Diagnostic performance of COVID-19 serology assays
Z Zainol Rashid 1, S N Othman, M N Abdul Samat, U K Ali, K K Wong
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PMID: 32342927Free article

Abstract


Introduction: The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19.

Materials and methods: A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently.

Results: From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed.

Conclusions: There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.

Cited by 8 articles
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2
Review
Malays J Pathol




. 2020 Apr;42(1):3-11.
Properties of Coronavirus and SARS-CoV-2
Y A Malik 1
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PMID: 32342926Free article

Abstract


were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,β,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and β-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a β-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.

Cited by 8 articles
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3
Review
Malays J Pathol




. 2020 Apr;42(1):23-35.
Upper respiratory tract sampling in COVID-19
A Mawaddah 1, H S Gendeh, S G Lum, M B Marina
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PMID: 32342928Free article

Abstract


Introduction: To review the present literature on upper respiratory tract sampling in COVID-19 and provide recommendations to improve healthcare practices and directions in future studies.

Methods: Twelve relevant manuscripts were sourced from a total of 7288 search results obtained using PubMed, Medline and Google Scholar. The search keywords used were COVID-19, nasopharyngeal, oropharyngeal, swabs, SARS and CoV2. Original manuscripts were obtained and analysed by all authors. The review included manuscripts which have not undergone rigorous peer-review process in view of the magnitude of the topic discussed.

Results: The viral load of SARS-CoV-2 RNA in the upper respiratory tract was significantly higher during the first week and peaked at 4-6 days after onset of symptoms, during which it can be potentially sampled. Nasopharyngeal swab has demonstrated higher viral load than oropharyngeal swab, where the difference in paired samples is best seen at 0-9 days after the onset of illness. Sensitivity of nasopharyngeal swab was higher than oropharyngeal swabs in COVID-19 patients. Patient self-collected throat washing has been shown to contain higher viral load than nasopharyngeal or oropharyngeal swab, with significantly higher sensitivity when compared with paired nasopharyngeal swab.

Recommendations: Routine nasopharyngeal swab of suspected COVID-19 infection should take anatomy of the nasal cavity into consideration to increase patient comfort and diagnostic yield. Routine oropharyngeal swab should be replaced by throat washing which has demonstrated better diagnostic accuracy, and it is safe towards others.

Cited by 2 articles
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4
Editorial
Malays J Pathol




. 2020 Apr;42(1):1.
Challenges of Covid-19 testing
G C Tan 1, S K Cheong
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PMID: 32342925Free article

Abstract


No abstract available.
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5
Malays J Pathol




. 2020 Aug;42(2):215-225.
A pilot study on pattern B lipoprotein profile in Malaysia
C S Thambiah 1, N A Mohamed Pesri, N Mazalan, I N Samsudin, S Mohamad Ismuddin, G Appannah, M Osman, S Y Zahari Sham
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PMID: 32860374Free article

Abstract


Introduction: 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.
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6
Malays J Pathol




. 2020 Apr;42(1):51-57.
Practice and performance of lupus anticoagulant tests: A single centre experience
K Tay Za 1, S Jayaranee, H Shanmugam
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PMID: 32342930Free article

Abstract


Introduction: Lupus anticoagulant (LA) is a well-known risk factor for thrombosis. Correct diagnosis of LA is essential in patient management with anticoagulation. The objectives of this study were to document the clinical and laboratory characteristics of patients tested for LA and to evaluate existing LA testing methods in our laboratory with the aim of improving the performance of LA test interpretation and reporting.

Methods: Tests for LA include dilute Russell's viper venom time (dRVVT) and Kaolin clotting time (KCT). Patients with LA ratio (dRVVT screen ratio/dRVVT confirm ratio) of ≥1.2 were considered as LA positive irrespective of KCT results. KCT was considered positive if there was a prolongation in KCT screening test which was not corrected on mixing with normal plasma.

Results: Of 577 patients' results, 295 were normal, 178 were KCT positive with negative dRVVT and 104 were LA positive. Incidences of thrombosis, connective tissue disease (CTD) and bad obstetric events were noted in 13%, 16% and 44% of normal patients, 9%, 22% and 49% of KCT+ patients and 23%, 37% and 17% of LA+ patients respectively. On further evaluation of dRVVT screen ratios, 431 had a ratio of <1.1, 59 had a ratio between 1.1 and 1.2 and 87 had a ratio of >1.2. Positive LA results were found in 3%, 29% and 87% of patients with dRVVT screen ratios of <1.1, 1.1 - 1.2 and >1.2 respectively.

Conclusion: LA+ patients had higher incidences of thrombosis and CTD as compared to normal and KCT only positive patients. There was no significant difference in clinical characteristics between normal and KCT+ patients which suggests the presence of a high rate of false-positive KCT results. Since confirmatory testing for KCT is not widely used, the option of using another LA screening test method should be considered. In regard to dRVVT testing, confirmatory test should only be performed in patients with prolonged dRVVT screening result which was not corrected upon mixing with normal plasma as required by the International Society of Thrombosis and Haemostasis guidelines on LA testing. This practice will not only result in significant cost reduction but also avoid diagnostic confusion.
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7
Malays J Pathol




. 2020 Apr;42(1):77-84.
Is Procalcitonin more superior to hs-CRP in the diagnosis of infection in diabetic foot ulcer?
N A Zakariah 1, M Y Bajuri, R Hassan, Z Ismail, M Md Mansor, H Othman, D N Nasuruddin
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PMID: 32342934Free article

Abstract


Introduction: Procalcitonin (PCT) has recently emerged as a marker for diagnosing infection. This study aimed to compare the performance of PCT and other infection markers in diagnosing infected diabetic foot ulcer (IDFU).

