Metastatic alveolar rhabdomyosarcoma on the fine-needle aspiration cytology of cervical lymph node in an elderly patient, with FISH confirmation: A case report.

INTRODUCTION: Alveolar rhabdomyosarcoma (RMS) usually occurs in adolescents and young adults, and most frequently arises in the extremities. CASE REPORT: We present a rare case of metastatic alveolar RMS from a nasal primary to cervical lymph nodes (LNs) in an elderly patient, diagnosed on the fine-needle aspiration (FNA) biopsy. Smears showed malignant round cells featuring focal rhabdoid appearance, with rhabdomyoblastic differentiation further supported by immunocytochemical stains. Diagnosis of alveolar RMS was confirmed by fluorescence in situ hybridization (FISH) identifying FOXO1 gene involvement with dual colour break-apart probes at locus 13q14. DISCUSSION: The differential diagnosis for a small round blue cell tumour in the elderly generally includes metastatic small cell carcinoma, lymphoma, malignant melanoma, RMS, desmoplastic small round cell tumour and Ewing's sarcoma/primitive neuroectodermal tumour. Subtle morphological analysis and expression pattern of immunostaining for skeletal muscle differentiation led to the diagnosis of RMS. Cytogenetic testing on the FOXO1 gene rearrangement helps definite subtyping of alveolar RMS.

Electrochemical sensing of nicotine using CuWO4 decorated reduced graphene oxide immobilized glassy carbon electrode.

A novel and selective electrochemical sensing of nicotine is studied using copper tungstate decorated reduced graphene oxide nanocomposite (CuWO4/rGO) nafion (Nf) immobilized GC electrode (GCE). The CuWO4/rGO nanocomposite is synthesized using sonication method and characterized by HR-TEM (High resolution transmission electron microscopy), SEM (Scanning electron microscopy), FT-IR (Fourier transform infrared spectroscopy), SAED (Selected area of electron diffraction pattern), XRD (X-ray diffraction), Raman spectroscopy, Thermo gravimetric analysis (TGA) and EDX (Energy dispersive X-ray diffraction) techniques. The CuWO4/rGO/Nf immobilized GCE shows better electrocatalytic response for the detection of nicotine as compared to bare GCE. A better selectivity and sensitivity is achieved using CuWO4/rGO/Nf immobilized GCE to detect 0.1 µM nicotine in the presence of 100-fold excess concentrations of different interferents. The present CuWO4/rGO/Nf immobilized GCE electrochemical sensor exhibits an ample range of sensing from 0.1 µM to 0.9 µM and the low detection limit is found to be 0.035 µM (S/N = 3). Comparable results are achieved for the determination of nicotine in various real samples such as cigarettes (Gold flake and Wills) and urine samples with improved recoveries.

A radiological and histological comparison of two unusual adrenal incidentalomas.

INTRODUCTION: The increasing use of radiological imaging studies has given rise to 'incidentalomas'. CASE REPORT: We describe two unusual and diverse incidental adrenal gland lesions, an adenomatoid nodule and a mature ganglioneuroma. Both are deemed 'indeterminate' on radiological assessment. On histology, an adenomatoid nodule is composed of variably-dilated thin-walled cysts lined by bland flattened cells and solid areas of tubules lined by eosinophilic cells with plump nuclei and prominent nucleoli. The lining cells are immunoreactive for calretinin and WT1 while negative for CK5/6, ERG and CD31. Mature ganglioneuroma features fascicles of bland spindle cells with intermixed mature ganglion cells disposed within a background myxoid stroma with no immature neuroblastic component. These spindled Schwann cells are S100 positive. DISCUSSION: Both adenomatoid nodule and mature ganglioneuroma are rare benign adrenal tumours that need to be differentiated from other, more common adrenal lesions. The management of adrenal incidentalomas is challenging. Surgical excision is indicated if an adrenal incidentaloma is more than 4 cm in size, shows malignant features on imaging or evidence of hormone excess.

Effect of cabergoline monotherapy in Cushing's disease: an individual participant data meta-analysis.

