Histological Criteria Research Articles

STEM-12. A NEURONAL STEM-LIKE PHENOTYPE IN GRADE 4 IDH-MUTANT ASTROCYTOMA WITH CDKN2A/B LOSS IS ASSOCIATED WITH CUX2 DEFICIENCY

Abstract Diffuse gliomas represent the most common type of primary adult malignant brain tumor historically diagnosed and graded from histologic criteria alone. Gliomas harboring isocitrate dehydrogenase (IDH) 1 or 2 mutations are associated with lower grade tumors and portend a favorable prognosis relative to IDH-wildtype glioma. However, the loss of CDKN2A/B in IDH-mutant astrocytoma confers an aggressive high grade phenotype and is the strongest implicated molecular alteration associated poor clinical survival, thus is now sufficient to define a grade 4 tumor regardless of histologic grade. However, there remains no effective therapies targeted at molecular subgroups in aggressive gliomas to date. Here, we sought to elucidate the biologic pathways and functional outcomes associated with the acquisition of high-grade behavior under loss of CDKN2A/B in IDH-mutant astrocytoma to inform future therapeutic strategies. We analyzed a cohort of patient IDH-mutant astrocytomas with RNA sequencing data and found the increased expression of regulators of embryonic nervous system development and signaling concurrent with CDKN2A/B loss. Using grade 4 IDH-mutant astrocytoma patient-derived (PDX) and cell-lines harboring CDKN2A/B homozygous deletion, we stably re-expressed p14ARF, p15INK4B, and p16INK4A using a Tet-inducible system. IDH-mutant cell lines with re-expression of p14, p15, or p16 displayed differential transcription factor activation, impaired neurosphere capability, decreased colony formation, and lower neurosphere proliferation. Intriguingly, RNA-seq data revealed CUX2, a transcription factor known to control neuronal precursor behavior, as the likely candidate regulating the differential expression profile across CDKN2A/B status. We observed increased CUX2 expression in cell lines stably re-expressing p14, p15, and p16. We validated the CUX2 signature across publicly available datasets of IDH-mutant astrocytoma where CUX2 expression negatively correlated with loss of CDKN2A/B in patient tumors. Together our work suggests CUX2 deficiency in IDH-mutant astrocytoma with CDKN2A/B deletion enables an increased neuronal stem-like phenotype in these grade 4 tumors.

Retrospective investigation of porcine circoviruses in cases of porcine dermatitis and nephropathy syndrome

Porcine dermatitis and nephropathy syndrome (PDNS) is a severe condition that affects mainly growing pigs and is considered to be caused by a type III hypersensitivity reaction. Although porcine circovirus 2 (PCV-2) is the antigen linked to this condition, porcine circovirus 3 (PCV-3) has also been proposed to be causally associated with PDNS. Moreover, the initial description of porcine circovirus 4 (PCV-4) also related this novel agent to this clinicopathological entity. Therefore, this retrospective study included a large number of PDNS cases (n = 102) fulfilling specific histologic criteria in search of known porcine circoviruses (PCV-1 to PCV-4) by conventional and/or quantitative PCR (qPCR). All the samples were subjected to PCV-2 immunohistochemistry (IHC) or conventional in situ hybridization (C-ISH), and RNAscope® (R-ISH) was used to study PCV-2 and PCV-3 localization in a subset of the samples. All PDNS cases were PCV-2 positive by qPCR, while 30 of them (29.4%) yielded PCV-3 qPCR positivity; PCV-2 viral loads were significantly greater than PCV-3 viral loads. All animals were negative for PCV-1 and PCV-4. By C-ISH/IHC, 63 cases (61.8%) were positive for PCV-2, with low to moderate amounts of antigen. R-ISH demonstrated higher sensitivity, as all studied cases were positive; however, neither PCV-2 nor PCV-3 were consistently found within characteristic PDNS lesions. These results indicate that all PDNS-affected pigs were infected with PCV-2, emphasizing the likelihood that this viral antigen is causally linked to this condition. In contrast, no evidence of the association of PCV-1, PCV-3 or PCV-4 with PDNS was found.