Materials and methods: A total of 128 diabetic patients with foot ulcers were recruited and divided into two groups, consisting of 73 patients in the IDFU group and 55 in the non-infected diabetic foot ulcer (NIDFU). The severity of infection in IDFU patients was graded based on the Infectious Disease Society of America-International Working Group on the Diabetic Foot classification. Blood samples from all the patients were collected for measurement of PCT, high sensitivity C-reactive protein (hs-CRP) and white cell count (WBC). The area under the receiver operating curves (AUC) were then constructed and analysed.

Results: PCT, hs-CRP and WBC levels were significantly higher in the IDFU group compared to NIDFU with hs-CRP demonstrated the highest AUC (0.91; p <0.001) followed by PCT (0.814; p < 0.001) and lastly WBC (0.775; p < 0.001). The best cut off value, sensitivity and specificity for the presence of infection in diabetic foot, were 3.47 mg/dL, 80% and 89% for hs-CRP, 0.11 ng/ml, 70% and 87% for PCT and 11.8x109/L, 60% and 90% for WBC. All the infection markers showed significant positive correlations with infection severity of DFU.

Conclusion: This study showed that hs-CRP is a more sensitive marker for diagnosing IDFU. Although PCT is useful in differentiating IDFU from NIDFU, the use of PCT is not necessary as it adds little value to the current practice.
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8
Malays J Pathol




. 2020 Apr;42(1):65-70.
Medico-legal autopsies of homicidal deaths: A five-year retrospective study in Hospital Sungai Buloh
R Rahimi 1, N A Mohd Kasim, K A Zainun, N A Mohamad A' Azizan, M A Mansor, N S Ahmad Kamal, Z Z Daud
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PMID: 32342932Free article

Abstract


Introduction: Homicide is the act of killing one human being by another, encompassing death as a result of criminal act including justifiable homicide such as judicial killing and self-defence. This study aimed to ascertain the epidemiology and patterns of injury of homicide victims.

Materials and methods: We reviewed records of medico-legal autopsy cases performed at the Department of Forensic Medicine, Hospital Sungai Buloh, for a period of five years, from January 2012 until December 2016. Subjects' demographic data such as age, gender, nationality, ethnicity and cause of death were recorded.

Results: A total of 122 homicide cases were documented. 90% of the victims were 18 to 65 years old. Males contributed 80% of the subjects. An alarming 42% of the subjects comprised of non-Malaysians. Indonesian subjects contributed one-third of the non-citizen category, followed by Bangladeshis at 20.4%. Other nationalities were Burmese, Nepalese, Pakistani, Vietnamese and unspecified. Among Malaysians, 50% of the subjects were Indians, followed by Malay (31.5%) and Chinese (17.8%). Sharp and blunt force traumas were the most common injuries found, contributing 33% and 32% respectively. Asphyxiation and firearm injuries recorded an almost similar frequency, contributing 25% in combination. Other patterns included combined sharp and blunt objects (4.9%) and burns (3%).

Conclusions: A large number of immigrants in the country have significantly increased the forensic casework. Sharp and blunt objects continue to be the weapon of choice due to its easy accessibility. As domestic violence including fatal spousal and child abuse continue to rise, in-depth study in the area is warranted.
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9
Malays J Pathol




. 2020 Aug;42(2):203-207.
Screening for phaeochromocytoma in patients with acute cerebrovascular disease: Is it necessary?
N Mohamed Zainuddin 1, P Sthaneshwar, J Ratnasingam
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PMID: 32860372Free article

Abstract


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.
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10
Malays J Pathol




. 2020 Apr;42(1):59-64.
Evaluation of coagulation factor activity and sterility of thawed fresh frozen plasma during storage up to 5 days at 4°C
S Shamsudin 1, R Yousuf, Y L Tang, C H Ding, C F Leong
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PMID: 32342931Free article

Abstract


Introduction: Fresh frozen plasma (FFP) is a blood component containing functional quantities of all coagulation factors stored at -18°C or below. FFP has to be thawed and transfused as soon as possible to prevent the loss of certain coagulation factor activities and to minimise microbial contamination.

Materials and methods: Thirty units of FFP kept at -20°C were thawed using a 37°C water bath and immediately sampled for baseline Factor II (FII), Factor VIII (FVIII) and fibrinogen activity levels and sterility testing. Each unit was then divided into two smaller bags (i.e. Bag I and Bag II) and kept at 4°C. At 6 hours and Day 3, representative samples were taken from Bag I for coagulation factor activity assays, while at Day 5 representative samples were taken from Bag II for coagulation factor activity assays and sterility testing.

Results: FII activities at the four time points were 73.43%, 73.73%, 71% and 69.8%, respectively, while FVIII activities were 177.63%, 144.37%, 80.8% and 70.97%, respectively. Fibrinogen levels at the four time points were 3.24 g/L, 3.24 g/L, 3.21 g/L and 3.20 g/L, respectively. All samples were free from microbial contamination even at Day 5.

