Presence Of Giant Cells Research Articles

Fine-needle Aspiration Biopsy of Pilomatrixoma (Cytological Features of Six Cases Histologically Approved).

Pilomatrixoma is a rare, benign, slow-growing tumor of the hair matrix. Excisional biopsy is often the preferred method of diagnosis for cutaneous masses including pilomatrixoma. However, fine-needle aspiration is also performed on these lesions. There are very few reports on the cytologic features of pilomatrixoma in fine-needle aspiration. In this study, we aimed to evaluate the clinical and cytological features of six cases of pilomatrixoma, which were confirmed histopathologically. The study includes six cases of pilomatrixoma, which were diagnosed by two cytopathologists in 2019 and 2022. A detailed cytological analysis was done by a semiquantitative method. Cellularity, basaloid cells, squamous cells, giant cells, shadow cells, naked nuclei, calcium deposits, inflammation, and debris were semiquantified from 0 to 3+. The ages of patients ranged from 8 to 63 years old. The male-to-female ratio was 2:1. All cases occurred in the head and neck area. The cytological diagnosis was pilomatrixoma in five cases and epidermoid/dermoid cyst in one case. The surgical excision was performed in all patients. The diagnosis of pilomatrixoma was confirmed histologically in all cases. Fine-needle aspiration biopsy (FNAB) of pilomatrixoma can be a diagnostic challenge. There are very few reports on the cytologic features of pilomatrixoma in FNAB smears. The presence of ghost cells and basaloid cells should suggest the possibility of pilomatrixoma. The presence of giant cells, fibrillary matrix, calcium deposits, squamous cells, naked nuclei, inflammation, and debris are cytological findings supporting the diagnosis.

P16 Expression in Multinucleated Stromal Cells of Fibroepithelial Polyps of the Anus (FEPA): A Comprehensive Review and Our Experience

Fibroepithelial polyps of the anus (FEPA) are a common benign polypoid proliferation of the stroma covered by squamous epithelium. They are also an often-overlooked part of pathological practice. Currently, immunohistochemistry (IHC) for p16 is the only recommended test for anal intraepithelial neoplasia, but the expression of p16 in stromal multinucleated atypical cells in FEPA has not been described. We aimed to evaluate the expression of p16 in stromal multinucleated atypical cells in FEPA and its role as a diagnostic biomarker to determine the origin of the atypical multinucleated cells in the stroma of FEPA and to rule out the possibility of a neoplastic process. Therefore, we researched a series of 15 FEPA in middle-aged patients histologically and by IHC. Examination of the subepithelial connective tissue from the FEPA showed bizarre, multinucleated cells, while their causal relationship with human papillomavirus (HPV) infection was rejected. In all cases, these cells showed mild to moderate atypical nuclear features and positive expression for p16, while the overlying squamous epithelium was negative. We concluded that FEPA are benign lesions in the stroma where mononuclear and multinucleated (sometimes atypical) cells showing fibroblastic and myofibroblastic differentiation can be found. Nevertheless, we believe that these cells have a practical diagnostic significance, although sometimes the presence of giant cells is difficult to establish, especially in the inflammatory context. The histological similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent the reactive hyperplasia of subepithelial fibrous connective tissue of the anal mucosa.

Giant cells in temporal artery biopsies and the risk of large vessel involvement in patients with giant cell arteritis.

Giant cell arteritis (GCA) is a systemic disease with variable vascular involvement. The objective was to investigate predictors of time-dependent large vessel involvement (LVI) in a population-based cohort of patients with GCA. GCA patients with positive temporal artery biopsies (TAB) between 1997- 2010 were identified through a regional pathology register. A structured review of histopathology reports and relevant imaging studies was performed. Cases with LVI through July 2016 were identified. Patients were followed to first LVI, death, migration from the area or July 29, 2016. Event free survival by clinical and histopathologic features was estimated using the Kaplan-Meier method. Potential predictors of LVI were examined using Cox regression models. A total of 274 patients were included. The mean age at GCA diagnosis was 75.7 years. Fifty-one patients (19 %) had documented LVI during the follow-up, corresponding to an incidence rate of 2.4/100 person-years. The median time from GCA diagnosis to the diagnosis of LVI was 4.5 years (interquartile range 0.6-7.4). Thirty-four patients had aortic involvement (67% of those with LVI; 12% of all GCA cases). Survival free of LVI was longer in patients with giant cells in the TAB (75th percentile 14.0 vs 6.7 years; p=0.014). In age-adjusted analysis, the presence of giant cells in the TAB was associated with reduced risk of LVI (hazard ratio 0.48; 95 % confidence interval 0.27-0.86). The negative association with giant cells in the TAB suggests that patients with LVI constitute a subset of GCA with particular disease mechanisms.

