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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

Hematuria, either glomerular or extraglomerular, is defined as 3 or more red blood cells (RBCs)/high power field. Currently, urinalyses are commonly performed using automated urine sediment analyzers. To assess whether RBC counting by automated urine sediment analyzers is reliable for defining hematuria in glomerular disease, random specimen urinalyses of men with nephritic glomerular disease (7674 urinalyses) and bladder cancer (12,510 urinalyses) were retrospectively reviewed. Urine RBCs were counted by an automated urine sediment analyzer based on flow cytometry (UF-1000i, Sysmex Corporation) or digital image analysis (Cobas 6500, Roche Diagnostics GmbH). In about 20% of urine specimens, the specific gravity was less than 1.010, making the RBC counts unreliable. In the urine specimens with specific gravity ≥ 1.010, RBC counts measured using either UF-1000i or Cobas 6500 were well correlated with the positive grades in the dipstick blood test. However, at a trace, 1+, or higher positive dipstick tests for blood, RBC counts were graded significantly lower in glomerular disease than in bladder cancer. The findings suggest that RBC counting by UF-1000i or Cobas 6500 underestimates the severity of hematuria in glomerular disease, possibly because dysmorphic RBCs in glomerular disease are susceptible to hemolysis and/or fail to be properly recognized.

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.

Background Immunoglobulin G4 (IgG4)-related disease is a chronic inflammatory disease that was recognized in 2011. Pleuritis associated with IgG4-related disease is rare and can be difficult to diagnose. Although there have been previous reports on pleuritis associated with IgG4-related disease by thoracoscopic findings, this is the first to observe pleuritis with IgG4-related disease from normal pleural thoracoscopic findings. Case presentation A 70-year-old Japanese female treated for breast cancer 33 years ago was referred to our hospital complaining of dyspnea on exertion. Chest computed tomography (CT) revealed left pleural effusion that was exudative and predominant with lymphocytes, elevated adenosine deaminase (ADA) and Class III cytology (malignancy suspected). Subsequently, thoracoscopic pleural biopsy was performed for definitive diagnosis. Although pleural macroscopic findings appeared normal, we performed pleural biopsy at random sites. This patient was negative for mycobacterium tuberculosis, and neither granulomas nor malignant cells were found in the collected specimens. An infiltration of inflammatory cells, mainly plasma cells and lymphocytes, was observed. Immunostaining revealed the number of IgG4-positive plasma cells was 102/high power field (HPF), and the percentage of IgG4 positive/immunoglobulin G (IgG)-positive cells was 41.4%. Since IgG4 serum levels were high and IgG4-related submandibular sialadenitis was also observed, a definitive diagnose of pleuritis associated with IgG4-related disease was confirmed. Conclusions We diagnosed pleuritis associated with IgG4-related disease by thoracoscopic pleural biopsy samples taken from a visually normal pleura. Although exudative pleural effusion with high ADA and lymphocyte predominance is a characteristic of tuberculous pleuritis, other diseases might be present. Since thoracoscopy can increase the diagnostic yield, pleural biopsy should be considered even if thoracoscopic pleural findings are deemed normal.

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.

Neurofibromatosis type 1 (NF-1) is strongly associated with neurofibromas and malignancies. Solid pancreatic neuroendocrine tumors (PanNETs) have been recently reported in patients with NF-1. PanNETs are always solid and rarely present with a cystic appearance due to central necrosis and hemorrhage caused by rapid growth. A 33-year-old female diagnosed with NF-1 at age 16 was referred for evaluation of a pelvic mass found on abdominal ultrasound. Magnetic resonance imaging showed a 6 cm solid pelvic mass adjacent to the left external iliac artery, and contrast-enhanced computed tomography scan showed a 3-cm solid para-aortic mass and a 3-cm cystic mass in the pancreatic tail. Endoscopic ultrasonography showed a cystic tumor with necrotic tissue and septa. Preoperative diagnosis was pancreatic cystic malignancy with para-aortic lymph node metastasis accompanied with a pelvic neurofibroma. These lesions were resected simultaneously. The specimen resected from the pancreas showed a necrotizing cystic tumor invading abutting lymph nodes. Immunohistochemical analysis showed positive chromogranin A and synaptophysin. The Ki-67 index was