Conclusion: The mean reduction in FII and fibrinogen activities on Day 5 was 5% and 1%, respectively. However, FVIII activity declined significantly by approximately 60% at Day 5. Despite these reductions, thawed plasma stored for up to 5 days at 4°C is still suitable for use as the coagulation factor activity levels still exceed the minimum release criteria recommended in quality assurance regulations.
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11
Malays J Pathol




. 2020 Apr;42(1):127-130.
Tetraploid/near-tetraploid acute promyelocytic leukaemia with double (15;17) translocation
K Tay Za 1, N Jackson, E F M Chin
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PMID: 32342942Free article

Abstract


A 57-year-old man presented with intermittent fever and bleeding following dental surgery. Peripheral smear and bone marrow aspirate exhibited unusually large and bizarre-looking abnormal cells which were found to be myeloblasts with aberrant CD56 and CD2 expression on immunophenotyping. Fluorescence in situ hybridization analysis revealed an extra RARA gene rearrangement. This finding correlated well with a near-tetraploid karyotype with double t(15;17)(q22;q21). Bcr-3 type PML/ RARA copies were identified in reverse transcriptase-polymerase chain reaction. The diagnosis of near-tetraploid acute promyelocytic leukaemia (APML) was established. The patient was treated with all-trans retinoic acid and idarubicin and six weeks later achieved complete remission. Tetraploid/ near-tetraploid APML is exceedingly rare. It is a distinct cytogenetic subgroup with unique clinical and biological features as highlighted by atypical morphology, frequent CD2 expression and association with the bcr-3 type PML/RARA fusion transcripts. Early recognition of this rare entity is essential for timely and appropriate treatment.
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12
Malays J Pathol




. 2020 Apr;42(1):85-90.
High expression of LC3A, LC3B, and p62/SQSTM1 autophagic proteins in human colonic ganglion cells
N J Awi 1, S Armon, K B Peh, S C Peh, S Y Teow
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PMID: 32342935Free article

Abstract


Introduction: Autophagy is a mechanism that degrades large damaged organelles and misfolded proteins to maintain the homeostasis in all cells. It plays double-faceted roles in tumourigenesis and prevention of various cancers. In our side observation of investigating the prognostic value of autophagy in colorectal cancer (CRC), we found high expression of autophagy proteins (LC3A, LC3B, and p62/SQSTM1) in the colonic ganglion cells. To our best understanding, this is the first paper reporting such finding.

Materials and methods: Formalin-fixed paraffin-embedded (FFPE) CRC tissues blocks were retrieved and confirmed by haematoxylin & eosin (H&E) staining. Immunohistochemistry (IHC) targeting autophagy proteins (LC3A, LC3B, and p62/SQSTM1) was then performed followed by pathological examination.

Results: All three autophagy proteins were present in both normal and tumour tissues of CRC patients. Interestingly, high expression of autophagy proteins in colonic ganglion cells was consistently seen regardless of tissue type (normal or cancer) or tumour site (caecum, ascending, transverse, descending, sigmoid colon and rectum).

Conclusions: This work highlights the high autophagic activities in human colonic ganglion cells.
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13
Malays J Pathol




. 2020 Apr;42(1):137-141.
Nasal eosinophilic angiocentric fibrosis with IgG4-positive plasma cell infiltration
B Saenz-Ibarra 1, L A Ceceñas-Falcon, J A Cardenas-De la Garza, M A Garza-Elizondo, R De Hoyos, M Dieste, O Barboza-Quintana
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PMID: 32342944Free article

Abstract


Introduction: Eosinophilic angiocentric fibrosis (EAF) is a rare lesion that predominantly affects the upper respiratory tract. Its etiology is unknown and it has been recently associated with the IgG4- related disease (IgG4-RD) spectrum. To the author's knowledge, this is the sixth case report of the relationship between EAF and IgG4-RD.

Case report: We report the case of a 37-year-old woman with nasal deformity and facial pain. The lesion was surgically excised. Histological examination revealed features of EAF with an IgG4/IgG plasma cell ratio ≷73% and 31 IgG4 stained cells per high power field. No clinical or radiological recurrence was detected during follow-up. Serum IgG4 quantification one year after surgery was within normal limits.

Discussion: The relationship between both entities may have therapeutic impact because IgG4-RD of the head and neck has a high remission rate with corticosteroids and immunosuppressive therapy. Additional reports of this infrequent disease are necessary to elucidate appropriate treatment and prognosis.
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14
Malays J Pathol




. 2020 Apr;42(1):99-105.
Methanol related death in National Institute of Forensic Medicine, Hospital Kuala Lumpur: A case series
K L Chng 1, P S Lai, S F Siew, S W Md Yaro, M S Mahmood
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PMID: 32342937Free article

Abstract


Introduction: Methanol is a widely available chemical with a range of uses including as solvent, as a fuel, in chemical synthesis and anti-freeze preparations. Most of the cases are accidental exposures to drinking beverages contaminated with methanol.

Materials and methods: In mid-September 2018, there was a single outbreak of methanol poisoning in Malaysia especially involving the state of Federal Territory Kuala Lumpur and Selangor. There were 33 reported deaths suspected due to methanol poisoning in this current outbreak where 11 of them were brought in to the Institute of Forensic Medicine (NIFM), Kuala Lumpur. The last outbreak was in the year 2013 with 29 deaths reported out of 44 cases.

Results: There were 3 cases (27.2%) died in hospital and the remaining 8 cases (72.8%) were found dead at home and were later brought in dead to the hospital. A full autopsy was carried out for each case. Autopsy findings, as well as lab results pertaining to cases that survived and directly brought in dead, were of a different spectrum.