Cytologic analysis of metaplastic breast carcinoma: Review of 66 cases diagnosed at the Institut Curie.

Cytology reports of metaplastic breast carcinoma (MBC) are rare and limited to short series and simple case reports. To adapt cytology diagnostic criteria to the most recent fifth edition of the World Health Organization Classification of Breast Tumours from 2019, we have reviewed our series from the files of the Institut Curie. A cohort of 66 female patients investigated by cytology with corresponding histologic diagnosis of MBC was identified. Eight cytologic characteristics were analyzed: cellularity, adenocarcinoma cells, squamous cells, spindle cells, giant cells, cytonuclear atypia, necrosis, and osseous/chondroid matrix and compared with histology. Cytologic diagnoses were malignant in 58 (88%) cases (of which 29 cases were typed cytologically as MBC), suspicious in 6 (9%) cases, and nondiagnostic in 2 (3%) cases. None of the cytologic examinations was a benign diagnosis. Low-grade adenosquamous carcinoma and fibromatosis-like metaplastic carcinoma exhibited a low degree of cellular atypia. Fibromatosis-like metaplastic carcinoma and spindle cell carcinoma (SpCC) presented spindle cells, while SpCC also demonstrated varying degrees of atypia, the presence of giant cells, and necrosis. Squamous cell carcinoma was characterized by the presence of squamous cells, and metaplastic carcinoma with osseous/chondroid differentiation displayed an osseous/chondroid matrix. Fine-needle aspiration holds considerable potential as a valid, independent, and complementary approach to histologic examination of MBC.

Internal feedback in the cortical perception–action loop enables fast and accurate behavior

Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.

Case Series: Recurrence of Cardiac Sarcoidosis After Orthotopic Heart Transplantation

Orthotopic heart transplantation for cardiac sarcoidosis (CS) is becoming increasingly common. Historically, there have been concerns regarding disease recurrence within the allograft. Although rarely reported in the literature, cases of recurrent CS tend to be observed in patients after dose reduction of immunosuppressive therapy and cessation of corticosteroids. Here, we present 2 cases of recurrent CS after orthotopic heart transplantation, confirmed on endomyocardial biopsy. Case 1 reports a 50-year-old man with a fulminant course of giant cell myocarditis who developed allograft recurrence with granulomas 5 years after transplantation despite maintenance corticosteroid therapy. Case 2 reports a 47-year-old man with CS who developed recurrence with the presence of giant cells 2 years after transplantation, with a benign clinical course. With these cases, we demonstrate the clinical overlap between CS and giant cell myocarditis and highlight the spectrum of the disease process. We also demonstrate that CS can recur despite corticosteroid maintenance therapy.

A rare case of bilateral pulse granuloma of maxilla

Pulse or hyaline ring granulomas are rare but are well-defined oral and extraoral lesions due to implantation of the cellulose moiety of plant foods in contrast starch components. Implantation could be through extraction sockets, deep periodontal pockets, associated with tumor growth, interdental areas of teeth, unfilled root canals, and grossly decayed teeth. These get rapidly digested and altered by host responses. It is Microscopic oral inflammatory lesion characterized by the presence of giant cells and hyaline rings. The features of pulse granuloma are not considered clinically distinctive and remain primarily microscopic. Extensive knowledge of abnormal sites of origin and clinical manifestations enables clinicians to recognize the diagnostic risks of confusing pulse granuloma with other entities.