Introduction: IgA nephropathy (IgAN) is the most common form of glomerulonephritis across the world. Oxford classification defines criteria and effects of endocapillary hypercellularity on E score but the reproducibility of the same is debatable. Hence, there is a need for an objective marker that could establish a gold standard in assessing endocapillary hypercellularity. Methods: Forty biopsies of proven IgAN were taken and grouped into two groups based on the presence or absence of endocapillary hypercellularity (n = 20 each). These biopsies were then stained by CD68 immune stain and the glomerular macrophages were quantified. Mean serum creatinine, presence of hypertension, degree of proteinuria and haematuria at the time of biopsy were also recorded and the correlation between these parameters and endocapillary hypercellularity was also studied. Results: Mean glomerular CD 68+ cell count was significantly higher in glomeruli showing endocapillary hypercellularity. Utilising the objective cutoff values of 0.6 CD68+ per glomerulus, more than 8 glomerular CD68+ cells in the entire biopsy and/or around 4 CD68+ cells in the most inflamed glomerulus, endocapillary hypercellularity can be predicted with a sensitivity of 70–80% and specificity of 70%. After regrouping the biopsies based on the cutoff values obtained from the receiver operating curve analysis the mean urine RBC count per high power field showed a significant correlation with endocapillary hypercellularity. Conclusion: Glomerular CD68+ macrophage count seems to be a promising approach in assessing endocapillary hypercellularity. Further studies with emphasis on correlation with the clinical outcome are needed to validate its utility as an objective tool.

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.

Background The importance of this paper is to help to emphasize the importance of chemotherapy for children with pure intratesticular rhabdomyosarcoma after radical inguinal orchiectomy is done as first treatment of rhabdomyosarcoma. The information provided in this paper about the follow-up outcomes of the patient described in this paper, it highlights that, recurrence and even metastasis of intratesticular rhabdomyosarcoma in children are more likely to occur if surgery it not combined with chemotherapy. Case presentation Herein, we present a 6-year old African male child with a 3 months history of a painless right intratesticular tumour. The tumour was poorly vascularized and was in continuity with the spermatic cord. Pelvic computer tomography (CT) scan showed a heterogeneous mass with well-defined margins without microcalcification and multiple bilateral inguinal enlarged lymph nodes were noticed without pelvic lymphadenopathy. The tumour measured 3.8 × 2.8 × 3.9 cm. The tumour marker panel showed: lactate dehydrogenase of (472 UI/l), alpha-fetoprotein (1.43 UI/ml) and human chorionic gonadotrophin beta (2.9 mUI/ml). Microscopically, the tumour was composed of small to medium size undifferentiated cells. These were oval to spindle, hyperchromatic cells to stromal myxoid degeneration were noted. Tunica albuginea and rete testis both were infiltrated by tumour. The tumour showed high mitotic count which measured 50 mitoses per 10 High Power Field (HPF). The diagnosis of rhabdomyosarcoma (RMS) was confirmed by immunohistochemistry (IHC) testing using myoD antibody which showed strong and diffuse intranuclear staining of the tumour cells. Currently, he is on cyclophosphamide and vincristine chemotherapy regime and his condition has improved much. Conclusions The experience obtained from the index case is crucial for the management of patients with intratesticular rhabdomyosarcoma which should always make sure that radical inguinal orchiectomy is covered by chemotherapy and/or radiotherapy. This will potentially lower the possibilities of recurrence and/or metastasis of the tumour, hence improving the prognosis of the patients. We report the clinical, radiological, and laboratory characteristics as well as the outcome of the patient.

