1.Phage typing of methicillin-resistant Staphylococcus aureus.
The Malaysian journal of pathology 1990;12(2):107-9
448 isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical specimens of patients from the University Hospital, Kuala Lumpur, were phage-typed. These included 35 strains causing two separate outbreaks of infection, one in surgical Ward 6B and another in the Special Care Nursery (SCN). Antibiograms of these outbreak strains in Ward 6B and SCN were entirely different. Phage-typing revealed that 72% of the MRSA isolates were typable. They were typed entirely by Group III phages, the majority (76%) of which were phage type 85. There was only one isolate in SCN which was typed by Group I (phage 80) and Group III phages. None were typed by phages 94, 95, 96 and Group II phages. 14.6% of the typable isolates gave the long pattern reaction of the phage 6/47/54/75/77/83A/84/85 complex. The majority of the outbreak strains in Ward 6B were of phage type 85, whereas those in the SCN were all of the 6/47/54/75/77/83A/84 phage pattern with the exception of one isolate which was also typed by phage 80, a Group I phage.
Bacteriophages
;
Group I
;
Staphylococcus aureus
;
Patients' Rooms
;
Methicillin
2.Therapeutic potentials of neural stem cells in Alzheimer’s disease
The Malaysian Journal of Pathology 2020;42(2):157-170
The commonest cause of dementia among the elderly population is Alzheimer’s disease (AD). It
is a health concern globally as the number of people affected by dementia worldwide is rapidly
increasing. Several genes have been linked to AD and the pathogenesis of the disease has been
extensively and vigorously examined. Thus far, only a few drugs have been approved by the Food
and Drug Administration (FDA) for the pharmacological treatment of AD and a growing body
of research has turned to alternative options such as stem cell therapy. This review will give an
overview of the pathological and clinical aspects of AD. Although researchers have explored the
suitability and feasibility of using various types of stems cells to treat AD, this review will focus
mainly on neural stem cells (NSCs)/ neural progenitor cells (NPCs). The behaviour and properties
of NSCs will be described, accompanied by a comprehensive discussion of the therapeutic strategies
involving the use of NSCs/NPCs in the treatment of the disease
3.Gene therapy: An updated overview on the promising success stories
The Malaysian Journal of Pathology 2020;42(2):171-185
Gene therapy is a method of treatment of disease aimed at its molecular level. The progress of gene
therapy, however, was as promising as it was tardy mainly due to the limitations in the resources
and financial part of its development as well as owing to the rarity of most diseases it can offer
its benefits to. The methods of gene therapy can vary depending on factors such as the physiology
of tissue of interest, affinity of vectors to a certain type of cells, depth and accessibility of the
tissue of interest, and size of the gene to be replaced or edited. The concept behind gene therapy
has inspired scientists and clinicians alike leading to a rapid expansion of its clinical utility that
has become so widespread to not only include diseases of monogenic origin, but also polygenic
diseases, albeit not so commonly. This article delves into notable success stories of gene therapy
which has been regarded as the beacon of medical novelty expected to blossom in the near future
to provide a holistic, targeted, precise, and individualistic personalised-medicine as well as laying
out the future hopes of gene therapy in the treatment of debilitating diseases such as solid tumours,
AIDS, Tuberculosis, Diabetes Mellitus, psychiatric illnesses, which are still at a standstill, from a
gene therapy point of view
4.Different pathological processes for acute white matter lesions in multiple sclerosis
The Malaysian Journal of Pathology 2020;42(2):187-194
Introduction: Multiple sclerosis (MS) has variable clinical presentations, prognoses, pathogeneses,
and pathological patterns. We conducted a pathological review of acute MS-associated lesions that
focused on the degree of axonal injury, myelin loss, and glial reaction to determine whether the
observed demyelination was of the primary or secondary type. Materials and Methods: After searching
the records for a 15-year period at the London Health Sciences Centre Pathology Department, we
identified 8 cases of surgical acute lesion biopsies in which clinical MS diagnoses were made before
or after the biopsy. Results: The white matter pathologies in these cases could be sorted into 3
morphological patterns. The first pattern, which represents typical demyelinated plaques, was observed
in 4 cases and was characterised by nearly complete demyelination accompanied by variable degrees
of axon preservation and axonal swelling. The second pattern was observed in 3 cases and was
characterised by demyelinating lesions containing variable numbers of myelinated axons mixed with
a few demyelinated axons and variable numbers of axonal swellings. The myelinated axons ranged
from scattered fibres to bands of variable thickness, and the demyelination was a mixture of primary
and secondary demyelination. The third pattern was observed in 1 case and was characterised by
well-demarcated areas of reduced myelin staining and numerous apoptotic nuclei. Axonal staining
revealed many fragmented axons with reduced myelin staining but no definitely demyelinated axons.
