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Unexpected infant death secondary to a pulmonary infiltration due to acute myelocytic leukaemia

Ben Khelil M, Chkirbene Y, Mlika M, Haouet S, Hamdoun M

Malays J Pathol, 2017 Aug;39(2):193-196.
PMID: 28866704

Acute myeloid leukaemia (AML) often presents with non-specific symptoms such as fatigue, anaemia or infection. Pulmonary involvement is uncommon in AML during the course of the disease and is usually caused by infection, haemorrhage, leukaemic pulmonary infiltrates and leukostasis. Lung localization of AML is very uncommon and potentially life threatening if not diagnosed and treated rapidly. The authors describe the sudden death of an asymptomatic five-month-infant because of a misdiagnosed lung localization of AML. Autopsy examination followed by histopathological studies showed an extensive leukostasis and extramedullary leukaemic infiltrating the lungs. Special stains and immunohistochemical studies revealed findings consistent with acute myelogenous leukaemia. This case suggests that underlying acute leukaemia should be considered as a cause of flu-like symptoms in infants. Medical personnel are urged to be alert to fever, sore throat, weakness and dyspnea that may be characteristic of serious systemic diseases.
Fulltext Ultrastructural characteristics of synovial effusion cells in some arthropathies

Kapitonova MY, Othman M

Malays J Pathol, 2004 Dec;26(2):73-87.
PMID: 16329559

OBJECTIVE: To evaluate the range of activation changes of polymorphonuclear leukocytes (PMN) and the ratio of apoptosis and necrosis in synovial effusions of patients with various arthropathies, and to reveal possible correlations with clinical variants of joint inflammation.
METHODS: Synovial effusions were aspirated from the knee joints of patients with rheumatoid arthritis (RA, 28 cases), and seronegative spondyloarthritides (SSA): Reiter's disease (RD, 9 cases), peripheral form of the ankylosing spondyloarthritis (6 cases) and psoriatic arthritis (6 cases); and primary osteoarthritis (OA, 9 cases). Cytospin preparations were processed for transmission electron microscopy and assessed for the incidence of apoptosis, necrosis, and cytophagocytic cells (CPC) in the synovial fluid (SF). The range of activation changes of the neutrophil granulocytes, the dominating cell population in the arthritic SF, was evaluated.
RESULTS: In all arthropathies under investigation most of the synovial effusion cells had intact ultrastructure with a certain amount of apoptotic cells dominating over the cells with signs of necrosis, and a few CPC. The highest rate of apoptosis was discovered in the synovial effusions of patients with RA, the lowest in those with OA, while the rate of CPC among the inflammatory joint diseases was the lowest in RA. In RA the current disease activity correlated with the incidence of apoptotic cells and CPC, while the clinical stage was related only to the CPC rate. These data suggest that in RA, despite exposure to the anti-apoptotic signals, apoptosis of the synovial effusion PMN is maintained at a significantly higher level than in non-rheumatoid arthropathies, both inflammatory (SSA) and degenerative (OA), providing elimination of the neutrophils accumulating in the joint cavity and thus stimulating resolution of the joint inflammation.
Fulltext Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death

Kapitonova MY, Mansor O

Malays J Pathol, 2003 Jun;25(1):15-27.
PMID: 16196374

OBJECTIVE: To determine in situ using TEM the balance of apoptosis and necrosis in the articular cartilage of patients with inflammatory (rheumatoid arthritis and seronegative spondyloarthritis) and degenerative (osteoarthritis) joint diseases and to establish possible correlation between the cell death rate and the matrix vesicles formation.
METHODS: Cartilage samples of the knee joint were obtained from patients with rheumatoid arthritis (RA, 18 cases), osteoarthritis (OA, 22 cases), Reiter's disease (RD, 9 cases), peripheral form of the ankylosing spondyloarthritis (AS, 6 cases) and psoriatic arthritis (PA, 6 cases) during arthroscopy or knee surgery. Normal samples taken from autopsy cases without a history of joint diseases were used as control. Samples were processed for TEM with subsequent semi-quantitative estimation of the cell death rate in the superficial, middle and deep zone of non-calcified articular cartilage, and computer-aided ultramorphometric evaluation of the matrix vesicles of different types.
RESULTS: Both apoptotic and necrotic cell death could be identified in the cartilage of patients with inflammatory joint diseases, including seronegative spondyloarthritides and degenerative arthropathies. Apoptosis dominated over necrosis in all examined arthritides, including RA patients in which necrosis of the chondrocyte was the most frequent among arthropathies, while the highest apoptotic cell death rate was discovered in OA in which it correlated with the volume and numeric density of the matrix vesicles. These data provide evidence that apoptosis may contribute to the cartilage breakdown not only in RA and OA but also in the seronegative spondyloarthritides, which had a significantly higher apoptotic rate than the normal cartilage.
Ultrastructural aspects of sylvatic dengue virus infection in Vero cell

