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Signet ring cell carcinoma, in general, is a peculiar tumour. There is always a query regarding its exact site of origin. Even, immunohistochemistry shows overlapping staining patterns between various sites. On one hand, signet ring cell carcinoma of the bladder is a rare occurrence, but on the other hand metastatic signet ring cell carcinoma to the bladder is not uncommon. However, without prior knowledge of the primary site of tumour clinically and radiologically, definitive diagnosis is challenging based on morphology and immunohistochemistry.

Aims Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. Methods and results From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. Conclusions In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

Objectives This study sought to report P-wave morphology (PWM) from a series of paraseptal (PS) atrial tachycardia (AT), revise then prospectively evaluate a simplified PWM algorithm against a contemporary consecutive cohort with focal AT. Background The 2006 PWM algorithm was useful in predicting the origin of focal AT. An updated algorithm was developed given advances in multipolar 3-dimensional mapping, potential limitations of PWM in separating PS sites, and a renewed interest in the P-wave in mapping non–pulmonary vein triggers. Methods The PWM from a consecutive series of 67 patients with PS AT were analyzed. PS sites included were coronary sinus ostium, perinodal, left and right septum, septal tricuspid annulus, superior mitral annulus, and noncoronary cusp. Next the P-wave algorithm was revised and prospectively evaluated by 3 blinded assessors. Results The P-wave for PS sites was neg/pos (n = 50), iso/pos (n = 10), or isoelectric (n = 4) in lead V1 (96%). The P-wave algorithm was modified and prospectively applied to 30 consecutive patients with focal AT who underwent successful ablation. Foci (n = 30) originated from the right atrium (33.3%), left atrium (30%), and PS (36.7%). Using the PW algorithm, the correct anatomic location was identified in 93%. Incorrect interpretation of the terminal positive P-wave component (n = 3) and initial negative P-wave deflection (n = 1) in lead V1 misidentified 4 paraseptal cases. Conclusions The revised PWM algorithm offers a simplified and accurate method of localizing the responsible site for focal AT. The P-wave remains an important first step in mapping atrial arrhythmias.

INTRODUCTION Before ablation, predicting the site of origin (SOO) of outflow tract ventricular arrhythmia (OTVA), can inform patient consent and facilitate appropriate procedural planning. We set out to determine if OTVA variability can accurately predict SOO. METHODS Consecutive patients with a clear SOO identified at OTVA ablation had their prior 24-h ambulatory ECGs retrospectively analysed (derivation cohort). Percentage ventricular ectopic (VE) burden, hourly VE values, episodes of trigeminy/bigeminy, and the variability in these parameters were evaluated for their ability to distinguish right from left-sided SOO. Effective parameters were then prospectively tested on a validation cohort of consecutive patients undergoing their first OTVA ablation. RESULTS High VE variability (coefficient of variation ≥0.7) and the presence of any hour with

Background Electrocardiographic (ECG) criteria have been proposed to localize the site of origin of outflow region ventricular arrhythmias (VAs). Many factors influence the QRS morphology of VAs and may limit the accuracy of these criteria. Objective The purpose of this study was to assess the accuracy of ECG criteria that differentiate right from left outflow region VAs and localize VAs within the aortic sinus of Valsalva (ASV). Methods One hundred one patients (mean age 52 ± 16 years; 55 [54%] women) undergoing catheter ablation of right ventricular outflow tract (RVOT) or ASV VAs with a left bundle branch block, inferior axis morphology were studied. ECG measurements including V2 transition ratio, transition zone index, R-wave duration index, R/S amplitude index, V2S/V3R index, V1–3 QRS morphology, R-wave amplitude in the inferior leads were tabulated for all VAs. Comparisons were made between the predicted site of origin using these criteria and the successful ablation site. Results Patients had successful ablation of 71 RVOT and 38 ASV VAs. For the differentiation of RVOT from ASV VAs, the positive predictive values and negative predictive values for all tested ECG criteria ranged from 42% to 75% and from 71% to 82%, respectively, with the V2S/V3R index having the largest area under the curve of 0.852. Morphological QRS criteria in leads V1 through V3 did not localize ASV VAs. The maximum R-wave amplitude in the inferior leads was the sole criterion demonstrating a significant difference between right ASV, right-left ASV commissure, and left ASV sites. Conclusion ECG criteria for differentiating right from left ventricular outflow region VAs and for localizing ASV VAs have a limited accuracy.

