Displaying publications 1 - 20 of 63 in total

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  1. Aleukemic bcr-abl positive granulocytic sarcoma
    Kuan JW, Pathmanathan R, Chang KM, Tan SM
    Leuk. Res., 2009 Nov;33(11):1574-7.
    PMID: 19215983 DOI: 10.1016/j.leukres.2009.01.016
    Granulocytic sarcoma (GS) can occur de novo or in association with intramedullary myeloid disorders. With the advent of sophisticated molecular detection techniques to detect diagnostic genes such as bcr-abl, PML-RARA and CBFB/MYH11 in bone marrow or peripheral blood, many cases of the so called 'primary' GS are questionable. We report a case of primary GS where the tumor mass bcr-abl translocation was demonstrated by fluorescent in situ hybridization in which there was no evidence of chronic myeloid leukemia (CML). This is an important finding as it highlights the possibility that CML may present as a sole extramedullary form, and illustrates potential treatment by tyrosine kinase inhibitor.
  2. Fulltext Alveolar rhabdomyosarcoma of the neck in a two-months-old baby: diagnostic challenges
    Nordashima, A.S., Azyani, Y., Amizatul Aini, S., Boekhren, K.B., Hamidah A., Pathmanathan R.
    Medicine & Health, 2019;14(1):228-233.
    MyJurnal
    Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. The rarity of its occurrence in infant poses a great difficulty in terms of diagnosis and management. Here, we report an aggressive case of alveolar rhabdomyosarcoma in an infant who presented with neck swelling and neurological complications. The Magnetic Resonance Imaging (MRI) revealed a soft tissue swelling of the neck with intraspinal extension and spinal cord compression, raising the possibility of a neurogenic or malignant nerve sheath tumour. Histopathological examination revealed a primitive, small round cell tumour with no rhabdoid differentiation. The clinical presentation, neurological symptoms, tumor location and the histopathologic features were highly suggestive of neuroblastoma. However, the tumour cells were positive for desmin with focal and weak nuclear positivity for myogenin and MyoD1; immunoexpressions which were in favour of rhabdomyosarcoma. Fluorescent in situ hybridization (FISH) confirmed the presence of a translocation t(2;13)(q35;q14), supporting the diagnosis of alveolar rhabdomyosarcoma. Despite chemotherapy, patient succumbed to death after two months due to septic shock. Rhabdomyosarcoma is highly aggressive mesenchymal neoplasm which may present with diagnostic difficulty. This case highlights the importance of molecular studies in making an accurate diagnosis so that appropriate chemotherapy may be instituted.

