Successful Treatment of Extraosseous Plasmacytoma of the Oropharynx with Cervical Lymph Node Involvement.

Extraosseous plasmacytoma, a rare plasma cell neoplasm, was observed in a 52-year-old male with uncommon presentation in the oropharynx with cervical lymph node involvement. The patient presented with dysphonia and left neck swelling. This case report primarily focuses on the management, resulting in a successful treatment through radiotherapy.

Worldwide Prevalence of Epstein-Barr Virus in Patients with Burkitt Lymphoma: A Systematic Review and Meta-Analysis.

Burkitt lymphoma (BL) is a form of B-cell malignancy that progresses aggressively and is most often seen in children. While Epstein-Barr virus (EBV) is a double-stranded DNA virus that has been linked to a variety of cancers, it can transform B lymphocytes into immortalized cells, as shown in BL. Therefore, the estimated prevalence of EBV in a population may assist in the prediction of whether this population has a high risk of increased BL cases. This systematic review and meta-analysis aimed to estimate the prevalence of Epstein-Barr virus in patients with Burkitt lymphoma. Using the appropriate keywords, four electronic databases were searched. The quality of the included studies was assessed using the Joanna Briggs Institute's critical appraisal tool. The results were reported as percentages with a 95% confidence interval using a random-effects model (CI). PROSPERO was used to register the protocol (CRD42022372293), and 135 studies were included. The prevalence of Epstein-Barr virus in patients with Burkitt lymphoma was 57.5% (95% CI: 51.5 to 63.4, n = 4837). The sensitivity analyses demonstrated consistent results, and 65.2% of studies were of high quality. Egger's test revealed that there was a significant publication bias. EBV was found in a significantly high proportion of BL patients (more than 50% of BL patients). This study recommends EBV testing as an alternative for predictions and the assessment of the clinical disease status of BL.

Evaluation of Signal Transducer and Activator of Transcription 3 (STAT-3) Protein Expression in Non-Hodgkin Lymphoma Cases in Hospital USM.

BACKGROUND: Evolving targeted therapy on Janus Associated Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway, especially pertaining to STAT-3 protein in non-Hodgkin lymphoma (NHL), provides new treatment strategies. STAT-3 protein also relates to the prognostication of NHL. Hence, we aimed to evaluate the expression of STAT-3 protein in NHL cases diagnosed in Hospital Universiti Sains Malaysia (USM). METHODS: A retrospective cross sectional study using formalin fixed paraffin embedded (FFPE) tissue blocks of 95 NHL cases were obtained. STAT-3 immunostaining was performed and evaluated. The proportion and association between the expression of STAT-3 protein with subtypes of NHL were statistically analyzed. RESULTS: The majority of the cases (78.9%) had positive STAT-3 protein expression. 64.2% were among aggressive B cell NHL, whilst 20.0% of them were diffuse large B cell lymphoma, a non-germinal center B subtype (DLBCL-NGCB). There is also an association between STAT-3 protein expression with DLBCL subtypes (p = 0.046). CONCLUSION: Our study demonstrated a remarkable expression of STAT-3 protein in NHL, in which DLBCL subtypes had significant association. A larger scale study with a combination of JAK protein evaluation should be undertaken in the future.

Application of Baculovirus Expression Vector system (BEV) for COVID-19 diagnostics and therapeutics: a review.

