Heavy Inflammatory Infiltrate Research Articles

Purified L-glutaminase effects against multidrug-resistant Pseudomonas aeruginosa in experimental vaginosis model: An immunological and histopathological observation

The antimicrobial activity of crude and purified L-glutaminase (EC 3.5.1.2), obtained from Lactobacillus gasseri, was evaluated against multidrug-resistant Pseudomonas aeruginosa in the in vivo vaginosis condition. The L-glutaminase possessed significant antimicrobial and anti-biofilm formation activity against multi-drug resistance P. aeruginosa, which were confirmed in the BALBc rat vaginosis model, together with its effects on the immunological and histopathological aspects. The untreated animals showed heavy vaginitis, characterized by sub-epithelial edema and infiltration of mononuclear leukocytes, perivascular heavy inflammatory cells infiltration in the vaginal tissue, and moderate stromal edema. However, the L-glutaminase treatment exhibited no changes in vaginal tissue structure with normal appearance of the epithelium and lamina propria with marked repair of the vaginal section when compared with normal, uninfected, control group A. The immunomodulatory actions of the L-glutaminase were confirmed by observance of higher concentrations of tumor necrosis factor-γ (TNF-γ), and interleukin −12 (IL-12) in treated animals, while the interleukin-10 (IL-10) was higher in the infected, untreated animals' sera samples. Therefore, the L-glutaminase showed corrective and healing actions, which were observed through histopathological observations of the vaginal tissue. The investigations led to imply that L-glutaminase may have the potential to be an effective antimicrobial agent for preventing and inhibiting bacterial growth, as well as inhibiting the biofilm formation in the P. aeruginosa-originated vaginosis. The observations may be of promising value for future clinical use.

Impact of e-cigarettes on colonic mucosa and the role of recovery: involvement of oxidative and inflammatory pathway.

Electronic cigarettes (e-cigarettes) (EC) are often advertised as a safer alternative to conventional cigarettes. Its widespread use has led to increased interest in its adverse health effects, thanks to few restrictions and a lack of regulatory guidelines. The study aimed to evaluate the influence of exposure to e-cigarette aerosol inhalation in rat colon model and conduct a follow-up after cessation of exposure. The experiment included 30 male adult Albino rats. The animals were divided into three groups: group I (control), non-exposed animals; group II (exposed), was exposed to electronic cigarette liquid vapor for four consecutive weeks; and group III (recovery), was followed up for another 4 weeks after exposure to an e-cigarette as exposed group and for the same duration. In the exposed group, malondialdehyde (MDA) and total nitric oxide (NO) increased significantly in colonic tissue, while superoxide dismutase (SOD) decreased. On histological examination, colonic mucosa showed distortion and loss of its epithelial lining with heavy inflammatory cell infiltration. Also, there was a significant decrease in periodic acid-Schiff-positive goblet cells and area percent of proliferating cell nuclear antigen expression. Tumor necrosis factor-alpha (TNFα) expression significantly increased in colonic mucosa. After 4 weeks of EC cessation, the colonic mucosal histological structure showed recovery with downregulated TNFα immunoexpression and restored oxidant/antioxidant balance. In conclusion, the usage of electronic cigarettes resulted in marked pathological alterations in the colonic mucosa, which could be attributed to oxidative and inflammatory stresses. In contrast, the cessation of exposure led to recovery.

Scoring systems for PD-L1 expression and their prognostic impact in patients with resectable gastric cancer.

