TTF-1 immunohistochemistry in primary CNS tumors: A systematic review.

Thyroid transcription factor-1 (TTF-1) is a nuclear protein primarily recognized for its role in the development and differentiation of thyroid, lung, and certain diencephalic tissues. Although well-established as an immunohistochemical marker in thyroid and lung cancers, recent studies have explored its expression and diagnostic value in primary central nervous system (CNS) tumors. This systematic review aims to consolidate current knowledge on TTF-1 immunohistochemistry in primary CNS tumors, assessing its prevalence, diagnostic utility, and clinical implications. The review encompasses various CNS tumor types, including subependymal giant cell astrocytoma, chordoid glioma, pituicytoma, ependymomas, astrocytomas, glioblastomas, medulloblastomas, and choroid plexus tumors, highlighting the potential role of TTF-1 in differentiating these neoplasms from other CNS and metastatic tumors. By synthesizing findings from multiple studies, this review underscores the diagnostic value of TTF-1 in the neuropathological evaluation of CNS tumors and suggests directions for future research to refine its clinical application.

Malignancy arising in adamantinomatous craniopharyngioma: Report of a rare case with unusual morphologic features.

Adamantinomatous craniopharyngioma is a grade 1 tumor that arises in a sellar/suprasellar location. Despite being a grade 1 tumor, there is high recurrence and endocrinal insufficiency. Malignancy arising in craniopharyngioma is extremely rare, has a dismal prognosis, and is currently not included as a separate entity in the World Health Organization Classification of Central Nervous System 5th edition. Here we describe a case of adamantinomatous craniopharyngioma and its malignant counterpart. The malignant part had unique histomorphology and basaloid cells with pseudoglandular architecture and a myxoid background. It bore a striking resemblance to adenoid cystic carcinoma. Both the benign and malignant counterparts were beta-catenin and SOX-2 positive, providing proof of the malignant part arising from the benign part. Tumors like squamous cell carcinoma and odontogenic ghost cell carcinoma have been described in cranipharyngioma. This case study is the first to describe this unique morphology of adenoid cystic carcinoma-like features. The possibility of adenoid cystic carcinoma was excluded by immunohistochemistry.

Spinal astroblastoma, MN1 altered in 3-year-old child: An uncommon tumor at an unusual site.

Astroblastoma is an uncommon circumscribed glial tumor mostly involving the cerebral hemisphere. The characteristic molecular alteration is meningioma (disrupted in balanced translocation) 1 (MN1) rearrangement. No definite World Health Organization grade has been assigned as both low- and high-grade tumors are known to occur. Tumors in the spine are extremely rare; to date only three cases have been reported in the literature. A vigilant microscopy and ancillary testing aid in diagnosis when the tumors present in unusual locations, as in our case. The prompt differentiation of this tumor from its mimickers is a mandate as modalities of management are different and not clearly established.

Primary intracranial dedifferentiated liposarcoma: An extremely rare site with unusual histopathological findings.

Primary intracranial sarcomas constitute a rare group of tumors, with the most common types described in the literature being chondrosarcoma and fibrosarcoma. Dedifferentiated liposarcoma (DDLS) is a high-grade sarcoma that sometimes metastasizes to the brain. However, a primary intracranial DDLS is exceedingly rare. A 45-year-old patient from the Middle East came to India for treatment. His magnetic resonance imaging (MRI) scans revealed a space-occupying lesion at the level of the lateral ventricle T2/fluid attenuated inversion recovery hyperintensity with peripheral edema. A T1 perfusion map showed high relative cerebral blood volume values in the peripheral part, suggesting a high-grade neoplasm. Gross total resection was performed, and histopathology showed a high-grade tumor composed of sheets of pleomorphic lipoblasts and epithelioid tumor cells arranged in nests and cords. Immunohistochemistry showed diffuse immunopositivity for MDM2, CDK4, and p16, while GFAP and OLIG2 were negative. Fluorescence in situ hybridization showed MDM2 amplification. Final diagnosis of DDLS was rendered. The patient had no systemic lesions elsewhere on positron emission tomography computed tomography scan.

Evaluation of KIAA1549::BRAF fusions and clinicopathological insights of pilocytic astrocytomas.

