HER2/ERBB2 overexpression in advanced gallbladder carcinoma: comprehensive evaluation by immunocytochemistry and fluorescence in situ hybridisation on fine-needle aspiration cytology samples.

AIMS: Advanced gallbladder carcinoma (AGBC) carries a poor prognosis with dismal survival. There are no data regarding HER2/ERBB2 expression in AGBC. This study evaluated the overexpression of HER2/ERBB2 in cytological aspirates from AGBCs to identify potential patients for whom anti-HER2 targeted therapies can benefit. METHODS: This prospective, case-control study was performed on 50 primary AGBC cases. A detailed cytomorphological assessment, followed by immunocytochemistry (ICC) for HER2/ERBB2, was performed on AGBC cell blocks. A similar number of age-matched and gender-matched resected chronic cholecystitis specimens were included as controls. Fluorescence in situ hybridisation (FISH) was performed in equivocal cases. RESULTS: A total of 10 (20%) cases showed positive (3+), 19 (38%) equivocal (2+) expression and 21 (42%) were negative on HER2/ERBB2 ICC. None of the equivocal cases demonstrated HER2 amplification by FISH. Among the controls, none showed positive (3+) immunoexpression, 23 (46%) demonstrated equivocal expression and 27 (54%) were negative. On statistical analysis, HER2/ERBB2 overexpression was significantly associated with AGBC compared with the controls. Of all the clinical, radiological and cytomorphological parameters, the predominant papillary or acinar arrangements of the tumour cells were significantly associated with HER2/ERBB2 overexpression. CONCLUSIONS: This is the first study to evaluate the expression of HER2/ERBB2 on cytological aspirates in AGBC using ICC and FISH. HER2/ERBB2 overexpression(20%) was significantly associated with AGBC. Furthermore, predominant papillary or acinar arrangements of tumour cells in the cytological smears were significantly associated with HER2/ERBB2 overexpression. They can serve as potential predictors of HER2/ERBB2 overexpression to select AGBC patients for anti-HER2 targeted therapies.

Cerebrospinal fluid cytology in a toddler with a posterior fossa space-occupying lesion.

An atypical teratoid rhabdoid tumour (AT/RT) is an extremely rare malignant neoplasm. Cerebrospinal fluid (CSF) involvement at presentation indicates intracranial dissemination and is associated with an aggressive course and worse outcomes. We present the characteristic cytomorphological features of AT/RT in the cerebrospinal fluid from a toddler presenting with a posterior fossa space-occupying lesion.

Prospective evaluation of the setup errors and its impact on safety margin for cervical cancer pelvic conformal radiotherapy.

AIM: The primary objective was to assess set-up errors (SE) and secondary objective was to determine optimal safety margin (SM). BACKGROUND: To evaluate the SE and its impact on the SM utilizing electronic portal imaging (EPI) for pelvic conformal radiotherapy. MATERIAL AND METHODS: 20 cervical cancer patients were enrolled in this prospective study. Supine position with ankle and knee rest was used during CT simulation. The contouring was done using consensus guideline for intact uterus. 50 Gy in 25 fractions were delivered at the isocenter with ≥95% PTV coverage. Two orthogonal (Anterior and Lateral) digitally reconstructed radiograph (DRR) was constructed as a reference image. The pair of orthogonal [Anterior-Posterior and Right Lateral] single exposure EPIs during radiation was taken. The reference DRR and EPIs were compared for shifts, and SE was calculated in the X-axis, Y-axis, and Z-axis directions. RESULTS: 320 images (40 DRRs and 280 EPIs) were assessed. The systematic error in the Z-axis (AP EPI), X-axis (AP EPI), and Y-axis (Lat EPI) ranged from -12.0 to 11.8 mm, -10.3 to 7.5 mm, and -8.50 to 9.70 mm, while the random error ranged from 1.60 to 6.15 mm, 0.59 to 4.93 mm, and 1.02 to -4.35 mm. The SM computed were 7.07, 6.36, and 7.79 mm in the Y-axis, X-axis, and Z-axis by Van Herk's equation, and 6.0, 5.51, and 6.74 mm by Stroom's equation. CONCLUSION: The computed SE helps defining SM, and it may differ between institutions. In our study, the calculated SM was approximately 8 mm in the Z-axis, 7 mm in X and Y axis for pelvic conformal radiotherapy.