The combined positive score (CPS) and tumor proportion score (TPS) have been developed to evaluate programmed death ligand-1 (PD-L1) expression, especially due to the potential benefit of the targeted therapy. However, the prognostic value of PD-L1 scoring systems in gastric cancer (GC) remains unclear. This study aimed to evaluate PD-L1 expression according to CPS and TPS in curative resected GC patients and its correlation with prognosis. We retrospectively evaluated 284 GC patients who underwent D2-gastrectomy by tissue microarray. PD-L1 expression was analyzed by immunohistochemistry. PD-L1 positivity by CPS and TPS was observed in 45 (15.8%) and 34 (12%) patients, respectively. Larger tumor size (p = 0.028), undetermined Lauren type (p < 0.001), and heavy inflammatory infiltrate (p = 0.009) were associated with CPS-positive GC. TPS-positive were more frequent in patients with larger tumor size (p = 0.004), undetermined type (p < 0.001), moderate/severe inflammatory infiltrate (p = 0.001), total gastrectomy (p = 0.036), and poorly differentiated histology (p = 0.025). No differences were observed in the pT, pN, and pTNM status according to the PD-L1 scores. Both scores were associated with Epstein-Barr virus positivity, microsatellite instability and p53-normal expression. The disease-free survival (DFS) was worse for CPS-negative compared to CPS-positive group (p = 0.052). No difference was observed between TPS-positive and negative groups (p = 0.436). Total gastrectomy, advanced pT status, and CPS-negative were independent factor for worse survival in GC. CPS was an independent prognostic factor for survival and could be used as a prognostic biomarker in patients with resectable GC.

Toxicokinetics of Titanium Dioxide (Tio2) Nanoparticles After Intraperitoneal Injection in Male Mice

In the present study, male albino mice were used to estimate the effects of titanium dioxide nanoparticles (TiO2) suspension used in two doses (150, 600 mg/kg) through intraperitoneal route. The results revealed a significant difference (p≤0.05) among the control and experimental groups in all haematological parameters, including a significant increase in White Blood Cell (W.B.C) count, Mean Cell Volume (MCV), Mean Cell Haemoglobin Concentration (MCHC), and Mean Cell Haemoglobin (MCH). Also, the results showed a significant decrease in Red Blood Cell (R.B.C.) count and Haemoglobin (Hb). Biochemical tests included AST and ALT and showed a significant elevation in all exposed groups, while ALP was decreased after fourteen and thirty days of exposure. In the case of kidney function, creatinine was increased in all groups during the experiment, whereas uric acid was increase in many cases and recorded the highest mean value after fourteen days of exposure to the dose of 150mg/kg and after thirty days of exposure to the dose of 600mg/kg. Level of urea was decreased in the fourteen-days and thirty-days treatment groups, while its mean values after using the two doses did not change significantly after one day. Cholesterol level was decreased after thirty days, recording the lowest mean value at 600mg/kg, whereas the level of HDL was significantly (p≤0.05) decreased and that of LDL significantly increased. The study of bioaccumulation demonstrated that the TiO2 NPs are accumulated mainly in the spleen, followed by the liver and kidneys of mice, respectively. Also, the doses used caused histological alterations such as changes in the congested dilated portal tract, with heavy inflammatory cells infiltration and dilated central venule in the liver, along with glomerular congestion, tubular congestion, atrophy, chronic inflammatory cells infiltration, and dilated tubules with flat atrophied lining epithelium in the kidneys. The histologic alterations observed may represent an indication of different degrees of organ injury due to the toxicity of TiO2 NPs, resulting in an inability to deal with accumulated residues from the metabolic and structural disturbances caused by these nanoparticles.