BACKGROUND: Pilocytic astrocytoma (PAs) represents a significant portion of childhood primary brain tumors, with distinct histological and radiological features. The prevalence of KIAA1549::BRAF fusion in PAs has been well-established, this study aims to assess the prevalence of KIAA1549::BRAF fusions and explore their associations with tumor characteristics, radiological findings, and patient outcomes in PAs. METHODS: Histologically confirmed cases of PAs from a 5-year period were included in the study. Demographic, histopathological, and radiological data were collected, and immunohistochemistry was performed to characterize tumor markers. FISH and qRT-PCR assays were employed to detect KIAA1549::BRAF fusions. Statistical analyses were conducted to examine associations between fusion status and various other parameters. RESULTS: Histological analysis revealed no significant differences in tumor features based on fusion status. However, younger age groups showed higher fusion prevalence. Radiologically, fusion-positive cases were distributed across different tumor subtypes SE, CWE and NCWE. Survival analysis did not demonstrate a significant impact of fusion status on overall survival, however most cases with recurrence and death harboured KIAA1549::BRAF fusion. Of 200 PAs, KIAA1549::BRAF fusions were detected in 64 % and 74 % of cases via qRT-PCR and FISH, respectively. Concordance between the two platforms was substantial (86 %). CONCLUSION: KIAA1549::BRAF fusions are prevalent in PAs and can be reliably detected using both FISH and qRT-PCR assays. Cost considerations suggest qRT-PCR as a more economical option for fusion detection in routine clinical practice.

Isolation and Characterization of a Plant Growth-Promoting Bacterium Acinetobacter sp. SuKIC24 From in vitro-Grown Basilicum polystachyon (L.) Moench.

In the present study, a plant growth-promoting bacterium isolated from contaminated in vitro-grown Basilicum polystachyon (L.) Moench, an herbaceous plant, was studied and identified as Acinetobacter strain SuKIC24 based on the 16S rRNA gene sequence analysis. The results revealed that the identified strain exhibited a strong ability to solubilize the phosphate with phosphate solubilization index of 4.0 and produced 387 µg/ml of soluble phosphate in Pikovskaya media after 7 days of incubation, whereas zinc solubilization efficacy was determined to be 175%. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed that the bacterium strain produced 77.36 µg/ml of indole-3-acetic acid. Plant inoculated with the bacterium strain was found to demonstrate a significant increase in height of B. polystachyon as compared to the control plant. The present findings indicated that the identified bacterium strain might act as plant growth-promoting bacterium (PGPB).

Dynamics of confined water and its interplay with alkali cations in sodium aluminosilicate hydrate gel: insights from reactive force field molecular dynamics.

This paper presents the dynamics of confined water and its interplay with alkali cations in disordered sodium aluminosilicate hydrate (N-A-S-H) gel using reactive force field molecular dynamics. N-A-S-H gel is the primary binding phase in geopolymers formed via alkaline activation of fly ash. Despite attractive mechanical properties, geopolymers suffer from durability issues, particularly the alkali leaching problem which has motivated this study. Here, the dynamics of confined water and the mobility of alkali cations in N-A-S-H is evaluated by obtaining the evolution of mean squared displacements and Van Hove correlation function. To evaluate the influence of the composition of N-A-S-H on the water dynamics and diffusion of alkali cations, atomistic structures of N-A-S-H with Si/Al ratio ranging from 1 to 3 are constructed. It is observed that the diffusion of confined water and sodium is significantly influenced by the Si/Al ratio. The confined water molecules in N-A-S-H exhibit a multistage dynamic behavior where they can be classified as mobile and immobile water molecules. While the mobility of water molecules gets progressively restricted with an increase in Si/Al ratio, the diffusion coefficient of sodium also decreases as the Si/Al ratio increases. The diffusion coefficient of water molecules in the N-A-S-H structure exhibits a lower value than those of the calcium-silicate-hydrate (C-S-H) structure. This is mainly due to the random disordered structure of N-A-S-H as compared to the layered C-S-H structure. To further evaluate the influence of water content in N-A-S-H, atomistic structures of N-A-S-H with water contents ranging from 5-20% are constructed. Qn distribution of the structures indicates significant depolymerization of N-A-S-H structure with increasing water content. Increased conversion of Si-O-Na network to Si-O-H and Na-OH components with an increase in water content helps explain the alkali-leaching issue in fly ash-based geopolymers observed macroscopically. Overall, the results in this study can be used as a starting point towards multiscale simulation-based design and development of durable geopolymers.

Strongly Correlated Photon Transport in Waveguide Quantum Electrodynamics with Weakly Coupled Emitters.

We show that strongly correlated photon transport can be observed in waveguides containing optically dense ensembles of emitters. Remarkably, this occurs even for weak coupling efficiencies. Specifically, we compute the photon transport properties through a chirally coupled system of N two-level systems driven by a weak coherent field, where each emitter can also scatter photons out of the waveguide. The photon correlations arise due to an interplay of nonlinearity and coupling to a loss reservoir, which creates a strong effective interaction between transmitted photons. The highly correlated photon states are less susceptible to losses than uncorrelated photons and have a power-law decay with N. This is described using a simple universal asymptotic solution governed by a single scaling parameter which describes photon bunching and power transmission. We show numerically that, for randomly placed emitters, these results hold even in systems without chirality. The effect can be observed in existing tapered fiber setups with trapped atoms.

Interfacing Superconducting Qubits and Single Optical Photons Using Molecules in Waveguides.

We propose an efficient light-matter interface at optical frequencies between a single photon and a superconducting qubit. The desired interface is based on a hybrid architecture composed of an organic molecule embedded inside an optical waveguide and electrically coupled to a superconducting qubit placed near the outside surface of the waveguide. We show that high fidelity, photon-mediated, entanglement between distant superconducting qubits can be achieved with incident pulses at the single photon level. Such a low light level is highly desirable for achieving a coherent optical interface with superconducting qubit, since it minimizes decoherence arising from the absorption of light.

Microwave-controlled efficient Raman sub-harmonic generation.

We propose a novel scheme for efficient Raman sub-harmonic generation in a system of inhomogeneously broadened atomic vapor with atoms in a closed three-level Λ-configuration. The key feature underlying Raman sub-harmonics generation is microwave-induced hyperfine coherence between the two lower level metastable states. We show explicitly how the amplitude and phase of the microwave field generate controllable spectral amplitudes of Raman sub-harmonics. Our scheme is viable in currently available atomic vapor cells thereby opening the way for efficient sub-harmonic generation in standard experimental setups.

Epithelioid Hemangioma of the Nasal Cavity: a Diagnostic Challenge.

Epithelioid hemangioma also known as angio-lymphoid hyperplasia with eosinophilia is a rare benign vascular neoplasm of unknown etiology. It very rarely involves the nasal cavity. It always poses a diagnostic challenge for clinicians and is usually misdiagnosed as Kimura's, IgG4-related disease, or malignant vascular tumors. The present case report describes an extremely rare presentation of epithelioid hemangioma inside the left nasal cavity causing complete obstruction and nasal septal deviation towards the right side in a young male. Hematoxylin and eosin-stained sections depicted a lobular proliferation of small capillary-sized vessels lined by plump epithelioid endothelial cells surrounding central vessels and scattered around them. These cells had abundant eosinophilic to amphophilic cytoplasm and enlarged nuclei with fine chromatin and central nucleoli. On immunohistochemistry, CD34 and CD31 highlighted the vascular proliferation and epithelioid endothelial cells. Erythroblast transformation-specific (ETS)-related gene (ERG) showed strong nuclear positivity in neoplastic plump epithelioid endothelial cells. EH is a benign vascular proliferation, but a high chance of recurrence is seen if complete resection is not done. As a result, the treatment of choice is complete surgical excision with clear margins. The case highlights a non-conventional presentation of epithelioid hemangioma and the importance of histomorphological features in diagnosing this entity.

Rare presentation of solitary fibrous tumour in the floor of the mouth.

A male in his 20s, a tobacco chewer, presented to the outpatient department with a history of painless, slowly progressive swelling in the floor of the mouth. After a thorough history and clinical examination, MRI was done and the tumour was completely excised. Histopathological examination revealed the mass to be a solitary fibrous tumour, confirmed with immunohistochemical markers. On subsequent follow-ups, the patient was found to be asymptomatic with no clinical signs of recurrence.

Sarcoma diagnosis by DNA methylation classifier: A systematic review, current status and future prospects.

Sarcomas, a diverse group of malignant tumors originating from connective tissues, present substantial diagnostic challenges due to their histological heterogeneity. Traditional diagnostic methods include histomorphology along with immunohistochemistry is necessary for primary evaluation. Fluorescence in situ hybridization (FISH) is a supplementary tool that helps with additional findings. However it is very difficult sometimes to accurately classify sarcoma subtypes despite all these tools. Recent advancements in DNA methylation profiling have emerged as a promising approach to enhance the precision of sarcoma diagnosis. This paper delves into the role of DNA methylation classifiers in diagnosing sarcomas, emphasizing their potential to improve diagnostic accuracy, inform treatment decisions, and ultimately enhance patient outcomes.

