Displaying publications 1 - 20 of 39 in total

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  1. Sazafi MS, Salina H, Asma A, Masir N, Primuharsa Putra SH
    Acta Otorhinolaryngol Ital, 2013 Dec;33(6):428-30.
    PMID: 24376301
    We report a case of keratoacanthoma in a non-sun-exposed nasal vestibule of an 84-year-old man. He presented with a progressively growing left nasal mass that had been present for 8 months. Examination showed a non-tender protruding mass arising from medial vestibular wall of the left nostril. Histopathology indicated it was a keratoacanthoma. In an elderly patient with a history of a progressively growing mass in the nose, a differential diagnosis of malignancy should be ruled out, and histological conformation is essential. To our knowledge, only a very small number of cases of nasal vestibular keratoacanthoma have been reported.
  2. Ameli F, Rose IM, Masir N
    Asian Pac J Cancer Prev, 2015;16(6):2385-90.
    PMID: 25824769
    BACKGROUND: Invasive ductal (IDC) and lobular (ILC) carcinomas are the common histological types of breast carcinoma which are difficult to distinguish when poorly differentiated. Discoidin domain receptor (DDR1) and Drosophila dishevelled protein (DVL1) were recently suggested to differentiate IDC from ILC.

    OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.

    MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.

    RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.

    CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.

  3. Binti Yusof NS, Ameli F, Sabrina Florence Ch, Mustangin M, Abd Rahman F, Masir N
    Asian Pac J Cancer Prev, 2017 04 01;18(4):1045-1050.
    PMID: 28547939
    Aim: Abnormal expression patterns of beta-tubulin isotypes may provide a molecular rationale for the behaviour
    of lymphoma subtypes. In the present study class II and III beta-tubulin expression was assessed in non-neoplastic and
    neoplastic lymphoid tissues with reference to potential utility as new tumour biomarkers. Methods and results: In this
    cross-sectional study class II and III beta-tubulin expression was assessed in 304 neoplastic and 20 normal lymphoid
    tissues using qualitative and semi-quantitative immunohistochemistry. Class II beta-tubulin was found to be positive in
    the germinal centres, mantle zone and interfollicular regions of normal lymphoid tissues. It was also expressed in 15/15
    (100%) lymphoblastic lymphomas, 229/231 (99%) mature B cell lymphomas, 22/22 (100%) T/NK-cell lymphomas and
    36/36(100%) classical Hodgkin lymphomas. Class III beta-tubulin in contrast was germinal centre restricted and more
    selective, being found mainly in classical Hodgkin lymphomas (34/36 (94%)). It was also expressed in 58/171(34%)
    DLBCL, 11/12 (92%) mantle cell lymphomas and 6/6 (100%) Burkitt lymphomas. Other mature B cell, T/NK cell
    lymphomas and precursor lymphoblastic lymphomas were usually negative. Conclusions: Class II beta-tubulin shows
    ubiquitous expression in neoplastic and non-neoplastic lymphoisd tissues. In contrast, Class III beta-tubulin is germinal
    centre-restricted. Its consistent expression in classical Hodgkin lymphomas may point to use in the identification of
    Reed-Sternberg and Hodgkin cells. Its expression in a proportion of DLBCL, Burkitt and mantle cell lymphomas is of
    interest as this may be related to their aggressiveness.
  4. Ameli F, Ghafourina Nassab F, Masir N, Kahtib F
    Asian Pac J Cancer Prev, 2021 Aug 01;22(8):2603-2609.
    PMID: 34452576 DOI: 10.31557/APJCP.2021.22.8.2603
    INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).

    MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

    RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

    CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.

