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Light chain multiple myeloma: an evaluation of its biochemical investigations

Siti Yazmin Zahari Sham ; Subashini C. THAMBIAH ; Intan Nureslyna SAMSUDIN ; Say Min LIM

The Malaysian Journal of Pathology.2017;39(3):311-315.

Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein ormonoclonal (M)-protein in serum or urine. The M-protein may consist of an intact immunoglobulin,the heavy chain only or the light chain only. The latter, designated as light chain multiplemyeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heraldedby hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions,reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free lightchain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. Thiscase illustrates a typical presentation of LCMM with focal discussion on its initial and diagnostic,as well as prognostic biochemical investigations.

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Severe asymptomatic hypophosphataemia in a child with T-acute lymphoblastic leukaemia

Nur Haidar ZAKARIA ; Pavai STHANESHWAR ; Hemalatha SHANMUGAM

The Malaysian Journal of Pathology.2017;39(3):317-320.

Hypophosphataemia is a metabolic disorder that is commonly encountered in critically ill patients.Phosphate has many roles in physiological functions, thus the depletion of serum phosphate could leadto impairment in multiple organ systems, which include the respiratory, cardiovascular, neurologicaland muscular systems and haematological and metabolic functions. Hypophosphataemia is defined asplasma phosphate level below 0.80 mmol per litre (mmol/L) and can be further divided into subgroupsof mild (plasma phosphate of 0.66 to 0.79 mmol/L), moderate (plasma phosphate of 0.32 to 0.65mmol/L) and severe (plasma phosphate of less than 0.32 mmol/L). The causes of hypophosphataemiainclude inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphateloss, and redistribution of phosphate into cells. Symptomatic hypophosphataemia associated withhaematological malignancies has been reported infrequently. We report here a case of asymptomaticsevere hypophosphataemia in a child with acute T-cell lymphoblastic leukaemia.A 14-year-old Chinese boy was diagnosed to have acute T cell lymphoblastic leukaemia (ALL).His serum biochemistry results were normal except inorganic phosphate and lactate dehydrogenaselevels. The serum inorganic phosphate level was 0.1mmol/L and the level was low on repeatedanalysis. The child had no symptoms related to low phosphate levels. The possible causes of lowphosphate were ruled out and urine Tmp/GFR was normal. Chemotherapy regime was started andthe serum phosphate levels started to increase. Hypophosphataemia in leukaemia was attributed toshift of phosphorus into leukemic cells and excessive cellular phosphate consumption by rapidlyproliferating cells. Several reports of symptomatic hypophosphataemia in myelogenous andlymphoblastic leukaemia in adults have been reported. To our knowledge this is the first case ofsevere asymptomatic hypophosphataemia in a child with ALL.

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Secondary polycythaemia in a Malay girl with homozygous Hb Tak

Hanizah Salwa AMRAN ; Mimi Azura AZIZ ; Elizabeth GEORGE ; Noraesah MAHMUD ; Tze Yan LEE ; Sabariah Md NOOR

The Malaysian Journal of Pathology.2017;39(3):321-326.

Hb Tak is one of more than 200 high affinity haemoglobin variants reported worldwide. It resultsfrom the insertion of two nucleotides (AC) at the termination codon, between codon 146 and codon147 of the beta-globin gene [Beta 147 (+AC)]. Polycythaemia is the main clinical feature althoughaffected carriers are usually asymptomatic and do not require intervention. Several case studies inthis region have reported the co-inheritance of Hb Tak with Hb E, delta beta and beta thalassaemiawith one case of homozygous Hb Tak in a Thai boy. In this case report, a cluster of haemoglobinTak was found in a family of Malay ethnic origin. Cascade family screening was conducted whileinvestigating a 4-year old girl who presented with symptomatic polycythaemia. She had 2 previousHb analysis done, at 7-month and 2-year-old with the diagnosis of possible Hb Q Thailand andHomozygous Hb D, respectively. Both diagnosis did not fit her clinical presentations. She was plethoric,had reduced exercise tolerance as well as cardiomyopathy. Her parents were consanguineouslymarried and later diagnosed as asymptomatic carriers of Hb Tak. Consequently, re-analysis of thegirl’s blood sample revealed a homozygous state of Hb Tak. In conclusion, high oxygen affinityhaemoglobin like Hb Tak should be considered in the investigation of polycythaemic patients withabnormal Hb analyses. In this case, DNA analysis was crucial in determining the correct diagnosis.

