PASS

 

 

 

Results of College Exam 2020 (Council Meeting 29 September 2020)

 

Fellowship Assessment:

 

EXAM NO.	RESULT
E20201	PASS
E20202	PASS
E20203	FAIL
E20204	PASS
E20205	PASS
E20206	FAIL
E20207	PASS
E20208	FAIL
E20209	PASS
E20210	PASS
E20211	PASS
E20212	PASS
E20213	PASS
E20214	PASS
E20215	PASS
E20216	FAIL
E20217	FAIL
E20218	PASS
E20219	FAIL
E20220	FAIL
E20222	PASS

 

Membership Examination:

 

EXAM NO.	RESULT
E20101	FAIL
E20102	PASS
E20103	PASS
E20104	PASS
E20105	PASS
E20106	PASS
E20107	PASS
E20108	PASS
E20109	PASS
E20110	PASS
E20111	FAIL
E20112	PASS
E20113	PASS
E20114	PASS
E20115	PASS
E20116	FAIL

 

 

 

Volume 29, Issue 1 (click here to download the full pdf version)

Message from the President

In this issue of the College Newsletter, I am saddened to bring the news to all Members and Fellows that one of our Honorary Fellows, Professor WU Bing Quan passed away peacefully on 21 June 2020. Professor WU was a pioneer in the development of Pathology in China. He was one of the first group of scientists to be sent to the United States for training where he met Professor Joseph CK LEE, Former Dean and current Honorary Clinical Professor of The Chinese University of Hong Kong. They became good friends during their time together in the United States and hence Professor WU became associated with our College. Professor LEE has kindly written an obituary for Professor WU and our College also sends its condolences to Professor WU’s family.

The 15th Trainee Presentation Session, the 28th Annual General Meeting and Conferment Ceremony, the 28th T.B. TEOH Foundation Lecture and Dinner were successfully held on 23rd November 2019 when the social unrest was quietening down. All attending Members, Fellows and their families enjoyed a wonderful evening. Professor KWONG Yok Lam, our 28th T.B. TEOH Foundation Lecturer, delivered a lecture entitled “An amazing journey from micro to macro and back” with a human touch of his interest in reading science fiction. The winner of the 15th Trainee Presentation Session was Dr. CHENG Hua Tse Timothy who presented his work on ‘Comprehensive characterization and resolution of eltrombopag interference on bilirubin measurement’.

The Academies of Medicine for Singapore and Malaysia organised the 53rd Singapore Malaysia Congress of Medicine in Singapore in January 2020. I attended the Congress as well as the Joint Academy Council Meeting on behalf of the College. In the Congress Symposium, a fascinating talk on how big data and social media affects the hierarchical relationship and massive manipulation was presented by Mr. George YEO, the Former Cabinet Minister of Singapore.

The Topical Update in this issue was on “Liver Injury associated with Immune Checkpoint Inhibitors – An Update on Clinicopathological Features“, by Dr. LO Cheuk Lam Regina of The University of Hong Kong. In response to the recent COVID-19 pandemic, Professor LAI Koon Chi Christopher of The Chinese Unive rsity of Hong Kong, and Professor Siddharth SRIDHAR of The University of Hong Kong, jointly published an article on “Coronavirus Diversity and Infection through Host Receptor” in Ming Pao on 7th April 2020. On 29th April 2020, our College also released a press statement to the general public on the “Use of Over-the-Counter COVID-19 Test Kits”, explaining the risks associated with false positives and false negatives of the point-of-care test kits based on IgG and IgM antibodies. Apart from numerous reports in various newspapers, our College also noted about 40,000 ‘shares’ on social media.

Different parts of College Examinations have been or will be conducted from July to September 2020. It is challenging to conduct examinations in a pandemic situation, but with the approval from the Academy Council, Colleges are allowed to conduct examinations using telecommunication technology where appropriate and possible. I would like to thank our External Examiners, Chief Examiners, Deputy Chief Examiner and Local Examiners in advance for their tremendous effort in making it possible for the College Examinations to be conducted as scheduled.

Finally, allow me to wish you all ‘good health’ going forward !

Dr. CHAN Ho Ming
President

July 2020

Drowning: A Rational Approach to its Diagnosis

Volume 15, Issue 2, July 2020  (download full article in pdf)

Editorial note:

Drowning often presents in various scenarios depending on the circumstances. This Topical Update provides a proper approach to the diagnosis. We welcome any feedback or suggestions. Please direct them to Dr. FOO Ka-chung of Education Committee, the Hong Kong College of Pathologists. Opinions expressed are those of the authors or named individuals, and are not necessarily those of the Hong Kong College of Pathologists.

Dr. FOO Ka-chung

Specialty Coordinator (Forensic Pathology), Education Committee

The Hong Kong College of Pathologists

Introduction

Drowning is referred as “death occurring within 24 hours of a submersion incident”. Definition by World Health Organization is "the process of experiencing respiratory impairment from submersion or immersion in liquid ". [1,2] It is a form of asphyxia with a distinct pathophysiology and mechanism of death. It is also a diagnosis by exclusion, and therefore every piece of information should be regarded as crucial. Pathologists are obliged to work under Coroner’s jurisdiction in interviewing the next-of-kin (if available), reviewing antemortem medical records and preliminary findings provided by investigating officer, performing an autopsy as directed and compiling reports capable of addressing anticipated issues.

As Forensic Pathologists mostly deal with sudden and unexpected deaths, cases of drowning with unsalvageable outcome are often encountered. Hospital Pathologists, on the other hand, are dealing with patients presenting a clinical picture in which death eventually occurred after vigorous cardiopulmonary resuscitation followed by development of various systemic complications, e.g. pneumonia, acute respiratory distress syndrome, multi-organ failure, disseminated intravascular coagulopathy, hypoxic-ischaemic encephalopathy etc.

