Does the use of intraoperative frozen section of bone marrow from the cut end of the mandible help assess the adequacy of bone margins following mandibulectomy for oral cancer?

BACKGROUND: The adequacy of the cut end of the mandible following a segmental mandibulectomy done for oral cancer intraoperatively is at times assessed using a frozen section (FS) of the bone marrow (BM) at the cut ends. The study aimed to assess its utility to guide the intraoperative decision on the adequacy of bony margins. MATERIALS AND METHODS: All patients with oral squamous cell carcinoma (OSCC) who underwent segmental mandibulectomy from January 2012 to December 2021 at our institute and for whom intraoperative FS of BM was utilized were included. We analyzed the sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of this in predicting positive bone margins. RESULTS: A total of 457 patients were included in the study. The majority of the cases were per premium cases (n = 372, 81.4%). The median age of the cohort was 52 years (range: 22-80 years). Most patients had T4 disease (n = 406, 88.8%). On FS, BM was positive in only 18 patients (3.9%) for whom the bone margin was revised. BM biopsy report in the final histopathology was positive in 12 patients (2.2%). The sensitivity, specificity PPV, and NPV were 52.3%, 98.65%, 64.7%, and 97.7% respectively. No factors predicting BM positivity on FS could be identified in this cohort. CONCLUSIONS: The BM FS was positive in only a small percentage of patients, and it helped in reducing the bone margin positivity rate from 3.9% to 2.2% only. Hence the intraoperative BM FS seems to have limited utility as seen from our study.

Computational pathology in cancer diagnosis, prognosis, and prediction - present day and prospects.

Computational pathology refers to applying deep learning techniques and algorithms to analyse and interpret histopathology images. Advances in artificial intelligence (AI) have led to an explosion in innovation in computational pathology, ranging from the prospect of automation of routine diagnostic tasks to the discovery of new prognostic and predictive biomarkers from tissue morphology. Despite the promising potential of computational pathology, its integration in clinical settings has been limited by a range of obstacles including operational, technical, regulatory, ethical, financial, and cultural challenges. Here, we focus on the pathologists' perspective of computational pathology: we map its current translational research landscape, evaluate its clinical utility, and address the more common challenges slowing clinical adoption and implementation. We conclude by describing contemporary approaches to drive forward these techniques. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Multiscale deep learning framework captures systemic immune features in lymph nodes predictive of triple negative breast cancer outcome in large-scale studies.

The suggestion that the systemic immune response in lymph nodes (LNs) conveys prognostic value for triple-negative breast cancer (TNBC) patients has not previously been investigated in large cohorts. We used a deep learning (DL) framework to quantify morphological features in haematoxylin and eosin-stained LNs on digitised whole slide images. From 345 breast cancer patients, 5,228 axillary LNs, cancer-free and involved, were assessed. Generalisable multiscale DL frameworks were developed to capture and quantify germinal centres (GCs) and sinuses. Cox regression proportional hazard models tested the association between smuLymphNet-captured GC and sinus quantifications and distant metastasis-free survival (DMFS). smuLymphNet achieved a Dice coefficient of 0.86 and 0.74 for capturing GCs and sinuses, respectively, and was comparable to an interpathologist Dice coefficient of 0.66 (GC) and 0.60 (sinus). smuLymphNet-captured sinuses were increased in LNs harbouring GCs (p < 0.001). smuLymphNet-captured GCs retained clinical relevance in LN-positive TNBC patients whose cancer-free LNs had on average ≥2 GCs, had longer DMFS (hazard ratio [HR] = 0.28, p = 0.02) and extended GCs' prognostic value to LN-negative TNBC patients (HR = 0.14, p = 0.002). Enlarged smuLymphNet-captured sinuses in involved LNs were associated with superior DMFS in LN-positive TNBC patients in a cohort from Guy's Hospital (multivariate HR = 0.39, p = 0.039) and with distant recurrence-free survival in 95 LN-positive TNBC patients of the Dutch-N4plus trial (HR = 0.44, p = 0.024). Heuristic scoring of subcapsular sinuses in LNs of LN-positive Tianjin TNBC patients (n = 85) cross-validated the association of enlarged sinuses with shorter DMFS (involved LNs: HR = 0.33, p = 0.029 and cancer-free LNs: HR = 0.21 p = 0.01). Morphological LN features reflective of cancer-associated responses are robustly quantifiable by smuLymphNet. Our findings further strengthen the value of assessment of LN properties beyond the detection of metastatic deposits for prognostication of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Prognostic and predictive roles of cancer stem cell markers in head and neck squamous cell carcinoma patients receiving chemoradiotherapy with or without nimotuzumab.

BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are needed to identify the patients most likely to benefit from these therapies. Here, we present predictive and prognostic associations of different cancer stem cell markers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Pretreatment tumour tissues of 404 HPV-negative LA-HNSCCs patients, a subset of-phase 3-randomised study comparing cisplatin-radiation(CRT) and nimotuzumab plus cisplatin-radiation(NCRT) were examined. The expression levels of CD44, CD44v6, CD98hc, ALDH1A1, SOX2 and OCT4A were evaluated using immunohistochemistry. Progression-free survival(PFS), loco-regional control(LRC),- and overall survival(OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: NCRT showed significantly improved OS with low membrane expression of CD44 compared to CRT [HR (95% CI) = 0.63 (0.46-0.88)]. Patients with low CD44v6 also showed better outcomes with NCRT [LRC: HR (95% CI) = 0.25 (0.10-0.62); OS: HR (95% CI) = 0.38 (0.19-0.74)]. No similar benefit with NCRT observed in patients with high CD44 or CD44v6 expression. Bootstrap resampling confirmed the predictive effect of CD44 (Interaction P = 0.015) and CD44v6 (Interaction P = 0.041) for OS. Multivariable Cox analysis revealed an independent negative prognostic role of CD98hc membrane expression for LRC [HR (95% CI) = 0.63(0.39-1.0)] and OS[HR (95% CI) = 0.62 (0.40-0.95)]. CONCLUSIONS: CD44 and CD44v6 are potential predictive biomarkers for NCRT response. CD98hc emerged as an independent negative prognostic biomarker. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).

Weakly supervised learning on unannotated H&E-stained slides predicts BRAF mutation in thyroid cancer with high accuracy.

Deep neural networks (DNNs) that predict mutational status from H&E slides of cancers can enable inexpensive and timely precision oncology. Although expert knowledge is reliable for annotating regions informative of malignancy and other known histologic patterns (strong supervision), it is unreliable for identifying regions informative of mutational status. This poses a serious impediment to obtaining higher prognostic accuracy and discovering new knowledge of pathobiology. We used a weakly supervised learning technique to train a DNN to predict BRAF V600E mutational status, determined using DNA testing, in H&E-stained images of thyroid cancer tissue without regional annotations. Our discovery cohort was a tissue microarray of only 85 patients from a single hospital. On a large independent external cohort of 444 patients from other hospitals, the trained model gave an area under the receiver operating characteristic curve of 0.98 (95% CI 0.97-1.00), which is much higher than the previously reported results for detecting any mutation using H&E by DNNs trained using strong supervision. We also developed a visualization technique that can automatically highlight regions the DNN found most informative for predicting mutational status. Our visualization is spatially granular and highly specific in highlighting strong negative and positive regions and moves us toward explainable artificial intelligence. Using t-tests, we confirmed that the proportions of follicular or papillary histology and oncocytic cytology, as noted for each patient by a pathologist who was blinded to the mutational status, were significantly different between mutated and wildtype patients. However, based solely on these features noted by the pathologist, a logistic regression classifier gave an average area under the receiver operating characteristic curve of 0.78 in five-fold cross-validation, which is much lower than that obtained using the DNN. These results highlight the potential of weakly supervised learning for training DNN models for problems where the informative visual patterns and their locations are not known a priori. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Solitary Bone Plasmacytoma of Humerus Presenting as a Nonhealing Fracture in a Child: A Rare Entity.

Solitary bone plasmacytoma is an extremely rare entity and is characterized by localized proliferation of monoclonal plasma cells. Plasmacytomas are extremely rare in the pediatric population. The median age at diagnosis is usually the fifth or sixth decade, with axial skeleton being more commonly involved than appendicular. We hereby, report the case of a 13-year-old boy with solitary bone plasmacytoma of the right humerus. Though extremely rare in the pediatric age group, plasmacytomas may be considered as one of the remote differentials in children presenting with solitary bone tumors.

Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab.

BACKGROUND: Anti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients. METHODS: Treatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models. RESULTS: Baseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42-0.93)], LRC [HR (95% CI) = 0.56 (0.37-0.86)] and OS [HR (95% CI) = 0.63 (0.43-0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37-0.82), LRC:HR (95% CI) = 0.55 (0.36-0.85) and OS:HR (95% CI) = 0.54 (0.36-0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008). CONCLUSIONS: High HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT. CLINICAL TRIAL REGISTRATION: Registered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).

