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INTRODUCTION The medical demand for lymphedema treatment is huge since the disease mechanism remains unclear, and management are difficult. Our purpose was to develop a reliable lymphedema model mimicking the clinical scenario and allows a microsurgical approach. MATERIALS AND METHODS Male Lewis rats weighing 400 to 450 g were used to create lymphedema with groin and popliteal lymph node dissection and creation of 5 mm circumferential skin defect (n = 6). A skin incision was made and closed primarily for control group (n = 5). Evaluation included indocyanine green (ICG) lymphangiography 1 and 2 months postoperatively, volume difference between bilateral hindlimbs measured using micro-CT, and the skin was harvested for histological evaluation 2 months postoperatively. RESULTS Larger volume differences present in the lymphedema group (17.50 ± 7.76 vs. 3.73 ± 2.66%, p

A 54-year-old male presented with a three-year history of bilateral upper eyelid and peri-orbital swelling and adult-onset asthma. Histopathology of a left orbital biopsy showed lymphoid follicles with foamy macrophages and Touton giant cells. Clinical, histological and radiological features were consistent with adult-onset asthma and periocular xanthogranuloma. Treatment with rituximab led to a complete clinical and radiological remission. Nine years later, his condition relapsed with a biopsy of the left orbit and lacrimal gland demonstrating features of IgG4-related disease and adult-onset asthma and periocular xanthogranuloma. Immunohistochemistry showed increased numbers of IgG4+ plasma cells (290 per high power field) and an elevated IgG4+/IgG+ plasma cell ratio of 480%. Involvement by both disorders in the orbit and ocular adnexa of a single patient has not previously been reported in the literature, to the best of our knowledge, and suggests a possible aetiologic or pathophysiologic association.

AimTo retrospectively evaluate the characteristic clinicopathological spectrum in patients with suspicion of IgG4-related disease (IgG4RD).MethodsWinpath histology database from January 2011 to April 2018 identified all suspected IgG4RD cases wherein IgG4 immunohistochemistry was performed. The histology slides were reviewed to categorise cases into Boston criteria groups—highly suggestive of IgG4RD, probable IgG4RD and insufficient evidence. Information regarding clinical data, treatment received, follow-up and serum IgG4 levels was obtained from medical records and AllScripts Patient Administration System (APAS) clinical database.ResultsThe study included 204 patients and the most common sites of biopsy/resection were pancreas and duodenum. The most common clinical presentation was fibroinflammatory lesion or mass/lump. On histology, 54/204 (26.47%) cases showed typical storiform fibrosis, 65/204 (32.64%) had >10 IgG4+ plasma cells per high power field and only one case showed thrombophlebitis (0.49%). There were 14/204 (6.78%) cases categorised as highly suggestive of IgG4RD; 8 of these showed high serum IgG4 levels and were managed clinically as true IgG4RD.ConclusionHistological diagnosis of IgG4RD remains challenging, as not all characteristic features are always present especially in small biopsies. Due to the novelty of its experience, fear of over diagnosis in the context of malignancy and features overlapping with diseases of similar clinical scenario, diagnosis of IgG4RD has become more puzzling. Further multicentre clinical trials/studies are advisable.

Chronic rhinosinusitis (CRS) can be classified as eosinophilic (eCRS) or non-eosinophilic (neCRS) based on infiltration type. The SWI/SNF complex may be involved in the pathophysiology of CRS.To assess the expression of the SWI/SNF complex in both CRS groups; to correlate blood eosinophil count (BEC), and histopathology eosinophil count (HPEC) with the SWI/SNF expression level in eCRS and neCRS.The study population consisted of 96 patients (68 eCRS, 28 neCRS). Immunohistochemical staining was performed on sinonasal mucosa for assessment of SWI/SNF protein expression. Type of tissue infiltration was assessed in samples obtained from examined groups (HPEC). The diagnostic value of eCRS was 10 cells/HPF (high power field). Complete blood count was analysed in order to calculate BEC.BEC and HPEC correlated negatively with all the SWI/SNF subunits. HPEC and BEC correlated positively with clinical findings (L-M and SNOT-22), while SWI/SNF correlated negatively with clinical findings (L-M and SNOT-22).The SWI/SNF was observed in both eCRS and neCRS, with lower expression in former. The meaning of its negative correlation with BEC, HPEC and clinical findings in eCRS group remains to be understood.Il complesso SWI/SNF nella rinosinusite cronica eosinofila e non eosinofila.La rinosinusite cronica (CRS) può essere classificata come eosinofila (eCRS) o non-eosinofila (neCRS), in base al tipo di infiltrato cellulare. Il complesso SWI/SNF potrebbe avere un ruolo nella fisiopatologia della CRS.Valutare l’espressione del complesso SWI/SNF in entrambi i gruppi di CRS; correlare la conta degli eosinofili nel sangue (BEC) e la conta degli eosinofili nel preparato istopatologico (HPEC) con il livello di espressione SWI/SNF nei gruppi eCRS e neCRS.La popolazione dello studio è composta da 96 pazienti (68-eCRS, 28-neCRS), è stata eseguita la colorazione immunoistochimica sulla mucosa rinosinusale per valutare i livelli di espressione della proteina SWI/SNF, è stato valutato il tipo di infiltrato cellulare nei campioni ottenuti (HPEC). Valore di eosinofili, diagnostico di eCRS: 10 cellule / HPF. È stato analizzato l’emocromo completo per calcolare il BEC.BEC e HPEC sono risultati inversamente correlati con tutte le subunità SWI/SNF e correlati positivamente con i dati clinici (L-M e SNOT-22), mentre SWI/SNF erano correlati negativamente con i risultati clinici (L-M e SNOT-22).Il complesso SWI/SNF è risultato presente sia in eCRS che in neCRS, con un’espressione inferiore nel primo tipo di rinosinusite cronica. Il significato della sua correlazione negativa con BEC, HPEC e risultati clinici nel gruppo eCRS resta da indagare.

Gastrointestinal stromal tumors (GISTs) are the dominant mesenchymal tumors of the digestive tract. Extragastrointestinal stromal tumors (EGISTs) usually originate outside the gastrointestinal tract without connection to the gastric or intestinal wall. However, EGISTs arising from the vaginal wall are very rare. Here, we report a case of EGIST that occurred in the vagina of a 60-year-old woman. The tumor was present in the posterior vaginal wall. It was surgically excised, and histological examination revealed spindle cell morphology with up to 14 mitoses per 50 high power field (HPF) and necrosis with the tumor-negative margins. Immunohistochemical analyses showed strongly positive CD34, CD117, and DOG-1 expression, but negative SMA, S-100, CD10, desmin, and actin expression. The patient underwent surgery and is currently being followed up. A literature review of EGSTs and treatments is also discussed in this report.

Background: Tumor budding is recognized as an important independent prognostic factor in colorectal carcinoma. The aim of this study was to evaluate the grade of tumor budding and association with other clinical and pathological features in patients with cervical carcinoma. Material and methods: We evaluated pathohistological data from 91 cervical carcinoma patients (mean age: 53.8 years) who underwent radical hysterectomy and pelvic lymphatic dissection at the Oncology Institute of Vojvodina between January 2010 and December 2018. Tumor budding was evaluated in invasive front of the tumor. Based on the number of bud counts/10 high power field, three groups were formed: with no budding, with less than 15 buds, and with more than 15 buds. Results: Eighty (87.91%) of evaluated cervical carcinomas were squamous-cell type, while 12.09% were adenocarcinomas. All carcinomas were graded (HG1-HG3). Average diameter of the tumors was 25 mm (81.6% < 4 cm and 18.4% > 4 cm). Metastases in lymph nodes were present in 30 (32.9%) cases. Based on the number of bud counts/10 high power field there were 35.1% with no budding, 32.9% with less than 15 buds and 37.3% with more than 15 buds. There was a significant association between tumor budding grade and histological grade (p=0.04), as well as with tumor budding grade and the diameter of the tumor (p=0.04). Conclusion: As a quantitative measure of cancer cell dissociation, tumor budding is associated with poor prognosis in cervical carcinoma and should be considered as a prognostic factor.