  3. Anorectal melanoma
    Jalleh RP, Pathmanathan R, Krishnan MM, Mukherjee A
    Postgrad Med J, 1988 Sep;64(755):669-71.
    PMID: 3251217
    Four cases of anorectal melanoma are presented. The authors believe that this is the first report of the occurrence of this tumour in Malays. Advanced disease at initial presentation accounts for the poor prognosis observed in this series. Surgery remains the principal treatment modality, although controversy exists regarding optimal extent of resection.
  4. Carcinoma of the vulva in pregnancy: a rare occurrence
    Sivanesaratnam V, Pathmanathan R
    Asia Oceania J Obstet Gynaecol, 1990 Sep;16(3):207-10.
    PMID: 2088243
    A rare case of squamous cell carcinoma diagnosed in early pregnancy in a 28-year-old woman is described. At the time of radical surgery, which was carried out in the puerperium, the growth had already advanced to Stage IV disease. The rapid growth of the tumor seen in this patient suggests that although treatment needs to be individualised, the definitive radical surgery should not be delayed.
  5. Clear cell "sugar" tumour of the lung: a case report
    Shiran MS, Tan GC, Arunachalam N, Sabariah AR, Pathmanathan R
    Malays J Pathol, 2006 Dec;28(2):113-6.
    PMID: 18376801
    We report a case of clear cell "sugar" tumour of the lung (CCTL) occurring in a 26-year-old lady. The patient was asymptomatic and the lesion was picked up in the course of a pre-employment medical examination. A well-defined 5 cm nodule in the right lower lobe was detected on routine chest X-Ray. Microscopical examination of the coin lesion showed clear cells containing abundant diastase-sensitive intracytoplasmic glycogen, as demohstrated with periodic acid-Schiff stains. Tumour immunoreactivity for HMB-45 and non-reactivity for cytokeratin support the histological diagnosis. To our knowledge, this is the first reported case of CCTL in Malaysia.
  6. Fulltext Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma
    Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N
    N Engl J Med, 1995 Sep 14;333(11):693-8.
    PMID: 7637746 DOI: 10.1056/NEJM199509143331103
    BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
    METHODS: EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.
    RESULTS: Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.
    CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.
  7. Fulltext Clonorchiasis/opisthorchiasis in Malaysians case reports and review
    Shekhar KC, Nazarina AR, Lee SH, Pathmanathan R
    Med J Malaysia, 1995 Jun;50(2):182-6.
    PMID: 7565193
    Clonorchiasis and opisthorchiasis are snail-transmitted trematode infections. The disease is endemic in many parts of Asia. Local case reports have been predominantly in Chinese with a history of travel to endemic countries. Thus far, 20 cases of liver fluke infestation have been reported in this country. This report presents another two cases of clonorchiasis and a case of opisthorchiasis. We also briefly review pertinent aspects of the disease.
  8. Cryptococcosis in the University Hospital, Kuala Lumpur and review of published cases
    Pathmanathan R, Soo-Hoo Tuck Soon
    Trans R Soc Trop Med Hyg, 1982;76(1):21-4.
    PMID: 7080152
    Between January 1974 and June 1980, 85 cases of cryptococcosis were diagnosed in the University Hospital, Kuala Lumpur, Malaysia. The diagnosis was based on positive culture of the organism in 81 cases; the remaining four were diagnosed on histopathological findings. Cerebral cryptococcosis was the most common presentation and Chinese are particularly susceptible (72% of cases). The incidence of the disease is shown to be far greater than previously suspected. Association with compromised host status is uncommon (14%). The local literature is briefly reviewed and the findings discussed.
  9. Fulltext Cutaneous mycobacterial spindle cell pseudotumour
    Tan GC, Yap YP, Shiran MS, Sabariah AR, Pathmanathan R
    BMJ Case Rep, 2009;2009.
    PMID: 21686408 DOI: 10.1136/bcr.11.2008.1221
    Mycobacterial spindle cell pseudotumour (MSCP) has been reported in various sites, including skin, lymph nodes, bone marrow, lung and spleen. Cutaneous lesions are extremely rare and the differential diagnoses include various spindle cell lesions. Literature review shows that this lesion has preponderance for upper limb involvement and occurs largely in immunosuppressed individuals. We report a case of MSCP of the skin due to atypical mycobacterium and discuss the risk of misdiagnosis as a sarcoma.
  10. Cystic lesion of the parotid gland with squamous metaplasia mistaken for squamous cell carcinoma. A case report
    Jayaram G, Pathmanathan R, Khanijow V
    Acta Cytol., 1998 Nov-Dec;42(6):1468-72.
    PMID: 9850664
    BACKGROUND: The diverse range of diseases that affect the salivary glands may lead to problems and pitfalls in cyto-diagnosis. While false negative diagnosis of cystic salivary gland tumors is well known, false positive cytodiagnosis in nonneoplastic salivary cysts is less well documented.

    CASE: An 85-year-old female presented with a painless left parotid gland swelling of three months' duration. Fine needle aspiration cytology yielded fluid, smears of which showed keratinizing squamous cells with nuclear atypia leading to a cytologic diagnosis of cystic squamous cell carcinoma. A total radical parotidectomy followed. Histopathologic study showed cystic dilatation of many of the salivary ducts, which were lined with metaplastic squamous epithelium that showed atypia. There was no evidence of squamous cell carcinoma.

    CONCLUSION: Squamous metaplasia is known to occur in benign salivary gland lesions, such as pleomorphic adenoma and Warthin's tumors, as well as in salivary duct cysts and necrotizing sialometaplasia. However, atypical squamous metaplasia of salivary duct cysts mimicking squamous cell carcinoma on cytology is unusual.
  11. Fulltext Declining post-mortems: a cause for concern
    Pathmanathan R, Chandrasekharan N
    Med J Malaysia, 1985 Dec;40(4):267-70.
    PMID: 3842725
  12. Detection of Epstein-Barr virus DNA in nasopharyngeal carcinoma using a non-radioactive digoxigenin-labelled probe
    Permeen AM, Sam CK, Pathmanathan R, Prasad U, Wolf H
    J Virol Methods, 1990 Mar;27(3):261-7.
    PMID: 2157729
    The presence of Epstein Barr virus (EBV) DNA in biopsies from the post-nasal space (PNS) of patients suspected of nasopharyngeal carcinoma (NPC) was detected by in situ cytohybridization with an EBV DNA probe labelled with the novel labelling compound digoxigenin. The digoxigenin probe was hybridised to cryostat sections of NPC biopsies and subsequently detected by an enzyme immunoassay procedure. It was found that in situ cytohybridization using the digoxigenin probe was much more rapid and sensitive (96 h compared to five weeks) than the current method of using 3H-labelled probe. Using the digoxigenin EBV probe, it was found that in all the eighteen NPC biopsies tested, EBV DNA was detected in malignant epithelial cells and infiltrating lymphocytes. EBV DNA was also detected in some normal epithelial cells in these NPC biopsies. EBV DNA was not detected in epithelial cells of non-malignant biopsies.
  13. Fulltext Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients
    Shi Yeen TN, Pathmanathan R, Shiran MS, Ahmad Zaid FA, Cheah YK
    J Biomed Sci, 2013 Apr 16;20:22.
    PMID: 23590575 DOI: 10.1186/1423-0127-20-22
    BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of these methods.