Tuberculous brain abscesses in immunocompetent patients: A decade long experience with nine patients.

OBJECTIVE: To describe the clinical presentation, radiological findings, management details, and outcome in nine cases of tuberculous brain abscess (TBA). MATERIALS AND METHODS: Nine patients (5 females, 4 males) harboring a TBA, as defined by the Whitener's criteria, were managed over a span of one and a half decade by the authors. All, except one patient, underwent contrast-enhanced magnetic resonance imaging scans, followed by surgical excision of the abscesses due to the failure of complete resolution of the lesion after its drainage using a burr-hole. RESULTS: The infra-tentorial location (n = 4) in TBAs was as common as the supra-tentorial location (n = 4). All large TBAs (more than 3 cm in diameter) failed to resolve after tapping of the purulent material and required surgical excision for a favorable long-term outcome. Two patients expired, while seven patients survived with Karnofsky Performance scale of 90 for 3, 80 for 3, and 70 for 1 patient. The follow-up ranged from 2 to 12 years (mean = 5.7 years). CONCLUSION: TBAs should be considered in the list of differential diagnoses for pyogenic abscesses, especially in developing countries, as it is difficult to differentiate between them on the basis of clinical or radiological findings. Hence, all pus samples should be sent for Ziehl-Neelsen staining and culture for Mycobacterium tuberculosis. Surgically excised and pathologically evaluated specimens remain the gold-standard for diagnosing TBAs. Larger abscesses warrant surgical excision, while concomitantly associated smaller lesions tend to resolve with prolonged antituberculous therapy.

Selection and evolution in the genomic landscape of copy number alterations in ductal carcinoma in situ (DCIS) and its progression to invasive carcinoma of ductal/no special type: a meta-analysis.

Ductal carcinoma in situ (DCIS) is a pre-invasive malignancy detected with an increasing frequency through screening mammography. One of the primary aims of therapy is to prevent local recurrence, as in situ or as invasive carcinoma, the latter arising in half of the recurrent cases. Reliable biomarkers predictive of its association with recurrence, particularly as invasive disease, are however lacking. In this study, we perform a meta-analysis of 26 studies which report somatic copy number aberrations (SCNAs) in 288 cases of 'pure' DCIS and 328 of DCIS associated with invasive carcinoma, along with additional unmatched cases of 145 invasive carcinoma of ductal/no special type (IDC) and 50 of atypical ductal hyperplasia (ADH). SCNA frequencies across the genome were calculated at cytoband resolution (UCSC genome build 19) to maximally utilize the available information in published literature. Fisher's exact test was used to identify significant differences in the gain-loss distribution in each cytoband in different group comparisons. We found synchronous DCIS to be at a more advanced stage of genetic aberrations than pure DCIS and was very similar to IDC. Differences in gains and losses in each disease process (i.e. invasive or in situ) at each cytoband were used to infer evidence of selection and conservation for each cytoband and to define an evolutionary conservation scale (ECS) as a tool to identify and distinguish driver SCNA from the passenger SCNA. Using ECS, we have identified aberrations that show evidence of selection from the early stages of neoplasia (i.e. in ADH and pure DCIS) and persist in IDC; we postulate these to be driver aberrations and that their presence may predict progression to invasive disease.

TFE3 rearranged epithelioid hemangioendothelioma of the lymph node: A rare primary presentation of vascular tumor.

ABSTRACT: Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor that has been described in numerous sites such as soft tissue, liver, and lungs. However, primary lymph nodal presentation of hemangioendothelioma is extremely rare. We present a 49-year-old male patient who presented with an inguinal mass but was otherwise asymptomatic. Clinical and radiological workup failed to reveal any other primary lesion. The lymph node was excised and the histomorphological examination showed an epithelioid and spindle neoplasm with chondromyxoid stroma. The diagnosis of epithelioid hemangioendothelioma was suspected based on histomorphology and immunohistochemistry, which showed diffuse positivity for CD31, CD34, and TFE3 stains. This was further confirmed by the fluorescent in-situ hybridization (FISH) technique that showed TFE3 gene rearrangement.

Spindle Cell Lipoma and Pleomorphic Lipoma in the Head and Neck: A Comprehensive Study of Six Cases With Review of Literature.