AIM To determine whether single endometrial polyp (EP) or multiple EP (polyp number ≥ 6) are associated with chronic endometritis (CE). METHODS From June 2017 to December 2018, this study enrolled a total of 277 patients, including 92 patients with multiple EP, 82 patients with a single EP and 103 patients without polyps who underwent hysteroscopic examination and polypectomy. Polyps and endometrium samples were obtained and subjected to immunohistochemistry for CD138 to identify plasma cells and CE was diagnosed as CD138-positive plasma cells greater than or equal to 5/high power field. The prevalence of CE was compared and analyzed using the logistic regression model. RESULTS All baseline parameters were comparable among the three groups except that the prevalence of abnormal uterine bleeding (AUB) was much higher in both polyp groups than the non-polyp control. The prevalence of CE was significantly higher in the multiple EP group than in the single EP group (58.7% vs 28.0%, P

Background & Objective: Meningiomas are the most frequently encountered primary non-glial tumors of the central nervous system (CNS). The Ki67 labelling index (Ki67LI) is a proliferation marker that may prove useful in determining the histological grade. This study aims at: 1) Studying the frequency, grade and histomorphological spectrum of meningiomas, 2) Evaluating 20 histological parameters and determining its utility in grading meningiomas and 3) Comparing the Ki67LI in the various subtypes and WHO grades. Methods: The cases of meningiomas diagnosed in our Department from June 2009 to May 2014 were included. The clinical details, grade and 20 histological parameters: mitosis, vesicular nuclei, macronucleoli, nuclear pleomorphism, scattered bizarre nuclei, hypercellularity, sheeting, lymphocytes, small cell change, foam cells, ossification, necrosis, papillary change, lipidization, psammoma bodies, vascularization, brain invasion, dural invasion, bone invasion and other soft tissue invasion were recorded for each case. The average and highest Ki67LI was recorded as percentage and number per high power field. Results: A total of 175 cases of meningioma were included: grade I (145), grade II (30). Atypical histological features like hypercellularity, sheeting, etc. were common in grade II tumors. Increased vascularity, lymphocytes and psammoma bodies were common in grade I tumors. Ki67LI (highest) ranged from 1-6% in grade I and 5-12% in grade II tumors. Conclusion: Among different methods showing mitotic activity, Ki67% (highest) was the most statistically significant LI in differentiating grade I and grade II tumors. The median Ki67% (highest) was 4% for grade I and 7% for grade II tumors.

OBJECTIVES Eosinophilic esophagitis (EoE) is characterized by remissions and relapses. Guidelines defining remission do not exist and therefore remission is inconsistently identified. We sought to define histology remission in EoE. METHODS Esophageal biopsies, obtained at the time the validated pediatric EoE symptoms scores v2.0 (PEESS v2.0) questionnaire was completed (N = 42), were scored using the validated EoE Histology Scoring System. An EoE Histology Remission Score (EoEHRS) was constructed and specified that in all esophageal sites sampled the peak eosinophil count was

BACKGROUND: Diagnosis of eosinophilic esophagitis (EoE) requires manual quantification of tissue eosinophils. Eosinophil peroxidase (EPX) is an eosinophil-specific, cytoplasmic granule protein released during degranulation. AIMS: The objective of this study was to evaluate image analysis of EPX immunohistochemistry as an automated method for histologic diagnosis of EoE. METHODS: We performed a secondary analysis of prospectively collected esophageal biopsies obtained from adult subjects with EoE and controls. Tissue sections were stained with hematoxylin and eosin (H&E) and evaluated for peak eosinophils per high power field (eos/hpf). The same slides were de-stained and re-stained to detect EPX for direct comparison. Slides were digitized and EPX staining area/mm(2) was quantified using image analysis. Paired samples were compared for changes in EPX staining in treatment responders and non-responders. RESULTS: Thirty-eight EoE cases and 49 controls were analyzed. Among EoE subjects, matched post-treatment biopsies were available for 21 responders and 10 non-responders. Baseline EPX/mm(2) was significantly increased in EoE subjects and decreased in treatment responders. EPX quantification correlated strongly with eos/hpf (r = 0.84, p < 0.0001) and identified EoE subjects with high diagnostic accuracy (AUC 0.95, p < 0.0001). The optimal diagnostic EPX-positive pixel/area threshold was 17,379 EPX/mm(2). Several controls (5/49) with < 15 eos/hpf on H&E staining exceeded this cutoff. CONCLUSIONS: EPX/mm(2) correlates strongly with eos/hpf, accurately identifies subjects with EoE, and decreases in treatment responders. Automated quantification of intact eosinophils and their degranulation products may enhance pathologic assessment. Future studies are needed to correlate EPX/mm(2) with symptoms, endoscopic findings, and esophageal distensibility.

The aim of the study was to investigate vasa venarum of great saphenous vein and their endothelial proliferation and to evaluate the modification of the microvessel density in case of atherosclerosis and associated diabetes mellitus. Material and methods. The present study included nine venous fragments of human saphenous veins collected from the patients whose lower limbs were amputated. The causes of the limb ablation were: trauma (1 case) and atherosclerosis complicated with occlusion or thrombosis of the lower limbs arteries (8 cases). There were two cases presenting associated diabetes mellitus among the eight cases of atherosclerosis. Formalin-fixed tissues were paraffin embedded and cut into 3μm transverse sections. The slides were stained by a double immunostaining technique using the monoclonal antibodies anti-CD34 and anti-Ki67. The microvessel density was determined by counting the vessels of three “hot spots” and represented by the average values of three “hot spot” areas divided on the surface of high power field (0.0625 mm2). The endothelial cell proliferation index was calculated as the percentage of all nuclei of Ki67-stained endothelial cells that also co-expressed positive cytoplasmic staining in CD34-positive cells. Results. Vasa venarum of the examined segments of human great saphenous veins were found both in the adventitia and the tunica media. In case of the traumatic injury of the lower limb the adventitial vasa venarum were 4.5 times more numerous (299 vessels/mm2) than those of great saphenous vein media (64 vessels/mm2). In case of associated metabolic disorders we found increased number of vasa venarum of saphenous vein media, 247±109 vessels/mm2 and 253±51 vessels/mm2, respectively. However, the adventitial microvessel density was lower in case of atherosclerosis (151±23 vessels/mm2) and associated diabetes mellitus (125±3 vessels/mm2). The endothelial cell proliferation index was between 20% and 25% in saphenous vein from the patient with the traumatic injury. Moreover, the proliferation index was higher, ranged between 25% and 30%, in saphenous vein from the patients with metabolic disorders. In the adventitia and the media sprouting and non-sprouting angiogenesis were observed. Conclusions. Under normal conditions, the microcirculatory vessels predominate in the adventitia, but under pathological conditions (atherosclerosis, diabetes mellitus) the microvessels of the media can exceed numerically the microvessels of the adventitia. The vasa venarum of the tunica media can be located in its outer layer. The Ki67-endothelial proliferation index can be higher (25–30%) in case of the atherosclerosis and associated diabetes mellitus than that in normal conditions (20–25%). The formation of the neovasa vasorum occur through both sprouting and non-sprouting angiogenesis. The aim of the study was to investigate vasa venarum of great saphenous vein and their endothelial proliferation and to evaluate the modification of the microvessel density in case of atherosclerosis and associated diabetes mellitus. Material and methods. The present study included nine venous fragments of human saphenous veins collected from the patients whose lower limbs were amputated. The causes of the limb ablation were: trauma (1 case) and atherosclerosis complicated with occlusion or thrombosis of the lower limbs arteries (8 cases). There were two cases presenting associated diabetes mellitus among the eight cases of atherosclerosis. Formalin-fixed tissues were paraffin embedded and cut into 3μm transverse sections. The slides were stained by a double immunostaining technique using the monoclonal antibodies anti-CD34 and anti-Ki67. The microvessel density was determined by counting the vessels of three “hot spots” and represented by the average values of three “hot spot” areas divided on the surface of high power field (0.0625 mm2). The endothelial cell proliferation index was calculated as the percentage of all nuclei of Ki67-stained endothelial cells that also co-expressed positive cytoplasmic staining in CD34-positive cells. Results. Vasa venarum of the examined segments of human great saphenous veins were found both in the adventitia and the tunica media. In case of the traumatic injury of the lower limb the adventitial vasa venarum were 4.5 times more numerous (299 vessels/mm2) than those of great saphenous vein media (64 vessels/mm2). In case of associated metabolic disorders we found increased number of vasa venarum of saphenous vein media, 247±109 vessels/mm2 and 253±51 vessels/mm2, respectively. However, the adventitial microvessel density was lower in case of atherosclerosis (151±23 vessels/mm2) and associated diabetes mellitus (125±3 vessels/mm2). The endothelial cell proliferation index was between 20% and 25% in saphenous vein from the patient with the traumatic injury. Moreover, the proliferation index was higher, ranged between 25% and 30%, in saphenous vein from the patients with metabolic disorders. In the adventitia and the media sprouting and non-sprouting angiogenesis were observed. Conclusions. Under normal conditions, the microcirculatory vessels predominate in the adventitia, but under pathological conditions (atherosclerosis, diabetes mellitus) the microvessels of the media can exceed numerically the microvessels of the adventitia. The vasa venarum of the tunica media can be located in its outer layer. The Ki67-endothelial proliferation index can be higher (25–30%) in case of the atherosclerosis and associated diabetes mellitus than that in normal conditions (20–25%). The formation of the neovasa vasorum occur through both sprouting and non-sprouting angiogenesis.

