Eosinophil Granule Research Articles

Eosinophilic esophagitis auxiliary diagnosis based on a peptide ligand to eosinophil cationic protein in esophageal mucus of pediatric patients

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils’ counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.

Effect of light-emitting diodes with different color rendering indexes on the ocular tissues of rat

To compare the damage of light-emitting diodes (LEDs) with different color rendering indexes (CRIs) to the ocular surface and retina of rats. Totally 20 Sprague-Dawley (SD) rats were randomly divided into four groups: the first group was normal control group without any intervention, other three groups were exposed by LEDs with low (LED-L), medium (LED-M), and high (LED-H) CRI respectively for 12h a day, continuously for 4wk. The changes in tear secretion (Schirmer I test, SIt), tear film break-up time (BUT), and corneal fluorescein sodium staining (CFS) scores were compared at different times (1d before experiment, 2 and 4wk after the experiment). The histopathological changes of rat lacrimal gland and retina were observed at 4wk, and the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lacrimal gland were detected by immunofluorescence method. With the increase of light exposed time, the CFS value of each light exposed group continued to increase, and the BUT and SIt scores continued to decrease, which were different from the control group, and the differences between the light exposed groups were statistically significant. Hematoxylin-eosin (HE) results showed that the lacrimal glands of each exposed group were seen varying degrees of acinar atrophy, vacuole distribution, increasing of eosinophil granules, etc.; the retina showed obvious reduction of photoreceptor cell layer and changes in retinal thickness; LED-L group has the most significant change in all tests. Immunofluorescence suggested that the positive expressions of TNF-α and IL-6 in the lacrimal glands of each exposed group were higher than those of the control group. LED exposure for 4wk can cause the pathological changes of lacrimal gland and retina of rats, and increase the expression of TNF-α and IL-6 in lacrimal gland, the degree of damage is negatively correlated with the CRI.

Essential Role of Enzymatic Activity in the Leishmanicidal Mechanism of the Eosinophil Cationic Protein (RNase 3).

The recruitment of eosinophils into Leishmania lesions is frequently associated with a favorable evolution. A feasible effector for this process is eosinophil cationic protein (ECP, RNase 3), one of the main human eosinophil granule proteins, endowed with a broad spectrum of antimicrobial activity, including parasites. ECP was active on Leishmania promastigotes and axenic amastigotes (LC50’s = 3 and 16 μM, respectively) but, in contrast to the irreversible membrane damage caused on bacteria and reproduced by its N-terminal peptides, it only induced a mild and transient plasma membrane destabilization on Leishmania donovani promastigotes. To assess the contribution of RNase activity to the overall leishmanicidal activity of ECP, parasites were challenged in parallel with a single-mutant version, ECP-H15A, devoid of RNase activity, that fully preserves the conformation and liposome permeabilization ability. ECP-H15A showed a similar uptake to ECP on promastigotes, but with higher LC50’s (>25 μM) for both parasite stages. ECP-treated promastigotes showed a degraded RNA pattern, absent in ECP-H15A-treated samples. Moreover ECP, but not ECP-H15A, reduced more than 2-fold the parasite burden of infected macrophages. Altogether, our results suggest that ECP enters the Leishmania cytoplasm by an endocytic pathway, ultimately leading to RNA degradation as a key contribution to the leishmanicidal mechanism. Thus, ECP combines both membrane destabilization and enzymatic activities to effect parasite killing. Taken together, our data highlight the microbicidal versatility of ECP as an innate immunity component and support the development of cell-penetrating RNases as putative leishmanicidal agents.

Bulboma: A Benign Keratosis With Differentiation Toward the Lower Segment of the Hair Follicle.

:Bulboma is an appellation proposed to designate a distinctive solitary keratosis exhibiting differentiation toward the bulb of the lower segment of the hair follicle. Bulboma is composed of a papillated proliferation of epithelial cells beneath which is a broad front of interconnected follicular papillae. Overlying these coalescing follicular papillae are follicular germinative cells ascending into matrical cells and supramatrical cells. Cells demonstrating differentiation toward Huxley's and Henle's layer of the inner root sheath at the level of the bulb are present including strikingly bright eosinophilic trichohyalin granules and the blue-grey corneocytes of the stem. There is overlying hypergranulosis and orthokeratosis. The clinical and histopathological findings in 4 cases of bulboma, a rare, benign solitary keratosis are presented.

Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma.

Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids. Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear. To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness. Patients with severe asthma according to European Respiratory Society/American Thoracic Society criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-week course of prednisolone. 132 severe asthmatics were included in the study. 39 (29.5%) patients had ≥10 pack-years of smoking history: 36 (27.3%) were former smokers and three (2.3%) current smokers; and 93 (70.5%) had <10 pack-years exposure. Eosinophilic airway inflammation was more prevalent among patients with ≥10 pack-years (66.7%), compared to patients with <10 pack-years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO (p<0.05 and p<0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a ≥10 pack-year smoking history. In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation and relative insensitivity to steroids, as well as airway autoimmunity.

Acupoint catgut embedment may reduce airway inflammation reaction by down-regulating ICAM-1 and EOS by suppressing p38MAPK signaling in lung tissue of asthmatic rats

To observe the effect of acupoint catgut embedment(ACE) on expression of p38 mitogen activated protein kinase (p38MAPK), intercellular adhesion molecule-1(ICAM-1), interleukin-4 (IL-4) and eosinophils (EOS) in lung tissue of asthmatic rats, so as to explore its mechanism underlying improvement of asthma. Forty male Wistar rats were randomly divided into control, model, ACE and dexamethasone (DEX) groups, with 10 rats in each group. The asthmatic model was established by intraperitoneal injection of mixture suspension (1 mL) of ovalbumin (OVA,10%) and 10% Al (OH)3+ normal saline, followed by inhalation of atomized 1% OVA solution for 30 min, once daily for 2 weeks to trigger occurrence of asthmatic symptoms. The ACE was applied once to "Feishu" (BL13), "Dingchuan" (EX-B1) and "Danzhong" (CV17). Rats of the DEX group were given intraperitoneal injection of DEX once a day for 2 weeks. H.E. staining was used to evaluate histopathological changes of the lung tissue. The relative number of EOS in the bronchoalveolar lavage fluid (BALF) was detected by Wright Giemsa staining. The apoptosis level of EOS in the lung tissue was detected by TUNEL staining. The ultrastructural changes of EOS in the lung tissues were observed by transmission electron microscope (TEM). The expression of p38MAPK, ICAM-1 and IL-4 mRNAs in the lung tissue was detected by quantitative real-time PCR. Findings of optical microscope and TEM showed obvious bronchial deformation and inflammatory cell infiltration, rupture of EOS cell membrane, uneven cytoplasm with swelling and uneven density of eosinophilic granules in EOS of the model group, which was relatively milder in the ACE and DEX groups. Compared with the control group, the EOS number in BALF and the expressions of p38MAPK, ICAM-1 and IL-4 mRNAs in the lung tissue were significantly increased (P<0.01), and the apoptosis index of EOS in the lung tissue was significantly decreased (P<0.01) in the model group. After intervention, the EOS number in BALF and expression levels of p38MAPK, ICAM-1 and IL-4 mRNAs in the lung tissue of ACE and DEX groups were significantly decreased (P<0.01, P<0.05), as well as the apoptosis index of EOS in the lung tissue was significantly increased in both ACE and DEX groups (P<0.01) in comparison with the model group. The EOS number in BALF and expression of ICAM-1 mRNA were significantly lower in the DEX group than those in the ACE group (P<0.05). Catgut embedding at acupoints may alleviate the airway inflammatory response in asthma rats, which may be related with its effects in down-regulating p38MAPK signaling, ICAM-1 and IL-4 mRNA expression, reducing the aggregation of EOS, and promoting the apoptosis of EOS.

