COVID-19 Impact on Newly Diagnosed Breast Cancers at Regional Cancer Centre, Thiruvananthapuram-An Audit.

Geethu Babu The coronavirus pandemic has created havoc in every aspect of life including cancer care and was declared a pandemic. This audit was conducted to study the impact of the pandemic on diagnosis and treatment of newly diagnosed breast cancer patients at a tertiary cancer center in South India. A total of 1,647 patients who registered at Regional Cancer Centre (RCC), Thiruvananthapuram, Kerala, India for breast cancer during the period April 1, 2020, to September 30, 2020 (COVID-19 period) as well as April 1, 2019, to September 30, 2019 (pre-COVID-19 period) were included in the study. Data regarding the geographic distribution, stage at presentation, time factors for reporting for care, diagnosis, and treatment, referral for care elsewhere were collected and analyzed. The study was approved by the Institutional Review Board. Means and ranges were calculated for continuous type variables, and numbers and percentages for categorical variables. To determine whether there were significant differences between the two groups, independent t -test was used for continuous variables and chi-square test for categorical type of variables. A notable reduction (36%) in newly diagnosed breast cancer patients was seen in 2020 when compared with 2019. There was a significant difference in the geographic distribution of patients in both cohorts ( p = 0.001) and a notable reduction in the number of patients reporting to RCC for treatment from the northern districts of Kerala (81%) and outside Kerala (89.5%). There was no significant difference in the time (in weeks) since symptom onset and reporting to hospital or the clinical stage at diagnosis between the groups. Also, coronavirus disease 2019 (COVID-19) did not seem to negatively impact time intervals between date of registration and pathological diagnosis or start of primary treatment. More patients received neoadjuvant systemic therapy during 2020 compared with 2019, and this difference was statistically significant ( p = 0.004). There was no difference in the type of surgery (breast-conserving surgery vs. modified radical mastectomy). The results demonstrate that COVID-19 did not appear to negatively impact the diagnosis and treatment of newly diagnosed breast cancer patients. However, this is largely attributable to the significantly less number of patients who registered, for whom the departments were able to maintain timely cancer care despite the difficult pandemic times. Significantly more patients received neoadjuvant systemic therapy in 2020.

Clinicopathological spectrum of central nervous system germ cell tumors: A single-institution retrospective study.

CONTEXT: Central nervous system germ cell tumors (CNSGCTs) though rare is the second most common extragonadal site for GCTs. AIMS: To determine the clinicopathological features of CNSGCTs diagnosed at our center. SETTINGS AND DESIGN: A retrospective study of all histologically diagnosed CNSGCTs, during 2006-2019. MATERIALS AND METHODS: The patients' data were retrieved from the hospital information systems and analyzed. STATISTICAL ANALYSIS: Data on categorical variables were analyzed as percentages, and data on continuous variables calculated as mean. Chi-square test or Fisher's exact test was used to study association between variables. RESULTS: Of the total 34 cases with CNSGCT, age ranged from 1 to 27 years, majority in the second decade (19/34; 56%). Male: female (M: F) ratio was 1.6:1. Single site involvement was seen in 27 cases (27/34; 79%), whereas seven (7/34; 21%) showed bi/multifocal involvement. Among the unifocal cases, common sites involved were suprasellar (12/27; 44.4%), closely followed by the pineal (10/27; 37%). All multifocal tumors affected suprasellar compartment, being bifocal with pineal in four cases. A male gender predilection was noted among pineal region (9/10;90%) and multifocal tumors (5/7;71%). Germinoma was the commonest subtype (21/34; 61.8%) with male gender predilection (17/21; 81%) (M: F =4.3:1), with female predilection seen among mixed GCTs (MGCTs) (8/10; 80%) (M: F =1:4) and suprasellar location (M: F =1:2). Serum tumor markers (25 cases) and CSF markers (7 cases) were concordant with histology in all, except two cases. CONCLUSION: Though histology and immunohistochemistry were diagnostic, correlation between serum and/or CSF marker was essential to rule out GCT component(s) that may be missed on biopsy due to sampling error.

Metastasis from renal cell carcinoma-unusual presentations.

ABSTRACT: Renal cell carcinoma is one of the most lethal tumors of the urologic system and has high metastatic potential. The usual sites of metastasis are lung, bone, liver adrenal, lymph node, and brain. Thumb and oral cavity metastasis are unusual sites of metastasis. This case report describes two cases reported with unusual thumb and oral cavity metastasis. Patients with acral and oral metastasis are often misdiagnosed as benign inflammatory disease and treatment initiation is often delayed. This case report helps in drawing the attention that such lesions can be metastatic also.