Fish-Low CY, Abubakar S, Othman F, Chee HY

Malays J Pathol, 2019 Apr;41(1):41-46.
PMID: 31025636

INTRODUCTION: Dengue virus (DENV), the causative agent of dengue disease exists in sylvatic and endemic ecotypes. The cell morphological changes and viral morphogenesis of two dengue ecotypes were examined at the ultrastructural level to identify potential similarities and differences in the surrogate model of enzootic host.
MATERIALS AND METHODS: Vero cells were inoculated with virus at a multiplicity of infection (MOI) of 0.1. Cell cultures were harvested over a time course and processed for transmission electron microscopic imaging.
RESULTS: The filopodia protrusions on cell periphery preceded virus entry. Additionally, sylvatic DENV infection was found spreading slower than the endemic DENV. Morphogenesis of both dengue ecotypes was alike but at different level of efficiency in the permissive cells.
CONCLUSIONS: This is the first ultrastructural study on sylvatic DENV and this comparative study revealed the similarities and differences of cellular responses and morphogenesis of two dengue ecotypes in vitro. The study revealed the weaker infectivity of sylvatic DENV in the surrogate model of enzootic host, which supposed to support better replication of enzootic DENV than endemic DENV.
Ulcerated bleeding palisaded encapsulated neuroma of the tongue

Dhanuka S, Rodrigues G, Carnello S

Malays J Pathol, 2019 Aug;41(2):229-232.
PMID: 31427561

INTRODUCTION: Palisaded encapsulated neuroma (PEN) is a benign lesion of Schwann cells and its occurrence in the oral mucosa especially the tongue is very rare.
CASE REPORT: This article describes a case of a 41-year-old male, a chronic smoker with an actively bleeding, ulcerated, solitary, firm lesion on the lateral border of the tongue which had bled thrice before. A differential diagnosis of pyogenic granuloma, haemangioma, fibroma, nerve sheath tumour, salivary gland tumour and malignancy was made and surgically excised. Histopathology of the excised specimen revealed a well-circumscribed lesion with spindle-shaped cells arranged in interlacing fascicles and with the help of immunohistochemical markers confirmed it to be a PEN.
DISCUSSION: To our knowledge, this is the first description of an ulcerated PEN presented with an active bleed.
Tumours and tumour-like lesions of the eye: a clinicopathological study from Hospital University Sains Malaysia

Reddy SC, Das PK

Malays J Pathol, 1996 Dec;18(2):113-20.
PMID: 10879232

A total of 89 histopathologically proven ocular tumours and tumour-like lesions treated in Hospital University Sains Malaysia, Kubang Kerian, Kelantan over a period of nine years were reviewed for their age distribution, site of lesion and histological type. The tumours were observed in all age groups with a maximum prevalence in the first decade. Twenty lesions were malignant and 69 were benign. The eyelid was the most frequent location (51%), followed by the conjunctiva (32%). Retinoblastoma was the most common malignant tumour (10 cases) and dermoid cyst was the most common tumour-like lesion (16 cases).
Fulltext Triple negative breast cancer: the role of metabolic pathways

Dean SJ, Rhodes A

Malays J Pathol, 2014 Dec;36(3):155-62.
PMID: 25500513 MyJurnal

The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.
Trichosporon Asahii fungaemia in an immunocompetent polytrauma patient who received multiple antibiotics

