Malaysian Journal of Pathology最新文献

Introduction: Haemoglobin (Hb) Quong Sze is a non-deletional α-thalassaemia subtype that occurs due to missense mutation at codon 125 of the HBA2 gene. Interaction between Hb QS with Southeast Asian double α-globin gene deletion results in non-deletional HbH disease, which is more severe than deletional HbH.

Case report: A 3-month-old baby boy was presented with neonatal anaemia and mild hepatomegaly. Full blood count revealed severe hypochromic microcytic anaemia. There was an abundance of HbH inclusion bodies in his red blood cells. High-performance liquid chromatography showed a reduced HbA2 level with the presence of pre-run peak. Capillary electrophoresis showed the presence of HbH and Hb Barts. Molecular analysis found a common α⁰-thalassaemia (--^SEA) in one allele and mutation in codon 125 in the other allele.

Discussion: Non-deletional HbH disease due to a combination of deletional and non-deletional mutations may present with severe clinical manifestations than those with deletion mutations, which warrants accurate diagnosis using molecular techniques.

Congenital Adrenal Hyperplasia (CAH) is primarily caused by mutations in genes responsible to produce enzymes involved in the synthesis of cortisol, aldosterone, or both. This study aims to determine the prevalence, sociodemographic distributions, and clinical factors associated with CAH in the Malaysian population. This retrospective study reviewed laboratory records of 17-hydroxyprogesterone (17OHP) test requests received at the Institute for Medical Research, Kuala Lumpur from January 2021 to December 2021. Descriptive statistics were employed for most variables, and logistic regression analysis was conducted to determine factors associated with CAH. The dataset included a total of 775 patients (64.2%) from 1,207 test requests screened. The prevalence of newly diagnosed CAH in the year 2021 was 13.5% (n=105). The majority were Malays (15.1%), neonates (13.8%), and females (45.7%). Higher baseline 17-OHP (cOR:1.31, 95% CI:1.19, 1.45), unknown gender at birth (cOR:7.82, 95% CI:2.86, 21.37), and neonatal age group at presentation (cOR:29.3, 95% CI:12.07, 71.03) independently predict CAH. The high prevalence of CAH in our region has been speculated to be due to the cultural consanguinity norms, resulting in genetic aberrations. CAH may manifest as ambiguous genitalia, particularly in females, due to the overproduction of androgens in-utero, resulting in atypical genitalia, necessitating thorough investigation. To the best of our knowledge, the data presented are the latest report on CAH prevalence, distribution, and description of positive CAH cases in the Malaysian population. These findings are essential for further public health planning to improve the diagnostic capacity and clinical management of CAH.

Introduction: Thalassemia and haemoglobinopathies are relatively common among Malaysians. One of the rare haemoglobinopathies reported is Haemoglobin (Hb) Arya, which occurs due to substitution of aspartic acid at residue 47 of the alpha chain by asparagine. Here, we report the detection of Hb Arya in a Malaysian family, which was detected incidentally during family screening.

Case report: A 16 years-old girl, clinically asymptomatic was noted to have low mean corpuscular haemoglobin (MCV) with normal Hb level. Hb analysis using capillary electrophoresis (CE) showed reduced Hb A of 76.5%, Hb A2 of 1.6% with presence of small peak at Zone 1 likely A2'. There was also a small peak noted at Hb D zone and Hb S zones which quantified as 1.5% and 20% respectively. Supplementary test by high performance liquid chromatography (HPLC) showed a prominent peak at D-window (19.6%) and a small peak at S-window (0.6%). DNA analysis revealed a heterozygous state of α2 codon 47 Hb Arya mutation. Subsequent family study showed a similar mutation in the father and sister of the index case.

Conclusion: Very few reports are available up to date regarding Hb Arya. This report highlights the rare haemoglobinopathy in a Malay family in Malaysia that contributes to the growing literature of this rare haemoglobin variant.

Introduction: Electrocution related death remains an ambiguous judgement and requires numerous valid evidence for proper medico-legal diagnosis. While the presence of electrical burn marks is a significant macroscopic indicator, it can be absent, especially on moist skin. The electrical mark still represents a fundamental indicator above all in the medico-legal field, but the identification of pathognomonic elements and signs not limited to the skin alone could be a valid help in the future, especially in unclear cases.

