Successful Laparoscopic Management of Zinner Syndrome in a Pediatric Patient.

Zinner syndrome, a rare congenital anomaly affecting males, is characterized by atresia of the ejaculatory duct, seminal vesicle cysts, and ipsilateral renal agenesis. This case report details a 2-year-old boy successfully treated with laparoscopic excision of a dilated vas deferens and seminal vesicle cyst. The rarity of Zinner syndrome in pediatric patients underscores the importance of understanding its diagnosis and minimally invasive surgical management.

Comparison of conventional diffusion-weighted imaging, diffusion kurtosis imaging and intravoxel incoherent motion in characterization of sonographically indeterminate adnexal masses.

PURPOSE: To evaluate the role of conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) in distinguishing benign from malignant adnexal masses. METHODS: 38 patients with 45 adnexal masses were enrolled in this prospective study and assessed with multiparametric MRI, including the IVIM-DKI sequence, on a 3 T MRI system. The mean apparent diffusion coefficient (ADC) from conventional DWI, the apparent diffusion coefficient derived from DKI (Dapp), the apparent kurtosis coefficient (Kapp), true diffusion coefficient (Dt), perfusion fraction (f) and pseudo-diffusion coefficient (Dp) were measured. RESULTS: The mean ADC, Dapp, and Dt were significantly higher in benign adnexal masses than in malignant adnexal masses (p < 0.001). f and Dp were also significantly higher in benign adnexal masses, with p values of 0.026 and 0.002, respectively. Kapp was higher in malignant masses (p < 0.001). Among mean ADC, Dapp, and Dt, mean ADC had the highest area under the curve (AUC) of 0.885. However, no statistically significant differences were observed between the ROCs of various diffusion parameters. CONCLUSION: The mean ADC, Dapp, and Kapp are useful parameters in discriminating between benign and malignant adnexal masses. Dt derived from IVIM also helps in distinguishing benign and malignant adnexal masses; however, no incremental role of IVIM and DKI over ADC could be identified in our study.

Benign paediatric liver tumours: The radiological maze demystified.

The trajectory from the clinical identification of a benign liver mass to establishing a precise diagnosis is perplexing and arduous. Related contributory factors are that such lesions are encountered infrequently and that there is a nonavailability of dedicated paediatric radiologists in the developing world. The objective of this study was to review the spectrum of benign liver lesions in children and their typical imaging features. Cross-sectional imaging of all paediatric patients (< 18 years) with liver lesions (single and multiple) performed in the institute from 01 January 2018 to 01 January 2019 as well as those acquired at outside institutions and referred to the institute for management was included. Ultrasound was done as the first line of investigation in all the cases with suspicious liver masses and retrospectively performed in referral cases in whom CT or MRI was already done. Images were analysed by two senior radiologists. Most of the cases were diagnosed based on clinical, biochemical and imaging findings, and biopsy was only performed in equivocal cases. Most of the benign liver lesions in the paediatric age group were hepatic haemangioma and mesenchymal hamartomas. A simplified clinical-radiologic paradigm should be established for benign liver lesions in children to assist in reaching the correct diagnosis. Contribution: The article demonstrates the salient radiological findings of various benign liver lesions in the paediatric age group and the role of demographic, clinical and biochemical findings, which plays a substantial role in the diagnosis and avoids unnecessary biopsies.

68Ga-DOTANOC PET/CT in 2 Siblings With Von Hippel-Lindau Disease.

ABSTRACT: Von Hippel-Lindau disease is a rare multisystem disorder that shows autosomal dominant inheritance. It is a cancer syndrome that is characterized by the development of a variety of benign and malignant tumors-CNS hemangioblastomas, retinal angiomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, adrenal pheochromocytomas, and epididymal cystadenomas. Here we present the 68Ga-labeled DOTANOC scans of 2 siblings who show an interesting spectrum of findings consistent with Von Hippel-Lindau disease.

Study of Intrahepatic Biliary Architecture in Patients Operated for Extrahepatic Biliary Atresia using Magnetic Resonance Cholangiopancreatography.