BACKGROUND: The baculovirus expression vector system has been developed for expressing a wide range of proteins, including enzymes, glycoproteins, recombinant viruses, and vaccines. The availability of the SARS-CoV-2 genome sequence has enabled the synthesis of SARS-CoV2 proteins in a baculovirus-insect cell platform for various applications. The most cloned SARS-CoV-2 protein is the spike protein, which plays a critical role in SARS-CoV-2 infection. It is available in its whole length or as subunits like S1 or the receptor-binding domain (RBD). Non-structural proteins (Nsps), another recombinant SARS-CoV-2 protein generated by the baculovirus expression vector system (BEV), are used in the identification of new medications or the repurposing of existing therapies for the treatment of COVID-19. Non-SARS-CoV-2 proteins generated by BEV for SARS-CoV-2 diagnosis or treatment include moloney murine leukemia virus reverse transcriptase (MMLVRT), angiotensin converting enzyme 2 (ACE2), therapeutic proteins, and recombinant antibodies. The recombinant proteins were modified to boost the yield or to stabilize the protein. CONCLUSION: This review covers the wide application of the recombinant protein produced using the baculovirus expression technology for COVID-19 research. A lot of improvements have been made to produce functional proteins with high yields. However, there is still room for improvement and there are parts of this field of research that have not been investigated yet.

The Role of NOTCH1, GATA3, and c-MYC in T Cell Non-Hodgkin Lymphomas.

Lymphomas are heterogeneous malignant tumours of white blood cells characterised by the aberrant proliferation of mature lymphoid cells or their precursors. Lymphomas are classified into main types depending on the histopathologic evidence of biopsy taken from an enlarged lymph node, progress stages, treatment strategies, and outcomes: Hodgkin and non-Hodgkin lymphoma (NHL). Moreover, lymphomas can be further divided into subtypes depending on the cell origin, and immunophenotypic and genetic aberrations. Many factors play vital roles in the progression, pathogenicity, incidence, and mortality rate of lymphomas. Among NHLs, peripheral T cell lymphomas (PTCLs) are rare lymphoid malignancies, that have various cellular morphology and genetic mutations. The clinical presentations are usually observed at the advanced stage of the disease. Many recent studies have reported that the expressions of NOTCH1, GATA3, and c-MYC are associated with poorer prognosis in PTCL and are involved in downstream activities. However, questions have been raised about the pathological relationship between these factors in PTCLs. Therefore, in this review, we investigate the role and relationship of the NOTCH1 pathway, transcriptional factor GATA3 and proto-oncogene c-MYC in normal T cell development and malignant PTCL subtypes.

Advanced Nasopharyngeal Carcinoma with Generalized Lymphadenopathy Masquerade as Lymphoma.

Introduction: Nasopharyngeal carcinoma (NPC) is a nasopharyngeal epithelial neoplasm that has distinct aetiological, epidemiological and biological characteristics compared to other head and neck malignancies. Patients usually present late due to non-specific symptoms and deep location of the tumour in the nasopharynx. Case Report: We would like to highlight a case of advanced NPC presenting with generalised lymphadenopathy, without the presence of an obvious nasopharyngeal mass that masqueraded as lymphoma in the initial stage. Conclusions: NPC may share clinical features with other sinonasal pathologies or other malignant lymphoproliferative disorders that lead to a delay in diagnosis. NPC should be one of the differential diagnoses for any cases presenting with cervical lymphadenopathy, especially in adult male patients originating from East or Southeast Asia. Early diagnosis and treatment are crucial because early-stage NPC has an excellent chemoradiotherapy response and high survival rate.

Submandibular Gland Basal Cell Adenoma.

Introduction: Basal cell adenoma (BCA) is a rare benign epithelial tumour of the salivary gland majorly involving the parotid gland, and rarely the submandibular gland. Case Report: We describe a rare case of BCA of the submandibular gland diagnosed preoperatively using fine needle aspiration cytology in a 60-year-old woman presenting with painless submandibular swelling. The surgery went uneventfully, and the histopathological examination confirmed the diagnosis. Conclusions: BCA can be accurately diagnosed only through histological observations due to its resemblance to various benign and malignant salivary and non-salivary gland tumours, which are difficult to biopsy.

Master of mimicry: Rare primary cutaneous anaplastic large cell lymphoma presenting as fungating parotid tumor-case report and review.