Infratentorial atypical choroid plexus papilloma in an adult: A case report and literature review.

Atypical choroid plexus papilloma is classified as WHO (World Health Organization) Grade II subtype of choroid plexus tumor, and it has intermediate pathological features, prognosis, and clinical outcome rates between choroid plexus papilloma and choroid plexus carcinoma. These tumors are more common in children compared with adults and are usually located in the lateral ventricles. We present a case of an adult with atypical choroid plexus papilloma located in the infratentorial region. A 41-year-old woman underwent evaluation for headache and dull aching neck pain. Magnetic resonance imaging (MRI) of the brain revealed a well-defined intraventricular mass lesion in the fourth ventricle and foramen of Luschka. She underwent craniotomy and gross total excision of the lesion. Histopathological and immunohistochemical findings confirmed the diagnosis of atypical choroid plexus papilloma (WHO Grade II). We discuss the various treatment options for this condition and review the relevant literature.

Clinical Spectrum of Biopsy Proven Mitochondrial Myopathy.

Objectives: Clinical spectrum of mitochondrial myopathy extends beyond chronic progressive external ophthalmoplegia (CPEO). While information on encephalomyopathies is abundant, clinical data on predominant myopathic presentation of mitochondrial disorders are lacking. Materials and Methods: Clinical, electrophysiological, biochemical, and follow-up data of patients with predominant myopathic presentation and muscle biopsy confirmed primary mitochondrial myopathy was obtained. We excluded known syndromes of mitochondrial cytopathies and encephalomyopathies. Results: Among 16 patients, 7 had CPEO, 4 had CPEO with limb-girdle muscle weakness (LGMW), and 5 had isolated LGMW. Systemic features included seizures with photosensitivity (n = 3), diabetes (n = 1), cardiomyopathy (n = 1), and sensorineural hearing loss (n = 1) and were more common in isolated LGMW. Elevated serum creatine kinase (CK) and lactate levels and electromyography (EMG) myopathic potentials were more frequent with LGMW. During follow-up, LGMW had more severe progression of weakness. Conclusion: We identified three subsets of mitochondrial myopathy with distinct clinical features and evolutionary patterns. Isolated LGMW was seen in 30% of patients and would represent severe end of the spectrum.

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study.

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups - Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades. Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Is Young Age an Independent Prognostic Factor in Carcinoma Breast? A Single-Institution Retrospective Comparative Study from South India.

Breast cancer is the most common cancer in women globally(1). It is usually a disease of old age. The incidence of breast cancer in females younger than 40 years is as low as 0.5%. Disease in patients with age less than or equal to 40 years at diagnosis is usually considered a young breast cancer(2). Occurrence of more adverse pathological features like triple negative and Her2 positive breast cancer as well as lacking reliable screening methods in young women leads to the poor prognosis in this group of patients(3). In the present study we aim to find the clinical and pathological characteristics of breast cancer in young women and their survival outcome for 5 years comparing the same with those characteristics of the older patients. Patients with nonmetastatic carcinoma breast who had registered at Regional Cancer Centre, Trivandrum, during the year 2012 were selected for the study. Patient's details including the clinicopathological features, treatment details, oncologic outcomes including recurrence, and survival data until 31 July 2019 were collected from treatment files kept in the hospital and via telephonic interview. Kaplan-Meier method was employed for survival analysis. Survival comparison was done using the log-rank test. Cox proportional hazards regression analysis was done for assessing the risk. Out of 1611 curatively treated patients with carcinoma breast, 281 (17.44%) were young breast cancer (equal to or less than 40 years). The median follow-up period was 82 months. Median age of diagnosis was 51.3 years. Young patients presented with larger tumour size, but nodal stage and composite stage, were not different. They had more TNBC status, 35% vs. 24%, p = 0.001. Young patient group had a drop in 5-year OS but statistically insignificant (75.9% vs. 82.5%, p = 0.179) and marginally significant drop in DFS (68.1% vs. 73.8%, p = 0.064). The proportion of young breast cancer is very high in the Indian population. Age is not an independent risk factor for worse prognosis. T and N stage, Her2nue status, and adequacy of nodal clearance are the most important independent risk factors deciding the 5-year OS.

Renal Cell Carcinoma Presenting as Bulky Parotid Mass-a Case Report and Review of Literature.