Aim: The aim is to study intrahepatic biliary architecture in patients following Kasai's portoenterostomy for extrahepatic biliary atresia using magnetic resonance cholangiopancreatography (MRCP). Materials and Methods: It is a prospective observational study in a cohort of patients who have survived with a complete jaundice-free period for at least 1 year. MRCP was done to look for various intrahepatic architectural changes during their last visit. Findings were correlated with liver functions and growth and development. Results: Twenty-one patients were included in the study. The male-to-female sex ratio was 1.6:1, the median age at surgery was 75 days (18-140 days), and the median age at magnetic resonance imaging (MRI) was 4 years (18 months-18 years). More than 2 years of follow-up was in seven patients. Left lobe hypertrophy was observed in six patients, right lobe hypertrophy was in three patients, intrahepatic biliary tract dilatation was in five patients, and altered signal intensity between intrahepatic ducts was seen in five patients. In addition, hypointense foci in the spleen were seen in one patient. Twelve children had normal weight for their age, ten children had the normal height for their age, and gamma-glutamyl transferase was elevated in all children. Only four children had a history of fever and jaundice. Conclusions: The patients who survive after successful surgical intervention have near-normal liver gross architecture as on MRI/MRCP. Occasional findings of dilatation and lobar atrophy/hypertrophy are possible, especially in those with a history of cholangitis. The survivors also have acceptable growth parameters and normal liver functions.

Fully automatic deep learning-based lung parenchyma segmentation and boundary correction in thoracic CT scans.

PURPOSE: The proposed work aims to develop an algorithm to precisely segment the lung parenchyma in thoracic CT scans. To achieve this goal, the proposed technique utilized a combination of deep learning and traditional image processing algorithms. The initial step utilized a trained convolutional neural network (CNN) to generate preliminary lung masks, followed by the proposed post-processing algorithm for lung boundary correction. METHODS: First, the proposed method trained an improved 2D U-Net CNN model with Inception-ResNet-v2 as its backbone. The model was trained on 32 CT scans from two different sources: one from the VESSEL12 grand challenge and the other from AIIMS Delhi. Further, the model's performance was evaluated on a test dataset of 16 CT scans with juxta-pleural nodules obtained from AIIMS Delhi and the LUNA16 challenge. The model's performance was assessed using evaluation metrics such as average volumetric dice coefficient (DSCavg), average IoU score (IoUavg), and average F1 score (F1avg). Finally, the proposed post-processing algorithm was implemented to eliminate false positives from the model's prediction and to include juxta-pleural nodules in the final lung masks. RESULTS: The trained model reported a DSCavg of 0.9791 ± 0.008, IoUavg of 0.9624 ± 0.007, and F1avg of 0.9792 ± 0.004 on the test dataset. Applying the post-processing algorithm to the predicted lung masks obtained a DSCavg of 0.9713 ± 0.007, IoUavg of 0.9486 ± 0.007, and F1avg of 0.9701 ± 0.008. The post-processing algorithm successfully included juxta-pleural nodules in the final lung mask. CONCLUSIONS: Using a CNN model, the proposed method for lung parenchyma segmentation produced precise segmentation results. Furthermore, the post-processing algorithm addressed false positives and negatives in the model's predictions. Overall, the proposed approach demonstrated promising results for lung parenchyma segmentation. The method has the potential to be valuable in the advancement of computer-aided diagnosis (CAD) systems for automatic nodule detection.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Comparison of Neck Ultrasonography, Dual Phase 99mTc-Sestamibi with early SPECT-CT & 18F-Fluorocholine PET-CT as First Line Imaging in Patients with Primary Hyperparathyroidism.

Introduction: Successful surgical treatment for primary hyperparathyroidism requires accurate localization of abnormal parathyroid tissue in terms of location and number. Imaging is important for localizing the parathyroid adenoma, and there has been significant interest in 18F-fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for this purpose. Aim: This study attempted to ascertain the utility of 18F-FCH PET/CT as a first-line investigation in preoperative localization of abnormal parathyroid tissue in primary hyperparathyroidism, in comparison with 99mTc-sestamibi dual-phase scintigraphy with early single-photon emission computed tomography (SPECT)/CT and neck ultrasonography. Materials and Methods: Fifty-five patients with biochemical features of primary hyperparathyroidism were enrolled in this study. They underwent neck ultrasonography, 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT, and 18F-FCH PET/CT for localization of parathyroid lesions. Thirty-three patients underwent surgical resection of the detected lesions. For two patients, clinical and biochemical follow-up was used as a gold standard. Results: A total of 40 lesions were resected in the 33 patients who underwent surgery. A further two lesions were localized in two patients with clinical and biochemical follow-up as the gold standard. Of these 42 lesions, 41 were detected in preoperative imaging and 1 lesion was noted intraoperatively and resected. 41/42 lesions were detected by 18F-FCH PET/CT (detection rate: 97.6%), 33/42 by 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT (detection rate: 78.5%), and 30/42 by neck ultrasonography (detection rate: 71.4%). Conclusion: Detection rates on 18F-FCH PET/CT were superior to both 99mTc-sestamibi dual-phase scintigraphy with early SPECT/CT and neck ultrasonography in preoperative localization of parathyroid lesions in patients with primary hyperparathyroidism.