A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance

Glioblastoma is among the most lethal cancers, with no known cure. A multitude of therapeutics are being developed or in clinical trials, but currently there are no ways to predict which patient may benefit the most from which drug. Assays that allow prediction of the tumor’s response to anti-cancer drugs may improve clinical decision-making. Here, we present a high-density 3D primary cell culture model for short-term testing from resected glioblastoma tissue that is set up on the day of surgery, established within 7 days and viable for at least 3 weeks. High-density 3D cultures contain tumor and host cells, including microglia, and retain key histopathological characteristics of their parent tumors, including proliferative activity, expression of the marker GFAP, and presence of giant cells. This provides a proof-of-concept that 3D primary cultures may be useful to model tumor heterogeneity. Importantly, we show that high-density 3D cultures can be used to test chemotherapy response within a 2–3-week timeframe and are predictive of patient response to Temozolomide therapy. Thus, primary high-density 3D cultures could be a useful tool for brain cancer research and prediction of therapeutic resistance.

Significance Of Tumor Giant Cells In Oral Squamous Cell Carcinoma: A Case Report

Background : Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity. OSCC presents with some typical histopathological characteristics like dysplastic epithelial cells with variable degrees of squamous differentiation. These histopathological features make it relatively easy to diagnose conventional squamous cell carcinoma. However, some cases show certain unique features that help in determining the prognosis of the disease. These features include epithelial-mesenchymal interaction, stromal hyalinization, clear cell change, stromal desmoplasia, perineural invasion, vascular invasion, tissue eosinophilia, giant cells and tertiary lymphoid follicle formation. The presence of giant cells in OSCC can be the result of foreign body reaction to keratin or due to formation of malignant tumor giant cells in poorly differentiated carcinomas. The giant cells showing pleomorphic features can be helpful in predicting the prognosis of the disease.

Sub-chronic restraint stress exposure in adult rats: An insight into possible inhibitory mechanism on testicular function in relation to germ cell dynamics.

Psychological stress is now widely recognized as one of the major risk factors for male fertility. Its impact on the dynamics of testicular germ cells, however, has yet to be fully investigated. Therefore, we used the rat restraint stress (RS) model as a psychological stressor to assess the impact of psychological stress on testicular germ cell dynamics. Adult male SD rats were exposed to sub-chronic RS for 1.5 and 3h per day for 30 days. The quality of cauda epididymis spermatozoa was adversely affected by RS exposure, and the frequency of spermatozoa with tail abnormalities was higher than that of spermatozoa with head abnormalities. RS exposure adversely affected testicular daily sperm production by disturbing the meiotic and post meiotic germ cell kinetics in the testis. The histomorphology of the testis was altered by loosening and vacuolization in the seminiferous epithelium, germ cell exfoliation and the presence of giant cells. Seminiferous tubules of stage I-VI and VII-VIII were severely affected in rats exposed to RS for 3h. By interfering with steroidogenic enzymes, RS exposure disrupts testosterone biosynthesis. The testicular oxidative balance was also disturbed by RS exposure, which disrupted the levels/activities of lipid peroxidation, Nrf-2, superoxide dismutase and catalase. There was also an increase in caspase-3 activity and a decrease in the Bax-Bcl2 ratio. In conclusion, our findings suggest that psychological stressors like RS impair testicular functions in rats by disrupting germ cell dynamics, downregulating testicular androgenesis and increasing oxidative stress and apoptosis.

Falciform ligament abscess with disseminated intrahepatic foci: a case report

BackgroundFalciform ligament abscess (FLA) is a rare disease, and its diagnosis can be challenging without typical image findings of an abscess. We report a patient with FLA that presented as a mass, with an indistinct border between it and the liver, in addition to disseminated foci within the liver. This made it difficult to determine whether it was FLA or a malignancy.Case presentationA 69-year-old man presented with epigastric pain. Contrast-enhanced computed tomography revealed a 25-mm mass below the middle of the diaphragm. Based on an initial diagnosis of infection of the falciform ligament, we administered conservative antibiotic treatment and there was initial improvement in the patient’s clinical condition and laboratory data. However, he continued to experience mild epigastric pain. A month later, imaging studies revealed enlargement of the falciform ligament mass and the emergence of a new nodule in the liver, whereas laboratory findings showed re-elevated C-reactive protein levels. Since conservative treatment had failed, we decided to perform surgery. Considering the imaging study findings, malignant disease could not be ruled out. Based on the operative findings, we performed combined resection of the falciform ligament, left liver, and gallbladder. Histopathological examination of the resected specimens revealed extensive neutrophil infiltration and the presence of giant cells and foam cells within the lesions. These findings were indicative of abscess. Pseudomonas aeruginosa was cultured from the pus in the falciform ligament mass and bile in the gallbladder. Although multiple abscesses postoperatively developed in the residual portion of the liver, they could be treated through antibiotic therapy.ConclusionsFLA can spread to both adjacent and distant organs via its rich vascular and lymphatic networks. When FLA displays atypical image findings and/or an atypical clinical course, it can be difficult to distinguish it from malignant disease. In such cases, surgical treatment, with intraoperative pathological diagnosis, should be attempted.

