Context.—:Breast-conserving surgery (BCS) offers comparable overall survival rates to mastectomy. However, 14% to 37% of cases require re-excision owing to tumor-positive margins after BCS. Hyperspectral imaging (HSI) provides rapid, real-time, thorough margin assessment, reducing the burden of re-excisions. Objective.—:To systematically review studies published up to January 2026 investigating HSI or multispectral imaging for breast cancer margin assessment. Data Sources.—:Twenty-four primary studies involving HSI or multispectral imaging of fresh lumpectomy specimens or histologic slides in breast cancer were included, focusing on reporting methodology, imaging setup, machine learning models, diagnostic performance, and comparisons to standard techniques. Key data on sample types, imaging acquisition (spectral range, modality), preprocessing, algorithms (conventional classifiers and deep learning), validation methods, and diagnostic accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve [AUC]) were extracted. Conclusions.—:HSI consistently differentiated malignant from normal breast tissue across studies. In ex vivo lumpectomy specimens, HSI classifiers achieved sensitivity of 83% to 96% and specificity of 72% to 96% for margin-level detection, with AUC approximating 0.9. Machine learning ranged from linear discriminant analysis and support vector machines to convolutional neural networks and clustering algorithms, leveraging visible spectrum to near-infrared spectral range. HSI was integrated into simulated surgical workflows, imaging a lumpectomy surface within ∼10 minutes and providing automated margin maps in 3 minutes. Bulky hardware, calibration requirements, reduced spectral resolution, and regulatory approval remain major challenges to clinical adoption. No HSI devices have regulatory approval for intraoperative margin assessment in BCS. HSI enables whole-surface visualization of tumor margins. Translating HSI requires multidisciplinary efforts and prospective multisite trials.

Adrenocortical carcinoma is a rare and clinically heterogeneous malignancy, often posing difficulty in accurate prognostication. Existing clinicopathological scoring systems, the Weiss, AFIP/Wieneke, and Lin-Weiss-Bisceglia (LWB) criteria, are constrained by their age/subtype-specific applicability and are not suitable for evaluating the rare myxoid and sarcomatoid morphologies or needle biopsies. The Reticulin Algorithm (RA) is a simplified approach for the histopathological assessment of adrenocortical neoplasms, but its prognostic utility requires further validation. We evaluated the prognostic performance of RA and its pediatric-adaptation (pRA) in 157 adrenocortical neoplasms, comprising 140 resection specimens and 17 needle biopsies from 118 adult and 39 pediatric patients, representing all histomorphological subtypes. Among adult tumors, the RA demonstrated diagnostic accuracy exceeding 90%, comparable to the Weiss system but with higher specificity and a markedly superior positive likelihood ratio, highlighting its stronger prognostic value. Its greatest impact was observed in oncocytic tumors, where it outperformed the LWB criteria and correctly reclassified most lesions previously designated as having uncertain malignant potential. In pediatric cases, RA’s performance was comparable to the AFIP/Wieneke criteria. Notably, pRA further improved predictive precision. All myxoid and sarcomatoid tumors were appropriately classified using the algorithm. RA application to needle biopsies showed complete concordance with clinical outcomes. Survival analyses confirmed significant stratification between RA-defined benign and malignant groups. In this large single-center study, RA demonstrated broad applicability and prognostic utility across age groups, histologic subtypes, and specimen types, supporting its potential role in risk stratification of adrenocortical neoplasms.

Pediatric adrenal tumors are uncommon, with the most common being peripheral neuroblastic tumors. Other neoplasms like adrenal cortical tumors, pheochromocytoma, and myelolipoma may also be encountered in this age group. Rare instances of mesenchymal tumors such as Ewing sarcoma and rhabdomyosarcoma have been described. We report the fine needle aspiration cytology (FNAC) findings of the first case of BCOR-altered sarcoma occurring in the adrenal gland. A 13-year-old boy presented with severe abdominal pain. Imaging revealed a mass in the right adrenal gland. FNAC showed loosely cohesive clusters and singly dispersed medium-sized polygonal to spindled tumor cells with scant to moderate delicate cytoplasm and normochromic, mildly pleomorphic nuclei with fine granular chromatin. Slender fibrovascular cores traversed tumor fragments. Histopathology of the adrenalectomy showed sheets of round to spindled tumor cells interrupted by thin fibrovascular septae, with foci of necrosis. BCOR, SATB2, and cyclin D1 were positive, while CD99, NKX2.2, WT1, desmin, and myogenin were negative. Fluorescence in situ hybridization revealed BCOR::CCNB3 fusion, consistent with BCOR-rearranged sarcoma. BCOR-rearranged sarcomas are rare malignant neoplasms. As primary treatment is chemotherapy, accurate diagnosis on limited material such as FNAC is critical. The recognition of cytological features and follow up with appropriate ancillary testing has the potential to improve management of these patients.