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 and study aims Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) performs poorly in the histological diagnosis of type 1 autoimmune pancreatitis (AIP). The aim of this study was to assess the performance of fine-needle biopsy (FNB) comparing reverse bevel (RB) and fork-tip (FT) needles. Patients and methods A retrospective study of prospectively maintained databases was performed. Patients with a final diagnosis of type 1 AIP who underwent EUS-FNB during diagnostic workup were included. Pathology reports were reviewed and classified as per international consensus diagnostic criteria (ICDC). The Primary outcome was EUS-FNB sensitivity in diagnosing type 1 AIP. Results Between March 2011 and December 2018, 24 patients with a final diagnosis of type 1 AIP underwent FNB. Six patients underwent biopsy with the RB needle and 18 with the FT needle. Mean age (± SD) 62.2 (± 11.4), 17 (70.8 %) male. No RB samples were diagnostic compared to 14 (78 %) FT; P = 0.001; of which 13 (72 %) were level 1. In eight (44 %) of FT cases a diagnosis was not possible without histology. Initial biopsy was diagnostic in five (62.5 %) of these cases. Including repeat biopsy, seven (87 %) had a diagnosis made by FT needle. Obliterative phlebitis (44 %) was the least frequently identified pathological feature and immunoglobulin (IgG)4 + plasma cells > 10 per high power field (78 %) the most common. Conclusion The FT needle demonstrated good performance for diagnosing type 1 AIP. The results support the preferential use of this core biopsy needle for EUS pancreatic tissue sampling.

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.

Objective To assess intra- and interobserver agreement among non-expert pathologists in identifying features of the eosinophilic esophagitis histologic scoring system (EoEHSS) in pediatric patients. Patients and methods The authors used 50 slides from patients (aged 1-15 years; 72% male) with EoE. EoEHSS evaluates eosinophilic inflammation and other features including epithelial basal zone hyperplasia, eosinophilic abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Grade and stage of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change). Four pathologists determined EoEHSS findings on two occasions. Intra- and interobserver agreement was assessed using Kappa (κ) statistics and intra-class correlation coefficients. Results Intra- and interobserver agreement for the identification of eosinophil counts ≥ 15/high power field (HPF) was excellent, however varied when assessing additional features of the EoEHSS. For the more experienced pathologist, agreement for most EoEHSS items and the composite scores was substantial to excellent. For the less experienced pathologists, intraobserver agreement ranged from absent to substantial for individual features and ranged from moderate to substantial for the composite scores. Conclusion Most items of the EoEHSS had substantial to excellent reliability when assessed by a pathologist experienced in the diagnosis of EoE but presented lower repeatability among less experienced pathologists. These findings suggest that specific training of pathologists is required for the identification of EoEHSS characteristics beyond eosinophil count, as these features are considered useful in the evaluation of response to treatment and correlation with clinical manifestations and endoscopic findings.

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.

Keloids are fibroproliferative disorders characterized by high recurrence rates, with few factors known to influence the same. We conducted a study to determine whether keloid histology influences recurrence. This was a prospective longitudinal study to determine whether histopathological parameters of keloid influence recurrence. Patients with keloids managed by surgical excision were followed up at Kenyatta National Hospital between August 2018 and July 2020. The excised keloids were processed for histology using hematoxylin,/eosin, Masson, and trichrome stains. The slides were analyzed for inflammatory cells, fibroblasts, and capillary density using the hot spot technique and correlated to keloid recurrence. Postoperative follow-up was for a minimum of 1 year. A total of 90 patients with 104 keloids were recruited in the study. Overall keloid recurrence rate was 28.6%. There was a correlation between the absolute count of more than 50 per High power field of lymphocytes, fibroblasts, and macrophages with recurrence of the disease. The sensitivity and specificity for the above parameters were lymphocytes 48% and 81%, macrophages 57% and 83%, mast cells 32% and 33%, and fibroblasts 41% and 91%, respectively. There was no correlation between mast cells and vascularity status with recurrence. Routine histology should, therefore, be performed to determine these parameters. Close monitoring and second-line therapy should be considered for patients with elevated macrophages and/or lymphocytes so as to reduce the risk of recurrence.