CONTEXT: The primary treatment of choice for Cushing's disease (CD) is the removal of the pituitary adenoma by transsphenoidal surgery (TSS). The surgical failure is seen in up to 75% of cases depending on the experience of the surgeon in different studies. Medical therapy is one of the options for the treatment of recurrent or persistent CD. METHODOLOGY: The primary outcome of this meta-analysis was to find the proportion of patients achieving normalisation of 24-h urinary free cortisol (remission of CD) following cabergoline monotherapy. Literature search was conducted in January 2018 in PubMed/MEDLINE database from its date of inception to 31st December 2017. The search strategy used was "[(cushing) OR Cushing's] AND cabergoline". Individual participant data were extracted from the included studies and risk of bias was analysed by review checklist proposed by MOOSE. RESULTS: The individual participant data of 124 patients from six observational studies were included in this meta-analysis. 92 patients (74.2%) had past pituitary surgery. The proportion of patients achieving remission of Cushing's disease (CD) with cabergoline monotherapy was 34% (95% confidence interval 0.26­0.43; P = 0.001) [corrected]. The previous surgery [odds ratio (OR) 28.4], duration of cabergoline monotherapy (OR 1.31) and maximum cabergoline dose (OR 0.19) were predictors for remission of CD. Mild and severe side effects were reported in 37.3% and 5.6% of patients, respectively, during cabergoline monotherapy. CONCLUSIONS: This meta-analysis shows that cabergoline monotherapy is a reasonable alternative for subjects with persistent or recurrent CD after TSS. It can also be used in CD patients either as a bridge therapy while waiting for surgery or in those unwilling for surgery or have contraindication to it.

A novel highly selective and sensitive detection of serotonin based on Ag/polypyrrole/Cu2O nanocomposite modified glassy carbon electrode.

A silver/polypyrrole/copper oxide (Ag/PPy/Cu2O) ternary nanocomposite was prepared by sonochemical and oxidative polymerization simple way, in which Cu2O was decorated with Ag nanoparticles, and covered by polyprrole (PPy) layer. The as prepared materials was characterized by UV-vis-spectroscopy (UV-vis), FT-IR, X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM) with EDX, high resolution transmission electron microscopy (HR-TEM) and X-ray photoelectron spectroscopy (XPS). Sensing of serotonin (5HT) was evaluated electrocatalyst using polypyrrole/glassy carbon electrode (PPy/GCE), polypyrrole/copper oxide/glassy carbon electrode (PPy/Cu2O/GCE) and silver/polypyrrole/copper oxide/glassy carbon electrode (Ag/PPy/Cu2O/GCE). The Ag/PPy/Cu2O/GCE was electrochemically treated in 0.1MPBS solution through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The peak current response increases linearly with 5-HT concentration from 0.01 to 250 µmol L-1 and the detection limit was found to be 0.0124 µmol L-1. It exhibits high electrocatalytic activity, satisfactory repeatability, stability, fast response and good selectivity against potentially interfering species, which suggests its potential in the development of sensitive, selective, easy-operation and low-cost serotonin sensor for practical routine analyses. The proposed method is potential to expand the possible applied range of the nanocomposite material for detection of various concerned electro active substances.

Fabrication of g-C3N4/NiO heterostructured nanocomposite modified glassy carbon electrode for quercetin biosensor.

Herein, we report a one-pot synthesis of structurally uniform and electrochemically active graphitic carbon nitride/nickel oxide (g-C3N4/NiO) nanocomposite and an investigation on the electrocatalytic oxidation of quercetin (QR). The synthesized g-C3N4/NiO nanocomposite has uniform surface distribution, which was characterized with scanning electron microscopy (SEM). Moreover, the composition of synthesized g-C3N4/NiO nanocomposite was characterized by UV-vis-spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR spectra), BET, SEM and HRTEM. The g-C3N4/NiO was electrochemically treated in 0.1 MPBS solution through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The peak current response increases linearly with QR concentration from 0.010 µM to 250 µM with a fast response time of less than 2 s and a detection limit of 0.002 µM. To further evaluate the feasibility of using this sensor for real sample analysis, QR content in various real samples including green tea, green apple, honey suckle were determined and satisfactory results were achieved.

Spindle Cell Lipoma in an End-Stage Renal Allograft: Case Report.