Conclusion: This report shows that the predominant pathology underlying acute MS-related lesions
is not limited to demyelination but can include axonal degeneration alone or in combination with
primary demyelination which reflect different pathogenesis for these acute lesions.
5.Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia
The Malaysian Journal of Pathology 2020;42(2):195-201
Introduction: Differentiating between thalassaemia and iron deficiency anaemia (IDA) in hypochromic
anaemia is a challenge to pathologists as it influences the choice of subsequent specialized confirmatory
tests. In this study, we aimed to evaluate the performance of microcytic to hypochromic ratio (MicroR/
Hypo-He, M/H ratio) as a discriminant index in hypochromic anaemia. Materials and Methods: A
retrospective study was carried out on 318 subjects with hypochromic anaemia, which comprised
162 IDA and 156 thalassaemia trait subjects with α-thalassemia, β-thalassemia and HbE trait.
Optimal cut-off value, sensitivity and specificity of M/H ratio for thalassaemia trait discrimination
was determined using Receiver Operating Characteristic (ROC) analysis. Results: Subjects with
thalassaemia trait showed higher MicroR compared to IDA ( p< 0.001) while subjects with IDA
demonstrated higher Hypo-He than thalassaemia trait (p < 0.001). M/H ratio was significantly higher
in thalassaemia trait compared to IDA, with medians of 3.77 (interquartile range: 2.57 – 6.52) and
1.73 (interquartile range: 1.27 – 2.38), respectively (p < 0.001). M/H ratio > 2.25 was the optimal
cut-off value for discriminating thalassaemia trait from IDA in hypochromic anaemia, with the
area under ROC curve (AUC) of 0.83, sensitivity of 80.8% and specificity of 71.6%. Conclusions:
M/H ratio is a useful discriminant index to distinguish thalassaemia trait from IDA in hypochromic
anaemia prior to diagnostic analysis for thalassaemia confirmation. High M/H ratio is suggestive
of thalassaemia trait than of IDA. However, more studies are required to establish the role of M/H
ratio as a screening tool for thalassaemia discrimination in hypochromic anaemia.
6.Screening for phaeochromocytoma in patients with acute cerebrovascular disease: Is it necessary?
The Malaysian Journal of Pathology 2020;42(2):203-207
Introduction: Phaeochromocytoma may present with uncontrolled hypertension leading to haemorrhagic
stroke (HS), ischaemic stroke (IS) and transient ischaemic attack (TIA). False elevation in the levels
of CATS/ METS has been reported in acute cerebrovascular disease. Our aim was to analyse the
frequency and pattern of elevations of CATS/METS in patients with acute cerebrovascular disease
and to determine associated factors. Materials and Methods: This is a retrospective study of 112
samples of CATS/ METS received by the laboratory over a two-year period, from patients with acute
cerebrovascular disease. CATS/METS were measured using LC/MS/MS method. Clinical details and
CATS/METS level were obtained from the database. Mann-Whitney U test and Kruskal Wallis test
were used for statistical analysis. These statistical analyses were performed using SPSS v.20.0 (IBM
Corp., Armonk, NY, USA). Results: Of the 112 patients, 39% had HS, 54% had IS and 7% had TIA.