Manner of Death

Information derived from the Coroner’s Report [3] and the Centre for Health Protection [4] suggested that majority of cases were accidental or suicidal in nature. Only a few were homicides. However, it should be remembered that a body found immersed in water does not necessarily imply a diagnosis of drowning. Nor its manner be automatically presumed basing on the prevalent trend. The deceased can die of natural conditions preceding or during submersion as well as unnatural elements that contributed to the drowning process, explaining the failure of extrication from water versus genuine lethal trauma before or while in water. [5,6]

Pathophysiology

The mechanism of death is complex involving changes to viscera, biochemical alterations and also at a cellular level. The culprit is the medium imposing hydrostatic and osmotic effect to the lungs. [7] The acute change in intravascular volume with electrolyte imbalance is the consequence. Several stages of drowning present in response to the rising levels of carbon dioxide and decreasing oxygen tension in blood. Voluntary breath holding for about 1 to 2 minutes is followed by a stage of involuntary urge to breath with aspiration of fluid for about 1 to 3 minutes. Tonic-clonic seizures, together with some degree of respiratory activity, will occur in the next 1.5 minutes with eventual involuntary breath holding and terminal gasping before cessation of cardiac activity. [1]

It has even been mentioned that only a few inches of water is sufficient to drown a person, as in the case of sudden incapacitation by onset of acute illness while standing close to a washbasin or bucket. [5,6] It was reported that about 1 mL/kg to 11 mL/kg of water aspirated can result in drowning. [7]

A rare entity underdiagnosed in daily practice, or seldom made by pathologists, is referred as "dry drowning" or "immersion syndrome", with negative autopsy findings of typically drowned lungs due to severe laryngeal spasm, therefore preventing further intake while stimulating the sensitive receptors and subsequently triggering cardio-inhibitory reflexes (Ebbecke reflex, Aschner reflex, Hering reflex). [1,5,6,7,8]

Diagnosis of Drowning

The possibility of drowning should always be considered when a deceased was recovered from a body of fluid or the head was found submerged inside a medium of fluid. The deceased could be found near a body of fluid where it could be washed onto the rocky shore, beach, or riverbank. Domestic environments such as bathtub also house this potential danger affecting all walks of life, especially for those who have chronic illness with sudden unexpected precipitation or the young. While the diagnosis of drowning could be straightforward one, such as a witnessed fall into water with subsequent submersion, it can be extremely difficult when critical information derived from the case is absent or inconclusive. Challenging scenarios can appear with unclear circumstances preventing proper formulation of the manner of death. Moreover, while findings derived from postmortem and ancillary investigations may collaborate with the diagnosis, it can be equally confusing when concomitant conditions are unveiled.

Presence of a natural condition which may contribute to death

Let’s consider the following case:

A 51 year-old female was found collapsed underwater in a public swimming pool of about 1.4 meters deep and was certified dead despite intensive resuscitation. There was no eye witness leading to her collapse. Autopsy revealed severe ischaemic heart disease with no evidence of acute infarction. Both lungs were congested and oedematous but frothy fluid was absent probably due to suction during resuscitation. Cause of death is labelled as drowning as the overall features were compatible with drowning.

The presence of a co-existing medical condition, be it undiagnosed or known to the deceased, has to be evaluated carefully to attribute its extent of contribution to death. A sudden precipitation into cardiac arrhythmia explained the reason why a habitual swimmer is incapacitated and eventually succumbed in the water. From the investigator’s point of view, possible legal issues regarding adequate supervision of the swimming environment may be raised which could lead to possible lawsuit and inquest. As such, the pathologist should be ready to address the extent of contribution of medical condition to the tragic outcome.

Medical background of the deceased has to be thoroughly reviewed including conditions such as asthma, epilepsy, cardiovascular conditions (e.g. Long QT syndrome type 1). Psychiatric history including substance abuse should also be elicited.

Presence of trauma which may be related to death

Another case is presented here:

An 87 year-old female was found floating off shore from a pier. She was known to be a habitual swimmer and there was no known chronic illness. There were multiple lacerations on chest and right upper limb. The thoracic cavity was breached and right lung had collapsed. Tinge of frothy fluid was noticed briefly by paramedics before transportation to mortuary. Autopsy revealed severe coronary stenosis and the left lung was mildly hyperinflated.

The presence of trauma may or may not be related to death as injuries inflicted can be produced ante-mortem or post-mortem. Assessment for vital reactions at the wound margin may be helpful to determine its nature.

All forms of injuries must be explained correlating inanimate objects in the environment. Sliding abrasions may be inflicted upon skidding down a slope while blunt force injuries may be a genuine assault. Self-inflicted injuries may occur in suicide as a back-up technique, for example, a stab to the chest or incised wound on the neck, yet it might at times mimic a homicide.

Dragging effects as a result of contact with river bed or ocean floor propelled by sea waves or tidal current is not uncommon and should be interpreted in light of such movement in water. Abrasions or lacerations may be found on forehead, dorsum, knees and toes. In addition, aquatic animal activity, such as crustaceans, will produce bites and nipping around orifices. The body, on the other hand, may be struck by watercraft or its parts including the propeller, predominantly located below the waist and over the extremities while the subject is maintaining a vertical position. It should be located posteriorly upon floating postmortem. [5,6] At times injuries could be severe enough to hinder the diagnosis by producing serious disruption of the viscera. The presence of postmortem mutilation further complicate the diagnosis, let alone in jeopardizing the facial features and hindering identity as often encountered in mass fatalities.

