Prominent Eosinophilic Infiltration Research Articles

Urogenital schistosomiasis, a leading cause of bladder squamous cell carcinoma

Abstract Introduction/Objective Schistosoma, genus of trematodes, commonly known as blood flukes are parasitic flatworms responsible for a group of infections in humans termed schistosomiasis and hundreds of millions of people are infected worldwide. In areas where Shistosoma is not endemic to the region most cases of bladder malignancy are of urothelial origin. In areas where Shistosoma is endemic bladder malignancy is more commonly squamous cell carcinoma. However, with increased travel, migration and tourism it is important to potentially consider Shistosoma infection in areas that are not typically considered endemic regions. Methods/Case Report A 62-year-old male presented to our hospital and revealed through an interpreter he has had 1.5 years hematuria with “pieces of meat or brown dirt”. Cystoscopy was performed and showed a large necrotic mass. CT scan showed an 8.2 cm exophytic bladder dome mass. TURBT was performed and a diagnosis of invasive high-grade urothelial carcinoma with squamous differentiation and with multiple Schistosoma organisms identified.The patient received Schistosoma treatment and was scheduled for radical cystectomy and ileal conduct. A few days before the scheduled procedure the patient presented to our emergency department with acute abdominal pain. He was subsequently diagnosed with progressive bladder cancer with new left malignant ureteral obstruction, which lead to hydronephrosis, DVT, abdominopelvic ascites and intraperitoneal bladder perforation. Abdominal fluid cytology showed atypical keratinizing squamous cells suspicous for malignancy and marked acute inflammation. Patient underwent cystectomy with ileal conduit and the specimen was sent to pathology for examination. Results (if a Case Study enter NA) NA Conclusion Gross examination showed an irregular perforated bladder. Microscopic examination showed a high grade urothelial carcinoma with squamous and sarcomatoid differentiation with detrusor muscle invasion. Additionally, Schistosoma organisms with a terminal spine and calcified eggs were identified. Some of the calcified egg material was engulfed by giant cells. The organisms are surrounded by a prominent eosinophilic infiltrate. Lymphovascular invasion is also noted. Schistosomiasis is associated with the development of squamous cell carcinoma of the bladder. It is important to maintain high oncological alertness for squamous cell carcinoma, particularly for patients arriving from endemic areas. Such as in our case, a patient from Somalia living in Kansas City.

Granular C3 dermatosis-A report of two cases and a mini-review of literature.

Granular C3 dermatosis (GCD) is characterized by bullous, erythematous, and eczematous skin lesions similar to dermatitis herpetiformis, and granular deposition of complement C3 and C5b-9 along the epidermal basement membrane zone (BMZ) by direct immunofluorescence (IF). Here, we present two cases of GCD with different clinical features. Case 1, a 49-year-old man, showed pruritic blisters and erythema of the extremities. Case 2, a 53-year-old woman, showed severely pruritic papules, erythema, and erosions on the entire body with scattered blisters, mainly on the lower extremities. Both patients showed mild eosinophilia on blood tests, subepidermal blisters and prominent eosinophilic infiltration in the upper dermis on histopathological examination, and granular BMZ deposition of C3, but not of immunoglobulins or other complement components, on direct IF. No circulating autoantibodies were detected on enzyme-linked immunosorbent assays, chemiluminescent enzyme immunoassays, indirect IF using 1 mol/L NaCl-split normal human skin, or immunoblotting. Diagnosis of GCD was made in both cases. Case 1 was successfully treated with topical steroids, oral minocycline, and nicotinamide without any recurrence of symptoms. Case 2 was treated with oral steroids and showed remarkable improvement, although mild pruritic papules remained. We reviewed 30 reported GCD cases, including the two cases presented here, since Hashimoto etal. first described GCD in 2016. GCD should be more widely recognized, and further accumulation and validation of cases are required.

Eosinophilic Gastroenteritis with Ascites, Elevated Serum IgG4, and Hypereosinophilic Syndrome: A Manifestation of IgG4-related Disease?