Cancer of unknown primary (CUP) is a heterogenous group of cancers for which the anatomical site of origin is unidentifiable on the basis of standard evaluation and imaging. CUPs account for 2-5% of all malignancies and are characterized by early metastatic dissemination, aggressive clinical course, and poor response to palliative chemotherapy. It is important to identify favorable-risk CUP patients (10-20%), as they harbor chemo-sensitive and potentially curable tumors, and may require long-term disease control. Empirical combination chemotherapy has traditionally been the standard first-line therapy for most patients (80-90%), who do not belong to favorable-risk subsets; however, this approach has only modest benefits, with a median overall survival of < 1 year. Evidence supporting the clinical use of molecular tissue of origin (TOO) tests is still lacking. Two recent randomized clinical trials failed to show the benefit of TOO-based site-specific therapy over empirical chemotherapy. In an era of precision medicine, the use of comprehensive molecular profiling will provide opportunities to identify patient subsets who are susceptible to targeted therapies and immunotherapies. (Korean J Med 2021;96:408-414)

Multiple ECG algorithms exist to localize outflow tract PVCs. They can be invaluable in pre-procedure planning and patient counseling. We describe a case where the published algorithm for PVC localization did not predict the site of origin and successful ablation site. This case highlights the strengths and limitations of established ECG PVC localization algorithms.

Multiple theories have been discussed about the etiopathogenesis of congenital middle ear cholesteatoma (CMEC) and its specific site of origin. The intraoperative identification of the precise location of the keratinous mass is important to guarantee its complete removal, in order to reduce the risk of recurrence. This study proposes the tensor tympani tendon (TTT) as a possible site of origin of CMEC. All CMECs treated between 2013 and 2019 were reviewed. Only Potsic stage I lesions were included. Preoperative radiologic images were compared to intraoperative findings. Three removed TTT were sent for histologic evaluation. Seven patients were included (M:F = 3:4). Preoperative CT images were classified as type A in 2 cases (28.6%) and type B in 5 cases (71.4%). At intraoperative evaluation all CMEC sacs were found pedunculated on the TTT. The histologic examinations confirmed the connection between the cholesteatomatous sac and the TTT. According to the correlation of imaging, intraoperative findings and histology, we proposed that the TTT could be the primary site from which CMEC originates.

Cancer of unknown primary (CUP) origin is an enigmatic group of diagnoses in which the primary anatomical site of tumour origin cannot be determined1,2. This poses a considerable challenge, as modern therapeutics are predominantly specific to the primary tumour3. Recent research has focused on using genomics and transcriptomics to identify the origin of a tumour4–9. However, genomic testing is not always performed and lacks clinical penetration in low-resource settings. Here, to overcome these challenges, we present a deep-learning-based algorithm—Tumour Origin Assessment via Deep Learning (TOAD)—that can provide a differential diagnosis for the origin of the primary tumour using routinely acquired histology slides. We used whole-slide images of tumours with known primary origins to train a model that simultaneously identifies the tumour as primary or metastatic and predicts its site of origin. On our held-out test set of tumours with known primary origins, the model achieved a top-1 accuracy of 0.83 and a top-3 accuracy of 0.96, whereas on our external test set it achieved top-1 and top-3 accuracies of 0.80 and 0.93, respectively. We further curated a dataset of 317 cases of CUP for which a differential diagnosis was assigned. Our model predictions resulted in concordance for 61% of cases and a top-3 agreement of 82%. TOAD can be used as an assistive tool to assign a differential diagnosis to complicated cases of metastatic tumours and CUPs and could be used in conjunction with or in lieu of ancillary tests and extensive diagnostic work-ups to reduce the occurrence of CUP. A deep-learning-based algorithm uses routinely acquired histology slides to provide a differential diagnosis for the origin of the primary tumour for complicated cases of metastatic tumours and cancers of unknown primary origin.