Micropapillary pattern in serous borderline ovarian tumor and the risk of extraovarian localization of low-grade serous carcinoma (‘invasive implants’): A systematic review and meta-analysis

In serous borderline ovarian tumor (SBOT), a micropapillary (MP) pattern has been considered analogous to intraepithelial low-grade serous carcinoma (LGSC). On this account, it is reasonable to hypothesize that MP-SBOT is more likely to be associated with extraovarian LGSC localizations (also referred to as 'invasive implants') compared to conventional SBOT. The aim of this study was to investigate the potential association between a MP pattern and invasive implants in SBOT. Three electronic databases were searched from 2000 (year of publication of histological criteria for MP-SBOT) to 2023 for all studies assessing the presence of invasive implants in conventional SBOT vs MP-SBOT. Exclusion criteria were sample size <20, overlapping patient data, reviews. The association between MP pattern and invasive implants was assessed by using odds ratio (OR), with a significant p-value<0.05. Seven studies with 1766 SBOT were included, out of which 205 (11.5 %) were MP-SBOT, 462 (26 %) had implants and 62 (3.5 %) had invasive implants. A MP pattern was significantly associated with the presence of invasive implants (OR=7.33, 95 % CI 3.61–14.86) (p<0.001), with low heterogeneity among studies (I2=28 %). In conclusion, a MP pattern in SBOT is significantly associated with extraovarian LGSC localization, supporting that it represents intraepithelial LGSC.

Histopathologic Perspective of Nail Lichen Planus: A 10-year Case Series From a Tertiary Care Center in South India.

Nail involvement is seen in 10% of lichen planus patients, with a subset developing severe destruction of the nail matrix. Nail biopsy is a complex procedure usually done when nails are the only site of involvement. The pathology of nail lichen planus (NLP) has been the subject of very few studies. Most studies refer to the major and minor histopathologic criteria proposed by Hanno et al. This study aims to characterize the histopathologic features of NLP. Twenty five patients of NLP with nail biopsies, diagnosed in the last 10 years were included in the study. Lichen planus was suspected in all patients, and the alternative diagnosis was psoriasis/onychomycosis and melanoma. On histopathology, the common features included acanthosis (88%), lichenoid lymphocytic inflammation (96%), and hypergranulosis (72%). Detachment of epithelium from the subepithelium, a hitherto unreported feature, was noted in 60% of cases. Less common features were lymphocytic exocytosis (48%), melanophages (40%), basal vacuolar alteration (24%), apoptotic keratinocytes (28%), fraying of the nail plate (24%), and spongiosis (20%). Understanding the common and less common histopathologic features and their correlation with clinical findings is essential to diagnose NLP accurately rather than stressing histologic criteria as major/minor, which may lead to the underdiagnosis of cases.

Curved multiplanar reformatting allows the accurate histological delineation of hippocampal subfields.

Hippocampal subfields perform specific roles in normal cognitive functioning and have distinct vulnerabilities in neurological disorders. However, measurement of subfields with MRI is technically difficult in the head and tail of the hippocampus. Recent studies have utilized curved multiplanar reconstruction (CMPR) to improve subfield visualization in the head and tail, but this method has not yet been applied to histological data. We utilized BigBrain data, an open-source database of serially sectioned histological data for our analyses. The left hippocampus was segmented according to histological criteria by two raters in order to evaluate intra- and inter-rater reliability of histology-based segmentation throughout the long axis. Segmentation according to our previous protocol for the hippocampal body was then compared to these histological measurements to evaluate for histological validity. Agreement between segmentations was evaluated using Dice similarity coefficients (DSCs). Intra-rater reliability (DSCs) of histological segmentation was excellent for all subfields: CA1 (0.8599), CA2 (0.7586), CA3/CA4/DG (0.8907), SLM (0.9123), subiculum (0.8149). Similarly, inter-rater reliability analysis demonstrated excellent agreement (DSCs) for all subfield locations: CA1 (0.8203), CA2 (0.7253), CA3/CA4/DG (0.8439), SLM (0.8700), subiculum (0.7794). Finally, histological accuracy (DSCs) for our previous protocol was excellent for all subfields: CA1 (0.8821), CA2 (0.8810), CA3/CA4/DG (0.9802), SLM (0.9879), subiculum (0.8774). When subfields in the hippocampus head, body, and tail were analyzed independently, DSCs also showed excellent agreement. CMPR allows reliable subfield segmentation based on histological criteria throughout the hippocampal head, body, and tail. Our previous protocol for the hippocampal body can be applied to provide histologically valid subfield measurements throughout the entire hippocampal long axis.

An update on EBV-related cutaneous lymphoproliferative disorders: a systematic review.