BACKGROUND: Spindle cell lipomas (SL) and pleomorphic lipomas (PL) are rare variants of lipomas, occurring predominantly in the head and neck region. Laryngeal SL/PL is very uncommon and causes obstructive symptoms needing immediate intervention. These tumors are often challenging in radiology due to the admixture of elements and the presence of adipose tissue may help in diagnosis. From a surgeon's perspective, understanding the nuances of SL/PL is paramount. Histology is the gold standard for diagnosis; however, it often causes diagnostic challenges in biopsy.  Method: A retrospective review of the clinical and pathologic features of archival cases of SL/PL was performed. RESULTS: A total of six cases of head and neck region SL/PL were identified. The age of patients ranged from 21 to 58 years and the male-to-female ratio was 5:1. The tumors were distributed in the nape of the neck (n=3), laryngeal region (n=2), and orbit (n=1). Histology in all the cases showed a low-grade neoplasm composed of a variable amount of spindle cells and adipose tissue. The stroma was myxoid in most cases. CD34 was diffusely positive in all the cases. CONCLUSION: SLs are a rare and uncommon variant of lipoma with a predilection in the head and neck region. They are low-grade neoplasms with a propensity to recur after years. Having knowledge of this tumor can improve surgical outcomes and better patient care.

Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging.

PURPOSE: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. METHODS: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. RESULTS: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model's accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). CONCLUSIONS: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.

Light chain proximal tubulopathy without crystals in a case of Burkitt lymphoma presenting with acute kidney injury.

Acute kidney injury is a common manifestation of malignancies, either directly by the tumor or indirectly from anticancer therapy. The pathologic correlates of acute kidney injury in malignancies are many and can be diagnosed conclusively using kidney biopsy. We report a rare case of a patient with light chain proximal tubulopathy without crystals who presented with acute kidney injury. Kidney biopsy showed proximal tubulopathy without crystals with λ light chain restriction. Detailed investigations lead to a diagnosis of Burkitt lymphoma with surface λ light chain restriction.

Hepatocellular carcinoma (HCC) masquerading as hilar cholangiocarcinoma: An unusual presentation of jaundice.

Jaundice usually occurs in the late stages of hepatocellular carcinoma (HCC). Obstructive jaundice is rarely seen as an initial presentation of HCC, as opposed to cholangiocarcinoma. Various causes of obstructive jaundice in these cases also known as "Icteric HCC" have been described such as tumour thrombi, compression, infiltration or tumours arising from native hepatocytes in the bile duct. We present a case of 74-year-old gentleman with "Icteric HCC" that clinically and radiologically mimicked cholangiocarcinoma for which the patient underwent left hepatectomy with Roux-en-Y hepaticojejunostomy. Histopathology revealed dilated large duct with polygonal sheets of cells of hepatoid morphology which stained diffusely positive for both glypican 3 and Hep-par 1. The epicentre was in the left hepatic duct with no discernible liver lesion and the tumour probably originated from the ectopic hepatocytes within the biliary duct The patient was disease free at 1.5 years of follow up. In conclusion, HCC should be a differential for obstructive jaundice. Patients with such "Icteric HCC" benefit from surgical resection with favourable outcomes. The prognosis in such patients is better than in patients of HCC with jaundice due to hepatic insufficiency.

Nonsalivary Primary Adenocarcinomas of the Base of the Tongue: A Single Tertiary-Care Oncology Center Series of 6 Cases.

