Clinicopathologic Features of Gastrointestinal Tract Langerhans Cell Histiocytosis.

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin- and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed non-polypoid lesions. Seven (88%) showed multifocal GI disease, including five with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single-system), with the remaining 14 (36%) exhibiting multi-system disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multi-system LCH more frequently presented with GI symptoms (92%, P<0.001), non-colorectal GI site involvement (50%, P=0.02), multifocal GI lesions (43%, P=0.005), non-polypoid lesions (71%, P<0.001), infiltrative histologic growth pattern (78%, P=0.04), and persistent disease (57%, P<0.001). Adult multi-system LCH patients appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrate that adults with single-system LCH involving the GI tract have an excellent prognosis, while multi-system LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, non-colorectal GI involvement, multifocal GI disease, non-polypoid lesions, and infiltrative growth pattern.

α-Catenin phosphorylation promotes intercellular adhesion through a dual-kinase mechanism.

The cadherin-catenin adhesion complex is a key contributor to epithelial tissue stability and dynamic cell movements during development and tissue renewal. How this complex is regulated to accomplish these functions is not fully understood. We identified several phosphorylation sites in mammalian αE-catenin (also known as catenin α-1) and Drosophila α-Catenin within a flexible linker located between the middle (M)-region and the carboxy-terminal actin-binding domain. We show that this phospho-linker (P-linker) is the main phosphorylated region of α-catenin in cells and is sequentially modified at casein kinase 2 and 1 consensus sites. In Drosophila, the P-linker is required for normal α-catenin function during development and collective cell migration, although no obvious defects were found in cadherin-catenin complex assembly or adherens junction formation. In mammalian cells, non-phosphorylatable forms of α-catenin showed defects in intercellular adhesion using a mechanical dispersion assay. Epithelial sheets expressing phosphomimetic forms of α-catenin showed faster and more coordinated migrations after scratch wounding. These findings suggest that phosphorylation and dephosphorylation of the α-catenin P-linker are required for normal cadherin-catenin complex function in Drosophila and mammalian cells.

Imaging of pancreatic serous cystadenoma and common imitators.

Pancreatic cystic neoplasms are lesions comprised of cystic components that show different biological behaviors, epidemiology, clinical manifestations, imaging features, and malignant potential and management. Benign cystic neoplasms include serous cystic neoplasms (SCAs). Other pancreatic cystic lesions have malignant potential, such as intraductal papillary mucinous neoplasms and mucinous cystic neoplasms. SCAs can be divided into microcystic (classic appearance), honeycomb, oligocystic/macrocystic, and solid patterns based on imaging appearance. They are usually solitary but may be multiple in von Hippel-Lindau disease, which may depict disseminated involvement. The variable appearances of SCAs can mimic other types of pancreatic cystic lesions, and cross-sectional imaging plays an important role in their differential diagnosis. Endoscopic ultrasonography has helped in improving diagnostic accuracy of pancreatic cystic lesions by guiding tissue sampling (biopsy) or cyst fluid analysis. Immunohistochemistry and newer techniques such as radiomics have shown improved performance for preoperatively discriminating SCAs and their mimickers.

"Imaging Findings of Eosinophilic Gastrointestinal Diseases in Adults".

Eosinophilic gastrointestinal (GI) disorders are a group of conditions marked by pathologic eosinophilic infiltration of one or multiple locations in the GI tract. Conditions include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis. The site and depth of eosinophilic infiltration of the GI tract usually determines clinical presentation. These conditions should be considered in the differential diagnosis for several GI symptoms, such as food impaction or dysphagia. Histopathology is the gold standard for diagnosis of eosinophilic disorders. Nevertheless, findings from endoscopy, barium studies, computed tomography or magnetic resonance imaging, can aid in the diagnosis, by allowing for earlier diagnosis as well as proper management. Eosinophilic gastrointestinal disorders are typically managed with corticosteroids or dietary elimination. A high index of suspicion is required for diagnosis as it can often be challenging.

HER2+ esophageal carcinoma leptomeningeal metastases treated with intrathecal trastuzumab regimen.

Materials & methods: We recently reported the largest trial of breast cancer patients with HER2 positive leptomeningeal metastases (LM) treated with trastuzumab. An additional treatment indication was explored as part of a single institution retrospective case series of HER2 positive esophageal adenocarcinoma LM (n = 2). Results: One patient received intrathecal trastuzumab (80 mg twice weekly) as part of their treatment regimen with durable long-term response and clearance of circulating tumor cells in the cerebral spinal fluid. The other patient demonstrated rapid progression and death as previously described in the literature. Conclusion: Intrathecal trastuzumab is a well-tolerated and reasonable therapeutic option worthy of further exploration for patients with HER2 positive esophageal carcinoma LM. An associative, but not a causal relationship, can be made regarding therapeutic intervention.

Cancer of the esophagus, the tube that connects the mouth to the stomach, tends to be aggressive. Very rarely, this cancer can spread to the lining that surrounds your brain, called the leptomeninges. Previous reports of patients who have experienced this specific spreading pattern of esophageal cancer to the leptomeninges are quite grim, with patients experiencing rapid decline and death within weeks to months. However, we write with two cases of esophageal cancer with this leptomeningeal spreading pattern, one of which involves a patient treated with a medication known as trastuzumab. As part of his long and complex course of treatment, this patient was given trastuzumab through a tube traveling directly to the area of the leptomeninges. This patient, now almost 2 years out from his initial diagnosis, has responded well to the treatment. As such, we believe that this specific treatment regimen as well as the ways in which our clinical team tracked this patient's response to medications are worth exploring further.

An RNAi screen reveals intestinal regulators of branching morphogenesis, differentiation, and stem cell proliferation in planarians.

Planarians grow and regenerate organs by coordinating proliferation and differentiation of pluripotent stem cells with remodeling of postmitotic tissues. Understanding how these processes are orchestrated requires characterizing cell-type-specific gene expression programs and their regulation during regeneration and homeostasis. To this end, we analyzed the expression profile of planarian intestinal phagocytes, cells responsible for digestion and nutrient storage/distribution. Utilizing RNA interference, we identified cytoskeletal regulators required for intestinal branching morphogenesis and a modulator of bioactive sphingolipid metabolism, ceramide synthase, required for the production of functional phagocytes. Additionally, we found that a gut-enriched homeobox transcription factor, nkx-2.2, is required for somatic stem cell proliferation, suggesting a niche-like role for phagocytes. Identification of evolutionarily conserved regulators of intestinal branching, differentiation, and stem cell dynamics demonstrates the utility of the planarian digestive system as a model for elucidating the mechanisms controlling postembryonic organogenesis.