Introduction: Prostate cancer exhibits a complex genetic and heterogeneous histological pattern reflecting its multifactorial phenotype. Mast cells mainly known for their role in allergy and anaphylaxis, now regarded as key factor cell in angiogenesis, tissue remodeling and repair, whereas their importance in tumor pathology as either cancer promoter or inhibitor is still debated. Materials and Methods: Study included 100 cases of prostatic lesions with 74 cases of benign prostatic lesions and 26 cases of adenocarcinoma prostate, received in the form of transurethral resection of prostate chips for histopathological examination. The tissues were routinely processed, the paraffin sections stained by hematoxylin and eosin and 1% toluidine blue. Histological diagnosis was made. Mast cell count was done taking a standard of 10 high power fields(x40) and mean were calculated. Distributions of mast cells were noted in stroma, perivascular, periglandular and intraglandular regions. Results: Mast cell count was significantly higher in benign prostatic hyperplasia with mean of 3.6 per high power field whereas absence or low count was found in adenocarcinoma prostate with mean of 1.7 per high power field. Mast cells were located predominantly in stromal region in both BPH and adenocarcinoma prostate; in rest of the areas the numbers were comparable. Conclusion: In this study we observed significant increase in mast cell count in stroma of BPH compared to adenocarcinoma indicating that mast cell density is inversely proportional to malignancy. This suggests high mast cell count favors the prognosis. Keywords: Mast cells, Benign Prostatic Hyperplasia, Adenocarcinoma.

Eosinophilic esophagitis (EoE) is an eosinophil-rich, Th2 antigen-mediated disease of increasing worldwideprevalence. Originally considered common in children and young adults, it can be seen at any age, withthe highest prevalence between 30 and 40 years. Symptoms reflect esophageal dysfunction, and typicalendoscopic pictures consist of rings, furrows, exudates and edema. Progressive disease leads to pathologictissue remodeling, with ensuing esophageal rigidity and loss of luminal diameter caused by strictures. Thedefinitive diagnosis is histological (at least 15 eosinophils/HPF, high power field), upper gastrointestinalendoscopy with multiple esophageal biopsies being mandatory. Current therapeutic options include dietaryand pharmacologic treatments. Despite being successful in a high proportion of patients, elemental diet hasmultiple disadvantages. Therefore, a step-up approach (using a two-, four- and six food elimination diets) ispreferred, being globally effective in up to 79% of cases and avoiding unnecessary restrictions. Drug therapyrelies on proton pump inhibitors and topical corticosteroids. Esophageal dilation may be required to increaseluminal patency, leading to immediate symptomatic improvement in 95% of EoE patients, who have stricturesor narrow caliber esophagus. The chronic nature of the disease necessitates long-term therapy. In this review,current diagnostic and treatment options are discussed and a treatment algorithm is proposed.

Background Esophageal gastrointestinal stromal tumors(GISTs) are extremely rare. We sought to determine whether endoscopic treatment can be a viable therapeutic option for esophageal GISTs. Methods A total of 20 cases with histological diagnosis of esophageal GISTs were obtained from our center between 2008 and 2020. Data on the clinicopathological features and treatment were recorded. Results There were 9 males (45%) and 11 females (55%) in this study, with a median age of 56 years. The tumors preferentially occurred in the middle and lower parts of the thoracic esophagus (45 and 40%, respectively). The mean size of the tumors was 2.27 cm and mitotic index was no more than 5/50 high power field (HPF) in all patients. In this study, 11 patients received endoscopic treatment and nine patients underwent surgical resection. Tumors ranged from 0.6 to 4 cm in the endoscopic treatment patients and 0.5 to 7 cm in the surgical patients. There were no significant differences in gender, age, symptoms, tumor location, tumor size, mitotic index, and adjuvant imatinib therapy between the endoscopic treatment group and the surgery group (all p > .05). The Kaplan-Meier curve suggested that there was also no significant difference in disease-free survival between the two groups (p = .264). Conclusions Endoscopic treatment may be an option for the treatment of esophageal GISTs smaller than 5 cm with a mitotic index no more than 5/50 HPF.

Background and aim Glomerular erythrocyturia (GlomEry) is usually associated with proliferative kidney diseases. In our retrospective cohort, we aimed to validate the predictive value of GlomEry criteria ≥ 40% dysmorphic erythrocytes (DysEry) or ≥ 5% acanthocytes (AcaEry) or at least 1 erythrocytic cast (CastEry) and of two new indices - the count of DysEry per high power field (HPF) and per microliter of urine (Stansfeld-Webb (SW)) method, for proliferative disease. Materials and methods We included patients with erythrocyturia from 2015 to 2016. Based on renal histology, we divided them into a proliferative and a non-proliferative disease group. Urine erythrocyte count was done using SW and urinary sediment examination was carried out by skilled nephrologists. Sensitivity, specificity, and cutoff values were determined using ROC curves. Results We included 90 patients (33% women), median age of 63 (IQR 51, 71) years. In the proliferative group, proteinuria was lower (2.4 vs. 6.6 g/day), and SW erythrocyturia was higher (174 (IQR 60, 353) vs. 44 (IQR 20, 67) × 106/L) than in the non-proliferative group. The threshold to differentiate between the proliferative and non-proliferative group was determined at ˃ 43% of DysEry (sensitivity 73%, specificity 79%, AUC 0.808) and at ˃ 2% AcaEry (sensitivity 71%, specificity 56%, AUC 0.647). No significant difference in CastEry was found between groups. Among tested parameters, the calculated number of DysEry/HPF > 6.7 (sensitivity 77%, specificity 92%, AUC 0.878), followed by DysEry/SW > 28 × 106/L (sensitivity 76%, specificity 86%, AUC 0.879), discriminated those two groups best. Conclusion In concordance with known GlomEry criteria, > 43% of DysEry predicted proliferative kidney disease, whereas CastEry did not, and AcaEry predicted poorly. The best predictor of proliferative glomerular disease was DysEry/HPF, closely followed by DysEry/SW.

Gallbladder carcinoma is an uncommon malignancy with an overall 5-year survival of less than 5%. Gallbladder carcinoma has been strongly linked with cholelithiasis and chronic inflammation. Case reports and series have described cholecystitis with acute (neutrophilic) inflammation in association with gallbladder carcinoma, although a clear relationship to patient outcome has not been established. Our series included 8 cases of gallbladder carcinoma with high tumor-associated neutrophils (>25 per high power field) that were associated with shorter patient survival (Cox regression coefficient 6.2, p = 0.004) than age- and stage-matched controls. High tumor-associated neutrophils were not associated with gallbladder rupture/perforation or increased bacterial load measured by 16S PCR. Neutrophilic inflammation with gallbladder carcinoma correlates to shorter survival, independent of patient age and stage of carcinoma. The findings suggest that the degree of neutrophilic inflammation may have prognostic significance in specimens from patients with gallbladder carcinoma after cholecystectomy. Further studies with larger case numbers are needed to confirm and generalize these findings.

Objective The histopathological characteristics of primary vs recurrent nasal polyps in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have not been studied comprehensively. Identification of these features may be helpful for prognostication, postoperative management, and consideration of novel eosinophil‐targeting biologic therapy. This study investigates the histopathological differences in primary vs recurrent CRSwNP tissue. Methods Patients undergoing endoscopic sinus surgery for CRSwNP were included if all 13 histopathological and mucin characteristics on a standardized report were available. Histopathology parameters were compared in surgical tissue and mucin from primary vs recurrent CRSwNP. Results Complete structured histopathology reports were available for 96 patients (39 primary polyps and 57 recurrent polyps). Compared to primary polyp tissue, recurrent CRSwNP mucin was significantly more likely to feature eosinophil aggregates (57.9% vs 35.9%; P = .047). Tissue eosinophilia (using a threshold >10 per high power field [HPF]) was not significantly different in primary and recurrent CRSwNP tissue. Other histopathologic parameters and clinical characteristics were similar. Conclusion Eosinophil aggregates on histopathology are significantly more likely to be present in recurrent CRSwNP. In the limited series, tissue eosinophilia (>10 per HPF) was not significantly different in primary and recurrent CRSwNP. Therefore, in addition to the study of tissue eosinophilia levels, Rhinologic surgeons should also direct attention to CRSwNP mucin. Mucin eosinophilic aggregates are an independent marker of severe inflammation that is associated more likely with recurrent vs primary polyposis. Further study of this marker may help determine its role of choice of postoperative medical therapies, including anti‐eosinophilic biologics. Level of Evidence 4

BACKGROUND: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need in EG for more precise diagnostic tools. OBJECTIVE: We aimed to develop tissue- and blood-based diagnostic platforms for EG. METHODS: Patients with EG and non-EG controls were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. The EGDP(18) scores were derived from the expression of 18 highly dysregulated genes and Blood EG scores from dysregulated cytokines/chemokine levels. RESULTS: Gastric biopsies and blood samples from 185 subjects (EG 74, non-EG 111) were analyzed. The EGDP a) identified patients with active EG (P < .0001, AUC ≥0.95); b) effectively monitored disease activity in longitudinal samples (P = .0078); c) highly correlated in same-patient samples (antrum vs. body, r = 0.85, P < .0001); and d) inversely correlated with gastric peak eosinophil levels (r = −0.83, P < .0001), periglandular circumferential collars (r = − 0.73, P < .0001), and endoscopic nodularity (r = −0.45, P < .0001). For blood-based platforms, eotaxin-3, TARC, IL-5, and TSLP levels were significantly increased. Blood EG scores a) distinguished patients with EG from non-EG controls (P < .0001, AUC ≥0.91); b) correlated with gastric eosinophil levels (plasma r = 0.72, P = .0002; serum r = 0.54, P = .0015); and c) inversely correlated with EGDP(18) scores (plasma r = −0.64, P = .0015; serum r = −0.46, P = .0084). Plasma eotaxin-3 strongly associated with gastric CCL26 expression (r = 0.81, P < .0001). CONCLUSION: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and tools for this emerging rare disease.

Objectives To evaluate histologic changes occurring in patients having chronic hepatitis C and autoimmune hepatitis overlap (HCV-AIH), and who achieved virologic cure using direct-acting antiviral agents (DAA). Methods Characteristics of HCV-AIH patients who underwent paired liver biopsies before and after receiving DAA treatment from 2011 to 2018 were evaluated. Results Five HCV-AIH patients (three male; mean age, 60.4 years) underwent paired liver biopsies (average interval, 2.3 years) before and after achieving cure with DAA treatment. All patients showed virologic response, while four showed decreased inflammation, and three cases showed features of fibrosis regression. Immunohistochemical staining demonstrated significant decrease in plasma cell count in three patients (20.6 vs 11.9 plasma cells/high power field; P = .02, t test). Conclusions Histologic improvements in inflammation and fibrosis are noted in most HCV-AIH patients after DAA treatment, suggesting that the autoimmune component of the HCV-AIH overlap syndrome is merely a secondary phenomenon of viral infection.

International audience; OBJECTIVE: Eosinophilic esophagitis (EoE) is an increasingly recognized childhood disease. Esophageal atresia (EA) is the most frequent congenital malformation of the esophagus. Recently, cases of EoE occurring in patients with EA have been reported, although the exact prevalence of EoE in EA remains unknown. The aim is to investigate the prevalence of EoE among EA in adolescents and to describe these patients' characteristics.METHODS: Systematic upper gastrointestinal endoscopies with multistage esophageal biopsies were prospectively performed in 63 adolescents with EA. A standardized form was used to collect clinical and endoscopic data. Diagnosis of EoE was made as ≥15 intraepithelial eosinophils/high power field, whatever the response on proton pump inhibitors therapy.RESULTS: Six patients (9.5%) presented an EoE (17-100 eosinophils/high power field). An atopic condition was reported more frequently in the eosinophil ≥15 group than in patients with no EoE (66% vs 16%; P = 0.014). Except for chest pain, symptoms and endoscopic features were similar in patients with EoE and patients with no EoE.CONCLUSIONS: In our series of 63 patients born with EA, mainly distal tracheoesophageal fistula, the prevalence of EoE is increased, and therefore should be considered in adolescents with EA.

Objective Langerhans cell histiocytosis (LCH) is a rare disease affecting predominantly children and young adults but can be found in any age group. Diagnosis of LCH is often difficult and can be delayed because of its rarity. The present study highlights the cytomorphological features in a large cohort of cases. An accurate cytological diagnosis may avoid unnecessary biopsy and guide appropriate management. Method Fourty seven (47) cases of LCH diagnosed on cytological material & fine-needle aspiration (FNA) over a period of 14 years (2003-2016) were retrieved from the archives. The cytological smears were evaluated and microscopic findings collected by semi-quantitative assessment done by two different pathologists RESULT: The age at the diagnosis of the patients ranged from 9 months to 28 years. The majority of cases were in the age group of 0-5 years. The most common site was head and neck region, which included cervical lymphadenopathy and scalp swelling. Two cases were diagnosed each from inguinal lymph node and bronchio-alveolar lavage (BAL). Cytological smears in the majority of the cases were moderate to highly cellular (58%) and showing abundant Langerhans cell in (72%) of cases. Areas of necrosis were seen in 38%, while 78% of cases showed giant cells. The majority of cases showed mild eosinophilia (61%), sparse lymphocytosis (83%) and mild neutrophilic infiltration (64%). There were 1-2 mitoses per 10 high power field in 12 cases (25.5%). No abnormal mitoses were identified. Conclusion The presence of cells with features of Langerhans cells associated with the expression of selected immunohistochemical markers allow the diagnosis of LCH on cytological samples, sparing more invasive procedure as a biopsy.

Eosinophilic oesophagitis is a disease that has been recognized in the past 30 years. It causes dysphagia and other symptoms of oesophageal dysfunction. Eosinophilic oesophagitis presents either with a chronic feeling of difficulty swallowing, with food moving slowly through the oesophagus, or as an acute food bolus obstruction requiring emergency attention. Patients may also experience chest pain at this time. It is an inflammatory disorder, thought to be driven by food or environmental antigens, where the most distinctive cell type is eosinophils. Eosinophilic oesophagitis is mediated through a local IgG4 mechanism and does not manifest as a systemic disease. It is diagnosed only on endoscopy and biopsy – there are characteristic endoscopic appearances with oedema, rings, furrows and strictures but the golden rule in its diagnosis is to perform multiple biopsies from multiple sites in the oesophagus in all patients with dysphagia or other oesophageal dysfunction. Finding a peak concentration of >15 eosinophils per high power field in this situation is diagnostic of eosinophilic oesophagitis. Eosinophilic oesophagitis is not usually related to gastro-oesophageal reflux disease, but the two conditions may co-exist. Current therapies include topical steroids (oro-dispersible formulation of budesonide), proton pump inhibitors and dietary exclusions. Therapeutic oesophageal dilatation is reserved for refractory symptoms or tight strictures.