Multiple neural tube defects: rare developmental anomaly with an elusive embryological explanation.

Neural tube defect is a congenital anomaly resulting from the failure of fusion of the neural folds in the midline which occurs in the third and the fourth week of embryonic development. These defects can occur at any of the three embryological stages-gastrulation, primary neurulation and secondary neurulation. Presence of neural tube defects at multiple (two or more) sites along the craniospinal axis is an extremely rare anomaly and the management depends on clinical as well as imaging findings. These multiple defects are not well explained by the "Zipper closure" theory and can be better explained by the "Multisite closure theory", which will be highlighted in this manuscript. Few of these multiple site anomalies cannot be fully explained even by the multisite closure theory and more research is needed to decipher this entity.

Incidence of Prediabetes/Diabetes among Women with Prior Gestational Diabetes and Non-Alcoholic Fatty Liver Disease: A Prospective Observational Study.

Background and Objectives: This prospective longitudinal study aims to evaluate and compare the incidence of prediabetes/diabetes among women stratified at the baseline postpartum visit according to the prior GDM and NAFLD status. Methods: Of the 309 women with baseline postpartum assessment at a median of 16 months following the index delivery, 200 (64.7%) [GDM: 137 (68.5%), normoglycaemia: 63 (31.5%)] were available for the follow-up analysis (performed at median of 54 months following the index delivery) and were participants for this study. We obtained relevant demographic, medical and obstetric details and performed a 75 g OGTT with glucose estimation at 0 and 120 min. NAFLD status was defined by ultrasonography at the baseline visit. Participants were divided into four groups: no NAFLD and no prior GDM (group 1), NAFLD but no prior GDM (group 2), prior GDM but no NAFLD (group 3), and NAFLD and prior GDM (group 4). Results: The mean age of study participants (n = 200) was 32.2 ± 5.1 years, and the mean interval between the two visits was 34.8 ± 5.5 months. A total of 74 (37%) women had progression to prediabetes/diabetes [incidence rate of 12.8/100 woman-years]. The incidence rates (per 100 woman-years) were 8.6, 8.9, 13.4 and 15.3 in groups 1, 2, 3 and 4, respectively. The adjusted hazard ratio for incident (new-onset) prediabetes/diabetes in group 4 (reference: group 1) was 1.99 (95% CI 0.80, 4.96, P = 0.140). Among women with baseline NAFLD (irrespective of GDM status), the risk of incident prediabetes/diabetes increased with an increase in the duration of follow-up (3.03-fold higher per year of follow-up, P = 0.029) and was significantly higher in women who were not employed (6.43, 95% CI 1.74, 23.7, P = 0.005) and in women with GDM requiring insulin/metformin during pregnancy (4.46, 95% CI 1.27, 15.64, P = 0.019). Conclusion: NAFLD and GDM increased the risk for glycaemic deterioration in young Indian women. Future studies should focus on evaluating the effectiveness of lifestyle and behavioural interventions in such high-risk women.

Diagnostic accuracy of whole-body magnetic resonance imaging versus positron emission tomography-computed tomography for the staging of pediatric lymphoma: a systematic review and meta-analysis.

BACKGROUND: Whole-body magnetic resonance imaging (MRI) has been investigated by multiple authors as a radiation-free alternative to positron emission tomography computed tomography (PET-CT) in children with lymphoma. OBJECTIVE: To evaluate the sensitivity, specificity, and diagnostic odds ratio of whole-body MRI compared to PET-CT for the staging of pediatric lymphoma. METHODS: The databases PubMed, Embase, and Scopus were searched for studies that reported the accuracy of whole-body MRI compared to PET-CT for lymphoma staging in children. Data was collected from included studies to formulate 2 × 2 contingency tables, including the number of true positive, true negative, false positive, and false negative. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. Summary receiver operating characteristic curves were drawn and the area under the curve (AUC) calculated. In addition, the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) tool was used to assess the risk of bias and applicability concerns. RESULTS: A total of seven studies were included in the final analysis. Of these, six studies used unenhanced whole-body MRI. The pooled sensitivity of whole-body MRI-based staging was 95.8%, while the pooled specificity was 21.8%. The DOR for whole-body MRI was 1.19. For extranodal staging, the pooled sensitivity was 88.9%, specificity was 97.4%, and DOR was 25.29. The partial AUC for overall staging was 0.63, whereas that for extranodal staging stood at 0.88. Based on the QUADAS 2 tool, all seven studies were at risk of bias (six at high risk, one at unclear risk). CONCLUSION: Whole-body MRI has high sensitivity for staging of pediatric lymphoma and may be a useful alternative to PET-CT.