Background Noninvasive electroanatomic mapping (NIEAM) demonstrate patterns of depolarization that are useful in identifying the chamber of origin (COO) in outflow tract ventricular arrhythmias (OTVA). However, its use in predicting exact site of origin (SOO) has not yet been validated. Methods NIEAMs (CardioInsight, Medtronic) from 40 patients (age 62.5 ± 2.6) undergoing ablation for OTVA were reviewed for diagnostic accuracy in predicting the SOO. Earliest arrhythmia breakout and directionality of earliest instantaneous unipolar electrograms (uEGMs) on NIEAMs were evaluated subjectively by two observers for quality and amplitude. Sites with most negative earliest uEGMs on right and left ventricular outflow tracts, as well as epicardial surface were manually identified. Using NIEAM-based activation timing of the lateral mitral annulus and basal septum COO was identified for each OTVA. Predictions of SOO using NIEAMs was compared with true SOO from invasive study. NIEAMs SOO predictions were compared with subjective 12 lead electrocardiogram (ECG) review by two observers. Results Review of arrhythmia breakout and signal directionality had poor diagnostic value in predicting SOO in OTVA (50.6% and 49.4%, 56.6% and 43.4%, respectively) and underperformed compared with ECG interpretation (59.1% and 80.5%). After excluding uEGMs with poor characteristics, the uEGM with most negative amplitude at the COO was predictive of the true SOO with 96.4% sensitivity and specificity. Conclusion We propose a stepwise approach when interpreting NIEAMs for OTVA where patterns of activation are evaluated first to determine the COO, followed by identification of the site with most negative amplitude instantaneous uEGM to determine SOO.

Desmoid fibromatosis (DF) arising from musculoaponeurotic structures rarely affects the head and neck region with the abdomen being the most common site of origin. These are benign tumors with locally infiltrative nature usually presenting as painless swellings that are rapidly growing. The infratemporal fossa DF is an extremely rare location with few clinical reports. This article discusses the management of a 2-year-old child with DF of the infratemporal fossa (ITF) along with literature review.

Metastasis is the ultimate “survival of the fittest” test for cancer cells, as only a small fraction of disseminated tumor cells can overcome the numerous hurdles they encounter during the transition from the site of origin to a distinctly different distant organ in the face of immune and therapeutic attacks and various other stresses. During cancer progression, tumor cells develop a variety of mechanisms to cope with the stresses they encounter, and acquire the ability to form metastases. Restraining these stress-releasing pathways could serve as potentially effective strategies to prevent or reduce metastasis and improve the survival of cancer patients. Here, we provide an overview of the tumor-intrinsic, microenvironment- and treatment-induced stresses that tumor cells encounter in the metastatic cascade and the molecular pathways they develop to relieve these stresses. We also summarize the preclinical and clinical studies that evaluate the potential therapeutic benefit of targeting these stress-relieving pathways.

Recently, Muhlemann et al. (2018) and Krause-Kyora et al. (2018) discovered 15 ancient Hepatitis B virus (aHBV) sequences dating back to the Neolithic age (NA) and the Bronze age (BA). Being published simultaneously, neither of these studies could include sequences from the other for analyses. In the present research, aHBV sequences from these studies were collective re-analysed with reference to a comprehensive database comprising extant HBV diversity to understand their relatedness and role in the evolution of extant HBV diversity. Present analyses revealed several interesting findings on distribution, dispersal, phylogenetic and recombinational relatedness of ancient HBV to extant genotypes, which were not recognized previously. Several interesting recombination patterns were observed, which corroborated well with ancient human migration, shown by the human genetic studies. Present analyses suggest that comparable to the replacement of the Neolithic European farmer associated Y chromosome haplogroups by haplogroups associated with the steppe people during Steppe migration, HBV genotype associated with the early Neolithic European farming cultures was also replaced by the ancestral HBV genotype A probably carried by the migrating steppe people, and a variant of this genotype is the prevalent HBV genotype in contemporary European populations. Additionally, based on recent literature, this research also indicates that HBV genotype divergence estimates proposed by Muhlemann et al., and others cannot sufficiently explain distribution of certain extant HBV genotypes. Hence, an alternative possibility to explain long distance and trans-oceanic distribution of phylogenetically related HBV genotypes was reviewed and discussed in the light of currently available knowledge. Through this manuscript, novel and important findings of the present analyses are communicated.

Objectives This study sought to establish a mapping and ablation strategy to target intramural ventricular arrhythmias (VAs) by identifying the precise arrhythmia site of origin (SOO). Background Radiofrequency ablation of intramural VAs is challenging because the arrhythmia origin is difficult to localize. Methods In 83 consecutive patients with intramural VAs, a stepwise mapping approach was performed: ablation targeted directly the SOO when possible followed by the closest adjacent anatomical structure when necessary. If the SOO could not be identified, the earliest endocardial breakout sites were ablated. Safety and procedural outcomes between patients in whom the SOO could and could not be identified were compared. Results The SOO was identified in 19 of 83 (23%) patients, and radiofrequency ablation was effective in eliminating VAs in all 19 (100%) patients by ablation at the SOO alone (n = 3), at the SOO and an anatomically adjacent area (n = 7), or at an anatomically adjacent area alone (n = 9). Breakout site mapping and ablation in the remaining 64 patients in whom the SOO was not identified was effective in 43 of 64 patients, which was significantly less than in patients in whom the SOO was identified (67% vs. 100%; p Conclusions Identification of the SOO was associated with a successful ablation procedure by either targeting the SOO directly or targeting an adjacent anatomical structure. Ablation at the breakout sites of intramural VAs has a lower efficacy than when the SOO can be directly targeted.