INTRODUCTION: Primary cutaneous anaplastic large cell lymphomas (PC-ALCL) are rare. They fall within non-Hodgkin's lymphomas spectrum. Commonly misdiagnosed, this malignancy involving the skin has favorable prognosis. To the best of our knowledge, this is the first reported case of PC-ALCL involving the parotid gland. This clinical presentation can mislead surgeons. We highlight this diagnostic conundrum. CASE PRESENTATION: A 73-year-old gentleman presented with two painless, ulcerating nodules over the right pre-auricular and angle of the mandible. Prior to that, he had right pre-auricular swelling that enlarged over a year. Skin nodules erupted few weeks before seeking treatment. Computed Tomography scan reported homogenously enhancing masses at posterior part of parotid gland's superficial lobe with diffuse lobe enlargement and no regional lymphadenopathy. A hypodense lesion at the liver indicated metastasis. Biopsy revealed PC-ALCL. He responded well to chemotherapy. DISCUSSION: PC-ALCL commonly presents as solitary nodules that can ulcerate over the head and neck region. Reports of PC-ALCL involving the eyelids, lips, and breast were found in our literature review. Multifocal lesions occur in 20% of cases. Malignant parotid tumors are aggressive and require parotidectomy which carry the risk of facial nerve injury. Treatment of PC-ALCL however, is local excision and radiotherapy for solitary lesions; and chemotherapy for those with extracutaneous spread. The 5-year survival rate is 90% in PC-ALCL. CONCLUSION: PC-ALCL is a master of mimicry. To prevent serious morbidity, awareness regarding this entity as a differential diagnosis compared to the common malignant parotid tumors need to be raised.

Association between c-Myc Expression with Clinicopathological Features in T And NK Cell Lymphomas.

BACKGROUND: c-Myc has become significantly involved in aggressive B-cell non Hodgkin lymphoma (NHL), but little is known about its importance in T and NK cell NHL (TNKcNHLs) in association with prognostic factors. The study is to investigate the significance of c-Myc expression with clinicopathological features of TNKcNHLs patients. METHODOLOGY: A cross-sectional study of 32 archived tissue blocks of TNKcNHLs were immunohistochemically stained with c-Myc. The results were microscopically evaluated and statistically analysed to examine the association between the clinicopathological data with the c-Myc expression. RESULTS: c-Myc protein expressions were detected in 25/32 (78.1%) cases. The median age was 38-years.  Malay ethnicity (92.0%) with 21 males and 11 females. c-Myc expressions were seen in T lymphoblastic lymphoma (20%), ALK-positive ALCL (16%) ,PTCL,NOS (16%), extra nodal NK/T-cell lymphoma, nasal type (12%), extra-nodal involvement (78.1%), elevated serum LDH (83.3%) and high ECOG performance status (82.4%). However, no statistical significant of c-Myc in association with the clinicopathological parameters (p > 0.05). CONCLUSION: There was no statistically significant association of clinicopathological parameters and histological subtypes of TNKcNHLs contributed by small samples tested. However, the attribution of c-Myc in this disease should be further explored.

Unilateral Tubarial Oncocytic Papillary Cystadenoma Presenting with Epistaxis.

Oncocytic papillary cystadenoma (OPC) is a relatively rare benign tumor of the salivary glands, frequently seen in minor salivary glands, and occasionally in major salivary glands, such as the parotid gland. Patients only become symptomatic upon progression of the swelling, causing obstructive symptoms depending on its location. To our knowledge, there are no reports of presentation with bleeding tumor. Herein, we report a case of an OPC of the right torus tubarius in a 54-year-old man who presented with recurrent epistaxis.

Pediatric Sinonasal Rhabdomyosarcoma Presented as Squint: A Case Report and Literature Review.