Prikaz rijetkog slučaja sporadične ponovne pojave kerubizma

Cherubism is a rare bone dysplasia in children characterized by symmetrical bone resorption limited only to the jaws and diagnosed as bone lesions filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. Most patients have germline mutations in the gene encoding SH3BP2, a signaling adaptor protein involved in adaptive and innate immune responses. Treatment depends on the clinical course of the disease. The current case report presents a young patient with cysts in frontal region of maxilla without family history, that had recurrences of cysts, and is representing a less documented, rare case. Histological finding at that time was indicating a giant cell granuloma and later a grey tumor. Due to the existence of other pathological findings in the jaws with the presence of giant cells, we had difficulties to diagnose cherubism as surgeons.

A novel histopathological classification of chalazion: A series of 540 cases

Introduction: A chalazion is a common localized lipogranulomatous inflammation of the eyelid. Histopathological diagnosis of chalazia is essential to rule out malignancy in particular sebaceous carcinoma. Our aim is to understand and classify the histopathological findings of chalazia and to determine any association with a patient's demographics.Materials and Methods: H and E sections were reviewed and classified into four categories: (1) lipogranulomas only, (2) lipogranulomas with multinucleated giant cells, (3) lipogranulomas with abscess, and (4) fibrosis without lipogranulomas or granulomatous inflammation. Patients' sex, age, and location of the lesion were analyzed.Results: Five hundred and forty cases included men (54.6%) and women (45.4%) with the mean age of 45.3 (13–89; standard deviation, 16.8). Five hundred and eight had information regarding location: left lower eyelid, 21.1%; right lower eyelid, 19.5%; left upper eyelid, 30.5%; and right upper eyelid, 28.9%. Category 1 accounted for 44.6%; category 2, 41.5%; category 3, 7.0%; and category 4, 6.9%. There was no significant correlation between classification and sex (P = 0.210) or age group (0–50 and > 50) (P = 0.369) nor between presence of giant cells and/or abscess and location (P = 0.826). Mean ages of category 1 (47.0) and 2 (43.1) were significantly different (P = 0.011).Conclusion: Four histopathological subtypes were equally distributed across sexes and eyelid locations. Individuals in category 1 are older than category 2. Favoring a systematic way to analyze the histopathology of chalazia may result in fewer missed diagnoses of malignancy and other inflammatory or infectious diseases.

Valuation of angiogenesis in bovine xenografts implanted in intracorporal sites of rabbits as models of in-vivo bioreactors

ABSTRACT The aim of this study was to evaluate neovascularization of bovine xenografts implanted in intracorporeal sites of rabbits (bioreactors). 30 rabbits were used, divided into 6 groups, according to the evaluation time (7, 15, 30, 45, and 60 days); each animal received xenogenic implants in 3 different intracorporeal sites (A1 - omentum bag; A2 - intermuscular space of quadriceps femoris; A3 - subperiosteal of ilium bone). Histological assessments graded the presence of angiogenesis, the number of inflammatory cells, newly formed bone tissue, and the presence of giant cells. Histological analyses showed intense angiogenesis in all implanted xenografts. Presence of inflammatory infiltrate and giant cells at the A1 implant site and presence of bone neoformation at the A3 implant site were noted. Degeneration of implants and formation of a fibrous capsule were noted. When comparing the interaction of the site with the days of evaluation, statistical analysis showed a significant difference (p≤0.05) in any time of neovascularization analysis. The vascular endothelial growth factor (VEGF) and inflammatory cells of the omentum in its structure, may have contributed to the greater presence of neovessels and inflammatory cells, a fact that may indicate functionality as a possible bone substitute.