Healthy adults who can swim rarely drown unless there is an intervening reason such as superimposed injury, fatigue or dangerous environment. The level of fitness, history of risk-taking behaviour, pre-swim activities, swimming ability and experience should be explored.

In the present case, the cause of death is labelled as drowning and suggested an accidental manner with sudden precipitation of undiagnosed cardiac condition, complicated by postmortem propeller injuries by marine traffic, evidenced by lack of blood infiltration at the site of traumatic amputation.

Let’s consider another case:

An 80 year old male, who was an inmate of old aged home with multiple comorbidities confined to a wheelchair, was found submerged underneath river. He was last seen swaying around a footbridge about 3 meters above the river several hours earlier. Probable suicidal intention was identified. Autopsy revealed extensive comminuted fractures of the vault, subarachnoid haemorrhages and cortical contusions. Both lungs did not appear to be waterlogged.

Injuries may also be produced before or upon entering water and their extent have to be assessed. This could be related to subsequent question of survivability. In this case, considering the severity of the head injuries, it would appear that the deceased was unable to survive in water (or at most only a transient period) and succumbed rapidly. The cause of death is therefore attributed to head injuries upon falling with his top of head bumping the river bed.

Another case to ponder:

A 33 year-old female was found submerged about 20 meters off shore. Linear reddish bruising was found on the anterior neck. The face and eyes were congested with petechiae. Small amount of frothy fluid was present. Both lungs were congested and oedematous. Dissection also revealed deep bruising of strap muscles suggestive of pressure applied to neck. Subsequent investigation revealed spouse’s involvement with manual strangulation during a quarrel.

Suspicious injuries should be noticed which may be an act of homicidal drowning. In the present case, the cause of death is a combination of drowning and pressure on neck, with latter being a significant event rendering the deceased unconscious when pressure was applied and succumbed to the effects of immersion.

Presence of drugs which may be related to death

Let’s consider the following case:

A 29 year-old male was found floating in the river reported by local residents. No personal property could be found. No suicide note was present. He was last seen alive by wife 3 days ago and was believed to have quarreled with a female acquaintance, exhibiting violent behavior and soon disappeared afterwards. Wife reported missing to Police the next day and his personal belongings were discovered in a shopping mall. Autopsy revealed features of drowning. Postmortem toxicology analysis showed presence of cocaine and its metabolite benzoylecgonine in blood. It was not known to the family whether he had a history of drug abuse.

Toxicology samples are crucial to exclude conditions that may mimic autopsy features of drowning, such as pulmonary oedema. It may help to exclude an accident, explain for failure to extricate or survival in water, as well as inferring an intention to end one’s life or a deliberate intoxication. In the present case, analysis of hair samples was performed to address the issue whether he was exposed to illicit drug on a chronic basis and therefore exhibiting tolerance.

Presence of decomposition features may obscure the effects of drowning

Let’s consider the following case:

A 32 year-old male was found in the reservoir exhibiting moderate decomposition changes. Suicide note was found in personal property placed neatly on the shore. Autopsy did not reveal any significant trauma or lethal disease conditions. Both lungs were not hyperinflated but huge amount of serosanguinous effusion was present in chest cavities. Police investigation also revealed a strong suicidal intention and third party was not involved.

Typical findings of drowning are often masked by decomposition changes. In addition, the time of death has to be determined during investigation. For fresh bodies examined at scene, corrective factors should be applied while measuring the core temperature against ambient temperature as the rate of cooling in flowing and still water are different. Casper's dictum refers to the rate of putrefaction after 1 week in air being equivalent to 2 weeks in water and 8 weeks burial in soil. The varying features of decomposition hint to the postmortem interval and is generally slower in cold water than a body discovered on land, but may be accelerated in bacterial laden stagnant water. As micro-organisms continue to disseminate and distribute throughout various body compartments, decomposition will be accelerated upon retrieval.

While the cause of death can remain unascertainable due to decomposition, the pathologist could nonetheless leave a remark stating the overall findings was not inconsistent with that of drowning. This is dependent on the degree of diagnostic certainty dictated by the available circumstances and likelihood of other intervening events, such as injuries (which could also be obscured by decomposition).

Let’s consider another case:

A 69 year-old female with a history of psychotic illness was found floating in the sea, three days after her husband had reported missing to Police. No suicide note was found. Body exhibited early decomposition changes. Postmortem toxicology analysis revealed a toxic level of amisulpride in the blood samples. As there was no concrete evidence about the suicidal intention or actual clinical progress on the psychiatric condition, it remained unclear whether the deceased fell into the water out of her intention.

Destruction of micro-architecture by decomposition permit considerable degree of postmortem redistribution of drugs which possibly account for the elevated levels in the specimen. The cause of death and manner can remain inconclusive.

Mysterious circumstances

Let’s consider a case with apparently suspicious circumstances:

A 32 year-old male with a known history of mood disorder was found floating near a port. His leg was tied to a dumbbell. Suicide note was found at home. He was last seen alive two days ago and reported missing by family another two days later. The body exhibited early decomposition changes but the lungs appeared hyperinflated. Further Police investigation tracked the last whereabouts of the deceased including the use of surveillance camera in the vicinity and revealed no evidence of third party involvement. The shopkeeper selling the dumbbell clearly recalled visit by the deceased on the day of death.

Forensic Pathologists do not interpret a case relying solely on the autopsy findings. Circumstantial information can play a role to hint the pathologist appropriate features that should be looked for during scene and body examination. In the present case, there could be an underlying psychiatric vulnerability suggestive of a suicidal intent. A body with weight affixed to limbs can of course represent an unlawful disposal, but may as well indicate a determination to kill oneself. Examination of the knot tying at the involved body part is crucial.

For suspicious case a detailed investigation into the events before death is expected. The salient areas of such are briefly mentioned here.