Intra-cerebellar schwannoma with various degenerative changes: a case report and a systematic review

BackgroundIntra-cranial schwannomas account for less than 8% of brain tumors, among which more than 80% arise from the vestibular nerve. Intra-cerebellar schwannomas are extremely rare. Several cases have been previously reported but without remarkable degenerative changes on histology.Case presentationA 61-year-old man presented with worsening disorientation, and an imaging study revealed a cystic lesion (6.5 cm in the largest diameter) in the left hemisphere of the cerebellum accompanied by a mural nodule (2.5 cm) located just inside the skull with enhancement and focal calcification, in addition to hydrocephalus. The lesion was more than 5 mm from the left acoustic nerve. The patient underwent gross total resection. Pathological examination revealed remarkable degenerative changes with various morphological features. Tumor cells were pleomorphic with rich cytoplasm containing numerous eosinophilic granules. Blood vessels and extracellular matrix showed remarkable hyalinization. Immunohistochemical staining revealed that the tumor cells were positive for S-100 protein and negative for Olig2. The tumor was diagnosed as a schwannoma with marked degenerative changes.ConclusionsThe present case is discussed with reference to a systematic review of previous reports of intra-cerebellar schwannoma. Intra-cerebellar schwannoma should be included in the differential diagnosis of cystic lesions with heterogeneous histopathological morphology in the cerebellum.

Oncocytoma of the Eyelid

Purpose: To report a case of oncocytoma of the eyelid.Case summary: A 70-year-old male visited the ophthalmic clinic, complaining of a mass on his right lower eyelid that had grown steadily in size over the period of 1 year. At the time of his visit, his best-corrected visual acuity was 0.8 in the right eye and 0.8 in the left eye. The eyelid mass had a shape similar to that of a conjunctival nevus, and there was neither pain nor discharge. The eyelid mass was excised under local anesthesia. The mass biopsy presented as oval polygonal cells rich in eosinophilic granules in the cytoplasm. Based on this finding, the patient was diagnosed with oncocytoma of the eyelid. The patient has been under follow-up without further treatment or recurrence. Conclusions: Oncocytoma of the eyelids is rare and has not been reported in Koreans; however, very rare but aggressive forms have been reported. Thus, it is necessary to make an accurate diagnosis through biopsy and close follow-up.

Ex Vivo Fluorescence Confocal Microscopy in Specimens of the Liver: A Proof-of-Concept Study.

Simple SummaryFluorescence confocal microscopy (FCM) is a novel micro-imaging technique providing optical sections of native tissue. The method is increasingly used for the routine diagnosis of tumors and inflammatory lesions of the skin and shows promising results for the diagnosis of other organ tumors. Very few publications exist about examinations of liver tissue thus far. In this study, we compare findings of FCM-examinations of biopsies and surgical specimens of the liver with the final diagnoses from conventional histology.Ex vivo Fluorescence Confocal Microscopy (FCM) is a technique providing high-resolution images of native tissues. The method is increasingly used in surgical settings in areas of dermatology and urology. Only a few publications exist about examinations of tumors and non-neoplastic lesions of the liver. We report on the application of FCM in biopsies, surgical specimens and autopsy material (33 patients, 39 specimens) of the liver and compare the results to conventional histology. Our preliminary examinations indicated a perfect suitability for tumor diagnosis (ĸ = 1.00) and moderate/good suitability for the assessment of inflammation (ĸ = 0.4–0.6) with regard to their severity and localization. Macro-vesicular steatosis was reliably detected, micro-vesicular steatosis tended to be underestimated. Cholestasis and eosinophilic granules in granulocytes were not represented in the scans. The tissue was preserved as native material and maintained its quality for downstream histological, immunohistological and molecular examinations. In summary, FCM is a material sparing method that provides rapid feedback to the clinician about the presence of tumor, the degree of inflammation and structural changes. This can lead to faster therapeutic decisions in the management of liver tumors, treatment of hepatitis or in liver transplant medicine.

Secretory Leukocyte Protease Inhibitor Is Present in Circulating and Tissue-Recruited Human Eosinophils and Regulates Their Migratory Function.

