Diagnostic pitfall in fine needle aspiration cytology of pilomatrixoma with unusual clinical presentation

Pilomatrixoma (PMX) is a benign skin adnexal tumour with matrical differentiation. It frequently presents as a painless and slow growing solitary skin nodule primarily at the head, face and neck regions. Although there is increasing understanding on the clinical presentations and morphological features of PMX, difficulties are still expected in establishing the clinical and cytological diagnosis. We report a young girl who presented with a painless post-auricular swelling for one year with sudden increased in size. Computed Tomography (CT) scan and fine needle aspiration cytology (FNAC) findings were suggestive of a malignancy. Diagnosis of PMX was established and confirmed by tissue histopathological examination. The purpose of this study is to demonstrate the diagnostic pitfall of PMX in FNAC specimens, especially in patients with unusual clinical presentations

Evaluating the p53 as diagnostic marker by using liquid based cervical sample in cervical carcinogenesis

Background: p53 is known as the guardian genome and tumour suppressor gene as it involved in the induction of cell cycles and preventing mutation by activating cellular apoptosis. P53 mutation is observed in numerous types of malignancies such as in ovary, lungs, breast, colorectal , uterus and cervical cancer. Cervical cancer is one of the most common cancer in the female population. According to the Malaysian National Cancer Registry 2007-2011, the prevalence of cervical cancer among other female cancer in Malaysia was observed at 7.7%. The association between the Human Papillomavirus (HPV) infection and cervical cancer is well established. The emergence of the HPV negative squamous lesion could hamper the high-risk HPV (hrHPV) detection in Pap smear. Instead of looking into the HPV protein, we explored the expression of p53 in various stages of cervical carcinogenesis and determine the utility of p53 as potential diagnostic marker for cervical cancer. Materials and Methods: This is a cross-sectional study using left over samples of routine liquid based cytology (LBP) from Ministry of Health facilities in Johor Bahru, Johor and Kota Bharu. Kelantan from May 2016 to May 2018. All the LBP samples were selected according to cervical carcinogenesis; negative for intraepithelial malignancy (NILM), low grade squamous intraepitheliallesion (LSIL}, high grade squamous intraepitheliallesion (HSIL} and squamous cell carcinoma (SCC) and fulfilled the inclusion and exclusion criterion. Each LBP smear underwent cytopathological examination by respective resident pathologists and certified medical laboratory technicians, results were classified according The Bethesda System (TBS) 2014. The selected left over samples were converted to cell blocks and were subjected for p53 IHC staining. The nuclear expression of p53 IHC stain was assessed and quantified by usingHisto-score (H-Score). The cytological diagnosis was not known during the interpretation of the IHC Result: The p53 IHC scores obtained showed an increase in p53 expression in more severe cervical dysplasia and SCC and showed good sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The statistical analysis between the mean p53 IHC score with cervical carcinogenesis categories were done using analysis of variance (ANOVA) which showed statistically significant result, p value <0.05. Post-hoc test (Tukey) among the cervical carcinogenesis categories showed statistically significant results, p value <0.05. Conclusion: Our findings suggest that p53 can be used as a diagnostic tool to differentiate normal cervical pap smear samples from the sample that has undergone different stages of cervical carcinogenesis. p53 also manage to stratify each category of cervical carcinogenesis. The cell blocks are also providing an excellent ancillary test for routine cervical pap smears

Detection of Isocitrate Dehydrogenase (IDH-1), Epidermal Growth Factor Receptor (EGFR), P53 and C-erbB2/HER2 mutation in glial tumour

Introduction: In the last decade, several molecular pathways in gliomagenesis have been discovered, with each involving a unique set of molecular alterations. IDH1 has become a diagnostic tool in the latest 2016 WHO Clas- sification. The tumour protein, p53, is involved in the IDH-mutant arm, observed in astrocytoma and oligodendro- glioma (grades II and III), and secondary glioblastoma. Meanwhile, EGFR and c-erbB2/HER2 were postulated to be expressed in higher-grade glioma as the disease progresses. Methods: A retrospective cross-sectional study was conducted to evaluate the association of IDH1, EGFR, p53 and c-erbB2/HER2 protein expression in astrocytic and oligodendroglial tumours with clinicopathological data in HUSM, Kota Bharu, Kelantan, Malaysia. This study ex- amined 61 archived formalin-fixed paraffin-embedded (FFPE) tissue blocks of patients diagnosed with glioma. The immunohistochemistry (IHC) test was performed using antibodies, IDH1, EGFR, p53 and c-erbB2/HER2, and the protein expressions were evaluated microscopically. Finally, the association between IDH1, p53, EGFR and c-erbB2/ HER with the clinicopathology variables were statistically analysed. Results: A total of 61 glioma cases consisting of 36 (59%) males and 25 (41%) females were included in this study. The IDH1 protein was positively expressed in 14 cases (23%), P53 was highly expressed in 26 cases (42.6%), and EGFR was substantially observed in 34 cases (55.7%). For glioblastoma cases, IDH1 was expressed in two cases (11.1%), EGFR in 14 cases (77.7%), p53 in 12 cases (66.7%) and c-erbB2 in 1 case (5.6%). Significant associations exist between IDH1, p53 and EGFR expressions in astrocytoma and oligodendroglial tumours with the histological types and WHO tumour grades. Conclusion: Re- cently, our knowledge regarding the genetics of central nervous system (CNS) tumors has expanded; hence, newer antibodies or molecular markers, which can be used in IHC, are continuously being developed. These antibodies, IDH1, p53 and EGFR markers are useful for diagnostic, prognostication and therapeutic. In addition, help to clarify the nature of cellular maturation, tissue differentiation, and tumor progression to be considered as an integral part of WHO classification of CNS tumours

Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy

Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&amp;E) stain for myocyte size and Masson’s Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy

Primary small cell neuroendocrine carcinoma: a rare entity of bladder neoplasm

Primary small cell neuroendocrine carcinoma (SCNEC) is a rare high-grade malignant neoplasm with neuroen- docrine differentiation derived from the urothelium. Herein, we report a case which presented with symptomatic anaemia secondary to haematuria, complicated with acute kidney injury following obstructive uropathy caused by the SCNEC, along with the discussion of the clinical presentation, radiological imaging and pathological findings of the disease

Dataset of acute oral toxicity and subacute neurotoxicity risk assessments of flavonoid-enriched fraction extracted from Oroxylum Indicum on Sprague Dawley rats

Oroxylum indicum is a medicinal herb that garnered enormous attention in drug discovery for human diseases such as neurodegenerative, cardiovascular, arthritis and hepatitis diseases. Pharmacokinetic study confirmed that the pharmacological actions of this herb are associated with its prominent flavonoid bioactive components. Here, the data set of liquid chromatography-mass spectroscopy (LC-MS), neurological functions, relative organ weight (ROW), hematological, biochemical and histopathological parameters of flavonoid-enriched fraction (FEF)-treated Sprague Dawley (SD) rats were presented. The data set was generated from three study groups namely: Sighting Study, Acute Toxicity Study and Subacute Neurotoxicity Study with study duration of 14 days (for Sighting Study and Acute Toxicity Study) and 28 days (for Subacute Neurotoxicity Study) by strictly following the procedures set in Organisation for Economic Co-operation and Development (OECD) Guidelines 420 and 424 in vivo. Rats in sighting study were treated with dosage of 5, 50, 300 and 2000 mg/kg FEF (n = 1/dosage/gender), respectively, and were observed for mortality, toxicity signs and behavioural changes. The highest dosage at which none of the animal showed sign of mortality in the sighting study was selected as the test dosage for subsequent acute toxicity study (n = 5/dosage/gender). Meanwhile, for subacute neurotoxicity study, SD rats (n = 5/dosage/gender) were treated with repeated dosage of 50 mg/kg for 28 days. Neurological behaviours of treated rats were observed daily, while their body weight were measured weekly. Whole blood was collected at the end of the study via cardiac puncture into ethylenediaminetetraacetic acid (EDTA) tubes for hematological evaluation that included the measurements of red blood cells (RBC), hemoglobin (Hb), packed cell volumes (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet, white blood cells (WBC) count and WBC differentials. Meanwhile, blood serum were collected into slow sand filter (SST) tubes for biochemical evaluation that included measurements of total protein (TP), albumin, bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Vital organs such as brain, liver, kidneys, heart, lungs and reproductive organs also were collected, sliced and stained with hematoxylin and eosin (H&E) at the end of the study for histopathological assessments

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72–0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer

Tualang honey modulated nociceptive responses in the thalamus of rem sleep deprivation rat model

Sleep deprivation has been shown to alter pain responses in humans and animals. The present study investigated whether the administration of Tualang honey in the rapid eye movement (REM) sleep deprivation rat model would modulate nociceptive responses with associated changes in the thalamus. Forty-eight Sprague Dawley male rats were randomised into four groups (n=12 for each group): control group (FMC), REM sleep deprivation (REMsd), REM sleep deprivation pretreated with Tualang Honey for 1 month (REMsdH) and tank control (TC). Following sleep deprivation for 72 hours, a formalin test was conducted and pain behaviour was recorded and analysed. The rats were sacrificed, and the brains were removed for histological examination and assessment of N-methyl-D-aspartate receptor (NMDA R2) level in the thalamus. REMsdH group showed a significantly lower level of pain behaviour score and NMDA R2 compared to the REMsd group (p<0.05). In addition, REMsdH also demonstrated a significantly higher number of Nissl stained neurons in comparison with the REMsd group (p<0.05). Furthermore, dark neurons, suggestive of neuronal damage, were observed in the REMsd group. In conclusion, administration of Tualang honey before REM sleep deprivation modulated nociceptive responses and prevent changes in thalamic neurons and NMDA R2 level

Primary aggressive osteosarcoma of sphenoid bone

Osteosarcoma is a malignant intra-osseous neoplasm producing osteoid. Osteosarcoma of the skull is very rare and it usually involves the cranial vault. The occurrence in the skull base is extremely rare. We report a case of primary osteosarcoma in 59-year-old lady, occur in left sphenoid wing with intracranial and intranasal extension manifesting as left facial pain, headache and left epistaxis. She underwent radiotherapy as the surgical resection of the tumour is not feasible due to the critical extent of the tumour. We describe the clinical, radiological and histopathological findings of the case