Original Slides Research Articles

RETROSPECTIVE ANALYSIS OF DISCORDANT RESULTS BETWEEN UROVYSION FISH AND URINE CYTOLOGY IN THE DETECTION OF HIGH-GRADE UROTHELIAL CARCINOMA (HGUC): A STUDY OF 118 PATIENTS

Abstract Introduction/Objective Accurate detection of high-grade urothelial carcinoma (HGUC) relies on multiple diagnostic modalities, including UroVysion FISH and urine cytology; however, discordant results between these diagnostic tools can present a challenge. We present this study, scrutinizing the discordant results between UroVysion FISH and urine cytology to explore the potential factors that could contribute to discrepancies. Methods/Case Report A cohort of 118 patients, who underwent both UroVysion FISH and urine cytology testing for evaluation of HGUC, was selected from our cytopathology archives. Results of both the modalities were compared, and a retrospective review of original slides was done by experienced cytopathologists. Results (if a Case Study enter NA) Among the 118 cases, Urovysion FISH yielded positive results in 14 cases and negative in 104. In contrast, urine cytology reported 1 case as positive, 102 as negative, 10 as atypical (8 atypical and 2 rare atypical), and 5 as suspicious. Discordant findings were observed in 20 cases, accounting for 17% of the cases. After retrospective review of original slides, few cases were reclassified. 2 cases as atypical (initially labeled as negative), 2 cases as negative (initially labeled as atypical), 3 cases as positive (initially labeled as atypical/suspicious), 3 cases as suspicious (initially labeled as negative/atypical). Conclusion This reclassification highlights complexity of cytological interpretation, including the challenges of distinguishing between benign cellular alterations, reactive changes, ambiguous findings, suspicious features and malignant cytological changes. Integrating molecular and morphological assessment is essential for evaluation of urothelial carcinoma. Discrepancy between the two is an area which is open to study and can be related to differences in sensitivity and specificity of the testing modalities, sampling methods, variation in interpretation, limitations of testing modality and varying tumor characteristics. Review of clinical history, imaging studies, cystoscopy, and repeat testing may be considered in such cases for diagnostic accuracy.

Shear-induced depinning of thin droplets on rough substrates

Depinning of liquid droplets on substrates by flow of a surrounding immiscible fluid is central to applications such as cross-flow microemulsification, oil recovery and waste cleanup. Surface roughness, either natural or engineered, can cause droplet pinning, so it is of both fundamental and practical interest to determine the flow strength of the surrounding fluid required for droplet depinning on rough substrates. Here, we develop a lubrication-theory-based model for droplet depinning on a substrate with topographical defects by flow of a surrounding immiscible fluid. The droplet and surrounding fluid are in a rectangular channel, a pressure gradient is imposed to drive flow and the defects are modelled as Gaussian-shaped bumps. Using a precursor-film/disjoining-pressure approach to capture contact-line motion, a nonlinear evolution equation is derived describing the droplet thickness as a function of distance along the channel and time. Numerical solutions of the evolution equation are used to investigate how the critical pressure gradient for droplet depinning depends on the viscosity ratio, surface wettability and droplet volume. Simple analytical models are able to account for many of the features observed in the numerical simulations. The influence of defect height is also investigated, and it is found that, when the maximum defect slope is larger than the receding contact angle of the droplet, smaller residual droplets are left behind at the defect after the original droplet depins and slides away. The model presented here yields considerably more information than commonly used models based on simple force balances, and provides a framework that can readily be extended to study more complicated situations involving chemical heterogeneity and three-dimensional effects.

Unusual presentation and delayed diagnosis of cardiac angiosarcoma

BackgroundPrimary cardiac angiosarcomas are very rare and present aggressively with high rates of metastasis. Given the poor prognosis, particularly once disease has spread, early diagnosis and multidisciplinary treatment is essential.Case presentationWe present the case of a 46-year-old male who presented with chest pain, intermittent fevers, and dyspnea. Workup with computed tomography scan and transesophageal echocardiography demonstrated a right atrial pseudoaneurysm. Given the concern for rupture, the patient was taken to the operating room, where resection of the pseudoaneurysm and repair using a bovine pericardial patch was performed. Histopathology report initially demonstrated perivascular lymphocyte infiltrate. Six weeks later, the patient represented with chest pain and new word finding difficulty. Workup revealed multiple solid lung, pericardial, brain, and bone nodules. Eventual biopsy of a cardiophrenic nodule demonstrated angiosarcoma, and rereview of the original pathology slides confirmed the diagnosis of primary cardiac angiosarcoma.ConclusionsPrimary cardiac angiosarcomas are often misdiagnosed given the rarity of these tumors, but early diagnosis and initiation of treatment is essential. The unique presentation of our case demonstrates that clinical suspicion for cardiac angiosarcoma should be maintained for spontaneous pseudoaneurysm originating from the right atrium.

