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Nodular regenerative hyperplasia (NRH) can manifest as alternating parenchymal compression/expansion on hematoxylin and eosin (H&E) staining and as reticulin collapse/nodularity on reticulin staining. Histologic diagnosis can be challenging, especially when there is mild disease and on limited biopsy samples. We reviewed clinical and histologic parameters in a large series of NRH. We identified 60 liver specimens convincingly showing changes of NRH and reviewed them for clinical (age, sex, symptoms, lab values, portal hypertension [PHTN], NRH etiology) and histologic (inflammation, sinusoidal dilation, cholestasis, architectural change, portal vascular abnormalities, degree of changes on reticulin) parameters. The cases came from 28 women and 32 men (median age: 54 years). Most (55, 92%) were biopsies. Thirty patients were symptomatic. Forty-five cases showed mild NRH changes on reticulin; 24 of these (53%) showed them on H&E as well. Fifteen demonstrated well-developed changes on reticulin, which were always seen on H&E as well. Sinusoidal dilation was commonly observed in both of these subgroups (88% overall). Portal vascular abnormalities were seen in 33%. Well-developed NRH was diffuse more often than mild NRH (53% vs. 4%, P < 0.0001). Twenty-nine patients had clinically confirmed or likely PHTN. Of these, 21 showed mild and 8 showed well-developed NRH changes; only 3 had concomitant advanced fibrosis. Chemotherapy was the most frequent known cause of NRH; 30 patients lacked any definite etiology. NRH can be difficult to diagnose on biopsy, particularly since mild changes may be visible on reticulin but not H even these patients can have PHTN. Additionally, NRH is often idiopathic, potentially lowering clinical and pathologic suspicion. Pathologists should have a low threshold for ordering reticulin stains, especially when a patient is known to have PHTN. Sinusoidal dilation, while nonspecific, commonly accompanies NRH.

The objectives are to precisely identify the cells that incite the formation of lesions that are generally known as “pulse granuloma” or “hyaline ring granuloma” that occur mostly in the oral cavity, in the lungs, in and around the gastrointestinal tract, and other sites, and to suggest an alternative name for these lesions that accurately reflects their etiology. Critical review of the medical and dental literature was undertaken, and the microscopic appearances of granuloma-inciting cells depicted in the literature and seen in our practices were compared with seeds and their contents originating from a variety of leguminous and non-leguminous plants. Sections of selected seeds were examined microscopically before and after digestion with saliva and alpha amylase and subsequent routine processing and staining with H&E, PAS, and iodine. Pre- and post-digestion slides were examined with polarized light. The morphology of the granuloma-inciting cells is identical to the storage cells present in seeds from a variety of leguminous and non-leguminous plants. The cells that trigger the formation of “pulse granulomas”/“hyaline ring granulomas” are storage cells that are derived from ingested seeds of leguminous and non-leguminous plants. The terms “pulse,” “legume,” and “lentil,” which have been applied to these cells, are misnomers. Our findings indicate that the terms “pulse granuloma” and “hyaline ring granuloma” are not appropriate descriptors of these lesions. We recommend that they be replaced by “seed storage cell granuloma,” a term that now accurately reflects the etiology of these lesions.

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA. Combined hepatocellular-cholangiocarcinomas (cHCC-CCA) are challenging to diagnose, as they exhibit features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). Here, the authors use deep learning to re-classify cHCC-CCA tumours into HCC or ICCA based on histopathology images.

Anogenital mammary-like glands (AGMLGs) are present in the anogenital region that bear striking morphologic and protein-expression similarities to mammary glands in the breast. AGMLGs can give rise to both benign and malignant lesions which mimic primary breast lesions. Herein, we report two mammary-type adenocarcinomas arising from AGMLGs, including one in the previously unreported site of the rectum. Recognition of mammary-type adenocarcinoma in the rectal and anogenital regions is crucial as clinical management options may differ compared to conventional colorectal adenocarcinomas.

