Fundic gland polyps related to diverse aetiologies show subtle morphological differences: a multicentre retrospective study.

AIMS: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes. METHODS AND RESULTS: We performed a retrospective analysis of 118 FGPs from 109 patients for the architecture of fundic glands, microcyst lining, parietal cell hyperplasia and surface foveolar epithelial changes. Age, gender and history of FAP or GAPPS were collected. Based on combinations of histological features, three distinct patterns (A, B and C) of FGPs were delineated and correlated to the aetiologies. Non-syndromic FGPs were well-formed polyps composed of disordered fundic glands with intermediate-sized microcysts typically lined by a mixture of oxyntic and mucin-secreting cells (73%). Parietal cell hyperplasia (80%) and foveolar surface hyperplasia (78%) were common. FAP-associated cases demonstrated small microcysts that were predominantly lined by fundic epithelium (77%), with limited parietal cell hyperplasia (27%); foveolar hyperplasia was uncommon. GAPPS-related polyps were the largest, with prominent, mucin-secreting epithelium-lined microcysts (73%). Hyperproliferative aberrant pits were universally present, whereas parietal cell hyperplasia was uncommon. Pattern A was identified in most non-syndromic FGPs (74%) and in a minority of FAP-related FGPs (26%). The majority (82%) of FAP-related FGPs showed pattern B, but only 18% of non-syndromic FGPs did. Pattern C consisted exclusively of GAPPS-associated polyps. CONCLUSIONS: We conclude that, although FGPs share similar histomorphology, subtle differences exist between polyps of different aetiology. In the appropriate clinical setting, the recognition of these variations may help to consider syndromic aetiologies.

Morphological characteristics, classifications and difficulties in the use of diagnostic criteria for serrated lesions of the large intestine

Abstract: Introduction Colorectal carcinoma (CRC) is the most common gastrointestinal neoplasm in the world, accounting for 15% of cancer-related deaths. This condition is related to different molecular pathways, among them the recently described serrated pathway, whose characteristic entities, serrated lesions, have undergone important changes in their names and diagnostic criteria in the past thirty years. The multiplicity of denominations and criteria over the last years may be responsible for the low interobserver concordance (IOC) described in the literature. Objectives: The present study aims to describe the evolution in classification of serrated lesions, based on the last three publications of theWorld Health Organization (WHO) and the reproducibility of these criteria by pathologists, based on the evaluation of the IOC. Methods: A search was conducted in the PubMed, ResearchGate and Portal Capes databases, with the following terms: sessile serrated lesion; serrated lesions; serrated adenoma; interobserver concordance; andreproducibility.Articlespublished since 1990were researched. Results and Discussion: The classification of serrated lesions in the past thirty years showed different denominations and diagnostic criteria. The reproducibility and IOC of these criteria in the literature, based on the kappa coefficient, varied in most studies, from very poor to moderate. Conclusions: Interobserver concordance and the reproducibility of microscopic criteria may represent a limitation for the diagnosis andappropriatemanagementof these lesions. It is necessary to investigate diagnostic tools to improve the performance of the pathologist's evaluation, for better concordance, and, consequently, adequate diagnosis and treatment. (AU)

Single Shot Multibox Detector Automatic Polyp Detection Network Based on Gastrointestinal Endoscopic Images.

PURPOSE: In order to resolve the situation of high missed diagnosis rate and high misdiagnosis rate of the pathological analysis of the gastrointestinal endoscopic images by experts, we propose an automatic polyp detection algorithm based on Single Shot Multibox Detector (SSD). METHOD: In the paper, SSD is based on VGG-16, the fully connected layer is changed to a convolutional layer, and four convolutional layers with successively decreasing scales are added as a new network structure. In order to verify the practicability, it is not only compared with manual polyp detection but also with Mask R-CNN. RESULTS: Multiple experimental results show that the mean Average Precision (mAP) of the SSD network is 95.74%, which is 12.4% higher than the manual detection and 5.7% higher than the Mask R-CNN. When detecting a single frame of image, the detection speed of SSD is 8.41 times that of manual detection. CONCLUSION: Based on the traditional pattern recognition algorithm and the target detection algorithm using deep learning, we select a variety of algorithms to identify and classify polyps to achieve efficient detection results. Our research demonstrates that deep learning has a lot of room for development in the field of gastrointestinal image recognition.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. METHODS: One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. RESULTS: GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. CONCLUSIONS: We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

Pachychoroid Spectrum Disease: Underlying Pathology, Classification, and Phenotypes.

