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Fulltext SNP array technology: an array of hope in breast cancer research

Ho CC, Mun KS, Naidu R

Malays J Pathol, 2013 Jun;35(1):33-43.
PMID: 23817393 MyJurnal

Breast cancer is the most common malignancy in women worldwide. The incidence of breast cancer in Malaysia is lower compared to international statistics, with peak occurrence in the age group between 50 to 59 years of age and mortality rates of 18.6%. Despite current diagnostic and prognostic methods, the outcome for individual subjects remain poor. This is in part due to breast cancers' wide genetic heterogeneity. Various platforms for genetics studies are now employed to determine the identity of these genetic abnormalities, including microarray methods like high density single-nucleotide-polymorphism (SNP) oligonucleotide arrays which combine the power of chromosomal comparative genomic hybridization (cCGH) and loss of heterozygosity (LOH) in the offering of higher-resolution mappings. These platforms and their applications in highlighting the genomic alteration frameworks manifested in breast carcinoma will be discussed.
Fulltext Extra-adrenal paraganglioma: presentation in three uncommon locations

Mun KS, Pailoor J, Chan KS, Pillay B

Malays J Pathol, 2009 Jun;31(1):57-61.
PMID: 19694315 MyJurnal

Extra-adrenal paragangliomata are uncommon entities. They can be classified into four basic groups according to their anatomical sites, i.e. branchiomeric, intravagal, aorticosympathetic and visceral autonomic. Similar tumours may arise in sites away from the usual distribution of the sympathetic and parasympathetic ganglia, e.g. orbit, nose, small intestine and even in the pancreas. We report three instructive cases of extra-adrenal paraganglioma which were found in unusual sites such as urinary bladder, thyroid gland and on the wall of the inferior vena cava.
Silent bony calcification of coronaries in an adolescent--an unusual case

Murty OP, Mun KS, Hussin H

J Forensic Leg Med, 2008 Jan;15(1):37-41.
PMID: 18309549

This is a case report of 16-year-old adolescent school boy who died due to unusual calcification of coronary arteries. He died while cycling with his friends. While cycling fast he fell. He was brought dead to hospital. At times unsuspected cardiac lesions cause sudden death during extraneous physical activities in healthy persons. Sudden death in adolescents is not very common. It is an unusual case as apparently healthy adolescent boy actively participating in sports had stony hard coronary arteries. The coronaries showed advanced calcification and early bone formation. The myocardial septum had extensive fibrosis. The pathogenesis and other possible similar conditions are also discussed in the report.
Primary localised deep cutaneous amyloidosis of the eyelid

Mun KS, Pailoor J, Reddy SC

Malays J Pathol, 2005 Dec;27(2):113-5.
PMID: 17191394

A 62-year-old lady presented with a six-month history of swelling of the left upper eyelid, resulting in mild mechanical ptosis. Clinical assessment suggested a provisional diagnosis of dermoid cyst. The lesion was excised and histology revealed nodular deposits of amorphous eosinophilic material surrounded by lymphocytes and plasma cells. Special histochemistry and immunoperoxidase stain results showed deposition of amyloid, non-AA type. The lesion recurred 6 months later.
Fulltext Haemorrhaging lesion in the breast: is there a role for embolisation?

Taib N, Yip Ch, Ranganathan S, Moosa F, Mun K

Biomed Imaging Interv J, 2006 Jul;2(3):e30.
PMID: 21614243 MyJurnal DOI: 10.2349/biij.2.3.e30

Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.
Fulltext Cutaneous malignant melanoma: clinical and histopathological review of cases in a Malaysian tertiary referral centre

Pailoor J, Mun KS, Leow M

Malays J Pathol, 2012 Dec;34(2):97-101.
PMID: 23424771 MyJurnal

Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.
Fulltext Small Cell Transformation and T790M Mutation as Coresistance Mechanisms for First-line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy Failure