Conclusion: Methanol related deaths are almost always as a result of greed. The running truism is 'methanol poisoning is a result of deliberate addition/adulteration with industrial methanol'. Prevention of the illegal production of methanol and methylated spirits should be established to curb this matter in the future.
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15
Malays J Pathol




. 2020 Aug;42(2):187-194.
Different pathological processes for acute white matter lesions in multiple sclerosis
M Alturkustani 1, B Bahakeem, Q Zhang, L C Ang
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PMID: 32860370Free article

Abstract


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.

Conclusions: 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.
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16
Malays J Pathol




. 2020 Aug;42(2):227-236.
CIP2A expression in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue mıcroarray study
S G Celikden 1, S Baspinar, S A Ozturk, A Karaibrahimoglu
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PMID: 32860375Free article

Abstract


Introduction: 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).

Conclusions: 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.
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17
Malays J Pathol




. 2020 Apr;42(1):91-97.
Construction of a doxycycline inducible lentivirus that expresses stem cell-specific miR-302 cluster
G C Tan 1, Y P Wong, W Cui, N Dibb
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PMID: 32342936Free article

Abstract


Introduction: The polycistronic miR-302 cluster encodes five miRNA genes that have an important role in the regulation of embryonic stem cell function. Studies showed that the miR-302 cluster can reprogram both mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) with high efficiency. The aim of this study was to generate an inducible lentivirus that expresses miR-302 cluster in order to further investigate somatic cell reprogramming by these miRNAs.

Materials and methods: The miR-302 cluster was amplified by polymerase chain reaction technique from human genomic DNA and was ligated into pTRIPz, an inducible lentiviral vector.

Results: MRC5 fibroblasts and HEK293 (human embryonic kidney) cells were infected with pTRIPz-302 cluster lentivirus and the family of 302 miRNAs were strongly expressed in HEK293 cells but lowly expressed in MRC5 fibroblasts. When cultured in hESC conditions, MRC5 cells expressed only low levels of DNMT3B, Nanog, Oct4 and Lin28 and failed to show stem cell induction. The red fluorescent expression seen in the majority of MRC5 cells, indicated that the rate of infection by lentivirus was efficient.

Discussion: The efficiency of reprogramming may be improved perhaps by either using a different cell type or a high expression vector with a different type of promoter.
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18
Malays J Pathol




. 2020 Apr;42(1):143-150.
Early relapse after complete remission of primary plasma cell leukaemia manifesting clonal evolution: A case report
W W T Nyunt 1, D Abdul Jalil, N A Zakariah, N Abdul Karim, M R Mohd Idris, D N Nasuruddin, S H U I B Salwati, H Alauddin, N R Tumian, C F Leong, S F S Abdul Wahid
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PMID: 32342945Free article

Abstract


Introduction: Plasma cell leukaemia (PCL) is a rare variant of multiple myeloma. We report a case of PCL to demonstrate the clonal evolution, resulting in disease relapse after achieving complete remission, and its aggressive nature of the disease, leading to poor clinical outcome.

Case report: A 69-year-old man presented with a three-day-history of worsening generalized body weakness, poor oral intake, nausea, significant loss of weight and lower back pain. He was diagnosed as primary PCL, based on hypercalcaemia, renal insufficiency, anaemia, thrombocytopenia, lytic bone lesions, 24% abnormal plasma cells in peripheral blood, immunophenotype of clonal plasma cells which were positive for CD38, CD138 and CD56 markers with kappa light chain restriction, 49% abnormal plasma cells in bone marrow, monoclonal paraprotein (IgG kappa) in serum and urine, and positive IGH rearrangement (Fluorescence in-situ hybridisation, FISH). He achieved complete remission after four cycles of Bortezomib-based therapy. There was a plan for high-dose therapy plus autologous haematopoietic cell transplantation. A month later, the disease relapsed, as evidenced by 94% abnormal plasma cells in his bone marrow aspirate, complex karyotype and abnormal FISH results. He passed away a few days later, from severe septicaemia. Time-to-progression of disease was 1 month and overall survival was 5 months.

Discussion: This case report illustrates the clonal evolution and aggressive nature of primary PCL with older age at presentation, leading to a shorter duration of remission and overall survival.
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19
Malays J Pathol




. 2020 Apr;42(1):107-110.
Imported Falciparum Malaria: A case series in a tertiary hospital
N A Mohamed 1, F A F Mansur, N Abdul Rahman
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PMID: 32342938Free article

Abstract


Introduction: Malaysia declared its intent to eliminate malaria by 2020, with a phased goal of achieving zero local transmission. Nonetheless, Malaysia is highl susceptible to malaria importation due to geographical proximity to high-burden countries e.g. Thailand, Myanmar and high influx of foreign workers and students from Asia and Africa.

Case series: We accumulated all malaria cases diagnosed in a tertiary hospital within a period of two years. Three cases were reported, where all of the patients were foreigners with recent travel history to African countries. All of them were infected by P. falciparum, responded to treatment and discharged well.

Discussion: This case series highlighted the importance of acquiring recent travel history during history taking and having a high index of suspicions on malaria when dealing with feverish patients originated particularly from African countries.
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20
Malays J Pathol




. 2020 Apr;42(1):111-114.
Endocrine mucin-producing sweat gland carcinoma - newly described skin appendageal tumours
I H Bakrin 1, P S Rajaintharan, Z Tawil, H Mahayidin
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PMID: 32342939Free article

Abstract


Introduction: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a recently described adnexal tumour with a predilection for the face particularly the eye-lids. Considered to be a precursor lesion of mucinous adenocarcinoma, it may represent part of a morphological spectrum. We described a case of this entity, which we believe is the first case to be reported in Malaysia.