Witness account

This is valuable and gives considerable weight to the case. For example, witnessed jumping into the water, signs of mental impairment, activities prior to submersion, the duration of immersion, bystander resuscitation with possibility of repositioning of body, accounts provided by lifeguard and nearby video surveillance, are all hints to the state of mind prior to drowning. [5,6] Homicidal drowning is rare unless one is being incapacitated by alcohol, drugs or physical weakness, or taken by an element of surprise such as being pushed unexpectedly into water. [9]

Scene and environment

Water temperature, current, terrain, water depth, underwater condition, floating objects, marine animal activities or plants, presence of safety and rescue measures are important to consider. A seemingly innocent river with slow volume of flow may harbor strong underwater currents creating significant eddies and vortex sucking the swimmer rapidly, coupled by additional injuries inflicted by submerged rocks and waterfalls, or falling log from trees nearby. [10]

Body floats owing to formation of putrefactive gas producing buoyancy and is affected by lung volume. It could even overcome weights added to the body in concealed homicide. The body will continue to sink as hydrostatic force exert pressure to the chest and abdominal compartments creating negative buoyancy. In extremely cold water with minimal bacterial activity, the body will never resurface and decompose through formation of adipocere. [1,5,6,7,8] Coupled together with witness account about the last seen at the point of immersion, an estimation of current speed and body drop rate (about 1.5 and 2 feet in salt and fresh water respectively) can allow back-calculation of the site of drowning in moving water, i.e. the distance from shore, which is useful for rescue and case reconstruction. [5,6]

For indoor environment a bathroom may present with wet, floor, wet towels and soap scum level in the tub (if water has been drained already). The presence of bucket and mop, and other cleansing material maybe an attempt to disturb the scene. [5,6] A discovery of electrical appliances would call for a proper investigation to the possibility of electrocution.

Location of body

The place where body is discovered does not necessarily indicate the site of drowning. A body can be brought by a receding tide to the shore and there is always a possibility of drowning in another place, such as an indoor environment. [5,6,7] The body maybe disposed into the sea as an act of mimicking suicide. Differentiation between genuine drowning versus other causes; as well as fresh versus salt water immersion would be helpful. The appropriateness of the subject to the location is important. A restricted access may suggest unauthorized entry to the premises and should be investigated.

State of body

The condition of body regarding to its state of dryness or wetness, any attachment by aquatic debris and clothing identified are important. [5,6,7] Minute pieces of evidence pertaining to the identity, drug habit, personal property, weapon and suicide note should not be overlooked. Clothing and status of equipment, especially in diving related fatality should be examined. A naked body may be a deliberate act of hindering proper identification, or could be linked to a sexually motivated homicide. The body composition, water temperature, current action, type of clothing, method of water entry may all affect the presence or absence of clothing on body and should be interpreted with care. [6]

The presence of sand, seaweed or other vegetation should be documented and described, with the possibility of sampling for trace evidence and hinting the location of drowning in doubtful situations. A pair of shriveled and pale hands or feet can be found regardless of whether the individual was alive or not. Commonly referred as "washerwoman's skin”, there is wrinkling and grayish white discoloration of skin at sites devoid of sebaceous glands. Histological features of swelling of epidermis keratinizing squamous epithelium, detachment of horny layer, fraying of keratin lamellae and vacuolation in the basal layer are observed. There are reports in older literature with reference to such histological changes in an attempt to determine the postmortem interval, though subjecting to environmental factors of water type, temperature, movement, pollution and dermal characteristics of the subject. [11]

Hospital Pathologists are familiar with the appearance of hypostasis but such phenomenon would be present on face, upper chest and distal end of extremities. This is explained by dangling position adopted by the body with head and limbs pointing downwards owing its specific gravity while the posterior trunk is floating backup. [1,5,6,7] On the other hand, hypostasis can be minimal when exposed to fast flowing water. [5,6] For bodies lying in bath tub there may be a line of demarcation corresponding to the water level. [7] The importance of visiting a scene cannot be emphasized more.

Clear or blood tinged oedema is usually described as a plume of froth around the nose and mouth. It is non-specific in nature and consists of bronchial mucus, oedematous fluid, air and the drowning medium. The redness is accounted by the ruptured capillaries exuding into the respiratory tract. [7,8,] And most importantly it is transient in nature. In addition, slit, mud, sand, vegetation, algae and shell fragments may be present in bronchi and bronchioles visible both grossly and microscopically. [5,6]

Autopsy Findings

The role of an autopsy is to retrieve relevant findings that support the diagnosis. Not all the features will be present, depending on the nature of drowning process. Interpretation is only meaningful when combined with sufficient circumstantial information.

Emphysema aquosum

A pair of waterlogged lungs is a result of over-distension due to strenuous effort in an attempt to overcome oxygen depletion upon water influx. It is more prominent in the periphery and a combination of both lungs with effusion weighing more than 1000 g is usual. [7,8] There is also overlapping of medial edges in the anterior mediastinum with indentation or imprints by the corresponding ribs. It is distinguished from chronic emphysema by protrusion of sectioned bronchial and vessels at the cut surface for the latter. Histology shows flattened inter-alveolar septa, dilated pulmonary alveoli and compression of septal capillaries. [11] Alveolar macrophages stained CD 68+ (smoker cells) may be washed from the alveoli to heart allowing its detection, as well as stimulation of certain subsets of myelomonocytes in lung tissues [8], though the validity of such remains low from a practical point of view. In addition, aspirated particles such as plant material in the distal bronchioles may be suggestive of ante-mortem aspiration.

Paltauf's spots

These are subpleural haemorrhages located in middle lobe fissure of about the size of a fingernail due to rupture of capillaries by overdistension and haemolysis by fresh water drowning.