Shee-Chai C, Liam CK, Mun KS

J Thorac Oncol, 2017 10;12(10):e171-e173.
PMID: 28939153 DOI: 10.1016/j.jtho.2017.06.068
The correlation of EMT and p53 immunohistochemical markers with cisplatin resistance in muscle invasive bladder cancer patients: A single-centred study

Paramanantham Y, B M Said NA, Mun KS

Malays J Pathol, 2023 Apr;45(1):19-29.
PMID: 37119243

INTRODUCTION: Although epithelial-mesenchymal transition (EMT) and p53 have been established to play a pivotal role in the aggressiveness of muscle-invasive bladder cancer (MIBC), its pathological correlation to cisplatin treatment in the Malaysian patient cohort is lacking. This study aimed to evaluate the association of EMT markers, e-cadherin, vimentin and actin, as well as tumour suppressor gene, p53, in cisplatin-receiving MIBC patients.
MATERIALS AND METHODS: Formalin-fixed paraffinembedded (FFPE) blocks of muscle-invasive bladder cancer patients receiving cisplatin-based chemotherapy between January 2010 to December 2020 were traced. Immunohistochemistry staining was performed on traced blocks using antibodies to e-cadherin, vimentin and actin, and p53.
RESULTS: p53 and e-cadherin were stained positive in most cases (p=0.515 and 0.242 respectively), although e-cadherin showed stronger positive expression in pre-cisplatin receiving MIBC cases. All the cases stained negative for actin and vimentin except for faint staining observed in one pre-cisplatin case.
CONCLUSION: Although this study does not show a significant correlation between EMT markers and p53 with cisplatin-responsiveness in MIBC patients, the results serve as preliminary findings on the heterogeneous outcomes of molecular staining in the Malaysian MIBC patient cohort.
Fulltext Cervical abscesses due to co-infection with Burkholderia pseudomallei, Salmonella enterica serovar Stanley and Mycobacterium tuberculosis in a patient with diabetes mellitus

Sulaiman H, Ponnampalavanar S, Mun KS, Italiano CM

BMC Infect Dis, 2013 Nov 09;13:527.
PMID: 24209898 DOI: 10.1186/1471-2334-13-527

BACKGROUND: Infections due to Mycobacterium tuberculosis, Burkholderia pseudomallei and non-typhoidal Salmonella cause significant morbidity and mortality throughout the world. These intracellular pathogens share some common predisposing factors and clinical features. Co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.
CASE PRESENTATION: In September 2010, a 58-year-old diabetic Malaysian male presented with fever and a fluctuant mass on the right side of his neck. B. pseudomallei was isolated from an aspirate of this lesion and there was radiological evidence of disseminated infection in the liver and spleen. The recurrence of clinical symptoms over ensuing months prompted further aspiration and biopsy of a cervical abscess and underlying lymph nodes. Salmonella enterica serovar Stanley and then M. tuberculosis were identified from these specimens by culture and molecular methods. The patient responded to targeted medical management of each of these infections.
CONCLUSION: In endemic settings, a high index of suspicion and adequate tissue sampling are imperative in identifying these pathogenic organisms. Diabetes was identified as a predisposing factor in this case while our understanding of other potential risk factors is evolving.
Fulltext Imaging findings of a primary bladder maltoma

Maninderpal KG, Amir FH, Azad HA, Mun KS

Br J Radiol, 2011 Sep;84(1005):e186-90.
PMID: 21849361 DOI: 10.1259/bjr/66130737

Secondary involvement of the urinary bladder in non-Hodgkin's lymphoma is relatively common; however, primary malignant lymphoma of this organ is extremely rare. The most common type of primary bladder lymphoma is a low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. We report here on the imaging findings of a primary bladder lymphoma with bone marrow infiltration.
Fulltext Proliferating cell nuclear antigen (PCNA) activity in hepatocellular carcinoma, benign peri-neoplastic and normal liver