Case report: A 59-year-old Chinese male presented with a slow-growing cystic lesion over the left lower lateral canthal region. The lesion became progressively larger and nodular within the last 6 months. Histologically, the lesion is a well-circumscribed intradermal tumour with pushing borders extending into the subcutaneous tissue. The tumour cells were arranged in lobules of solid, papillary and cribriform architecture. The cells displayed uniform, medium-sized, round to oval nuclei with stippled chromatin pattern and ample eosinophilic granular cytoplasm. Intracellular mucin (as highlighted by mucicarmine stain) was observed in areas with focal extracellular mucin seen. Mitotic figures were not particularly impressive. By immunohistochemistry study, the tumour cells expressed ER, PR, CK7, GCDFP-15, mammaglobin and EMA diffusely. Chromogranin A and synaptophysin highlighted a significant number of tumour cells.

Discussion: The morphology and immunohistochemical profile similarities between EMPSGC and solid papillary carcinoma of the breast (SPCOTB) makes the former considered as the cutaneous analogue of the latter. In fact, one should rule out the possibility of metastatic SPCOTB before considering the diagnosis of EMPSGC.
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21
Malays J Pathol




. 2020 Apr;42(1):121-125.
Ewing Sarcoma presenting as a gluteal mass in adult woman: Diagnostic approach and its challenges
S E Tuan Sharif 1, O Alzallal, W F Wan Ismail, R R Md Zin
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PMID: 32342941Free article

Abstract


Introduction: Sarcomas of the Ewing family of tumours are aggressive neoplasms occurring in bone and soft tissue of mostly children and young adults. It usually affects male more than female with peak incidence 10 to 15 years of age, and rarely encountered in adults especially in more than 40 years old. It is an aggressive, rare tumour with a tendency toward recurrence after resection and early metastasis.

Case report: We reported a rare case of Ewing Sarcoma in a 62-year-old woman who had an unusual clinical presentation. She had right painless buttock swelling only for a month. Magnetic resonance imaging (MRI) revealed soft tissue sarcoma originated from right gluteal muscle. The diagnosis of Ewing sarcoma (ES) was made in a limited diagnostic material in an initial tru-cut biopsy, followed by an excision supported by immunohistochemistry (IHC) and Fluorescent In-Situ Hybridization (FISH).

Discussion: The purpose of this study is to document ES in an adult woman and its diagnostic challenges in histopathologic perspective.
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22
Malays J Pathol




. 2020 Aug;42(2):237-243.
Frequent loss of CD10 expression in follicular lymphoma with leukaemic presentation
S W Chen 1, S T Chang, Y C Hsieh, C C Kuo, H C Wu, Y H Feng, S S Chuang
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PMID: 32860376Free article

Abstract


Introduction: 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.
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23
Malays J Pathol




. 2020 Aug;42(2):293-296.
Trichosporon Asahii fungaemia in an immunocompetent polytrauma patient who received multiple antibiotics
C H Ding 1, T M N Khaithir, A A Wahab, M A Faiz, W R Saarah
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PMID: 32860385Free article

Abstract


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.
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24
Malays J Pathol




. 2020 Apr;42(1):151-155.
Occult primary breast carcinoma presented as an axillary mass: A Diagnostic Challenge
Y P Wong 1, G C Tan, R Muhammad, P Rajadurai
Affiliations expand
PMID: 32342946Free article

Abstract


Introduction: Occult primary breast carcinoma (OBC) manifesting as axillary nodal metastasis without an identifiable breast primary is exceptionally rare. It continues to pose a diagnostic challenge to pathologists. Here, we report a case of OBC with emphasis on the usefulness of immunohistochemistry to determine the primary site of tumour.

Case report: A 58-year-old female presented with a 3-cm painless right axillary mass. Extensive radiological investigations that include mammography, ultrasonography of the breasts and positron emission tomography (PET) scan failed to conclude the primary site of the tumour. Histological examination of the lymph node revealed loosely cohesive sheets of poorly differentiated malignant cells, without discernible glandular or squamous differentiation. Immunohistochemically, the malignant cells exhibited diffuse immunoreactivity toward pan-cytokeratin and CK7, while leukocyte common antigen, S100 and CK20 were negative. A second panel of immunomarkers was carried out. The malignant cells expressed breast-specific markers (GATA-3, GCDFP-15 and mammaglobin), and were negative for ER, PR and TTF-1 immunohistochemistry. A diagnosis of OBC was rendered.

Discussion: Breast primary must always be considered in the differential diagnosis in patients with sole presentation of axillary lymphadenopathy. The breast-specific immunomarkers play a pivotal role in the diagnosis of ER, PR-negative occult breast cancer.
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25
Malays J Pathol




. 2020 Apr;42(1):71-76.
Appropriateness of metformin prescription for type 2 diabetes mellitus patients with chronic kidney disease (Stages 3-5)
M Ramachandran 1, B Loi, N Mat Ariff, O C Ng, S Y Zahari Sham, S C Thambiah, I N Samsudin
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PMID: 32342933Free article

Abstract


Introduction: Metformin is the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM). Guidelines recommend metformin to be given at reduced dosages for those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and omitted in those with eGFR<30 mL/min/1.73m2. Lactic acidosis is a known complication of those on metformin. This study aimed to determine the appropriateness of metformin prescription in T2DM patients with chronic kidney disease (CKD) stages 3-5 in a tertiary centre in Malaysia.