Haemorrhage in neck muscles

The strap muscles and posterior occipital muscles may show tiny haemorrhages and altered histological appearance of the myofibrils with fiber degeneration, abnormal clumps of red material and ragged red fibers, owing to anoxic and ischaemic insult secondary to violent convulsive movements. At an ultra-structural level there is myofibrillar disruption and abnormal mitochondria. [12] A prudent approach is to exclude a mechanical cause before ascribing such to the effects of drowning.

Spleen

A contracted and anaemic spleen due to hypoperfusion and sympathetic stimulation with vasoconstriction is often nonspecific. [8]

Mastoid ear haemorrhages

Haemorrhage into ear compartment occurs as a result of pressure difference subsequent to blockage of Eustachian tube by water. [8,9]

Aspiration of fluid in the sphenoidal sinus:

“Svechnikov's sign” refers to presence of fluid (about 9 ml) in sphenoid and maxillary sinus by water penetration, which could also occur during postmortem. [7,8] It has been studied in literature with recent attempt to quantify and be detected by postmortem CT scan. [13]

Gastric dilatation

“Wydler's sign” refers to swallowing of water with resultant layer of sediment separating into three layers. This is also reported in recent postmortem imaging modalities with a certain degree of diagnostic confidence. [14] Oesophageal mucosal tears can be found occasionally due to distension by water. The presence of superficial radial ruptures of gastric mucosa is referred as "Sehrt's sign".

Ancillary Investigations

These tools can diagnose drowning with a higher degree of confidence, yet their limitations should be observed at the same time.

Histology

A differential staining of the intimal of aortic and pulmonary trunk is reported in the literature between saltwater and freshwater drowning. [15]

Immunohistochemical staining

Intrarenal aquaporin-2 (AQP2), intracerebral expression of aquaporin-4, aquaporin-5, HSP70, fibronectin are studied and reported with variable results. Surfactant protein A (SP-A) is produced by type II alveolar cells and showed increased expression with granular pattern in drowning case, despite that these stains could not readily differentiate between fresh and salt water drowning. AQP2, a channel protein for controlling flow of water molecules in the cellular interface, has shown apical expression in the apical membrane of the collecting in salt water drowning. [16] Arginine-vasopressin (AVP) was similarly expressed in the cytoplasm of renal tubules. Both have potentially served as markers to distinguish between salt and fresh water drowning, accounted by the increased binding and expression in a hyperosmolar environment. [17] While differentiation is necessary to exclude unlawful disposal of body, this can occur "naturally" when the body was dragged by sea currents from river in some regions.

Biochemistry

There are literatures studying derangement of electrolytes including sodium, chloride, and magnesium between left and right ventricles basing on the effect of hypertonic and hypotonic action of the aspirated water in drowning, referred as the “Getter’s test”. Results were not promising and appeared to be controversial and not adopted for routine use. Strontium was also studied to a certain extent as an indicator of drowning. It has been reported that a difference of 75 µg/L between cardiac chambers could be an indicator of drowning. This test also falls short if the drowning medium has relatively low strontium concentration. [7,8]

Diatom test

This test has often been quoted as a gold standard for some to prove that drowning has occurred. Diatoms are microscopic unicellular algae coated with silica that exist in soil, water and atmosphere. If an individual is drowned in fluid which contains diatoms, they may be identified in the lungs and other organs if circulation is maintained at the time of aspiration. The diatoms can reach various organs such as brain, kidney, liver and bone marrow (femur being the most protected bodily compartment therefore its detection is generally regarding as true positive). The technique in collection of proper bodily samples should be strictly free from environmental contamination. Aided by the oxidizing property of strong acids, detergent or enzyme, the rest of the diatom tissue is consumed leaving a pellet to be centrifuged and then examined microscopically. [1,7,8,11,18] A sample of water must be taken from the suspected site of drowning for comparison. One should notice that a negative result does not rule out drowning as the cause of death.

Its application in cases with advanced decomposition explained why it is often regarded as a gold standard. [19] The confounding factor is often the presence and concentration of diatoms in the environment plus the amount being aspirated. Unfortunately there is scanty environmental data about the species and frequency of their occurrence in local waters. Much data is needed for quantification for the profile of these algae in the environment, before designing an appropriate cut off value and proper positive species identification to achieve a reasonable sensitivity and specificity. Comparison may not be possible when the original site of drowning is unknown.

Postmortem imaging

Postmortem CT scan may show accumulation of aspirated fluid in the maxillary and sphenoidal sinuses (Svechnikov's sign), apart from detection of fluid in trachea and patchy ground glass opacities in the lung parenchyma. In another study, the presence of three layers consisting frothy material, fluid materials and dense component, visualized via different image contrasting features [13,14]. Care should be exercised during transportation as movement of body may result in reshuffling of content.

Conclusion

Despite ever expanding literature on the research about the pathophysiology and findings, as well as validity of ancillary investigations, pathologists are still facing challenges with vague circumstantial information, presence of ante/post-mortem trauma, decomposition changes, as well as non-specific autopsy findings. Nevertheless, as part of the indispensable team in death investigation, pathologists are obliged to take a proactive role in analyzing all available findings which might eventually shed light on any interpretable direction despite circumstantial evidence might still remain unclear. An inquest may be held after careful consideration by the Coroner and this has been the practice adopted to rebut unfounded allegations and refute rumors, when submitted evidence would be intensely examined. It is hoped that evidence presented and testimony of witnesses can address the appropriate issues and allow the next-of-kin to understand the circumstances before the final moment.