Biopsy Confirmed Subacute Thyroiditis Associated With COVID-19

Subacute thyroiditis is a transient inflammatory disease of the thyroid associated with anterior neck pain, and systemic symptoms. The diagnosis is generally reserved for a specific type of thyroiditis characterized by granulomatous inflammation and the presence of giant cells. We hereby present a case of a woman with a COVID-19 diagnosis, and a compatible biopsy result for subacute thyroiditis.On 06/03/2020, a 28 year old woman with previous history of ankylosing spondylitis managed with certolizumab pegmol, presented with fatigue, headache, odynophagia, and fever (38.1°C). 2 days later an oropharyngeal swab (PCR) for SARS-CoV-2 turned out positive. On the 4th day the fever spiked to 39°C with added malaise. Acetaminophen 1 gr PO TID was prescribed. The patient denied dyspnea, and thorax CT-Scan was normal. Complete remission was achieved in 3 weeks. On 08/01/20 she returned to work after a negative swab test. On 08/04/20, she presented with fever (38.7°C), malaise, distal tremors, anorexia, tachycardia, myalgias, arthralgias, and fatigue. 2 days later anterior neck pain that radiated to the jaw, and diffuse goiter was noticed. A thyroid function panel reported Total T4: 24 µg/dL (4.5-12.5), fT4 5.2 ng/dl (0.8-1.8), TSH: 0.001 mUI/L (0.37-4.7), thyroglobulin 135 ng/ml (3-42). TPO-Ab <35 IU/mL and TgAb <20 IU/mL.A neck US showed increased volume in the right lobe with multiple hypoechoic regions on both lobes, and diminished vascularization at color Doppler. I-131 scan showed no uptake. A biopsy of the right lobe reported fibrosis with inflammatory infiltrate composed of lymphocytes, plasma cells, histiocytes, and scarce neutrophils. Some cells with epithelioid appearance and a multinucleated giant cell were also found. Residual thyroid follicles showed colloid depletion and degenerative changes to the epithelium, which was consistent with a diagnosis of subacute thyroiditis.Treatment was initiated with prednisone 10 mg PO QD, propranolol 20 mg PO BID for 2 weeks, and acetaminophen 1 gr PO TID PRN. Fever and pain were intermittent for 6 weeks, but the rest of the symptoms subsided within 2 weeks. On 11/15/20, the patient attended a check-up with lab results that were consistent with hypothyroidism, negative IgM, and positive IgG SARS-CoV-2. Replacement therapy with levothyroxine 88 mcg per day was initiated.This case, which confirms the diagnosis of subacute thyroiditis via biopsy, among the others reported worldwide suggests that there’s an increased risk for women for subacute thyroiditis associated with COVID-19. Further research is needed to confirm risk factors for the development of the disease.

Effects of Dietary Crude Glycerin Concentration on Testicular Morphology and Oxidative Stress Markers and on Plasma Testosterone Concentrations

We evaluated the effects of feeding 6%, 12% or 18% crude glycerin, containing 80.5% glycerol, on testicular histomorphometry and markers of oxidative stress and on plasma testosterone concentrations in lambs. Body weight, testicular biometric measurements, gonadosomatic index and net weight of the testicles were higher for the treated groups (P<0.05) compared with a control group that did not receive dietary glycerin. The mean total length of seminiferous tubules was higher in the 6% group (P<0.05), while the mean total tubular and seminiferous epithelium volumes increased in all treated groups (P<0.05). The volume of Leydig cells increased in the 12% group, while their number per gram of testicle decreased (P<0.05). There was a decrease in mean nuclear diameter and mean volume of Leydig cells, and an increase in the mean number of these cells per gram of testicle, in the 18% group (P<0.05). Plasma testosterone concentrations were unaffected. There was desquamation of seminiferous epithelium and vacuolation of Sertoli cells in the treated groups. Variable degrees of spermatocyte necrosis and the presence of giant cells were seen in all groups and there was intense vacuolation of Sertoli cells in the 12% and 18% groups. Superoxide dismutase and catalase production increased most in the 12% and 18% groups (P<0.05), while glutathione production was higher in the 18% group (P<0.05). Mean nitric oxide concentration decreased in all treated groups (P<0.05), while malondialdehyde production was higher in the 18% group than in the control and 6% groups (P<0.05). We conclude that the inclusion of 6% glycerin in the diet of lambs results in changes in testicular morphology that have been previously associated with improved reproductive function, but without evidence of oxidative stress.