Renal cell carcinoma is the third most common malignancy to metastasize to the head and neck region. Among them, parotid is a well-reported site, although limited to case reports. Tumours with predominance of clear cells found in the head and neck, namely oncocytoma, clear cell carcinoma, acinic cell carcinoma, mucoepidermoid carcinoma and epithelial-myoepithelial carcinoma should be distinguished from clear cell renal cell carcinoma. This case report is regarding a patient with renal cell carcinoma presenting as bulky parotid metastasis. This literature review is to reiterate the possibility of renal cell carcinoma with parotid metastasis, as to aid in good science and better practice.

Protection of mouse brain from paracetamol-induced stress by Centella asiatica methanol extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (CA) is a medicinal herb traditionally used as a brain tonic in Ayurvedic medicine. Various ethnomedical leads revealed the effective use of CA in the treatment of symptoms associated to oxidative stress and inflammation. AIM OF THE STUDY: The aim of this study was to evaluate the therapeutic ability of CA methanol extract (CAM) in protecting mouse brain and astrocytes from oxidative stress and inflammation induced by Paracetamol, and thus to substantiate the allied traditional/ethnomedical claims of CA. MATERIALS AND METHODS: Chemical profiling of CAM and quantification of its major constituents were carried out by HPTLC-densitometry. Mice were administered with CAM and Paracetamol in various combinations, and oxidative stress parameters (lipid peroxidation, radical scavenging) as well as nitric oxide stress were estimated from isolated mouse brain. Cellular toxicity was investigated by apoptosis/necrosis in primary astrocytes isolated from brain tissues of mouse (which was challenged by CAM/Paracetamol) by flow cytometry and fluorescent microscopy. Expression of inflammatory cytokine mediators (monocyte chemo attractant protein 1, interleukin 1, interferon γ, tumor necrosis factor ß, interleukin 10 and mitogen activated protein kinase 14 gene) in CAM/Paracetamol administered mouse brain tissues was analyzed by real time PCR. Mouse brain tissues challenged by CAM/Paracetamol were also assessed for gross and histopathology. In addition, staining with acridine orange was carried out in C6 cell lines treated with CAM, and viewed under fluorescent microscopy. RESULTS: Paracetamol elicited reactive oxygen species generation was revealed through Ferric Reducing Antioxidant Power (FRAP) activity. CAM reversed the Paracetamol induced free radical and reactive nitrogen species production and increased the scavenging activity which was more pronounced at the higher dose (80 mg/kg b.wt). CAM negated the Paracetamol-induced damage by inhibiting expression of pro-inflammatory cytokines (MCP 1, IL 1, TNF ß), and increasing the expression of the anti-inflammatory cytokine (IL 10) profoundly. Interestingly, MAPK 14 gene expression was decreased gradually and became same as normal control with increase in the dose of CAM. Also, it was evident that CAM protected mouse primary astrocytes from Paracetamol by maintaining a normal morphology. Similarly, apoptosis of primary astrocytes (treated with Paracetamol/CAM) decreased with the increase in CAM dose (80 mg/kg b.wt.) which was evident from flow cytometric data. Severe brain damage in the form of lesions was apparent from the histology of Paracetamol alone treated mouse brain. Whereas, CAM treated together with Paracetamol upturned these lesions. Surprisingly, CAM alone proved to be cytotoxic to C6 Glioma cells. CONCLUSIONS: CAM showed antioxidant and anti-inflammatory effects (which were pronounced at higher doses) against Paracetamol-induced oxidative stress and associated inflammation in mouse brain. The underlying mechanisms may be mediated by inhibiting the pro-inflammatory cytokines TNF ß, IL 1 and MCP 1 via regulation of the antioxidant mediated INF γ and MAPK 14 gene signalling pathways. The major bioactive constituents in CAM are the triterpenoid saponins, asiaticoside and madecassoside. The present results provide pharmacological evidence that CAM acts as an antioxidant and anti-inflammatory agent. Furthermore, this study validates the use of CA as an antioxidant and anti-inflammatory agent in ethnomedicine.

In vitro neurosphere formation correlates with poor survival in glioma.