Standard-of-care (SoC) imaging for assessing colorectal polyps during colonoscopy, based on white-light colonoscopy (WLC) and narrow-band imaging (NBI), does not have sufficient accuracy to assess the invasion depth of complex polyps non-invasively during colonoscopy. We aimed to evaluate the feasibility of a custom endoscopic optical coherence tomography (OCT) probe for assessing colorectal polyps during routine colonoscopy. Patients referred for endoscopic treatment of large colorectal polyps were enrolled in this pilot clinical study, which used a side-viewing OCT catheter developed for use with an adult colonoscope. OCT images of polyps were captured during colonoscopy immediately before SoC treatment. A deep learning model was trained to differentiate benign from deeply invasive lesions for real-time diagnosis. 35 polyps from 32 patients were included. OCT imaging added on average 3:40 min (range 1:54–8:20) to the total procedure time. No complications due to OCT were observed. OCT revealed distinct subsurface tissue structures that correlated with histological findings, including tubular adenoma ( n  = 20), tubulovillous adenoma ( n  = 10), sessile serrated polyps ( n  = 3), and invasive cancer ( n  = 2). The deep learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.984 (95%CI 0.972–0.996) and Cohen’s kappa of 0.845 (95%CI 0.774–0.915) when compared to gold standard histopathology. OCT is feasible and safe for polyp assessment during routine colonoscopy. When combined with deep learning, OCT offers clinicians increase confidence in identifying deeply invasive cancers, potentially improving clinical decision-making. Compared to previous studies, ours offers a nuanced comparison between not just benign and malignant lesions, but across multiple histological subtypes of polyps.

AimsForegut cystic malformations are rare developmental abnormalities, which may involve the hepatopancreaticobiliary tract (HPBT). These cysts are composed of inner ciliated epithelium; subepithelial connective tissue layer; smooth muscle layer; and an outer fibrous layer. While radiopathologic findings are often diagnostic, atypical location and histologic features can pose a diagnostic challenge. We aimed to study ciliated foregut cysts (CFCs) in the HPBT, assess their clinicopathological features with a focus on atypical features.MethodsWe collected cases of CFCs involving the HPBT from three large academic medical centres. H&E-stained slides and immunohistochemical stains (where available) were reviewed for each case. Relevant demographic, clinical and pathological information was collected from the medical records.Results21 cases were identified. The median age was 53 years (range, 3–78 years). 17 cysts were identified within the liver (segment 4 was the most common location, n=10) and 4 in the pancreas. Cysts were mostly identified incidentally (n=13), abdominal pain was a common symptom (n=5). Cyst size ranged from 0.7 to 17.0 cm (median, 2.5 cm). Radiological findings were available in 17 cases. Cilia were identified in all cases. 19 of 21 cases demonstrated the presence of a smooth muscle layer (thickness, <0.1 mm to 3.0 mm). Three cases showed gastric metaplasia, while one case revealed additional low-grade dysplasia, with features similar to intraductal papillary neoplasm of the bile duct.ConclusionsWe highlight clinicopathological features of CFCs in the HPBT. The histomorphology is usually straightforward; however, unusual location and atypical features can pose a diagnostic challenge.

Background: 2008 World Health Organization (WHO) classification of hematolymphoid neoplasms (HLN) has classified them based on morphology, results of various ancillary techniques, and clinical features.[1] There are no studies looking at the applicability of WHO classification. Aims: The aim of the study was to calculate proportions of all HLN subtypes seen during 1-year period based on 2008 WHO classification of HLN and study applicability and also shortcomings of practices in a tertiary care center in India. Materials and Methods: This was a 1-year retrospective study (January 1st, to December 31st, 2010) where cases were identified using hospital/laboratory electronic records. Old follow-up and referral cases were excluded from the study. Only newly diagnosed cases classified into categories laid down by 2008 WHO classification of HLN included. Results: Out of 2118 newly diagnosed classifiable cases, 1602 (75.6%) cases were of lymphoid neoplasms, 489 (23.1%) cases of myeloid neoplasms, 16 (0.8%) cases of histiocytic and dendritic cell neoplasms, and 11 (0.5%) cases of acute leukemias of ambiguous lineage. Overall, most common HLN subtype was diffuse large B-cell lymphoma (n = 361, 17.0%). Precursor B-lymphoblastic leukaemia/lymphoma (n = 177, 48.2%) was the most common subtype within pediatric age group. Conclusions: All major subtypes of HLN were seen at our center and showed trends almost similar to those seen in other Indian studies. Molecular/cytogenetic studies could not be performed on a significant number of cases owing to logistic reasons (unavailability of complete panels and also cost-related issues) and such cases could not be classified as per the WHO classification system.