Unmasking the great imitators-noninfectious conditions masquerading as spinal tuberculosis in a developing country: A single-center case series analysis.

Background: The diagnosis of spinal tuberculosis often relies on clinical, radiological, and laboratory findings, particularly in resource-constrained settings. However, numerous noninfectious conditions exhibit similar clinical and radiological features to spinal tuberculosis, leading to potential misdiagnosis in the absence of microbiological or histopathological confirmation. This study aims to present a case series from a developing country, highlighting noninfectious conditions that mimic spinal tuberculosis. Methods: A retrospective analysis was conducted on hospital records and imaging of patients diagnosed with spinal tuberculosis, lacking microbiological or histopathological evidence, and unresponsive to empirical antitubercular treatment. Patients displaying noninfectious conditions resembling spinal tuberculosis upon further investigation were included. Clinical and radiological findings of these patients were thoroughly analyzed. Results: Among a total of 23 patients observed over a 6-year period (2015-2020), various noninfectious conditions were identified as mimickers of spinal tuberculosis. These conditions included vertebral body haemangioma, ankylosing spondylitis (with or without Andersson lesion), rheumatoid pannus, osteoid osteoma, cystic hygroma, multiple myeloma, vertebral metastasis, malignant small round-cell tumor, pancreatic pseudocyst, esophageal duplication cyst, Modic changes in degenerative disc disease, Paget's disease, and psoas hematoma. Conclusion: Noninfectious spinal conditions can masquerade as spinal tuberculosis, underscoring the importance of obtaining a definitive tissue diagnosis before initiating antitubercular treatment. Particular attention should be given to features such as central lesions and the absence of soft tissue involvement in suspected cases of spinal tuberculosis, warranting a careful reconsideration of the diagnosis.

A proposed methodology for detecting the malignant potential of pulmonary nodules in sarcoma using computed tomographic imaging and artificial intelligence-based models.

The presence of lung metastases in patients with primary malignancies is an important criterion for treatment management and prognostication. Computed tomography (CT) of the chest is the preferred method to detect lung metastasis. However, CT has limited efficacy in differentiating metastatic nodules from benign nodules (e.g., granulomas due to tuberculosis) especially at early stages (<5 mm). There is also a significant subjectivity associated in making this distinction, leading to frequent CT follow-ups and additional radiation exposure along with financial and emotional burden to the patients and family. Even 18F-fluoro-deoxyglucose positron emission technology-computed tomography (18F-FDG PET-CT) is not always confirmatory for this clinical problem. While pathological biopsy is the gold standard to demonstrate malignancy, invasive sampling of small lung nodules is often not clinically feasible. Currently, there is no non-invasive imaging technique that can reliably characterize lung metastases. The lung is one of the favored sites of metastasis in sarcomas. Hence, patients with sarcomas, especially from tuberculosis prevalent developing countries, can provide an ideal platform to develop a model to differentiate lung metastases from benign nodules. To overcome the lack of optimal specificity of CT scan in detecting pulmonary metastasis, a novel artificial intelligence (AI)-based protocol is proposed utilizing a combination of radiological and clinical biomarkers to identify lung nodules and characterize it as benign or metastasis. This protocol includes a retrospective cohort of nearly 2,000-2,250 sample nodules (from at least 450 patients) for training and testing and an ambispective cohort of nearly 500 nodules (from 100 patients; 50 patients each from the retrospective and prospective cohort) for validation. Ground-truth annotation of lung nodules will be performed using an in-house-built segmentation tool. Ground-truth labeling of lung nodules (metastatic/benign) will be performed based on histopathological results or baseline and/or follow-up radiological findings along with clinical outcome of the patient. Optimal methods for data handling and statistical analysis are included to develop a robust protocol for early detection and classification of pulmonary metastasis at baseline and at follow-up and identification of associated potential clinical and radiological markers.

ABDA Score: A Non-invasive Model to Identify Subjects with Fibrotic Non-alcoholic Steatohepatitis in the Community.

Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.

Radiologists' Rating for Comparative Qualitative Assessment of Intravoxel Incoherent Motion Using Novel Analysis Methods.