Sphere formation is an indicator of tumor aggressiveness independent of the tumor grade; however, its relation to progression-free survival (PFS) is less known. This study was designed to assess the neurosphere forming ability among low grade glioma (LGG) and high-grade glioma (HGG), its stem cell marker expression, and correlation to PFS. Tumor samples of 140 patients, including (LGG; n = 67) and (HGG; n = 73) were analyzed. We used sphere forming assay, immunofluorescence, and immunohistochemistry to characterize the tumors. Our study shows that, irrespective of the pathological sub type, both LGG and HGG formed neurospheres in vitro under conventional sphere forming conditions. However, the number of neurospheres formed from tumor tissues were significantly higher in HGG compared to LGG (P < 0.0001). Different grades of glioma were further characterized for the expression of stem cell marker proteins and lineage markers. When neurospheres were analyzed, CD133 positive cells were identified in addition to CD15 and nestin positive cells in both LGG and HGG. When these neurospheres were subjected to differentiation, cells positive for GFAP and ß-tubulin III were observed. Expression of stem cell markers and ß-tubulin III were prominent in HGG compared to LGG, whereas GFAP expression was higher in LGG than in HGG. Kaplan-Meier survival analysis demonstrated that neurosphere forming ability was significantly associated with shorter PFS (P < 0.05) in both LGG and HGG. Our results supports earlier studies that neurosphere formation may serve as a definitive indicator of stem cell population within the tumor and thus a better predictor of PFS than the tumor grades alone. © 2018 IUBMB Life, 71(1):244-253, 2019.

CNS small vessel vasculitis: Distinct MRI features and histopathological correlation.

BACKGROUND: Central nervous system (CNS) vasculitis is an uncommon disease, which is a diagnostic and therapeutic challenge for physicians. Large and medium vessel vasculitis is relatively easy to diagnose by angiogram compared to small vessel vasculitis, where angiograms are often normal; imaging features described till date are sensitive but not specific. PURPOSE: Here, we describe distinct magnetic resonance (MR) imaging features of CNS small vessel vasculitis. MATERIALS AND METHODS: Five histologically proven small vessel vasculitis cases were retrospectively reviewed from medical records between January 2008 to July 2012. Angiogram (magnetic resonance angiography in all and digital subtraction angiography in three patients) were normal, ruling out associated large and medium vessel vasculitis. The MR imaging findings were analyzed for T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities and blooming on susceptibility weighted imaging (SWI). RESULTS: Five patients (3 males) with a mean age of 34.2 years (range: 18 to 62 years) were included for analysis. Three patients with lymphocytic vasculitis had 43 discrete T2/FLAIR hyperintense lesions in brain parenchyma. All the brain lesions revealed central areas of SWI blooming in linear and/or lace-like pattern, surrounded by FLAIR hyperintensity. Corresponding T1-weighted contrast-enhanced images revealed subtle linear and lace-like enhancement. Coarse granular pattern of SWI blooming was seen in the patient with tuberculous vasculitis and no parenchymal abnormalities were seen in the patient with hypertrophic pachymeningitis. CONCLUSIONS: The linear SWI blooming along the course of small cerebral vessels and lace-like enhancement pattern in spin echo post-contrast T1-weighted sequences are suggestive MR imaging features for lymphocytic CNS small vessel vasculitis.

Early resective surgery causes favorable seizure outcome in malformations of cortical development.

PURPOSE: We analyzed consecutive cases of a large cohort of the spectrum of malformations of cortical development (MCDs) including focal cortical dysplasias (FCDs) who underwent presurgical evaluation through our epilepsy program from January 2000-December 2010. We analyzed factors predicting surgical candidacy, predictors of seizure outcome and reasons for deferring surgery. METHODS: 148 patients with MCD underwent detailed presurgical evaluation and 69 were operated. MCD was diagnosed based on characteristic findings in MRI and re-confirmation by histopathology in operated patients. Post-operative seizure outcome of non-operated and operated patients were assessed every 3 and 12 months and yearly intervals. Multivariate analysis and backward step-wise logistic regression analyzed factors predicting seizure outcome. Kaplan-Meier analysis predicted seizure-free survival rates. RESULTS: 66.67% patients were seizure-free and aura-free at last follow-up. On multivariate logistic regression, the predictors of seizure freedom in operated MCDs were completeness of resection (odds ratio 8.2; 95% CI 1.43-64.96, p=0.01), shorter duration of epilepsy (odds ratio 1.19, 95% CI 1.02-1.39, p=0.02), and absence of spikes in post-operative EEG at one year (odds ratio 4.2; 95% CI 2.52-16.6; p<0.002). In FCD sub-group, shorter duration of epilepsy (11.1 versus 16.1 years, p=0.03), absence of secondary generalized seizures (p=0.05), absence of spikes in post-operative EEG on seventh day (p=0.009) and one year (p=0.002) were associated with favorable seizure outcome. CONCLUSION: Majority of patients with MCD and refractory epilepsy when operated early remains seizure-free. Shorter duration of epilepsy is the single most important pre-operative variable and absence of spikes in post-operative EEG, predicts a long-term favorable seizure outcome.