Reference

1. Dettmeyer RB, Verhoff MA, Schütz HF. Forensic Medicine: Fundamentals and Perspectives. 1st ed. Springer; 2014. 243-260 p.
2. Byard RW. Drowning and near drowning-definitions and terminology. Forensic Sci Med Pathol. 2017 Dec;13(4):529-530. doi: 10.1007/s12024-017-9890-5. Epub 2017 Jun 20.
3. Hong Kong Judiciary. Coroners’ Report 2018. Hong Kong; 2019. 62-73 p. Department of Health, HKSAR. Hong Kong Drowning Report. Hong Kong; 2019. 8-12 p.
4. Armstrong EJ, Erskine KL. Investigation of Drowning Deaths: A Practical Review. Acad Forensic Pathol. 2018 Mar;8(1):8-43. doi: 10.23907/2018.002. Epub 2018 Mar 7.
5. Armstrong EJ, Erskine KL. Water-Related Death Investigation Practical Methods and Forensic Applications. 1st edition. CRC Press; 2013. 27-149 p.
6. Shkrum MJ, Ramsay DA. Forensic Pathology of Trauma: Common Problems for the Pathologist. 1st ed. Humana Press; 2007. 243-293 p.
7. Lunetta P, Modell JH. Macroscopical, Microscopical and Laboratory Findings in Drowning Victims: A Comprehensive Review. Forensic Pathology Review Volume 3. 1st ed. Humana Press; 2005. 3-77 p.
8. Leth PM. Homicide by drowning. Forensic Sci Med Pathol. 2019 Jun;15(2):233-238. doi: 10.1007/s12024-018-0065-9. Epub 2019 Jan 5.
9. Byard RW. Drowning deaths in rivers. Forensic Sci Med Pathol. 2017 Sep;13(3):388-389. doi: 10.1007/s12024-017-9857-6. Epub 2017 Mar 11.
10. Dettmeyer RB. Forensic Histopathology: Fundamentals and Perspectives. 2nd ed. Springer; 2018. 60-65 p.
11. Girela-López E, Ruz-Caracuel I, Beltrán C, Jimena I, Leiva-Cepas F, Jiménez-Reina L, Peña J. Histological Changes in Skeletal Muscle During Death by Drowning: An Experimental Study. Am J Forensic Med Pathol. 2016 Jun;37(2):118-26. doi: 10.1097/PAF.0000000000000233.
12. Lo Re G, Vernuccio F, Galfano MC, Picone D, Milone L, La Tona G, Argo A, Zerbo S, Salerno S, Procaccianti P, Midiri M, Lagalla R. Role of virtopsy in the post-mortem diagnosis of drownig. Radiol Med. 2015 Mar;120(3):304-8. doi: 10.1007/s11547-014-0438-4. Epub 2014 Jul 11.
13. Gotsmy W, Lombardo P, Jackowski C, Brencicova E, Zech WD. Layering of stomach contents in drowning cases in post-mortem computed tomography compared to forensic autopsy. Int J Legal Med. 2019 Jan;133(1):181-188. doi: 10.1007/s00414-018-1850-4. Epub 2018 Apr 24.
14. Byard RW. Aortic intimal staining in drowning. Forensic Sci Med Pathol. 2015 Sep; 11(3):442-4. doi: 10.1007/s12024-014-9563-6. Epub 2014 Apr 22.
15. Barranco R, Castiglioni C, Ventura F, Fracasso T. Immunohistochemical expression of P-selectin, SP-A, HSP70, aquaporin 5, and fibronectin in saltwater drowning and freshwater drowning. Int J Legal Med. 2019 Sep;133(5):1461-1467. doi: 10.1007/s00414-019-02105-1. Epub 2019 Jun 20.
16. Barranco R, Ventura F, Fracasso T. Immunohistochemical renal expression of aquaporin 2, arginine-vasopressin, vasopressin receptor 2, and renin in saltwater drowning and freshwater drowning. Int J Legal Med. 2020 Apr 2. doi: 10.1007/s00414-020-02274-4. [Epub ahead of print]
17. Hürlimann J, Feer P, Elber F, Niederberger K, Dirnhofer R, Wyler D. Diatom detection in the diagnosis of death by drowning. Int J Legal Med. 2000;114(1-2):6-14.
18. Nobuhiro Y, Eiji K, Shuji K. Diatom and Laboratory Tests to Support a Conclusion of Death by Drowning. Essentials of Autopsy Practice Innovations, Updates and Advance in Practice. 1st ed. Springer; 2013. 1-36 p.

Results of College Written Exam in Chemical Pathology & Clinical Microbiology and Infection 2020
 

EXAM NO.	RESULT
E20114	PASS
E20115	PASS
E20116	FAIL
E20217	PASS
E20218	PASS
E20219	FAIL

Candidates who failed in written exam cannot proceed further in Membership or Fellowship Assessment in 2020.
Passed candidates can proceed further in Membership or Fellowship Assessment in 2020.

PRESS STATEMENT

Use of Over-the-counter COVID-19 Test Kits

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The College has noticed that a variety of over-the-counter Coronavirus Disease 2019 (COVID-19) self-test kits are being promoted in the market. We are concerned that the public could be misled by the results of these kits.

These over-the-counter test kits usually utilize pinprick blood samples to detect IgG or IgM antibodies against the SARS-CoV-2 virus. Antibodies are produced over days to weeks after infection; the level and timing of response vary among individuals. The performance of these kits, including sensitivity and specificity (i.e. respectively whether the test can accurately exclude COVID-19 infection and whether a positive result is reliable to indicate actual infection), also varies among assays. Thus, the public must be aware of the risk of false negative and false positive results.

A false negative result may cause a false sense of security, which could potentially increase transmission of the virus to others and result in delay in seeking medical consultation and management. On the other hand, a false positive result will lead to undue anxiety and unnecessary investigations, and even public health measures such as isolation of the person and his or her close contacts.