A 76-year-old woman with persistent diarrhea was referred to our hospital. She had purpura, peripheral eosinophilia (18,177/μL), and an elevated serum IgG4 level (819 mg/dL). Abdominal computed tomography revealed massive ascites and bowel edema. A skin biopsy of the purpura revealed leukocytoclastic vasculitis with prominent eosinophilic infiltration. Biopsies of the gastrointestinal mucosa revealed dense eosinophilic infiltration, indicating eosinophilic gastroenteritis (EG) associated with the hypereosinophilic syndrome. The number of IgG4-positive cells increased in the duodenal mucosa; however, the diagnostic criteria for IgG4-related disease (IgG4-RD) were not met. Whether or not EG with ascites is a manifestation of IgG4-RD warrants further investigation.

Development of ANCA-Negative Eosinophilic Granulomatosis With Polyangiitis 19 years After Onset of Eosinophilic Pustular Folliculitis.

To the Editor: A 47-year-old Japanese man visited our department, complaining of itchy erythema on the bilateral cheeks. Physical examination showed symmetrical infiltrative erythematous plaques with small papules and tiny pustules at the periphery, as well as papular lesions under the nostrils and around the lips (Fig. 1A). Biopsy revealed infiltration of neutrophils and eosinophils in the sebaceous glands (Fig. 1B). The patient was diagnosed as having eosinophilic pustular folliculitis (EPF), and oral intake of indomethacin (200 mg/d) resulted in a favorable effect. At the age of 56 years, he developed bronchial asthma, and a few years later, he complained of numbness of the bilateral lower legs, which was diagnosed as neuropathy. Nineteen years after the initial visit to us, he was referred to us for skin lesions. Physical examination showed brownish infiltrative plaques, papules, and vesicles on the lower extremities (Fig. 1C). Laboratory examination showed an elevated eosinophil rate in the peripheral blood (14%), and serum IgE was elevated (213 IU/mL; normal <170). Neither proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibody (ANCA) nor myeloperoxidase (MPO)-ANCA was detected in the serum. HIV was negative. Histopathological examination revealed prominent infiltration of eosinophils in and around the sebaceous glands and vessels in the mid dermis (Fig. 1D). Higher magnification revealed a number of eosinophil infiltration in the vessel walls with degranulation of the infiltrated eosinophils and alteration of the affected pale-stained vessel walls, loss of endothelial cells of the affected venous vessel in the mid dermis (Fig. 1E), consistent with eosinophilic vasculitis. Neither fibrinoid degeneration of the vessel walls nor neutrophil infiltration with nuclear dust was observed. Extravascular giant cells were scattered in the dermis (Fig. 1F). Elastica van Gieson staining revealed that the affected vessels were venules. Renal disease was not observed. The patient was treated with inhaled corticosteroid for bronchial asthma, and his skin lesions were treated with topical corticosteroid ointment.FIGURE 1.: A, Facial infiltrative erythematous plaques with small papules and tiny pustules at the periphery. B, Biopsy specimen taken from the cheek showed marked infiltration of neutrophils and eosinophils in the sebaceous glands. C, Brownish infiltrative plaques, papules, and vesicles on the lower extremities. D, Histopathological features showing dermal infiltration of a number of eosinophils in and around the sebaceous glands and vessels in the mid dermis. E, Higher magnification reveals prominent infiltration of eosinophils in and around the vessel walls with eosinophilic degranulation (arrows), alteration of the affected vessel walls, and loss of endothelial cells (encircled by dotted square). F, Extravascular giant cells in the dermis. H–E, stain, original magnification: B; ×200, d; ×100, e; ×400, f; ×400).Eosinophilic pustular folliculitis is a sterile inflammatory dermatosis, frequently involving the face, presenting with annular erythematous plaques with superficial papulopustules at the periphery.1 Eosinophilic pustular folliculitis is histopathologically associated with folliculotropic infiltration of eosinophils. Our case was diagnosed as classic EPF and successfully treated with indomethacin. Thereafter, EPF did not recur, but the patient developed eosinophilic granulomatosis with polyangiitis (EGPA) 19 years later. Eosinophils play a crucial role in the pathogenesis of EGPA and release of mediators, that is, major basic protein, eosinophilic cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin, as well as various cytokines by degranulation is important in the development of eosinophilic vasculitis.2 In EGPA, cutaneous eosinophilic vasculitis is rarely seen. The inflammatory process of eosinophilic vasculitis in EGPA begins as an angiocentric infiltrate of eosinophils in and around the small vessels.3 In the present case, angiocentric infiltrates of inflammatory cells in the affected vessels' wall were almost exclusively eosinophils without either neutrophils or histiocytes. The affected vessels were venules, and the arteries were intact. These findings suggest that the present case is the initial stage of EGPA with eosinophilic vasculitis. In addition, the present case was ANCA negative and renal involvement was absent. Previous studies have suggested that MPO-ANCA–positive patients frequently develop neutrophilic vasculitis with renal involvement, while those with eosinophil-predominant eosinophilic vasculitis frequently revealed serological ANCA negative and developed lung infiltrates, myocardiopathy, and gastrointestinal manifestations but the absence of renal involvement.4,5 Further studies are necessary to investigate the associations of cutaneous manifestations, eosinophilic vasculitis, and ANCA. Histopathological features of hypereosinophilic syndrome are eosinophilic spongiosis in the epidermis, superficial and deep dermal perivascular and interstitial infiltrate of numerous eosinophils and lymphocytes6; however, neither vasculitis nor histiocytic giant cells are observed. Therefore, hypereosinophilic syndrome was excluded in the present case. To the best of our knowledge, this is the first report of concurrent EPF and EGPA. Because EGPA occurred nearly 20 years later, the coexistence may be incidental. Nevertheless, eosinophil activation may have played a role in the induction of both disorders in our patient.

Recent topics on gastrointestinal allergic disorders.

Gastrointestinal (GI) allergies are broadly associated with food allergies and divided into groups based on the degree of allergen-specific immunoglobulin E (IgE) involvement: IgE-mediated, non-IgE-mediated, and mixed. Non-IgE-mediated GI food allergies are mostly observed in neonates and infants and include food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). In addition to the classical phenotype, unique phenotypes such as vomiting and bloody stool, suspected sepsis, and overlapping eosinophilic GI disorders (EGIDs) have increased in Japan over the past 2 decades. Some of these cases were defined as having chronic FPIES. More recently, cases of hen's-egg FPIES in Japan have increased dramatically since 2018, albeit for unknown reasons. Typical mixed-type food allergies are EGIDs, characterized by prominent eosinophil infiltration in the GI tract leading to GI symptoms. EGIDs are broadly classified into eosinophilic esophagitis (EoE) and non-EoE EGIDs that involve the GI tract with the exception of the esophagus. Of the EGIDs, EoE is the best known, as the number of cases has increased dramatically in Western countries, whereas pediatric EoE remains rare in Asia and non-EoE EGIDs may be more prevalent in Japan. A recent Japanese national survey showed that pediatric non-EoE EGIDs were persistent and severe compared to those in adults, possibly requiring further effective therapeutic options. Among the EGIDs, FPIAP is pathologically diagnosed as an infantile form of eosinophilic colitis. In addition, recent FPIES and FPE cases also involved eosinophilic inflammation. Recent cases of GI allergies may be associated with type 2 inflammation. A better understanding of the interactions between GI allergies and type 2 inflammation may clarify the pathogenesis of the recent increase in GI allergies.

An Unusual Case of Intermittent Fever With Multiple Liver Lesions

Question: A 46-year-old man with a history of hypertension presented to our hospital with a chief compliant of intermittent fever for 2 weeks. He denied a history of nausea, vomiting, abdominal pain, diarrhea, abdominal distention, loss of appetite, or weight loss. Physical examination on admission was unremarkable. Laboratory studies showed white blood cells 15.32 × 109/L (reference 3.5–9.5 × 109/L) with 38.3% (reference 0.4%–8.0%) eosinophils, C-reactive protein 49.72 mg/L (reference 0–10 mg/L), and erythrocyte sedimentation rate 44 mm/h (reference 0–15 mm/h). No parasite eggs or larvae were found in microscopic examination of direct smears of the stool. Liver function tests revealed alanine transaminase 50.5 IU/L (reference 9–50 IU/L), alkaline phosphatase 134 IU/L (reference 15–40 IU/L), gamma-glutamyltransferase 224 IU/L (reference 10–60 IU/L), total protein 40.1 g/L (reference 65–85 g/L), and albumin 21.6 g/L (reference 40–55 g/L). His renal function and tumor markers, such as alpha-fetoprotein, carcino-embryonic antigen, and carbohydrate antigen 19-9 were all within normal ranges. Tests for hepatitis B, hepatitis C, antinuclear antibodies, extractable nuclear antigen antibodies, and anti–neutrophil cytoplasm antibodies were all negative. No significant abnormalities were detected on electrocardiography, echocardiography, and chest computed tomography (CT). Routine ultrasound revealed multiple hypoechoic areas with unclear borders in the left lobe and right posterior lobe of the liver. Magnetic resonance imaging (MRI) of the liver was subsequently performed and showed multiple nodular or clumpy lesions as low signal intensity on T1-weighted imaging (WI) (Figure A) and high signal intensity on fat-suppressed T2-WI (Figure B) and diffusion WI (Figure C). Contrast-enhanced scan exhibited slightly heterogeneous enhancement (Figure D) or annular enhancement (Figure E). MRI did not indicate any anatomic malformations or intrahepatic or extrahepatic bile duct dilation. Positron emission tomography–computed tomography (PET-CT) revealed increased 18F-fluorodeoxyglucose uptake in the liver lesions (maximum standardized uptake value 3.8–5.2) (Figure F). The patient subsequently underwent CT-guided liver biopsy. Histopathology demonstrated chronic hepatic inflammation with prominent eosinophilic infiltration in portal areas and some acinar areas (Figure G).

An Unusual Cause of Acute Gastroenteritis, Ascites, and Eosinophilia in a 29-Year-Old Woman

An Unusual Cause of Acute Gastroenteritis, Ascites, and Eosinophilia in a 29-Year-Old Woman

The Percentage of PNAd-Expressing Vessels is Correlated with Disease Severity in Eosinophilic Chronic Rhinosinusitis.

Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory condition of the paranasal sinuses characterized by intractable nasal polyps with prominent eosinophil infiltration. These eosinophils are presumably recruited from peripheral blood via vessels expressing peripheral lymph node addressin (PNAd), a set of glycoproteins decorated with 6-sulfo sialyl Lewis x (sLex) glycans that serve as L-selectin ligands. Based on the severity classification algorithm proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group, ECRS is divided into mild, moderate and severe groups; however, as yet there are few reports comparing the clinicopathological differences among these groups. Our goal was to elucidate clinicopathological differences among the three different severities of ECRS with special reference to eosinophils and PNAd-expressing vessels. We performed quantitative immunohistochemical analysis of PNAd-expressing vessels using surgical specimens of nasal polyps from patients exhibiting varying severity of ECRS (n = 35) and from individuals with non-ECRS (n = 10). To this end, we immunostained tissue sections with anti-PNAd and anti-CD34 monoclonal antibodies, and then determined the number of vessels immunolabeled with each antibody. The number of eosinophils infiltrating nasal polyps was correlated with ECRS severity. We also found that the PNAd + /CD34 + vessel ratio, namely, the percentage of PNAd-expressing vessels among all vessels, was positively correlated not only with ECRS severity but also with the number of eosinophils infiltrating nasal polyps formed in ECRS. These results strongly suggest that PNAd-expressing vessels play at least a partial role in eosinophil recruitment to nasal polyps and consequent severity of ECRS.

Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model.

Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.

The need for a reliable non-invasive diagnostic biomarker for eosinophilic oesophagitis

Eosinophilic oesophagitis is part of the spectrum of primary eosinophilic gastrointestinal disorders and is characterised by a chronic, Th2-mediated, inflammatory process within the oesophageal mucosa, leading to prominent eosinophilic infiltration (≥15 eosinophils per high-power field).1 The most common view of the pathogenesis of eosinophilic oesophagitis is that it marks the endpoint of an atopic progression, moving from atopic dermatitis, food allergy, asthma, allergic rhinitis, and, eventually, eosinophilic oesophagitis, although its pathogenesis remains largely elusive.

Palisading granulomatous dermatitis and panniculitis (palisading granuloma) of dogs.

Palisading granulomatous dermatitis and panniculitis is recognized in various cutaneous inflammatory lesions secondary to presumed collagen damage. Cutaneous nodules with a palisading arrangement of histiocytes surrounding foci of collagen degeneration have been clinically termed palisading granuloma in dogs. Study aims were to characterize the cellular infiltrate of canine palisading granuloma and document salient clinical features. Inclusion criteria were met for 36 dogs and encompassed nodular dermal and subcutaneous histiocyte-predominant cellular infiltrates targeting and enveloping collagen fibers/necrotic foci with palisading configurations. Infectious causes were ruled out via standard histochemical stains and/or clinical data. Medical records were reviewed for signalment, clinical features, treatment, outcome, and comorbidities. Immunohistochemistry (IBA1, CD204, E-cadherin) and Masson's trichrome stain were used to assess histiocytic populations and dermal collagen, respectively. The histiocytes had moderate or strong immunolabeling for IBA1 and CD204 in 36/36 dogs (100%) and mild positive immunolabeling for E-cadherin in 3/36 dogs (8%). Alteration of collagen was graded as moderate or strong in 32/36 dogs (89%) and mild in 3/36 dogs (8%). Large breeds predominated with 30/36 dogs (83%) being ≥23 kg. Focal nodules were identified in 31/36 dogs (86%). The head/face were involved in 19/36 dogs (53%) and the extremities in 18/36 dogs (50%). Lesions from the 5/36 dogs (14%) with multiple nodules contained prominent eosinophilic infiltrates. Following excision, there was no evidence of recurrence. In conclusion, palisading granulomas are a distinct, non-neoplastic, histiocyte-predominant inflammatory condition in dogs associated with altered dermal collagen and favorable prognosis.

Eosinophil rich infiltrate in secondary syphilis a rare histopathological variant

&lt;p class="abstract"&gt;Secondary syphilis is a sexually transmitted infection, which is referred to as “the great imitator” and has a wide spectrum of clinical manifestations. Syphilis is classically associated with plasma cells and the presence of eosinophils usually argues against a diagnosis of syphilis. The differential diagnosis for eosinophil-rich skin lesions often includes a drug reaction, arthropod-bite reaction, allergic contact dermatitis, and a response to a helminth infestation. However, many unrelated entities, such as infections, neoplasms, and inflammatory dermatoses can have prominent eosinophilic infiltrate. We report a case of secondary syphilis which on histopathology showing psoriasiform hyperplasia with superficial perivascular infiltrate and on higher magnification these infiltrate were predominantly lymphohistiocytic along with the moderate amount of eosinophils with a paucity of plasma cells. This case report is presented to highlight the need for including secondary syphilis as one of the differential diagnoses in the presence of eosinophil-rich infiltrate when it is suspected clinically.&lt;/p&gt;

Granulomatous Variant of Food Protein-Induced Allergic Proctocolitis.

A 7-month-old infant on commercial cow milk formula presented with a 4-week history of bloody stools without vomiting, diarrhea, fever, or skin rash. The patient did not appear ill, had a normal physical examination, and took his feeds well. Laboratory results showed a leukocyte count of 17,400/mm3 (reference range, 4400–19,100/mm3) with 12% eosinophils (0.0%–5.0%), hemoglobin level of 12.7 g/dL (10.1–14.2 g/dL), and albumin level of 4.3 g/dL (3.2–4.8. g/dL). Stool cultures were unremarkable. A stool smear showed a large number of eosinophils. Serum IgE, IgG, IgM, and IgA levels were unremarkable, and radioallergosorbent test, performed to determine the presence of specific IgE against cow milk, α-lactalbumin, or casein were all negative. Rectosigmoidoscopy revealed patchy erythema with congestion of the rectal and sigmoid colon mucosa (Fig. 1). Biopsy specimens revealed numerous eosinophils and degranulation in the mucosa (Fig. 2), and notably, granulomatous infiltrates composed of multinucleate giant cells with prominent eosinophils and degranulation in the submucosa (Fig. 3).FIGURE 1.: Rectosigmoidoscopy results showing patchy erythema with congestion of the mucosa in the rectum and sigmoid colon.FIGURE 2.: Biopsy specimens showing numerous eosinophils and degranulation in the mucosa of the sigmoid colon (hematoxylin and eosin staining; original magnification, 200X).FIGURE 3.: Biopsy specimens showing granulomatous infiltrates composed of multinucleate giant cells with prominent eosinophils and degranulation in the submucosa of the sigmoid colon (arrow: multinucleate giant cell, hematoxylin and eosin staining; original magnification, 200X).Immunodeficiency was considered, but history of unusual, severe, or recurrent infections was negative, and serum immunoglobulin levels were normal. Although presentation with granulomas is atypical, the patient was diagnosed with food protein-induced allergic proctocolitis (FPIAP) based on the clinical and histological findings. The commercial cow milk formula was replaced with an extensively hydrolyzed formula, resulting in a dramatic improvement in the condition of the patient. The patient has remained on an extensively hydrolyzed formula and has been consuming a variety of solid foods. No relapse of symptoms has been observed, 5 months after the diagnosis. FPIAP is a common cause of rectal bleeding in an otherwise healthy young infant (1). In most cases of FPIAP, biopsy specimens show prominent eosinophilic infiltration of the rectosigmoid mucosa (2,3). Occurrence of a granulomatous component, as seen in this patient, is a distinctly rare phenomenon in this disease. To date, only two studies have shown the presence of granulomas in FPIAP (4,5). The presence of a granulomatous infiltrate may indicate a severe form of FPIAP (4). Generally, the prognosis of FPIAP is favorable, and tolerance is acquired by around the 1-year of age (6,7). The presence of granulomas in FPIAP should not lead to a diagnosis of any other disease that presents with granulomas based on histological findings, such as early-onset inflammatory bowel disease, primary immunodeficiency, or various infectious diseases (8). Awareness of such unusual and misleading features in FPIAP is, therefore, necessary to avoid unfortunate misdiagnosis as another disease. ACKNOWLEDGMENTS We would like to thank Editage (www.editage.com) for English language editing.

Nodal histiocytic sarcoma with prominent eosinophilic infiltration: expression of eotaxin-2 on tumor cells

BackgroundHistiocytic sarcoma (HS) is a rare neoplasm showing morphological and immunophenotypic features of mature tissue histiocytes. We report a patient with nodal HS exhibiting prominent reactive eosinophilic infiltration.Case presentationA 68-year-old man presented with intermittent left lower abdominal pain and weight loss over 3 months. A computed tomography scan revealed multiple abdominal nodules. Open biopsy of the mesenteric tumors was performed for definitive diagnosis. Histologically, the tumor was comprised of a diffuse noncohesive proliferation of pleomorphic large cells, including multinucleated cells. Neoplastic cells were positive for histiocytic markers (CD68, CD163, and LIGHT) and PD-L1 but lacked markers of Langerhans cells, follicular dendritic cells, and epithelial cells. Frequent reactive inflammatory cells were intermingled in the background. Interestingly, prominent eosinophilic infiltration was also noted. Spindle neoplastic cells were prone to be present around areas with little to no eosinophilic infiltration and exhibiting fibrosis and lymphatic vessel proliferation. Conversely, polygonal neoplastic cells were prone to be present around areas with relatively large amounts of eosinophilic infiltration without fibrosis or lymphatic vessel proliferation. Immunohistochemically, the tumor cells and reactive eosinophils expressed eotaxin-2 and eotaxin-3, respectively.ConclusionWe revealed that eotaxins induced the selective migration of eosinophils into tissues in this case. These eosinophils may affect the tumor remodeling and tumor biology characteristics of HS, such as fibrosis and lymphatic vessel proliferation.

Schistosomiasis with Duodenal Involvement Presenting as Irritable Bowel Syndrome in a 9-Year-Old Patient

Abstract Introduction/Objective Schistosomiasis is extremely rare in the United States. Most patients diagnosed in the US have an international travel history or recently immigrated from endemic areas. We report a case of a 9-year-old boy who presented with a three-month history of daily abdominal pain, decreased appetite, weight loss, and microcytic anemia. The patient had alternating symptoms of constipation and diarrhea mimicking Irritable Bowel Syndrome (IBS). Methods CT scans showed distal sigmoid colon with wall thickening and hyperenhancement. Stool Helicobacter pylori antigen test was positive and hemoglobin levels were low (11 g/dL). The blood eosinophil count was initially within the normal range but was significantly elevated three months later (2,115 cells/µL). Esophagogastroduodenoscopy and colonoscopy were performed, which showed patchy areas of erythema and punctate bleeding within the descending and sigmoid colon. Results Gastrointestinal tract biopsies revealed focal, prominent eosinophilic infiltrates in the lamina propria. There were multifocal granulomas and fibrosis surrounding Schistosoma ova in the lamina propria and submucosa of duodenum, cecum, colon, and rectum. Acid-fast stain highlights the shell and spine of the ova. A retrospective chart review revealed that the patient had traveled to Yemen one month before the onset of symptoms. Schistosomiasis is among the top differentials for marked, sustained eosinophilia, especially with relevant travel history. Distortions caused by processing and sectioning can make speciation difficult on tissue sections. Acid-fast staining of the shell would favor S. mansoni over S. intercalatum; however, the S. intercalatum-S. hematobium hybrid also has an acid fast–positive shell. The duodenum is an uncommon location to find Schistosoma ova, which are usually found in the rectum and sigmoid colon. Conclusion The symptoms of gastrointestinal schistosomiasis may mimic IBS, and eosinophilia may initially be not evident as in this case. However, a high degree of suspicion is required in diagnosing schistosomiasis in patients from endemic areas.