Epstein Barr virus (EBV) positive B lymphoproliferative disorders (LPD) with cutaneous involvement include a series of rare entities that go from indolent processes to aggressive lymphomas. Since the latest WHO-EORTC classification of cutaneous lymphomas in 2018, significant changes have been included in the new classifications of hematological malignancies. B-cell EBV+ LPD mainly affect immunocompromised patients while T-cell EBV+ LPD are more prevalent in specific geographic regions such as Asia, Central America, and South America. This systematic review summarizes the main clinical, histological, immunophenotypic and molecular characteristics of B- and T-cell EBV+ LPD that may compromise the skin at diagnosis. B-cell EBV+ LPD include primary cutaneous lymphomas such as EBV-MCU, as well as cutaneous systemic lymphomas that may present such as lymphomatoid granulomatosis (LG), EBV+ diffuse large B cell lymphoma, NOS, plasmablastic lymphoma (PBL), and extracavitary primary effusion lymphoma (EC-PEL). EBV+, EBV-positive polymorphic B cell LPD, or post-transplant lymphoproliferative disorders (PTLD). Regarding T-cell EBV+ LPD, most of these entities are categorized within T/NK-cell lymphoproliferative processes and lymphomas of childhood, including extranodal T/NK lymphoma, and even more exceptional forms such as EBV-positive T-cell centrofollicular lymphoma and intravascular T/NK-cell lymphoma. Diagnosis is based on integrating the clinical, histological, immunohistochemical, and genetic criteria discussed throughout this article. Management is multidisciplinary, posing a challenge for dermatologists and hematologists involved in the management of these patients. Having scientific evidence available in this field is of paramount importance because overtreatment must be carefully avoided.

Multilocular Cystic Renal Neoplasia of Low-grade Malignant Potential: Evolving Diagnostic Criteria: A Case Report with Review of Literature

Multilocular Cystic Renal Neoplasm of Low Malignant Potential (MCRNLMP) is a distinct type of clear cell renal tumor. The diagnostic histological criteria for this entity have evolved, and specific histological features have been modified over the years. The WHO 2022 of Male Urinary System and Male Genital Tumours respecified diagnostic histopathological features. Maximum tumors are asymptomatic and are incidentally detected on radiological examination. Computed tomography using contrast agents is still the gold standard for classifying cystic tumors of kidney. The Bosniak category of renal cystic lesions is crucial for the management of other imaging modalities such as magnetic resonance imaging (MRI) and contrast-enhanced ultrasound, which can be used with the same effectiveness. The prognosis is excellent in MCRNLMP, and there are no reports of cancer progression or metastasis. Minimally invasive nephron-sparing surgery with strict clinical including imaging follow-up with contrast-enhanced computerized tomography and magnetic resonance imaging is a choice of treatment.

A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design.

Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival. We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients. We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420). These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.

Retroperitoneal Myoepithelial Carcinoma with Heterologous Bone Formation and EWSR1::ZNF444

Abstract Introduction/Objective Soft tissue myoepithelial tumors are rare tumors that affect a wide age range and diverse tissue sites. Fewer than five cases have been reported in the retroperitoneum. Most tumors are benign with the only histologic criterion for malignancy being cytologic atypia. The morphology is broad ranging from spindled to epithelioid cells of varying cellularity in sclerotic to myxoid stroma. Heterologous differentiation may be present. These tumors usually express cytokeratin, EMA, S100, and GFAP and show EWSR1 and FUS rearrangements. Here we present an unusual case of retroperitoneal myoepithelial carcinoma. Methods/Case Report A 29-year-old female presented with rash and painless jaundice. CT and MRCP revealed a relatively circumscribed 3.7 cm mass in the porta hepatis. On fine needle aspiration, a possible gastrointestinal stromal tumor was considered due to DOG1 expression. The patient underwent a Whipple procedure with negative margins showing tumor in soft tissue adjacent to the common bile duct. The tumor was multinodular and consisted predominantly of mild to moderately pleomorphic epithelioid cells in fibromyxoid stroma with interspersed woven bone. Mitoses were not appreciated, and necrosis not seen. The tumor was focally positive for CK AE1/AE3, GFAP, and DOG1 and negative for S100, SOX10, p63, and CD117. INI1 was retained. NGS identified EWSR1::ZNF44 and a diagnosis of myoepithelial carcinoma was rendered. The patient received no adjuvant therapy and has not shown any evidence of metastasis or recurrence for 17 months. Results (if a Case Study enter NA) NA Conclusion Soft tissue myoepithelial carcinomas are aggressive tumors with approximately 40% recurrence and over 50% metastasis. Standard treatment is complete surgical resection. The efficacy of radiation and chemotherapy is not clear. EWSR1 fusions with various partners including POU5F1, PBX1/3, and ZNF44 have been identified. Due to their rarity and varying histology and immunohistochemical expression, identification of gene fusions can be invaluable in diagnosing soft tissue myoepithelial tumors, especially in unusual locations.

