Number Of Multinucleated Giant Cells Research Articles

Case report: Systemic granulomatous disease with vasculitis in a bull due to hairy vetch (Vicia villosa) toxicosis

A 5-year-old Angus bull presented for generalized alopecia, thickened pleated skin and profuse malodorous watery diarrhea. This bull, along with 6 other beef bulls, had been grazing in a pasture containing hairy vetch (Vicia villosa) for 5-6 months. Diagnostic samples included blood for CBC and chemistry, skin biopsy and scrapings, fecal sample and liver biopsy. Biopsy of skin revealed a chronic, moderate, perivascular and perifollicular, eosinophilic to histiocytic-lymphocytic dermatitis with moderate acanthosis and hyperkeratosis indicative of an ongoing hypersensitivity reaction. The bull did not respond to treatment and was euthanized due to poor prognosis. At necropsy, disseminated systemic granulomatous disease with variable numbers of multinucleated giant cells and eosinophils was observed in multiple organs indicative of systemic granulomatous disease, along with vasculitis in the kidney, liver, and adrenal gland, indicative that vasculitis is involved in the pathogenesis of the lesions. Viral diseases were ruled out by immunohistochemistry of sections of kidney and by in situ hybridization on kidney sections. CD3, CD20, and CD79a lymphocyte markers immunostaining of sections of kidney revealed predominance of CD3 positive lymphocytes, indicative of predominance of T-cell lymphocytes supporting a type-IV hypersensitivity. The vasculitis observed prompted formulating a list of differential diagnoses for infectious diseases that have evidence of vasculitis, including bovine virus diarrhea virus and malignant catarrhal fever. Vasculitis, although previously described in cases of hairy vetch poisoning, is not observed in every single case of the disease. The remaining bulls were not removed from the pasture and none developed clinical signs.

EMD-liquid contributes to tissue thickness gain in soft tissue augmentation using a collagen matrix.

To investigate the function of enamel matrix derivative (EMD)-liquid compared to EMD-gel (original Emdogain® with polyglycolic acid-carrier) in inducing soft tissue regeneration using a rat dorsal model. Four subcutaneous pouches were created through dorsal skin incisions in 18 female Wistar rats and randomly allocated to the following groups: (1) sterile saline + non-crosslinked collagen matrix (CM), (2) EMD-gel + CM, and (3) EMD-liquid + CM. After 2 and 4weeks of healing, the specimens were harvested and stained with Goldner's trichrome, hematoxylin and eosin, and were immunohistochemically stained with an anti-CD31 antibody. The EMD-liquid group showed the thickest connective tissue compared to the other groups, with statistical significance both at 2 (p < 0.001) and 4weeks (p = 0.011 and 0.023, respectively). The number of multinucleated giant cells was not significantly different among the groups for both periods. Moreover, there was a tendency to have more blood vessels over a longer period, and the highest number of blood vessels was observed in the EMD-liquid group at 4weeks (p = 0.009 and 0036, respectively). EMD-liquid-treated CM is advantageous compared to using CM alone or EMD-gel-treated CM, owing to the histomorphometric results that show significantly increased soft tissue thickness and number of blood vessels when EMD-liquid was pre-primed to CM. EMD with a liquid carrier may be an appropriate biologic supplement to provide cell-inducing properties to the CM scaffold and is clinically more beneficial for phenotype modification therapy than CM only and EMD-gel-treated CM.

Aneurysmal Bone Cyst (ABC), A Rare Diagnosis in Oral Pathology Based on Our 15-Year Institutional Experience