Eosinophils and secretory leukocyte protease inhibitor (SLPI) are both associated with Th2 immune responses and allergic diseases, but whether the fact that they are both implicated in these conditions is pathophysiologically related remains unknown. Here we demonstrate that human eosinophils derived from normal individuals are one of the major sources of SLPI among circulating leukocytes. SLPI was found to be stored in the crystalline core of eosinophil granules, and its dislocation/rearrangement in the crystalline core likely resulted in changes in immunostaining for SLPI in these cells. High levels of SLPI were also detected in blood eosinophils from patients with allergy-associated diseases marked by eosinophilia. These include individuals with eosinophilic granulomatosis with polyangiitis (EGPA) and atopic dermatitis (AD), who were also found to have elevated SLPI levels in their plasma. In addition to the circulating eosinophils, diseased skin of AD patients also contained SLPI-positive eosinophils. Exogenous, recombinant SLPI increased numbers of migratory eosinophils and supported their chemotactic response to CCL11, one of the key chemokines that regulate eosinophil migratory cues. Together, these findings suggest a role for SLPI in controlling Th2 pathophysiologic processes via its impact on and/or from eosinophils.

An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions

BackgroundThe detailed neuropathological features of patients with autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (TCC) and SPG11 mutations are poorly understood, as only a few autopsies have been reported. Herein, we describe the clinicopathological findings of a patient with this disease who received long-term care at our medical facility.Case presentationA Japanese man exhibited a mild developmental delay in early childhood and intellectual disability, followed by the appearance of a spastic gait by age 13. At the age of 25 years, he became bedridden and needed a ventilator. Genetic analysis revealed a homozygous splice site variant in the SPG11 gene (c. 4162–2A > G) after the provision of genetic counselling and acquisition of informed consent from his parents. He died of pneumonia at the age of 44. His brain weighed 967 g and was characterized by a TCC, and his spinal cord was flattened. Microscopically, degeneration was observed in the posterior spinocerebellar tract, the gracile fasciculus, and the posterior column in addition to the corticospinal tract. Marked neuronal loss and gliosis were observed in the anterior horn, Clarke’s column, and hypoglossal and facial nuclei. Various types of neurons, in addition to motor neurons, showed coarse eosinophilic granules that were immunoreactive for p62. The loss of pigmented neurons with gliosis was apparent in both the substantia nigra and locus coeruleus. Lateral geniculate body degeneration was a characteristic feature of this patient. Furthermore, peripheral Lewy body-related α-synucleinopathy and scattered α-synuclein–immunoreactive neurites in the locus coeruleus and reticular formation of the brainstem were observed.ConclusionsIn patients with hereditary spastic paraplegia with SPG11 mutations, a variety of clinical phenotypes develop due to widespread lesions containing p62-immunoreactive neuronal cytoplasmic inclusions. We herein report the lateral geniculate body as another degenerative site related to SPG11-related pathologies that should be studied in future investigations.

A case of spontaneous rete testis adenoma in a Sprague–Dawley rat

A 104-week-old male CD (SD) rat exhibited enlargement of the left testis. Microscopically, this mass was demarcated from the testis by fibrous connective tissue and characterized by cystic dilatation with single-layered columnar cells and papillary proliferation connected to the solid growth area without clear boundaries. In the solid growth area, cells were dissected into irregular alveolar nests by scant fibrous tissue with small blood vessels. The nuclei of proliferating cells were variable in size and round- to oval-shaped, and their cytoplasm was pale or eosinophilic and sometimes contained vacuoles or eosinophilic granules. Immunohistochemically, the tumor cells were positive for vimentin and cytokeratin (CK) 7. Since CK7 was exclusively positive in the rete testis epithelium of the naïve rat, it was valuable to diagnose this tumor as rete testis-originated. Based on these results and the lack of apparent pleomorphism, mitotic figures, and metastasis, the present case was diagnosed as rete testis adenoma.