Mun KS, Cheah PL, Baharudin NB, Looi LM

Malays J Pathol, 2006 Dec;28(2):73-7.
PMID: 18376794 MyJurnal

Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes.
Fulltext Malignant Transformation of a Rosette-Forming Glioneuronal Tumor with IDH1 Mutation: A Case Report and Literature Review

Jayapalan RR, Mun KS, Wong KT, Sia SF

World Neurosurg X, 2019 Apr;2:100006.
PMID: 31218281 DOI: 10.1016/j.wnsx.2018.100006

Background: Rosette-forming glioneuronal tumor (World Health Organization grade I) is considered as a benign tumor with very low potential for progression. The potential for malignant transformation of this tumor is not known and has never been reported before in literature.
Case Description: We report a 42-year-old man, diagnosed with rosette-forming glioneuronal tumor of the fourth ventricle with a positive isocitrate dehydrogenase 1 mutation, progressed to glioblastoma after 6 years from diagnosis. We discuss the clinical history, radiological findings, and histopathological characteristic with immunohistochemistry findings observed in this unique case.
Conclusions: Despite being acceptable as benign, based on our observations in this case, there is a potential for malignant transformation of rosette-forming glioneuronal tumor. The role of isocitrate dehydrogenase 1 mutation leading to malignant transformation could not be established as our finding is novel and further prospective studies are required to prove this association.
Malignant epithelioid haemangioendothelioma of the maxillary sinus

Wong HT, Mun KS, Zulkiflee AB, Prepageran N

Pathology, 2016 Jan;48(1):95-6.
PMID: 27020222 DOI: 10.1016/j.pathol.2015.11.022
Interdigitating dendritic reticulum cell sarcoma: cytologic, histologic and immunocytochemical features

Jayaram G, Mun KS, Elsayed EM, Sangkar JV

Diagn Cytopathol, 2005 Jul;33(1):43-8.
PMID: 15945093

Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant morphologic overlap with other malignancies. Fine-needle aspiration cytologic appearances of this neoplasm are not well understood. A 33-yr-old woman presented with a rapidly growing nodular mass in the right upper cervical region and right-sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid forms with prominent nucleoli and chromatin clumping as well as binucleated cells and cells with lobulated nuclei were seen. Numerous mitoses were observed. The tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the growth showed nodal tissue effaced by a tumor composed of large, pleomorphic neoplastic cells with some binucleate and multinucleate forms resembling Reed-Sternberg cells. The intervening stroma contained numerous small lymphocytes. Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino-embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme, smooth-muscle actin, and desmin. The combined histologic and immunohistologic features suggested a histiocytic/dendritic reticulum cell neoplasm and a diagnosis of interdigitating dendritic reticulum cell sarcoma was made.
Fulltext Kombiglyze (metformin and saxagliptin)-induced hepatotoxicity in a patient with non-alcoholic fatty liver disease