The latest WHO classification cleanly divides gastrointestinal neuroendocrine neoplasms into neuroendocrine tumor (NET; well-differentiated, any grade) and neuroendocrine carcinoma (NEC; poorly differentiated, high-grade by definition), along with mixed neuroendocrine-non-neuroendocrine neoplasms. NECs are always aggressive, with multiple mutations; they are treated with chemotherapy. NETs have widely different presentations, behavior, and management depending on site of origin. Esophageal examples are vanishingly rare. Most gastric and appendiceal tumors are indolent, as are many colonic and rectal tumors. The duodenum is home to some unusual variants of NET, and jejunal/ileal NETs frequently metastasize, which impacts their staging and clinical management.

Aims Assess the minimal number of ECGI leads needed to obtain a good spatial resolution. Methods We enrolled 20 patients that underwent ablation of premature ventricular or atrial contractions using Carto and ECGI with AMYCARD. We evaluated the agreement regarding the site of origin of the arrhythmia between the ECGI and Carto, the area and diameter of the earliest activation site obtained with the ECGI (EASa and EASd). Based on previous studies with pacemapping, we considered a good spatial resolution of the ECGI when the EASd measured on the isopotential map was less than 18 mm. In presence of agreement the ECGI was reprocessed: a) with half the number of electrode bands (8 leads per electrode band) and b) with 6 electrode bands. Results The initial map was obtained with 23 (22-23) electrode bands per patient, corresponding to 143 (130-170) leads. Agreement rate was 85%, the median EASa and EASd were: 0.7 (0.5-1.3) cm2 and 9 (8-13) mm. With half the number of electrode bands including 73 (60-79) leads, agreement rate was 80%, the EASa and EASd were: 2.1 (1.5-6.2) cm2 and 16 (14 -28) mm. With only six electrode bands using 38 (30-42) leads, agreement rate was 55%, EASa and EASd were: 4.0 (3.3-5.0) cm2 and 23 (21-25) mm. The number of leads was a predictor of agreement with a good spatial resolution, OR (95% CI) of 1.138 (1.050–1.234), p = .002. According to the ROC curve, the minimal number of leads was 74 (AUC 0.981; 95% CI: 0.949–1.00, p Conclusion Reducing the number of leads was associated with a lower agreement rate and a significant reduction of spatial resolution. However, the number of leads needed to achieve a good spatial resolution was less than the maximal available.

Accessory pathway (AP) mapping is currently based on point-by-point mapping and identifying if a local electrogram’s origin is atrial, pathway, or ventricular, which is time-consuming and prone to insufficient mapping. We sought to determine the feasibility of automated and high-density mapping to define AP location using open-window mapping (OWM), which does not rely on defining the electrogram’s origin but simply detects the sharpest local signal at each point. We enrolled 23 consecutive patients undergoing catheter ablation for atrioventricular reentrant tachycardia. High-density mapping was performed using OWM and ablation was performed. The successful site of ablation was determined by the loss of pathway function. OWM was 100% effective at identifying the successful site of ablation (average mapping time 7.3 ± 4.3 min.) Permanent AP elimination was achieved using a mean radiofrequency energy time of 18.5 ± 24.5 s/patient. Transiently successful ablations were 4.0 ± 1.8 mm from permanently successful sites and had lower contact force (5.1 ± 2.5 g vs. 11.7 ± 9.0 g; P = 0.041). Unsuccessful sites had similar contact force to permanently successful sites (12.2 ± 9.2 g vs. 11.7 ± 9.0 g; P = 0.856) but were 6.4 ± 2.0 mm away from successful sites. A novel technique of high-density, automated, and open-window mapping (OWM) effectively localizes APs without the need to differentiate the signal’s site of origin. These findings suggest that OWM can be used to rapidly and successfully map and ablate APs. Both distances from the pathway and contact force were shown to be important for pathway ablation.

