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.

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.

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.

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.

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.

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.

Association of Cutibacterium acnes with human thyroid cancer.

Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.

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.

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.

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.

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.

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.

MR imaging-based risk stratification scoring system to predict clinical outcomes in carotid body tumors.

Objectives: This study aims to evaluate the role of pretherapy MRI in predicting outcomes in carotid body tumors and propose a grading system for high- and low-risk characteristics. Materials and methods: A retrospective observational study of 44 patients with 51 lesions was carried out from year 2005 to 2020. MR images were reviewed for characteristics of carotid body tumor, and a score was given that was correlated with intra- and postoperative findings. The various other classifications and our proposed Mahajan classification were compared with Shamblin's classification. The area under the curve and ROC curves were used to present the accuracy of different predictive models. Results: Our scoring system allotted a score of 0 to 15 on the basis of MRI characteristics, with scores calculated for patients in our study ranging from 0 to 13. Lesions with scores of 0-6 were considered low risk (45%), and scores of 7-15 were regarded as high risk for surgery (55%). The Mahajan classification stages tumors into four grades: I (10%), II (20%), IIIa (8%), and IIIb (62%). The frequency of vascular injury was 50% in category I and 64% in category IIIb. The frequency of cranial nerve injury was 50%, 66%, and 27% in categories I, II, and IIIb. Conclusion: The Mahajan classification of CBTs evaluates high-risk factors like the distance of the tumor from the skull base and the angle of contact with ICA, which form the major predictors of neurovascular damage and morbidity associated with its surgery. Though the Shamblin classification of CBT is the most widely accepted classification, our proposed Mahajan classification system provides an imaging-based alternative to prognosticate surgical candidates preoperatively.

Cautious Artificial Intelligence Improves Outcomes and Trust by Flagging Outlier Cases.

PURPOSE: Artificial intelligence (AI) models for medical image diagnosis are often trained and validated on curated data. However, in a clinical setting, images that are outliers with respect to the training data, such as those representing rare disease conditions or acquired using a slightly different setup, can lead to wrong decisions. It is not practical to expect clinicians to be trained to discount results for such outlier images. Toward clinical deployment, we have designed a method to train cautious AI that can automatically flag outlier cases. MATERIALS AND METHODS: Our method-ClassClust-forms tight clusters of training images using supervised contrastive learning, which helps it identify outliers during testing. We compared ClassClust's ability to detect outliers with three competing methods on four publicly available data sets covering pathology, dermatoscopy, and radiology. We held out certain diseases, artifacts, and types of images from training data and examined the ability of various models to detect these as outliers during testing. We compared the decision accuracy of the models on held-out nonoutlier images also. We visualized the regions of the images that the models used for their decisions. RESULTS: Area under receiver operating characteristic curve for outlier detection was consistently higher using ClassClust compared with the previous methods. Average accuracy on held-out nonoutlier images was also higher, and the visualizations of image regions were more informative using ClassClust. CONCLUSION: The ability to flag outlier test cases need not be at odds with the ability to accurately classify nonoutliers in AI models. Although the latter capability has received research and regulatory attention, AI models for clinical deployment should possess the former as well.

Prevention of carcinogen-induced oral cancers by polymeric black tea polyphenols via modulation of EGFR-Akt-mTOR pathway.

The overexpression of Epidermal Growth Factor Receptor (EGFR) and dysregulation of its downstream effector pathways are important molecular hallmarks of oral cancers. Present study investigates the chemopreventive potential of polymeric black tea polyphenols (PBPs)/thearubigins (TRs) in the hamster model of oral carcinogenesis as well as determine the effect of PBPs on EGFR and the molecular players in the EGFR pathway. In dose-dependent manner, pre and concurrent treatment with PBPs (1.5%, 5%, 10%) decreased the number and volume of macroscopic tumors as well as the number and area of microscopic lesions. Interestingly, at 10% dose of PBPs, no macroscopic or microscopic tumors were observed. We observed PBPs mediated dose-dependent decrease in oxidative DNA damage (8OHdG); inflammation (COX-2); proliferation (PCNA, Cyclin D1); expression of EGFR, and its downstream signaling kinases (pAkt, Akt, and mTOR); hypoxia (HIF1α) and angiogenesis (VEGF). There was also a PBPs mediated dose-dependent increase in apoptosis (Bax). Thus, our data clearly indicate that the observed chemopreventive potential of PBPs was due to modulation in the EGFR pathway associated with cell proliferation, hypoxia, and angiogenesis. Taken together, our results demonstrate preclinical chemopreventive efficacy of PBPs and give an insight into its mechanistic role in the chemoprevention of experimental oral cancer.