OBJECTIVES:Acid-fast bacillus (AFB) detection by microscopy remains a cornerstone of laboratory diagnosis for mycobacterial infections, despite the limitations of variable sensitivity, labor-intensive workflows, and interobserver variability. Recent advances in artificial intelligence, particularly deep learning, offer promising solutions to automate and augment AFB detection on microscopy images. METHODS:A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with protocol registration in PROSPERO (registration No. CRD42025633886). PubMed and Embase were searched for studies published in the past decade that applied deep learning-based methods to microscopy-based AFB detection. Eligible studies included original research and review articles using Ziehl-Neelsen-stained or auramine-stained specimens and reporting quantitative diagnostic performance metrics. Data on model architectures, annotation strategies, evaluation metrics, and accuracy were extracted. A forest plot was constructed to summarize pooled accuracy estimates across eligible studies. RESULTS:Forty-nine studies met the inclusion criteria. Deep learning models, including convolutional neural networks, object detectors, and transformer-based architectures, demonstrated high accuracies (80%-98%), despite substantial heterogeneity. Weakly supervised learning, multiview and z-stack imaging, and domain adaptation techniques are being used to address variability in staining, focus, and laboratory conditions. Object detection and segmentation models have enabled improved bacillus localization and quantification, while foundation models and transfer learning approaches are reducing annotation burden and improving generalizability. CONCLUSIONS:Deep learning-based AFB detection systems demonstrate high accuracy and strong potential to enhance tuberculosis microscopy. Heterogeneity in study design and limited external validation, however, highlight the need for standardized evaluation and multicenter clinical studies before widespread implementation.

INTRODUCTION:Peritoneal cytology (PC) is a useful predictor of ovarian surface involvement and intraperitoneal metastasis in epithelial malignancies. Most malignancies involving serous cavity effusions are adenocarcinomas; however, nonepithelial tumors such as lymphomas and germ cell tumors (GCTs) rarely cause malignant effusion. Data on PC in malignant ovarian germ cell tumor (MOGCT) are limited to isolated case reports with lack of systematic cytohistologic correlation, hence the need for this study. MATERIALS AND METHODS:All PC samples of surgically resected MOGCTs were classified using The International System (TIS) for the Reporting of Serous Cytopathology. Immunohistochemistry (IHC) was performed on cell blocks of all atypical and malignant cases. Tumor markers and histopathological parameters of surgical resection specimen were correlated with cytology findings using statistical tests. RESULTS:Nine (19%) of 48 MOGCTs showed features suspicious or definitive for metastasis on PC with three cases initially misdiagnosed as carcinomas. Spalt-like transcription factor 4 IHC resulted in upgradation of one TIS3 category case to TIS4/5. Cytological detection of metastasis correlated with intra-abdominal spread, omental involvement, and advanced pathological stage (P< 0.05). CONCLUSIONS:Cytological detection of intraperitoneal MOGCT metastases on PC correlates with other histopathological staging parameters. Cell blocks and Spalt-like transcription factor 4 IHC aided in confirming MOGCT origin in ambiguous and misdiagnosed cases. Further validation of atypia of undetermined significance is warranted to improve diagnostic accuracy.