Unraveling the urban climate crisis: Exploring the nexus of urbanization, climate change, and their impacts on the environment and human well-being - A global perspective.

The accelerating pace of urbanization, coupled with the intensifying impacts of climate change, poses unprecedented challenges to both the environment and human well-being. In this review, we delved into the intricate interaction between climate change and urbanization and the various effects they have on the environment and human well-being, shedding light on the emergent urban climate crisis. Urban areas serve as epicenters for diverse socio-economic activities, yet they also contribute significantly to global greenhouse gas emissions and environmental degradation. Through an interdisciplinary lens, we explored the root causes of the urban climate crisis, examining how rapid urbanization exacerbates climate change and vice versa. By synthesizing current research and case studies, we elucidate the various environmental and social ramifications of this nexus, ranging from urban heat island effects to heightened vulnerability to extreme weather events. Furthermore, we delve into the unequal distribution of climate risks within urban populations, highlighting the disproportionate burden borne by marginalized communities. Finally, the chapter presents strategies and interventions for mitigating and adapting to the urban climate crisis, emphasizing the imperative of holistic and equitable approaches that prioritize both environmental sustainability and human well-being. Overall, this review calls for concerted efforts to unravel the complexities of the urban climate crisis and forge a path toward resilient, sustainable, and equitable urban futures.

Predicted and Experimental Bending Behaviour of Glulam Bonded by RPF Adhesive.

In this study, alder, spruce, and beech woods were used for homogeneous symmetric, inhomogeneous symmetric (combined) and inhomogeneous non-symmetric glued laminated timber (glulam) beams glued with resorcinol phenol formaldehyde (RPF) adhesive. The aim of this paper is to determine and compare the modulus of elasticity of glulam beams using three methods, i.e., analytical calculation, numerical model (FEM) and experimental testing. As an additional characteristic, the bending strength (MOR) of the beams was determined during experimental testing. Analytical calculation was used to calculate the modulus of elasticity (MOE) of glued laminated timber based on the knowledge of the modulus of elasticity of solid wood and to estimate the location of the neutral axis during bending. According to calculations, for symmetrical combinations, the deviation from the real neutral axis does not exceed 5%. In the case of the modulus of elasticity, the deviation is an average of 4.1% from that of the actual measured beams. The numerical model includes finite element modelling, where the deflection of the modelled beams can be calculated with a deviation of up to 10%. The last method was experimental testing of glued beams using four-point bending, in which, among homogeneous beams, beech glulam beams achieved the highest MOE and MOR, while alder glulam beams achieved the lowest. The combination of wood species resulted in an increase in both MOE and MOR compared to homogeneous spruce and alder beams.

Astroblastoma: A molecularly defined entity, its clinico-radiological & pathological analysis of eight cases and review of literature.

Astroblastoma, a unique entity of glial tumor, predominantly occur in young women with distinctive MN1 rearrangement, Given its limited documentation in existing literature, we report eight cases of astroblastoma, detailing their clinical, radiological, and histopathological characteristics along with molecular analysis. We conducted a retrospective analysis of our neuropathology archive database spanning the past 8 years. We included all cases that underwent Magnetic Resonance Imaging (MRI), surgical resection, histopathological examination, molecular testing, and follow-up. Histopathological examination involving immunohistochemistry and Fluorescence In Situ Hybridization (FISH) was carried out for all cases. All tumors were found to be located in the supratentorial region (cerebral hemisphere). The median age of the group was 35.1 years, with a female-to-male ratio of 1.6:1. The most common clinical presentation was headache. Morphologically, all tumors exhibited astroblastic features with pseudorosettes and perivascular hyalinization. Immunohistochemistry consistently revealed positivity for EMA and variable immunoreactivity for GFAP, OLIG2, and D2-40. Fluorescence In Situ Hybridization (FISH) analysis conducted for all cases showed MN1 rearrangement in 7 cases. The mean follow-up period was 45 months (ranging from 12 to 105 months). Radiotherapy was administered for high-grade and recurrent astroblastomas. All patients are currently alive and in good health. Astroblastomas are uncommon central nervous system (CNS) tumors with characteristics morphology and molecular signatures. They typically carry a favorable prognosis. High level suspicion is required for their diagnosis and molecular analysis is must to distinguish them from other morphological mimics.

Disseminated phaeohyphomycosis due to Cladophialophora bantiana in an immunocompetent child.

