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Context.--Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following anti-HER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH). Objective.--To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay. Design.--D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results. Results.--Concordance of 98.65% and a Cohen [kappa] value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and [kappa] values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (k values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively). Conclusions.--We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status. doi: 10.5858/arpa.2022-0543-0A, The human epidermal growth factor (HER2/neu) gene, located on the long arm of human chromosome 17 (17q12), is associated with aggressive tumor behavior and has emerged as an independent prognostic [...]

Byline: Tabassum. Wadasadawala, Shalaka. Joshi, Sushmita. Rath, Palak. Popat, Ayushi. Sahay, Seema. Gulia, Prabhat. Bhargava, Revathy. Krishnamurthy, Dileep. Hoysal, Jessicka. Shah, Mitchelle. Engineer, Jyoti. Bajpai, Bhavika. Kothari, Rima. Pathak, Dushyant. [...]

Introduction: Conventional magnetic resonance imaging (MRI) has limitations in differentiating tumor recurrence (TR) from radionecrosis (RN) in high-grade gliomas (HGG), which can present with morphologically similar appearances. Multiparametric advanced MR sequences and Positron Emission Tomography (PET) with amino acid tracers can aid in diagnosing tumor metabolism. The role of both modalities on an individual basis and combined performances were investigated in the current study. Materials and Methods: Patients with HGG with MRI and PET within three weeks were included in the retrospective analysis. The multiparametric MRI included T1- contrast, T2-weighted sequences, perfusion, diffusion, and spectroscopy. MRI was interpreted by a neuroradiologist without using information from PET imaging. 18F-Fluoroethyl-Tyrosine (FET) uptake was calculated from the areas of maximum enhancement/suspicion, which was assessed by a nuclear medicine physician (having access to MRI to determine tumor-to-white matter ratio over a specific region). A definitive diagnosis of TR or RN was made based on the combination of multidisciplinary joint clinic decisions, histopathological examination, and clinic-radiological follow-up as applicable. Results: 62 patients were included in the study between July 2018 and August 2021. The histology during initial diagnosis was glioblastoma, oligodendroglioma, and astrocytoma in 43, 7, and 6 patients, respectively, while in 6, no definitive histological characterization was available. The median time from radiation (RT) was 23 months. 46 and 16 patients had TR and RN recurrence, respectively. Sensitivity, specificity, and accuracy using MRI were 98, 77, and 94%, respectively. Using PET imaging with T/W cut-off of 2.65, sensitivity, specificity, and accuracy were 79, 84, and 80%, respectively. The best results were obtained using both imaging combined with sensitivity, specificity, and accuracy of 98, 100, and 98%, respectively. Conclusion: Combined imaging with MRI and FET-PET offers multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value. [ABSTRACT FROM AUTHOR]

This article, titled "Toll Like Receptor 4 Gene in Triple Breast Cancer: Prognostic Relevance," explores the role of Toll-like receptor 4 (TLR4) in the pathogenesis of triple-negative breast cancer (TNBC). TNBC is a subtype of breast cancer that lacks certain receptors and accounts for a significant percentage of cases in Indian women. The study examines the expression of TLR4 pathway-associated genes in TNBC tumors and validates the findings using a TNBC transcriptome dataset. The results suggest a synergistic association between TLR4 and IFNϒ signaling in the development of TNBC. [Extracted from the article]

Extracranial metastasis from high-grade glial tumors is an extremely rare condition with its reported incidence being <1%. The most common sites reported in the literature are leptomeninges and spinal cord, followed by the liver, lung, and skeletal system. Its low incidence is thought to be related to the intrinsic aggressive biology of the tumor, thus reducing median overall survival in patients. As there is lack of knowledge about the mechanism of extracranial spread of glioma cells, its diagnosis and management remain a major challenge. We report two cases of extracranial metastases from glial tumors to cervical nodes and postoperative site involving preauricular region detected on F18 Fluoro ethyl tyrosine (FET) positron emission tomography-computed tomography and later on confirmed with histopathology Fluoro ethyl tyrosine. [ABSTRACT FROM AUTHOR]

Tamoxifen is a selective estrogen receptor modulator and forms the mainstay of endocrine therapy in premenopausal women with breast cancer in both adjuvant and metastatic setting. Common adverse effects are menopausal symptoms with venous thrombosis and endometrial carcinoma being rarer but more sinister complications. Vasculitis is a rarely reported reaction to tamoxifen. We report a case of a 38-year-old woman with locally advanced breast cancer, who received neoadjuvant chemotherapy followed by modified radical mastectomy and adjuvant paclitaxel. She was on maintenance tamoxifen and leuprolide for 3 months, when she presented with pruritic bilateral maculopapular rash over all her limbs, legs more than hands. A skin biopsy from the left lower limb confirmed the diagnosis of vasculitis. Tamoxifen was stopped, and patient was switched to letrozole and leuprolide. She was given antihistamines, antibiotics, fusidic acid, vitamin C, and topical steroids. The lesions resolved completely in 1 month after stoppage of tamoxifen. We report this rare side effect of tamoxifen so that oncologists can effectively diagnose and treat this distressing but reversible condition. [ABSTRACT FROM AUTHOR]

Purpose: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. Methods: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. Results: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. Conclusion: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised. [ABSTRACT FROM AUTHOR]

Byline: Mukesh. Barange, Sridhar. Epari, Mamta. Gurav, Omshree. Shetty, Ayushi. Sahay, Prakash. Shetty, Jayantsastri. Goda, Aliasagar. Moyiadi, Tejpal. Gupta, Rakesh. Jalali Background: Telomerase reverse transcriptase promoter (pTERT) mutation is a [...]

Byline: Krunal. Khobragade, Shraddha. Patkar, Mahesh. Goel, Ayushi. Sahay Extraintestinal gastrointestinal stromal tumors (EGISTs) are mesenchymal tumor with no connection to tubular gastrointestinal system. They commonly arise from omentum and [...]