PURPOSE: Pachychoroid spectrum disease encompasses a set of macular disorders secondary to an abnormally thick choroid. However, the pathological process underlying pachychoroid spectrum disease and its overlap with age-related macular degeneration (AMD) remain unclear. This review aimed to understand the underlying pathology, classification, and phenotypes of pachychoroid spectrum disease. METHODS: This comprehensive literature review was performed based on a search of peer-reviewed published papers relevant to the current knowledge of pachychoroid disease spectrum. RESULTS: Pachychoroid is primarily a bilateral phenomenon; the main pathological lesions include choriocapillaris attenuation and abnormally dilated pachyvessels. Chronic central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV) show similar morphological changes and angiogenic cytokine levels. The subretinal fluid in PNV may not accurately indicate PNV activity. Besides, types 1 and 2 of choroidal neovascularization (CNV) may be involved in primary pachychoroidal disease. Both choroidal arteriosclerosis and higher hydrostatic pressure contribute to hyalinized choroidal arteries and aneurysmal dilatations, resulting in PNV progression to polypoidal choroidal vasculopathy (PCV). Thus, pachychoroid-related type 2 CNV and chronic CSC could be considered as PNV (IIIc) and as a precursor of PNV (IIIa), respectively. Tangled PCV on optical coherence tomography angiography that fails to develop aneurysms should be classified as a subtype of PNV or a forme fruste of PCV. CONCLUSIONS: Multiple disorders of the pachychoroid spectrum are considered as a continuous disease process, ultimately stimulated by choroidal malfunction. PCV overlaps both AMD and pachychoroid disease, especially for thin-choroid and bilateral types. The terminology and classification of pachychoroid spectrum disease should be used cautiously.

The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment.

The recently published 5th edition 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System brings significant changes from the 2010 4th edition. An emphasis on uniformity in nomenclature and grading for tumours across all organ systems is a particular feature of the 5th edition blue book series that is reflected in the gastrointestinal tract (GIT) classification. For example, simplified two tiered grading is reinforced for preinvasive lesions throughout the GIT, with dysplasia at all sites now being considered either low or high grade. Similarly, a uniform approach to classification and grading of GIT neuroendocrine neoplasms has been consolidated, with an emphasis on distinguishing grade 3 neuroendocrine tumours from neuroendocrine carcinomas. In this review, we discuss and critically assess the important and sometimes controversial changes made to the classification of tumours of the lower GIT, comprising the colorectum, vermiform appendix and anal canal. The particularly controversial decision to endorse the term 'sessile serrated lesion' for lesions previously termed 'sessile serrated polyp/adenoma' is explored. The morphological, molecular, and clinical insights behind the substitution of the term 'goblet cell adenocarcinoma' for 'goblet cell carcinoid' are assessed. The evolution of the classification of appendiceal mucinous neoplasms is considered. Inflammatory bowel disease related dysplasia and its evolving subtypes, with major implications for pathologists in routine practice, is explained.

Intracholecystic tubular non-mucinous neoplasm (ICTN) of the gallbladder: a clinicopathologically distinct, invasion-resistant entity.

Preinvasive tumor-forming gallbladder neoplasms that are composed of small, non-mucinous tubules with complex architecture remain a poorly characterized group. Here, we evaluated the clinicopathological characteristics of this entity. Twenty-eight examples were analyzed. Tumors were invariably pedunculated polyps with thin stalks, often presented as loosely attached intraluminal nodules, with cauliflower architecture (akin to cholesterol polyps) comprised of compact, back-to-back acinar-like, small tubular units with minimal/no cytoplasm showing variable complexity, creating a picture distinct from the other tubular type dysplasia in the gallbladder. Their limited stroma showed distinctive amorphous amyloid-like hyalinization (39%). While some had round nuclei with single prominent nucleoli, others exhibited slightly more elongated nuclei with washed out chromatin reminiscent of papillary thyroid carcinoma. Squamoid/meningothelial-like morules (71%) and subtle neuroendocrine cell clusters (39%) were frequent. The level of cytoarchitectural atypia qualified as high-grade dysplasia (HGD) in all cases, but none were invasive. The background mucosa showed no dysplasia, but cholesterolosis. The majority (n = 8/12) showed diffuse MUC6 expression and lacked MUC5AC expression. Based on these observations, 635 gallbladder carcinomas were re-analyzed for residual/adjacent lesions with entity-defining characteristics disclosed here, and none could be identified. Preinvasive tubular non-mucinous neoplasm of the gallbladder, which we propose to classify as intracholecystic tubular non-mucinous neoplasm, is a clinicopathologically discrete entity, which tends to occur in uninjured gallbladders and in association with cholesterol polyps. By being tubular, non-mucinous and MUC6-positive, it is akin to intraductal tubulopapillary neoplasms of pancreatobiliary tract, but it is also different in many other aspects. Although their cytoarchitectural complexity warrants an HGD/carcinoma classification, they do not show invasion and their distinct characteristics warrant their separate classification.