Abstract Introduction/Objective Aneurysmal bone cyst (ABC) is a rare, benign bone lesion that was first described by Jaffe and Lichtenstein in 1942. Primary ABC usually affects vertebrae and metaphyseal regions of long bones, particularly femur and tibia. Only 2-3% of ABCs occur in the head and neck region, with the mandible and maxilla being the most common. It arises mostly in children and young adults, mean age 20 yo, with no gender predilection. ABC can manifest with pain, swelling, and pathological fractures. Radiographically, it appears as a metaphyseal expansile lesion that thins the cortex and has a sclerotic rim. Lesions containing “fluid-fluid” levels are best appreciated on MRI. Approximately 70% of primary ABCs have rearrangements of the USP6 gene. The most common translocation seen in primary ABCs is t(16;17) (q22;p13) leading to the fusion of the cadherin 11 gene with USP6 gene. The USP6 gene product inhibits the differentiation of osteoblasts and dysregulates bone morphogenetic protein signaling pathway. Methods/Case Report A retrospective chart review of all oral pathology cases referred to our institution between 1996 and 2022 was performed; three patients diagnosed with primary ABC were identified. Patient demographic data, clinical presentation, treatment, slides, and pathologic features were reviewed. Results (if a Case Study Enter NA) We report of three primary ABCs of the mandible and maxilla. The mean age was 39 yo (range, 26-59 years). The mandible was affected in two cases, and the maxilla involved in one. Female: Male ratio was 2:1. All lesions were primary ABC, with no other associated lesion - they showed pseudocystic structures with fibrous stroma and a variable numbers of multinucleated giant cells in relation to sinusoidal blood spaces, as well as irregular trabeculae of osteoid and reactive woven bone. Conclusion Primary ABC is a rare tumor in oral pathology. The importance of this study is to increase awareness of this neoplasm in the head and neck region, as well as delineate features that help differentiate ABCs from other fibro- osseous lesions of the mandible and maxilla.

Giant cell tumor of the bone of maxillary sinus: A rare uncommon manifestation implicated in a new mosaic of disorders?

The goal is to show a rare case of Giant Cell Tumor of Bone in the maxillary sinus implicated in a process coincidentally or casually with another type of lesion primarily developed. A 33-year-old male patient attended a surgical service, presenting swelling, obstruction and firm mass externalizing through the right nostril and perceived during 6 months. During the anamnesis, the patient stated to been underwent an incisional biopsy 4 years ago of a tumor with histopathological diagnosis of the Nasal Paraganglioma, however the immunohistochemical study was negative for this tumor. During the Computed Tomography evaluate was observed a hyperdense mass occupying the entire maxillary sinus. In the Nuclear Magnetic Resonance evaluation, it was showed a hypersignal image in the entire maxillary sinus, invading the nasal cavity and portion of skull base. A bone window was performed in the right maxillary sinus and excisional biopsy was made. In the new histopathological examination, the diagnose was consistent with Giant Cell Tumor of Bone, being observed a large number of multinucleated giant cells, some with disorganized nuclei and others similar to Touton giant cells. A large proliferation of xanthomatous-looking cells was also observed without features of malignity. At the 3-year follow-up, the patient reported no complications such as facial paralysis, infection, relapse or spread. The association between lesions occurring in the same location requires further study, possibly implicated in a new model of clinical, microscopic, and genetic disorders. Thus, masses originating from chronic inflammatory tissue may have the potential to transform into GCTB?

Vaccine-Induced Subcutaneous Granulomas in Goats Reflect Differences in Host-Mycobacterium Interactions between BCG- and Recombinant BCG-Derivative Vaccines.

Tuberculous granulomas are highly dynamic structures reflecting the complex host–mycobacterium interactions. The objective of this study was to compare granuloma development at the site of vaccination with BCG and its recombinant derivatives in goats. To characterize the host response, epithelioid cells, multinucleated giant cells (MNGC), T cell subsets, B cells, plasma cells, dendritic cells and mycobacterial antigen were labelled by immunohistochemistry, and lipids and acid-fast bacteria (AFB) were labelled by specific staining. Granulomas with central caseous necrosis developed at the injection site of most goats though lesion size and extent of necrosis differed between vaccine strains. CD4+ T and B cells were more scarce and CD8+ cells were more numerous in granulomas induced by recombinant derivatives compared to their parental BCG strain. Further, the numbers of MNGCs and cells with lipid bodies were markedly lower in groups administered with recombinant BCG strains. Microscopic detection of AFB and mycobacterial antigen was rather frequent in the area of central necrosis, however, the isolation of bacteria in culture was rarely successful. In summary, BCG and its recombinant derivatives induced reproducibly subcutaneous caseous granulomas in goats that can be easily monitored and surgically removed for further studies. The granulomas reflected the genetic modifications of the recombinant BCG-derivatives and are therefore suitable models to compare reactions to different mycobacteria or TB vaccines.