A METHOD FOR DIGITAL QUANTIFICATION OF EOSINOPHILS INFILTRATE IN ORAL SQUAMOUS CELL CARCINOMA

Introduction:The recent advances in tumor immunotherapy triggered more attention towards analysis of tumor inflammation. Oral squamous cell carcinoma (OSCC) is malignancy that can be therapeutically challenging and resistant to treatment. Further investigation of the inflammatory profile in OSCC can enhance our understanding of the disease and hence patient response to immunotherapy. Eosinophils are suggested to play a significant role in tumor progression and have been described to be associated with advanced stage malignancies of several tumor subtypes. Objective: Here we wanted to assess a methodology to quantitatively measure eosinophils infiltrate in OSCC. Material and methods: Eosinophils infiltrate was analyzed in formalin fixed paraffin embedded tissue (FFPE) microarray cores of 30 oral squamous cell carcinomas (OSCC), and 10 normal oral epithelium controls. Digital analysis using the auto fluorescence of eosinophils accentuated by Alexa Fluor 488 stain, in FFPE tissue sections; we used Cytation 5 machine and Gen 5 software, to digitally quantify the extent of eosinophils infiltrate in OSCC. Results: Out of the inflamed OSCC examined sections with heavy inflammatory infiltrate rich in eosinophils, RBCs, neutrophils and monocytes, eosinophils were readily detected, and digitally quantified after staining with Alexa Fluor 488. The tumor cores showed eosinophils infiltrate in the peri-tumoral stroma of 26 (87%) of the 30 examined OSCC Conclusion: This study highlights the importance of assessment of the type and extent of inflammatory cells infiltrate as well as its digital quantification. It provides a novel quantification method of eosinophils that opens avenues to study the correlation between eosinophils infiltrate and tumor prognosis.

A PILOT STUDY OF PD-1 AND PD-L1 EXPRESSION IN A SPECTRUM OF ORAL DYSPLASIAS AND ORAL SQUAMOUS CELL CARCINOMAS

As our understanding of head and neck cancer increases, personalized therapy with targeted approaches is becoming more common. Recently, the FDA approved the checkpoint blocking antibody pembrolizumab to treat advanced head and neck squamous cell carcinoma (SCC). This cancer immunotherapeutic monoclonal antibody blocks the interaction of the programed cell death - 1 (PD-1) receptor on T-cells from interacting with the programed cell death receptor ligand - 1 (PD-L1) produced by tumor cells. Normal cells utilize the PD-1/PD-L1 pathway to control immune recognition. Tumor cells exploit this pathway by upregulating their expression of PD-L1, which results in downregulation of the immune response and ultimately apoptosis of inactive T-cells. To better understand PD-L1 and PD-1 interactions within oral tissue, we used immunohistochemistry on 12 severe oral epithelial dysplasias from high-risk sites and 10 oral SCCs, two of which were recurrent. The cases were additionally characterized based on inflammatory phenotype. Results showed 7 cases had epithelium that stained positive for PD-L1. Of the 7 positive cases, 5 were SCCs and 2 were dysplasias with a heavy inflammatory infiltrate including germinal center formation. Seventeen cases had PD-1 positive immune cells. Interestingly, 15 cases had immune cells that stained positive for PD-L1. Although the majority of severe dysplasia cases did not express PD-L1 on epithelial cells, elucidating the staining characteristics of immune cells may prove to be beneficial in better understanding these lesions and potential treatments.

Spectrum of lesions derived from branchial arches occurring in the thyroid: from solid cell nests to tumors

There is a group of lesions in the head and neck region derived from branchial arches and related structures which, when inflamed, are characterized by the formation of cysts lined by squamous or glandular epithelium and surrounded by a heavy inflammatory infiltrate rich in germinal centers. In the thyroid, the main source of various structures which may cause diagnostic dilemma is the ultimobranchial body. To investigate the spectrum of such thyroid lesions, the consultation files were reviewed for thyroid samples containing pathological structures regarded to arise from the ultimobranchial body. Positive reaction with antibodies against CK5/6, p63, galectin 3, and CEA, and negative reaction with antibodies against thyroglobulin, TTF-1, and calcitonin were used to confirm the diagnosis. The specific subtype of the ultimobranchial body-derived lesion was then determined based on histological examination of H&E-stained slides. Twenty-one cases of ultimobranchial body-derived lesions were retrieved from the consultation files, 20 of them along with clinical information (M/F=6/14, mean age 55years, range 36-68years). Lesions derived from the ultimobranchial body were classified as follows: (hyperplastic) solid cell nests (nine cases), solid cell nests with focal cystic change (five cases), cystic solid cell nests (two cases), branchial cleft-like cyst (four cases), and finally a peculiar Warthin tumor-like lesion (one case). We suggest that the common denominator of these structures is that they all arise due to activation of inflammatory cells around the vestigial structures, which leads to cystic dilatation and proliferation of the epithelial component.