BACKGROUND: Spindle cell lipoma is an uncommon variant of lipoma and usually occurs as a solitary, subcutaneous, and well circumscribed lesion in the posterior neck, shoulders, and back of older men. Primary renal lipomas are rarely reported. Spindle cell lipoma in the kidney has not been previously described in the literature. CASE REPORT: A 60-year-old Chinese man suffered graft failure 10 years after living related donor kidney transplantation. During cancer surveillance, he was found to have a mass in the renal allograft, which increased in size and was suspicious for renal cell carcinoma on computerized tomographic scan. The patient underwent renal graft explantation. Grossly, the kidney was atrophic, containing a 6.5 cm yellowish solid lesion without hemorrhage and necrosis in the renal sinus fat. Microscopically, the lesion was composed of variably sized adipocytes and cellular areas of bland spindle cells with no cytologic atypia. There were prominent slender blood vessels within the lesion, along with focal myxoid change as well as scattered mast cells and inflammatory cells. Lipoblasts were not identified. The spindle cells were positive for CD34 and negative for Melan-A, HMB45, S100, and SMA. Pax-2 stain was nonspecific. MDM2 amplification by means of fluorescence in situ hybridization (FISH) and overexpression by immunohistochemistry were negative. The Ki-67 proliferation index was <1%. Interphase FISH revealed loss of 13q and 16q in the tumor. CONCLUSIONS: Renal spindle cell lipoma is a rare benign tumor. Angiomyolipoma and well differentiated liposarcoma are the main differential diagnoses. Immunohistochemistry and cytogenetic techniques are helpful in differentiating it from malignant entities.

Intra-articular nodular fasciitis: an unexpected diagnosis for a joint lesion: a case report.

UNLABELLED: Pathological lesions in and around a joint can arise from underlying dermis, subcutis, deep muscle, bone or synovium. Clinical presentation can include joint pain, joint swelling, palpable masses and mechanical restriction. Whilst giant cell tumour of tendon sheath, pigmented villonodular synovitis, synovial chondromatosis, lipoma arborescens, juxta articular myxomas and inflammatory arthritis are the better-known conditions of the joint. Intra-articular nodular fasciitis, on the other hand, is less well recognized both clinically and radiologically. It is rarely seen in routine practice and is only described in case reports in the literature. Due to the non-specific clinical and radiological findings as well as the unfamiliarity with the entity, the diagnosis of intra-articular nodular fasciitis is usually clinched only after histological examination. We present a case of intra-articular nodular fasciitis arising in the knee joint which was not suspected clinically or radiologically. KEY WORDS: Intra-articular, nodular fasciitis, joint, knee, MRI.

Zuckerkandl tubercle of the thyroid: a common imaging finding that may mimic pathology.

BACKGROUND AND PURPOSE: The posterior thyroid tubercle, also known as ZT, is an important surgical landmark due to its close proximity to the recurrent laryngeal nerve. A recent case of ZT with a nodular configuration caused clinical concern but was shown on biopsy to be normal thyroid tissue. The purpose of this study was to review a series of CT neck studies to identify how often ZT-specifically, a nodular subtype-was present. MATERIALS AND METHODS: A total of 96 neck CTs from sequential patients were retrospectively identified from January 2010 to July 2010. ZT was defined on imaging as a thyroid lobe extending posterior to the tracheoesophageal groove. A nodular subtype was defined as having a narrowed neck at the level of the tracheoesophageal groove. RESULTS: There were 31 women and 45 men (mean age of 56.1 years, range 22-100 years) who met inclusion criteria. Sixty-seven patients had thyroid glands that extended posterior to the tracheoesophageal groove at CT imaging; this finding was bilateral in 43 patients, more commonly on the right (60 versus 49). Thirty-two of these patients (42.1%; 16 male, 16 female) had a nodular subtype. CONCLUSIONS: ZT is an important surgical landmark of the thyroid that has important radiologic variations. It has a nodular shape in over a third of CT neck studies in our series. Recognition of this feature of the thyroid gland at CT imaging can obviate the need for biopsy and avoid potential recurrent laryngeal nerve injury.

Prevalence of hypertension and correlates among adults of 45-60 years in a rural area of Tamil Nadu.

Hypertension is one of the major causes of cardiovascular morbidity and mortality. Community based studies in the rural areas of Tamil Nadu on the prevalence of hypertension and its associated risk factors are scarce. A cross-sectional study was undertaken among a sample of 406 individuals (45-60 years) selected by the standard 30 cluster systematic random sampling technique to find out prevalence of hypertension and its associated risk factors in a rural area of Tamil Nadu. Chi-square test and multiple logistic regression were employed using SPSS package. The overall prevalence of hypertension was 33% and higher among sedentary type (41%). In bivariate analysis many of the independent variables correlated with hypertension, but in multivariate analysis, only body-mass index, family history and age remained significant.