Sentinel node biopsy in node negative early oral cancers: Solution to the conundrum!

Ideal management of the node-negative neck in early oral cancers is a debated issue. Elective neck dissection (END) is recommended in these patients as it offers a survival benefit. However, about 50-70% of patients who do not harbor occult metastasis are overtreated with this approach. Surgery is associated with morbidity, predominantly shoulder dysfunction. Numerous attempts have been made to identify true node-negative patients through imaging and prediction models but none have high diagnostic accuracy to safely spare the neck dissection. The recent publications of 2 large randomized controlled trials comparing the outcomes of sentinel node biopsy (SNB) and END have spurred interest in SNB. Both the trials reported SNB to be an oncologically safe procedure and spared unnecessary neck dissections. The functional outcomes of the trials showed that SNB limits the morbidity compared to END, which albeit evens out at the end of one-year post-surgery. Despite its benefits, SNB has failed to gain widespread acceptability due to various limitations including the need for infrastructure, equipment costs, staff, and multidisciplinary collaboration of nuclear medicine, surgical, and pathology fraternity. The labor-intensive pathology protocol with serial step sectioning and immunohistochemistry poses a challenge to the feasibility at a high-volume center. This perspective discusses these limitations and propose plausible solutions to the conundrum. To make it widely applicable and feasible across the globe efforts should be directed to understand biology better, find novel solutions, and implement the lessons learned over decades from other sites.

Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy.

Objective: Extra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT. Materials and Methods: Open-label, investigator-initiated, randomized controlled trial (RCT) (2012-2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS). Results: A total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS. Conclusion: Pre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography-contrast-enhanced CT, and ultrasound.

An Audit of Systemic Therapy in Medullary Carcinoma Thyroid.

There is a paucity of evidence of the impact of sorafenib on MCT and it is the preferred therapy used in India. We decided to do an audit of all patients of MCT who were referred to us for systemic therapy. The objective of this exercise was to identify the treatment pattern, outcomes, and adverse events with therapy in MCT. Baseline demographics (age, gender, ECOG PS, comorbidities, habits), tumor details (site of metastasis), previous treatment details, clinical features at metastasis (symptomatic or asymptomatic), the pattern of treatment, adverse events (CTCAE version 4.02), date of progression, date of death and status, and follow-up were extracted from the rare tumor database and electronic medical records. Out of 75 patients referred for therapy for MCT, 47 (62.7%) patients were considered for immediate tyrosine kinase inhibitors as they had symptomatic status and 28 (37.3%) patients were kept on observation due to the asymptomatic nature of the disease. Out of the 28 patients, 15 (53.6%, n = 28) patients were subsequently started on TKI while in 13 (46.4%, n = 28) patients observation was continued. In the overall cohort, the median PFS was 18.9 months (95% CI 11.9-29.9) and OS was 26.6 months (95% CI 14.4-39.0). Among variables tested, only female gender had an impact on PFS (hazard ratio = 0.364 95% CI 0.148-0.895; P = 0.028) and the absence of lung metastasis had a positive impact on OS (hazard ratio = 0.443 95% CI 0.207-0.95; P = 0.037). Most commonly used TKI was sorafenib (n = 61) and sunitinib in 1 patient. The most common adverse events with TKI were palmo-plantar dysesthesia (50, 80.6%) and oral mucositis (25, 40.2%). The strategy of treating symptomatic MCT and observing in asymptomatic MCT is associated with reasonable PFS and OS. Sorafenib is the most commonly used TKI in our setup and provides similar outcomes as globally.