The effect of immobilization induced stress on the lung of the adult male albino rat and the possible protective role of melatonin: A light, electron microscopic and immunohistochemical study

Background: Stress is known as one of the most important reasons of many diseases. Immobilization is one of the most common performed stresses on animals. immobilization stress may induce the formation of reactive oxygen species and can lead to suppression of immune system. Melatonin as an antioxidant, has an important role in the immune function. The lung has a large surface that is constantly in contact with air oxygen and pollutants. It is one of the organs commonly affected by reactive oxygen species generation which induces oxidative damage. It is a site of major reactive oxygen species production.Aim of work: The present study aimed to investigate the effect of immobilization induced stress on the lung in the adult male albino rat and the possible protective role of melatonin.Material and Methods: 45 adult male albino rats weighing 200–250 g were used in this study. The rats were randomly divided into three equal groups (15 rats each). Group (I): the rats kept undisturbed and served as non-stress control group. They were sacrificed at the end of the experiment. Group (II): the rats subjected to stress and placed on a wooden plate with their trunks wrapped in a confining harness for 90 min 5 days/week for 6 weeks. The animal was able to move its limbs and head but not its trunk. Group (III): the rats were exposed to stress as previously described and concurrently injected melatonin intraperitoneally in a dose of 10 mg/kg/day at 4:00 pm. All animals were sacrificed by decapitation under anaesthesia at the same time, then lungs dissected out. The specimens of each group were randomly divided into three subgroups; the first was processed for the light microscopic study (H & E), the second for the transmission electron microscopic study and the third for the immunohistochemical study (Caspase-3 and iNOS). Morphometric studies and statistical analysis were performed.Results: The light microscopic and ultrastructural examination of the rat lungs after immobilization showed severe alveolar damage in the form of collapsed alveolar saccule and alveoli, markedly thickened interalveolar septa encroaching on alveoli, heavy inflammatory cellular infiltration and exudation. Pneumocyte type I showed indentation of its nuclear membrane, presence of chromatin clumps inside the nucleus and swollen mitochondria with disrupted cristae. Melatonin treated group revealed an evident reduction of all alveolar changes with nearly normal structure of the alveolar ducts, alveolar saccules and alveoli. Immunohistochemically stained lung sections for caspase-3 and iNOS after immobilization showed an intense brownish immune reactions. Melatonin treated group revealed a noticeable reduction in the immune reactions.Conclusion: Immobilization stress has a damaging effect on the histological structure of the lung and a concomitant treatment with an antioxidant (melatonin) effectively protected the lung tissue.