Depression in the elderly in Vellore, South India: the use of a two-question screen.

BACKGROUND: Depression in the elderly is a common and disabling condition. The aim of the study was to evaluate the sensitivity and specificity of a two-question screen to identify depression and common mental disorders in the elderly. METHOD: Residents of a ward in the town of Vellore were identified by a door-to-door survey from which 204 subjects aged over 60 years were selected for the study by systematic random sampling. They were screened using the two-question screen. The Revised Clinical Interview Schedule (CIS-R) was employed to confirm the diagnosis. RESULTS: The prevalence of depression and common mental disorder, using the CIS-R standard, was found to be 31.5%. The two-question screen has a sensitivity of 93.8% and specificity of 48.2%. CONCLUSIONS: The high sensitivity of the two-question screen makes it a useful screening method which can be employed by health workers in the field.

Ketamine and pulmonary oedema-report of two cases.

SUMMARY: Perioperative pulmonary oedema is one of the most challenging complications faced by anaesthesiologists. In most of the instances, coronary artery disease, valvular heart diseases, hypertension may precipitate pulmonary oedema due to increased hydrostatic pressure while acid aspiration, airway obstruction may cause it due to increased vascular permeability. In a few instances, acute pulmonary oedema can present in an otherwise healthy patient to cause diagnostic difficulties. We report two such cases of intra operative pulmonary oedema with the use of ketamine which were identified and managed successfully. The most probable cause is also described.

Parafibromin expression in breast cancer: a novel marker for prognostication?

BACKGROUND: Parafibromin is a novel protein product of HRPT2, a recently identified tumour suppressor gene. Mutations of the HRPT2 gene are common in parathyroid carcinomas, and these exhibit reduced protein expression. Parafibromin expression in breast cancer has not been previously studied. AIMS: To determine the distribution of parafibromin in breast cancer tissues, and correlate its expression with conventional pathological parameters. METHODS: Tissue microarrays were constructed from archival paraffin embedded breast cancer samples. Sections cut from tissue microarray blocks were subjected to immunohistochemistry. Immunopositivity for parafibromin and intensity-percentage scores were derived by blinded evaluation. Findings were correlated with clinicopathological parameters. RESULTS: 163 breast cancers were assessed. Larger tumours were less likely to express parafibromin than smaller ones, with the association approaching statistical significance (p = 0.05). Staining intensity correlated inversely with tumour size (p = 0.016) and pathological stage (p = 0.008); as did parafibromin intensity-percentage score with pathological stage (p = 0.03), lymphovascular invasion (p = 0.03) and cerbB2 intensity-percentage score (p = 0.04). CONCLUSION: Parafibromin in breast cancer, as in parathyroid tumours, appears to have tumour suppressor functions, with loss of protein expression associated with adverse pathological parameters. These findings may indicate a potential role of parafibromin as a prognostic marker in breast cancer.

Pathological diagnosis of columnar cell lesions of the breast: are there issues of reproducibility?

AIMS: To assess inter/intraobserver variability in the interpretation of a series of digitised images of columnar cell lesions (CCLs) of the breast. METHODS: After a tutorial on breast CCL, 39 images were presented to seven staff pathologists, who were instructed to categorize the lesions as follows: 0, no columnar cell change (CCC) or ductal carcinoma in situ (DCIS); 1, CCC; 2, columnar cell hyperplasia; 3, CCC with architectural atypia; 4, CCC with cytological atypia; 5, DCIS. Concordance with the tutor's diagnosis and degree of agreement among pathologists for each image were determined. The same set of images was re-presented to the pathologists one week later, their diagnoses collated, and inter/intraobservor reproducibility and level of agreement for individual images analysed. RESULTS: Diagnostic reproducibility with the tutor ranged from moderate to substantial (kappa values, 0.439-0.697) in the first exercise. At repeat evaluation, intraobserver agreement was fair to perfect (kappa values, 0.271-0.832), whereas concordance with the tutor varied from fair to substantial (kappa values, 0.334-0.669). There was unanimous agreement on more images during the second exercise, mainly because of agreement on the diagnosis of DCIS. The lowest agreement was seen for CCC with cytological atypia. CONCLUSIONS: Interobserver and intraobserver agreement is good for DCIS, but more effort is needed to improve diagnostic consistency in the category of CCC with cytological atypia. Continued awareness and study of these lesions are necessary to enhance recognition and understanding.

The HercepTest and routine C-erbB2 immunohistochemistry in breast cancer: any difference?

INTRODUCTION: The proto-oncogene c-erbB2, located on chromosome 17q21, encodes a 185-kD transmembrane glycoprotein. It is known to be overexpressed, amplified, or both in 20% to 30% of breast cancers. C-erbB2 belongs to the human epidermal growth factor receptor (tyrosine kinase receptor) family that plays an important role in cell cycle regulation and differentiation. Although there are various methods to assess c-erbB2 status in breast cancer, protein overexpression determined by immunohistochemistry and gene amplification using fluorescence in situ hybridisation are most commonly utilised. This study compares the results of the DAKO HercepTest with the immunohistochemical assay (A0485, DAKO), which is routinely used in our pathology laboratory. MATERIALS AND METHODS: Paraffin-embedded breast cancer tissues from 41 patients operated in a tertiary hospital during the year 2000 were subjected to immunohistochemistry by the above methods. C-erbB2 positivity was defined by cytoplasmic membrane staining of 2+ or 3+ intensity. RESULTS: Overexpression of c-erbB2 protein was present in 36.6% and 41.5% of cases when detected by HercepTest and the DAKO A0485 antibody, respectively. There was almost perfect agreement between both methods (k = 0.898) when positive versus negative results were considered, and moderate agreement in terms of individual staining intensities (k = 0.554). CONCLUSION: Routine immunohistochemistry using the DAKO A0485 antibody is a reliable, cost-effective alternative to the HercepTest in determining prognosis and suitability of patients for Herceptin therapy.

Stromelysin-1 regulates adipogenesis during mammary gland involution.

The matrix metalloproteinase MMP-3/stromelysin-1 (Str1) is highly expressed during mammary gland involution induced by weaning. During involution, programmed cell death of the secretory epithelium takes place concomitant with the repopulation of the mammary fat pad with adipocytes. In this study, we have used a genetic approach to determine the role of Str1 during mammary involution. Although Str1 has been shown to induce unscheduled apoptosis when expressed ectopically during late pregnancy (Alexander, C.M., E.W. Howard, M.J. Bissell, and Z. Werb. 1996. J. Cell Biol. 135:1669-1677), we found that during post-lactational involution, mammary glands from transgenic mice that overexpress the tissue inhibitor of metalloproteinases, TIMP-1 (TO), or mice carrying a targeted mutation in Str1 showed accelerated differentiation and hypertrophy of adipocytes, while epithelial apoptosis was unaffected. These data suggest that matrix metalloproteinases (MMPs) do not induce unscheduled epithelial cell death after weaning, but instead alter the stromal microenvironment. We used adipogenic 3T3-L1 cells as a cell culture model to test the function of MMPs during adipocyte differentiation. Fibroblastic 3T3-L1 progenitor cells expressed very low levels of MMPs or TIMPs. The transcription of a number of MMP and TIMP mRNAs [Str1, MT1-MMP, (MMP-14) collagenase-3 (MMP-13), gelatinase A (MMP-2), and TIMP-1, -2 and -3] was induced in committed preadipocytes, but only differentiated adipocytes expressed an activated MMP, gelatinase A. The addition of MMP inhibitors (GM 6001 and TIMP-1) dramatically accelerated the accumulation of lipid during differentiation. We conclude that MMPs, especially Str1, determine the rate of adipocyte differentiation during involutive mammary gland remodeling.

A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation.

Here we show that plasma kallikrein (PKal) mediates a plasminogen (Plg) cascade in adipocyte differentiation. Ecotin, an inhibitor of serine proteases, inhibits cell-shape change, adipocyte-specific gene expression, and lipid accumulation during adipogenesis in culture. Deficiency of Plg, but not of urokinase or tissue-type plasminogen activator, suppresses adipogenesis during differentiation of 3T3-L1 cells and mammary-gland involution. PKal, which is inhibited by ecotin, is required for adipose conversion, Plg activation and 3T3-L1 differentiation. Human plasma lacking PKal does not support differentiation of 3T3-L1 cells. PKal is therefore a physiological regulator that acts in the Plg cascade during adipogenesis. We propose that the Plg cascade fosters adipocyte differentiation by degradation of the fibronectin-rich preadipocyte stromal matrix.