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Expression of clusterin in colorectal carcinoma in relation to clinicopathological criteria

Wafaey GOMAA ; Mahmoud AL-AHWAL ; Haneen Al MAGHRABI ; Abdelbaset BUHMEIDA ; Mohammad AL-QAHTANI ; Bassam AL-MAGHRABI ; Jaudah AL-MAGHRABI

The Malaysian Journal of Pathology.2017;39(3):243-250.

Background/Aim: Colorectal carcinoma (CRC) carries a high incidence of morbidity and mortality.Prognosis is related to nodal metastasis and stage. Clusterin is a widely distributed glycoproteinwith not yet fully understood functions. Clusterin may be overexpressed in some tumours or underexpressed in other tumours. The aim behind this study is to examine the relation of clusterincytoplasmic immunostaining to tumour characteristics, disease relapse, and survival in CRC. Materialsand Methods: Paraffin blocks of 133 CRCs were retrieved from the Department of Pathology,King Abdulaziz University, Jeddah, Saudi Arabia. Immunostaining was done using antibody toclusterin. Staining expression in 10% of malignant cells was used as a cut-off to determine lowimmunostaining and high immunostaining. Statistical tests were used to evaluate the association ofclusterin immunostaining with clinicopathological parameters. Results: Immunohistochemical resultsshowed clusterin low immunostaining in CRC and nodal metastases. No association was foundbetween clusterin immunostaining and tumour grade, age, tumour invasiveness, distant metastases,vascular invasion, nodal metastases, relapse, and survival. Conclusion: Our study showed low clusterinimmunostaining in CRC with lack of association with prognostic indicators in CRC. These resultsraise the controversy of understanding the role of clusterin in CRC. Further molecular studies arerequired to explore more about possible mechanisms of clusterin association with tumorigenicity,apoptosis, tumour growth progression, local and vascular invasion, and metastasis of CRC.

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Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma - a rare vascular neoplasm with deceptive morphology and distinctive immunophenotype

Cheo Fan FOON ; Kesavan SITTAMPALAM

The Malaysian Journal of Pathology.2017;39(3):305-309.

Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a rare, low grade vascular(endothelial) neoplasm typically presenting as multicentric, superficial to deep nodules in extremitieswith a slight tendency of affecting young adult males. We report a case of pseudomyogenichemangioendothelioma in a 15-year-old boy presenting initially with a 1 cm right thigh painlesscutaneous lump. The lump was excised with the clinical impression of a sebaceous cyst. On microscopy,a poorly circumscribed, mild to moderately atypical spindle cell lesion in fascicular and storiformpatterns with strikingly myoid-like eosinophilic cytoplasm was identified. The spindle cells werehighlighted by pancytokeratin AE1/AE3, CD31, and ERG with retained INI-1, while being negativefor MNF116, S100, CD34, EMA, desmin, SMA, caldesmon, myogenin, MyoD1, HHV-8 and CD163.Following the first diagnostic report, a positron emission tomography–computed tomography(PET-CT) scan revealed another 4 cm ill-defined nodule accompanied by a smaller adjacent 0.7cm ipsilateral satellite nodule within the right psoas muscle that displayed similar morphologyand immunophenotype as the cutaneous lump, supporting the multicentric feature of this uniqueentity. It is an uncommon yet increasingly recognised neoplasm of endothelial origin possessing amisleading myoid morphology and distinctive immunophenotype worth notifying.

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Psychological markers underlying murder weapon profile: a quantitative study

Kamaluddin MR ; Othman A ; Ismail KH ; Mat Saat GA

The Malaysian Journal of Pathology.2017;39(3):217-226.