Ding CH, Khaithir TMN, Wahab AA, Faiz MA, Saarah WR

Malays J Pathol, 2020 Aug;42(2):293-296.
PMID: 32860385

Trichosporon asahii is a yeast-like fungus that is emerging as an important cause of invasive infections in tertiary medical centres. A 58-year-old Chinese man with no known medical illnesses presented with liver lacerations and multiple fractures following an alleged 12-foot fall at a construction site. The gravity of his injuries and poor haemodynamic status necessitated an intensive care unit (ICU) admission, during which several febrile episodes were detected and multiple antibiotics were administered. After being in the ICU for at least two weeks, a urease-positive yeast was isolated from the patient's blood. The yeast formed dry, fuzzy and wrinkled white colonies on Sabouraud dextrose agar following prolonged incubation, and produced blastoconidia, true hyphae, pseudohyphae and arthroconidia on slide culture. It was identified biochemically by the ID 32 C kit as T. asahii. The yeast had elevated minimal inhibitory concentration (MIC) values to fluconazole, amphotericin B, flucytosine and all echinocandins tested. In view of this, the patient was treated with voriconazole and was successfully transferred to the general medical ward.
Transperineal template-guided prostate saturation biopsies in men with suspicion of prostate cancer: a pilot study from Pakistan

Mehmood K, Mubarak M, Dhar M, Rafi M, Kinsella J

Malays J Pathol, 2017 Dec;39(3):285-288.
PMID: 29279591

Traditionally, transrectal ultrasound (TRUS)-guided biopsies are done for the diagnosis of prostate cancer (PCa) in Pakistan. The transperineal template-guided saturation biopsy (TTSB) approach has been recently introduced in Pakistan and we share diagnostic yields and pathological findings of specimens taken for PCa diagnosis in men with elevated serum total prostate specific antigen (PSA) and negative TRUS-guided prostate biopsies. In all, 16 patients investigated at the Department of Urology, Sindh Institute of Urology and Transplantation (SIUT), underwent TTSB. The mean age of patients was 67.8 ± 8.8 (range: 55 - 84) years. The median PSA was 9.5 (IQR: 7.9 - 19.8) ng/ ml. The duration of symptoms before biopsy ranged from 1 month to 144 months. The prostate was enlarged with mean weight of 73.5 ± 55.5 g. Histopathology revealed PCa in 5 of 16 (31.2%) cases. The Gleason score was 6 (3+3), 7 (3+4) and 8 (4+4) in 1 case each (6.3%) and 10 (5+5) in 2 cases (12.5%). At least two cores were positive in all positive cases. None of the patients required antibiotics post-procedure. In conclusion, the TTSB technique is a promising option for patients with elevated PSA level and negative transrectal prostate biopsies for the detection of PCa in our setting.
Fulltext Transient abnormal myelopoeisis in newborns with Down syndrome

Zarina AL, Hamidah A, Yong SC, Rohana J, Hamidah NH, Azma RZ, et al.

Malays J Pathol, 2007 Dec;29(2):107-11.
PMID: 19108403 MyJurnal

Transient abnormal myelopoeisis (TAM) is a haematological phenomenon commonly seen in newborns with Down syndrome. Although the majority show spontaneous resolution, this condition should not be dismissed too readily as there have been associated fatalities. Furthermore, even for those who do show spontaneous resolution, a significant percentage will develop acute megakaryoblastic leukaemia within the next few years of life. We report a series of four patients with TAM who presented with hepatosplenomegaly and leucocytosis detected on preliminary investigations.
Transfusion medicine knowledge among clinicians at a teaching hospital in Malaysia