Rhabdomyosarcoma (RMS) is the most common soft-tissue tumor in children, frequently affecting the nose, nasopharynx, and paranasal sinuses. RMS of this sinonasal region manifests with non-specific nasal symptoms of allergic rhinitis, sinusitis, or upper airway infection. Associated ocular symptoms are rare. We describe a young girl who presented with acute onset squint secondary to sinonasal RMS. Imaging showed an aggressive sinonasal tumor with oropharyngeal, intraorbital, and intracranial extension. Histopathological findings were consistent with a diagnosis of rhabdomyosarcoma, embryonal type. The patient deteriorated rapidly due to disease complications. We provide a literature review of pediatric sinonasal RMS with various manifestations.

The challenges and risk of laboratory handling on a histology specimen during COVID-19 pandemic.

The Coronavirus Disease 2019 (COVID-19) pandemic has taken the world into turmoil by surprise. The rapid spreading of this virus has led to an exponential increase in the number of cases. It has created a public health disaster, causing a collapse of the health system in every part of the world. Many sectors in the health area are affected, including histopathology services. The challenges and risk of viral transmission can come from various aspects and levels. For COVID-19 tests, there are even cases of no direct contact with the specimens; the specimens received infection from individuals of unknown status. The fixatives used for histopathology specimens are believed to be inactivated viruses, which can be an inactivate coronavirus. Even so, precautions have to be put in place to prevent the spread of infection to laboratory personnel, especially to those handling underfixed and fresh frozen cytology samples. Precautions must also be taken when dealing with histopathology services, by wearing full personal protective equipment and by executing other standard safety measures. The purpose of this review is to highlight the challenges faced in managing histopathology services in our centre during the COVID-19 pandemic.

Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma.

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.

Mantle Cell Lymphoma: A Rare Vallecular Tumour.

Vallecular lymphoma is an extremely rare tumour of oropharynx. We report a case of 61-year-old gentleman presented with severe dysphagia and globus sensation for two months. Patient underwent endoscopic transoral tumour debulking for diagnostic and therapeutic purpose. Histopathologically, patient was diagnosed as mantle cell lymphoma (MCL). In this case report, atypical presentation of the disease, histopathological features and its current treatments are discussed.

TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets.

Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4+; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4+; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p<0.01 and false discovery rate<0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.

Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine.

Background: Acute myeloid leukemia (AML) is the most common form of acute leukemias in adults which is clinically and molecularly heterogeneous. Several risk and genetic factors have been widely investigated to characterize AML. However, the concomitant epigenetic factors in controlling the gene expression lead to AML transformation was not fully understood. This study was aimed to identify epigenetically regulated genes in AML cell lines induced by epigenetic modulating agents, Trichostatin A (TSA) and 5-Azacytidine (5-Aza). Materials and Methods: MV4-11 and Kasumi 1 were treated with TSA and/or 5-Aza at IC50 concentration. Gene expression profiling by microarray was utilized using SurePrint G3 Human Gene Expression v3. Gene ontology and KEGG pathway annotations were analyzed by DAVID bioinformatics software using EASE enrichment score. mRNA expression of the differentially expressed genes were verified by quantitative real time PCR. Results: Gene expression analysis revealed a significant changes in the expression of 24,822, 15,720, 15,654 genes in MV4-11 and 12,598, 8828, 18,026 genes in Kasumi 1, in response to TSA, 5-Aza and combination treatments, respectively, compared to non-treated (p<0.05). 7 genes (SOCS3, TUBA1C, CCNA1, MAP3K6, PTPRC, STAT6 and RUNX1) and 4 genes (ANGPTL4, TUBB2A, ADAM12 and PTPN6) shown to be predominantly expressed in MV4-11 and Kasumi 1, respectively (EASE<0.1). The analysis also revealed phagosome pathway commonly activated in both cell lines. Conclusion: Our data showed a distinct optimal biological characteristic and pathway in different types of leukemic cell lines. These finding may help in the identification of cell-specific epigenetic biomarker in the pathogenesis of AML.

p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia

Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.

Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer.

Spermatogenesis-associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non-malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non-malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non-malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty-nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H-score) was not associated with overall survival or disease-specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease.