Diagnostic challenges and proposed classification of myeloid neoplasms with overlapping features of thrombocytosis, ring sideroblasts and concurrent del(5q) and SF3B1 mutations.

Not available.

Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies.

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patient management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs. In contrast to solid tumors, conventional sources of normal control (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we find nail cfDNA is a robust source of germline control for paired genomic studies. In a subset of patients, nail DNA may have tumor DNA contamination, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1482) compared to lymphoid diseases (5.4%; 61/1128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. For nails collected after allogeneic stem-cell transplantation, donor DNA was identified in 22% (11/50). In this cohort, an association with recent history of graft-vs-host disease was identified. These findings should be considered as a potential limitation for the use of nail as normal control but could also provide important diagnostic information regarding the disease process.

Unravelling the Complex Relationship Between Frontal Sinus Pneumatization and Paranasal Sinus Anatomical Variants: Insights from CT Imaging.

The aim of this study was to analyse the relationship between frontal sinus pneumatization and its effect on various variations of paranasal sinuses on paranasal sinus CT scan. A total number of 100 patients (51 males, 49 females) were included in this study. Patients were divided into three groups on the basis of their frontal sinus pneumatization extent on paranasal sinus CT as Type 1 pneumatization (aplasia and hypoplasia), Type 2 pneumatization (medium) and Type 3 pneumatization (hyperplasia). The prevalence of various variations like pneumatization of upper and middle turbinate, presence of agger nasi, Haller and Onodi cell, maxillary sinus hypoplasia, extent of sphenoid sinus pneumatization, pneumatization of anterior clinoid process, pterygoid process and greater wing of sphenoid sinus, dehiscence and protrusion of internal carotid artery and optic nerve types were ascertained and compared within each group. The prevalence of Onodi cell, anterior clinoid process and greater wing of sphenoid pneumatization and optic nerves type 3 and 4 were higher in Type 3 frontal sinus pneumatization group as compared with other groups. Excessive pneumatization of frontal sinus has various effects on paranasal sinus variations. Surgeons dealing with endoscopic sinus surgery, maxillofacial and skull base surgery must be vigilant of association between these variations preoperatively for avoiding complications.

Endoscopic Assessment of Cholesteatoma Following Microscope Assisted Tympano: Mastoidectomy: Study design: a cross section descriptive study.

Complete surgical removal of cholesteatoma has been traditionally performed by microscopic approaches. In recent years, use of endoscopes in middle ear surgery is gaining increasing importance. The wide field view offered by the endoscopes in comparison to the narrow field of view of the binocular microscope enables a surgeon to see and dissect around corners, thereby exposing 'hidden recesses' of the middle ear which can be useful during cholesteatoma surgery. To identify remnant cholesteatoma in difficult access sites of the middle ear cleft using endoscopes following a microscope assisted mastoidectomy. A cross sectional study was conducted in patients who were clinically diagnosed with cholesteatoma. Patients were subjected to High Resolution Computed Tomography of the temporal bone and pre-operative audiological tests. Mastoid exploration was performed microscopically followed by endoscopic evaluation and clearance of disease in the same setting. Patients were then followed up post-operative and endoscopically evaluated to look for any remnant disease. A total of 45 patients were included, all of which underwent microscopic assisted mastoidectomy. Remnant cholesteatoma was discovered in 15 out of 45 cases (33%) distributed in the hidden areas; in the region of sinus tympani 9(60%), anterior epitympanum 4(27%), hypotympanum 1(7%) and tip Cells 1(7%). It can be concluded that endoscopes have a definite role in evaluation and complete surgical clearance of cholesteatoma particularly from the hidden areas of middle ear cleft which would have otherwise been missed by the straight line view of a microscope thereby grossly reducing the rate of remnant disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04263-6.

Molecular Characterization and Seasonal Variation in Expression of HSP70.1 Gene in Gangatiri Cattle and Its Comparison with Buffalo.

Under tropical climate heat stress is a major challenge for livestock production. HSP70.1 is a ubiquitously expressed protein maintaining cellular machinery through proper folding of denatured proteins and prevents cellular apoptosis and protect cell from heat stress. Therefore, present investigation was undertaken to explore genetic variability in HSP70.1 gene in Gangatiri cattle, its comparison with buffalo sequences and differential expression in different season. The allelic variant was identified by sequencing amplified PCR product of HSP70.1 gene by primer walking. Season-wise total RNA samples was prepared for differential expression study. Brilliant SYBR Green QPCR technique was used to study the expression kinetics of this gene. DNA sequencing by primer walking identified four allelic variants in Gangatiri cattle. Sequence alignment study revealed four, six and one substitutions in the 5' untranslated region (5'UTR), coding and 3' untranslated region ((3'UTR) of HSP70.1 gene, respectively. Comparative analysis of HSP70.1 gene revealed that Cattle has shorter 5'UTR and 3' UTR than the buffalo. In Gangatiri cattle, summer season has significantly higher (P ≤ 0.05) expression of HSP70.1 than the spring and winter. The relative expression of HSP70.1 was increased by more than six folds in summer and nearly 1.5 folds higher in winter in comparison to the spring season. Therefore, HSP70.1 may be considered to have a critical role in the development of thermal tolerance in Gangatiri cattle.

Approach towards surveillance-based diagnosis of acute respiratory illness in India: Expert recommendations.

BACKGROUND: Emerging infectious diseases, often zoonotic, demand a collaborative "One-Health" surveillance approach due to human activities. The need for standardized diagnostic and surveillance algorithms is emphasized to address the difficulty in clinical differentiation and curb antimicrobial resistance. OBJECTIVE: The present recommendations are comprehensive diagnostic and surveillance algorithm for ARIs, developed by the Indian Council of Medical Research (ICMR), which aims to enhance early detection and treatment with improved surveillance. This algorithm shall be serving as a blueprint for respiratory infections landscape in the country and early detection of surge of respiratory infections in the country. CONTENT: The ICMR has risen up to the threat of emerging and re-emerging infections. Here, we seek to recommend a structured approach for diagnosing respiratory illnesses. The recommendations emphasize the significance of prioritizing respiratory pathogens based on factors such as the frequency of occurrence (seasonal or geographical), disease severity, ease of diagnosis and public health importance. The proposed surveillance-based diagnostic algorithm for ARI relies on a combination of gold-standard conventional methods, innovative serological and molecular techniques, as well as radiological approaches, which collectively contribute to the detection of various causative agents. The diagnostic part of the integrated algorithm can be dealt at the local microbiology laboratory of the healthcare facility with the few positive and negative specimens shipped to linked viral disease research laboratories (VRDLs) and other ICMR designated laboratories for genome characterisation, cluster identification and identification of novel agents.

Novel identification of t(14;18)(q32;q21)/IGH::MALT1 in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a clonal B-cell malignancy and remains a chronic disease despite improvements in clinical outcomes since the use of targeted therapies. Both clinical and biological parameters are important for determining prognosis. Unlike other mature B-cell lymphomas, translocations involving the immunoglobulin heavy chain (IGH) locus are uncommon in CLL. There have been few case reports of CLL harbouring t(14;18)/IGH::BCL2 and t(14;19)/IGH::BCL3. Here we describe the first two cases of patients with CLL with documented t(14;18)(q32;q21)/IGH::MALT1. Both cases in this report were associated with lower-risk biological parameters. Thus, FISH testing for MALT1 in cases with unknown IGH translocation partners in the setting of CLL should be implemented in clinical practice to better define such cases.

The clinical, molecular, and prognostic features of the 2022 WHO and ICC classification systems for myelodysplastic neoplasms.

Myelodysplastic neoplasms (MDS) are clonal disorders of bone marrow failure exhibiting a variable risk of progression to acute myeloid leukemia. MDS exhibit certain prognostic genetic or cytogenetic abnormalities, an observation that has led to both the pathologic reclassification of MDS in the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) systems, as well as to an updated prognostic schema, the Molecular International Prognostic Scoring System (IPSS-M). This single-institution study characterized the molecular patterns and clinical outcomes associated with the 2022 WHO and ICC classification schemas to assess their clinical utility. Strikingly, with the exception of one individual, all 210 patients in our cohort were classified into analogous categories by the two pathologic/diagnostic schemas. Most patients (70%) were classified morphologically while the remaining 30% had genetically classified disease by both criteria. Prognostic risk, as assessed by the IPSS-M score was highest in patients with MDS with biallelic/multi-hit TP53 mutations and lowest in pts with MDS-SF3B1. Median leukemia-free survival (LFS) was shortest for those with MDS with biallelic/multi-hit TP53 (0.7 years) and longest for those with MDS with low blasts (LFS not reached). These data demonstrate the clear ability of the 2022 WHO and ICC classifications to organize MDS patients into distinct prognostic risk groups and further show that both classification systems share more similarities than differences. Incorporation of the IPSS-M and IPSS-R features provide additive prognostic and survival components to both the WHO and ICC classifications, which together enhance their utility for evaluating and treating MDS patients.

Trigeminal Lipomatosis: A Rare Cause of Intractable Neuralgia.

Lipomatosis of nerve, earlier known as fibrolipomatous hamartoma is a rare condition which predominantly affects peripheral nerves, cranial nerve involvement being extremely uncommon. Preoperative consideration of this entity is of paramount importance as its inadvertent complete surgical resection may inevitably result in significant neurological deficit. We report a case of trigeminal lipomatosis in a young patient with trigeminal neuralgia.

Sinonasal Inflammation or Neoplasm: Raise the Red Flagsǃ-A Pictorial Review.

Inflammatory pathology remains the most common indication for sinonasal imaging. However, sinonasal region is also the epicenter of a variety of neoplasms. These are often missed both clinically and radiologically owing to nonspecific signs and symptoms and subtle imaging pointers. An early diagnosis of sinonasal neoplasms is critical for timely management and hence better prognosis and survival rate. This pictorial review aims to acquaint the reader with the "red flag" signs on computed tomography that should raise suspicion for an underlying neoplastic pathology and also highlights the imaging features of common sinonasal neoplasms.

Isolation and characterization of emerging Mpox virus from India.

Mpox (previously known as Monkeypox) has recently re-emerged, primarily through human-to-human transmission in non-endemic countries including India. Virus isolation is still considered as the gold standard for diagnosis of viral infections. Here, the qPCR positive skin lesion sample from a patient was inoculated in Vero E6 cell monolayer. Characteristic cytopathic effect exhibiting typical cell rounding and detachment was observed at passage-02. The virus isolation was confirmed by qPCR. The replication kinetics of the isolate was determined that revealed maximum viral titre of log 6.3 PFU/mL at 72 h postinfection. Further, whole genome analysis through next generation sequencing revealed that the Mpox virus (MPXV) isolate is characterized by several unique SNPs and INDELs. Phylogenetically, it belonged to A.2 lineage of clade IIb, forming a close group with all other Indian MPXV along with few from USA, UK, Portugal, Thailand and Nigeria. This study reports the first successful isolation and phenotypic and genotypic characterization of MPXV from India.

Correlation of ultrasound-based TIRADS and the Bethesda system for reporting of thyroid cytopathology: A study in a tertiary care centre.

BACKGROUND: The age-standardised incidence rate of thyroid cancer in India is 1 in 416 in the general population. This increased incidence has mainly been attributed to improved detection methods for small thyroid lesions. Two such methods are the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) and the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). AIMS AND OBJECTIVES: To study the correlation between ACR TIRADS and TBSRTC, and between each system and the final histopathological report. MATERIALS AND METHODS: Thyroid cytopathology cases were retrieved for the period January 2019 to July 2022. For each case, the TIRADS score and Bethesda category were noted. Histopathology specimens were also traced. RESULTS: The study comprised 1100 cases, with 955 female and 145 male patients (M:F = 1:6.59), and ages ranging between 7 and 85 years. The TIRADS scoring was available for 1036 cases. Histopathology was available for 231 cases. There was a significant correlation between TIRADS and TBSRTC, with a p-value of 0.000 and a substantial Kappa agreement of 0.688. Both TIRADS and TBSRTC also had significant correlations with the histopathology data, with a p-value of 0.000 for each. The sensitivity values for TBSRTC and TIRADS were 69.4% and 65.8%; specificity, 99.3% and 96.5%; positive predictive value (PPV), 98.3% and 91.8%; and negative predictive value (NPV) 84.7% and 84.4%, respectively. The risk of malignancy (ROM) was also calculated and was found to be high, especially for TBSRTC II, III, IV and V (11.3%, 20%, 61.5%, 97.4% respectively) and TIRADS 2 and 3 (10.3% and 29.6% respectively). CONCLUSION: The TIRADS and TBSRTC systems of categorisation of thyroid lesions are concordant and could help improve the overall survival rate of patients with thyroid malignancies.

TFG::ALK fusion in ALK positive large B-cell lymphoma: a case report and review of literature.

Anaplastic lymphoma kinase (ALK) positive large B-cell lymphoma (ALK+ LBCL) is an aggressive and rare subtype of B-cell lymphoma. Patients typically present with advanced clinical stage disease and do not respond to conventional chemotherapy; the median overall survival is 1.8 years. The genetic landscape of this entity remains poorly understood. Here we report a unique case of ALK+ LBCL harbouring a rare TFG::ALK fusion. Targeted next-generation sequencing showed no significant single nucleotide variants, insertions/deletions, or other structural variants beyond the TFG::ALK fusion; deep deletions of FOXO1, PRKCA, and the MYB locus were also detected. Our case report draws attention to this rare disease, highlights a need for larger genetic profiling studies, and focuses on the pathogenesis and potential therapeutic targets of this aggressive disease. To our knowledge, this is the first report of a TFG::ALK fusion in ALK+ LBCL.