OBJECTIVE: The objective was to assess qualitative interpretability and quantitative precision and reproducibility of intravoxel incoherent motion (IVIM) parametric images evaluated using novel IVIM analysis methods for diagnostic accuracy. METHODS: Intravoxel incoherent motion datasets of 55 patients (male/female = 41:14; age = 17.8 ± 5.5 years) with histopathology-proven osteosarcoma were analyzed. Intravoxel incoherent motion parameters-diffusion coefficient (D), perfusion fraction (f), and perfusion coefficient (D*)-were estimated using 5 IVIM analysis methods-(i) biexponential (BE) model, (ii) BE-segmented fitting 2-parameter (BESeg-2), (iii) BE-segmented fitting 1-parameter (BESeg-1), (iv) BE model with total variation penalty function (BE + TV), and (v) BE model with Huber penalty function (BE + HPF). Qualitative scoring in a 5-point Likert scale (uninterpretable: 1; poor: 2; fair: 3; good: 4; excellent: 5) was performed by 2 radiologists for 4 criteria: (a) tumor shape and margin, (b) morphologic correlation, (c) noise suppression, and (d) overall interpretability. Interobserver agreement was evaluated using Spearman rank-order correlation (rs). Precision and reproducibility were evaluated using within-subject coefficient of variation (wCV) and between-subject coefficient of variation (bCV). RESULTS: BE + TV and BE + HPF produced significantly (P < 10-3) higher qualitative scores for D (fair-good [3.3-3.8]) than BE (poor [2.3]) and for D* (poor-fair [2.2-2.7]) and f (fair-good [3.2-3.8]) than BE, BESeg-2, and BESeg-1 (D*: uninterpretable-poor [1.3-1.9] and f: poor-fair [1.5-3]). Interobserver agreement for qualitative scoring was rs = 0.48-0.59, P < 0.009. BE + TV and BE + HPF showed significantly (P < 0.05) improved reproducibility in estimating D (wCV: 24%-31%, bCV: 21%-31% improvement) than the BE method and D* (wCV: 4%-19%, bCV: 5%-19% improvement) and f (wCV: 25%-49%, bCV: 25%-47% improvement) than BE, BESeg-2, and BESeg-1 methods. CONCLUSIONS: BE + TV and BE + HPF demonstrated qualitatively and quantitatively improved IVIM parameter estimation and may be considered for clinical use further.

Macrofollicular Architecture in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Pitfall in Thyroid Practice.

BACKGROUND: Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We comprehensively evaluated the radiological, cytological, gross, microscopic, molecular and follow-up characteristics of four such cases, intending to increase its recognition and add our experience to the limited literature available. METHODS: All such histopathologically-proven cases of IEFVPTC-MF were retrieved from the departmental archives. The clinical details, thyroid ultrasound, cytology and thyroid scan findings were reviewed. Allele-specific PCR for BRAF p.V600E, KRAS, NRAS, and HRAS mutations, and FISH assays for ETV6::NTRK3 fusion and RET fusions were performed. RESULTS: There were four cases of IEFVPTC-MF diagnosed between 2021 and 2022, involving two males and two females. The median age at presentation was 27 years, and the duration of the disease was 1-10 years. Thyroid ultrasound was TR1 (benign; n = 1), TR2 (not suspicious; n = 2), or TR4 (moderately suspicious; n = 1). Cytology was categorized as nondiagnostic (n = 1), benign (n = 1), and atypia of undetermined significance (n = 1). The three nodules with available cytology smears showed abundant colloid. Cells were arranged as sheets/microfollicles/clusters. Nuclei were predominantly round with minimal/focal elongation, membrane irregularity, and cellular crowding. On gross examination, cut surfaces of the tumors showed variable amounts of colloid. The tumors were solid-cystic. Histopathology revealed partially encapsulated multinodular tumors. There were prominent pseudopapillae projecting into the lumina of macrofollicles. Nuclei were predominantly round with variable nuclear atypia, including chromatin clearing and multifocal presence of nuclear grooves. Pseudoinclusions were identified in two. Molecular analysis revealed NRAS codon 61 mutation and ETV6::NTRK3 fusion in one case each. Two patients had cervical lymph node and hematogenous metastases. Post-radio-active iodine, the response was structurally incomplete (n = 2), indeterminate (n = 1) and excellent (n = 1). CONCLUSIONS: Macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma is a major pitfall in thyroid oncology practice. Long-standing disease, and ultrasonographic and cytological features that overlap with benign disease, often lead to underdiagnosis during pre-operative evaluation. As patients may consequently develop distant metastases and have inadequate treatment response, there is a need for more vigilant understanding of the spectrum of macrofollicular thyroid disease for accurate diagnosis. ETV6::NTRK3 or other fusions, when found, present opportunities for targeted therapy.