A total of 29% of patients had elevated CATS/ METS. Elevated levels of CATS/METS were noted
in 41% and 25% of HS and IS patients, respectively (p=0.53). Median norepinephrine, epinephrine
and metanephrine levels in HS were significantly higher than IS (p< 0.05). Systolic blood pressure
was higher in those who had elevated CATS/ METS (p=0.04). Only for two patients with elevated
CATS/METS repeat testing was performed. Age, diastolic blood pressure and the time of sample
collection in relation to the presentation, for CATS/METS were not significantly different between
groups that had elevated levels of CATS/ METS versus those who did not. Conclusion: We noted
that CATS/METS were elevated in one-third of patients, especially in patients with high systolic
blood pressure. Increase in CATS/METS should be appropriately followed up with repeat testing.
Since false elevation in CATS/METS has been reported in cerebrovascular disease, screening for
phaeochromocytoma is best deferred for a month.
7.Diagnostic performance of prostate health index (PHI) in predicting prostate cancer on prostate biopsy
The Malaysian Journal of Pathology 2020;42(2):209-214
Prostate health index (PHI) has been shown to have better diagnostic accuracy in
predicting prostate cancer (PCa) in men with total prostate-specific antigen (PSA) levels between
4-10ng/ml. However, little is known of its value in men with elevated PSA beyond this range. This
study aimed to evaluate the diagnostic performance of PHI in Malaysian men with elevated PSA
values ≤ 20ng/ml. Materials and Methods: From March 2015 to August 2016, all men consecutively
undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with total PSA values ≤ 20ng/
ml were recruited. Blood samples were taken immediately before undergoing prostate biopsy.
The performance of total PSA, %fPSA, %p2PSA and PHI in determining the presence of PCa on
prostate biopsy were compared. Results: PCa was diagnosed in 25 of 84 patients (29.7%). %p2PSA
and PHI values were significantly higher (p<0.05) in patients with PCa than those without PCa.
The areas under the receiver operating characteristic curves for total PSA, %fPSA, %p2PSA and
PHI were 0.558, 0.560, 0.734 and 0.746, respectively. At 90% sensitivity, the specificity of PHI
(42.4%) was five times better than total PSA (8.5%) and two times better than %fPSA (20.3%).
By utilising PHI cut-off >22.52, 27 of 84 (32.1%) patients could have avoided undergoing biopsy.
Conclusion: Findings of our study support the potential clinical effectiveness of PHI in predicting
PCa in a wider concentration range of total PSA up to 20ng/ml.
8.A pilot study on pattern B lipoprotein profile in Malaysia
The Malaysian Journal of Pathology 2020;42(2):215-225
Dyslipidaemia is a recognised conventional risk factor for cardiovascular disease (CVD).
However, even when traditional lipid parameters are normal, CVD risk can exist. Small dense lowdensity lipoprotein cholesterol (sdLDL) has appeared as a significant risk marker for CVD. This
study aimed to determine the prevalence and associated factors of atherogenic lipoprotein Pattern
B in the Malaysian population. Materials and Methods: This cross-sectional study included 150
subjects aged 30 years and above who attended a health screening in a Malaysian tertiary institution.
Sociodemographics, clinical characteristics and laboratory parameters (lipids, glucose, and sdLDL)
were obtained. Lipoprotein subfraction was analysed using the polyacrylamide gel electrophoresis
method. Results: Malays and females made up the majority of subjects and the median age was
37 years. Normolipidaemic Pattern B was significantly higher in women (p=0.008). Significant
independent predictors of Pattern B were gender (p=0.02), race (p=0.01), body mass index (BMI)
[p=0.02] and lipid status (p=0.01). Triglyceride was the only independent predictor of sdLDL (p=0.001).