    RESULTS: All of the mutations were found in adenocarcinoma, except one that was in squamous cell carcinoma. The mutation rate was 45.7% (221/484). Complex mutations were also observed, wherein 8 tumours carried 2 mutations and 1 tumour carried 3 mutations.

    CONCLUSIONS: Both methods detected EGFR mutations in FFPE samples. HRM assays gave more EGFR positive results compared to Scorpion ARMS.

  14. Fulltext Diabetic mastopathy: a case report and literature review
    Neetu G, Pathmanathan R, Weng NK
    Case Rep Oncol, 2010 Jul 16;3(2):245-251.
    PMID: 20740205 DOI: 10.1159/000318641
    Diabetic mastopathy is a rare fibroinflammatory breast disease characterized by lymphocytic lobulitis, ductitis, and perivasculitis with stromal fibrosis. This lesion often presents as a discretely palpable uni- or bilateral mass in long-standing type I diabetes and other autoimmune diseases. We report a case of insulin-dependent diabetic mastopathy, which presented clinically as an indeterminate breast lump suspicious for malignancy. The patient is a 36-year-old woman who had type 1 insulin-dependent diabetes mellitus. Mammography and ultrasonography raised a suspicion of malignancy, and an excisional biopsy was performed. A previous biopsy had shown no evidence of malignancy. Histopathological examination now showed dense keloid-like stromal fibrosis with epithelioid-like and spindly myofibroblasts and a characteristic lymphocytic infiltration around blood vessels in and around lobules and ducts, features consistent with diabetic mastopathy. The literature is briefly reviewed.
  15. Fulltext Disseminated histoplasmosis presenting as a non-healing tongue ulcer
    Liam CK, Chua CT, Pathmanathan R
    Singapore Med J, 1990 Jun;31(3):286-8.
    PMID: 2392708
    A 51-year old man presented with a persistent tongue ulcer, fever, cervical lymphadenopathy and hepatomegaly. The diagnosis was initially thought to be tuberculosis. This led to the initiation of antituberculous chemotherapy to which the patient failed to respond. The correct diagnosis of histoplasmosis was made after the detection of Histoplasma capsulatum on further review of the tongue ulcer biopsy specimen. He responded to treatment with amphotericin B.
  16. ERG oncoprotein expression in prostate carcinoma patients of different ethnicities
    Kelly GM, Kong YH, Dobi A, Srivastava S, Sesterhenn IA, Pathmanathan R, et al.
    Molecular and clinical oncology, 2015 Jan;3(1):23-30.
    PMID: 25469265
    Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.
  17. Effect of dietary palm oils on mammary carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene
    Sundram K, Khor HT, Ong AS, Pathmanathan R
    Cancer Res, 1989 Mar 15;49(6):1447-51.
    PMID: 2493981
    Female Sprague-Dawley rats, 50 days of age, were treated with a single dose of 5 mg of 7,12-dimethylbenz(a)anthracene intragastrically. 3 days after carcinogen treatment, the rats were put on semisynthetic diets containing 20% by weight of corn oil (CO), soybean oil (SBO), crude palm oil (CPO), refined, bleached, deodorized palm oil (RBD PO) and metabisulfite-treated palm oil (MCPO) for 5 months. During the course of experiments, rats fed on different dietary fats had similar rate of growth. Rats fed 20% CO or SBO diet have higher tumor incidence than rats fed on palm oil (PO) diets; however differences of mean tumor latency periods among the groups were not statistically significant. At autopsy, rats fed on high CO or SBO diets had significantly more tumors than rats fed on the three PO diets. Our results showed that high PO diets did not promote chemically induced mammary tumorigenesis in female rats when compared to high CO or SBO diets. CO and SBO differ greatly from the palm oils in their contents of tocopherols, tocotrienols, and carotenes. But further experiments would be required to determine whether the observed differences in tumor incidence and tumor numbers were due to the differences in these minor components or due to the unique triglyceride structure of the palm oils. Analysis of the fatty acid profiles of plasma total lipids of tumor-bearing rats and of the tumor total lipids showed that, with the exception of arachidonic acid, the fatty acid profiles reflect the nature of the dietary fats. At autopsy, there were no differences in the plasma total cholesterol contents among rats fed on different dietary fats, but rats fed on palm oil diets had a significantly higher plasma triglyceride level than that of rats fed CO or SBO diets. As for the tumor lipids, there were no significant differences in the triglyceride, diglyceride, and phospholipid levels when the CO or SBO groups were compared to the palm oil groups.