A Cure for Coronary Artery Disease

To cure coronary artery disease, complete removal of atheroma from coronary arteries is necessary and may be achieved using pharmacological intervention. This hypothesis requires verification by a trial. The conditions that lead to the formation of atheroma are as follows: Insulin resistance and vascular endothelial dysfunction, Atherogenic dyslipidemia, Risk factors for coronary artery disease, Inflammation of coronary arteries, Drugs that increase insulin resistance. Atheroma formation begins with the formation of fatty streaks on the endothelium, which progress into stable or unstable atheromatous plaques. The unstable plaque has a thin fibrous cap that is prone to rupture. Unstable plaques contain a large lipid pool consisting of oxidized low-density lipoprotein (LDL), apoB and cholesterol that can grow; they are also have heavy inflammatory cell infiltration, including monocytes, macrophages and T cell lymphocytes. Moreover, debris from ruptured macrophages that were overloaded with lipids attracts more macrophages. The plaque can grow and protrude into the coronary artery lumen. Plaques exhibit overgrowth of vasa vasorum and they can rupture, leading to the formation of a large thrombus that may severely or completely obstruct the coronary artery. Hemorrhage may also occur in the plaque. Carvedilol and metformin promote plaque stability. The supply of lipids to the lipid pool in the plaque is reduced by statins and evolocumab, and lipids are removed from the lipid pool by apoA-1 and high-density lipoprotein (HDL) as their levels in the blood are increased. Severe inflammation is treated with carvedilol, metformin, statins and apoA. Growth of vasa vasorum is attributed to insulin resistance and can be reversed by carvedilol and metformin, thereby preventing hemorrhage. The size of the thrombus on a ruptured plaque can also be reduced by carvedilol, metformin and apoA-1, as these three agents prevent platelet aggregation. Thrombi are removed by endothelial thrombolysis. A thrombus may also form in the plaque from intraplaque hemorrhage; if present, the size of this type of thrombus will be small, as vasa vasorum are atrophic. In both cases, thrombi are removed by endothelial thrombolysis. Subsequently, healthy macrophages infiltrate and remove debris, after which the plaque changes to a fibrous nodule that can be removed by endothelial fibrinolysis. The plaque is then completely removed.

Inflammatory Fibroid Polyp of the Stomach Mimics Malignancy on 18F FDG PET/CT Imaging

Inflammatory fibroid polyps (IFPs) are rare non-neoplastic and proliferating submucosal lesions of the gastrointestinal tract. The classic IFP, which was first described by Vanek, consists of prominent blood vessels and is characterized by a heavy inflammatory infiltrate, which is rich in eosinophilic granulocytes. The clinical presentation depends on the size and location. Inflammatory fibroid polyps cannot be differentiated from malignancy without histological examination. We report a case of IFP in the stomach that mimicked a primary gastric malignancy showing an increased F-FDG uptake.

Fish oil attenuates neurologic severity of antiphospholipid syndrome in a mice experimental model

Introduction: Murine experimental models of antiphospholipid syndrome (eAPLS) showed neurologic dysfunction and therapeutic effect of the anticoagulant enoxaparin is well established. Omega-3 fatty acids and curcumin, tested in neuroinflammation and auto-immunity diseases, might be interesting therapeutic candidates. The aim of this study was to evaluate the effects of these candidates on neurologic severity in eAPLS. Methods: One month after immunization of BALB/c mice with beta-2-glycoprotein I, daily treatments were initiated with enoxaparin (1 mg/kg), omega-3 fatty acids (0.5 g/kg), and curcumin (200 mg/kg) for 3 months. Results: Mortality was significantly decreased by enoxaparin and omega-3 treatments. Fish oil and curcumin group exhibited the highest mean of swimming behavior in forced swim test in surviving mice. Mice under omega-3 fatty acids or curcumin presented low anxiety-like behavior in the elevated plus-maze test. Cerebral histopathology revealed heavy inflammatory infiltrates in cortical and subcortical regions with vacuolization, swelling, and degeneration of astrocytes in the control group, with aggravation under curcumin; no infiltrate was retrieved in enoxaparin and omega-3 groups. Conclusion: Our study is the first to demonstrate a potential therapeutic effect of omega-3 fatty acids in eAPLS. Enoxaparin and omega-3 fatty acids combination would be interesting for further investigation.

Aeromonas hydrophila induces intestinal inflammation in grass carp (Ctenopharyngodon idella): An experimental model