The Efficacy, Safety, and Persistence of Therapy after Non-Medical Switching from an Originator Adalimumab in Inflammatory Bowel Disease: Real-Life Experience from Two Tertiary Centres.

During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. Materials and Methods: This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. Aims: The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. Results: No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. Conclusions: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD.

The usefulness of evaluating PTEN expression for accurate grading of phyllodes tumors

Phyllodes tumors (PTs) are classified as benign, borderline, or malignant based on histologic characteristics. However, because histological criteria are subjective and diagnosis requires integrating multiple findings, discrepancies often occur between observers. Therefore, it is necessary to discover biomarkers based on the molecular characteristics of PTs. This study aimed to identify dysregulated microRNAs (miRNAs) in PTs through miRNA profiling and determine whether expression of their target genes could be useful as PT biomarkers. MiRNA profiling was performed on 13 PTs (three malignant, three borderline, seven benign) and six fibroadenomas, and predicted target genes of dysregulated miRNAs were selected using three computation algorithms. The expression of two miRNAs, miR-155 and miR-200c, was 1.69-fold and 1.61-fold higher, respectively, in borderline and malignant PT groups than in the benign PT group (p < 0.05). KEGG pathway analysis revealed that the 374 target genes of these two miRNAs (miR-155 and miR200c) participated in several signaling pathways, adherens junction, cell cycle, and pathway in cancer. Immunohistochemical staining for PTEN, one of candidate target genes of miR-200c, was performed on whole slides of PT tissue classified as malignant (n = 9), borderline (n = 12), or benign (n = 21). Stromal tumor cells of high-grade PTs (borderline and malignant) had significantly lower PTEN expression than those of low-grade PTs (benign) (p-value ≤0.001). Semiquantitative analysis of PTEN expression, score 0–8, revealed that it correlated with histologic findings. Low PTEN expression (s-score of 6 or less) was used as a diagnostic criterion for high-grade PTs, it showed 100 % sensitivity and 95.2 % specificity in 42 cases of PTs. Currently, PT grading based solely on subjective histologic findings is challenging, but semiquantitative PTEN expression analysis could provide a more accurate and objective way to grade PTs.

Impact on natural history of atypical meningioma after changes in 2016 edition of the world health organization (WHO) classification of central nervous system tumors: a literature review.

Meningiomas and their WHO histological diagnostic criteria is complex, especially for grade 2 tumors presenting a interobserverdiscordance as high as 12.2%. The 2016 edition of the WHO Classification of CNS tumors recommended brain invasion as a stand-alone grading criterion for diagnosing an atypical grade 2 meningioma (AM). To provide an overview of the classification of 2016 WHO impact on the natural history of atypical meningioma (AM) relative to previous classification. To achieve this goal, we selected articles from the period 2017-2024 in Medline search on atypical meningiomas and analyzed them after following the following criteria: 1) reports with confirmed histopathological diagnosis according to WHO 2016 and or 2021 criteria; 2) series and case reports; 3) detailed and individualized clinical outcomes for AM; and 4) papers written in English; after that a total of 3445 patients reported in 67 manuscripts from worldwide centers from 2017 to March 2024 were analyzed. The patient's age at the time of surgery ranged from 1month to 97years (mean 52.28 ± 18.7years). The most common tumor site was the convexity, accounting for 67.8%, followed by the skull base in 30.6%, ventricle in 1%, and spine in 0.6%; Gross total resection (GTR) was performed in 71.25% and subtotal resection (STR) in 28.75%; 1021 patients (29.63%) underwent adjuvant radiotherapy, and 22 patients (0.6%) were treated with adjuvant chemotherapy; tumor recurrence was reported in 1221 patients (35.44%) and 859 deaths (24.93%). 1) AM prevalence in females; 2) AM age distribution similar to the distribution of meningiomas in general; 3) AM recurrence rate of 35.44%, despite the high rate of GTR, which was higher than previously reported; 4) deepening knowledge in molecular mechanism of tumor progression will provide alternative therapeutic approaches for AM.

The impact of vildagliptin as an add-on therapy on matrix metalloproteinase-14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non-alcoholic steatohepatitis: A randomized controlled trial.

Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non-alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase-14 (MMP-14) is involved in cardiovascular disease and atherosclerosis. To assess the impact of oral dipeptidyl peptidase-4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP-14 levels and carotid intima media thickness (CIMT). Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP-14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP-14 was positively correlated to insulin dose (p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients (p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP-14 (p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post-therapy compared with baseline levels and compared with the control group (p < 0.001). Vildagliptin was safe and well-tolerated. Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP-14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.

Evaluation of DIAGNOdent pen for initial occlusal caries diagnosis in permanent teeth

BackgroundTo verify the validity of diagnosing initial caries on occlusal surface of permanent posterior teeth by laser fluorescence instrument DIAGNOdent pen.MethodsPatients from School of Stomatology in Wuhan University were selected and their posterior teeth were examined using DIAGNOdent pen and the International Caries Detection and Assessment System (ICDAS II) by an experienced dentist. After teeth extraction, histological criteria were used to determine the severity of the lesions. The sensitivity, specificity, accuracy, the area under the curve (AUC), and correlation of DIAGNOdent pen and ICDAS II were analyzed compared with histological criteria. Examiners’ agreement was measured.ResultsThe sensitivity range was 0.440-1 while that of specificity was 0.750–0.994. The accuracy and AUC were above 80% and 0.7 respectively. Consistency of examiners’ kappa values of ICDAS II, DIAGNOdent pen, and histological criteria were ranged from 0.629 to 0.840.ConclusionsICDAS II and DIAGNOdent pen can be effectively used in tandem or independently for the assessment of initial caries.

Contribution of major histocompatibility complex class II immunostaining in distinguishing idiopathic inflammatory myopathy subgroups: A histopathological cohort study.

Idiopathic inflammatory myopathies (IIM) are rare, acquired muscle diseases; their diagnosis of is based on clinical, serological, and histological criteria. MHC-I-positive immunostaining, although non-specific, is used as a marker for IIM diagnosis; however, the significance of major histocompatibility complex (MHC)-II immunostaining in IIM remains debated. We investigated patterns of MHC-II immunostaining in myofibers and capillaries in muscle biopsies from 103 patients with dermatomyositis ([DM], n = 31), inclusion body myositis ([IBM], n = 24), anti-synthetase syndrome ([ASyS], n = 10), immune-mediated necrotizing myopathy ([IMNM], n = 18), or overlap myositis ([OM], n = 20). MHC-II immunostaining of myofibers was abnormal in 63/103 of patients (61%) but the patterns differed according to the IIM subgroup. They were diffuse in IBM (96%), negative in IMNM (83%), perifascicular in ASyS (70%), negative (61%) or perifascicular (32%) in DM, and either clustered (40%), perifascicular (30%), or diffuse heterogeneous (15%) in OM. Capillary MHC-II immunostaining also identified quantitative (capillary dropout, n = 47/88, 53%) and qualitative abnormalities, that is, architectural abnormalities, including dilated and leaky capillaries, (n = 79/98, 81%) in all IIM subgroups. Thus, MHC-II myofiber expression patterns allow distinguishing among IIM subgroups. We suggest the addition of MHC-II immunostaining to routine histological panels for IIM diagnosis.

Facteurs pronostiques : degré d’invasion de la sous-séreuse, distance tumeur-séreuse et invasion de la limitante élastique de la sous-séreuse dans l’adénocarcinome colique

The aim was to study the prognostic impact of tumor infiltration of the subserosa in colonic adenocarcinoma, by evaluating the degree of tumor infiltration in the subserosa (DISS), tumor-serosa distance (DTS), and invasion of the elastic boundary of the subserosa (ILE) after elastic fiber staining.Material and methods: All patients operated on for colonic adenocarcinoma classified as pT3 without lymph node or visceral metastasis operated on at CHU-Amiens between 2004 and 2017 were included. All slides were reviewed by 2 pathologists. Bivariate and subgroup analyses were performed according to the presence of a DISS ≤5 mm or >5mm, a DTS ≤1mm or >1mm and the presence or absence of an ILE. These statistical analyses were then correlated with 5-year survival.Results: 101 patients were included in the study. We performed elastic fiber staining on an average of 2 tumor blocks per case, and 39.6% of patients had invasion of the elastic boundary. However, bivariate and subgroup analyses showed no statistically significant association between DISS, DTS or ILE and 5-year survival.Conclusion: None of these three histological criteria proved to have prognostic value in our series, contrary to some results in the literature. However, as these data are subject to a number of confounding factors, we do not recommend that pathologists specify these different criteria in their reports.