Osteoclastic variant of anaplastic thyroid carcinoma: An insight into a rarest of rare entity.

Anaplastic thyroid carcinoma is a rare and a very aggressive thyroid malignancy with a dismal prognosis. It has a short history and presents with a rapidly increasing neck mass associated with compressive symptoms like pain, hoarseness of voice, dysphagia and shortness of breath. Osteoclastic variant is an extremely rare variant, which is, characterize by presence of a large number of multinucleated giant cells, which resemble osteoclasts. Here we report two cases of this unusual variant in a 68 years old and 49 years old male with a short history of thyroid swelling.

A case of diffuse large B-cell lymphoma with a large number of multinucleated giant cells

A case of diffuse large B-cell lymphoma with a large number of multinucleated giant cells

Tenosynovial giant cell tumor.

Tenosynovial Giant Cell Tumor (TGCT) is a group of typically benign lesions arising from the synovium of joints, bursae and tendon sheaths. Depending on their growth pattern and clinical course, they are divided into localized and diffuse types. It is predominantly caused by a mutation in the stromal cells of the synovial membrane leading to overexpression of the colony stimulating factor 1 that recruits CSF1R-expressing cells of the mononuclear phagocyte lineage into the tumor mass. The lesions contain mainly histiocyte-like and synovial cells accompanied by varying numbers of multinucleated giant cells, mononuclear cells, foam cells, inflammatory cells and hemosiderin deposits. The gold standard for detect- ing and monitoring the disease is MRI, where the characteristic hemosiderin accumulation can be best appreciated, but it is a histological examination that is most conclusive. The main treatment is surgical resection of all pathological tissue, but radio- and chemotherapy are also viable options for certain groups of patients.

The Granule Size Mediates the In Vivo Foreign Body Response and the Integration Behavior of Bone Substitutes.

The physicochemical properties of synthetically produced bone substitute materials (BSM) have a major impact on biocompatibility. This affects bony tissue integration, osteoconduction, as well as the degradation pattern and the correlated inflammatory tissue responses including macrophages and multinucleated giant cells (MNGCs). Thus, influencing factors such as size, special surface morphologies, porosity, and interconnectivity have been the subject of extensive research. In the present publication, the influence of the granule size of three identically manufactured bone substitute granules based on the technology of hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which includes the inflammatory response in the surrounding tissue and especially the induction of MNGCs (as a parameter of the material degradation). For the in vivo study, granules of three different size ranges (small = 0.355–0.5 mm; medium = 0.5–1 mm; big = 1–2 mm) were implanted in the subcutaneous connective tissue of 45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials were explanted and histologically processed. The defect areas were initially examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages were quantified histomorphometrically after their immunohistochemical detection. The number of MNGCs was quantified as well using a histomorphometrical approach. The results showed a granule size-dependent integration behavior. The surrounding granulation tissue has passivated in the groups of the two bigger granules at 60 days post implantationem including a fibrotic encapsulation, while a granulation tissue was still present in the group of the small granules indicating an ongoing cell-based degradation process. The histomorphometrical analysis showed that the number of proinflammatory macrophages was significantly increased in the small granules at 60 days post implantationem. Similarly, a significant increase of MNGCs was detected in this group at 30 and 60 days post implantationem. Based on these data, it can be concluded that the integration and/or degradation behavior of synthetic bone substitutes can be influenced by granule size.