Immunohistochemical study of autophagy associated molecules and cell adhesion molecules in canine intracranial granular cell tumors

Granular cell tumors (GCTs) are characterized by abundant eosinophilic cytoplasmic granules. Based on the hypothesis that canine intracranial GCT is a subtype of meningioma and its cytoplasmic granules are formed through autophagy processes, histopathological and immunohistochemical examination were performed on biopsy samples from 7 cases of canine intracranial GCTs and 15 cases of conventional meningiomas. Histopathologically, 7/7 cases of GCTs involved the meninges; foci of meningothelial-like cells were observed in 3/7 cases; brain invasion was observed in 2/7 cases. Immunohistochemically, neoplastic cells of GCTs were positive for E-cadherin and negative for S100, cytokeratin, CD204, and β-catenin in 7/7 cases. Neoplastic cells of 15/15 cases of meningiomas were positive for E-cadherin, and negative for S100 and CD204. Immunoreactivity of meningiomas for cytokeratin and β-catenin was observed in 6/15 cases and 8/15 cases, respectively. Cytoplasmic granules of GCTs were positive for ubiquitin (5/7), p62 (5/7), and LC3 (7/7). Compared to GCTs, the ratios of ubiquitin (6/15) and p62 (3/15) positive cases were lower in meningiomas, and 15/15 cases were negative for LC3. These findings indicate that the biological natures of GCTs including anatomical location, histopathological features and immunoreactivity for E-cadherin are almost in conformity with those of meningiomas. The immunoreactivity for autophagy associated molecules may suggest the possible involvement of autophagy in cytoplasmic granule formation of canine intracranial GCTs.

The Effects of Early Diabetes on Duodenal Alterations in the Rats

Diabetes mellitus (DM) mainly affects functional changes in the duodenum, which plays an important role in the digestion and absorption of food. The impairment of duodenal function contributes to malnutrition, abdominal bloating and pain in diabetic patients. Thus, this study aimed to investigate the histological alterations and quantitative measurements of duodenal structures in the early stage of streptozotocin (STZ)-induced diabetic rats. Eight male Sprague-Dawley rats were divided into three control and five diabetic rats. Diabetes was induced by a single intraperitoneal dose of 60 mg/kg STZ. After four weeks of diabetic induction, the duodenum was prepared for histological study and morphometric analysis. In diabetic rats, there were deformed villi with disrupted surface epithelium and mildly distorted shapes of crypts, together with an increase in villus height and crypt depth. The epithelial cells detached from their underlying basement membrane. The goblet cells decreased in number, whereas an increased number of Cellula panethensis (Paneth cells) with pale-stained eosinophilic granules occurred in the DM group. A diabetic thickened submucosal layer was observed as enhanced duodenal glands (Brunner’s glands) hypertrophy and collagen accumulation. These findings indicated that histopathologic lesions of the duodenum developed in the early stage of diabetes. The destruction of villi, crypts, and epithelium may affect digestion and absorption. The structural changes in goblet and Cellula panethensis and duodenal glands may be associated with malfunction to protect duodenal mucosa from bacteria and stomach acid. These conditions can worsen the quality of life in diabetic individuals, leading to complications such as maldigestion, malabsorption, and duodenal ulcer.

Migrating and Nerve Fibers-Associated Eosinophilic Granule Cells in the Olfactory Organ of Catfish (Clarias garpienius): Light and Electron Microscopic Evidence.

Piscine mast cells or eosinophilic granule cells (EGCs) of fish are equivalent to the mammalian mast cells. Recently, a better understanding of EGCs functions is allowed because of the growing interest in fish models. Herein, we present a trial to furnish data regarding the distribution of the EGCs in the fish olfactory organ, an issue that has not been reported so far. Regarding their distribution, two kinds of EGCs had been identified. An intra-epithelial one was detected in the olfactory epithelium lining of the olfactory lamellae. The stromal one was identified in the connective tissue core of the olfactory lamellae and in the lamina propria underlying the olfactory epithelium. Some were detected in the capillary lumen. The cytoplasm of the EGCs reacted strongly with the MMP-9 antibody. Stimulating a migration perspective for the olfactory EGCs which was confirmed by their location in the blood capillaries. Several EGCs could be verified in close relation, some underneath the epineurium, with the nerve fiber. Mutually, this verifies the existence of intra-epithelial and stromal migrating EGCs in the catfish olfactory organ and their inclusion in the olfactory immune response. Additionally, this provides evidence for an immune–nervous interaction to influence both the immune reactions and the nervous scheme in catfish.