  5. Masir N, Campbell LJ, Goff LK, Jones M, Marafioti T, Cordell J, et al.
    Br J Haematol, 2009 Mar;144(5):716-25.
    PMID: 19120369 DOI: 10.1111/j.1365-2141.2008.07528.x
    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining.
  6. Wan Mohd Zohdi WA, Ismail AZ, Yusof N, Ithnin A, Shuib S, Masir N, et al.
    Clin Pathol, 2022 01 09;15:2632010X211070774.
    PMID: 35036912 DOI: 10.1177/2632010X211070774
    Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin Lymphoma commonly presenting as a solid tumor either by nodal or extra-nodal manifestations. Here we describe two atypical presentations of lymphoma, finally resulting in the diagnosis of DLBCL. Case 1: A 53-year-old man with a previous history of nasopharyngeal carcinoma presented with a two-week history of B-symptoms and hyperleukocytosis. Peripheral blood film showed 78% abnormal mononuclear cells. Immunohistochemical stain showing Ki-67 of 90%, negative c-myc, BCL2 and BCL6, and negative c-MYC with fluorescence in-situ hybridization studies on the trephine biopsy, concluded the diagnosis of CD5+ DLBCL of ABC subtype. He received intravenous cyclophosphamide and oral prednisolone for cytoreduction, followed by 6 cycles of chemo-immunotherapy. However, he succumbed due to severe sepsis after the completion of therapy. Case 2: A 56-year-old lady who was initially investigated for pyrexia of unknown origin was noted to have hemophagocytosis upon bone marrow aspirate examination. The bone marrow trephine biopsy revealed some atypical clusters of B-cells positive for CD20 which was inconclusive. PET-CT scan noted an enlarged hypermetabolic spleen without lymphadenopathy. Splenic biopsy with immunohistochemical studies revealed DLBCL of ABC subtype. The diagnosis was consistent with primary splenic DLBCL. She became unwell post splenic biopsy and was admitted to the intensive care unit where she passed away 2 weeks later from Candida and Sternotrophomonas septicemia. These cases highlight the atypical presentations of a common subtype of NHL in our center. Arriving at the definitive diagnosis can be difficult especially when patients are acutely ill, hampering the necessary invasive procedures for diagnosis. The outcomes of both cases are briefly discussed hoping to spread awareness among clinicians on the rare and acutely critical presentations of DLBCL.
  7. Akhter A, Mughal MK, Elyamany G, Sinclair G, Azma RZ, Masir N, et al.
    Diagn Pathol, 2016 Sep 15;11(1):89.
    PMID: 27632978 DOI: 10.1186/s13000-016-0541-z
    The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL.
  8. Masir N, Cheong SK, Noordin K
    Hematology, 2001;6(3):187-92.
    PMID: 27420125 DOI: 10.1080/10245332.2001.11746571
    A case of signet-ring cell lymphoma diagnosed initially by fine needle aspiration cytology is reported. This rare tumor is a variant of follicular lymphoma, which closely resembles metastatic adenocarcinoma and other tumors which exhibit signet-ring cell appearance. Correct diagnosis can be achieved by careful morphologic analysis together with positive reactivity with lymphoid markers. The cytohistologic, immunohistochemical and electron microscopic features are described, and the differ ential diagnostic considerations are discussed in the report.
  9. Masir N, Ghoddoosi M, Mansor S, Abdul-Rahman F, Florence CS, Mohamed-Ismail NA, et al.
    Histopathology, 2012 Apr;60(5):804-15.
    PMID: 22320393 DOI: 10.1111/j.1365-2559.2011.04127.x
    To investigate RCL2 as a fixative for tissue fixation in routine histopathological examination and to assess tissue suitability for ancillary investigations.
  10. Masir N, Jones M, Lee AM, Goff LK, Clear AJ, Lister A, et al.
    Histopathology, 2010 Apr;56(5):617-26.
    PMID: 20459572 DOI: 10.1111/j.1365-2559.2010.03524.x
    To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.
  11. Wong YP, Masir N, Chew MX
    Indian J Pathol Microbiol, 2021 8 4;64(3):579-583.
    PMID: 34341278 DOI: 10.4103/IJPM.IJPM_616_20
    Plasmablastic lymphoma (PBL) is a rare aggressive subtype of mature large B cell lymphoma involving almost exclusively the extranodal regions particularly the oral cavity, frequently described in immunocompromised patients. PBL is characterized histologically by diffuse proliferation of large neoplastic cells resembling B immunoblasts or plasmablasts. The diagnosis of PBL can be difficult due to its ambiguous histopathological features mimicking most large cell lymphomas and lacking a distinctive immunophenotypic pattern. They typically lack expression of CD20 and CD79a but may express plasma cell marker, CD138. Aberrant immunoexpression of CD3, a T-cell marker in PBL in the absence of other B-cell markers is exceptionally rare, may potentially lead to incorrect interpretation. Herein, we report a case series of CD3-positive PBL of oral cavity in two individuals, which were initially misdiagnosed as high-grade T-cell lymphomas including extranodal NK/T-cell lymphoma, nasal type. Useful distinguishing clinical settings, histomorphological features, immunohistochemistry and molecular expression profiles of PBL are discussed.
  12. Md Pauzi SH, Masir N, Yahaya A, Mohammed F, Tizen Laim NMS, Mustangin M, et al.
    Indian J Pathol Microbiol, 2021 10 22;64(4):677-682.
    PMID: 34673585 DOI: 10.4103/IJPM.IJPM_983_20
    Background: Human epidermal growth factor receptor 2 (HER2) over-expression in breast cancer is associated with aggressive tumor behavior and predicts response to targeted therapy. Accurate HER2 result is paramount for optimal patient management. However, routine HER2 immunohistochemistry (IHC) testing are subjected to intra- and inter-laboratory variability.