Histological Evaluation of Periradicular Tissue Inflammatory Reactions and Calcified Tissue Formations After Implantation of Experimental Calcium Silicate and Hydroxyapatite Based Nanostructural Cements Into Root Canals of Rabbits Teeth

Abstract The aim of the study was to evaluate inflammatory tissue reactions and the formation of calcified tissue after implantation of experimental nanostructured calcium silicate cement (CS) and hydroxyapatite with calcium silicate cement (HA-CS) into root canals of rabbits’ teeth. The study was conducted on four rabbits of the genus Oryctolagus cuniculus. After instrumentation and irrigation, the root canals of the central incisors were dried and filled with CS, HA-CS and control material (MTA Angelus). The animals were sacrificed after 28 days. After histological preparation and hematoxylin-eosin staining, tissue samples were evaluated for the intensity and extension of inflammatory tissue reaction; continuity, morphology and thickness of the newly formed calcified tissue; and presence of giant cells, materials particles and microorganisms. Kruskal Wallis and Dunn’s post hoc test were used for data analysis (α=0.05). There were no significant differences in the intensity of inflammatory reactions between CS, HA-CS and MTA control. HA-CS showed significantly better results than MTA and CS with respect to continuity of the newly formed calcified tissue (P=0.003 and P=0.010, respectively). Significant differences in thickness of the calcified tissue existed between CS and MTA (P=0.004) and between HA-CS and MTA (P=0.012). Application of CS and HA-CS resulted in minimal inflammatory tissue response, similar to the MTA control. CS and HA-CS were more efficient than MTA in supporting hard tissue formation. The best organized newly formed calcified tissue was seen after HA-CS application.

An aggressive central giant cell granuloma of maxilla: Diagnostic dilemma, Precise differential diagnosis and successful traditional surgical approach: A case report

Abstract Central Giant Cell Granuloma (CGCG) is a benign, proliferative, intraosseous and non-odontogenic lesion of unknown etiology accounting for approximately 10% of all benign lesions of the jawbones. Lesion usually occurs in patients younger than 30 years, is more common in females than males, and is more common in mandible than maxilla. The clinical feature of CGCG ranges from a slow growing asymptomatic swelling to a rapidly enlarging aggressive lesion. CGCG of the jaws are histologically benign lesions characterized by the presence of giant cells in the richly vascularized stroma of the spindle cells. Differential diagnosis should be performed with other lesions that have multinucleated giant cells (MGCs). Definitive diagnosis relies on correct interpretation of clinical, radiographical and histopathological data. The treatment of CGCG ranges from curettage to resection. Alternative treatments are worthy of consideration, although surgical excision remains the treatment of choice. The aim of this presented case highlights a diagnostic challenge of an aggressive CGCG arising from the maxilla and to discuss a precise differential diagnosis, as well as the surgical approach and follow up which is decisive for successful conventional surgical treatment with no lesion recurrence.