The College reiterates that the current test of choice for the diagnosis of active COVID-19 infection remains polymerase chain reaction (PCR)-based tests detecting viral nucleic acids. The detection of antibodies is neither a suitable nor a reliable alternative. The College urges the public to seek advice from medical professionals if COVID-19 infection is suspected.

End / Wednesday / 29 April 2020

Issued at HKT 14:00

hkcpath@hkcpath.org

Tel: +852 2871 8756

新聞稿

就市面上出售的新型冠狀病毒快速測試之聲明

下載原稿

近日坊間出現各式各樣的新型冠狀病毒快速測試,並透過不同媒體銷售。惟快速測試結果存疑，有誤導公眾之嫌,本學院非常關注。

市面上售賣之試劑盒，一般採用針刺血液樣本來檢測 SARS-CoV-2 病毒的 IgM 或 IgG 抗體。抗體於感染後數天至數週方能達至可偵測的水平，抗體之濃度及產生之時間亦因人而異。市場上不同牌子之測試劑,其敏感性 (sensitivity) 和特異性 (specificity) 不盡相同，因此市民應注意有假陰性和假陽性 結果之風險。

假陰性結果會令市民錯誤以為自己未有受感染，從而潛在增加將病毒傳播給他人的風險,及導致延誤最佳診治的時間。另一方面，假陽性結果則會引致不必要的焦慮,多重覆檢,甚至需要採取公共衞生措施，如本人及密切接觸者的隔離檢疫。

本學院重申，目前診斷新型冠狀病毒以聚合酶鏈反應(PCR)測試病毒核酸為首選。現時市場上出售之快速抗體測試並不適合及不可靠。本學院呼籲公眾如懷疑自己受感染,須及早向醫生求醫。

2020 年 4 月 29 日 (星期三) 2 時正

hkcpath@hkcpath.org

Tel: +852 2871 8756

Liver injury associated with immune checkpoint inhibitors - update on clinicopathological features

Volume 15, Issue 1, January 2020  (download full article in pdf)

Editorial note:

Immune checkpoint inhibitors revolutionize the field of immuno-oncology. They have demonstrated great potential in a wide range of adult cancers by reaching long-lasting objective responses and prolonging survival. Through completed and on-ongoing clinical trials, their indications continue to expand among different cancer types. However, one of their limitations is immune-related adverse events, which are most frequently reported in skin, gastrointestinal tract, and endocrine organs. Immune-related adverse events in liver are less common hepatotoxicity but still reported up to 4 to 10% of patients receiving immune checkpoint inhibitors. This Topical Update provides a concise review on the clinicopathological features of liver injury associated with immune checkpoint inhibitors. We welcome any feedback or suggestions. Please direct them to Dr. Anthony Chan (e-mail: awh_chan@alumni.cuhk.net) of Education Committee, the Hong Kong College of Pathologists. Opinions expressed are those of the authors or named individuals, and are not necessarily those of the Hong Kong College of Pathologists.

Dr. Regina Lo

Department of Pathology & State Key Laboratory of Liver Research

The University of Hong Kong

Current applications of immune checkpoint inhibitors

Immune checkpoint inhibitors [ICPI] have been introduced as a form of targeted therapy for human cancers. They exert anti-tumor effects by potentiating T cell functions via removing the inhibitory signals. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) are receptors located on T cells. Ligand-receptor interactions lead to inhibition of T cell activation, therefore suppressing T cell activity against tumor cells ⁽¹⁾. Currently, anti-PD1/PD-1 ligand (PD-L1) and anti-CTLA-4 are the two major forms of ICPI by exploiting an antagonistic approach using specific antibodies that target PD-1 and CTLA-4, respectively. Thus far, several ICPIs were approved by the US Food and Drug Administration for treating cancer ⁽²⁾. Nivolumab and pembrolizumab are FDA approved frontline anti-PD1 agents, while ipilimumab is an anti-CTLA-4 agent. These drugs are given either alone or in combination. Currently there are a number of on-going phase III/IV clinical trials with ICPI for various types of cancers ⁽³⁾.

Clinical features of hepatotoxicity associated with ICPI

Despite the encouraging clinical efficacy, adverse reactions related to ICPI administration have been observed, among which dermatological, gastrointestinal, endocrine manifestations were most frequently reported. These reactions are believed to result from the immune response elicited toward various organs. A meta-analysis of 17 studies revealed an increased risk of all-grade hepatotoxicity with ICPI compared with controls (pooled OR 4.10; PD-1 subgroup 1.94; CTLA-4 5.01) ⁽⁴⁾. Among all immune-related adverse reactions, hepatotoxicity was observed in a relatively small proportion of cases (up to 4-10%) in most reports ^{(2, 5-9)}. Susceptibility of adverse reactions in the liver appears to be dependent on the primary cancer, regimen/dose of ICPI, and host factors. It was reported that patients receiving ICPI for HCC were at a higher risk of hepatotoxicity in terms of transaminases levels compared with lung cancer and melanoma ⁽¹⁰⁾. Moreover, combination therapy or a higher dose of ICPI was associated with increased risk of hepatic injury ^{(6, 9, 11, 12)}. Patients may present with fever and jaundice but can also be asymptomatic ^(13,14). The median time from the first dose to immune-related hepatoxicity was 14.1 weeks (9.4–19.7) for anti-PD-1, 9.9 weeks (6.1–14.7) for anti-CTLA4, and 2.9 weeks for combined therapy ⁽¹⁵⁾. The biochemical derangement is usually of a hepatitic or mixed hepatitic/cholestatic pattern. Radiological findings most of the time do not offer additional diagnostic information. In general, hepatotoxicity associated with ICPI is classified according to Common Terminology Criteria for Adverse Events by the National Cancer Institute (CTCAE). This system comprises grades 1-5 (with grade 5 being fatal) based on the serum levels of AST, ALT, ALP, GGT and total bilirubin. Having said that, elevated bilirubin is a less frequent phenomenon than most forms of drug-induced liver injury.