Background: Chronic Rhinosinusitis is currently classified into eosinophilic and non-eosinophilic, according to the histologic quantification of the number of eosinophils in nasal mucosa biopsy. There is a lack of unanimous histopathologic criteria and methodology for this classification and no consensus regarding a cut-off point for Eosinophils per High power field. Methodology: A systematic electronic search was performed on BVS, PUBMED, PUBMED PMC, SCOPUS, WEB OF SCIENCE, EMBASE, COCHRANE and PROQUEST databases looking for studies that reported a cut point for classification of Eosinophilic Chronic Rhinosinusitis (eCRS), and data concerning methodology of classification was extracted. Results: We identified 142 studies that reported 29 different cut-off values for classification of eCRS, and different methods of histologic analysis. Out of these studies 13 reported their own methodology to establish the cut-off point, and used different reference standards as polyp recurrence, asthma and allergy, immunocytochemistry, quality of life index, standard deviation of the control population and cluster analysis. Conclusions: Further studies are needed to determine a precise cut-off point, especially international multicentered cluster analysis. Moreover, methodologic standardization of biopsy and analysis is needed to certify comparable results. Multiple biopsy sites, densest cellular infiltration area examination and oral steroids restriction at least four weeks before sampling are advisable.

The aim of the study was to investigate the clinical significance of various histomorphologic findings related to mucosal inflammation in negative appendectomy. We reviewed histopathologic findings of 118 negative appendectomies and correlated them with the appendicitis inflammatory response (AIR) score and appendiceal diameter. Among 118 patients with negative appendectomy, 94 (80%), 73 (78%) and 89 (75%) patients displayed mucosal inflammation, high neutrophil score (neutrophil count ≥10/5 high power field and surface epithelial flattening, respectively. Out of 118 patients with negative appendectomy, mucosal inflammation, high neutrophil score and surface epithelial flattening were associated with higher risk group according to the appendicitis inflammatory response (AIR) score (p &lt, 0.05, respectively). In addition, mucosal inflammation, high neutrophil score and surface epithelial flattening were frequently detected in 118 negative appendectomies, compared with 24 incidental appendectomies (p &lt, 0.05, respectively). In an analysis of 77 negative appendectomy patients with appendiceal diameter data available, increased appendiceal diameter was positively correlated with luminal inflammation, high neutrophil score and surface epithelial flattening (p &lt, 0.05, respectively). In conclusion, mucosal inflammation, high neutrophil score and surface epithelial flattening in negative appendectomy may be relevant to patients’ signs and symptoms, especially in cases with no other cause of the abdominal pain.

Background: The current guidelines for the diagnosis of acute pyelonephritis (APN) recommend that APN be diagnosed based on the clinical features and the presence of pyuria. However, we observed that some of the patients who are diagnosed with APN do not have characteristic clinical features or pyuria at the initial examination. We performed this study to investigate the characteristics of APN without pyuria.Methods: A retrospective, cross-sectional study was conducted on 391 patients diagnosed with APN based on clinical and radiologic findings, between 2015 and 2019. The clinical features, laboratory results, and computed tomography (CT) findings were compared between patients with normal white blood cell (WBC) counts and those with abnormal WBC counts (WBC of 0–5/high power field [HPF] vs. >5/HPF) in urine. Results: More than 50% of patients with APN had no typical urinary tract symptoms and one-third of them had no costovertebral angle (CVA) tenderness. Eighty-eight patients (22.5%) had normal WBC counts (0–5/HPF) on urine microscopy. There was a negative correlation between pyuria (WBC of >5/HPF) and previous antibiotic use (odds ratio, 0.249; 95% confidence interval, 0.140–0.441; p

Background: Urethral stricture is a relatively frequent problem often requiring multiple surgical interventions. The objective of this study was to compare the clinicopathologic features of urethral resections from patients who underwent open end-to-end anastomotic urethroplasty and later recurred compared to those who did not.Methods: A retrospective review of the pathology files identified 36 consecutive patients who underwent urethroplasty. The histopathological analysis included evaluation of the inflammatory infiltrate based on the predominant (>50%) cell type: lymphocyte-rich, neutrophil-rich, plasma cell-rich, and mixed; length and thickness of the fibrous plaque; and the cellularity of the fibrous plaque: cellular (>40 stroma nuclei/HPF) or paucicellular (

BACKGROUND Aim of the study was to evaluate the association between celiac disease and eosinophilic oesophagitis/oesophageal eosinophilia in children. METHODS A total of 278 patients with celiac disease (mean age: 7.12 ± 4.64 years, M/F: 0.77) were involved in the study. The patients were evaluated retrospectively in terms of clinical, endoscopic and histopathological findings. The association between celiac disease and eosinophilic oesophagitis/oesophageal eosinophilia was determined. RESULTS According to Marsh classification system 6 (2.1%) of the patients were graded type 3A, 10 (3.5%) were type 3B, 262 (94.4%) were type 3C. The histopathological examination of oesophageal biopsy specimens of the patients revealed

Fascin-1, an actin-bundling protein, is associated with poor prognosis in patients with various types of human carcinoma. However, research is limited on the role of fascin-1 in sarcoma. Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare sarcomas derived from the mesenchyme. Although the prognosis of SFT/HPC is generally favorable, fatalities are possible with repeated recurrence and distant metastasis. The current study included a total of 20 Japanese patients, who were diagnosed with SFT/HPC and underwent surgery at Kochi University Hospital from January 2000 to December 2019. The statistical relationship between recurrence and the following variables were examined: Sex, age of onset, tumor origin, tumor size, necrosis, mitosis ≥1/10 high power field (HPF; magnification, x400), Ki-67 >5% and Fascin-1. A significant association was determined between recurrence and necrosis, mitosis ≥1/10 HPF (magnification, x400), Ki-67 >5%, and Fascin-1 ≥'strongly positive' (P

Aims Eosinophilic esophagitis (EoE) is easily missed during endoscopy, either because physicians are not familiar with its endoscopic features or the morphologic changes are too subtle. In this preliminary paper, we present the first attempt to detect EoE in endoscopic white light (WL) images using a deep learning network (EoE-AI). Methods 401 WL images of eosinophilic esophagitis and 871 WL images of normal esophageal mucosa were evaluated. All images were assessed for the Endoscopic Reference score (EREFS) (edema, rings, exudates, furrows, strictures). Images with strictures were excluded. EoE was defined as the presence of at least 15 eosinophils per high power field on biopsy. A convolutional neural network based on the ResNet architecture with several five-fold cross-validation runs was used. Adding auxiliary EREFS-classification branches to the neural network allowed the inclusion of the scores as optimization criteria during training. EoE-AI was evaluated for sensitivity, specificity, and F1-score. In addition, two human endoscopists evaluated the images. Results EoE-AI showed a mean sensitivity, specificity, and F1 of 0.759, 0.976, and 0.834 respectively, averaged over the five distinct cross-validation runs. With the EREFS-augmented architecture, a mean sensitivity, specificity, and F1-score of 0.848, 0.945, and 0.861 could be demonstrated respectively. In comparison, the two human endoscopists had an average sensitivity, specificity, and F1-score of 0.718, 0.958, and 0.793. Conclusions To the best of our knowledge, this is the first application of deep learning to endoscopic images of EoE which were also assessed after augmentation with the EREFS-score. The next step is the evaluation of EoE-AI using an external dataset. We then plan to assess the EoE-AI tool on endoscopic videos, and also in real-time. This preliminary work is encouraging regarding the ability for AI to enhance physician detection of EoE, and potentially to do a true “optical biopsy” but more work is needed.