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup.

PURPOSE: To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings. DESIGN: Evaluation of diagnostic test results. PARTICIPANTS: Panel of retina specialists. METHODS: As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. MAIN OUTCOME MEASURES: Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. RESULTS: The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%. CONCLUSIONS: We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Intracholecystic Papillary-Tubular Neoplasms (ICPN) of the Gallbladder: A Short Review of Literature.

Increasing use of radiographic studies of the hepatobiliary system has led to a growing diagnostic rate of many asymptomatic polyps of the gallbladder which would have gone undiagnosed otherwise. Neoplastic polyps of the gallbladder are 5% of the total number of polyps of this organ. However, due to their malignant potential, the correct diagnosis and classification become of crucial importance. Lack of unified terminology and reporting criteria have led to a limited body of scientific evidence regarding their classification and management. Therefore in 2012 the novel and unified terminology, Intracholecystic papillary-tubular neoplasm was proposed for these lesions when they measure >1 cm. Smaller lesions are usually of no adverse outcome. Intracholecystic papillary-tubular neoplasms show 5 histologic subcategories: (1) pyloric gland subtype which is the most commonly encountered neoplastic polyp in the gallbladder and has the lowest rate of harboring high-grade dysplasia and invasive carcinoma and it shows diffuse cytoplasmic positivity with MUC6, a specific pyloric marker; (2) biliary subtype which is diffusely positive for MUC1 and has the highest risk of concurrent adenocarcinoma; (3) gastric foveolar subtype which is MUC5AC positive in all the cases. Most of the cases in this category are associated with some extent of high-grade dysplasia; (4) intestinal subtype which is the easiest one to recognize as it mimics tubular adenomas of the gastrointestinal tract and show MUC2 and CDX2 positivity; and (5) oncocytic subtype which is the least common.

The role of imaging and biopsy in the management and staging of large non-pedunculated rectal polyps.

INTRODUCTION: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are often used for benign and Sm1 large non-pedunculated rectal polyps (LNPRPs), although other surgical techniques including transanal endoscopic microsurgery (TEMS) and transanal minimal invasive surgery remain available. This review covers the role of pre-excisional imaging and selective biopsy of LNPRPs. Areas covered: Polyps between 2 and 3 cm with favorable features (Paris 1, Kudo III/IV pit patterns, and non-lateral spreading type [LST]) may have a one-stage EMR without biopsy and imaging, provided adequate expertise is available with other technologies such as magnifying chromoendoscopy. Higher-risk polyps (moderate/severe dysplasia, 0-IIa+c morphology, nongranular LST, Kudo pit pattern V or submucosal carcinoma, or those >3 cm) should have pre-EMR/ESD imaging with magnetic resonance imaging (MRI) and/or endorectal ultrasound (ERUS) ± biopsies and photographs prior to multidisciplinary team discussion. Expert commentary: In some centers, EMR and ESD are considered the primary modality of treatment, with TEMS as a back-up, while elsewhere, TEMS is the main modality for excision of significant polyps and early colorectal cancer lesions. Likewise, the exact roles of ERUS and MRI will depend on availability of local expertise, although it is suggested that the techniques are complementary.

EVEREST Report 5: Clinical Outcomes and Treatment Response of Polypoidal Choroidal Vasculopathy Subtypes in a Multicenter, Randomized Controlled Trial.

Purpose: The purpose of this study was to describe the characteristics of polypoidal choroidal vasculopathy (PCV) subtypes among patients from a multicenter randomized controlled trial and to determine the impact of PCV subtypes on clinical outcomes. Methods: This was a prospective cohort study of 61 patients with macular PCV from the EVEREST study. Indocyanine green (ICGA) and fluorescein angiography (FA) obtained using standardized imaging protocols were graded to classify PCV into three subtypes. Type A PCV had polyps with interconnecting channels, type B had polyps with branching vascular networks, but no significant leakage on FA, and type C had polyps with branching vascular networks and leakage on FA. The best-corrected visual acuity (BCVA) and proportion of patients with BCVA ≥ 20/40 were compared among the three PCV subtypes. Results: Of the 61 patients, 54 were gradable for PCV subtype. Among these, 8 had type A PCV (14.8%), 27 had type B (50%), and 19 had type C (35.2%). At baseline, BCVA was 67.1 letters for type A, 58.7 for type B, and 43.5 for type C (P < 0.001). At 6 months, BCVA was highest among patients with type A compared with types B and C (80.1 letters versus 67.2 versus 50.4, respectively; P < 0.001). Type A PCV gained 13 letters compared with 8.5 (type B) and 6.9 (type C). BCVA ≥ 20/40 was highest for type A compared with types B and C (100% vs. 51.9% vs. 10.5%; P < 0.001). On performing ANCOVA, PCV subtype and baseline BCVA significantly affected final BCVA. Conclusions: The visual outcome following treatment varies with PCV subtype classification. The distinction in clinical outcomes between the PCV subtypes is observed in the initial months following the start of treatment.

Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of 'expanded spectra' - a review.

The term aneurysmal type 1 neovascularization is derived from terminology, which is established in the literature but has fallen out of use. We believe that aneurysmal type 1 neovascularization accurately describes the lesions which define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last three decades, the clinical spectrum of PCV has expanded to recognize the occurrence of the aneurysmal (polypoidal) lesions in different contexts, resulting in a complex and unwieldy taxonomy based sometimes on circumstantial findings rather than mechanistic considerations. Advances in multimodal imaging provides increasingly convincing evidence that the lesions which define various forms of PCV are indeed vascular and arise from type 1 neovascular networks. The understanding of PCV as type 1 neovascularization with aneurysms renews focus on the question as to why some patients with type 1 neovascularization develop aneurysms while others do not. Conceptual themes and potential for further study are discussed.

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei.

The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.

Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy.

BACKGROUND/AIMS: To compare the short-term efficacy of intravitreal aflibercept treatment according to the subtypes of polypoidal choroidal vasculopathy (PCV) based on indocyanine green angiography (ICGA). METHODS: Twenty-nine patients (29 eyes) with treatment-naïve subfoveal PCV were consecutively enrolled in this institutional study. The subjects were classified into two subtypes (type 1, polypoidal choroidal neovascularisation (CNV), 16 eyes; and type 2, idiopathic PCV, 13 eyes) based on the presence or absence of both feeder and draining vessels on ICGA. Intravitreal aflibercept was administered at baseline and at 1, 2 and 4 months. The primary outcome was the polyp regression percentage after 3 monthly injections. Changes in the best-corrected visual acuity and subfoveal choroidal thickness (CT) were evaluated at 3 and 6 months. RESULTS: The complete polyp regression percentage was higher in type 1 than type 2 patients after 3 monthly injections (81% vs 30%, p=0.008). Type 1 patients showed better visual improvement at 3 months (-0.34 vs -0.08 logarithm of the minimum angle of resolution (logMAR), p=0.050) and 6 months (-0.30 vs -0.10 logMAR, p=0.168) than type 2 patients. Although subfoveal CT was significantly decreased after injections in both groups, type 2 patients with a thicker choroid at baseline showed a greater decrease than type 1 patients (p=0.032). CONCLUSIONS: There was a difference in early treatment response with aflibercept between two subtypes of PCV. Type 1 polypoidal CNV showed better visual improvement with a higher percentage of polyp regression than type 2 idiopathic PCV. TRIAL REGISTRATION NUMBER: NCT02597855, Results.

PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

PURPOSE: To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. METHODS: Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. RESULTS: Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). CONCLUSION: Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

Toward a specific classification of polypoidal choroidal vasculopathy: idiopathic disease or subtype of age-related macular degeneration.

PURPOSE: To suggest a clinical distinction between idiopathic polypoidal choroidal vasculopathy (PCV) and secondary polyps associated with neovascular age-related macular degeneration (NV-AMD). METHODS: The study was a retrospective case series of 52 eyes of 52 consecutive patients (31 females and 21 males) diagnosed with PCV. Initial diagnosis was based on scanning laser ophthalmoscope-indocyanine green angiography (SLO-ICGA) in association with fluorescein angiography (FA) and optical coherence tomography (OCT). All the data and images were analyzed in a masked fashion by four experienced examiners in two different sessions: the first, to classify patients into the two hypothesized groups (idiopathic polyps or NV-AMD-related polyps); the second, following a predetermined scheme, to describe objective features. The results obtained in each session underwent a cross multivariate analysis to identify statistically significant differences (P ≤ 0.05) between the two groups. RESULTS: The two groups were clinically different on the basis of FA (leakage origin [P = 0.001] and presence of drusen [P = 0.001]), ICGA (evidence of choroidal neovascularization [CNV; P = 0.001] and/or branching vascular network [BVN; P = 0.001]), OCT imaging (type of pigmented epithelium detachment [P = 0.001], presence of BVN [P = 0.001], and subfoveal choroidal thickness [P = 0.001]). Further significant differences were observed according to the location of lesion (uni- or multifocal) (P = 0.001), type of CNV (P = 0.001), and best-corrected visual acuity (P = 0.001). CONCLUSIONS: Our study demonstrated clinical and statistically significant differences between idiopathic PCV and NV-AMD-related polyps that could be considered as distinct entities. Although they share some similarities, mainly the sub-RPE location, the ability to identify a specific clinical pattern suggests a more specific therapeutic approach for these two entities.