The Aryl Hydrocarbon Receptor Suppresses Chronic Smoke-Induced Pulmonary Inflammation.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in the lungs that is activated by numerous xenobiotic, endogenous and dietary ligands. Although historically the AhR is known for mediating the deleterious response to the environmental pollutant dioxin, emerging evidence supports a prominent role for the AhR in numerous biological process including inflammation. We have shown that the AhR suppresses pulmonary neutrophilia in response to acute cigarette smoke exposure. Whether the AhR can also prevent lung inflammation from chronic smoke exposure is not known but highly relevant, given that people smoke for decades. Using our preclinical smoke model, we report that exposure to chronic cigarette smoke for 8-weeks or 4 months significantly increased pulmonary inflammation, the response of which was greater in Ahr−/− mice. Notably, there was an increased number of multinucleated giant cells (MNGCs) in smoke-exposed Ahr−/− mice without a change in cytokine levels. These data support a protective role for the AhR against the deleterious effects of cigarette smoke, warranting continued investigation into its therapeutic potential for chronic lung diseases.

Dysfunction in Sertoli cells participates in glucocorticoid-induced impairment of spermatogenesis.

The effect of stress on male fertility is a widespread public health issue, but less is known about the related signaling pathway. To investigate this, we established a hypercortisolism mouse model by supplementing the drinking water with corticosterone for four weeks. In the hypercortisolism mice, the serum corticosterone was much higher than in the control, and serum testosterone was significantly decreased. Moreover, corticosterone treatment induced decrease of sperm counts and increase of teratozoospermia. Increased numbers of multinucleated giant cells and apoptotic germ cells as well as downregulated meiotic markers suggested that corticosterone induced impaired spermatogenesis. Further, upregulation of macrophage-specific marker antigen F4/80 as well as inflammation-related genes suggested that corticosterone induced inflammation in the testis. Lactate content was found to be decreased in the testis and Sertoli cells after corticosterone treatment, and lactate metabolism-related genes were downregulated. In vitro phagocytosis assays showed that the phagocytic activity in corticosterone-treated Sertoli cells was downregulated and accompanied by decreased mitochondrial membrane potential, while pyruvate dehydrogenase kinase-4 inhibitor supplementation restored this process. Taken together, our results demonstrated that dysfunctional phagocytosis capacity and lactate metabolism in Sertoli cells participates in corticosterone-induced impairment of spermatogenesis.

SURGICAL TREATMENT OF EXTENSIVE INTRAORAL DERMOID CYST: CASE REPORT

The aim of the present work is to report a rare case of extensive intraoral dermoid cyst in a female patient, 54 years old, who complained of volume increase at the floor of the mouth. The extraoral physical examination showed submental swelling. The intraoral examination revealed a tumor, presenting mobility and sessile base. An excisional biopsy was performed and the specimen was sent to anatomopathological analysis. Histologic sections revealed fragments of cystic capsules coated with orthokeratinized stratified squamous epithelium exhibiting hyperkeratosis, with intense accumulation of intraluminal keratin. Capsular connective tissue was dense and permeated by foci of intense mononuclear inflammatory infiltrate, and large numbers of multinucleated giant cells. Cutaneous attachments such as sebaceous glands are observed. The patient is in clinical follow-up and she has no complaints or signs of recurrence. Dermoid cysts are rare lesions in the oral cavity, but their presence may lead to dysphagia, dysphonia, and masticatory difficulties.

The NAD+ Responsive Transcription Factor ERM-BP Functions Downstream of Cellular Aggregation and Is an Early Regulator of Development and Heat Shock Response in Entamoeba.

Entamoeba histolytica is a protozoan parasite and a major cause of dysentery and diarrheal disease in developing countries. Disease transmission from one host to another occurs via cysts which can survive in environmental extremes and are transmitted through contaminated food and water. Recent studies in our lab identified a novel transcription factor, Encystation Regulatory Motif- Binding Protein (ERM-BP), which is responsive to NAD+ and has an important role in encystation. The key residues important for ERM-BP function were demonstrated in vitro using recombinant protein. In this study we demonstrate the in vivo functional consequences of mutations in key domains and their impact on Entamoeba encystation. Our results show that mutations in the DNA binding domain (ERM-BP-DBM) and in the nicotinamidase domain (ERM-BP-C198A) lead to protein mis-localization in both trophozoites and cysts and significantly reduce encystation efficiency. Additionally, we showed that silencing of ERM-BP significantly decreased the size and number of multi-nucleated giant cells (MGC) that form during encystation, indicating that ERM-BP functions upstream of the cellular aggregation that precedes stage conversion. Dissection of epistatic interactions between ERM-BP and a second encystation-related transcription factor, NF-Y revealed that ERM-BP is upstream of NF-Y in controlling the developmental cascade and appears to be one of the earliest regulators of development identified to date in Entamoeba. We also demonstrated that ERM-BP is upregulated during heat stress in Entamoeba, another condition which increases intracellular NAD+ levels and that overexpression of ERM-BP makes E. histolytica and E. invadens parasites more resistant to heat stress. Overexpression of ERM-BP in E. histolytica also induced the formation of cyst-like quadrinucleated cells and formation of MGCs. Overall, our work has identified an important role of ERM-BP in Entamoeba stress response and links an NAD+-responsive transcription factor to both development and heat shock response. Characterization of stress and developmental cascades are important avenues to investigate for Entamoeba, an important human parasitic pathogen.

Cytological and Histopathological Correlation of Feline Giant Cell-Rich Osteosarcoma

Background: Primary bone tumours are uncommon and poorly reported in cats but osteosarcoma (OSA) is the most frequent, mostly in elderly animals. Giant cell-rich OSA is considered rare in the literature representing 3% of all OSA in humans. The mitotic index seems to have a significant effect on the survival time of cats affected by this neoplasm as well as the tumour histopathological grade. The objective of this study was to report the cytological and histopathological findings of a giant cell rich OSA in a 4-year old cat with persistent feline leukemia virus (FeLV) antigenaemia.Case: A 4-year-old male neutered cat was referred with a history of persistent FeLV viraemia and pelvic limb lameness with a firm swelling. Previous radiographs of the affected limb revealed bone lysis in the third and fourth metatarsals and increased soft tissue radiopacity in the tarsal region. The referral veterinary assumed it to be osteomyelitis and initiated clinical treatment with antibiotic and anti-inflammatory. The cat was referred after there was no response to medical treatment. The cat was presented with a 5cm diameter ulcerated mass, with putrid odor in the pelvic limb. Complementary exams were performed, and abnormalities were found, including increased urea, creatinine, calcium and potassium, and decreased sodium and phosphorus. A new radiograph showed exuberant bone proliferation, with increased radiopacity involving tarsal, metatarsal, distal third of tarsal I and II, and distal diaphysis of metatarsal V, without compromising the metaphyseal region of distal diaphysis of metatarsal IV. Chest radiographs and abdominal ultrasound were unremarkable. Fine-needle aspiration was performed for cytological analysis, which reavealed a moderate amount of pleomorphic mesenchymal cells with moderate adhesion, cytoplasm with a format ranging from fusiform to stellate, pronounced anisocytosis and cellular pleomorphism, and elevated nucleus:cytoplasm ratio. Nucleus was oval and presented loose chromatin, single to double large and evident nucleolus, frequent karyomegaly, along with marked anisocariosis and nuclear pleomorphism. Multinucleated giant cells were and there was a single mitotic figure in 12 high power fields (0.196 mm2 FN20/400x). Therefore, it was suggestive of malignant mesenchymal neoplasia with possibility of OSA, fibrosarcoma oe undifferentiated sarcoma. Limb amputation with femoral disarticulation was performed uneventfully. The material was conserved in 10% formalin, submitted to macroscopic and microscopic evaluation, which showed a large number of fusiform and stellate cells, with indistinct edges, scarce eosinophilic cytoplasm, high nucleus:cytoplasm ratio and oval nucleus, presenting moderate to marked anisocariosis, loose chromatin, with unique and evident nucleoli, besides of bone trabeculae. Nuclear pleomorphism was moderate and there was four mitotic figures in three random high-power fields (400x). It was observed areas of vascular ectasia, and neoplastic embolization in lymphatic and blood vessels. Among the cells, collagenous stroma was predominant but in some areas there was an eosinophilic amorphous material with the possibility of osteoid matrix or collagen. There was also a large numbers of multinucleated giant cells. The histopathological result was compatible with a grade III giant cell rich OSA.Discussion: Although bone tumours are uncommon in cats, OSA is the most frequent, affecting maingly middle-aged to elderly cats, with a mean age of 10 years, which is different from the present report in a 4-year old cat, with FeLV persistent viraemia. Retroviral status may have influenced the development of the disease at na early onset. FeLV induces uncontrolled cell proliferation through insertional mutagenesis (usually near myc) inducing malignant neoplasias, mainly lymphoma, but also multiple cartilaginous exostosis, which, along with osteomyelitis and bone cyst were included in this patient´s list of differential diagnoses. Despite the macroscopic and radiographical andagressiveness there was no metastasis identified through chest radiographs or abdominal ultrasound, and feline OSA is associated with a lower metastatic rate, if compared to canine OSA. Cytological analysis was compatible with malignant mesenchymal neoplasia, being suggestive of giant cell rich OSA. There is no cytological classification for OSA, however cytological findings of malignancy may be correlated with the patient's clinical course. Cytological features were in agreement with the histopathological findings, compatible with a grade III giant cell rich OSA. Therefore, it is concluded that the characteristics of malignancy presented by cytology were sufficient for the recommendation of amputation of the affected limb, once there was no imaging sign of metastases in the chest or abdomen.