Abstract Bacterial enteritis is a widespread inflammatory disease in most farmed fish, yet its pathogenesis is largely unknown, primarily because of the paucity of reproducible experimental models of intestinal inflammation in fish. The aim of the present study was to develop a model of intestinal inflammation in the grass carp by challenging it with a strain of Aeromonas hydrophila . To induce intestinal inflammation, the fish were challenged with A . hydrophila via anal intubation at 2.7 × 10 6 cfu/fish, an appropriate dose based on the disease activity index for inflammatory signs. The pathological changes occurring in the intestines over the 21 day experimental period were examined with light microscopy and scanning electron microscopy. Histopathological examinations showed that A . hydrophila infection caused severe intestinal lesions, including intestinal villus fusion and shedding, and induced heavy inflammatory cell infiltration on day 3 after challenge. Ultrastructural observations also revealed that bacterial infection caused microvillus effacement. The injured intestinal villi were gradually repaired during the subsequent 18 days of the experimental period. Our results also indicated that the inflammatory responses induced by A . hydrophila infection were closely associated with the expression of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-8, and tumor necrosis factor α (TNF-α) and myeloperoxidase (MPO) activity. The highest mRNA levels of these cytokines and highest MPO activity in the intestine were observed on day 3 after challenge. These results show that the intestinal lesions caused by A . hydrophila infection and their repair were completely consistent with the time course of inflammation-related genes or biomarkers. Thus, we have developed an experimental model of intestinal inflammation in an intensively farmed fish. This model is expected to be useful in clarifying the pathogenesis of bacterial enteritis in the grass carp and other farmed fish, and in testing antimicrobial drugs for potential use in aquaculture.

Primary central nervous system histiocytic sarcoma presenting as a postradiation sarcoma: case report and literature review

Histiocytic sarcoma (HS) is a rare neoplasm that occurs most commonly in the intestinal tract, skin, soft tissue, and lymph node. The incidence of primary central nervous system (CNS) HS is even rarer, with a total of 6 cases reported in the literature. An etiologic link has not been identified for CNS HS, and the current case of primary CNS HS is unique in that an etiologic link to prior radiation therapy is identified, associated with complex cytogenetic abnormalities in the tumor. Although radiation-associated sarcomas can present as any number of different pathologic entities, this is the first reported case of a radiation-associated CNS HS. The pathologic and immunophenotypic characteristics of this case, with a nearly obscuring heavy inflammatory infiltrate and expression of monocytic/histiocytic markers (CD163, CD68, CD4, fascin), are characteristic of CNS HS. A discussion of the differential diagnosis and review of relevant literature are presented.

Pseudogranulomatous Spitz nevus: a variant of Spitz nevus with heavy inflammatory infiltrate mimicking a granulomatous dermatitis

Spitz nevus is a benign melanocytic proliferation that shows relatively characteristic clinicopathologic features. Despite this, Spitz nevus is clinically confused with many other lesions, and histopathologically it is sometimes difficult to distinguish it from melanoma. However, Spitz nevus rarely causes differential diagnostic problems with granulomatous dermatitis. This article describes an 8-year-old girl who presented with a nodule on her right arm, a clinical appearance of a pyogenic granuloma. Histopathologically, there was a dermal lesion composed of aggregates of large epithelioid cells surrounded by a heavy inflammatory infiltrate, mimicking a sarcoid-like granulomatous dermatitis. Immunohistochemistry showed epithelioid cells with strong nuclear and cytoplasmic staining with S-100 protein, thus establishing the diagnosis of a melanocytic tumor. The heavy T-cell lymphocytic infiltrate that accompanies the large epithelioid cells caused its granulomatous appearance. Molecular assessment showed H27H mutation in the HRAS gene. We suggest the term 'pseudogranulomatous' for this variant of Spitz nevus because it indicates that the lesion is not authentically granulomatous and simply mimics a granulomatous dermatitis.

Apolipoprotein E COG 133 mimetic peptide improves 5-fluorouracil-induced intestinal mucositis