Case report: The deceased was brought-in-dead to the hospital from their workplace, with no signs of fatal natural diseases. External examination revealed a Y-shaped burn mark on the right side of the neck and collapsed blisters with greying rings on both heels. Internal examination showed no alarming findings. Further, histopathological analysis of the foot blisters and neck burn revealed intraepidermal detachment, elongated nuclei, and coagulative necrosis. Notably, the presence of muscle fibre casts in kidney tubules and microthrombi in lung sections which indicate rhabdomyolysis and vascular thrombosis supported electrocution-related death.

Conclusion: These positive findings of the electrical burn marks externally and significant histopathological changes, collectively support the death was due to electrocution, after excluding any major, fatal injuries. Albeit, a detailed inspection of the crime scene plays an important role, in order to classify the electrocution related death.

Diagnosis of extraintestinal microsporidiosis is always hampered due to non-specific symptoms and difficulty in diagnosis. This study aimed to compare the diagnostic utility of blood and faecal-based polymerase chain reaction (PCR) to detect microsporidiosis in immunocompromised patients. A total of 42 immunocompromised patients consisting of HIV-infected and chemotherapy-treated patients were enrolled. Paired faecal and blood samples were collected and subjected to PCR to detect Enterocytozoon bieneusi and Encephalitozoon spp. Faecal samples were microscopically screened for microsporidia spores. Overall, 42.9% (18/42) of patients were positive for microsporidiosis. Of this, 19.0% (8/42) and 4.8% (2/42) were positive by blood and stool PCR respectively. Meanwhile, 33.3% (14/42) of the faecal specimens were microscopically positive. Among the positive patients, 22.2% (4/18) had microsporidia confirmed by blood PCR and stool microscopy, suggestive of dissemination. Interestingly, the stool specimen in which microsporidia spores were detected via microscopy is not positive via PCR method. This highlights the limitation of the faecal-based detection method and the important use of blood samples for diagnosing extraintestinal microsporidiosis. Only E. bieneusi species were detected in all PCR-positive samples. This study highlights the diagnostic value of blood PCR in diagnosing extraintestinal microsporidiosis infections.

Introduction: The prevalence of suicide presents a significant public health challenge globally, affecting diverse populations around the world. This study is motivated by the urgency to tackle suicide as a crucial public health issue on a global level, according to the United Nations Sustainable Development Goals and the General Programme of Work and Mental Health Action by the World Health Organization.

Materials and methods: The research was performed at the Forensic Unit of Hospital Canselor Tuanku Muhriz, spanning a retrospective analysis covering 2012 to 2021. A descriptive analysis was conducted to analyse the patterns of suicide and the sociodemographic characteristics of the cases.

Results: The findings show monthly variations and a recent increase in suicide rates, especially during the pandemic of COVID-19. Analysis of suicide methods indicates that hanging is the most common suicide method, which accounts for almost half of the sample population, followed by jumping from a height and burning charcoal. Adult males are primarily implicated in suicidal acts, and the study reveals unique trends among different age groups, genders and employment statuses.

Conclusion: This study aims to offer thorough insights and comprehension into suicide within the Malaysian sociodemographic framework. Consequently, it could furnish valuable insights for public health authorities and governmental bodies.

Introduction: Diabetic retinopathy is characterised by retinal vascular impairment. A number of aberrant microRNAs (miRNAs) have a role in the pathophysiology of vascular dysfunction. However, the relevance of miR-424 in retinal vascular endothelial cell dysfunction during hyperglycemia stress remains unknown. The purpose of this study is to investigate this issue.

Materials and methods: Rhesus macaque choroid retinal endothelial cell line (RF/6A) cells were cultivated in normal glucose (NG) and high glucose (HG) conditions. The mRNA expression of miR-424 and Cyclin D1 (CCND1) was quantified using qPCR, and the protein quantity of CCND1 was detected using Western Blot. miR-424 mimics, miR-424 inhibitors, miR-424 inhibitor+ siRNA-CCND1 or vehicle molecules were transfected into RF/6A cells. MTT test was used to assess cell proliferation, and flow cytometric analysis was used to assess cell cycle. The interaction between miR-424 and CCND1 was predicted using bioinformatics and validated using dual luciferase reporter analysis.

Results: miR-424 was up-regulated, and cell viability was reduced in HG compared to NG. By reversing the expression of miR-424 in certain situations, the phenotypes can be changed. CCND1 has been identified as a miR-424 target gene, and it may be regulated at the transcriptional and translational levels. Manipulation of silencing CCND1 can counteract the effect of transfecting miR-424 inhibitor into RF/6A cells under HG such as proliferation stimulation.

Conclusions: Our findings indicate that miR-424 plays an important role in hyperglycemia induced ARPE-19 cells damage, and it could be a new therapeutic target for DR by preventing retinal vascular cells from HG-induced injury.

Introduction: Young onset colorectal cancer (YOCRC) is a heterogenous CRC phenotype with an increasing trend globally. This study aims to determine FOXP3+ Treg cells, Mismatch Repair (MMR) proteins, and proto-oncogene B-Raf (BRAF) V600E status among YOCRC patients at Hospital Universiti Sains Malaysia.

Materials and methods: This was a retrospective study of YOCRC (<50 years) over 8 years (January 2013 to December 2021). Immunohistochemistry staining of FOXP3, BRAFV600E, and MMR protein expression was performed using monoclonal antibodies. The staining intensity and percentage of positive cells were used to evaluate the staining using immunoreactive scoring. All data were analysed using descriptive and correlation statistics. A p-value of ≤ 0.05 was taken as statistically significant.

Results: A total of 65 YOCRC patients were diagnosed, out of which 53.8% had proficient MMR (pMMR) with a mean age of 41, while 46.2% had deficient MMR (dMMR) with a mean age of 35.5. The pMMR with the BRAFV600E+ group expressed higher FOXP3+Tregs (54.2%) than the dMMR with the BRAFV600E+ group (22.9%). Patients with lower FOXP3+Tregs were observed more in dMMR with BRAFV600E- (47%) than in pMMR with BRAFV600E- (5.9%). There was a statistically significant association between the density of expressed FOXP3+Tregs with MMR and BRAFV600E status (p=0.002).

Conclusion: While most of the YOCRC had pMMR, others exhibited dMMR with loss of one or more MMR proteins. The presence of BRAFV600E demonstrated the YOCRC's sporadic nature. A high FOXP3+Treg expression was significantly associated with MMR and BRAFV600E status. Future research must be expanded to cover other hospitals to increase the sample size and include MLH1 hypermethylation testing.

Introduction: Blood culture contamination remains a dilemma issue in the diagnosis of bloodstream infection. However, to date, there is no national data on blood culture contamination and the common organism isolated in Malaysia. This is a pioneer multi-centre study involving public hospitals with medical microbiologists in Malaysia to determine the blood culture contamination rate and the common organism isolated.

Materials and methods: This retrospective cross-sectional study involved record review of all blood culture results over 9 months period from 1st January 2018 until 30th September 2018 in 27 government hospitals in Malaysia. For each positive culture result, the type of isolated organism was classified to represent true bacteraemia or contamination.

Results: We analysed 448,109 blood culture records from the participating hospitals. The blood culture positivity rate was 12.5% (57395 of 448109) and 25.0% (14367 of 57395) of the positive blood culture represents contamination. The national blood culture contamination rate in Malaysia was 3.2%. The contamination rate in the adult population was significantly higher than the paediatric population (3.6% vs. 2.6%; p<0.001). The blood contamination rate by institution ranged from 1.5% to 6.8%. The most frequently isolated microorganisms in the contaminated cultures were coagulase-negative staphylococci (71.0%).

Conclusion: Blood culture contamination is a major issue that warrants priority in recognition, and interventions should be implemented to reduce the blood contamination rate in Malaysia.

Talaromyces marneffei is a thermally dimorphic fungus which causes opportunistic infections in immunocompromised individuals. The diagnosis of T. marneffei infection rests on the microscopic demonstration of the fungus in the tissues and/or isolation of the fungus from clinical specimens. In this report, we discuss a case involving a 23-year-old man who presented with a history of intermittent fever, cough and constitutional symptoms. Clinically, the patient exhibited pallor, jaundice, generalized seborrhoeic dermatitis, hepatomegaly, and small palpable cervical lymph nodes. A computed tomography (CT) scan of the abdomen showed homogenous hypodense lesions in both liver lobes. HIV screening result was reactive. Microscopic examination of the bone marrow aspirate smear and trephine biopsy identified fungal bodies, and culture of the marrow aspirate confirmed the presence of T. marneffei. Notably, the liver biopsy revealed Burkitt lymphoma alongside fungal bodies. He was treated with intravenous Amphotericin B but ultimately succumbed to the illness due to severe metabolic acidosis and multiorgan failure. This case underscores the importance of presumptive diagnosis through morphological or histological examination of bone marrow samples, as microbiologic culture methods can be time-consuming. Timely diagnosis and aggressive treatment are critical in managing patients with T. marneffei infection.