Hemophagocytic Histiocytic Sarcoma in Dog

Background: Histiocytic sarcoma can present in a localized or disseminated form, being a malignant neoplasm derived from interstitial dendritic cells. Another form of the disease is called hemophagocytic histiocystic sarcoma (HHS), which originates from macrophages located in the splenic red pulp and bone marrow. HHS is a rare neoplasm with unknown etiology and rapid development. It mainly affects middle-aged to elderly animals. It primarily affects the spleen and bone marrow, with occurence of metastases in other organs. Some canine breeds are considered more predisposed to this neoplasia, among them the Rottweiler. The aim of this study was to report a case of HHS in a Rottweiler dog.Case: An 8-year-old Rottweiler suffering from hyporexia and progressive weight loss for a month was attended at the Veterinary Hospital of State University of Maringá. On physical examination, he only presented mild discomfort on abdominal palpation. Blood count was performed, which revealed mild thrombocytopenia (145,000/µL, reference value for the species 150,000-500,000/µL). The Polymerase Chain Reaction (PCR) exam was requested for babesiosis and ehrlichiosis, due to a history of ectoparasites. The animal was released with the prescription of Doxycycline at a dose of 10 mg/kg orally for 28 days. After 5 days, the condition worsened and the animal returned with emesis, apathy and hyporexia, being hospitalized. Abdominal ultrasound, blood count, urinalysis, serum urea and creatinine tests were requested. Among the hematological changes, thrombocytopenia (116,000/µL) and the appearing of regenerative anemia and atypical round cells with ample and slightly basophilic cytoplasm in the smear, similar to histiocytes, stood out. On ultrasound examination, splenomegaly was observed with hypoechogenic areas. Ultrasound-guided fine-needle aspiration cytology (FNAC) of the spleen was performed, which revealed the presence of abundant cellularity consisting of round cells arranged individually and in small groups, with variable nucleus / cytoplasm ratio, slightly basophilic cytoplasm and, sometimes, vacuolized. Eccentric nucleus with chromatin ranging from loose to dense, with evident and often multiple nucleus. In addition, a large number of multinucleated giant cells, mitosis figures (sometimes atypical) and intense anisocytosis and anisocariosis were observed. Furthermore, it was possible to observe erythrophagocytic activity, alterations compatible with histiocytic sarcoma (HS). After 10 days of the first visit, the animal died. At necropsy, samples from altered areas of the spleen, lungs and lymph nodes were collected and sent for histopathological and immunohistochemical examination, in which the diagnosis of hemophagic histiocytic sarcoma was confirmed, in addition to lungs and lymph node metastasis.Discussion: The prognosis of HHS is the worst among histiocytic disorders, as it is associated with coagulopathies and severe anemia due to erythrophagocytic activity, as occurred in the case presented, with a maximum survival time between one to two months. The described animal died ten days after showing the first clinical signs. The immunohistochemistry technique using HLA-DR, CD18, CD163, and CD11d markers was essential to confirm the cell line. Positivity for CD11d marker was found, which allowed to classify the neoplasm as hemophagocytic HS. This report exposes the importance of cytological examination for screening and histopathological and immunohistochemical tests to confirm the diagnosis of this extremely aggressive neoplasm.