51 Eosinophilic Pancreatitis as a Benign Mimicker of Pancreatic Neoplasm: A Systematic Review

INTRODUCTION: Eosinophilic pancreatitis (EP) is a rare form of pancreatitis characterized by diffuse infiltration of the pancreas with eosinophils &amp; elevated serum immunoglobulin E levels. Diagnosis is clinically difficult as endoscopic/radiographic findings often mimic neoplasm, leading to surgical resection. The aim of this review is to chronicle all cases of EP, describe clinical &amp; radiographic presentation &amp; outcome. METHODS: A systematic search was performed with an experienced librarian of PubMed, Embase &amp; Scopus for search terms of “Eosinophilic Pancreatitis” from 1975–4/19/2019. We included all case reports, series, cohorts &amp; randomized studies with diagnosis of EP. Exclusion criteria were articles with other attributable pancreatitis etiology, fetal EP cases, or non-English language. All articles were reviewed by 2 authors. Data was collected on clinical &amp; radiographic findings, comorbidities &amp; outcome. RESULTS: The search yielded 1379 results of which 18 case reports/series of 23 total patients were included. 17/23 (73.9%) were men, mean age 43.6 ± 17.0 years (range 14–74). Most common symptoms at presentation were abdominal pain (18/23), jaundice (9/23), weight loss (6/23), nausea/vomiting (6/23), &amp; recurrent acute pancreatitis (2/23). Comorbidities included Diabetes Mellitus (2/23) &amp; asthma/allergies (4/23). Imaging revealed abnormalities (mass, hypodensity, or enlargement) located in the pancreatic head (13/23), body (2/23) &amp; tail (3/23). A pancreatic mass was most commonly found (11/23), followed by pancreatic enlargement (8/23), pancreatic duct dilatation (5/23) &amp; bile duct dilatation (8/23). 4/23 patients had a pseudocyst; none had necrosis. Pathology showed prominent eosinophilic infiltrate in all cases, with 5/23 having few lymphocytes &amp; 9/23 with diffuse inflammatory infiltrates. 16/23 patients underwent surgical resection with EP diagnosis made post-operatively. 5/23 patients had complications (4/23 resolved with steroids; 1 died from systemic hypereosinophilia with renal failure &amp; chylothorax). CONCLUSION: EP presents more commonly in men in a 3:1 ratio in the 5th decade. EP should be considered in patients with abdominal pain, jaundice, &amp; weight loss with imaging of a pancreatic mass or enlargement, or ductal dilation. EP masquerades as malignancy; however, diagnostic clues to EP include peripheral eosinophilia &amp; presence of diabetes or asthma/allergies. Awareness of EP may allow for potential non-operative diagnosis, avoidance of surgery, &amp; appropriate medical therapy.

Induction of peripheral lymph node addressin in human nasal mucosa with eosinophilic chronic rhinosinusitis

Eosinophilic chronic rhinosinusitis (ECRS) is characterised by formation of nasal polyps with prominent eosinophilic infiltration; however, how eosinophils are recruited in this pathological setting remains unclear. In the present study, we carried out quantitative immunohistochemical analysis of nasal polyps associated with ECRS (n=30) and non-ECRS (n=30) to evaluate expression of an L-selectin ligand peripheral lymph node addressin (PNAd) on vascular endothelial cells. We found that PNAd was induced primarily on the luminal surface of venular vessels present in nasal mucosa in both ECRS and non-ECRS, while the number of PNAd-expressing vessels in ECRS significantly exceeded that seen in non-ECRS. Moreover, the number of eosinophils attached to the luminal surface of PNAd-expressing vessels in ECRS was significantly greater than that in non-ECRS, while the number of neutrophils and lymphocytes attached did not differ significantly between conditions. Furthermore, eosinophils, which express cell surface L-selectin, adhered to PNAd-expressing Chinese hamster ovary (CHO) cells in a calcium-dependent manner, and that adhesion was significantly inhibited by pretreatment of eosinophils with DREG-56, an anti-human L-selectin monoclonal antibody. These findings combined suggest that interaction between L-selectin and PNAd plays at least a partial role in eosinophil recruitment in human nasal mucosa with ECRS.