The horrific nature of murder using different types of weapons has been an important focal point ofmany criminological studies. Weapons that are used in murders seem to play dominant roles in murderinvestigations as they may provide information leading to arrest. The established factors for weaponusage include environmental context, demography and availability of weapons. However, there isinsufficient research attention on the psychological functioning of murderers for particular weaponusage. In light of this, the current study seeks to narrow this gap of information by identifying theinfluences of psychological traits on weapon usage among a sample of male murderers. The presentcross-sectional study was conducted among 71 male murderers incarcerated in 11 prisons withinPeninsular Malaysia. The selection of the sample was based on predetermined selection criteriausing a purposive sampling method. A guided self-administered questionnaire comprising sociodemographyvariables and four Malay validated psychometric instruments: Zuckerman-KuhlmanPersonality Questionnaire-40-Cross-Culture, Self-control Scale, “How I Think” Questionnaire andAggression Questionnaire; was used. Independent sample t-test was performed to establish themean score differences of psychological traits between the murderers who used single and multipleweapons while Kruskal-Wallis tests were carried out to ascertain the differences between the specifictypes of weapons used among the murderers. Following this, one-way ANOVA was carried out toascertain the psychological trait differences among the murderers according to the different sourcesof weapon. Results indicated specific psychological traits influenced the number(s), source(s) andtype(s) of weapon used in committing murder. The findings have implications for the psychologicalprofiling of unknown murderers within the Malaysian context.

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Immunohistochemical expression of NANOG in urothelial carcinoma of the bladder

Mohd Khairul Anuar Md Akhir ; Huzlinda HUSSIN ; Abhimanyu VEERAKUMARASIVAM ; Chan Soon CHOY ; Maizaton Atmadini ABDULLAH ; Fauzah Abdul GHANI

The Malaysian Journal of Pathology.2017;39(3):227-234.

Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequencyof recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopyexamination is necessary for management of the disease. However, the monitoring and therapyregimen is expensive, incurring a massive burden to patients and the government. Therefore, thedevelopment of specific biomarkers for urothelial carcinoma at an early stage and recurrence detectionbecomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis.They might be potential prognostic markers for urothelial carcinoma. The study investigated theexpression pattern of NANOG which is one of a homeobox gene in different stages and grades ofurothelial carcinoma. NANOG expressions were also correlated with patient demographic factors andclinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embeddedurothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistryshowed positive expression of NANOG in all specimens with detection in the cytoplasm, nucleiand the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOGincreased across stages and grades of the tumour. The expression of NANOG was not significantlyassociated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) aswell as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p =0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOGexpression showed significant correlation with tumour invasion (p = 0.019). We concluded thatNANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.

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Distribution of gastric adenocarcinoma subtypes in different ethnicities in Kuala Lumpur, Malaysia

Asif SUKRI ; Alfizah HANAFIAH ; Nik Ritza KOSAI ; Mustafa Mohamed TAHER ; Isa Mohamed ROSE

The Malaysian Journal of Pathology.2017;39(3):235-242.

The multiracial population in Malaysia has lived together for almost a century, however, the risk ofgastric cancer among them varies. This study aimed to determine the distribution of different gastricadenocarcinoma subtypes and Helicobacter pylori infection status among gastric adenocarcinomapatients. Patients with gastric adenocarcinoma were enrolled from November 2013 to June 2015.Blood samples were collected for detection of H. pylori using ELISA method. Gastric adenocarcinomacases were more prevalent in the Chinese (52.8%), followed by the Malays (41.7%) and leastprevalent in the Indians (5.6%). Gastric adenocarcinoma located in the cardia was significantly moreprevalent in the Malays (66.7%) compared to the Chinese (26.3%), whereas non-cardia cancer wasdiagnosed more in the Chinese (73.7%) compared to the Malays (33.3%) [P = 0.019; OR = 5.6, 95CI: 1.27 to 24.64]. The Malays also had significantly higher prevalence of gastric tumour locatedat the cardia or fundus than other gastric sites compared to the Chinese (P = 0.002; OR: 11.2, 95%CI: 2.2 to 56.9). Among the cardia gastric cancer patients, 55.6% of the Malays showed intestinalhistological subtype, whereas all the Chinese had the diffuse subtype. More than half of the patients(55.3%) with gastric adenocarcinoma were positive for H. pylori infection and among them, 66.7%were Chinese patients. The risk of gastric adenocarcinoma in our population is different amongethnicities. Further studies on host factors are needed as it might play an important role in gastriccancer susceptibility in our population.