Human papillomaviruses (HPVs), particularly types 16 and 18, are major contributors to cervical cancer through the oncogenic activities of the E6 and E7 proteins. These viral proteins inactivate the tumour suppressors p53 and pRB, driving uncontrolled cellular proliferation. In this study, we investigated the interaction between the HPV E7 protein and the R2TP complex, a co-chaperone involved in essential cellular functions, including ribosome biogenesis, transcription, and macromolecular assembly. We identified PIH1D1, a core R2TP subunit, as an interacting partner of HPV16 and HPV18 E7 proteins. Mutagenesis and pull-down assays showed that phosphorylation of HPV E7 by casein kinase 2 (CK2) is critical for this interaction, as mutations of serine residues within the CK2 phospho-acceptor site on E7 disrupted the binding with PIH1D1. Furthermore, PIH1D1 facilitated the association of E7 with the retinoblastoma protein (pRB), forming a complex that likely promotes cancer cell proliferation. Immunohistochemical analysis of cervical cancer tissues revealed overexpression of PIH1D1, RUVBL1, and RPAP3-key components of the R2TP complex. Functional assays confirmed that PIH1D1 is crucial for cervical cancer cell growth and migration, as its silencing reduced E7 stability and impaired proliferation. Collectively, these findings highlight that PIH1D1, and by extension, the R2TP complex, is integral to the HPV-driven malignancy and suggest potential as therapeutic targets in HPV-related cancers.ImportanceDespite being largely preventable through vaccination, cervical cancer is a significant concern for public health. Research is essential to understand the factors contributing to its high incidence and mortality and to devise effective prevention and treatment strategies. We investigated the functional role of PIH1D1, a core subunit of the R2TP complex, in the HPV-mediated cervical carcinogenesis. The interaction of the R2TP complex, HPV E7, and the tumour suppressor pRB proteins may be essential in driving malignant transformation.

Posterior mediastinal yolk sac tumors (YSTs) with spinal cord compression are exceedingly rare in children. We report a 3-year-old boy with paraplegia due to a posterior mediastinal YST with intraspinal extension. Neoadjuvant chemotherapy followed by surgery led to neurological recovery and long-term remission, highlighting diagnostic and therapeutic challenges.

BACKGROUND:Wilms tumor (WT) and Neuroblastoma (Nb) are the two most common pediatric abdominal tumors that are difficult to differentiate due to anatomical proximity and often need an invasive procedure such as fine needle aspiration or biopsy. Pediatric tumors have differential expression of miRNA that can be used as a non invasive method to differentiate. Based upon the existing published literature, we designed a panel of four miRNAs (miR1180, miR143, miR124, and miR34a) to differentiate WT from Nb. METHODS:This was a prospective study conducted over 2 years (2019-2021) at our center. A total of 17 cases, including 10 cases of WT and seven cases of Nb, were included in this study. Ribonucleic acid (RNA) extraction was conducted after confirmation of diagnosis, which was reverse transcribed to complementary deoxyribonucleic acid (cDNA). Real time polymerase chain reaction using cDNA was performed for analyzing expression levels of miR1180, 143, 124, and 34a. RESULTS:The two biomarkers differentially expressed between these patients are miR143 and miR124 3p. miR143 is down regulated in WT (80% of cases), while up regulated in Nb (71.4% of cases), while miR124 3p is up regulated in WT (6/10:60%) and down-regulated in Nb cases. CONCLUSIONS:We conclude that miR143 and 124 might prove as useful biomarkers to differentiate between WT and Nb; however, more comprehensive evaluation is required for confirmation of the same.

BACKGROUND:Central nervous system (CNS) involvement in paediatric B-acute lymphoblastic leukaemia (B-ALL) significantly impacts relapse risk and survival. Conventional cytomorphology (CM) of cerebrospinal fluid (CSF) is rapid and specific but has low sensitivity because of limited cellularity and morphological overlap with reactive lymphocytes. OBJECTIVE:To evaluate the diagnostic utility and resource efficiency of immunocytochemistry (ICC) as an adjunct to CM in detecting leukaemic infiltration of CSF in paediatric B-ALL. METHODS:In Cohort 1 (n = 45), all CSF samples underwent CM and ICC using CD3, CD79a, and TdT. In Cohort 2 (n = 44), ICC was applied selectively to samples with pleocytosis (> 4 cells/μL) on the basis of a triage algorithm. RESULTS:In Cohort 1, ICC upgraded a subset of "doubtful" CM cases to definitive leukaemic infiltration, particularly with CD79a and TdT. CD3 reliably confirmed reactive T-cell morphology, enhancing specificity. In Cohort 2, selective ICC use maintained diagnostic yield, detecting blasts in doubtful cases while conserving slides and resources. Together, ICC demonstrated added diagnostic value, especially in morphologically equivocal and higher-cellularity specimens. CONCLUSION:ICC complements CM in CSF evaluation for paediatric B-ALL, improving sensitivity and supporting a pragmatic triage strategy. A combination of CD3 and CD79a is optimal when two smears are available; with limited material, marker choice should be guided by morphology. This cost-effective workflow enhances detection of CNS involvement where flow cytometry or molecular assays are not readily available.