CONTEXT.­: Nonsalivary primary adenocarcinomas of the base of the tongue (PABOTs) are extremely rare and worth reporting. OBJECTIVE.­: To study the detailed clinicopathologic features of PABOT. DESIGN.­: Cases of PABOT diagnosed on pathology material were retrieved from the archived electronic surgical pathology records. RESULTS.­: Six cases in 4 men and 2 women (M:F ratio, 2:1), with an age range of 31 to 76 years, satisfied the criteria. The tumor epicenter was the base of the tongue in all (6 of 6; 100%), with extension to the epiglottis in 50% (3 of 6), nodal metastasis in 66.7% (4 of 6), and distant metastasis in 33.3% (2 of 6). On histology, all but one were pure adenocarcinoma. Five of 6 cases (83.3%) had a gastrointestinal (GI) phenotype, of which 2 (40%) had a colonic/lower-GI-type (small groups of cells floating in mucin, CK20+, SATB2+, and CDX2+) and 3 (60%) had an upper-GI-like adenocarcinoma (UGI-LA; malignant glands with intracellular mucin, CK7+) histology. Cystic structure suggestive of teratomatous origin was identified in 2 of 5 cases (40%), both with UGI-LA phenotype. The non-GI-type case had a unique histology with squamous differentiation in addition to adenocarcinoma areas, diffuse nuclear ß-catenin on immunohistochemistry, and a corresponding exon 3 CTNNB1 mutation. One patient succumbed to disease, and 4 are alive with disease (follow-up of 1-9 months after completion of therapy). CONCLUSIONS.­: We suggest using the broad term primary adenocarcinomas of the base of tongue (PABOTs), which can be further subdivided into colonic-type adenocarcinoma of the tongue and oral cavity, UGI-LA, and not otherwise specified categories, and reiterate a need for recognition and distinction of PABOT from salivary gland tumors. A subset originates from teratoid/duplication cysts, necessitating extensive sampling. Multicentric studies are essential to clinically and biologically prognosticate each of these categories.

Histoplasmosis of the Head and Neck Region Mimicking Malignancy: A Clinic-Pathological Predicament.

OBJECTIVE: Histoplasmosis is a systemic, deep mycotic infection caused by Histoplasma capsulatum. Disseminated histoplasmosis (DH) is synonymous with HIV seropositive immunocompromised individuals; however, isolated histoplasmosis involving the head and neck mucosal sites mimicking malignancy is a clinical predicament. The result, in a superficial biopsy with marked pseudoepitheliomatous hyperplasia (PEH), in a tertiary care cancer center where the number of squamous carcinomas far outnumber the infectious diseases, could be catastrophic. MATERIAL AND METHOD: The archives of a tertiary care cancer hospital were searched (2010-2019) for cases of histoplasmosis involving the head and neck mucosal sites in HIV non-reactive patients. RESULTS: Six cases of isolated head and neck histoplasmosis were seen in biopsies from 4 men and 2 women, with an age range of 46-72 years. Three of these patients suffered from chronic illnesses. The most common site involved was the larynx (vocal cords) in three cases, two cases were involving lips, and one involving the tongue. The biopsies were reviewed in-house with a clinical diagnoses of malignancy in all and an outside biopsy diagnosis of "squamous cell carcinoma" in 2 cases. The important histological findings in the biopsy were PEH (3 cases), granulomas (2 cases), lymphoplasmacytic inflammation (all cases). Eosinophils were conspicuous by their absence. Intracellular histoplasma was seen in all cases, albeit to varying density, which was confirmed with GMS stain. CONCLUSION: A high index of suspicion, meticulous history taking by oncologists, and appropriate distinction of PEH from neoplastic squamous proliferation by pathologists in superficial biopsies and an apropos deeper wedge biopsy are essential to clinch the correct diagnosis.

HRAS-mutated primary thyroid malignant melanoma or medullary thyroid carcinoma with melanocytic dedifferentiation? A singular case with an ontogeny-phylogeny quandary.

Melanotic pigment in the thyroid is practically synonymous with chronic minocycline therapy and rare cases of melanotic medullary thyroid carcinoma. However, primary melanoma of the thyroid has not been reported yet. We report a rare case of a 25-year-old male with a locally aggressive thyroid mass and distant metastases at presentation. Radiologically, a 8.3×7.6-cm nodule was identified in the right thyroid lobe. Fine-needle aspiration cytology (FNAC) showed discohesive atypical plasmacytoid cells with prominent nucleoli and no cytoplasmic pigmentation. Serum calcitonin levels were normal. A trucut biopsy showed a malignant tumor with a similar cytomorphology, including marked nuclear pleomorphism. In addition, intracytoplasmic melanin was seen in <1% of cells. Tumor cells were immunonegative for AE1/AE3, TTF1, synaptophysin, and chromogranin while positive for SOX10, S100P, HMB45, and Melan A, confirming the diagnosis of malignant melanoma, without any detectable MTC component in the biopsy. An HRAS G13R mutation was detected on NGS, which, intriguingly, is a known mutation in MTC, and exceedingly rare in melanocytic lesions. No other clinically or radiologically apparent primary lesion was identified elsewhere in the patient. The unusual histology and hitherto unreported molecular findings make this case of primary thyroid melanocytic neoplasm worth reporting. Abstruse origin of melanoma cells in the thyroid gland with molecular signature suggestive of MTC in our case raises a nomenclature and management conundrum, prompting us to revisit the "ontogeny recapitulates phylogeny" theory.