GIANT CELL TUMOR IN SINUS MAXILLARY AND NASAL CAVITY: A RARE CASE REPORT

A 33-year-old male patient attended a surgical service reporting a swelling in the right nasal cavity for around 6 months. Magnetic resonance imaging showed a hypointense image on the upper wall of the right maxillary sinus invading the nasal cavity of the same side. There was a previous biopsy in the same region with an inconclusive diagnosis. The patient was submitted to excisional biopsy, and the surgical specimen was referred for a pathologic service with clinical suspicion of paraganglioma. Histopathologic examination evidenced a lesion characterized by proliferation of vascular spaces and fibroblastic cells with discrete collagen fibers and areas of hemorrhage surrounded by a large number of multinucleated giant cells, some with disorganized nuclei and others similar to Touton giant cells. A large proliferation of xanthomatous-looking cells was also observed. The diagnosis of giant cell tumor was established. Currently the patient is under follow-up with no signs of relapse. A 33-year-old male patient attended a surgical service reporting a swelling in the right nasal cavity for around 6 months. Magnetic resonance imaging showed a hypointense image on the upper wall of the right maxillary sinus invading the nasal cavity of the same side. There was a previous biopsy in the same region with an inconclusive diagnosis. The patient was submitted to excisional biopsy, and the surgical specimen was referred for a pathologic service with clinical suspicion of paraganglioma. Histopathologic examination evidenced a lesion characterized by proliferation of vascular spaces and fibroblastic cells with discrete collagen fibers and areas of hemorrhage surrounded by a large number of multinucleated giant cells, some with disorganized nuclei and others similar to Touton giant cells. A large proliferation of xanthomatous-looking cells was also observed. The diagnosis of giant cell tumor was established. Currently the patient is under follow-up with no signs of relapse.

The presence of multinucleated giant cells: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features vs the follicular variant of papillary thyroid carcinoma.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly described entity with an indolent clinical course as compared to the follicular variant of papillary thyroid carcinoma (FVPTC). As the cytologic features of NIFTP overlap those of the FVPTC, distinction between the two on FNA cytology poses diagnostic difficulties. This study analyzes the presence of multinucleated giant cells (MGCs). Twenty histologically confirmed NIFTP cases and 17 FVPTC cases each with a prior FNA and performed over a 2-year period were reviewed, the cytologic diagnoses compared and the number of MGCs counted. Of the 20 NIFTP cases, 55% were diagnoses as FLUS on FNA, 25% as FN/SFN and 10% as SPTC. Of the 17 FVPTC cases, 12% were diagnosed as FLUS, 53% as FN/SFN and 35% as SPTC. Fifteen (88%) FVTPC cases contained MGCs, whereas none of the 20 NIFTP cases contained MGCs. The presence or absence of MGCs may serve as an additional finding to differentiate NIFTP cases from FVTPC cases.