Materials and methods: A cross-sectional design using retrospective secondary data of T2DM patients on metformin attending nephrology and diabetic clinics in the year 2017. eGFR calculated using the CKD-EPI formula identified those in CKD stage 3-5 defined using the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Metformin prescription was considered appropriate when the metformin maximum daily dosage does not exceed 1500 mg in CKD stage 3a and 1000 mg in CKD stage 3b and metformin stopped in CKD stages 4 and 5.

Results: A total of 143 patients were included. Majority were in the elderly age group (62.9%), male (60.8%) and had concurrent hypertension (85.3%). Median HbA1c was 8.3% (67 mmol/mol) with most patients (88.8%) having HbA1c above 6.5% (48 mmol/ mol). Majority (92.3%) were categorised as stage 3 CKD. Eleven (7.7%) subjects had inappropriate metformin prescription. Seven of nine (78%) subjects in CKD stage 4 were on metformin with a maximum daily dose of 500 mg to1000 mg. Three patients had serum lactate measured.

Conclusion: The majority of CKD patients had appropriate metformin prescription. However, a considerable number of CKD stage 4 patients continued to be on metformin. The many benefits of metformin may be a reason why it is still continued against recommendations. Only three patients had lactate measured which, although may suggest that lactic acidosis is not a common occurrence, the potential for metformin-associated lactic acidosis especially in those at risk should be considered.
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26
Malays J Pathol




. 2020 Apr;42(1):37-49.
Is this a blast? An illustrated practical review on peripheral blood smear examination in the paediatric patient
G Rose 1, H Heidi Reinhard, S B Kahwash
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PMID: 32342929Free article

Abstract


The morphologic findings on a peripheral blood smear can provide important clues that help establish a diagnosis or guide the workup of many clinical disorders. Finding a blast - whether clinically expected or not - is one of the most impactful of such findings. Pathologists, clinical haematologists, technologists, and trainees in the medical field often feel the need to refer to an illustrated reference when encountering suspected blasts and blast-mimics. This article provides a practical concise resource that demonstrates the morphological features of the various types of blasts and illustrates the cytologic characteristics that help distinguish them from their benign mimickers in the paediatric population.
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27
Malays J Pathol




. 2020 Apr;42(1):131-135.
Collagenofibrotic glomerulopathy- report of a rare renal disease with serial biopsies
Y F Ng 1, C Y Chow, W S Yang, W C Lye, H L Loh
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PMID: 32342943Free article

Abstract


Introduction: Collagenofibrotic glomerulopathy or collagen type-III glomerulopathy is a rare glomerular disease characterised by the deposition of type III collagen fibres in the subendothelial space and mesangium of the glomerulus.

Case report: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity.

Discussion: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.
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28
Malays J Pathol




. 2020 Aug;42(2):157-170.
Therapeutic potentials of neural stem cells in Alzheimer's disease
R S Y Wong 1, S K Cheong
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PMID: 32860368Free article

Abstract


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.
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29
Malays J Pathol




. 2020 Aug;42(2):209-214.
Diagnostic performance of prostate health index (PHI) in predicting prostate cancer on prostate biopsy
H Othman 1, A H Abu Yamin, N Md Isa, B Bahadzor, S Z Syed Zakaria
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PMID: 32860373Free article

Abstract


Introduction: 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.
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30
Malays J Pathol




. 2020 Aug;42(2):253-257.
Haemoglobin Constant Spring (HbA2: c.427T>C) and Haemoglobin Adana (HbA2: c.179G>A) in jaundiced Malaysian term neonates with clinically significant hyperbilirubinemia
S Shwe 1, N Y Boo, H K Ong, S C Chee, M Maslina, M M M Ling, A K Ahluwalia
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PMID: 32860378Free article

Abstract


Introduction: Haemoglobin Constant Spring (Hb CoSp) and Haemoglobin Adana (Hb Adana), are two non-deletion type of α-thalassemia reported in Malaysia. Owing to their structural instability, they cause hemolysis and hyperbilirubinemia. This observational study was part of a large study investigating multiple factors associated with severe neonatal jaundice. In this part we aimed to determine the prevalence of Hb CoSp and Hb Adana and their association with clinically significant neonatal hyperbilirubinemia (SigNH, total serum bilirubin (TSB>290µmol/L)) among jaundiced Malaysian term neonates.

Materials and methods: The inclusion criteria were normal term-gestation neonates admitted consecutively for phototherapy. PCR-restriction fragment length polymorphism method was applied on DNA extracted from dry blood spot specimens of each neonate to detect for Hb CoSp and Hb Adana gene. Positive samples were verified by gene sequencing.

Results: Of the 1121 neonates recruited (719 SigNH and 402 no-SigNH), heterozygous Hb CoSp gene was detected in only two (0.27%) neonates. Both were SigNH neonates (0.3% or 2/719). No neonate had Hb Adana variant.

Conclusion: Hb CoSp was not common but could be a risk factor associated with SigNH. No Hb Adana was detected.
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31
Malays J Pathol




. 2020 Aug;42(2):195-201.
Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia
S Y Wee 1, S S Muhamed Said, R Z A Raja Sabudin, H Alauddin, A Ithnin
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PMID: 32860371Free article

Abstract


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.
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32
Malays J Pathol




. 2020 Aug;42(2):301-305.
Primary extragonadal vaginal yolk sac tumour: A case report
Y P Wong 1, A Yahaya, R Che Abdul Aziz, P Y Chia, C K Loh, G C Tan
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PMID: 32860387Free article

Abstract


Introduction: Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads.