Heart arrhythmias result from any disturbance in the rate, regularity, and site of origin or conduction of the cardiac electric pulse. Sporadic and underappreciated characteristics make diagnosis less timely, leading to stroke, heart failure, or even sudden death. Wearable electrocardiogram (ECG) devices are gradually becoming the main trend of intelligent diagnosis alongside the improvement of information transmission and computation power of the hardware. Therefore, a database for arrhythmia detection was planned to construct. Collaborating with hospital, this study presents a bipolar limb two-lead wearable device by collecting a large amount of real-time data and giving rise to readily available ECG databases. In total, the database contains 2000 30-s recordings of sinus, atrial and ventricular arrhythmias collected from more than 200 voluntary patients who had been diagnosed with heart diseases, ranging in age from 18 to 82. Meanwhile, manual annotations by cardiologists were proposed to benefit and instruct non-medical researchers to design the algorithm reasonably.

The left coronary cusp is the commonest site of origin for coronary cusp PVC. Catheter ablation without fluoroscopy is highly effective, feasible, and safe but it could be related to risks because of proximity to the coronary arteries. The use of ICE integration allowed an improvement in the safety and efficiency of these procedures.

Characterization of high-amplitude propagating pressure waves (HAPWs or HAPCs) plays a key role in diagnosis of colon dysmotility using any type of colonic manometry. With the introduction of high-resolution manometry, more insight is gained into this most prominent propulsive motor pattern. Here, we use a water-perfused catheter with 84 sensors with intervals between measuring points of 1 cm throughout the colon, for 6–8 h, in 19 healthy subjects. The catheter contained a balloon to evoke distention. We explored as stimuli a meal, balloon distention, oral prucalopride, and bisacodyl injection, with a goal to optimally evoke HAPWs. We developed a quantitative measure of HAPW activity, the “HAPW Index.” Our protocol elicited 290 HAPWs. 21% of HAPWs were confined to the proximal colon with an average amplitude of 75.3 ± 3.3 mmHg and an average HAPW Index of 440 ± 58 mmHg·m·s. 29% of HAPWs started in the proximal colon and ended in the transverse or descending colon, with an average amplitude of 87.9 ± 3.1 mmHg and an average HAPW Index of 3,344 ± 356 mmHg·m·s. Forty-nine percent of HAPWs started and ended in the transverse or descending colon with an average amplitude of 109.3 ± 3.3 mmHg and an average HAPW Index of 2,071 ± 195 mmHg·m·s. HAPWs with and without simultaneous pressure waves (SPWs) initiated the colo-anal reflex, often abolishing 100% of anal sphincter pressure. Rectal bisacodyl and proximal balloon distention were the most optimal stimuli to evoke HAPWs. These measures now allow for a confident diagnosis of abnormal motility in patients with colonic motor dysfunction. NEW & NOTEWORTHY High-amplitude propagating pressure waves (HAPWs) were characterized using 84 sensors throughout the entire colon in healthy subjects, taking note of site of origin, site of termination, amplitude, and velocity, and to identify optimal stimuli to evoke HAPWs. Three categories of HAPWs were identified, including the associated colo-anal reflex. Proximal balloon distention and rectal bisacodyl were recognized as reliable stimuli for evoking HAPWs, and a HAPW Index was devised to quantify this essential colonic motor pattern.

This review serves as a primer on contemporary neuroendocrine neoplasm classification, with an emphasis on gastroenteropancreatic well-differentiated neuroendocrine tumors. Topics discussed include general features of neuroendocrine neoplasms, general neuroendocrine marker immunohistochemistry, the distinction of well-differentiated neuroendocrine tumor from pheochromocytoma/paraganglioma and other diagnostic mimics and poorly differentiated neuroendocrine carcinoma from diagnostic mimics, the concepts of differentiation and grade and the application of Ki-67 immunohistochemistry to determine the latter, the various WHO classifications of neuroendocrine neoplasms including the 2019 WHO classification of gastroenteropancreatic tumors, organ-specific considerations for gastroenteropancreatic well-differentiated neuroendocrine tumors, immunohistochemistry to determine site of origin in metastatic well-differentiated neuroendocrine tumor of occult origin, immunohistochemistry in the distinction of well-differentiated neuroendocrine tumor G3 from large cell neuroendocrine carcinoma, and, finally, required and recommended reporting elements for biopsies and resections of gastroenteropancreatic neuroendocrine epithelial neoplasms.

Marker di staminalità nei carcinomi squamocellulari del cavo orale e orofaringe in relazione al sito di origine e a infezione da HPV: implicazioni cliniche.In questo studio è stata esaminata l’espressione di potenziali marcatori di staminalità nei carcinomi della testa e collo (HNSCC) per valutarne il loro possibile ruolo clinico. Sono stati arruolati 69 carcinomi squamocellulari del cavo orale (OSCC) e dell’orofaringe (OPSCC) primitivi e non precedentemente sottoposti a trattamento, raccogliendo i dati anagrafici, clinici e sul follow up. Abbiamo valutato l’eventuale infezione da HPV e l’espressione di 5 potenziali marker di staminalità (CD44, CD133, Oct-4, Nanog, and Sox-2). Gli OPSCC positivi per HPV hanno mostrato minor espressione di Nanog, mentre la sua espressione citoplasmatica è stata associata con una prognosi significativamente peggiore negli OPSCC ma non in OSCC. La colorazione di Sox-2 si è rivelata più intensa tra gli OPSCC, e la sua espressione nucleare è associata con una peggiore prognosi. L’espressione di Nanog è associata a OPSCC HPV-negativi e può avere un ruolo come marker diagnostico surrogato. In conclusione il profilo di espressione di alcuni marker di cellule staminali nei HNSCC sembra essere differente a seconda del sito di origine del tumore e dell’infezione da HPV. Inoltre Nanog e Sox-2 potrebbero presentare un significato prognostico.The expression of potential stem cell markers in HNSCCs was investigated to assess their potential clinical role. 69 primary, previously untreated oral (OSCC) and oropharyngeal squamous cell carcinomas (OPSCC) were enrolled; personal, clinical and follow-up data were collected. HPV infection and expression of 5 potential stem cell markers (CD44, CD133, Oct-4, Nanog, and Sox-2) were evaluated. HPV+ OPSCC showed lower expression of Nanog. The cytoplasmic expression of Nanog was associated with significantly worse prognosis in OPSCC, but not in OSCC. Sox-2 staining was more intense among OPSCCs. Sox-2 nuclear staining was associated with worse prognosis. Nanog expression was associated with HPV- OPSCC and may have a role as a surrogate diagnostic marker. In general, the expression profile of some stem cell markers in HNSCC seems to vary according to the site of origin and HPV infection. Nanog and Sox-2 may also have prognostic value.

This review is based on a presentation given at the Hans Popper Hepatopathology Society companion meeting at the 2019 United States and Canadian Academy of Pathology Annual Meeting. It presents updates on the diagnosis and classification of neuroendocrine neoplasms, with an emphasis on the role of immunohistochemistry. Neuroendocrine neoplasms often present in liver biopsies as metastases of occult origin. Specific topics covered include 1. general features of neuroendocrine neoplasms, 2. general neuroendocrine marker immunohistochemistry, with discussion of the emerging marker INSM1, 3. non-small cell carcinoma with (occult) neuroendocrine differentiation, 4. the WHO Classification of neuroendocrine neoplasms, with discussion of the 2019 classification of gastroenteropancreatic neoplasms, 5. use of Ki-67 immunohistochemistry, 6. immunohistochemistry to assign site of origin in neuroendocrine metastasis of occult origin, 7. immunohistochemistry to distinguish well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma, 8. lesions frequently misdiagnosed as well-differentiated neuroendocrine tumor, and 9. required and recommended data elements for biopsies and resections with associated immunohistochemical stains. Next-generation immunohistochemistry, including lineage-restricted transcription factors (e.g., CDX2, islet 1, OTP, SATB2) and protein correlates of molecular genetic events (e.g., p53, Rb), is indispensable for the accurate diagnosis and classification of these neoplasms.

Objective: To perform a literature review assessing role of MRI in predicting origin of indeterminate uterocervical carcinomas with emphasis on sequences and imaging parameters. Methods: Electronic literature search of PubMed was performed from its inception until May 2020 and PICO model used for study selection; population was female patients with known/clinical suspicion of uterocervical cancer, intervention was MRI, comparison was by histopathology and outcome was differentiation between primary endometrial and cervical cancers. Results: Eight out of nine reviewed articles reinforced role of MRI in uterocervical primary determination. T2 and Dynamic contrast were the most popular sequences determining tumor location, morphology, enhancement, and invasion patterns. Role of DWI and MR spectroscopy has been evaluated by even fewer studies with significant differences found in both apparent diffusion coefficient values and metabolite spectra. The four studies eligible for meta-analysis showed a pooled sensitivity of 88.4% (95% confidence interval 70.6 to 96.1%) and a pooled specificity of 39.5% (95% confidence interval 4.2 to 90.6%). Conclusions: MRI plays a pivotal role in uterocervical primary determination with both conventional and newer sequences assessing important morphometric and functional parameters. Socioeconomic impact of both primaries, different management guidelines and paucity of existing studies warrants further research. Prospective multicenter trials will help bridge this gap. Meanwhile, individual patient database meta-analysis can help corroborate existing data. Advances in knowledge: MRI with its classical and functional sequences helps in differentiation of the uterine ‘cancer gray zone’ which is imperative as both primary endometrial and cervical tumors have different management protocols.