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.

Background: Vitiligo is the most prevalent pigmentary disorder occurring worldwide. In most cases, the diagnosis is made by clinical examination alone. The disease status (active/stable) needs to be assessed to make appropriate therapeutic decisions. Objective: The aim of the present study was to evaluate the histopathological and immunohistochemical features in active and stable lesions. Materials and Methods: Biopsies from vitiliginous areas from 50 patients (25 each of clinically active and stable vitiligo); with hematoxylin and eosin, Masson Fontana (MF), S-100, and human melanoma black-45 (HMB-45) stained sections were studied. Results: Age of the patients ranged from 7 to 69 years (mean age: 33.6 ± 15.73 years). Of 50 patients, 27 (54%) were male and 23 (46%) were female. All the cases showed variable degree of basal hypopigmentation. Histopathological findings, epidermal spongiosis, basal vacuolar degeneration, dermal melanophages, and dermal lymphomononuclear cells were commonly observed in active lesions as compared to the stable ones. On MF staining, 23/25 cases (92%) of active vitiligo showed complete loss of basal melanin. Quantitative analysis of HMB-45 immunostaining in stable and active vitiligo revealed mean number of positive melanocytes as 2.52 ± 1.0/high power field (hpf) and 0.08 ± 0.28/hpf, respectively, while on S-100 immunostaining the mean values of positive Langerhans cells were 1.70 ± 0.38/hpf and 7.78 ± 4.11/hpf, respectively. Conclusion: The demonstration of overall reduction in the number of HMB-45-positive melanocytes and increase in S-100-positive Langerhans dendritic cells in the active vitiligo lesions is facilitated by immunohistochemistry. The technique is of immense help in differentiating active and stable stages of vitiligo, thus guiding therapy.

Objectives Structured histopathology reporting has been recently described for detailing immunopathological characteristics of chronic rhinosinusitis (CRS), and can be utilized for subtyping CRS and personalizing management. This study scrutinized elements of structured histopathology to identify characteristics that prognosticate outcomes following endoscopic sinus surgery (ESS) for CRS patients with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). Methods Outcomes following ESS were measured using the patient-reported 22-item sinonasal outcome test (SNOT-22). Changes in total SNOT-22 scores at 6 and 12 months postoperatively were analyzed. Thirteen parameters reported in structured histopathology of sinus surgical tissue were studied for association with outcomes postsurgery. The overall cohort of all CRS patients was studied, along with subgroup analyses of CRSwNP and CRSsNP patients. Results In the entire CRS cohort (n = 171), eosinophil count >10 per high power field (HPF) was associated with greater improvement in SNOT-22 scores at 6 months post-ESS (P = .039). At 12 months follow-up, no histopathological characteristic was associated with change in total SNOT-22 score. In the CRSwNP (n = 66) subgroup, the presence of fibrosis (P = .006) and eosinophil count ≤10 per HPF (P = .025) were associated with less favorable changes in SNOT-22 scores at 12 months follow-up. Fibrosis remained statistically significant in multivariable analysis (P = .007). Conclusions At 6 months post-ESS, tissue eosinophilia is associated with significantly higher improvement in SNOT-22 scores, but this difference is diluted by 12 months. Fibrosis was associated with less favorable outcomes in SNOT-22 scores for CRSwNP patients at 12 months and may be a prognosticator for poorer long-term outcomes. Level of evidence 4.

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.