Background & objectives Sudden death, defined as death occurring within one hour of symptom onset in witnessed cases or within 24 h of last being seen alive in unwitnessed cases, remains a major public health concern. This study aimed to evaluate the incidence, causes, and risk factors associated with sudden death in young adults. Methods A cross-sectional study was conducted over one year at a tertiary care centre in New Delhi. Cases meeting the definition of sudden death were included, excluding trauma, suicide, homicide, and drug abuse. Each case underwent whole-body imaging, autopsy, and histopathological examination. A multidisciplinary team comprising forensic experts, pathologists, radiologists, and clinicians determined the cause of death. Comparative analysis was performed between sudden death in young adults (18-45 yr) and older adults (46-65 yr). Results Out of 2214 autopsies, 180 cases (8.1%) met the criteria for sudden death. Sudden death in young accounted for 103 (57.2%) cases. Mean age was 33.6 yr in sudden death in young (IQR=10) and 53.8 years in sudden death in old, with male predominance in both. Cardiovascular causes were most common in young (n=40, 42.6%), followed by respiratory causes (n=20, 21.3%) and sudden unexplained deaths (n=20, 21.3%), where no pathology was identified. Other causes included gastrointestinal, central nervous system, and genitourinary pathologies. Smoking and alcohol intake was equally prevalent in those who died young and at old age. Interpretation & conclusions Sudden death in young adults is a significant concern requiring targeted public health strategies. Coronary artery disease remains the leading cause. Respiratory and unexplained deaths warrant further investigation.

Background. Hepatoblastoma has an aggressive course in a subset of children. Studying various markers related to the signaling pathways can aid in understanding its pathogenesis at the molecular level and may pave the way for targeted therapy. We conducted this study to evaluate the immunohistochemical expression of markers related to WNT and NOTCH signaling pathways in hepatoblastoma and to compare them among its histological subtypes. Methods. The specimens of hepatoblastoma diagnosed over a period of 8 years were retrieved. Clinicoradiological data was obtained. Slides were reviewed and detailed histopathological parameters, diagnosis, and subtypes were reevaluated. Immunohistochemistry for β-catenin, CCND1, glutamine synthetase, MYC, AXIN2, NOTCH2, DLK1, and HES1 was performed. Statistical analysis was done. Results. A total of 51 samples of hepatoblastoma were included in the study. Mixed epithelial-mesenchymal hepatoblastoma was the most common histologic subtype. PRETEXT IV, high-risk group, high mitotic index, and less differentiated histologic subtype were associated with worse outcomes. β-catenin, AXIN2, CCND1, expression was more in less differentiated subtypes. MYC, HES1, and glutamine synthetase expression was more common in the fetal component. NOTCH2 and DLK1 expression was seen across all types. A statistically significant association was observed among AXIN2 expression with β-catenin, CCND1, and MYC nuclear expression. Mean overall survival was 66.6 months and mean event-free survival was 54.7 months. Conclusions. The NOTCH pathway converges with the WNT pathway. Differential expression of the immunohistochemical markers of these pathways helps in the semiquantitation of various epithelial components, guides adjuvant treatment, and patient prognostication.