BackgroundIntestinal mucositis is one of the major troublesome side effects of anticancer chemotherapy leading to poor patient compliance. In this study we addressed the role of the novel apolipoprotein E (ApoE) COG 133 mimetic peptide in 5-fluorouracil (5-FU)-challenged Swiss mice and IEC-6 cell monolayers. Experiments were also conducted in C57BL6J ApoE knock-out mice to assess the effects of apoE peptide treatment.MethodsExperimental groups were as follows: unchallenged controls, 5-FU-challenged mice (450 mg/kg, i.p) with or without the ApoE peptide (0.3, 1, and 3 μM, given twice daily i.p. for 4 days). Mice were sacrificed 3 days after 5-FU challenge. Proximal small intestinal samples were harvested for molecular biology and histological processing. We conducted ELISA assays and RT-PCR to target IL-1β, TNF-α, IL-10, iNOS, and myeloperoxidase (MPO) to assess intestinal inflammation. Cell death and NF-κB assays were also conducted in apoE knock-out mice. In our in vitro models, IEC-6 cells were exposed to 1 mM of 5-FU in glutamine free media with or without the ApoE peptide (0.02, 0.2, 2, 5, 10, and 20 μM). We investigated IEC-6 cell proliferation and migration, 24 h after the 5-FU challenge. Additionally, apoptotic IEC-6 cells were measured by Tunel and flow cytometry. Equimolar doses of the ApoA-I (D4-F) peptide were also used in some experiments for comparative studies.ResultsVillus blunting and heavy inflammatory infiltrates were seen in the 5-FU-challenged group, findings that were partially ameliorated by the ApoE peptide. We found increased intestinal MPO and pro-inflammatory IL-1β and TNF-α levels, and TNF-α and iNOS transcripts, and reduction of IL-10 following 5-FU treatment, each of which were partially abrogated by the peptide. Improvements were also found in IEC-6 cell apoptosis and migration following ApoE and D-4F treatment.ConclusionAltogether, these findings suggest that the novel ApoE COG 133 mimetic peptide can reduce 5-FU-induced intestinal changes and potentially benefit mucositis.

Inflammatory angiomyolipomas of the liver: a clinicopathologic and immunohistochemical analysis of 5 cases

Hepatic angiomyolipoma (AML) may demonstrate a marked histologic diversity. We report 5 cases of hepatic AML exhibiting prominent inflammatory cells in the background (inflammatory AML). The patients were 4 females and 1 male, with age ranged from 21 to 48 years (mean, 39.2 years). Three tumors were in the left lobe and 2 in the right lobe. The tumor size was from 5.5 to 10 cm in the greatest dimension (mean, 7.46 cm). No patient had clinical features of tuberous sclerosis. Histologically, the striking feature was the infiltration of numerous inflammatory cells in the background of the tumors, including small lymphocytes, plasma cells, and histiocytes. The percentage of tumor area with heavy inflammatory infiltration was more than 50% in all cases. The myoid cells were spindled and epithelioid in shape, with eosinophilic or clear cytoplasm, and were arranged in fascicles and clusters. Scattered adipose cells and sinusoidal and thick-walled blood vessels were variably present in all tumors. Focal trabecular arrangement was present in 2 of the 5 tumors. There was no nuclear atypia, and mitotic figures were rare. The myoid cells were diffusely positive for vimentin, smooth muscle actin, and HMB-45 in all cases. All patients showed no evidence of disease after the initial surgical excision during a follow-up period from 3 to 9 years. The inflammatory AMLs should be distinguished from other tumors with inflammatory background such as inflammatory myofibroblastic tumor and follicular dendritic cell tumor.

Diagnosis and osseous healing of a lateral periodontal cyst mimicking a deep unusual interdental pocket in a young patient

A 17-year-old male patient presented for the evaluation of his nonhealing interdental deep pocket in relation to the mandibular second premolar and mandibular first molar. He denied any history of pain. Excessive food lodgment, salty taste, and smell related to the specific region were his chief complaints. The periapical radiograph exhibited well-defined interradicular unilocular radiolucency with sclerotic margins between the vital mandibular second premolar and mandibular first molar. The lesion was completely enucleated with deep curettage and root planning. Histopathologic reports showed a heavy inflammatory infiltrate. Successive radiographs showed excellent bone healing. Teeth were endodontically treated for severe sensitivity to cold. Step-by-step radiographic follow-up showed osseous repair with no evidence of disease till 25 months.