Case report: We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117.

Discussion: Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.
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33
Malays J Pathol




. 2020 Apr;42(1):115-119.
Metastatic alveolar rhabdomyosarcoma on the fine-needle aspiration cytology of cervical lymph node in an elderly patient, with FISH confirmation: A case report
Z Zhao 1, A Takano, A S T Lim, T H Lim, S Selvarajan
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PMID: 32342940Free article

Abstract


Introduction: Alveolar rhabdomyosarcoma (RMS) usually occurs in adolescents and young adults, and most frequently arises in the extremities.

Case report: We present a rare case of metastatic alveolar RMS from a nasal primary to cervical lymph nodes (LNs) in an elderly patient, diagnosed on the fine-needle aspiration (FNA) biopsy. Smears showed malignant round cells featuring focal rhabdoid appearance, with rhabdomyoblastic differentiation further supported by immunocytochemical stains. Diagnosis of alveolar RMS was confirmed by fluorescence in situ hybridization (FISH) identifying FOXO1 gene involvement with dual colour break-apart probes at locus 13q14.

Discussion: The differential diagnosis for a small round blue cell tumour in the elderly generally includes metastatic small cell carcinoma, lymphoma, malignant melanoma, RMS, desmoplastic small round cell tumour and Ewing's sarcoma/primitive neuroectodermal tumour. Subtle morphological analysis and expression pattern of immunostaining for skeletal muscle differentiation led to the diagnosis of RMS. Cytogenetic testing on the FOXO1 gene rearrangement helps definite subtyping of alveolar RMS.
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34
Malays J Pathol




. 2020 Aug;42(2):277-281.
Merkel cell carcinoma: Preparing to go the distance
M Arumugam 1, A Jamil, R A Amiseno, N Rosli, N Abdul Shukor
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PMID: 32860382Free article

Abstract


Introduction: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, with poor clinical outcomes. Typical conditions include a rapidly growing, solitary dome-shaped, violaceous nodule. Several root causes have been identified - sun exposure, age, lighter skin, immunocompromised state, and polyomavirus infection. Wide local excision is the best treatment. The tumour is radiotherapy-responsive. However, the success rate of the treatment with chemotherapy is rather limited. Immunotherapy has shown promising results. Early detection is important to prevent morbidity and mortality.

Case report: In this literature work, we reported on a particular case of MCC, as exhibited by an 84-year-old Chinese woman, and discussed the clinical features and management of MCC.

Discussion: We highlighted that MCC cases have a link to the polyomavirus 5. Patients who were identified with the Polyomavirus 5, and underwent immunotherapy, were seen to depict much better prognosis.
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35
Malays J Pathol




. 2020 Aug;42(2):259-265.
Histopathological study of carcinoma showing thymus-like differentiation (CASTLE)
Y Okubo 1, M Sakai, H Yamazaki, Y Sugawara, J Samejima, E Yoshioka, M Suzuki, K Washimi, K Kawachi, H Hayashi, H Ito, H Iwasaki, T Yokose
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PMID: 32860379Free article

Abstract


Introduction: Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumour that mainly arises from the thyroid gland, or occasionally, from the head and neck. Although the 10-year survival rate of patients with CASTLE is approximately 80%, local recurrence and distant metastasis are observed in some cases. A recent systematic review for CASTLE indicated that the prognostic factors are treatment-dependent, and postoperative radiotherapy significantly improves patient survival.

Case report: Herein, we describe and compare three cases of CASTLE, including a case with distant metastasis despite administering postoperative chemotherapy. Thus, the mechanisms underlying metastasis of CASTLE are unclear. This case study helps to elucidate the histopathological risk factors of metastasis in CASTLE.

Discussion: We found that prominent lymphovascular invasion and higher proliferative activities might be risk factors of metastasis in CASTLE. In addition, we have summarised the cytological, morphological, and immunohistochemical features of CASTLE for an accurate diagnosis.
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36
Malays J Pathol




. 2020 Aug;42(2):283-286.
Parotid gland oncocytic carcinoma: A rare entity in head and neck region
W S Wan Ahmad Kammal 1, M Azman, A A Salleh, S H Md Pauzi, N Abd Shukor
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PMID: 32860383Free article

Abstract


Oncocytic carcinoma of the salivary gland is an uncommon tumour in the head and neck region. Owing to its rarity, identifying the histopathological features of a malignant tumour can be difficult and challenging. We report a case of a 70-year-old man who presented with a left facial weakness for six months in a background history of left parotid swelling over the past 10 years. Clinical examination revealed a 3x3cm left parotid mass and grade 4 facial nerve palsy. Fine needle aspiration of the mass showed scattered cohesive, monolayered sheets of uniform oncocytic cells. Subsequently, a left total parotidectomy and selective neck dissection were performed. Histological examination showed sheets of small oncocytes with minimal nuclear atypia. Evidence of nerve entrapment, capsular invasion and perivascular permeation were identified in focal areas. Thus, a final diagnosis of oncocytic carcinoma was rendered.
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37
Malays J Pathol




. 2020 Aug;42(2):287-291.
Lymphoma with superimposed tuberculosis and fungal infection mimicking parapharyngeal abscess complicated with recurrent neurocardiogenic syncope: a case report
S N Sharudin 1, A N Huda Al Firdas, S Hitam, Z Hamid, N J Nordin, N Othman, H Abd Rahman, S A Md Arepen, E Hassan
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PMID: 32860384Free article

Abstract


Introduction: Lymphoma of parapharyngeal space (PPS) is a rare condition. The clinical presentations may vary and often masquerades as infection or an inflammatory condition. A misdiagnosis will lead to a delay in treatment of the disease. Due to the complex anatomy of PPS, any attributed pressure from masses can lead to a life-threatening event such as cardiac syncope.