    Objective: This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories.

    Method: A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory.

    Results: A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50-88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0).

    Conclusion: Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.

  13. Azizan N, Hayati F, Tizen NMS, Farouk WI, Masir N
    Investig Clin Urol, 2018 07;59(4):232-237.
    PMID: 29984337 DOI: 10.4111/icu.2018.59.4.232
    Purpose: To evaluate the expression of estrogen receptor (ER)-beta and Ki67 in prostate cancer and study their relationship.

    Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.

    Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.

    Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.

  14. Ameen SA, Salina H, Zahedi FD, Primuharsa-Putra SH, Masir N
    Iran J Otorhinolaryngol, 2019 May;31(104):191-195.
    PMID: 31223601
    Introduction: Angiomyolipoma (AML), a benign mesenchymal tumor that commonly arises from the kidney, may be associated with tuberous sclerosis complex and perivascular epithelioid cell tumors (PEComas). Nasal angiomyolipoma is very rare and usually occurs in elderly individuals with epistaxis and nasal obstruction.

    Case Report: We report a rare case of nasal angiomyolipoma in a young male. To the best of our knowledge, this is the first documented case of angiomyolipoma originating from the posterior end of the inferior turbinate, clinically mimicking juvenile nasopharyngeal angiofibroma (JNA). The tumor was removed completely via coblator-assisted endoscopic sinus surgery. The patient was asymptomatic at a 2-year follow-up.

    Conclusion: Nasal AML located in the posterior nasal cavity in a male patient can mimic the presentation of JNA. A computed tomography scan of the paranasal sinuses played an important role in differentiating nasal AML from JNA. The coblator-assisted endoscopic technique is useful in controlling intraoperative hemostasis in the removal of a suspicious vascular tumor.

  15. Phang KC, Akhter A, Tizen NMS, Rahman FA, Zahratul Azma R, Elyamany G, et al.
    J Clin Pathol, 2018 Mar;71(3):215-220.
    PMID: 28775174 DOI: 10.1136/jclinpath-2017-204548
    AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.

    METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).

    RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).

    CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

  16. Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, et al.
    J Clin Pathol, 2019 Sep;72(9):630-635.
    PMID: 31189540 DOI: 10.1136/jclinpath-2019-205837
    AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.

    METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).

    RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).

    CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

  17. Ameli F, Ghafourian F, Masir N
    J Med Case Rep, 2014;8:288.
    PMID: 25163591 DOI: 10.1186/1752-1947-8-288
    Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy.
  18. Tamby, M.R., Juliana, M.B., Wan Hamilton, W.H., Masir, N., Hemlata, K.G.
    Medicine & Health, 2011;6(2):139-142.
    MyJurnal
    Primary fallopian tube carcinomas are rare and are difficult to diagnose preoperatively.
    We describe a fallopian tube carcinoma in a 50-year-old lady who presented with symptoms of pelvic inflammatory disease. Ultrasound examination showed bilateral hydrosalphinx. However, CT scan showed features suggestive of a malignant ovarian tumour. At surgery, a markedly dilated left fallopian tube was found and histopathological examination confirmed the presence of a primary serous adenocarcinoma. The uterus and both ovaries were free of tumour. This report highlights that carcinoma of the fallopian tube should be considered as a differential diagnosis in females who present with lower abdominal pain.
  19. Masir N, Jones M, Abdul-Rahman F, Florence CS, Mason DY
    Pathology, 2012 Apr;44(3):228-33.
    PMID: 22406486 DOI: 10.1097/PAT.0b013e3283513fb2
    The hallmark of follicular lymphoma is the t(14;18)(q32;q21) chromosomal translocations that lead to deregulation of BCL2 expression in tumour cells. However, not all cases of follicular lymphoma express BCL2, nor is the t(14;18) translocation always present. Follicular lymphomas lacking the BCL2 rearrangement are less well studied with regards to their immunohistochemical and molecular features. This study aims to investigate the BCL2 protein expression pattern in t(14;18) negative follicular lymphomas.
  20. Masir N, Campbell LJ, Jones M, Mason DY
    Pathology, 2010 Apr;42(3):212-6.
    PMID: 20350212 DOI: 10.3109/00313021003631296
    The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein expression in most follicular lymphomas. However, a small number of cases lack BCL2 expression despite carrying the t(14;18)(q32;q21) translocation. This study aims to explore the mechanism accounting for the lack of BCL2 protein expression when the t(14;18) translocation is present.
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