Poh KY, Jackson N

Malays J Pathol, 2023 Aug;45(2):187-194.
PMID: 37658528

INTRODUCTION: Inappropriate use of blood and blood products has been well reported from many countries including Malaysia and may be due to a deficit of transfusion medicine (TM) knowledge. This study is aimed to assess TM knowledge among clinicians in a tertiary hospital.
MATERIALS AND METHODS: The validated exam developed by the BEST collaborative group was used to assess TM knowledge of doctors, from junior residents up to senior specialists. Scores of 42%, 62%, and 82%, corresponding to basic, intermediate, and expert levels of knowledge, respectively. Convenience sampling was done from eight blood-using departments at University Malaya Medical Centre. The Kruskal-Wallis test was used to compare the candidates' exam scores between different variables.
RESULTS: A total of 184 doctors were assessed. The overall mean score was 40.1% (SD 12.7%). The most senior doctors had a significantly lower mean score compared with resident trainees and specialists. Doctors from haematology, anesthesiology, and internal medicine had significantly higher scores (51%, 47.4%, and 46.4% respectively, p<0.05). No correlations were found between the exam scores and the self-reported amount, or quality of prior TM teaching, nor with the year of postgraduate training. Participants did poorly on questions related to transfusion reactions, especially the question on transfusion-related acute lung injury.
CONCLUSION: Inadequate transfusion medicine knowledge was found across all the departments and levels of appointment. It is concerning that the most senior decision-making doctors had especially poor knowledge. TM training is needed by all residents, and regular updates should be given to established specialists.
Fulltext Transfected human mesenchymal stem cells do not lose their surface markers and differentiation properties

Yap FL, Cheong SK, Ammu R, Leong CF

Malays J Pathol, 2009 Dec;31(2):113-20.
PMID: 20514854 MyJurnal

In this study, we evaluated the biological properties of human mesenchymal stem cells transfected (hMSC) with a plasmid vector expressing human cytokine interleukin-12 (IL-12). Surface markers were analysed by immunophenotyping using flow cytometry. Differentiation capability was evaluated towards adipogenesis and osteogenesis. We demonstrated that successfully transfected hMSC retained their surface immunophenotypes and differentiation potential into adipocytes and osteocytes. These results indicate that hMSC may be a suitable vehicle for gene transduction.
Transducer-like enhancer of split 1 (TLE1) expression as a diagnostic immunohistochemical marker for synovial sarcoma and its association with morphological features

Bakrin IH, Hussain FA, Tuan Sharif SE

Malays J Pathol, 2016 Aug;38(2):117-22.
PMID: 27568668 MyJurnal

Synovial sarcoma (SS) is a malignant soft tissue tumour of uncertain histogenesis which is defined by the translocation t(X;18) that produces the fusion oncogenes SYT-SSX. The emergence of transducer-like enhancer of split 1 (TLE1) as a new immunohistochemical (IHC) marker for SS has offered an alternative to pathologists in differentiating SS from other histological mimics, especially in the setting of limited molecular facilities. We investigated the utility of IHC TLE1 expression against histomorphological features and other IHC markers in SS and non-SS tumours. Twenty-six cases of histologically diagnosed SS and 7 non-SS (for which SS was in the differential diagnosis) were subjected to TLE1 IHC staining, which was graded from 0 to 3+. Of the 26 SS cases, 12 each were biphasic and monophasic types and 2 were poorly-differentiated. TLE1 was expressed in 22/26 (84.6%) SS cases, of which 11/12 (91.7%) were biphasic, 10/12 (83.3%) monophasic and 1/2 (50%) poorly-differentiated tumours. Two of 7 (28.6%) non-SS cases were positive for TLE1. Immunopositivity of SS and non-SS cases for EMA were 20/26 (76.9%) and 2/7 (28.6%) respectively and for CK7 were 7/26 (26.9%) and 0/7 (0%) respectively. All cases were negative for CD34. Consistent histomorphological features for SS included mild nuclear pleomorphism, alternating tumour cellularity, fascicular growth pattern and thick ropy stromal collagen. In conclusion, TLE1 is not a stand-alone diagnostic IHC marker for SS. However, in the absence of molecular studies, it can contribute added diagnostic value in combination with morphological evaluation and other IHC markers such as EMA and CD34.
Fulltext Toxoplasmosis with special reference to peninsular Malaysia and Singapore

Thomas V

Malays J Pathol, 1979 Aug;2:23-31.
PMID: 263419
Fulltext Tocotrienols-rich diet decreases advanced glycosylation end-products in non-diabetic rats and improves glycemic control in streptozotocin-induced diabetic rats

Wan Nazaimoon WM, Khalid BA

Malays J Pathol, 2002 Dec;24(2):77-82.
PMID: 12887164

This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.
Fulltext Thyrotoxic periodic paralysis: a report of 3 Malaysian cases and a review of its pathology