A 3-year-old boy presented with acute headache, vomiting and right focal clonic seizures without history of fever, joint pain or altered sensorium. Neuroimaging showed multifocal contrast enhancing lesions with significant perilesional edema. CECT chest and abdomen showed multiple variable sized nodules in the lungs and hypodense lesion in liver with mesenteric lymphadenopathy. There was persistent eosinophilia with maximum upto 35 %. Liver biopsy and brain biopsy revealed Cladophialophora bantiana. He was treated with IV liposomal amphotericin and voriconazole for 6 weeks with repeat neuroimaging showing more than 50 % resolution of the intracranial lesions. He was transitioned to oral combination of flucytosine and voriconazole. At 14 months follow-up, he remained symptom free with complete radiological resolution of the lesions and no eosinophilia. High suspicion, an aggressive approach in obtaining microbiological diagnosis and timely combination antifungal therapy may give satisfactory outcome without surgery.

Pediatric high grade gliomas: A comprehensive histopathological, immunohistochemical and molecular integrated approach in routine practice.

Pediatric high grade gliomas have undergone remarkable changes in recent time with discovery of new molecular pathways. They have been added separately in current WHO 2021 blue book. All the entities show characteristic morphology and immunohistochemistry. Methylation data correctly identifies these entities into particular group of clusters. The pediatric group high grade glioma comprises- Diffuse midline glioma, H3K27-altered; Diffuse hemispheric glioma, H3G34-mutant; Diffuse pediatric-type high-grade glioma, H3-wild type & IDH-wild type; Infant hemispheric glioma and Epithelioid glioblastoma/Grade 3 pleomorphic xanthoastrocytoma and very rare IDH-mutant astrocytoma. However it is not always feasible to perform these molecular tests where cost-effective diagnosis is a major concern. Here we discuss the major entities with their characteristic histopathology, immunohistochemistry and molecular findings that may help to reach to suggest the diagnosis and help the clinician for appropriate treatment strategies. We have also made a simple algorithmic flow chart integrated with histopathology, immunohistochemistry and molecular characteristics for better understanding.

Papillary Tumors of Pineal Region: A Single-Center Experience in Management of 11 Cases.

BACKGROUND: Papillary tumors of pineal region (PTPR) comprise a very rare subset of pineal region tumors that have been recently described. Literature on the management and outcome of PTPR is scarce owing to the rarity of these tumors. To address this lacuna, we analyzed our experience in management of PTPR. METHODS: We retrospectively analyzed the outcome of 11 patients with histopathologically proven PTPR who underwent surgical excision at our center. RESULTS: Mean patient age was 33.3 years (range, 12-45 years), and male-to-female ratio was 1.75:1. Headache was the most common presentation followed by visual disturbances, altered sensorium, Perinaud syndrome, and seizures. Cerebrospinal fluid diversion was required in 6 patients. Krause approach was the most common approach used for tumor excision (9/11 cases). There was no perioperative mortality. Two patients were lost to follow-up. In the remaining 9 patients, the average follow-up period was 45 months (range, 12-79 months). On first postoperative magnetic resonance imaging, 8 patients showed no evidence of residual tumor (gross total resection), while 1 patient had small residual tumor (near-total resection) that remained stable during follow-up. Four patients underwent adjuvant chemoradiotherapy. None of the patients developed recurrence during follow-up. CONCLUSIONS: PTPR are a rare subgroup of pineal region tumors with distinct cells of origin but presentation similar to other pineal region tumors. Surgical resection constitutes the mainstay of management, and the extent of resection appears to be the most important determinant of prognosis. The role of adjuvant therapy still needs to be determined.

Clinical utility of plasma cell-free DNA (cfDNA) in diffuse gliomas for the detection of IDH1 R132H mutation.

Liquid biopsy for CNS tumors is in its nascent phase, hindered by the low levels of circulating tumor DNA (ctDNA). Overcoming this challenge requires highly sensitive molecular techniques. DD-PCR emerges as a standout technique due to its ability to identify rare mutations, copy number variations, and circulating nucleic acids, making it one of the best methods for identifying somatic mutations in cell-free DNA (cfDNA). Despite promising results from various studies demonstrating the feasibility of obtaining informative ctDNA profiles from liquid biopsy samples, challenges persist, including the need to standardize sample collection, storage, and processing methods, define clear assay positivity thresholds, and address the overall low assay sensitivity. Our two-phase study began by assessing DD-PCR efficacy in FFPE tissues, revealing robust concordance with immunohistochemistry. In Phase 1 (85 cases), DD-PCR on FFPE tissues demonstrated 100 % sensitivity and specificity for IDH1 R132H mutations. In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.