  18. Elevated secretory IgA antibodies to Epstein-Barr virus (EBV) and presence of EBV DNA and EBV receptors in patients with cervical carcinoma
    Se Thoe SY, Wong KK, Pathmanathan R, Sam CK, Cheng HM, Prasad U
    Gynecol Oncol, 1993 Aug;50(2):168-72.
    PMID: 8397152
    Epstein-Barr virus (EBV) receptors (EBV/C3d receptors) were detected, using the monoclonal antibody HB5, on 23 ectocervical and 5 endocervical biopsies of the uterine cervix. Elevated IgA titers against the viral capsid antigen and early antigen of EBV were also found in the cervical secretions from cervical carcinoma patients (83%), compared with samples from patients with cervical intraepithelial neoplasia (75%), herpes simplex virus-infected patients (0%), and gynecologic patients with nonmalignant conditions (0%). EBV DNA was present in 63% of cervical carcinoma biopsies detected by in situ hybridization. These observations suggest a positive association between EBV and carcinoma of the cervix.
  19. Epstein-Barr virus associated diseases: an update
    Pathmanathan R
    Malays J Pathol, 1993 Dec;15(2):105-13.
    PMID: 8065170
    The Epstein-Barr virus (EBV), traditionally linked etiologically with infectious mononucleosis (IM), endemic Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) has in recent years been associated with a host of other conditions. Viral strategies for entry into cells and persistence, as well as various molecular mechanisms involved in latency, replication and transformation have been elucidated. EBV termini analysis has demonstrated the essentially clonal nature of BL, NPC and preneoplastic lesions of the nasopharynx. Strain variation between isolates of EBV suggests that differences in epithelial cell tropism among strains may exist. Treatment of EBV-associated syndromes is largely supportive although antivirals may play a role in the management of oral hairy leukoplakia. At the present time, the development of an effective vaccine remains a viable proposition.
  20. Evaluation of the possible role of glucose, carnitine, coenzyme Q10 and steroids in the treatment of Reye's syndrome using the margosa oil animal model
    Sinniah D, Sinniah R, Baskaran G, Pathmanathan R, Yamashita F, Yoshino M
    Acta Paediatr Jpn, 1990 Aug;32(4):462-8.
    PMID: 2288230
    Glucose and steroids have been used in the treatment of children with Reye's syndrome, while carnitine and coenzyme Q10 have been the subject of some recent studies which suggest that these agents may have a role in the treatment of Reye's syndrome and Reye-like syndrome due to margosa oil poisoning. Because of the paucity of causes of Reye's syndrome seen at any one centre, the clinical variability of the disease, and limited knowledge of definite aetiologic factors, controlled clinical trials are not easy to carry out or to interpret in human cases. These caveats were overcome by evaluation of these four treatment modalities in an established margosa-oil-induced animal model of Reye's syndrome. Effectiveness of the treatment modalities was determined from clinical response and histopathologic parameters (grading of light microscopic fatty changes and ultrastructural changes in the hepatocytes). Results show that carnitine per se produces a small improvement in survival, but statistically, more significant benefit is seen with glucose administration. Carnitine plus 10% dextrose appears to produce better results. Evaluation of coenzyme Q10 and carnitine on histopathologic parameters in the liver after a sublethal dose of margosa oil showed no obvious ameliorating effect on liver pathology. Steroids (dexamethasone/methylprednisolone) had no beneficial effects in reducing mortality, affecting glycogen storage or lipid accumulation. Changes in the mitochondria, ribosomes and endoplasmic reticulum were unaltered from the groups treated with margosa oil alone. While glucose and carnitine supplements appear to be beneficial, the other modes of therapy do not seem to hold much promise in the treatment of Reye-like syndrome in the margosa-oil-induced animal model.
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