Thalha AM, Mahadeva S, Boon Tan AT, Mun KS

JGH Open, 2018 Oct;2(5):242-245.
PMID: 30483596 DOI: 10.1002/jgh3.12083

A 33-year-old man was referred with hyperosmotic symptoms of 4 weeks. Clinical examination showed palpable hepatomegaly and no stigmata of liver disease. Findings were random glucose 16.6 mmol/L, HbA1c 12.4%, triglyceride 6.2 mmol/L, normal LFTs and ultrasound liver: increased echogenicity. Management consisted of dietician referral and commencement of metformin 500 mg bd, diamicron MR 60 mg od, and fenofibrate 145 mg od. He was non-compliant, complaining of "heaviness of head" after consuming oral diabetic agents, without symptoms of hypoglycemia. Treatment was switched to Kombiglyze XR (saxaglipitin 5 mg + metformin 1000 mg) and empagliflozin 25 mg od. He presented 1 week later with generalised pruritus with ALT 307 IU/L and serum GGT 808 IU/L. Following this, a percutaneous liver biopsy was performed, revealing steatohepatitis and marked intra-hepatic cholestasis. Kombiglyze XR was withheld, with resolution of LFTs to baseline. Phenotypes of liver injury are categorised according to R value, defined as ratio ALT/ULN:ALP/ULN. R value of ≥5:hepatocellular injury, ≤2:cholestatic injury, 2-5:mixed-type injury. Here, R value points toward mixed type (R = 3.203). Hepatotoxicity in patients with NASH is difficult to diagnose, based on laboratory parameters. Liver histology was useful in indicating additional changes apart from NASH, causing liver derangement. The Rousal Uclaf Causality Assessment Method is a scoring method to determine the probability of drug induced liver injury. RUCAM score for this case was 6 (probable adverse drug reaction). Hepatotoxicity from saxagliptin not been reported prior. Clinicians need to be more vigilant, particularly in patients with NASH.
Carbonic anhydrase IX immunohistochemistry has potential to predict renal cell carcinoma outcomes: A systematic review and meta-analyses

Samberkar S, Rajandram R, Mun KS, Samberkar P, Danaee M, Zulkafli IS

Malays J Pathol, 2019 Dec;41(3):233-242.
PMID: 31901907

INTRODUCTION: Tissue biomarker carbonic anhydrase IX (CAIX) is purported to have prognostic value for renal cell carcinoma (RCC) but contradicting findings from previous studies have also been documented. This study aims to perform a systematic review and meta-analysis on the role of CAIX in RCC disease progression.
MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, online searches of multiple databases were performed to retrieve articles from their inception until December 2017. Inclusion criteria included all English-based original articles of immunohistochemistry (IHC) studies investigating CAIX expression in human RCC tissue. Four articles were finally selected for meta-analysis with a total of 1964 patients. Standard meta-analysis methods were applied to evaluate the role of CAIX in RCC prognosis. The relative risk (RR) and its 95% confidence interval (CI) were recorded for the association between biomarker and prognosis, and data were analysed using MedCalc statistical software.
RESULTS: The meta-analysis showed that high CAIX expression was associated with low tumour stage (RR 0.90%, 95% CI 0.849-0.969, p= 0.004), low tumour grade (RR 0.835%, 95% CI 0.732-0.983, p= 0.028), absence of nodal involvement (RR 0.814%, 95% CI 0.712-0.931, p= 0.003) and better ECOS-PS index (RR 0.888%, 95% CI 0.818-0.969, p= 0.007). The high tissue CAIX expression in RCC is hence an indication of an early malignancy with a potential to predict favourable disease progression and outcome.
CONCLUSION: The measurement of this marker may be beneficial to determine the course of the illness. It is hoped that CAIX can be developed as a specific tissue biomarker for RCC in the near future.
Fulltext A rare case of perivascular epithelioid cell tumour metastases to the brain

Jayapalan RR, Bahuri NFA, Mun KS, Narayanan V

SAGE Open Med Case Rep, 2019;7:2050313X19828539.
PMID: 30783531 DOI: 10.1177/2050313X19828539

Perivascular epithelioid cell tumour is a rare mesenchymal tumour with distinct immunohistochemical profile. While it is known to occur in various anatomical sites, the central nervous system had always been a protected site for primary or secondary perivascular epithelioid cell tumours. We describe a 61-year-old lady who presented with symptoms of raised intracranial pressure, 3 months after the resection of duodenal and thoracic tumours which were histologically consistent with perivascular epithelioid cell tumour. She was investigated and then subsequently subjected to resection of two metastatic intracranial lesions. The radiological, intraoperative as well as histopathological findings of the metastatic lesions are discussed. Metastatic perivascular epithelioid cell tumour of the brain is extremely rare. However, patients who are stratified as high risk for recurrence or metastases should undergo an early magnetic resonance imaging/computed tomography of the brain in addition to a whole-body positron emission tomography scan, to allow for early detection and management of these tumours.
Fulltext Expression of osteopontin, matrix metalloproteinase-2 and -9 proteins in vascular instability in brain arteriovenous malformation