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DNA vaccination with a plasmid encoding LACK-TSA fusion against Leishmania major infection in BALB/c mice

Nahid MASPI ; Fatemeh GHAFFARIFAR ; Zohreh SHARIFI ; Abdolhossein DALIMI ; Seyedeh Zahra KHADEMI

The Malaysian Journal of Pathology.2017;39(3):267-275.

Vaccination would be the most important strategy for the prevention and elimination of leishmaniasis.The aim of the present study was to compare the immune responses induced following DNA vaccinationwith LACK (Leishmania analogue of the receptor kinase C), TSA (Thiol-specific-antioxidant) genesalone or LACK-TSA fusion against cutaneous leishmaniasis (CL). Cellular and humoral immuneresponses were evaluated before and after challenge with Leishmania major (L. major). In addition,the mean lesion size was also measured from 3th week post-infection. All immunized mice showed apartial immunity characterized by higher interferon (IFN)-γ and Immunoglobulin G (IgG2a) levelscompared to control groups (p<0.05). IFN-γ/ Interleukin (IL)-4 and IgG2a/IgG1 ratios demonstratedthe highest IFN-γ and IgG2a levels in the group receiving LACK–TSA fusion. Mean lesion sizesreduced significantly in all immunized mice compared with control groups at 7th week post-infection(p<0.05). In addition, there was a significant reduction in mean lesion size of LACK-TSA andTSA groups than LACK group after challenge (p<0.05). In the present study, DNA immunizationpromoted Th1 immune response and confirmed the previous observations on immunogenicity ofLACK and TSA antigens against CL. Furthermore, this study demonstrated that a bivalent vaccinecan induce stronger immune responses and protection against infectious challenge with L. major.

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Distribution of adeB and NDM-1 genes in multidrug resistant Acinetobacter baumannii isolated from infected wound of patients admitted in a tertiary care hospital in Bangladesh

Mohammad Jahirul HASAN ; SM SHAMSUZZAMAN

The Malaysian Journal of Pathology.2017;39(3):277-283.

Background: The adeB gene in Acinetobacter baumannii regulates the bacterial internal drug effluxpump that plays a significant role in drug resistance. The aim of our study was to determine theoccurrence of adeB gene in multidrug resistant and New Delhi metallo-beta-lactamase-1 (NDM-1) gene in imipenem resistant Acinetobacter baumannii isolated from wound swab samples in atertiary care hospital of Bangladesh. Methods: A total of 345 wound swab samples were testedfor bacterial pathogens. Acinetobacter baumannii was identified by culture and biochemical tests.Antimicrobial susceptibility pattern was determined by the disc diffusion method according toCLSI standards. Extended spectrum beta-lactamases were screened using the double disc synergytechnique. Gene encoding AdeB efflux pump and NDM-1 were detected by Polymerase ChainReaction (PCR). Results: A total 22 (6.37%) Acinetobacter baumannii were identified from 345wound swab samples and 20 (91%) of them were multidrug resistant. High resistance rates to someantibiotics were seen namely, cefotaxime (95%), amoxyclavulanic acid (90%) and ceftriaxone (82%).All the identified Acinetobacter baumannii were sensitive to colistin and 82% to imipenem. Two(9%) ESBL producing Acinetobacter baumannii strains were detected. adeB gene was detectedin 16 (80%) out of 20 multidrug resistant Acinetobacter baumannii. 4 (18%) of 22 Acinetobacterbaumannii were imipenem resistant. NDM-1 gene was detected in 2 (50%) of the imipenem resistantstrains of Acinetobacter baumannii. Conclusion: The results of this study provide insight into the roleof adeB gene as a potential regulator of drug resistance in Acinetobacter baumanni in Bangladesh.NDM-1 gene also contributes in developing such resistance for Acinetobacter baumannii.

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