Eosinophilic esophagitis has a strong male predominance that appears at least partially due to genetic susceptibility. However, data regarding sex-related differences in patients with EoE are scarce.We analyzed prospectively collected data from adults enrolled into the Swiss Eosinophilic Esophagitis Cohort Study. Patients with and without dilation in the past 12 months completed patient-reported Eosinophilic Esophagitis Activity Index (EEsAI) and EoE-specific quality of life in adults (EoE-QoL-A) and underwent endoscopy with biopsies. We used linear regression with EEsAI or EoE-QoL-A as the outcome, eosinophils per high power field, rings and strictures, current therapy use, and disease duration as predictors.A total of 266 patients (77% male, median age at diagnosis 35.8 years, median disease duration 10.4 years) were seen during 408 visits. Men had a longer diagnostic delay (62 months vs 36 months; P = .022), higher endoscopic disease activity (median endoscopic reference score 3.0 [interquartile range, 1.0-6.0] vs 2.0 [interquartile range, 0.0-4.0]; P = .010), more microabscesses (25% vs 13%; P = .025), and more often fibrosis of the lamina propria (mild/moderate 74.7% vs 61.5%, severe 9.1% vs 5.8%; P = .047) than women. When adjusting for objective measures of disease activity, disease duration, and current therapy use, we did not observe differences in EEsAI or EoE-QoL-A between women and men.Male EoE patients had higher endoscopic and histologic disease activity than female patients. When adjusting for biologic activity and therapy use, we did not identify differences in symptom severity or EoE-QoL between male and female eosinophilic esophagitis patients.

The malignant counterpart of cutaneous clear cell hidradenoma (CCH), hidradenocarcinoma, is an aggressive neoplasm that may have a fatal outcome. However, some cases of benign looking CCH with isolated lymph node involvement and excellent prognosis have been described. "CCH-like neoplasm of uncertain malignant potential" or "atypical hidradenoma" have been proposed as designations for these lesions. We report 3 cases of CCH with lymph node involvement. Ages ranged from 29 to 51 years old. All cases involved the inguinal lymph nodes: 2 of them presented with an isolated lymph node lesion, and the third case had lymph node and cutaneous involvement following the resection of a previous cutaneous lesion. Imaging studies showed no systemic involvement. None of the lesions exhibited histopathologic features of malignancy. All neoplasms were well circumscribed, had cystic spaces, did not display atypia or necrosis, and had less than 4 mitoses per high power field. No recurrence has been observed at follow-up after resection in all cases. All published cases of CCH with lymph node involvement so far affected a single lymph node in the axillary or inguinal regions, lacked features of malignancy, and had excellent long-term prognosis. Some cases previously reported as hidradenocarcinoma probably fit into this category. Our series adds more evidence to this rare phenomenon of "benign metastasis." Aggressive treatment should be avoided in these cases, and a long-term follow-up is warranted.

Background Each subgroup of immune cells has a different prognostic role in breast cancer; however, the prognostic impact of tumor-infiltrating natural killer cells (TINKs) is still not well established. Our aim was to assess the prognostic impact of natural killer (NK) cells in breast carcinomas. Materials and Methods NK cells infiltration were assessed by immunohistochemistry (IHC). Statistical analyses were performed to evaluate the correlation of NK cells with clinical-pathological features and outcome. Results CD56 IHC was realized in 126 patients. NK cells infiltration showed significant and positive association with tumor high Scarff-Bloom-Richardson (SBR) grade. NK cells were significantly associated with HER2-positive breast cancer and triple-negative breast cancer subtypes. Analyses showed significant and inverse correlation with progesterone and estrogen receptors expression status. High NK cells were significantly related to high Ki-67 labeling index. Our data showed that high NK cells infiltrate was significantly associated with tumor-infiltrating lymphocytes in breast cancer tissues. At a median follow-up of 5.5 years, high CD56 expression (≥ 5 cells/10 high power field) was associated significantly with a good overall survival and with good disease-free survival. Conclusion In this study, we assessed the important prognostic role of TINKs in breast carcinomas, which seems to be evident despite its association with aggressive pathological features. Thus evaluation of NK cells can be standardized and integrated in daily routine.

Cellular senescence is a molecular hallmark of ageing that is associated with multiple pathologies, and DNA damage marker γH2AX, together with cell cycle inhibitor p21, have been used as senescence markers in multiple species including dogs. Idiopathic canine chronic hepatitis has recognised breed-related differences in predisposition and prognosis, but reasons behind this are poorly understood. This retrospective study using archived post mortem tissue aimed to provide insight into liver ageing in 51 microscopically normal canine livers across seven breed categories, including those with and without increased risk of chronic hepatitis. Immunohistochemistry was conducted for γH2AX, p21, and cell proliferation marker Ki67, and the mean number of positive hepatocytes per high power field was determined. All three markers were strongly correlated to each other, but no age-dependent expression was seen in the combined study population. Overall expression levels were low in most dogs, with median values representing less than 1.5% of hepatocytes, but this increased to 20–30% in individual dogs at the upper end of the range. Individual breed differences were noted in two breeds that have increased risk of chronic hepatitis, with English Springer Spaniels having lower expression of Ki67 than other dogs, and Labradors having higher expression of Ki67 and γH2AX than other dogs. These results warrant further investigation in these breeds and highlight a need to validate reliable markers of cellular senescence in dogs. Supplementary Information The online version contains supplementary material available at 10.1007/s11259-020-09784-x.

Endoscopy plays an important role in the management of eosinophilic esophagitis (EoE), since it is involved in the diagnosis, follow up and treatment of this condition. In patients presenting with food impaction, dysphagia and other symptoms of suspected EoE, esophago-gastric-duodenoscopy (EGD) with multiple esophageal biopsies should be performed to confirm or rule out the diagnosis of EoE. The EREFS system, a validated instrument for assessment of the endoscopically-identified esophageal features in EoE (edema, rings, exudates, longitudinal furrows and strictures), is currently used in the clinical practice for the evaluation of the macroscopic aspects of esophageal mucosa during EGD. Multiple esophageal biopsies are mandatory to further confirm EoE diagnosis and subsequent response to treatement, since symptoms reported by patients do not always correlate with histological activity, and considering the low sensitivity of endoscopic assessment; a cut-off of ≥ 15 eosinophils in at least one high power field is the density threshold considered the standard for diagnosis (sensitivity 100%, specificity 96%). Other histological features, included in the EoE histologic scoring system (EoEHSS), are supportive for the diagnosis and for the assessment of inflammatory activity during follow-up. Esophageal dilation, performed either with Savary dilators/bougie or hydrostatic baloon, is an effective and safe treatment in both adult and pediatric EoE patients with fibrostenotic features, mainly in association with other therapeutic strategies which can control eosinophilic inflammation.

Introduction Preoperative identification of high-grade bladder cancer presence can optimize patient management. The aim of this study was to assess the association between preoperative pyuria and the pathological features of bladder cancer. Material and methods This retrospective analysis enrolled 943 patients undergoing transurethral resection of a bladder tumor. Patients were divided into two study groups based on the presence of pyuria in preoperative urine analysis, defined as the presence of >5 leukocytes in the high power field. Pyuria status as a potential predictive factor was then confronted with pathological features based on standard microscopic examination of the surgical specimen. Results Among 943 recruited patients, 294 (31.2%) presented with pyuria. Patients with pyuria were older (71 vs. 68 years, p

OBJECTIVE: Phyllodes tumor (PT) is a rare entity accounting for 1% of breast neoplasms with a high propensity of recurrence. This study aimed to identify factors that are predictive of early recurrence in patients with PT. MATERIALS AND METHODS: This study reviewed clinical data of patients with PT (n=57) treated at our tertiary care referral center in South India between February 2010 and December 2019. The Pearson χ(2) test was used to investigate the relationship between patient’s clinical features and tumor histotypes. Survival curves were obtained using the Kaplan-Meier method based on the log-rank test. Multivariate Cox regression analyses were performed to identify predictors of early recurrence or local recurrence-free-interval (LRFI). RESULTS: The mean age was 38.3 [standard deviation (SD)=13.6] years, and the mean follow-up was 18 (SD=13.5) months. The median tumor size was 5 cm (interquartile range 3 and range: 3–22 cm). Moreover, 64.9% (n=37) of the tumors were benign, 21.1% (n=12) were borderline, and 14% (n=8) were malignant. Of the 57 patients, 17 (29.8%) developed local recurrence and one developed distant metastasis. Of the 17 patients, three were unwilling to undergo completion surgery. The median LRFI was 20 (range: 7–60) months. Multivariate cox regression analyses showed that mitotic rate >10/high power field [hazard ratio (HR) 0.147; p=0.04], stromal overgrowth (HR: 4.904; p=0.05), margin status (HR: 0.037; p3.5 were associated with early recurrence. These attributes mandate stringent follow-up, especially in a resource-limited setting.