Anbarasen L, Lim J, Rajandram R, Mun KS, Sia SF

PeerJ, 2019;7:e7058.
PMID: 31275742 DOI: 10.7717/peerj.7058

Background: Matrix metalloproteinase (MMP)-2 and -9 are Osteopontin (OPN) dependent molecules implicated in the destabilization of blood vessels. OPN and MMPs have been studied in brain arteriovenous malformation (BAVM) patients' tissues and blood samples before intervention. In this study, we compared the serum level of these markers before and after treatment, as well as assessed their protein expressions in BAVM tissues to evaluate their roles in this disease.
Methodology: Serum samples from six BAVM patients and three control subjects were analyzed using enzyme-linked immunoabsorbent assay (ELISA) for OPN. A total of 10 BAVM patients and five control subjects were analyzed using Multiplex ELISA for MMPs. A total of 16 BAVM tissue samples and two normal brain tissue samples were analyzed using immunohistochemistry.
Result: MMP-2 and -9 were significantly higher in the serum of BAVM patients before and after treatment than in control patients. There were no significant differences of OPN and MMP-9 serum level in BAVM patients before and after treatment. MMP-2 showed a significant elevation after the treatment. Expression of OPN, MMP-2 and -9 proteins were seen in endothelial cells, perivascular cells and brain parenchyma of BAVM tissues.
Conclusion: Findings revealed that the level of MMP-2 and -9 in the serum correlated well with the expression in BAVM tissues in several cases. Knockdown studies will be required to determine the relationships and mechanisms of action of these markers in the near future. In addition, studies will be required to investigate the expression of these markers' potential applications as primary medical therapy targets for BAVM patients.
Fulltext Hemangiopericytoma 11 years later: delayed recurrence of a rare soft tissue sarcoma

Cheng KP, Wong WJ, Hashim S, Mun KS

J Thorac Dis, 2017 Sep;9(9):E752-E756.
PMID: 29221336 DOI: 10.21037/jtd.2017.08.74

Hemangiopericytomas (HPCs) are uncommon tumours. We present the case of a 41-year-old female with multiple resections at different sites over the course of 11 years. The approach considerations, as well as treatment options and prognosis are discussed. A 41-year-old female with two previous resections for intracranial meningeal HPC in 2004 and 2008, as well as adjuvant radiotherapy, presented in 2015 with left intrathoracic and left hip recurrence confirmed by positron emission tomography/computed tomography (PET/CT). She underwent left proximal femur resection/reconstruction and video-assisted thoracoscopic surgery (VATS) resection of the intrathoracic tumour was attempted. She was discharged home on her 4th post-operative day with minimal pain. There were no neurosensory or motor deficits. Any patient who has been diagnosed with HPC in the past who develops new symptoms should be worked up for recurrence, regardless of the length of disease-free interval, as our case study suggested. There has yet to be a standardized follow-up regime due to the rarity of these tumours. HPC remains a rare soft tissue sarcoma with high recurrence rate. Planned VATS evaluation and resection is possible provided complete resection with clear surgical margins can be achieved, as clear surgical margins offer the best chance of survival.
Fulltext Aneurysmal bone cyst of the maxilla

Tang IP, Shashinder S, Loganathan A, Anura MM, Zakarya S, Mun KS

Singapore Med J, 2009 Sep;50(9):e326-8.
PMID: 19787162

An aneurysmal bone cyst is a rare bone lesion. Its origin and precise nature remain unknown. It is seen as a locally-destructive, rapidly expandable, benign multicystic mass. We report a 17-year-old boy with an aneurysmal bone cyst of the maxilla, with extensive local involvement and bony destruction that was treated surgically. There was no recurrence noted after four years of follow-up.

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