Clinicopathological characteristics and diagnosis of IgG4related sialadenitis

Immunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated disease and one of immunoglobulin G4-related diseases (IgG4-RD). Our multidisciplinary research group investigated the clinicopathological characteristics and diagnosis of IgG4-RS during the past 10 years. Clinically, it showed multiple bilateral enlargement of major salivary glands (including sublingual and accessory parotid glands) and lacrimal glands. The comorbid diseases of head and neck region including rhinosinusitis, allergic rhinitis, and lymphadenopathy were commonly seen, which could occur more early than enlargement of major salivary glands. Internal organ involvements, such as autoimmune pancreatitis, sclerosing cholangitis, and interstitial pneumonia could also be seen. Thirty-five (38.5%) patients had the symptom of xerostomia. Saliva flow at rest was lower than normal. Secretory function was reduced more severely in the submandibular glands than in the parotid glands. Serum levels of IgG4 were elevated in almost all the cases and the majority of the patients had increased IgE levels. CT, ultrasonography, and sialography showed their imaging characteristics. Histologically it showed marked lymphoplasmacytic inflammation, large irregular lymphoid follicles with expanded germinal centers, prominent cellular interlobular fibrosis, eosinophil infiltration, and obliterative phlebitis. Their immunohistological examination showed marked IgG-positive and IgG4-positive plasma cell infiltration and high IgG4/IgG ratio. The disease could be divided into three stages according to severity of glandular fibrosis. The serum IgG4 level was higher and the saliva secretion lower as glandular fibrosis increased. IgG4-RS should be differentiated from other diseases with enlargement of major salivary gland and lacrimal gland, such as primary Sjögren syndrome, chronic obstructive submandibular sialadenitis, and eosinophilic hyperplastic lymphogranuloma.

Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory upper airway disease, accompanied mainly by eosinophilia and/or asthma. In addition, the disease correlates with a high rate of hyposmia, following a marked infiltration of eosinophils into the inflamed site, the paranasal sinus. Although eosinophils are known to contribute to the development of hyposmia and CRSwNP pathology, the underlying mechanisms remain unclear. This study aimed to investigate whether eosinophilic upper airway inflammation induces hyposmia and CRSwNP in a murine model using an adoptive transfer system. Methods: To induce eosinophilic rhinosinusitis, splenocytes, including a high proportion (over 50%) of activated eosinophils (SPLhEos), were collected from interleukin-5 transgenic mice following double intraperitoneal injections of antigens, such as ovalbumin, house dust mite, or fungus. Activated SPLhEos with corresponding antigens were then transferred into the nasal cavity of recipient mice, which were sensitized and challenged by the corresponding antigen four times per week. Olfactory function, histopathological, and computed tomography (CT) analyses were performed 2 days after the final transfer of eosinophils. Results: Hyposmia was induced significantly in mice that received SPLhEos transfer compared with healthy and allergic mice, but it did not promote morphological alteration of the paranasal sinus. Pathological analysis revealed that epithelial layer injury and metaplasia similar to polyps, with prominent eosinophil infiltration, was induced in recipient tissue. However, there was no nasal polyp development with interstitial edema that was similar to those recognized in human chronic rhinosinusitis. Conclusions: This study supports the previously unsuspected contribution of eosinophils to CRS development in the murine model and suggests that murine-activated eosinophilic splenocytes contribute to the development of hyposmia due to more mucosal inflammation than physical airway obstruction and epithelial layer injury with convex lesions.

Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.

BackgroundInsect‐bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type‐I/type‐IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin‐5 (IL‐5) is the key cytokine for eosinophils and we have previously shown that targeting IL‐5 by vaccination reduces disease symptoms in horses.ObjectiveHere, we analyzed the potential for long‐term therapy by assessing a second follow‐up year of the previously published study.MethodsThe vaccine consisted of equine IL‐5 (eIL‐5) covalently linked to a cucumber mosaic virus‐like particle (VLP) containing a universal T cell epitope (CuMVTT) using a semi‐crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 μg of eIL‐5‐CuMVTT without adjuvant.ResultsThe vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti‐eIL‐5 auto‐antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms.ConclusionYearly vaccination against IL‐5 may be a long‐term solution for the treatment of IBH and other eosinophil‐mediated diseases in horses and other species including humans.