AimsSo far, little has been known on whether myocardial inflammatory infiltration influences heart failure (HF) progression. Thus, the aim of this study was to test the impact of intramyocardial infiltration on clinical outcomes.MethodsBiopsy samples from 358 patients with stable HF secondary to dilated cardiomyopathy were studied. Immunohistochemistry for lymphocyte (CD3) and macrophage (CD68) markers was performed and counted. After a 1-year follow-up, patients were classified as improved based on the predefined definition of improvement. The clinical data were collected from 324 patients (90.5%).ResultsAccording to the predefined definition of improvement, 133 patients improved (41.0%) but 191 remained unchanged or deteriorated (58.9%). After a 12-month follow-up, the OR with 95% CI of counts of myocardial inflammatory CD68-positive ≥4 cell/high power field (HPF) compared with CD68-positive ConclusionsThe current results provide evidence that high macrophage counts may be a predisposing factor for HF progression.

Immunoglobulin G subclass 4 (IgG4)-related disease is a recently described fibroinflammatory condition. Reports of appendix involvement are extremely limited. A young man with abdominal pain and symptoms of acute appendicitis accompanied by the finding of an appendix-dependent tumor during surgery is presented. Histopathological study revealed lymphoplasmocytic infiltrate, storiform fibrosis and obliterative phlebitis. The number of IgG4-positive plasma cells was greater than 50 per high power field. Postsurgical steroid treatment and radiological findings are also described.

Background & Aims Rates of postoperative Crohn’s disease recurrence remain high, although the ability to predict this risk of recurrence remains limited. As such, we aimed to determine the association of histologic features at the time of resection with postoperative recurrence. Methods Electronic databases were searched through February 2020 for studies that reported risk of clinical, endoscopic, or surgical postoperative recurrence in patients with positive resection margins, plexitis, or granulomas in the index specimen. Pooled risk ratios (RRs) with 95% CIs were calculated for this risk in patients with and without these histologic features. Results Twenty-one studies (2481 patients) assessed positive resection margins, 10 studies (808 patients) assessed plexitis, and 19 studies (1777 patients) assessed granulomas. Positive resection margins increased the risk of clinical (RR, 1.26; 95% CI, 1.06–1.49; I2 = 41%) and surgical (RR, 1.87; 95% CI, 1.14–3.08; I2 = 71%) recurrence, with a trend toward endoscopic recurrence (RR, 1.56; 95% CI, 0.79–3.05; I2 = 85%). Granulomas increased the risk of clinical (RR, 1.31; 95% CI, 1.05–1.64; I2 = 36%) and endoscopic (RR, 1.37; 95% CI, 1.00–1.87; I2 = 49%) recurrence, with a trend toward surgical recurrence (RR, 1.58; 95% CI, 0.89–2.80; I2 = 75%). Plexitis increased the risk of endoscopic recurrence (RR, 1.31; 95% CI, 1.00–1.72; I2 = 20%), with a trend toward clinical recurrence (RR, 1.34; 95% CI, 0.95–1.91; I2 = 46%). Conclusions Positive resection margins, granulomas, and plexitis are predictive of postoperative Crohn’s disease recurrence and should be recorded at the time of index resection.

Background Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose-effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity. Purpose The aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy-induced cardiotoxicity. Methods A cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post-treatment on a 7T MRI system. The protocol included short-axis cine MRI covering the left ventricle (LV) and mid-ventricular short-axis tissue phase mapping (TPM), pre- and post-contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks. Results Global peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1-2 apoptotic cell/high power field), suggesting early-stage cardiotoxicity. Conclusions In a mouse model of chemotherapy-induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment-related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.

A 27-year-old Caucasian female was hospitalized three times over a four-month period for recurrent, intermittent abdominal pain associated with nausea and diarrhea. No signs or symptoms of gastrointestinal (GI) bleeding were present. A stool occult blood test and stool enteric pathogen tests were negative. A complete blood count (CBC) revealed a peripheral blood eosinophil count of 1080 cells /µL without any inflammatory reaction. An upper endoscopy showed grossly normal-appearing esophageal and duodenal mucosa; however, a gastric mucosal biopsy showed an eosinophil infiltration of ≥20 eosinophils/high power field (HPF). Based on these findings, she was diagnosed with eosinophilic gastroenteritis (EGE). A definitive diagnosis of EGE should be confirmed with both an analysis of gastrointestinal mucosal biopsy and an elevated peripheral blood eosinophil count. Specifically, histological evaluation of the mucosal tissue must show an eosinophilic infiltration rate of 20 eosinophils/HPF. The diagnosis should be followed by an extensive review of the patient’s allergic disease history.

Background: Enteroendocrine cells (EEC) have been suggested to have a role in the pathogenesis of irritable bowel syndrome (IBS). Although many studies have analysed possible numeric changes of EEC in IBS, the results differ between different studies. One reason might be due to difficulties in standardising the morphometric method.Aim: The aim of this study was to compare two different methods for counting EEC in jejunum biopsies from patients with IBS and healthy controls.Method: Fifty-one patients with IBS and 35 healthy controls were included in the study. Jejunum mucosa was procured using a Watson capsule. Slides were immunostained for serotonin and chromogranin A and then scanned digitally. The morphometry was done by counting cells per high power field (hpf) and per mm2 after defining area of the mucosa. The two methods were compared using Bland Altman analysis.Results: There was no difference in the number of EEC in patients with IBS compared to healthy controls. The number of cells detected by per mm2 area of mucosa were higher than number of cells per hpf. Counting EEC per high power field systematically underestimated the number of cells in the mucosal area.Conclusions: Counting cells per mm2 mucosal area gives a better representation of the number of EEC in small bowel mucosa. The finding of no difference in EEC numbers does not imply an equal function and further studies are needed to evaluate the role, if any of EEC, in IBS.

Background The positive predictive value (PPV) of urinary decoy cells for diagnosing BK polyomavirus associated-nephropathy (BKPyVAN) is low. This study was designed to increase the PPV of urinary decoy cells for diagnosing BKPyVAN in kidney transplant recipients. Methods A total of 105 urine sediment samples from 105 patients with positive BK viruria and decoy cells were evaluated by automatic double-immunostaining with anti-HGD (a renal tubular marker) antibody + anti-SV40-T antibody or anti-S100P (an urothelial marker) antibody + anti-SV40-T antibody. Results Of the 105 patients, 76 (72.4%) had both HGD(+)/SV40-T(+) cells and S100P(+)/SV40-T(+) cells (group A), 24 (22.9%) had only S100P(+)/SV40-T(+) cells (group B), and 5 (4.6%) had only S100P(-)/HGD(-)/SV40-T(+) cells (group C). Seventy patients in group A (92.1%), 3 patients in group B (12.5%), and no patients in group C were diagnosed with BKPyVAN. The area under the ROC curve of predicting BKPyVAN by decoy cells was 0.531 (0.431-0.630), with an optimal cut-off value of 29 (per 10 high power field), a sensitivity of 45.8% (95% CI: 34.0-58.0%), and a specificity of 68.8% (95% CI: 50.0-83.9%). Besides, the area under the ROC curve of predicting BKPyVAN by plasma BKPyV load was 0.735 (95% CI: 0.632-0.822), with an optimal cut-off value of 1,000 copies/mL, a sensitivity of 61.1% (95% CI: 48.9-72.4%) and a specificity of 84.2% (95% CI: 60.4-96.6%). In contrast, the PPV, negative predictive value, sensitivity, and specificity of HGD(+)/SV40-T(+) cells for diagnosing BKPyVAN were 92.1% [95% confidence interval (CI): 83.0-96.7%], 89.7% (95% CI: 71.5-97.3%), 95.9% (95% CI: 87.7-98.9%), and 81.3% (95% CI: 63.0-92.1%) respectively. Conclusions Double-immunostaining with anti-HGD or anti-S100P and anti-SV40-T antibodies helps to identify the origin of decoy cells and diagnose BKPyVAN.

