Abstract
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Biren Parikh
Introduction
Hormonal status and HER2 expression are valuable biomarkers and dictate the management of the patients diagnosed with ...invasive breast cancer (IBC). It is crucial to identify the patients who truly respond to anti-HER2 targeted therapy. Updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines has recommended certain modifications in HER2 interpretation by fluorescence in situ hybridization (FISH) with concomitant immunohistochemistry (IHC).
Objectives
We aimed to evaluate HER2 FISH interpretation in IBC with equivocal IHC results as per 2018 ASCO/CAP recommendations and compare FISH results with hormonal receptor status.
Materials and Methods
FISH results of 502 cases of IBC with equivocal IHC report between January 2016 to January 2022 were reviewed retrospectively. FISH results were categorized according to ASCO/CAP guidelines 2018 into five respective groups.
Results
FISH testing in IHC equivocal cases showed 219 (43.6%) cases were classic amplified (positive) belonged to group 1, 217(43.2%) cases were classic nonamplified (negative) fell into group 5, 39 (7.8%) and 02 (0.4%) patients were in group 2 (negative) and group 3 (positive), and 25 (5.0%) cases were in group 4 (negative). About 52.1 and 49.3% of cases with estrogen receptor and progesterone receptor positivity were reported as HER2 positive. Among 502 cases, 25 equivocal cases according to the 2013 guidelines were redefined as HER2 negative and 02 (0.4%) cases reported positive were classified negative as per updated 2018 guidelines.
Conclusion
Revised 2018 guidelines is helpful in accurate identification of HER2 status and in avoiding targeted therapy in unwarranted cases. Updated 2018 guidelines has removed equivocal HER2-FISH category that has eliminated management dilemma in these cases. Only long-term clinical follow-up will establish the validity of the updated guidelines.
Ewing sarcoma usually arises in the bones of children. Extra-skeletal Ewing sarcoma commonly occurs in soft tissue and rarely involves other organs of the body. The mesentery besides the intestine is ...an extremely uncommon location. The diagnosis poses a challenge as other malignant small round cell tumors come in the differential diagnosis in this location. Early histopathological diagnosis and immunohistochemical confirmation are crucial to outline an appropriate treatment plan. Expression of membranous CD99 and nuclear FLI-1 and NKX2.2 are fairly specific for diagnosis. The molecular study is reserved for difficult cases. Prognosis is poor in an extra-skeletal location in older individuals.
Retinoblastoma, the most common primary intraocular malignant neoplasm in young children, show frequent metastasis to lymph nodes, central nervous system and bones. However, retinoblastoma ...metastasizing to parotid gland is very rare. We here present 2 cases of isolated parotid gland metastasis in two children with unilateral retinoblastoma.
Case 1 was a one-year-old child presenting with left globe lesion which was diagnosed as Retinoblastoma. Post chemotherapy, enucleation was done which on histopathology examination showed retinoblastoma with scleral invasion and anterior chamber seeding. On 3 month follow up, patient presented with left parotid swelling. He underwent Fine needle aspiration cytology (FNAC) and Core needle biopsy which confirmed retinoblastoma metastasizing to parotid following which superficial parotidectomy was done as it was a solitary hotspot on PET-CT followed by localized radiotherapy and chemotherapy.
While case 2, a 6-year-old child presented with left parotid swelling with a history of undergoing enucleation 3 months earlier in an outside hospital; Enucleation slides were reviewed in addition to patient undergoing FNAC and Biopsy from parotid swelling, all of which were consistent with Retinoblastoma metastasizing to parotid; This patient was lost to follow up;
Although rare with only a few case reports in literature, both the pathologist and the clinician should be aware of retinoblastoma metastasizing to parotid, which when diagnosed and treated promptly has overall better prognosis in the cases reported so far.
: In developing countries for all palpable breast lesions, Fine needle aspiration Biopsy (FNAB) is the most suitable test as FNAB is minimally invasive and cost-effective.
The present study was ...undertaken to categorise the Breast Fine Needle Aspiration Biopsy (FNAB) samples according to the IAC Yokohama system of reporting and to assess the Risk of malignancy (ROM) for each category as well as to elucidate other quality indicators of the Breast FNAB.
: Among the total 102 cases in which FNAC were performed, 9 were insufficient/ inadequate (8.80%), 11 were benign (10.80%), 5 were atypical (4.95%), 3 were suspicious (2.95%) and the rest 74 FNACs were malignant (72.5%). ROM of insufficient/inadequate, benign, atypical, suspicious and malignant ware 37.5%, 0%, 50%, 100% and 100% respectively. Absolute sensitivity (only category V) was 90.1 and complete sensitivity (including category III to V) was 96.3%. Specificity of IAC Yokohama system is 100% when considering category 5 as positive and is 88.9% when considering category 3 to 5 as positive.
: The IAC Yokohama Reporting System for breast cytology has high sensitivity, specificity. The ROM in our study done in Indian population ware comparable to the proposed IAC Yokohama system which suggests the IAC Yokohama system has high reproducibility and can be applied in Indian population. Usage of FNAC for the evaluation of breast lumps and categorization based on the Yokohama system helps in ideal management of the patient, reducing the requirement of core needle biopsy.
We present a case of a 33-year-old female with a slow growing, right peribronchial vascular mass and associated symptoms of progressive cough, dyspnea on exertion, and hemoptysis. On routine ...diagnostic flexible bronchoscopy with needle biopsy, the lesion hemorrhaged extensively requiring emergent thoracotomy, right lower and middle bilobectomy. The histopathology of the specimen was consistent with the rare and unusually located entity Rosai-Dorfman disease.
Emotional Intelligence is one of the most talked topics in the human resource domain today. Many organisations have recognized the importance of studying and analyzing the Emotional Intelligence of ...their employees as it helps the organisation in understanding their employees, solving critical interpersonal problems, curating appropriate training programs and on a broader basis helps improving productivity. The study involves in assessment of the relationship between Emotional Intelligence and Organisational Commitment in manufacturing sector with special reference to a private tea manufacturing company in Nilgiris with 60 employees. The factors of Emotional Intelligence that have a significant impact on Organisational Commitment have also been analyzed and insights have been obtained.
This research introduces a novel method that leverages Spirulina extract (S.E) as a bio-surfactant in the ultrasound-assisted synthesis (UAS) of Pd
(0.25-10 mol%) doped tin oxide (SnO
) ...self-assembled superstructures. Nanotechnology has witnessed significant advancements in recent years, driven by the exploration of novel synthesis methods and the development of advanced nanomaterials tailored for specific applications. Metal oxide nanoparticles, particularly SnO
, have garnered considerable attention due to their versatile properties and potential applications in various fields, including gas sensing, catalysis, and biomedical engineering. The study explores how varying influential parameters like S.E concentration, sonication time, pH, and sonication power can influence the resulting superstructures' morphology, size, and shape. A theoretical model for forming different hierarchical superstructures (HS) is proposed. X-ray diffraction (XRD) analysis confirms the crystalline tetragonal rutile phase of the SnO
:Pd HS. Raman spectroscopy reveals a red shift in the A1g mode, indicating phonon confinement due to various defects in the SnO
structure. Further characterization using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) provides insights into particle size, surface morphology, elemental composition, and binding energy. The study also demonstrates the application of optimized SnO
:3Pd HS in developing latent fingerprints (LFPs) on different surfaces using a simple powder dusting (PD) method, with the fingerprints (FPs) visualized under normal light. A mathematical model developed in Python-based software is used to analyze various features of the developed FPs, including pore properties such as number, position, inter-spacing, area, and shape. Additionally, an in vitro MTT assay shows concentration-dependent anticancer activity of SnO
:3Pd nanoparticles (NPs) on MCF7 cell lines, highlighting their potential as a promising cancer treatment option. Overall, the study suggests that the optimized HS can serve as multifunctional platforms for biomedical and dermatoglyphics applications, demonstrating the versatility and potential of the synthesized materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase. However, whether peroxidase ...intermediates generated inside human cells or biofluids are involved in the biodegradation of carbon nanotubes has not been explored. Here, we show that hypochlorite and reactive radical intermediates of the human neutrophil enzyme myeloperoxidase catalyse the biodegradation of single-walled carbon nanotubes in vitro, in neutrophils and to a lesser degree in macrophages. Molecular modelling suggests that interactions of basic amino acids of the enzyme with the carboxyls on the carbon nanotubes position the nanotubes near the catalytic site. Importantly, the biodegraded nanotubes do not generate an inflammatory response when aspirated into the lungs of mice. Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Macrophage recognition of apoptotic cells depends on externalization of phosphatidylserine (PS), which is normally maintained within the cytosolic leaflet of the plasma membrane by aminophospholipid ...translocase (APLT). APLT is sensitive to redox modifications of its -SH groups. Because activated macrophages produce reactive oxygen and nitrogen species, we hypothesized that macrophages can directly participate in apoptotic cell clearance by S-nitrosylation/oxidation and inhibition of APLT causing PS externalization. Here we report that exposure of target HL-60 cells to nitrosative stress inhibited APLT, induced PS externalization, and enhanced recognition and elimination of "nitrosatively" modified cells by RAW 264.7 macrophages. Using S-nitroso-L-cysteine-ethyl ester (SNCEE) and S-nitrosoglutathione (GSNO) that cause intracellular and extracellular trans-nitrosylation of proteins, respectively, we found that SNCEE (but not GSNO) caused significant S-nitrosylation/oxidation of thiols in HL-60 cells. SNCEE also strongly inhibited APLT, activated scramblase, and caused PS externalization. However, SNCEE did not induce caspase activation or nuclear condensation/fragmentation suggesting that PS externalization was dissociated from the common apoptotic pathway. Dithiothreitol reversed SNCEE-induced S-nitrosylation, APLT inhibition, and PS externalization. SNCEE but not GSNO stimulated phagocytosis of HL-60 cells. Moreover, phagocytosis of target cells by lipopolysaccharide-stimulated macrophages was significantly suppressed by an NO. scavenger, DAF-2. Thus, macrophage-induced nitrosylation/oxidation plays an important role in cell clearance, and hence in the resolution of inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Broad applications of single-walled carbon nanotubes (SWCNT) dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive ...towards controlling their biological action. We report that SWCNT coating with a phospholipid "eat-me" signal, phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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