Efficient quality control of whole slide pathology images with human-in-the-loop training.

Histopathology whole slide images (WSIs) are being widely used to develop deep learning-based diagnostic solutions, especially for precision oncology. Most of these diagnostic softwares are vulnerable to biases and impurities in the training and test data which can lead to inaccurate diagnoses. For instance, WSIs contain multiple types of tissue regions, at least some of which might not be relevant to the diagnosis. We introduce HistoROI, a robust yet lightweight deep learning-based classifier to segregate WSI into 6 broad tissue regions-epithelium, stroma, lymphocytes, adipose, artifacts, and miscellaneous. HistoROI is trained using a novel human in-the-loop and active learning paradigm that ensures variations in training data for labeling efficient generalization. HistoROI consistently performs well across multiple organs, despite being trained on only a single dataset, demonstrating strong generalization. Further, we have examined the utility of HistoROI in improving the performance of downstream deep learning-based tasks using the CAMELYON breast cancer lymph node and TCGA lung cancer datasets. For the former dataset, the area under the receiver operating characteristic curve (AUC) for metastasis versus normal tissue of a neural network trained using weakly supervised learning increased from 0.88 to 0.92 by filtering the data using HistoROI. Similarly, the AUC increased from 0.88 to 0.93 for the classification between adenocarcinoma and squamous cell carcinoma on the lung cancer dataset. We also found that the performance of the HistoROI improves upon HistoQC for artifact detection on a test dataset of 93 annotated WSIs. The limitations of the proposed model are analyzed, and potential extensions are also discussed.

Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial.

Objective: Interpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation. Methods: Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status. Results: Out of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%. Conclusion: The accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.

Role of imaging in the management of thyroglossal duct cyst carcinomas (TGC-TIRADS): a single centre retrospective study over 16 years.

Introduction: Thyroglossal duct cyst (TGDC) is the most frequently encountered developmental anomaly in thyroid genesis with a reported incidence of 7% in the adult population. The cyst is known to develop anywhere along the pathway of thyroid descent but is more frequently seen in the infrahyoid neck in the midline. The incidence of malignancy in a TGDC is approximately 1%; a majority of these are papillary carcinomas. This study was conducted at a single tertiary care centre which spanned over a decade which adds practice changing evidence-based knowledge to existing literature on this rare entity. A comprehensive study which conclusively establishes the imaging features predictive of malignancy in TGDC carcinomas (TGDCa), the protocol for optimal management, clinical outcome and long-term survival of these patients is not available. Although TGDC carcinoma is thought to have an excellent prognosis, there is not enough data available on the long-term survival of these patients. The aim of this study was to identify whether neck ultrasound (US) can serve as an accurate imaging tool for the preoperative diagnosis of TGDC carcinomas. Methods: We accessed the electronic medical records of 86 patients with TGDC between January 2005 to December 2021. Of these, 22 patients were detected with TGDC papillary carcinoma on histopathologic examination. Relevant imaging, treatment and follow up information for all cases of TGDC carcinoma were retrospectively reviewed. We compared US characteristics predictive of malignancy across outcomes groups; malignant vs benign using the Chi-square test. Based on the results, a TGC-TIRADS classification was proposed with calculation of the percentage likelihood of malignancy for each category. Results: Compared to benign TGDCs, malignant TGDCs were more likely to present with following US characteristics: irregular or lobulated margins (90.40 vs. 38.10%), solid-cystic composition (61.90 vs. 17.07%), internal vascularity (47.62 vs. 4.88 %), internal calcification (76.19 vs. 7.32 %) (each p value < 0.005). Calcifications and internal vascularity were the most specific while irregular/lobulated margins were the most sensitive feature for malignancy. AUC under the ROC curve was 0.88. Allpatients were operated and were disease free at the end of 5 years or till the recent follow up. Discussion: US is the imaging modality of choice for pre-operative diagnosis of TGDC carcinoma. Thepre-operative diagnosis and risk stratification of thyroglossal lesions will be aided by the application of the proposed TGC-TIRADS classification, for which the percentage likelihood of malignancy correlated well with the results in our study. Sistrunk procedure is adequate for isolated TGDC carcinoma; suspicious neck nodes on imaging also necessitates selective nodal dissection. Papillary carcinomas have an excellent prognosis with low incidence of disease recurrence.