Ventricular outflow is a common site for idiopathic PVCs and repetitive ventricular arrhythmias. Sites of origin of these arrhythmias may vary from the sites of earliest activation mapped. Better definition of the site of origin can help avoid unnecessary large volume ablation to suppress these arrhythmia.

Premature ventricular contractions in the absence of structural heart disease are among the most common arrhythmias in clinical practice, with well-defined sites of origin in the right and left ventricle. In this review, starting from the electrocardiographic localization of premature ventricular contractions, we investigated the mechanisms, prevalence in the general population, diagnostic work-up, prognosis and treatment of premature ventricular contractions, according to current scientific evidence.

Background and AimsIn the annual pasture legume Trifolium subterraneum, ssp. yanninicum exhibits higher waterlogging tolerance than ssp. brachycalycinum and ssp. subterraneum. This study investigates waterlogging tolerance within ssp. yanninicum ecotypes and explores correlations with seedling phenotypic traits and site of origin eco-geographic variables.MethodsTwenty eight diverse ssp. yanninicum ecotypes collected from the Mediterranean region and four cultivars were grown in a controlled environment glasshouse. After 14 days of growth seedling traits were measured. After 21 days of growth, free-drained (control) and waterlogged treatments were imposed for 28 days. Eco-geographic variables were generated from ‘WorldClim’ using collection site locations.ResultsUnder waterlogging, shoot relative growth rate (RGR) ranged from 87–108% and root RGR ranged from 80–116% of controls. Waterlogging reduced shoot dry weight (DW) in four of 32 genotypes, while root DW was reduced in 13 genotypes. Leaf size was maintained, or even increased, under waterlogging in 31 genotypes. However, petiole length was more affected by waterlogging and has value as a waterlogging tolerance indicator. Waterlogging tolerance was not significantly correlated with seedling DW, flowering time or precipitation at the site of origin, while shoot growth under waterlogging had a positive correlation with summer temperatures at origin.ConclusionsGenotypes of ssp. yanninicum tolerated transient waterlogging and greater tolerance was observed among ecotypes, rather than cultivars. An easy-to-measure indicator of tolerance was found in petiole length reduction. This study highlights untapped genotypic variability for breeders to improve the productivity and persistence of ssp. yanninicum under waterlogging.

Squamous cell carcinoma (SCC) has many histologic variants, such as clear cell SCC, signet ring SCC, basaloid SCC, desmoplastic SCC, verrucous and pigmented SCC, among others. Pigmented SCC is a rare histopathological variant with oral mucosa being common site of origin.

Aims Idiopathic epicardial ventricular arrhythmias (VAs) are clustered in the areas of the summit and crux. This study was to report a group of idiopathic epicardial VAs remote from the summit and crux areas. Methods In total, 9 patients (6 males, mean age 32±13 years) were enrolled. The locations were identified by epicardial mapping and ablation. The electrocardiographic and electrophysiological characteristics were compared to those of 9 patients who had VAs ablated at the opposite endocardial site. Results VAs were identified at the epicardium, with 4 patients had VAs located at the inferior wall, one at the anterior wall, one at the apex and 3 patients had VAs at the lateral wall. A “QS” type at the location-related leads was the only identified surface electrocardiogram indication suggesting epicardial origin (compared to that of the controls, 100% vs 0%, p

Primary malignant cardiac tumors are rare, with a prevalence of about 0.01% among all cancer histotypes. At least 60% of them are primary soft tissue sarcomas of the heart (pSTS-h) that represent almost 1% of all STSs. The cardiac site of origin is the best way to classify pSTS-h as it is directly linked to the surgical approach for cancer removal. Indeed, histological differentiation should integrate the classification to provide insights into prognosis and survival expectancy of the patients. The prognosis of pSTS-h is severe and mostly influenced by the primary localization of the tumor, the difficulty in achieving complete surgical and pharmacological eradication, and the aggressive biological features of malignant cells. This review aims to provide a detailed literature overview of the most relevant issues on primary soft tissue sarcoma of the heart and highlight potential diagnostic and therapeutic future perspectives.

Background Data regarding the successful ablation site of idiopathic outflow tract (OT) ventricular arrhythmias (VAs) in the modern era of mapping and ablation are limited. Methods and results Over a 4-year period, a total of 309 patients underwent detailed activation mapping of OT VAs including the right ventricular outflow tract (RVOT), the left ventricular outflow tract (LVOT) and the aortic cusps (AC), and the coronary venous system. 244 cases were successfully ablated at the index procedure (78.9%). The successful ablation site was more frequently located at the LVOT/ACs (51.6%) followed by RVOT (36.2%). In particular, the ACs was the predominant successful ablation site of idiopathic OT VAs (46.7%). An epicardial site of origin was predictor of ablation failure (p Conclusions The ACs is the predominant successful ablation site of idiopathic OT VAs. Take-home message The aortic cusps are the predominant successful ablation site of idiopathic idiopathic outflow tract ventricular arrhythmias.

Recent deployment of minimally invasive procedures often yield smaller biopsies, demanding more meticulous tissue handling and proper orientation, ie, obtaining histological section perpendicular to the mucosal surface. But most often the biopsied tissue tends to curl up when suspended in tissue fixative, or undergo tangential or horizontal sectioning resulting in poor orientation. A well-oriented histological section is the prerequisite for precise assessment of gastrointestinal disorders like degree of villous atrophy, depth of invasion of a tumour, proper delineation of the site of origin of growth and hence further guiding the proper management. Literature review highlights many methods already worked on for orientation of duodenal,1 2 cervical,3 urinary bladder4 and conjunctival biopsies.5 These methods include use of filter paper, vegetable matrix including cucumber paper, Gelfoam, direct mount on paper before fixation. We hypothesised that the application of albumin and introduction of lens paper could improve the orientation of the tissue, as compared with use of Whatman filter paper. Hence, an attempt was made to compare percentage oriented length of the biopsy when processed in lens paper versus Whatman filter paper, with and without application of albumin. To the best of our knowledge, we could not find any literature as per this protocol. In addition, the tissue fragmentation and loss during handling and processing was also evaluated. We have analysed consecutive 150 small-intestinal biopsies …

Whitish pale looking mass in the middle ear space is a diagnostic challenge not only to a novice otologic surgeon but also for an experienced surgeon. The array of differentials should be known for appropriate site of origin and its true nature. We have discussed a case of pale looking tympanic paraganglioma behind an intact tympanic membrane with few differentials to consider.

Most benign tumors of the larynx are epithelial in origin, with nearly 85% being laryngeal papilloma. Nonepithelial laryngeal tumors are uncommon and more than 50% of these are malignant. Therefore, benign nonepithelial solid tumors of the larynx are quite rare. The management of these tumors varies based on the site of origin, specific pathology, tumor size, and risk for malignant transformation. Most are ultimately treated with complete surgical excision, although the potential response of the tumor to adjuvant therapy may play a role in decision making. In this article, general approaches to surgical excision of these benign nonepithelial laryngeal tumors is discussed.

Breast cancer is the main site of origin of orbital metastatic disease. Although invasive lobular breast carcinoma accounts for 10-15% of all breast cancer cases, it has been noticed that it metastasizes to the orbit more often compared to breast cancer of no special type (NST). The pathogenesis of this metastasis is not entirely understood; however, it seems that the unique tissue-specific characteristics of orbital microenvironment might contribute to metastatic disease in this particular site. Given the increasing survival of breast cancer patients and the prolonged metastatic potential of invasive lobular breast carcinoma, it is possible that the incidence of this rare metastasis might increase in the future. The purpose of this review is to present clinical manifestations, immunohistochemical characteristics and therapeutic options for orbital metastases from invasive lobular carcinoma.

Imaging plays an active role in the surveillance of gastrointestinal stromal tumours (GISTs). Risk stratification schemes, based on size, mitotic count, and anatomical site of origin of the GIST, help in planning preoperative and postoperative imaging strategies especially in determining the frequency and duration of surveillance; however, there is no clear consensus on the optimal imaging strategies in patients with GISTs who are completely cured by surgery and patients who are at risk of recurrence. In addition, current surveillance protocols depend on the resectability of the primary tumour and presence of metastatic disease. The objective of this article is to provide a comprehensive review of the role of the different imaging methods for surveillance of GISTs, focusing on the guidelines recommended by National Comprehensive Cancer Network and European Society of Medical Oncology - European Network for Rare adult solid Cancers, and to propose practical guidelines for surveillance of GISTs for various risk categories.