Histological features of liver injury associated with ICPI

The commonest histological features of ICPI-associated hepatotoxicity are lobular hepatitis, portal lymphoid infiltrates and variable degrees of hepatocytic necrosis ^(16-19). A predominant biliary pattern has been reported but is much less frequently encountered ^{(20, 21)}. Cholestasis is not commonly seen, with bland cholestasis reported in 1 of 10 cases treated with pembrolizumab ⁽²²⁾. Two cases of ICPI-induced hepatitis histologically presenting with fibrin-ring granulomas have also been reported ⁽²³⁾. Steatosis is rare. Some histological features may be more readily observed with the use of a specific type of inhibitor. For instance, microgranulomas and central vein endotheliitis were seen in patients who received anti-CTLA4 therapy. With anti-PD1 therapy, more prominent portal tract inflammation was encountered. In contrast to autoimmune hepatitis, plasma cells are usually low in number ⁽²⁴⁾, which is line with the observation that serum IgG level is mostly normal and autoimmune serological markers are negative. Likewise, in a report comparing 7 cases of ICPI-associated hepatitis versus 10 cases of AIH and 10 cases of drug-induced liver injury (DILI) ⁽²⁴⁾, hepatocytic rosettes and emperipolesis were less commonly observed than AIH. When compared with DILI, bile plugs and eosinophils were less readily seen in ICPI-associated hepatitis. On immunohistochemical delineation of the lymphoid cell population in ICPI-associated hepatitis, several reports have consistently demonstrated a predominance of CD8+ lymphocytes ^{(17, 18, 22)}. This could be distinguishing feature with AIH, in which CD20+ or CD4+ lymphoid cells are frequently encountered.

Diagnostic considerations and implications

The diagnosis of ICPI-liver injury can seldom be made by histology alone as there are no pathognomonic features. Before attributing the cause to ICPI, potential etiologies for liver function derangement should be considered. In particular, exclusion of hepatic involvement by tumor and viral hepatitis is needed. According to a recent report, among 491 patients treated with pembrolizumab for melanoma, lung cancer or urothelial cancer, 70 developed liver injury. Among which, a probably drug-related cause was only made in 20 cases after adjudication ⁽²⁵⁾. Liver histology can help to exclude some differential diagnoses and assess the severity of liver tissue injury, which could be useful to guide management plan. The treatment options for adverse reactions would depend on the severity, and include withdrawal/discontinuation of ICPI, corticosteroids (oral or IV) +/- additional immunosuppressant e.g. mycophenolate mofetil ⁽²⁶⁾. The drugs are usually permanently discontinued in cases presenting with Grade 3 or Grade 4 adverse reactions. There are no standard guidelines with reference to reintroducing ICPI after recovery from Grade 1-2 adverse reactions. As far as histology is concerned, it remains an open question whether histological parameters could offer added values in the grading of ICPI-associated hepatotoxicity. Besides, further studies are awaited to better understand the histological features associated different types of ICPI, and to depict the development and progression of fibrosis in this subset of drug-induced liver injury.

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6. Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(13):1270-1.
7. Motzer RJ, Rini BI, McDermott DF, Redman BG, Kuzel TM, Harrison MR, et al. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol. 2015;33(13):1430-7.
8. Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):2691-7.
9. Cheung V, Gupta T, Payne M, Middleton MR, Collier JD, Simmons A, et al. Immunotherapy-related hepatitis: real-world experience from a tertiary centre. Frontline Gastroenterol. 2019;10(4):364-71.
10. Brown ZJ, Heinrich B, Steinberg SM, Yu SJ, Greten TF. Safety in treatment of hepatocellular carcinoma with immune checkpoint inhibitors as compared to melanoma and non-small cell lung cancer. J Immunother Cancer. 2017;5(1):93.
11. Weber JS, Postow M, Lao CD, Schadendorf D. Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. Oncologist. 2016;21(10):1230-40.
12. Sanjeevaiah A, Kerr T, Beg MS. Approach and management of checkpoint inhibitor-related immune hepatitis. J Gastrointest Oncol. 2018;9(1):220-4
13. Johnson DB, Chandra S, Sosman JA. Immune Checkpoint Inhibitor Toxicity in 2018. JAMA. 2018;320(16):1702-3.
14. De Martin E, Michot JM, Papouin B, Champiat S, Mateus C, Lambotte O, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol. 2018;68(6):1181-90.
15. Gauci ML, Baroudjian B, Zeboulon C, Pages C, Pote N, Roux O, et al. Immune-related hepatitis with immunotherapy: Are corticosteroids always needed? J Hepatol. 2018;69(2):548-50.
16. Karamchandani DM, Chetty R. Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists' perspective. J Clin Pathol 2018;71(8):665-71.
17. Kleiner DE, Berman D. Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma. Dig Dis Sci. 2012;57(8):2233-40.
18. Johncilla M, Misdraji J, Pratt DS, Agoston AT, Lauwers GY, Srivastava A, et al. Ipilimumab-associated Hepatitis: Clinicopathologic Characterization in a Series of 11 Cases. Am J Surg Pathol. 2015;39(8):1075-84.
19. Zen Y, Yeh MM. Checkpoint inhibitor-induced liver injury: A novel form of liver disease emerging in the era of cancer immunotherapy. Semin Diagn Pathol. 2019.
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