Comparison of High‐Hydrostatic‐Pressure Decellularized Versus Freeze‐Thawed Porcine Menisci

The meniscus functions as a load distributor and secondary stabilizer in the knee, and the loss of the meniscus increases the risk of osteoarthritis. Freeze-thawed menisci are used in clinical practice to replace defective menisci; however, the disadvantages of freeze-thawed tissues include disease transmission and immune rejection. In this study, we decellularized menisci using high hydrostatic pressure (HHP) and compared the decellularized menisci with freeze-thawed menisci. Porcine menisci were either pressurized at 1,000 MPa for 10 min and then washed with DNase solution or frozen at -80°C for 2 days and thawed. These menisci then underwent in vitro histological, biochemical, and biomechanical comparisons with native menisci. The HHP-treated and freeze-thawed menisci were also subcutaneously implanted in a pig, and later harvested for histological analysis. The numbers of histologically detected cells were significantly lower and the amount of biochemically detected DNA was approximately 100-fold lower in HHP-treated than in native and freeze-thawed menisci. The compression strength of the HHP-decellularized menisci was decreased after 1 and 50 cycles at 20% strain but was unchanged in the freeze-thawed menisci. After implantation, the numbers of multinucleated giant cells were significantly lower around the HHP-treated menisci than around the freeze-thawed menisci. Recellularization of the HHP-decellularized menisci was confirmed. Thus, although the HHP-decellularized menisci were mechanically inferior to the freeze-thawed meniscus in vitro, they were immunologically superior. Our study is the first to demonstrate the use of HHP for decellularization of the meniscus. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2466-2475, 2019.

Multiwell three-dimensional systems enable in vivo screening of immune reactions to biomaterials: a new strategy toward translational biomaterial research.

In vivo experiments are accompanied by ethical issues, including sacrificing a large number of animals as well as large costs. A new in vivo 3D screening system was developed to reduce the number of required animals without compromising the results. The present pilot study examined a multiwell array system in combination with three different collagen-based biomaterials (A, B and C) using subcutaneous implantation for 10 days and histological and histomorphometrical evaluations. The tissue reaction towards the device itself was dominated by mononuclear cells. However, three independent biomaterial-specific tissue reactions were observed in three chambers. The results showed a mononuclear cell-based tissue reaction in one chamber (A) and foreign body reaction by multinucleated giant cells in the other two chambers (B and C). Statistical analysis showed a significantly higher number of multinucleated giant cells in cases B and C than in case A (A vs. B; ***P < 0.001), (A vs. C; P < 0.01). These outcomes were comparable to previously published observations with conventional biomaterial implantation. The present data lead to the conclusion that this 3D screening system could be an alternative tool to enhance the effectiveness of in vivo experiments, thus offering a more economic strategy to screen biomaterial-related cellular reactions, while saving animals, without influencing the final outcome.

Tissue response to porous high density polyethylene as a three-dimensional scaffold for bone tissue engineering: An experimental study

High density polyethylene (HDPE) is a synthetic biomaterial used as a three-dimensional scaffold for bone defect reconstruction. Reports differ with regard to its biological response, particularly its osteoconductive capacity. The aim of the present work was to histologically and histomorphometrically evaluate tissue response to porous HDPE. An in vivo study was conducted in rat tibia to evaluate osteogenic capacity, angiogenesis, inflammatory response, and the presence of multinucleated giant cells 14 and 60 days post-biomaterial implantation. Histological examination 14 days post-implantation showed fibrovascular tissue inside pores and on the surface of porous HDPE, acute inflammatory response, scant multinucleated giant cells (MNGCs), and lamellar bone in contact with the biomaterial. An increase in the proportion of lamellar bone tissue, no inflammatory response, and a decrease in the number of MNGCs were observed at 60 days. The histomorphometric study showed a significant time-dependent increase both in the area of bone tissue formed in contact with the porous HDPE (14d: 24.450 ± 11.623 µm2 vs. 60d: 77.104 ± 26.217 µm2, p < 0.05) and in the percentage of bone tissue in contact with the porous HDPE (osseointegration). A significant decrease in the number of MNGCs was also observed at 60 days post-implantation. Porous HDPE showed adequate osteoconductive properties, and only caused an initial inflammatory response. Although this biomaterial has traditionally been used juxtaosseoulsy, its adequate osteoconductive properties broaden the scope of its application to include intraosseous placement.