Primary MALT lymphoma of the breast: pathological and radiological characteristics.

Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4years and 7.5months, and all patients were alive at the last follow-up. Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

Digital Pathology in the Detection of Infectious Microorganisms: An Evaluation of Its Strengths and Weaknesses Across a Panel of Immunohistochemical and Histochemical Stains Routinely Used in Diagnostic Surgical Pathology.

The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated. To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology. Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images. Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa. Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.

Fusion of old and new: Employing touch imprint slides for next generation sequencing in solid tumors.

Cytomorphological evaluation of tissue touch imprints during rapid on-site evaluation or intraoperative pathology consultation has crucial value. However, literature on their utility for molecular testing is limited. In this study, we emphasize a further benefit of touch imprint slides and scrutinize our institutional experience on their use in molecular testing, specifically next generation sequencing (NGS). NGS-based reports (2019-2023) of Koç University Hospital were retrospectively analyzed and circumstances in which sequencing was conducted on touch imprint slides were retrieved (n = 18). Type/location of the biopsy, diagnosis, results, and quality metrics were recorded. Touch imprints were addressed when they harbored more neoplastic cells compared with permanent biopsies, when suboptimal fixation mitigated deoxyribonucleic acid/ribonucleic acid (DNA/RNA) yield in resections or when the sample was obtained from bone and required decalcification. Diagnoses were diverse, namely non-small-cell lung cancer, gastric adenocarcinoma, glial tumor, Ewing sarcoma, and carcinoma of unknown primary. The percentage of tumor cells on slides stretched between 15% and 70%. Molecular findings ranged from KRAS mutations to TRIM1::NTRK2 and EWSR::FLI1 fusions. For five cases, sequencing did not yield any alteration, one study was not completed because it did not yield high-quality RNA. Touch imprint slides provide a reliable alternative, especially when neoplastic cells are scarce in permanent biopsies or decalcification deters nucleic acid quality. Based on our experience, we suggest making touch imprints on a routine basis, especially for every bone biopsy. Once digitally scanned duplicates are made, original slides can be safely used for DNA-/RNA-based molecular studies.

Multimedia design for learner interest and achievement: a visual guide to pharmacology.

Medical education increasingly relies on digital learning materials. Despite recognition by the Association of American Medical Colleges Institute for Improving Medical Education, medical education design often fails to consider quality multimedia design principles. Further, the AAMC-IIME issued a call to study the role of design principles in medical education. Thus, the current study investigated the cognitive and affective effects of redesigning PowerPoint slides used to support pharmacology content during the preclinical years of medical school training. Researchers implemented a quasi-experimental design, using traditionally-designed (original) slides with a Traditional group (n = 100) and slides redesigned to follow principles from the Cognitive Theory of Multimedia Learning with an Experimental group (n = 40). Participants in the Experimental group completed a post-survey incorporating the Situational Interest Survey for Multimedia to indicate motivational engagement with the media. Students in the Experimental group also responded to additional preference questions. Researchers analyzed survey responses and students' scores in pharmacology-related coursework across the preclinical Foundations Phase of training to determine the impact on achievement and motivation. Findings related to learner achievement showed a modest but significant increase in the Experimental group compared to the Traditional group in the Cardiac, Pulmonary, and Renal (CPR) educational block (105%, normalized to Traditional group, p = 0.013) and cumulative pharmacology grades (101%, normalized to Traditional group, p = 0.043). Additionally, participants in the Experimental group indicated a significantly higher average triggered situational interest in redesigned slides (M = 4.85, SD = 0.25) than the original slides (M = 3.23, SD = 1.40, t=-6.33, p < 0.001). Similarly, the interest rating of the redesigned slides (M = 4.87, SD = 0.24) was significantly greater than that of the original slides (M = 3.89, SD = 0.86, t=-6.824, p < 0.001). Moreover, results further indicated significant differences in the maintained-feeling and maintained-value constructs, and all participants in the Experimental group indicated a preference for the redesigned slides. The findings provide strong evidence in support of using the Cognitive Theory of Multimedia Learning design principles to intentionally design media in medical education. In addition to increased achievement scores, students in the Experimental group demonstrated significantly higher levels of situational interest in the redesigned slides, especially triggered interest and maintained-feeling interest. Medical education learning designers should seriously consider redesigning media to achieve similar results.

Prediction of disease recurrence or residual disease after primary endoscopic resection of pT1 colorectal cancer—results from a large nationwide Danish study

PurposeRisk assessment of disease recurrence in pT1 colorectal cancer is crucial in order to select the appropriate treatment strategy. The study aimed to develop a prediction model, based on histopathological data, for the probability of disease recurrence and residual disease in patients with pT1 colorectal cancer.MethodsThe model dataset consisted of 558 patients with pT1 CRC who had undergone endoscopic resection only (n = 339) or endoscopic resection followed by subsequent bowel resection (n = 219). Tissue blocks and slides were retrieved from Pathology Departments from all regions in Denmark. All original slides were evaluated by one experienced gastrointestinal pathologist (TPK). New sections were cut and stained for haematoxylin and eosin (HE) and immunohistochemical markers. Missing values were multiple imputed. A logistic regression model with backward elimination was used to construct the prediction model.ResultsThe final prediction model for disease recurrence demonstrated good performance with AUC of 0.75 [95% CI 0.72–0.78], HL chi-squared test of 0.59 and scaled Brier score of 10%. The final prediction model for residual disease demonstrated medium performance with an AUC of 0.68 [0.63–0.72].ConclusionWe developed a prediction model for the probability of disease recurrence in pT1 CRC with good performance and calibration based on histopathological data. Together with lymphatic and venous invasion, an involved resection margin (0 mm) as opposed to a margin of ≤ 1 mm was an independent risk factor for both disease recurrence and residual disease.

Optimizing Storage and Computational Efficiency: An Efficient Algorithm for Whole Slide Image Size Reduction

ObjectiveTo efficiently store, transfer, and analyze whole slide imaging (WSI), we developed an image-processing algorithm to remove the unneeded background in a WSI and assemble tissue-containing parts into smaller WSIs without any change in tissue area image resolution. Patients and MethodsWe used histology slides of nondysplastic Barrett esophagus, low-grade dysplasia, and high-grade dysplasia, which were digitized using Aperio AT2 Scanner from January 1992 to September 2020. The algorithm involved converting color images to grayscale images, binarizing images by assigning zero to the background and 1 to the foreground, filling the holes and dilating the foreground masks, and extracting connected components. Using the coordinates of each component, the vertices of the smallest surrounding bounding box were calculated, and tissue-containing parts were cropped from the original slide. The smallest possible rectangle that encloses all bounding boxes containing tissue was found using the rectangle-packer package. ResultsThe algorithm resulted in a mean reduction of 7.11×. The performance of a previously developed deep learning model for the detection of Barrett esophagus dysplasia grade on the size-reduced WSIs was comparable with that on the original WSIs. ConclusionOur algorithm for WSI size reduction can assist researchers in storing, transferring, and analyzing WSIs while optimally using them in their workflow.

The diatom genus Humidophila (Bacillariophyta) in an historic Delogne sample with the description of 2 new species

ABSTRACT During the analysis of a voucher sample from Frahan (Belgium) collected by the Belgian diatomist Charles-Henri Delogne, seven species from the genus Humidophila (Bacillariophyta) have been observed. Two species could not be identified using the currently available literature and are described as new to science. Humidophila delognei sp. nov. has always been identified in the past as H. contenta, but based on recent analysis of the original type material of the latter, it was clear that the currently accepted concept of the species was wrong. The new species is characterised by parallel valve margins, a linear valve outline, a distinct central fascia and T- or Y-shaped raphe endings. The other new species, H. aspera sp. nov., has undulating valve margins and distinct, though irregular siliceous markings in the central and axial area. The sample from Frahan was also indicated in 1885 by Henri Van Heurck as being the original material for the newly described species Humidophila (Navicula) flotowii, long considered a synonym of H. perpusilla. Both species can, however, be separated based on a different length/width ratio, with H. flotowii showing more slender, elongated valves. Other Humidophila species in the sample include H. contenta, H. laevissima, H. perpusilla and H. simplex. Navicula fragilarioides, a new name once introduced for Fragilaria laevissima, the basionym of H. laevissima, is lectotypified based on an original Krasske slide.

A historical look using virtual microscopy: the first case report of adrenomyeloneuropathy (AMN).

The history of adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN) and other peroxisomal diseases is exemplary for the stunning progress of scientific medicine within the past 50 years. Like many breakthroughs in medicine, the detailed analysis of patients' pathologically affected tissues was instrumental, resulting in stepwise systematic clarification of what had remained enigmatic until the 1970s. This flashback paper is a recollection of the first neuropathological description of a slowly evolving clinical phenotype, spastic paraparesis with adrenal insufficiency, in a young adult by Budka et al. 1976 [3], using virtual microscopy of the original histologic slides. The clinico-pathological presentation derives from the classical cerebral ALD phenotype in boys, where electron microscopy demonstrated the underlying pathological hallmark of characteristic lipid inclusions shared by both phenotypes. Our report allowed the delineation of a new disease type almost simultaneously described in more cases as AMN by Griffin et al. 1977 [4] and Schaumburg et al. 1977 [11]. Moreover, our report indicated clinical heterogeneity in the ALD disease group that, as shown later, extends further to females, to Addison-only, and even to asymptomatic subjects. The gene underlying ALD was discovered in 1993 as a defect in the ABCD1 gene. Yet, it has hitherto remained unclear how the gene defect causes the strikingly broad and unpredictable phenotypic spectrum of ALD/AMN.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Specifics of slope movements on slopes with contrasting structural conditions: Evidence from tree-ring records

The geological structure of a slope is one of the key factors that drives the development of landslide types. Various landslide types, although occurring in the same locality, can result in different spatio-temporal dynamics of their movements. Moreover, the presence of shallow creep movements on such slopes can modify the effect of slide movements and possibly cause the false impression of landslide activity. The nonstandard combination of detailed tree-ring-based (dendrogeomorphic) approaches involving the careful assessment of growth disturbance properties (the duration, intensity, mutual ratio of different disturbances), the statistical testing of the spatial pattern of disturbed trees, the analysis of possible extreme precipitation triggers, and geophysical sounding was used in this study in an attempt to distinguish creep and slide movements and assess the general slope movement activity on slopes with contrasting geological structures. Data from 1032 tree-ring series of 516 disturbed individuals of common spruce (Picea abies (L.) Karst.) enabled the reconstruction of 13 slope movements on all three studied sites (3, 7, and 3) for the last approximately 70 years. Although some indices correspond with the general assumption of a specific landslide type to the structure of induced growth disturbances (e.g., an increased ratio of reaction wood on rotational landslides), the advanced dendrogeomorphic approach used suggests that not all dated events are of slide origin and that creep movements significantly modify the effect of original slide movement on tree growth. Some dated events are probably the result of only creep movements themselves. Thus, the present study critically assesses results of the dendrogeomorphic dating of various landslides, presents contrasting behavior of slope movements on slopes with contrasting geological structures, and recommends the use of more advanced tree-ring-based approaches for more effective dendrogeomorphic research of landslides.

Mismatch repair system in colorectal cancer. Frequency, cancer phenotype, and follow-up

Introduction and aimsA frequent task in the study of colorectal carcinomas (CRC) is to identify tumors harboring deficient DNA mismatch repair systems (dMMR), which are associated with microsatellite instability. Given that there is scant information on those tumors in Mexican patients, our aim was to describe their frequency, clinical and pathologic characteristics, and results, which are necessary for future trials. Materials and methodsA consecutive series of CRC patients, treated and followed at a tertiary care center was performed. The clinical and pathologic variables and the risk of hereditary or familial cancer syndrome were retrieved. The original slides and hMLH1, hPMS2, hMSH2, hMSH6 immunohistochemistry were evaluated. Tumors with an absence of at least one protein were considered dMMR. Differences were contrasted, utilizing non-parametric tests. ResultsOne hundred and forty-four patients were included, with a median age of 65 years. A total of 134/93% patients presented with sporadic CRC, 8/5.6% had a family history of CRC, and 2/1.4% met the diagnostic criteria for hereditary non-polyposis colon cancer, according to the Amsterdam and Bethesda criteria. dMMR tumors were found in 39 patients, distributed among the three groups. They were locally advanced (p<0.001), right-sided, had the mucinous phenotype, and harbored a Crohn’s-like lymphoid reaction (all three features, p<0.04). Adjuvant or palliative chemotherapy was administered to 57 (39.6%), concomitant chemoradiotherapy to 24 (16.7%), but 63 (43.8%) patients received no additional treatment to surgery. Five-year follow-up was completed in 131 of the patients and the outcomes alive-with-disease or died-of-disease were more frequently observed in the proficient (pMMR) lesions. ConclusionsIn the present pre-FOLFOX case series, outcomes were better in dMMR CRC than in proficient lesions.

Endocervical adenocarcinoma biomarkers for immunotherapy: Descriptive analysis.

e17526 Background: Adenocarcinoma and adenosquamous carcinoma of the cervix are subtypes of HPV related cervical cancer. As virally mediated tumors, they have become an obvious choice for immunotherapy treatment approach. Currently, there is little information about the presence of immunological tumor markers among patients with endocervical adenocarcinomas. We hypothesized cervical adenocarcinomas highly express immunotherapy markers. Here we characterize the protein status of immunotherapy markers in a large single institution dataset. Methods: An IRB approved retrospective review of cervical adenocarcinoma and adenosquamous carcinoma was performed. We gathered original slides for each patient and performed immunohistochemistry (IHC) for tumor markers CD8, PDL1, TIM3 and LAG3. Demographic and pathologic data was captured. Patients were categorized by positivity percentage for each marker. Descriptive statistics and univariate analysis were used. Results: A total of 97 patients met criteria for the study and slides were available for staining in 68 patients. Demographic data showed a median age of 42 years old with majority of patients identifying as White at 66%, followed by Hispanic (13%), Asian (10%), other (7%) and Black (1%). Of the entire cohort, 75% were adenocarcinoma, 25% were adenosquamous carcinoma. Among those with recorded status, 82% were HPV positive, 14% had metastasis, and 13% had recurrence. On univariate analysis, adenocarcinoma was significantly more common in patients who were LAG3 &lt; 1% or PDL &lt; 1% (p = 0.002, p = 0.007). Patients who were LAG3 &lt; 1% or PDL &lt; 1% were also less likely to have Grade 1 tumors (p = 0.006, 0.03). When analyzing by respective immune marker percentage group there were no statistically significant differences in LVSI, depth of invasion, stage, or recurrence rate. By IHC, 68% were PDL1 &gt; 1% positive, 63% were LAG3 &gt; 1% positive, 100% were TIM3 &gt; 1% positive, 100% were CD8 &gt; 1% positive. Seven of the 68 patients had a recurrence. Of those patients with recurrence, one was treated with immunotherapy. Conclusions: A large proportion of cervical adenocarcinomas displayed immunotherapy targets by IHC suggesting that combined immunotherapy agents may be useful in this population. Further study is needed to assess whether IHC is predictive of outcome or response.[Table: see text]

Sistema de reparación de errores de emparejamiento en carcinoma colorrectal. Frecuencia, fenotipo y seguimiento

Introduction and aimsA frequent task in the study of colorectal carcinomas (CRC) is to identify tumors harboring deficient DNA mismatch repair systems (dMMR), which are associated with microsatellite instability. Given that there is scant information on those tumors in Mexican patients, our aim was to describe their frequency, clinical and pathologic characteristics, and results, which are necessary for future trials. Materials and methodsA consecutive series of CRC patients, treated and followed at a tertiary care center was performed. The clinical and pathologic variables and the risk of hereditary or familial cancer syndrome were retrieved. The original slides and hMLH1, hPMS2, hMSH2, hMSH6 immunohistochemistry were evaluated. Tumors with an absence of at least one protein were considered dMMR. Differences were contrasted, utilizing non-parametric tests. ResultsOne hundred and forty-four patients were included, with a median age of 65 years. A total of 134/93% patients presented with sporadic CRC, 8/5.6% had a family history of CRC, and 2/1.4% met the diagnostic criteria for hereditary non-polyposis colon cancer, according to the Amsterdam and Bethesda criteria. dMMR tumors were found in 39 patients, distributed among the 3groups. They were locally advanced (P<.001), right-sided, had the mucinous phenotype, and harbored a Crohn's-like lymphoid reaction (all 3features, P<.04). Adjuvant or palliative chemotherapy was administered to 57 (39.6%), concomitant chemoradiotherapy to 24 (16.7%), but 63 (43.8%) patients received no additional treatment to surgery. Five-year follow-up was completed in 131 of the patients and the outcomes alive-with-disease or died-of-disease were more frequently observed in the proficient (pMMR) lesions. ConclusionsIn the present pre-FOLFOX case series, outcomes were better in dMMR CRC than in proficient lesions.

Case series of Adenomatoid Odontogenic Tumors: Clinical, Radiographic, and Histologic Features

<h3>Objective</h3> We present a case series of adenomatoid odontogenic tumor (AOT), a benign odontogenic tumor from a large biopsy service. AOT has a limited growth potential and is often seen in children and young adults, between the ages of 10-19 years. AOT has uncertain pathogenesis and studies suggest enamel organ, reduced enamel epithelium, and rests of Malassez as potential sources. Clinically, AOT's are asymptomatic and identified upon routine radio- graphic examination. <h3>Methods</h3> Information was collected from the University of Florida Oral Pathology Biopsy Service archives (1994-2019). The clinical and demographic data along with any accompanying radiographic images and original slides were evaluated. <h3>Results</h3> A total of 26 cases of AOT were identified, with a mean age of 22.3 years (range: 12-67). A slight female predilection was noted (57.7%, n=15). Most cases presented in the anterior region of the jaw (73%, n=19) and a slight maxillary predilection was observed (61.5%, 16 cases). Most patients were aged under 20 (69.2%, n=18). Clinical impression included dentigerous cyst, lateral periodontal cyst, and odontogenic keratocyst (57.7%, n=15). Radiographs were available for six cases and all presented as a unilocular radiolucency. The histologic diagnosis was consistent with AOT in 24 cases and peripheral AOT in two cases.One case had a fo- cal area of CEOT that tested positive with a Congo Red stain. <h3>Conclusion</h3> In almost all cases within the study the clinical impression of AOT was not rendered. This implied that AOT is rarely considered in the differential of such lesions. In addition, while most patients were children or young adults, there were a few outliers above thirty (19.2%, n=5). This may suggest that AOT is diagnosed late in some cases due to its benign nature. Clinicians should be sentient of this lesion as the treatment and prognosis differs from other odontogenic cysts and tumors.

THREE CASES OF AMELOBLASTIC CARCINOMA WITH REVIEW OF CLINICAL, RADIOGRAPHIC AND HISTOPATHOLOGIC FEATURES

<h3>Introduction</h3> Ameloblastic carcinoma (AC) is a rare malignant primary epithelial odontogenic tumor demonstrat- ing histologic features of ameloblastoma with signs of overt malignancy. In this case series, we describe the clinical, radiographic and histologic features of 3 cases of AC. <h3>Methods</h3> Three cases of AC were identified from the University of Florida Oral Pathology Biopsy archives. Clinical data and original slides were retrospectively analyzed. Immuno- histochemical (IHC) stains for cytokeratin 19 (CK19) was performed on all cases to demonstrate odontogenic epithe- lial origin. <h3>Results</h3> All cases of AC in this series occurred in elderly males, with two presenting in the mandible and one in maxilla. Radiographically, all presented as ill-defined radiolucencies and demonstrated cortical expansion, consistent with features of malignancy. The first case involved a 60-year-old male with an erosive soft tissue mass along the anterior mandible between teeth #27 and #28 and corresponding radiolucent lesion on films. The second case occurred in a 75-year-old male presenting with gingival swelling and an expansile radiolucent lesion in the right maxilla, extending from tooth #3 to #7. The third case was seen in a 75-year-old male displaying a large oste- olytic lesion of the mandibular ramus surrounded by a bulky soft tissue mass extending deep into the right lateral and medial pterygoid muscles. Histologically, all cases revealed large sheets of interconnecting islands and strands of malignant cells displaying peripheral palisading, reverse nuclear polarity and apical vacuolization. In addition, the malignant islands exhibited central necrosis and neoplastic cells showed significant hyperchromatism with nu- clear pleomorphism. IHC staining with CK19 were strongly positive in two cases and focally positive in one case. <h3>Conclusion</h3> This case series documents 3 cases of a rare odontogenic malignancy and highlights the importance of including this entity in a differential diagnosis of aggressive lesions of the jaws, especially in older patients.

Primary intraosseous squamous cell carcinoma arising in odontogenic cysts: a series of three cases with immunohistochemical analysis

<h3>Introduction</h3> Carcinomatous transformation in odontogenic cysts is rare, with few cases described in the literature. Squamous cell carcinoma (SCC) is the most common form of malignant transformation in odontogenic cysts. Radicular and dentigerous cysts are the most common odontogenic cysts to undergo malignant transformation. We present three cases of primary intraosseous carcinoma (PIOC) arising in odontogenic cysts. <h3>Method and Materials</h3> Following IRB approval, cases were identified from the University of Florida Biopsy Service archives (1994-2020). The clinical and demographic data was reviewed, along with radiographs and original slides. An immunohistochemistry (IHC) panel including CK19, p53, and Ki-67 was performed on all cases. <h3>Results</h3> The first case occurred in a 67-year-old male with a radiolucency around impacted #17. Microscopically, a verrucous carcinoma was diagnosed arising within a developmental odontogenic cyst, most likely an orthokeratinized odontogenic cyst. The second case involved a 59-year-old male with a lesion adjacent to tooth #15. Histologic examination revealed a well differentiated SCC arising from an odontogenic keratocyst (OKC). The final case involved a 13-year-old male with a radiolucency near teeth #6-7. A well differentiated SCC was diagnosed arising from an OKC. Further investigation to assess for Nevoid Basal Cell Carcinoma Syndrome was recommended for this case, but the outcome was unavailable. IHC analysis revealed P53 positivity for all cases. Ki67 showed 80-90% positivity in the basal layer of the odontogenic epithelium for cases 1 and 3, and 50% positivity for case two. Ck19 was only focal positivity in all cases. <h3>Conclusion</h3> We present three cases of squamous cell carcinoma arising within odontogenic cysts. P53 and Ki-67 positivity aid in confirmation of the aggressive nature of each tumor. CK19 staining was weak, despite the obvious odontogenic nature of the epithelium in all cases. Careful follow-up for odontogenic cysts demonstrating recurrence or progressive growth is imperative.

Deep Learning Facilitates Distinguishing Histologic Subtypes of Pulmonary Neuroendocrine Tumors on Digital Whole-Slide Images.

Simple SummaryChallenges persist in diagnosing pulmonary neuroendocrine tumors. Our case study shows that deep learning combined with convolutional neural networks has the potential to assist in the diagnosis of pulmonary neuroendocrine tumors from digital whole-slide images.The histological distinction of lung neuroendocrine carcinoma, including small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC), can be challenging in some cases, while bearing prognostic and therapeutic significance. To assist pathologists with the differentiation of histologic subtyping, we applied a deep learning classifier equipped with a convolutional neural network (CNN) to recognize lung neuroendocrine neoplasms. Slides of primary lung SCLC, LCNEC and AC were obtained from the Laboratory of Clinical and Experimental Pathology (University Hospital Nice, France). Three thoracic pathologists blindly established gold standard diagnoses. The HALO-AI module (Indica Labs, UK) trained with 18,752 image tiles extracted from 60 slides (SCLC = 20, LCNEC = 20, AC = 20 cases) was then tested on 90 slides (SCLC = 26, LCNEC = 22, AC = 13 and combined SCLC with LCNEC = 4 cases; NSCLC = 25 cases) by F1-score and accuracy. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The tumor maps were false colored and displayed side by side to original hematoxylin and eosin slides with superimposed pathologist annotations. The trained HALO-AI yielded a mean F1-score of 0.99 (95% CI, 0.939–0.999) on the testing set. Our CNN model, providing further larger validation, has the potential to work side by side with the pathologist to accurately differentiate between the different lung neuroendocrine carcinoma in challenging cases.