Case report: We report a rare case of PPS B-cell non-Hodgkin lymphoma with superimposed Tuberculosis (TB) and fungal infection that presents with several episodes of syncope and hemodynamic depression.

Discussion: The clinical entities in PPS lesions syncope and its associated syndromes, pathophysiology, and differential diagnosis together with possible managements are further discussed.
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38
Malays J Pathol




. 2020 Aug;42(2):171-185.
Gene therapy: An updated overview on the promising success stories
R A Rashid 1, R Ankathil
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PMID: 32860369Free article

Abstract


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.
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39
Malays J Pathol




. 2020 Aug;42(2):267-271.
Wilms tumour with poor response to pre-operative chemotherapy: A report of 2 cases
H C L Tan 1, J H Tan, V M Vellusamy, Y Vasavan, C S Lim
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PMID: 32860380Free article

Abstract


Introduction: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy.

Case report: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.

Discussion: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.
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40
Malays J Pathol




. 2020 Aug;42(2):297-300.
The role of biochemical testing in cystic fibrosis
F H Abdul Rahim 1, C S Thambiah, I N Samsudin, N Mohamed Mokhtar
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PMID: 32860386Free article

Abstract


Introduction: Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder as a result of CF transmembrane conductance regulator gene mutation. It has a wide range of disease severity in patients with the same genotype.

Case report: A 5-year-old Malay boy with a history of recurrent pneumonia, presented with productive cough, fever and worsening tachypnoea. Physical examination revealed coarse crepitations, reduced breath sounds and clubbing. Biochemical investigations showed that he had respiratory type 2 failure as a result of bronchiectasis. Sweat conductivity done twice was raised supporting a diagnosis of CF. Other investigations such as bronchoscopy to look for congenital anomaly of the lung, infectious disease screening and tuberculosis, fungal and viral culture and sensitivity were negative. Further cascade screening revealed high sweat conductivity results in his siblings.

Discussion: Although CF prevalence is low in Malaysia, it is nevertheless an important diagnosis to be recognised as it is associated with increased morbidity.
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41
Malays J Pathol




. 2020 Aug;42(2):245-252.
Susceptibility patterns of anaerobes isolated from clinical specimens in tertiary Hospital, Malaysia
N Ishak 1, Z Abdul Wahab, S Amin Nordin, R Ibrahim
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PMID: 32860377Free article

Abstract


Introduction: The susceptibility patterns of anaerobes are becoming less predictable due to the emergence of anaerobic resistance trends to antibiotics; hence increasing the importance of the isolation and antimicrobial susceptibility testing of anaerobes.

Materials and methods: This study investigated the isolation of anaerobes from the clinical specimens of Hospital Sungai Buloh, Malaysia, from January 2015 to December 2015. All isolates were identified using the API 20A system (bioMérieux, France). Antimicrobial susceptibility testing was performed using the E-test (bioMérieux, France).

Results: The proportion of obligate anaerobes isolated from the clinical specimens was 0.83%. The Gram-positive anaerobes were most susceptible to vancomycin and imipenem, showing 100% sensitivity to these antimicrobials, followed by clindamycin (86.3%), penicillin (76.7%), and metronidazole (48.9%). Meanwhile, Gram-negative anaerobes were most susceptible to metronidazole (96%) followed by imipenem (89%), clindamycin (79%), and ampicillin (32%). The present study also showed that 3 out of 12 Bacteroides fragilis isolates were resistant to imipenem.

Conclusion: This study demonstrated the differences in the susceptibility patterns of anaerobes towards commonly used antimicrobials for the treatment of anaerobic infections. In summary, continuous monitoring of antimicrobial resistance trends among anaerobes is needed to ensure the appropriateness of treatment.
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42
Malays J Pathol




. 2020 Aug;42(2):273-276.
Extramedullary CD20-positive B-lymphoblastic lymphoma in a 5-year-old child: A diagnostic challenge
D Abdul Jalil 1, R Z A Raja Sabudin, Y L Tang, N Masir
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PMID: 32860381Free article

Abstract


Lymphoblastic leukaemia/lymphoma may present as an isolated extramedullary mass, which includes the musculoskeletal region involvement with normal or near-normal blood counts. The tumour may be in the form of B or T-lymphoblastic leukaemia/lymphoma. The clinical features and histological morphology of extramedullary B-lymphoblastic lymphoma (B-LBL) may mimic mature B-cell neoplasms, thus posing a diagnostic challenge. Arriving at the right diagnosis is crucial because these two diseases differ in their prognosis and management. A high index of suspicion is therefore important so as not to miss the correct diagnosis. The diagnosis may be overlooked because the clinical presentation may not be typical of B-LBL or the blood counts do not show any abnormalities. In this report, we highlight one such case where the diagnosis of B-LBL was missed because of its atypical presentation.
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