Association of Lifestyle Risk Factors with Metabolic Syndrome Components: A Cross-sectional Study in Eastern India.

BACKGROUND: Approximately 20%-25% of the world adult population and nearly 30% of Indians have metabolic syndrome disorder. Our objective was designed to find out the association between important nutrients and potential lifestyle risk factors such as diet, physical inactivity, and smoking and alcohol consumption with the number of metabolic syndrome components. METHODS: This was a cross-sectional study. A total of 205 patients of metabolic syndrome were enrolled for this study. Diagnosis of metabolic syndrome was done on the basis of National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III 2004). Dietary data were collected with the validated food frequency questionnaire and 24 h dietary recall method, and the nutrient intake was calculated with the specially designed software. RESULTS: Unhealthy dietary habits were seen more among the participants who had more than 3 risk factors. Results showed the odds of taking >5 times junk foods was 3 times higher (odds ratio [OR]: 2.97; 95% confidence interval [CI]: 1.61-5.47), and sweet dishes was 2.3 times higher (OR: 2.33; 95% CI: 1.28-4.24) among the participants who had 4-5 risk factors. However, milk and dairy products > 4 servings/day (OR: 0.54; 95% CI: 0.175-1.67) and pulses and legumes more than 2 servings/day (OR: 0.57; 95% CI: 0.25-1.29) was protective against hypertension. Mean carbohydrate, saturated fat, and sodium intake was significantly higher in the participants who had 4-5 metabolic risk factors compared to 3 risk factors (P < 0.0001). CONCLUSIONS: It was concluded that low intake of fruits, vegetables, and higher intake of flesh food and inadequate physical activity significantly associated with the metabolic syndrome risk factors.

Multiconfiguration Pair-Density Functional Theory Predicts Spin-State Ordering in Iron Complexes with the Same Accuracy as Complete Active Space Second-Order Perturbation Theory at a Significantly Reduced Computational Cost.

The spin-state orderings in nine Fe(II) and Fe(III) complexes with ligands of diverse ligand-field strength were investigated with multiconfiguration pair-density functional theory (MC-PDFT). The performance of this method was compared to that of complete active space second-order perturbation theory (CASPT2) and Kohn-Sham density functional theory. We also investigated the dependence of CASPT2 and MC-PDFT results on the size of the active-space. MC-PDFT reproduces the CASPT2 spin-state ordering, the dependence on the ligand field strength, and the dependence on active space at a computational cost that is significantly reduced as compared to CASPT2.

Carcinoma ex pleomorphic adenoma: A diagnostic challenge on cytology.

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a malignant neoplasm arising from primary or recurrent benign pleomorphic adenoma. It is rare with an annual incidence rate of 0.17 tumors per million. Histopathology remains the gold standard for the diagnosis of Ca ex PA, with only a handful of cases reported on cytology. In our case a 66-year-old male presented with the right parotid mass for 5 years rapidly increasing for the last 3 months. Fine needle aspiration cytology (FNAC) smears showed malignant tumor cells in clusters along with benign myoepithelial cells in chondromyxoid background. Histopathologically, highly pleomorphic malignant epithelial cells in sheets along with foci of comedonecrosis and areas corresponding to benign pleomorphic adenoma were observed on careful scrutiny. Immunohistochemistry revealed positivity for cytokeratin (CK 7) and gross cystic disease fluid protein 15 (GCDFP-15) while CK5/6 and high molecular weight CK (34 ßE12) were negative in the malignant tumor cells. So, the final impression was Ca ex PA with salivary duct carcinoma as malignant component. We hereby report this case to highlight the significance of FNAC in the diagnosis of Ca ex PA which can be easily missed on cytopathology. However, it is important to corroborate the cytological findings with clinical suspicion of malignancy as well as radiology. Diagn. Cytopathol. 2017;45:651-654. © 2017 Wiley Periodicals, Inc.

Malignant granular cell tumor of the breast; literature review.