Background Wide-spectrum antibiotics have been favored to treat acute uncomplicated cystitis (AUC) for a long time, leading to the emergence of multi-drug resistant bacteria. We hypothesize that narrow-spectrum antibiotics might mitigate the issue and aim to investigate the clinical efficacy of cefaclor in patients with AUC. Methods We retrospectively reviewed the clinical data of female outpatients with AUC treated with cefaclor and evaluated the safety and clinical efficacy. Clinical cure was defined as the elimination of clinical symptom under 4 white blood cells (WBCs) per high power field on microscopy. Results Overall, 223 women with AUC were enrolled. Escherichia coli was the dominant pathogen (n = 160; 68.6%), followed by Klebsiella species and E. coli-extended spectrum β-lactamase (ESBL) (n = 19; 8.1% and n = 18; 7.7%). Overall success rate was 94.0% (n = 219) and susceptibility rate of cefazolin was 84.1%, which was close to that of levofloxacin (82.9%). Ampicillin showed the lowest rate of 63.7% with a significantly greater resistance rate of 35.3% among all antibiotics (P n = 24) or 93.3% (n = 14). The rate in patients with resistance to both antibiotics was 60.0% (n = 9), and the pathogens in the other 40.0% (n = 6) of patients with treatment failure were E. coli-ESBL. Conclusion Cefaclor showed excellent efficacy in AUC patients, even in those with in vitro resistance to cefazolin or levofloxacin. Cefaclor may be considered as a first-line option in patients with AUC and a second-line option for those with levofloxacin treatment failure.

Background & Aims Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD. Methods Subjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings. Results Of 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis—an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts. Conclusions In an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. ( ClinicalTrials.gov , Number: NCT03496571)

Background: CD 117 (Cluster Differentiation 117), encoded by the proto-oncogene C-Kit is a transmembrane tyrosine kinase growth factor receptor which inhibits apoptosis and potentiates cell proliferation. In normal breast epithelium, c-kit is highly expressed; however, its expression is low or completely lost in primary invasive breast carcinoma, suggesting its role in breast carcinogenesis. Objective: To evaluate the expression of CD 117 in invasive breast carcinoma and to study its association with various prognostic factors. Materials and Methods: Fifty cases of invasive breast carcinoma of different histological types and grades were evaluated for CD117 immunoexpression and the association of the same was studied with respect to various prognostic factors, ER/PR receptor status and Her2/neu status. Results: A statistically significant association was seen between negative expression of CD 117 with increased age (p=0.04), higher tumor grade (p=0.02), positive hormone receptor status (ER; p=0.001, PR; 0.005), negative Her2/neu (p=0.006) and tumors having a microvascular density of more than 19 per high power field (p-0.01). Conclusion: CD 117 immunoexpression, either negative or positive in invasive breast carcinoma has to be reported on a routine basis as a negative expression projects the prognosis of breast carcinoma patients and a positive expression will identify patients for a potential therapeutic intervention.

Background We observed that patients with hypogonadism are at higher risk to experience artificial urinary sphincter cuff erosion. Sphincter erosions have been found to be associated with urethral atrophy or compromised urethras subsequent to events limiting its blood supply. We therefore analyzed possible mechanisms how a decrease in testosterone serum levels can result decreased urethral blood flow. Methods In a cohort of >1,200 urethroplasties, tissue specimens obtained during surgeries were analyzed for expression of androgen receptor (AR), AR-responsive TIE-2 associated with angiogenesis, and the endothelial cell marker CD31 for determination of vessel counts were analyzed immunohistochemically. A total of 11 patients were included in whom both tissue and serum testosterone levels within 2 years of the urethroplasty was available. Low serum testosterone level defined as

Background and Aims The management of subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors can be challenging and traditionally requires a surgical resection that is not only invasive but may carry a significant risk of morbidity and mortality. We aimed to assess the feasibility, safety, and efficacy of a novel endoscopic technique termed submucosal tunnel endoscopic resection for extraluminal tumors (STER-ET). Methods We prospectively enrolled patients who underwent STER-ET for GI subepithelial tumors with a predominant extraluminal growth pattern or extra-GI tumors located at the level of cardia or the proximal part of the lesser curvature of the stomach seen on cross-sectional imaging between January 2016 and March 2017. Results Eight patients underwent STER-ET. The mean (± standard deviation) tumor size was 2.8 ± 0.6 cm and 2.3 ± 0.8 cm in longest and shortest dimension, respectively. The average procedure time was 67 ± 4.4 minutes. The rates of curative en bloc resection and en bloc retrieval was 100% and 87.5%, respectively. On final histology, 6 tumors were GI stromal tumors, 1 was a schwannoma, and 1 was a foregut cyst. Five patients had capnoperitoneum during the procedure and required abdominal decompression. One patient had a small mucosotomy successfully treated with a hemostatic clip. There were no major adverse events or deaths. The median length of hospital stay was 3 days. There was no residual tumor on surveillance imaging after a mean follow-up period of 10.0 ± 2.1 months. Conclusions STER-ET is a novel technique that appears to be safe and effective in achieving a curative resection for GI subepithelial tumors with a predominantly extraluminal growth pattern or extraluminal tumors in a selected group of patients. However, larger studies are required to validate our finding.

Background: It has been shown that cigarette smoking is associated with decreased number of eosinophil cells in blood and lung. Cigarette smoking is one of the major causes of gingival problems and periodontitis. The effect of cigarette smoking on eosinophils in gingiva has not been elucidated. The aim of this study was to determine the effect of cigarette smoking on eosinophil count in periodontal inflammation. Methods: The study was a case-control study. Forty paraffin embedded block of periodontitis obtained from 20 cigarette smokers and 20 nonsmokers were evaluated histochemically for eosinophil count. Using hematoxylin-eosin stained sections, the number of eosinophils was determined per high power field at ×400 magnification. One-way analysis of variance (ANOVA), t test, Duncan and Pearson correlation coefficient tests were employed for data analyses at the level of P≤0.01. Results: The mean number of eosinophils in nonsmokers was significantly higher than that in smokers (P

Progressive transformation of germinal centers (PTGC) is a form of follicular hyperplasia recently associated with immunoglobulin G4-related disease (IgG4-RD), but the ophthalmic manifestations of this combination are poorly described. In this retrospective case series, we present three cases of IgG4-related orbital disease (IgG4-ROD) showing varying degrees of PTGC involving the orbit and lacrimal gland. Three adult women presented with ill-defined lacrimal gland enlargement. Histologic sections showed variable fibrosis and large, irregular lymphoid follicles with prominent mantle zones penetrating the germinal centers, highlighted by Bcl-2 and/or IgD immunostains. The interfollicular areas contained a mixture of plasma cells, scattered histiocytes and eosinophils. Mixed T and B-cells were present, and no signs of monoclonality were identified. All cases showed more than 100 IgG4 positive cells per high power field. Epstein-Barr virus in situ hybridization performed in one case was negative. The serum IgG4 level was tested in one case and showed elevation above the normal range. After 2–10 months of follow-up, the patients showed either near-complete resolution or no remaining signs of ophthalmic disease. Increasing awareness of these PTGC in extra-nodal locations, including the orbit, may provide a better understanding of the histologic spectrum of this disease. Keywords: IgG4-related disease, Orbit, Lacrimal gland, Progressive transformation of germinal centers, Follicular hyperplasia