Background Diagnosis of non-esophageal eosinophilic gastrointestinal disorders requires quantification of tissue eosinophils. Our objective was to evaluate eosinophil peroxidase (EPX) immunohistochemistry (IHC) as a method for histologic diagnosis of eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD). Methods We performed a retrospective analysis of biopsies from pediatric EG/EoD cases and controls. Subjects with EG or EoD had ≥30 eosinophils per high power field (eos/hpf) in ≥5 hpf in the stomach and/or ≥3 hpf in the duodenum, respectively. Controls had no histopathologic diagnosis recorded. Tissue eosinophil counts were assessed by hematoxylin & eosin stains. EPX stains were assessed using a unique histopathologic scoring system. Slides were digitized and EPX+ staining area/mm2 was quantified by image analysis. Results Twenty-six EG/EoD cases and 40 controls were analyzed. EPX scores and EPX/mm2 levels were markedly elevated in EG/EoD (p ≤ 0.0001). Eosinophil density (eos/mm2) correlated strongly with EPX scores and EPX/mm2 levels in the stomach (r ≥ 0.77) and moderately with EPX scores and EPX/mm2 levels in the duodenum (r ≥ 0.52); (p 2: AUC = 0.98 (95%CI 0.96-1) for EG, AUC = 0.91 (95%CI 0.81-1) for EoD). Conclusion EPX-based assessment of eosinophilic inflammation may facilitate automated histologic diagnosis.

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

Background & Aims IgG4-related disease (IgG4-RD) of the biliary tract and pancreas is often difficult to distinguish from pancreatobiliary cancer. The blood IgG4/IgG RNA ratio has been reported to discriminate IgG4-RD from primary sclerosing cholangitis/pancreatobiliary cancer with high accuracy. This study aimed to prospectively assess the diagnostic accuracy of the blood IgG4/IgG RNA ratio for distinguishing IgG4-RD from cancer in patients with a suspected pancreatobiliary malignancy. Methods In this prospective, single center, observational study, patients presenting at a specialized multidisciplinary, hepato-pancreato-biliary clinic with suspicion of pancreatobiliary malignancy were included. The IgG4/IgG RNA ratio (threshold 5.0%) was determined by quantitative PCR in addition to standard diagnostic procedures. Clinical, biochemical, radiological, and histo-/cytopathological findings were analyzed. For the diagnosis of IgG4-RD, the HISORt criteria were used as a reference standard. Malignancy was defined by the presence of neoplastic tissue at histo-/cytopathological examination. Results Overall, 213 consecutive patients (mean age 68 years) with a suspected pancreatobiliary malignancy were analyzed, of whom 3 patients were diagnosed with IgG4-RD and 178 patients were diagnosed with malignancy (165 patients with primary pancreatobiliary malignancy). The IgG4/IgG RNA ratio was true positive in 3 patients and false positive in 87 (40.8%) patients. In 123 (57.7%) patients the test was true negative. The sensitivity of blood IgG4/IgG RNA ratio was 100%, the specificity 58.6%, the positive predictive value 3.3%. Conclusion In the setting of a high a priori risk of malignancy, an elevated IgG4/IgG RNA ratio did not accurately discriminate pancreatobiliary cancer from IgG4-RD as illustrated by low specificity and concordant low positive predictive value. We advise against the use of this test to discriminate IgG4-RD from pancreatobiliary malignancies. Lay summary IgG4-related disease is a benign inflammatory multiorgan disease which predominantly affects the pancreas and biliary tree. Clinical symptoms, laboratory and imaging finding are often difficult to distinguish from pancreatic or biliary tract cancer. This prospective trial indicates that the recently proposed blood IgG4/IgG RNA ratio does not accurately distinguish benign IgG4-RD from malignant pancreatobiliary disease., Highlights • IgG4-related disease and malignancy of bile ducts/pancreas can be indistinguishable. • Blood IgG4/IgG RNA ratio was prospectively tested as an IgG4-RD marker when malignancy was suspected. • IgG4/IgG RNA ratio >5% did not accurately discriminate IgG4-RD from pancreatobiliary cancer.

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.