Differentiation of various salivary gland tumours using diffusion-weighted MRI and dynamic contrast-enhanced MRI.

Purpose: To determine the role of functional magnetic resonance imaging techniques (diffusion-weighted magnetic resonance imaging [DW-MRI] and dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI]) in the differentiation of various salivary gland tumours. Material and methods: In this prospective study, we evaluated 32 patients with salivary gland tumours using functional MRI. Diffusion parameters (mean apparent diffusion coefficient [ADC], normalized ADC and homogeneity index [HI]),semiquantitative DCE parameters (time signal intensity curves [TICs]) and quantitative DCE parameters (Kep, Ktrans and Ve) were analysed. Diagnostic efficiencies of all these parameters were determined to differentiate benign and malignant tumours as well as to characterize 3 major subgroups of salivary gland tumours, namely pleomorphic adenoma, Warthin tumour, and malignant tumours. Results: Mean ADC, normalized ADC and HI were insignificant in differentiating benign and malignant tumours but were significant in differentiating pleomorphic adenomas, Warthin tumours, and malignant tumours. Mean ADC was the best parameter in predicting both pleomorphic adenomas and Warthin tumours (AUC: 0.95 and 0.89, respectively). Amongst DCE parameters, only TIC pattern could differentiate between benign and malignant tumours, with an accuracy of 93.75% (AUC: 0.94). The quantitative perfusion parameters aided greatly in characterizing pleomorphic adenomas, Warthin tumours and malignant tumours. For predicting pleomorphic adenomas, the accuracy of Kep and Ktrans was 96.77% (AUC: 0.98) and 93.55% (AUC: 0.95), respectively and for predicting Warthin tumours, the accuracy of both Kep and Ktrans was 96.77% (AUC: 0.97). Conclusions: DCE parameters (particularly TIC, Kep and Ktrans) had higher accuracy in characterizing various tumour subgroups (pleomorphic adenomas, Warthin tumours, and malignant tumours) than DWI parameters. Hence, dynamic contrast-enhanced imaging adds immense value with only a minimum time penalty to the examination.

Variation in the Expression of Interstitial Cell of Cajal-like Cell (CD117) Across Congenital Pelvic-ureteric Junction Obstruction and its Renal Sonological and Functional Correlation: A Prospective Observational Study.

Aims and Objectives: This study aims to study the variation in the expression of CD117-positive interstitial cells of Cajal-like cells (ICC-LC) across the upper urinary tract region in children presenting with pelvic-ureteric junction obstruction (PUJO) and its association with renal functional and sonological parameters of patients. Materials and Methods: A prospective observational study was done on 20 children with congenital PUJO who underwent dismembered pyeloplasty. All children underwent renal sonography (anteroposterior pelvic diameter [APPD], pelvicalyceal ratio [P/C ratio], Mid polar renal parenchymal diameter [MPPD]) and functional imaging scan (LLEC scan or DTPA scan). Three specimens were taken intraoperatively from above PUJ, at the level of PUJ, and below PUJ. Those were examined immunohistochemically using CD117 to count ICC-LC using standard criteria. Variation in the expression of CD117-positive ICC-LC was correlated with the abovestated parameters. Results: The number of CD117-positive ICC-LC showed a continuous decreasing trend above downward. P/C ratio and APPD showed a parallel trend with ICC-LC distribution, whereas split renal function (SRF) showed an inverse relationship with the expression of ICC-LC. Children with lesser severity of obstruction (APPD <30 mm and SRF >40%) showed a uniform decreasing trend in the number of CD117-positive ICC-LC across PUJ. Children with more severe obstruction (APPD >30 mm and SRF <40%) showed a decrease in the expression of ICC-LC up to the level of PUJO followed by a sudden relatively increased expression of ICC-LC below the obstruction. Conclusion: The expression of ICC-LC shows a uniformly decreasing trend across obstruction when the severity of obstruction is less. Resurgence in the number of ICC-LC below PUJ in subjects with severe obstruction hints at the emergence of a new pacemaker area below severely blocked PUJ akin to that seen in complete heart block patients and deserves early attention.

COVID-Associated Sinonasal Mucormycosis: Radiological Pathological Correlation and Prognostic Value of MR Imaging.

Purpose Our aim was to assess the sinonasal magnetic resonance imaging (MRI) features of acute invasive fungal rhinosinusitis (AIFRS) in coronavirus disease (COVID)-associated mucormycosis (CAM) and to correlate these with histopathology and patient outcome in terms of duration of hospital stay and survival at 10 weeks. Methods Twenty patients with histopathologically confirmed sinonasal CAM underwent MRI (including postcontrast T1-weighted and diffusion-weighted imaging). Histopathological findings (presence of coagulative necrosis, granulomatous reaction, and fungal burden) were recorded and all patients were followed up at 6 and 10 weeks. Statistical analysis was done using chi-square test and Fischer's exact test. Results Enhancement patterns seen in our subjects included homogeneous, heterogeneous, and lack of contrast enhancement (LOC), with LOC being the most common (65%). Diffusion restriction was found in 90% patients. Statistically significant correlation was found between LOC pattern and presence of coagulative necrosis ( p -value = 0.007), extent of fungal hyphae ( p -value = 0.047), and duration of hospital stay ( p -value = 0.004). Restricted diffusion was also seen to correlate with a high fungal load ( p -value = 0.007). Conclusion Our study describes the MRI findings of AIFRS in CAM and highlights the imaging features which may be surrogate markers for coagulative necrosis and fungal burden.

Smoking status in acute myeloid leukemia is associated with worse overall survival and independent of prior nonhematopoietic malignancies, cytogenetic abnormalities, and WHO category.

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with several patient- and disease-associated variables known to impact prognosis. Tobacco smoking is an environmental factor associated with a greater incidence of AML, but there have been limited studies that evaluated smoking toward overall survival. We retrospectively searched for AML cases and collected clinical and diagnostic data for each case. We also used an independent next-generation sequencing (NGS) data set to assess for a distinct mutational signature associated with smoking. When stratified by smoking status, there was a greater number of males, patients aged ≥60 years, and patients with ≥2 comorbidities within the smoking category (P < .05). Survival analysis demonstrated decreased survival probability in the smokers, male smokers, smokers with 1 other comorbidity, and smokers without a prior history of nonhematopoietic malignancy (P < .05) as compared to nonsmokers. Smoking was associated with a decrease in survival within the World Health Organization categories of AML, not otherwise specified (AML NOS; P = .035) and AML with recurrent genetic abnormalities (AML RGA; P = .002). Multivariate analysis showed that patients who were smokers had a greater hazard ratio than nonsmokers after adjusting for the other covariates. Our findings demonstrated that smoking was independently associated with decreased overall survival after adjusting for other potentially confounding factors. In addition, our results suggest that a mutational signature can be recognized using NGS data in a subset of AML patients who smoke.

Copy Number Loss at Chromosome 14q11.2 Correlates With the Proportion of T Cells in Biopsies and Helps Identify T-Cell Neoplasms.

CONTEXT.­: Evidence of T-cell clonality is often critical in supporting the diagnosis of a T-cell lymphoma. OBJECTIVES.­: To retrospectively explore the significance of copy number losses at the 14q11.2 T-cell receptor α locus in relation to the presence of a T-cell neoplasm and proportion of T cells by targeted next-generation sequencing. DESIGN.­: Targeted next-generation sequencing data from 139 tissue biopsies, including T-cell lymphomas, B-cell lymphomas, classic Hodgkin lymphomas, nonhematopoietic malignancies, and normal samples, were reviewed for copy number losses involving the T-cell receptor α gene segments at chr14q11.2. RESULTS.­: We found that biallelic or homozygous deletion of 14q11.2 was found in most (28 of 33, 84.8%) T-cell lymphomas. The magnitude of 14q11.2 loss showed a statistically significant correlation with the proportion of T cells in lymphoma tissue samples. Copy number losses could also be detected in other lymphomas with high numbers of T cells (8 of 32, 25% of B-cell lymphomas, 4 of 4 classical Hodgkin lymphomas), though biallelic/homozygous deletion of 14q11.2 was not significantly observed outside of T-cell lymphomas. Most nonhematopoietic neoplasms and normal tissues (59 of 64, 92.2%) showed no significant copy number losses involving the T-cell receptor α locus at chr14q11.2. CONCLUSIONS.­: Analysis of copy number losses at the T-cell receptor α locus chr14q11.2 with targeted next-generation sequencing can potentially be used to estimate the proportion of T cells and detect T-cell neoplasms.