Conclusion: The prevalence of Pattern B of 33% in this study was comparatively high, of which
6.7% were normolipidaemic. Chinese males with dyslipidaemia and increased BMI independently
predicted Pattern B. Differences in triglyceride levels alone among these ethnic groups do not fully
explain the differences in the prevalence of Pattern B although it was the only lipid parameter to
independently predict sdLDL. Individuals with atherogenic normolipidaemia are at greater risk
for a CVD event as they are not included in the protective measures of primary CVD prevention.
9.CIP2A expression in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue microarray study
The Malaysian Journal of Pathology 2020;42(2):227-236
CIP2A is an oncoprotein involved in the progression of several human malignancies.
It has recently been described as a prognostic marker in many cancers. The present study aimed to
investigate the immunohistochemical expression of CIP2A in benign prostatic hyperplasia (BPH),
high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse the
association with the clinicopathological parameters in PC cases to define its role in the development and
progression of PC. Materials and Methods: Immunohistochemical staining for CIP2A was performed
on the tissue microarray sections of 105 PC, 27 HGPIN and 27 BPH tissues. The CIP2A expression
scores were compared with several clinicopathological parameters. Results: CIP2A was expressed
in 96,2% of PC, 55,6% of HGPIN and 40,7% of BPH tissues. The expression of CIP2A in PC was
significantly higher than in HGPIN (p<0.0001) and BPH (p<0.0001) cases. CIP2A expression score
was significantly associated with Gleason score (p=0.032) and lymphovascular invasion (p=0.039).
Nevertheless, there was no statistically significant association between the expression of CIP2A and
perineural invasion, pT stage, metastasis and recurrence (p>0.05). Multivariate analysis indicated
that GS, lymphovascular invasion, distant metastasis were independent prognostic factors for PC
patients but, CIP2A expression score was not found to be a prognostic factor. Additionally, there
was no significant difference between the survival times of patients according to CIP2A expression
(p=0.174). Conclusion: According to our results, the expression of CIP2A protein is increased in
PC and its expression may be involved in the development, differentiation, and aggressiveness of
PC. However, further studies are needed to confirm our findings and to clarify the role of CIP2A
in the development of PC.
10.Frequent loss of CD10 expression in follicular lymphoma with leukaemic presentation
The Malaysian Journal of Pathology 2020;42(2):237-243
Follicular lymphoma (FL) is usually a nodal lymphoma expressing CD10, rarely with
leukaemic presentation (FL-LP). Materials and Methods: We searched for FL-LP in our institution
from 2000 to 2018 and characterised the neoplastic cells by flow cytometry, immunohistochemistry
and fluorescence in situ hybridization. Thirteen (6.1%) of 212 FL cases were FL-LP, all de novo
neoplasms. The leukaemic cells were small in 12 cases and large in one. All had concurrent FL,
mostly (92%; 12/13) low-grade. The single case with large leukaemic cells had a concurrent primary
splenic low-grade FL and a double-hit large B-cell lymphoma in the marrow. Results: CD10 was
expressed in the leukaemic cells in 38% (5/13) cases by flow cytometry and in 77% (10/13) cases in
tumours (p= 0.0471). IGH/BCL2 reciprocal translocation was identified in 85% (11/13) cases. Most
patients were treated with chemotherapy. In a median follow-up time of 36 months, nine patients
were in complete remission. The 2- and 5-year survival rates were at 100% and 83%, respectively.
In this study, we characterised a series of de novo FL-LP in Taiwan. All patients had concurrent
nodal and/or tissue tumours, which might suggest that these patients seek medical help too late.
Conclusion: The lower CD10 expression rate by flow cytometry than by immunohistochemistry
might be due to different epitopes for these assays. Alternatively, loss of CD10 expression might play
a role in the pathogenesis of leukaemic change. The clinical course of FL-LP could be aggressive,
but a significant proportion of the patients obtained complete remission with chemotherapy.