INNATE IMMUNE SENSING AND TISSUE REMODELING OF A BIODEGRADABLE TEMPERING MATRIX SUPPORTED ISLET GRAFT

Introduction: The subcutaneous site represents an accessible alternative islet transplant site, but suffers from poor vascularisation. Here we test a clinically proven Biodegradable-Temporising-Matrix; NovoSorb™ (IDT) repurposed from use in burn and wound treatment that may provide a platform for subcutaneous islet-transplants. Materials and Methods: Human, neonatal porcine and murine islets were isolated using standard techniques. Islet viability & function was assessed using Annexin/Propodium iodide staining, Glucose Stimulated Insulin Secretion, ELISA and histology. Diabetes was induced using alloxan tetrahydrate i.v. in injectable grade water (20 mg/ml) at a dose of 110 mg/kg body weight. All transplants were surgically placed under the left renal capsule. Microscopy data was obtained using a Zeiss 7MP two-photon microscope. Results and Discussion: When tested in in-vitro co-culture experiments with human islets, IDT showed no impact on islet viability and function. Mouse islets were then transplanted under the renal capsule of diabetic recipients pre-implanted with IDT and resulted in complete recovery and long-term maintenance of euglycemia (>100 days). Also, neonatal porcine islets transplanted with IDT showed increasing porcine insulin production through time (>300 days). These data demonstrate that IDT is non-toxic for human, mouse and porcine islets and does not interfere with normal physiological function of islet grafts. Mice were then transplanted with IDT alone and the in-vivo foreign body reaction and tissue remodelling was assessed using transgenic (LysM-GFP+/tdTomTg) mice: blood vessels express tdTomato red and Lysozyme+ myeloid cells express GFP. Post-operative day (POD) 7 showed LysM-GFP+ myeloid cells infiltrating the graft. By POD 14, LysM-GFP+ myeloid cell-fusion events had occurred evidenced by the presence of giant cells and scattered immature vascular networks with dispersed loose collagen-fibrils. At POD 30, dendritic-like cells were observed, the vascular network was denser and the collagen fibres had increased in thickness. Further; to assess whether innate sensing of the islet graft would occur in the absence of a supportive scaffold, we transplanted islets from whole body tdTomTg mice (Tomato positive islets) into LysM-GFP/+ mice (syngeneic). 24hrs later LysM-GFP+ myeloid cells were migrating over the surface of the islets and were exhibiting neutrophil like ‘swarming’ behaviour with evident disruption of islet tissue. Conclusion: This analysis reveals that IDT can provide a neo-vascularization platform advantageous for subcutaneous islet transplantation and that there is a dynamic interaction between the innate-immune system and the syngeneic islet graft with or without IDT.

SAT-338 An Unusual Case of Brown Tumor in the Left Femur Associated with Secondary Hyperparathyroidism

Background: Brown tumor of hyperparathyroidism (BTHPT) are non-neoplastic bony lesions that arise from increased osteoclastic activity in the setting of uncontrolled hyperparathyroidism, (HPT). The prevalence is low, with a frequency of 3% in primary HPT and 2% in secondary HPT. It is rare as earlier detection and treatment of HPT prevents the progression and development of BTHPT. BTHPT is more common when HPT is untreated. BTHPT are benign tumors which usually show high 18Fludeoxyglucose-PET/CT (FDG) uptake. The mechanism of elevated FDG uptake has been suggested to be the presence of giant cells, and intracellular glucose metabolism of the macrophages may also play a role. We describe a case of a patient who presents with FDG uptake-negative BTHPT of the left femur. Clinical Case: 62-year-old male with end-stage renal disease (ESRD) and secondary HPT presented with severe left hip pain for many months. The patient had poor access to health care and had not received routine medical treatments at an outside facility prior to presentation at our facility. Laboratory studies showed PTH 1942 pg/ml (14–72), Calcium 8.7 ng/dl (8.4–10.2), phosphorus 3.6 mg/dl (2.5–4.9), Vitamin D total 19.7 ng/ml (30–140), Vit D 1,25 9 pg/ml (18–72), and creatinine 7.75 mg/dl (.66-1.28), alkaline phosphatase 57 u/L (33–94). FDG scan revealed several lucencies in the left proximal femur, with no uptake. The patient underwent left total hip arthroplasty due to impending pathological fracture. Surgical pathology revealed fragments of fibrous tissue with fibroblasts, hemosiderin and interstitial hemorrhage, consistent with brown tumor. Conclusion: We describe a unique case of BTHPT of the left femur which was the unrecognized cause of hip pain. BTHPT occurs late in the setting of HPT and is considered as a sign of poorly controlled disease. This is the first case of BTHPT to our knowledge that is not FDG-avid. This is unusual given the vascularity seen in these tumors and highlights that glucose utilization may not necessarily reflect the degree of osteoclastic activity in these tumors. Medical treatment has been shown to be sufficient in helping resolve these lesions, although the process is usually slow. Conversely, in cases of refractory disease, subtotal parathyroidectomy may be required. Our case describes an FDG-negative BTHPT, and highlights that although rare, this should be considered in the management of patients with ESRD, secondary HPT and hip pain. Patients can present with various imaging characteristics. Despite being rare, this case underscores the importance of recognition of BTHPT, so that intervention may be rendered early.