Intratumoral DNA electroporation induces anti-tumor immunity and tumor regression

In situ expression of a foreign antigen and an immune-modulating cytokine by intratumoral DNA electroporation was tested as a cancer therapy regimen. Transgene expression in the tumors was sustained for 2-3 weeks after intratumoral electroporation with mammalian expression plasmid containing firefly luciferase cDNA. Electroporation with cDNA encoding tetanus toxin fragment C (TetC) induced tetanus toxin-binding antibody, demonstrating immune recognition of the transgene product. Intratumoral electroporation with TetC and IL-12 cDNA after mice were treated with CD25 mAb to remove regulatory T cells induced IFN-gamma producing T-cell response to tumor-associated antigen, heavy inflammatory infiltration, regression of established tumors and immune memory to protect mice from repeated tumor challenge. Intratumoral expression of immune-modulating molecules may be most suitable in the neoadjuvant setting to enhance the therapeutic efficacy and provide long-term protection.

Inflammatory fibroid polyp of the small bowel with a mutation in exon 12 of PDGFRα

Inflammatory fibroid polyp (IFP) is a benign reactive uncommon submucosal lesion of the gastrointestinal tract, the small intestine being the most common site of origin. Histologically, IFPs are characterized by spindle cells, a heavy inflammatory infiltrate including eosinophils and onion-sheet-like formation of lesional cells around blood vessels. We present a case report of an IFP harboring an activation mutation in the PDGFR alpha gene. The lesion was positive for CD34, PDGFR alpha, and p-PDGFR alpha immunostaining but was negative for c-KIT and desmin. After a sequencing analysis of KIT and PDGFR alpha, a mutation consisting of an in-frame deletion of codons 567-571 and a missense mutation in codon 566 (S566R) of PDGFR alpha was observed. This mutation could activate key cellular pathways with involvement in the pathogenesis of this entity. We concluded that more studies are necessary in order to clarify if this finding is a biologically distinct behavior or, on the contrary, represents a specific feature of the IFP.

Clinical and Histopathologic Review of 18 Explanted Porous Polyethylene Orbital Implants

To review the clinical and histopathologic features of porous polyethylene (PP) orbital implants requiring explantation. Case series. Eighteen explanted PP orbital implants of 18 patients were studied. The charts and histopathologic findings were reviewed for all patients requiring explantation of PP orbital implants between 1997 and 2006 by 2 oculoplastic surgeons at the University of British Columbia. Clinical data obtained included patient demographics, the nature of the primary surgery, and the clinical presentation leading to eventual implant removal. The histopathologic data observed included the presence of anterior exposure, area of fibrovascular ingrowth, type of inflammation, and presence and type of bacterial colonies. Nine (50%) of the 18 patients studied were referred from other surgeons. The balance represented 3.2% of all PP implants placed by the 2 surgeons. The procedures for the primary surgery were 12 enucleations (67%), 5 eviscerations (28%), and 1 secondary implant (5%). Clinical findings included anterior implant exposure and discharge in all cases. Histopathologic analysis was performed in all of the implants and showed less than 50% fibrovascular ingrowth in 16 implants (89%) and predominantly acute or mixed inflammation in 15 (83%). Foreign body giant cells were seen adjacent to the implant material in all cases. Bacterial colonies on gram stain were identified in 12 specimens (67%); overall, gram-positive cocci in clusters or chains were found in 10 implants (56%), and gram-negative bacteria were found in 1 (5.5%). Thirteen patients (72%) lived in locations distant from Vancouver, the surgical center. This article presents the largest review of explanted porous polyethylene orbital spheres. The findings suggest that anterior exposure allows bacterial colonization and the development of a heavy inflammatory infiltrate. Poor tissue ingrowth may limit the penetration of topical or systemic antibiotic therapy, leading to the necessity for explantation. The author(s) have no proprietary or commercial interest in any materials discussed in this article.