Malignant granular cell tumor (MGCT) is rare tumors that comprise 1-2% of all granular cell tumors. They commonly arise on lower extremity, nuchal region, chest wall, gastrointestinal tract, head, and neck but very rarely in breast. We report a case of a MGCT of breast with review of literature. The patient had noticed a breast mass 4 years back which was operated, and wide local excision was done. The tumor was diagnosed as MGCT. The tumor fulfilled 3 of the 6 criteria of Fanburg-Smith et al. The patient received 8 cycles of chemotherapy thereafter with 4 cycles of antharacycline and 4 of taxanes. However, the tumor reoccurred 4 years after resection and grew rapidly. Contrast-enhanced computed tomography done showed a large lobulated breast mass with axillary lymph node metastasis. She underwent Modified Radical Mastectomy with axillary clearance. The histopathology this time also revealed similar malignant tumor. To the best of our knowledge, only 7 cases have been reported in indexed English literature occurring primarily in breast.

Mechanism of Oxidation of Ethane to Ethanol at Iron(IV)-Oxo Sites in Magnesium-Diluted Fe2(dobdc).

The catalytic properties of the metal-organic framework Fe2(dobdc), containing open Fe(II) sites, include hydroxylation of phenol by pure Fe2(dobdc) and hydroxylation of ethane by its magnesium-diluted analogue, Fe0.1Mg1.9(dobdc). In earlier work, the latter reaction was proposed to occur through a redox mechanism involving the generation of an iron(IV)-oxo species, which is an intermediate that is also observed or postulated (depending on the case) in some heme and nonheme enzymes and their model complexes. In the present work, we present a detailed mechanism by which the catalytic material, Fe0.1Mg1.9(dobdc), activates the strong C-H bonds of ethane. Kohn-Sham density functional and multireference wave function calculations have been performed to characterize the electronic structure of key species. We show that the catalytic nonheme-Fe hydroxylation of the strong C-H bond of ethane proceeds by a quintet single-state σ-attack pathway after the formation of highly reactive iron-oxo intermediate. The mechanistic pathway involves three key transition states, with the highest activation barrier for the transfer of oxygen from N2O to the Fe(II) center. The uncatalyzed reaction, where nitrous oxide directly oxidizes ethane to ethanol is found to have an activation barrier of 280 kJ/mol, in contrast to 82 kJ/mol for the slowest step in the iron(IV)-oxo catalytic mechanism. The energetics of the C-H bond activation steps of ethane and methane are also compared. Dehydrogenation and dissociation pathways that can compete with the formation of ethanol were shown to involve higher barriers than the hydroxylation pathway.

Oxidation of ethane to ethanol by N2O in a metal-organic framework with coordinatively unsaturated iron(II) sites.

Enzymatic haem and non-haem high-valent iron-oxo species are known to activate strong C-H bonds, yet duplicating this reactivity in a synthetic system remains a formidable challenge. Although instability of the terminal iron-oxo moiety is perhaps the foremost obstacle, steric and electronic factors also limit the activity of previously reported mononuclear iron(IV)-oxo compounds. In particular, although nature's non-haem iron(IV)-oxo compounds possess high-spin S = 2 ground states, this electronic configuration has proved difficult to achieve in a molecular species. These challenges may be mitigated within metal-organic frameworks that feature site-isolated iron centres in a constrained, weak-field ligand environment. Here, we show that the metal-organic framework Fe2(dobdc) (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate) and its magnesium-diluted analogue, Fe0.1Mg1.9(dobdc), are able to activate the C-H bonds of ethane and convert it into ethanol and acetaldehyde using nitrous oxide as the terminal oxidant. Electronic structure calculations indicate that the active oxidant is likely to be a high-spin S = 2 iron(IV)-oxo species.

Role of fine-needle aspiration cytology in the prompt diagnosis of recurrence of visceral leishmaniasis presented as isolated cervical leishmanial lymphadenopathy.

We report a case of isolated cervical leishmanial lymphadenopathy diagnosed by fine-needle aspiration cytology (FNAC) in apparently cured case of visceral leishmaniasis. A 28-year-old female presented with cervical lymphnode enlargement to surgery outpatient department and was subjected for FNAC. Smear showed numerous Leishmania donovani bodies in the cytoplasm of macrophages and giant cells, and extracellular spaces. She was treated by Amphotericin B for alternate 14 days and the size of the lymphnode regressed. She was found asymptomatic for 1 year of follow-up.