CCAAT/Enhancer-Binding Protein ε27 Antagonism of GATA-1 Transcriptional Activity in the Eosinophil Is Mediated by a Unique N-Terminal Repression Domain, Is Independent of Sumoylation and Does Not Require DNA Binding

CCAAT/enhancer binding protein epsilon (C/EBPε) is required for eosinophil differentiation, lineage-specific gene transcription, and expression of C/EBPε32 and shorter 27kD and 14kD isoforms is developmentally regulated during this process. We previously defined the 27kD isoform (C/EBPε27) as an antagonist of GATA-1 transactivation of the eosinophil’s major basic protein-1 (MBP1) P2-promoter, showing C/EBPε27 and GATA-1 physically interact. In the current study, we used a Tat-C/EBPε27 fusion protein for cell/nuclear transduction of an eosinophil myelocyte cell line to demonstrate that C/EBPε27 is a potent repressor of MBP1 transcription. We performed structure-function analyses of C/EBPε27 mapping its repressor domains, comparing it to C/EBPε32 and C/EBPε14, using GATA-1 co-transactivation of the MBP1-P2 promoter. Results show C/EBPε27 repression of GATA-1 is mediated by its unique 68aa N-terminus combined with previously identified RDI domain. This repressor activity does not require, but is enhanced by, DNA binding via the basic region of C/EBPε27 but independent of sumoylation of the RDI core “VKEEP” sumoylation site. These findings identify the N-terminus of C/EBPε27 as the minimum repressor domain required for antagonism of GATA-1 in the eosinophil. C/EBPε27 repression of GATA-1 occurs via a combination of both C/EBPε27-GATA-1 protein–protein interaction and C/EBPε27 binding to a C/EBP site in the MBP1 promoter. The C/EBPε27 isoform may serve to titrate and/or turn off eosinophil granule protein genes like MBP1 during eosinophil differentiation, as these genes are ultimately silenced in the mature cell. Understanding the functionality of C/EBPε27 in eosinophil development may prove promising in developing therapeutics that reduce eosinophil proliferation in allergic diseases.

Role of Eosinophils in Intestinal Inflammation and Fibrosis in Inflammatory Bowel Disease: An Overlooked Villain?

Eosinophils are leukocytes which reside in the gastrointestinal tract under homeostatic conditions, except for the esophagus which is normally devoid of eosinophils. Research on eosinophils has primarily focused on anti-helminth responses and type 2 immune disorders. In contrast, the search for a role of eosinophils in chronic intestinal inflammation and fibrosis has been limited. With a shift in research focus from adaptive to innate immunity and the fact that the eosinophilic granules are filled with inflammatory mediators, eosinophils are becoming a point of interest in inflammatory bowel diseases. In the current review we summarize eosinophil characteristics and recruitment as well as the current knowledge on presence, inflammatory and pro-fibrotic functions of eosinophils in inflammatory bowel disease and other chronic inflammatory conditions, and we identify research gaps which should be covered in the future.

S1573 A Rare Case of Ectopic Pancreas Spotted as a Small Nodularity in Distal Esophagus