Surgery for "Long-term epilepsy associated tumors (LEATs)": Seizure outcome and its predictors.

OBJECTIVES: "Long-term epilepsy associated tumors (LEATs)" by definition are tumors primarily causing drug-resistant seizures for two years or more. They include low-grade glial and glioneuronal tumors with normal life expectancy. We studied a large cohort of patients with LEATs who underwent surgery through our epilepsy program. PATIENTS & METHODS: From 1998-2011, 105 patients with LEATs underwent surgery in our center. We utilized their data archived in a prospective registry to evaluate their electro-clinical-imaging characteristics affecting the long-term seizure outcome. RESULTS: Of 105 patients (age 3-50 years), mean age at surgery was 20 years and mean pre-surgical duration of epilepsy was 10.9 years. 66 (62.8%) had secondary generalized seizures. 82 had temporal tumors, 23 had extra temporal (13 frontal, 3 parietal, 2 occipital and 5 multilobar lesions) and four had associated hippocampal sclerosis. The interictal discharges and ictal onset were concordant to the lesion in 82 (78%) and 98 (93%) patients respectively. Lesionectomy and/or adjoining corticectomy or temporal lobectomy was done. Ganglioglioma was the most dominant pathological substrate in 61 (58%). During a mean follow-up of 7.5 years (range 3-16 years), 78/105 (74.2%) were seizure-free and 45 (57.4%) were totally off drugs. Secondary generalized seizures (p-0.02), temporal location of tumor (p-0.008) and spikes in third month post-operative EEG (p-0.03) caused unfavorable seizure outcome. A pre-surgical duration of epilepsy of more than 6.6 years caused less than optimal surgical outcome CONCLUSIONS: Early surgery should be considered a priority in LEATs. Presence of secondary generalized seizures is the single most important predictor of a poor seizure outcome.

Characterizing the biocompatibility and tumor-imaging capability of Cu2S nanocrystals in vivo.

Multifunctional nanomaterial-based probes have had key impacts on high-resolution and high-sensitivity bioimaging and therapeutics. Typically, NIR-absorbing metal sulfide-based nanocrystals (NCs) are highly assuring due to their unique optical properties. Yet, their in vivo behavior remains undetermined, which in turn undermines their potential bioapplications. Herein, we have examined the application of PEGylated Cu2S NCs as tumor contrast optical nanoprobes as well as investigated the short- and long-term in vivo compatibility focusing on anti-oxidant defense mechanism, genetic material, immune system, and vital organs. The studies revealed an overall safe profile of the NCs with no apparent toxicity even at longer exposure periods. The acquired observations culminate into a set of primary safety data of this nanomaterial and the use of PEGylated Cu2S NCs as promising optical nanoprobes with immense futuristic bioapplications.

Rosette forming glioneuronal tumor of the fourth ventricle in squash cytology smear.

Rosette forming glioneuronal tumor (RGNT) is a recently recognized and extremely rare glioneuronal tumor occurring in the fourth ventricle. It is crucial for the cytopathologist to be aware of this entity as it can be easily mistaken for more common neoplasms occurring at this site. We present here the cytology of such a rare case of RGNT that was misdiagnosed as ependymoma. The varying cytological features of this entity, as well as the common diagnostic difficulties encountered in cytology, are highlighted in this report.

Neuroenteric cysts of the brain-comprehensive magnetic resonance imaging.

Neuroenteric cysts are developmental cysts that should be differentiated from other, more common non-neoplastic cysts as well as cystic neoplasms. While these lesions may have varied imaging findings, T1 hyperintense prepontine lesion due to mucinous/proteinaceous content is characteristic. Location and imaging characteristics aid in formulating the correct diagnosis of neuroepithelial/neuroenteric cysts. Magnetic resonance spectroscopy (MRS) has the specific finding of N-Acetyl Aspartate (NAA)-like peak at 2.02 ppm which is not seen in other cystic lesions. In this study, we aim to discuss the imaging findings of these lesions on conventional and advanced MRI findings and provide radiologic-pathologic correlation. We also briefly describe the pathogenesis, embryology and radiological differential diagnoses of these cysts.