Sthaneshwar P, Prathibha R, Yap SF

Malays J Pathol, 2005 Jun;27(1):29-32.
PMID: 16676690

Thyrotoxic periodic paralysis (TPP) is a medical emergency characterised by sudden onset of muscle weakness with hypokalemia that resolves with the treatment of hyperthyroidism. We report three cases of thyrotoxic periodic paralysis seen at the Accident and Emergency Care Department, University of Malaya Medical Centre in a period of four months. We also review the clinical presentation, pathophysiology, biochemical features and management of TPP. All three patients were young Asian males, presenting with muscle weakness of sudden onset. The first patient presented with lower limb weakness and had symptoms of thyrotoxicosis and goitre. He had a previous similar episode which resolved spontaneously. The second patient presented with quadriplegia, respiratory acidosis and had no signs and symptoms of thyrotoxicosis. The electrocardiogram of this patient showed normal sinus rhythm with U wave in V3 and a flat T wave, which are characteristic of hypokalaemia. The third patient, who was a known case of thyrotoxicosis, was admitted thrice for hypokalemic paralysis during the study period. All cases had low serum potassium, suppressed TSH and elevated T4 confirming thyrotoxic periodic paralysis. Potassium therapy was useful during the crisis; however prophylactic potassium has not been shown to prevent attacks as seen in one of our cases.
Thyroid storm: Is there a role for thyroid function test?

Tengku Ibrahim TZ, Thambiah SC, Samsudin IN, Nasuruddin AN, Zakaria MH

Malays J Pathol, 2019 Dec;41(3):355-358.
PMID: 31901922

INTRODUCTION: Thyroid storm (TS) is an endocrine emergency. Early diagnosis for prompt treatment is essential as it has a high mortality rate.
CASE REPORT: A 31-year-old lady with underlying hyperthyroidism, dilated cardiomyopathy with severe mitral regurgitation presented with shortness of breath. She was intubated and admitted due to decreasing Glasgow Coma Score. Her blood investigations revealed increased white cell count, raised free thyroxine with suppressed thyroid stimulating hormone, deranged liver, renal and coagulation profiles. As her condition did not improve with initial treatment, plasmapheresis was commenced on day 4. Biochemically, her thyroid function test (TFT) showed improvement; however, she succumbed due to multi-organ failure.
DISCUSSION: Plasmapheresis is considered in TS if there is no clinical improvement within 24-48 hours of initial treatment. The improvement in patient's TFT post plasmapheresis signifies its role in treating TS. Unfortunately, there was a delay in commencing plasmapheresis due to haemodynamic instability in this patient.
Therapeutic potentials of neural stem cells in Alzheimer's disease

Wong RSY, Cheong SK

Malays J Pathol, 2020 Aug;42(2):157-170.
PMID: 32860368

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.
Therapeutic potential of mesenchymal stem cells and their derivatives in sarcopenia

Wong RSY, Cheong SK

Malays J Pathol, 2022 Dec;44(3):429-442.
PMID: 36591711

Sarcopenia is a common condition in the geriatric population. It refers to age-related and progressive decline in muscle mass and function, which has a great impact on one's mobility and quality of life. Patients with sarcopenia are mainly treated with nutritional therapy, exercise therapy, or a combination of both. Since the identification of mesenchymal stem cells (MSCs) several decades ago, many studies have explored the application of MSCs in the field of regenerative medicine. MSCs are popular candidates for cell-based therapy owing to their multipotent nature and immunomodulatory properties. Even though MSCs do not naturally differentiate into myogenic cells, they are important players in skeletal muscle health, as MSCs support myogenic differentiation of other cells and promote recovery of injured skeletal muscle. Recent studies have found that MSCs may be of benefits in the treatment of sarcopenia. This article gives an overview of sarcopenia and the role of MSCs in skeletal muscle homeostasis. It also discusses the therapeutic potential of MSCs and their derivatives, as well as the underlying mechanisms of the therapeutic effects of MSCs and MSC-based products in sarcopenia.
The virology laboratory services in Malaysia

Lam SK

Malays J Pathol, 1982 Aug;5:19-22.
PMID: 7187455

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