INTRODUCTION:Malignant pleural effusion is a frequent manifestation in cancer patients, with effusion cytology playing a vital role in diagnosis and subtyping. Present study evaluated the effect of sample volume on malignancy detection and estimated the risk of malignancy (ROM) by using The International System for Reporting Serous Fluid Cytopathology (TIS). METHODS:Pleural effusions submitted from May 2021 to December 2022 were reclassified using The International System for Reporting Serous Fluid Cytopathology (TIS) into five categories: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance metrics were calculated based on follow-up histology and/or repeat cytology, ancillary tests, and clinico-radiology. Volume data from 493 samples were grouped into six bins (0-10 mL to >300 mL), and malignancy fractions were analyzed. Generalized estimating equation logistic regression assessed the impact of volume, sex, and age on diagnostic outcomes. Analysis was performed in R. RESULTS:Of 1,265 samples from 1,107 patients, 875 (69.2%) had follow-up data. ROM estimates were ND 23.6%, NFM 11.6%, AUS 57.1%, SFM 100%, MAL 97.5%. MAL samples had significantly higher median volume than NFM (100 vs. 35 mL; p < 0.000). False negatives had lower volumes than true positives (50 vs. 80 mL; p = 0.027). Malignancy detection was lowest in samples <10 mL (7.4%) and highest in >300 mL (40.4%). Volumes <25 mL were significantly associated with reduced odds of malignancy detection (p < 0.05). CONCLUSION:Sample volumes <25 mL are linked to lower malignancy detection, underscoring the importance of adequate volume and supporting TIS implementation in routine cytology.

Central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) is associated with a poor prognosis, making its accurate detection vital for treatment planning. This systematic review critically examines the role of conventional cytomorphology (CC) and multiparameter flow cytometry (FC) in analyzing cerebrospinal fluid in acute lymphoblastic leukemia cases. While CC remains the gold standard, its sensitivity is limited, particularly in cases with low cell counts. FC offers greater sensitivity in identifying cases of 'occult' CNS disease (FC+/CC-). Pre-analytical variables, such as CSF volume, processing time, and preservation techniques, also influence the accuracy of both methods. Despite the advantages of FC, challenges remain, including the lack of standardized positivity criteria and unclear prognostic implications and management strategies for occult CNS disease (FC+ and CC-). Future research is needed to establish uniform diagnostic guidelines and to assess the clinical relevance of occult CNS disease in ALL.

Neuroblastoma (NB) is the most common extracranial solid neoplasm affecting the pediatric population. It shows a high prevalence of bone marrow infiltration (BMI), which substantially impacts the disease's staging and prognostic assessment. Conventional methodologies, including bone marrow biopsy (BMB) and aspirate (BMA), have been extensively employed; nevertheless, the advent of novel technologies presents a promising avenue for diagnostic accuracy. This systematic review is designed to critically analyze and compare the established techniques (BMB and BMA) versus novel diagnostic approaches-such as immunocytology, RT-qPCR, and multiparametric flow cytometry (FCM), along with functional imaging like MIBG scintigraphy and FDG-PET/CT-in assessing BMI in pediatric NB. An exhaustive search was performed across the PubMed and Embase databases, identifying 2694 scholarly articles. Following a meticulous screening process and the application of inclusion criteria centered on diagnostic accuracy, sensitivity, and specificity about BMI, a total of 140 articles were selected for qualitative analysis. While BMB remains the gold standard for diagnosing and staging BMI in NB, recent advances in molecular techniques and functional imaging have shown superior sensitivity and specificity. Immunocytology and RT-qPCR can detect minimal residual disease (MRD) with higher sensitivity compared to traditional methods. Functional imaging modalities, particularly FDG-PET/CT and MIBG scintigraphy, have demonstrated improved accuracy in assessing bone marrow involvement with the added advantage of evaluating the entire bone marrow, overcoming the limitations of focal sampling in BMB. The integration of advanced molecular diagnostics and functional imaging with traditional biopsy methods enhances the accuracy of BMI in NB.

Germ cell tumors (GCTs) arise from primordial germ cells and can occur in any region along the path of migrating primordial germ cells. Retroperitoneal teratomas are such tumors usually arising in para-renal locations. These tumors have the propensity to grow to large sizes leading to distortion of the local anatomy and compressive symptoms. Surgical excision of these tumors is challenging, with high complication rates. Retrospective data of all the patients with retroperitoneal GCTs, managed from January 1998 through March 2020, was included. Patients with increased alpha-fetoprotein or with malignant histopathology were excluded. Maintained data sets of the included patients were evaluated for patient demographics, symptoms, radiologic and histologic findings, surgical procedures and postoperative outcomes. A total of 26 patients of retroperitoneal GCTs, comprising ten males and 16 females, were operated on at our centre. The median age at presentation was 10.5 months (1 day to 178 months). Most patients (n = 21/26) presented with a palpable abdominal mass. All the patients underwent operative intervention. Intraoperatively, 23