Introduction: Heterotopic pancreatic tissue or ectopic pancreas is a congenital phenomenon in which there is presence of pancreas tissue outside of the main pancreas. The tissue is located at a separate site and is not connected to the main pancreas by means of ducts or vascular supply. We present a case of ectopic pancreatic tissue in the esophagus found on endoscopy. Case Description/Methods: A 71-year-old male with a history of gastroparesis and chronic bloating who presented to gastroenterology clinic for evaluation of flatulence. Physical exam was unremarkable and basic labs were normal. Despite a trial of low FODMAP diet and rifaximin, symptoms persisted. Hence upper endoscopy was performed and revealed salmon colored mucosal nodularity in distal esophagus which was biopsied. The gastric and duodenal mucosa appeared normal and biopsies were negative for celiac disease or Helicobacter pylori infection. The biopsy of the esophagus revealed focal pancreatic heterotopia with histological evidence of well-circumscribed small lobules of pancreatic tissue located in the submucosa underneath the esophageal squamous mucosa. There were basophilic basal granules and eosinophilic apical granules of the pancreatic acinar glands. The ectopic tissue did not contribute to any symptoms and was discovered as an incidental finding. Discussion: Ectopic pancreas can be present in various sites in the gastrointestinal tract though more frequently found in the upper tract at sites such as the stomach, duodenum and jejunum. However other sites such as the esophagus are an unusual site. It can be discovered incidentally or can have a symptomatic presentation. It can present with complications such as pancreatitis, bleeding, obstruction and may even be associated with malignant transformation in some cases. Ectopic pancreas in the esophagus is very rare and given its pre-malignant potential, gastroenterologists need to be aware and these lesions should be resected.Figure 1.: Figure A: Salmon colored mucosa noted in distal esophagus being examined under narrow band imaging. Figure B showing pancreatic heterotopia in distal esophagus on hematoxylin and eosin stain at 200X magnification. There are well-circumscribed small lobules of pancreatic tissue located in the submucosa underneath the esophageal squamous mucosa. Note the presence of basophilic basal granules and eosinophilic apical granule of the pancreatic acinar glands. A few dilated ducts are also noted.

Hepatic perivascular epithelioid cell tumor: Clinicopathological analysis of 26 cases with emphasis on disease management and prognosis.

BACKGROUNDPerivascular epithelioid cell tumor (PEComa) is an uncommon tumor of mesenchymal origin. Cases of PEComa in the liver are extremely rare.AIMTo analyze the clinicopathological features and treatment of hepatic PEComa and to evaluate the prognosis after different treatments.METHODSClinical and pathological data of 26 patients with hepatic PEComa were collected. All cases were analyzed by immunohistochemistry and clinical follow-up.RESULTSThis study included 17 females and 9 males, with a median age of 50 years. Lesions were located in the left hepatic lobe in 13 cases, in the right lobe in 11, and in the caudate lobe in 2. The median tumor diameter was 6.5 cm. Light microscopy revealed that the tumor cells were mainly composed of epithelioid cells. The cytoplasm contained heterogeneous eosinophilic granules. There were thick-walled blood vessels, around which tumor cells were radially arranged. Immunohistochemical analysis of pigment-derived and myogenic markers in PEComas revealed that 25 cases were HMB45 (+), 23 were Melan-A (+), and 22 SMA (+). TFE3 and Desmin were negative in all cases. All the fluorescence in situ hybridization samples were negative for TFE3 gene break-apart probe. Tumor tissues were collected by extended hepatic lobe resection or simple hepatic tumor resection as the main treatments. Median follow-up was 62.5 mo. None of the patients had metastasis or recurrence, and there were no deaths due to the disease.CONCLUSIONHepatic PEComa highly expresses melanin and smooth muscle markers, and generally exhibits an inert biological behavior. The prognosis after extended hepatic lobe resection and simple hepatic tumor resection is semblable.

Mast cells and eosinophilic granule cells in Oncorhynchus mykiss: Are they similar or different?

Mast cells are important in inflammatory processes and in the nonspecific immune response, and there are also indications that these cells are associated with the effectors of the specific immune response. Eosinophilic granular cells are frequently compared to mast cells, and some authors maintain that they are the same cells. In this study, we take a fresh look at the similarities and differences between these two cell types in Oncorhynchus mykiss. We evaluated the cytomorphology of each cell type with optical microscopy, their staining affinities, and their ultrastructure. We observed that mast cells were positive for CD117 (c-kit), while eosinophilic granular cells were negative for this marker. We propose that these two cell types have certain common characteristics but represent well-differentiated populations distributed in several Oncorhynchus mykiss tissues.