FP4.9 - Adherence to post Colonic polypectomy surveillance guidelines

Abstract Aims The British Society of Gastroenterology updated its guidelines in 2020 regarding polyps follow-up following colonoscopy. The surveillance depends on type, size, number, and histology criteria. Our aim was to assess adherence of our hospital's endoscopy department to these new guidelines. Methods A retrospective analysis of all consecutive adult patients who underwent colonoscopy were included between January and March 2022 at our hospital. Data were collected and analyzed on excel. The endoscopy report was identified from MediLogik-EMS.Histology from PICS system. Demographics including the specialty of endoscopist was also included. Non-parametric data were expressed in their Median and IQR. Results Out of the 108 patients examined 50/108 (49%) were found to have polyps and were included in the analysis. F: M =1:2, median age 64 with IQR 18.5(59-77.5). Tubular adenoma was found in 58%, hyperplastic polyps in 12%, sessile serrated polyps in 10%, tubulovillous adenoma in 8%, adenocarcinoma in 8%, and inflammatory polyps in 4%. Histopathology revealed tubular adenoma with LGD in 58%, inflammatory polyps in 16%, adenocarcinoma in 8%. Polyps were removed using cold biopsy in 58% and hot snare in 38%. BSG guidelines were followed in 92% (46/50). The reason for not adherence was either histologically incomplete excision, requiring a site check within 2-6 months which was not performed in6%(3)or high-risk features requiring 3 yearly surveillance colonoscopy follow-ups not requested in 2%(1). Conclusion There is high adherence to the guidelines but still not 100%. Our aim is to achieve 100% adherence in the re-audit.

Duodenal and colonic mucosal S100A8/A9 (calprotectin) expression is increased and correlates with the severity of select histologic lesions in dogs with chronic inflammatory enteropathy

BackgroundCalprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE.ResultsMucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P < 0.05). Higher mucosal calprotectin levels in the duodenum and across all segments correlated with lower serum albumin concentrations (both P < 0.05); duodenal mucosal calprotectin concentrations were more than sixfold higher in hypoalbuminemic dogs (median: 1441 µg/g, n = 4) than normoalbuminemic dogs (median: 227 µg/g, n = 40). There was no significant association of mucosal calprotectin levels with CIBDAI scores or individual clinical outcomes.ConclusionsThese results show that duodenal and colonic mucosal calprotectin concentrations are increased in dogs with CIE, providing further supporting evidence for the diagnostic potential of fecal calprotectin (presumably reflecting mucosal) concentrations and in dogs with CIE. Further longitudinal research is needed to assess changes in mucosal calprotectin concentrations with clinical response to treatment vs. mucosal disease remission and to determine the clinical utility of fecal calprotectin concentrations to diagnose and monitor dogs with CIE in clinical practice.

Prognosis of Poorly Differentiated Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Poorly differentiated thyroid carcinoma (PDTC) accounts for a small portion of thyroid carcinomas but contributes to a significant proportion of thyroid carcinoma-associated deaths. The clinicopathological prognostic factors and clinical outcomes of PDTC remain unclear. We aimed to evaluate the clinical outcomes of patients with PDTC after curative treatment. A comprehensive search was performed up to September 2023. We included studies investigating treatment outcomes in patients with PDTC who underwent initial surgery. The 5-year disease-free survival (DFS) and overall survival (OS) were extracted. In this meta-analysis, the enrolled PDTC histological criteria included 3rd, 4th, and 5th World Health Organization (WHO) and Memorial Sloan Kettering Cancer Center (MSKCC) classification. A random-effects model was used for the pooled proportion analysis. Meta-regression analysis was conducted to evaluate the prognostic factors. Twenty retrospective studies published between 2007 and 2023, including 1,294 patients, met all inclusion criteria. Studies that diagnosed PDTC based on various histological criteria including 3rd WHO (n=5), 4th WHO (n=12), 5th WHO (n=2), and MSKCC (n=1) were included. Overall, 5-year DFS and 5-year OS were 49.4% (95% confidence interval [CI], 42.3 to 56.4) and 73.8% (95% CI, 66.5 to 79.9), with moderate heterogeneity of 58% and 55%, respectively. In meta-regression analysis, extrathyroidal extension (ETE) was a prognostic factor for OS. The meta-analysis of DFS and OS in patients with PDTC show the moderate heterogeneity with a variety of histological criteria. ETE appears to have a significant impact on OS, regardless of histological criteria.

Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD-L1 expression, and favourable prognosis.

Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs). Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02). SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis.