Number Of Multinucleated Giant Cells Research Articles

Anti-tumor necrosis factor treatment in cherubism — Clinical, radiological and histological findings in two children

Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype.We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated.Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism.

Bilateral intraventricular mass in a child

An 8-year-old boy presented with a history of holocranial headache for 4 weeks which was mild to moderate in intensity. There was history of intermittent vomiting for the same duration. The patient was drowsy for the last 10 days. Non-contrast CT scan of head showed a space-occupying lesion in lateral ventricles with hydrocephalus. MRI showed a large lobulated well-defined heterogeneous mass lesion filling up both lateral ventricles at the posterior and temporal horns, bilaterally reaching up to the level of the foramen magnum. The mass lesion was hypointense on T2-weighted images (T2W) and isointense to grey mater on T1W images. On contrast images there was intense homogeneous enhancement seen at the lesion (Fig. 1). Right fronto-temporo-parietal craniotomy with decompression of the tumor was performed. Perioperatively, the tumor was yellowish in color, firm, not able to be aspirated and minimally vascular. Clinical diagnosis of choroid plexus tumor was considered.

Osteoconductive Properties of β-Tricalcium Phosphate Matrix, Polylactic and Polyglycolic Acid Gel, and Calcium Phosphate Cement in Bone Defects

Extensive bone defects in maxillofacial region can be corrected with autogenous grafts; otherwise, the disadvantages of the therapeutics modality take the research for new bone substitutes. The aim of the study was to evaluate and compare the osteoconductive properties of 3 commercial available biomaterials. A total of 30 calvarial defects (5-mm diameter) were randomly divided into 5 treatment groups, with a total of 6 defects per treatment group (n = 6). The treatment groups were as follows: 500 to 1000 μm β-tricalcium phosphate (β-TCP), polylactic and polyglycolic acid (PL/PG) gel, calcium phosphate cement, untreated control, and autograft control. The evaluations were based on histomorphometric analysis at 60 postoperative days. The results have shown that β-TCP and autograft control supported bone formation at 60 postoperative days. β-Tricalcium phosphate showed the highest amount of mineralized area per total area and statistically significant compared with PL/PG, calcium phosphate cement, and untreated control groups. The PL/PG gel does not have osteoconductive properties and performed similar to empty control. Calcium phosphate cement showed higher number of multinucleated giant cells around the sites of the biomaterial and showed newly formed bone only at the edges of the biomaterial, without bone formation within the biomaterial. The findings presented herein indicate that bone formation reached a maximum level when rat calvarial defects were filled with β-TCP at 60 postoperative days. Further studies should be conducted with β-TCP to understand the potential of this biomaterial in bone regeneration.

Comparative Pathology of the Natural infections byMycobacterium bovisand byMycobacterium capraein Wild Boar (Sus scrofa)

The potential role of wild animals in the maintenance and spread of tuberculosis (TB) infection in domestic livestock is of particular importance in countries where eradication programs have substantially reduced the incidence of bovine tuberculosis but sporadic outbreaks still occur. Mycobacterium bovis is the agent mainly isolated in wildlife in Spain, but recently, infections by Mycobacterium caprae have increased substantially. In this study, we have analysed 43 mandibular lymph nodes samples containing TB-like lesions from 43 hunted wild boar from Madrid and Extremadura (central and south-western regions of Spain). After isolation, identification and typing of Mycobacterium tuberculosis complex isolates, we found that 23 mandibular lymph nodes involved M. caprae infections and 20 M. bovis. The lesions were compared for histopathology (different granuloma stage and number of multinucleated giant cells (MNGCs)), and acid-fast bacilli (AFBs) were quantified in the Ziehl-Neelsen-stained slides. Granulomas produced by M. caprae showed more stage IV granulomas, more MNGCs and higher AFBs counts than those induced by M. bovis. In conclusion, lesions caused by M. caprae would be more prone to the excretion of bacilli, and infected animals result as a high-risk source of infection for other animals.

Clinical and Histologic Features of 26 Canine Peripheral Giant Cell Granulomas (Formerly Giant Cell Epulis)

Clinical and histologic features of 26 cases of canine peripheral giant cell granuloma (formerly giant cell epulis) are reported. Two main histologic categories were evident: (1) "classic" peripheral giant cell granuloma, characterized by variable numbers of multinucleated giant cells (MNGCs) admixed with densely cellular mononuclear spindle-shaped cells in variable amounts of collagenous matrix, and (2) the "collision" peripheral giant cell granuloma, with features of both a peripheral giant cell granuloma and a fibromatous epulis of periodontal ligament origin. In the 16 dogs for which the outcome was known, 2 peripheral giant cell granulomas recurred after excision. No age or sex predilection was evident; however, lesions were more common in maxillary than in mandibular gingiva. In contrast to cats, peripheral giant cell granulomas in dogs behave like fibromatous epulides of periodontal ligament origin and seldom recur after excision. Positive staining with TRAP (tartrate-resistant acid phosphatase) of the MNGCs and a fraction of the mononuclear cell population is consistent with osteoclastic origin.

Primary ureteral giant cell sarcoma in a Pomeranian

An 8-year-old male neutered Pomeranian dog was presented to the Veterinary Teaching Hospital at Oregon State University for surgical treatment of hydronephrosis of the left kidney and a left cranial abdominal mass. A primary ureteral mass was found during exploratory surgery, and the mass was resected and ureteral anastomosis was performed. Cytologic evaluation of the mass revealed 3 distinct cell populations, including a large number of multinucleated giant cells, a moderate number of thin spindle-shaped cells, and cohesive clusters of transitional epithelial cells. The cytologic diagnosis was giant cell sarcoma. The diagnosis was confirmed by histologic examination, and immunohistochemical staining was performed. The spindle-shaped cells and multinucleated giant cells were both immunoreactive for vimentin and spindle-shaped cells for S-100. Tumor cells did not express wide-spectrum cytokeratin, broad-spectrum muscle actin, smooth muscle actin, sarcomeric actin, desmin, BLA36, Mac 387, synaptophysin, neuron-specific enolase, glial fibrillary acid protein, or von Willebrand factor. These findings are most consistent with an anaplastic sarcoma with giant cells. This is the first case report of a primary ureteral giant cell sarcoma in a dog.

下顎小臼歯部に発生した骨形成を伴う巨細胞エプーリスの1例

Giant cell epulis (peripheral giant cell granuloma) is a granuloma consisting of a large number of multinucleated giant cells. Its incidence is high in Europe and the United States, but is very low in Japan. Giant cell epulis accompanied by bone formation is extremely rare in Japan. We report a case of giant cell epulis accompanied by bone formation. A 46-year-old woman visited our hospital because of a mass in the left mandibular molar region. There was a well-demarcated, pedunculated mass in the left mandibular molar region. The mass was excised under the clinical diagnosis of epulis. Histopathologically, the resected specimen consisted of spindle cells resembling fibroblasts and many multinucleated giant cells. Moreover, newly synthesized bone was observed in the center of the mass. The pathological diagnosis was a giant cell granuloma. Two years six months after the operation, there has been no evidence of recurrence.

Intracranial Aspergillus Granuloma

Intracranial fungal granulomas are rare and of the histologically verified granulomas, Aspergillus spp. is the commonest causative fungal pathogen. Most of the reported large series of aspergillus granulomas are from countries with temperate climate like India, Pakistan, Sudan, and Saudi Arabia. In contrast to disseminated aspergillosis that occurs in immunosuppressed individuals, most of the intracranial aspergillus granulomas are reported in immunocompetent individuals. The temperature, humidity, high spore content in the atmosphere during ploughing, and occupation as agricultural worker are implicated in the pathogenesis. The sinocranial spread is the most common route of intracranial extension. Extracerebral firm fibrotic lesions and skull base lesions are common. Extensive fibrosis and large number of multinucleated giant cells are the characteristic histological features and these pathological features have therapeutic relevance.

Lack of cathepsin activities alter or prevent the development of lung granulomas in a mouse model of sarcoidosis

BackgroundRemodeling of lung tissues during the process of granuloma formation requires significant restructuring of the extra-cellular matrix and cathepsins K, L and S are among the strongest extra-cellular matrix degrading enzymes. Cathepsin K is highly expressed in various pathological granulomatous infiltrates and all three enzymes in their active form are detected in bronchoalveolar lavage fluids from patients with sarcoidosis. Granulomatous inflammation is driven by T-cell response and cathepsins S and L are actively involved in the regulation of antigen presentation and T-cell selection. Here, we show that the disruption of the activities of cathepsins K, L, or S affects the development of lung granulomas in a mouse model of sarcoidosis.MethodsApolipoprotein E-deficient mice lacking cathepsin K or L were fed Paigen diet for 16 weeks and lungs were analyzed and compared with their cathepsin-expressing littermates. The role of cathepsin S in the development of granulomas was evaluated using mice treated for 8 weeks with a potent and selective cathepsin S inhibitor.ResultsWhen compared to wild-type litters, more cathepsin K-deficient mice had lung granulomas, but individually affected mice developed smaller granulomas that were present in lower numbers. The absence of cathepsin K increased the number of multinucleated giant cells and the collagen content in granulomas. Cathepsin L deficiency resulted in decreased size and number of lung granulomas. Apoe-/- mice treated with a selective cathepsin S inhibitor did not develop lung granulomas and only individual epithelioid cells were observed.ConclusionsCathepsin K deficiency affected mostly the occurrence and composition of lung granulomas, whereas cathepsin L deficiency significantly reduced their number and cathepsin S inhibition prevented the formation of granulomas.

Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison

EXPAREL (bupivacaine extended-release liposome injection), DepoFoam bupivacaine, is in development for prolonged postsurgical analgesia. Repeat-dose toxicity studies were conducted in rabbits and dogs to compare the potential local and systemic toxicities of EXPAREL and bupivacaine HCl (Bsol), and the reversibility of any effects. Dogs tolerated much larger doses than rabbits. EXPAREL-related minimal-to-moderate granulomatous inflammation was noted at the injection sites. In recovery animals, the granulomatous inflammation was observed less frequently and was characterized by an increased number of multinucleated giant cells. These effects were considered a normal response to liposomes and nonadverse. Rabbits are more sensitive than dogs. In rabbits, convulsions were noted with EXPAREL and more frequently with Bsol; a NOAEL was not identified. In dogs, EXPAREL was well tolerated (NOAEL > 30 mg/kg/dose). The cumulative exposure of EXPAREL in these studies is well in excess of the proposed maximum single-dose exposure that is intended in humans.

Abstract 3414: EMT-associated genes are altered in giant cell tumor of bone

Abstract The giant cell tumor of bone (GCT) is a benign bone-destructive neoplasm, with uncertain biological behavior, with features such as a large number of multinucleated giant cells and aggressive behavior. The local recurrence of GCT is often observed, especially in the first three years after treatment, giving a rate of recurrence ranging from 20% to 50% of cases. Further aggravating the recurrence, is the fact that after a relapse, patients often also presents metastasis in other organs, mainly in the lungs. In this study we investigate the expressions of epithelial and mesenchymal (EMT) markers (ADAM23, CDH1, CDH3, MMP14, p16, TIMP2 and VIM) in GCTs by quantitative qPCR. The expression of the MMP14, TIMP2 and VIM genes increased in more than 96% samples and ADAM23, CDH1, CDH3 and p16 genes had expression reduced in more than 91% of GCTs samples. Since ADAM23, CDH1, CDH3 and p16 have CpG islands in their promoter regions and low expression in tumor tissue, their methylation patterns were analyzed by MSP-PCR. For ADAM23 and p16 genes were detected a high frequency of hypermethylation. The lower expression of ADAM23 and p16 are directly related to the recurrence and metastasis in GCTs. The genes MMP14, TIMP2 and VIM are related to angiogenesis, degradation of extracellular matrix and cell migration and presented with increased expression in GCT, also confirmed by immunohistochemistry. These observations suggest that dysregulation of these genes may be a key factor responsible for the initiation and perpetuation of EMT in GCT, leading to cellular migration and malignant transformation, contributing to development of metastases and tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3414. doi:10.1158/1538-7445.AM2011-3414

Cutaneous fungal granulomas due to Alternaria spp. infection in a horse in New Zealand

Equine cutaneous fungal granulomas have been previously referred to in New Zealand (Fairley 1998), and are described in the veterinary literature from around the world, including North America and Australia (Pascoe and Summers 1981; Genovese et al. 2001; Valentine et al. 2006), but no peer-reviewed reports appear published in the literature in New Zealand. Described here is a case of multiple cutaneous fungal granulomas caused by Alternaria spp. in a horse in New Zealand.

Effects of gentamicin and gentamicin–RGD coatings on bone ingrowth and biocompatibility of cementless joint prostheses: An experimental study in rabbits

Antimicrobial coatings are of interest as a means to improve infection prophylaxis in cementless joint arthroplasty. However, those coatings must not interfere with the essential bony integration of the implants. Gentamicin–hydroxyapatite (gentamicin–HA) and gentamicin–RGD (arginine–glycine–aspartate)–HA coatings have recently been shown to significantly reduce infection rates in a rabbit infection prophylaxis model. The purpose of the current study was to investigate the in vitro elution kinetics and in vivo effects of gentamicin–HA and gentamicin–RGD–HA coatings on new bone formation, implant integration and biocompatibility in a rabbit model. In vitro elution testing showed that 95% and 99% of the gentamicin was released after 12 and 24h, respectively. The in vivo study comprised 45 rabbits in total, with six animals for each of the gentamicin–HA, gentamicin–RGD–HA group and control pure HA coating groups for the 4week time period, and nine animals for each of the three groups for the 12week observation period. A 2.0mm steel K-wire with one of the coatings under test was placed in the intramedullary canal of the tibia. After 4 and 12weeks the tibiae were harvested and three different areas (proximal metaphysis, shaft area, distal metaphysis) were assessed by quantitative and qualitative histology for new bone formation, direct implant–bone contact and the formation of multinucleated giant cells. The results exhibited high standard deviations in all subgroups. There was a trend towards better bone formation and better direct implant contact in the pure HA coating group compared with both gentamicin coatings after 4 and 12weeks, which was, however, not statistically significant. The number of multinucleated giant cells did not differ significantly between the three groups at both time points. In summary, both gentamicin coatings with 99% release of gentamicin within 24h revealed good biocompatibility and bony integration, which was not statistically significant different compared with pure HA coating. Limitations of the study are the high standard deviation of the results and the limited number of animals per time point.

Thoracic Mass in a Cynomolgus Macaque (Macaca fascicularis)

A male cynomolgus macaque at the age of 3 years and 11 months suffered sudden cardiac arrest during a surgical operation. This animal had been clinically asymptomatic for 6 months from the acclimatization period to death. At necropsy, a white mass approximately 5 cm in diameter was found at the base of the heart. Histopathologically, the mass consisted of a granuloma with a number of multinucleated giant cells and multiple necrotic foci. Fungal hyphae characterized by parallel cell walls, distinct septa, and branching were observed in the lesion. The granuloma extended into the thoracic lymph nodes and the subepicardium of the left atrium, compressed the bronchioli, and was separated from the pulmonary parenchyma by a thick fibrous layer. The hyphal morphology and results of polymerase chain reaction assays demonstrated that the pathogen was Aspergillus sp.

Influence of β-tricalcium phosphate granule size and morphology on tissue reaction in vivo

In this study the tissue reaction to five different β-tricalcium phosphate (β-TCP)-based bone substitute materials differing only in size, shape and porosity was analyzed over 60 days, at 3, 10, 15, 30 and 60 days after implantation. Using the subcutaneous implantation model in Wistar rats both the inflammatory response within the implantation bed and the resulting vascularization of the biomaterials were qualitatively and quantitatively assessed by means of standard and special histological staining methods. The data from this study showed that all investigated β-TCP bone substitutes induced the formation of multinucleated giant cells. Changes in size, shape and porosity influenced the integration of the biomaterials within the implantation bed and the formation of tartrate-resistant acid phosphatase (TRAP)-positive and TRAP-negative multinucleated giant cells, as well as the rate of vascularization. While a high porosity generally allowed cell and fiber in-growth within the center of the bone substitute, a lower porosity resulted in a mosaic-like integration of the materials, with the granules serving as place holders. The number of multinucleated giant cells located in the implantation bed positively correlated with the vascularization rate. These data emphasize that all biomaterials investigated were capable of inducing the formation of TRAP-positive multinucleated giant cells as a sign of biomaterial stability. Furthermore, these cells directly influenced vascularization by secretion of vascular endothelial growth factor (VEGF), as well as other chemokines. Based on these findings, the role of multinucleated giant cells in the foreign body reaction to biomaterials might need to be reconsidered. This study demonstrates that variations in the physical properties of a bone substitute material clearly influence the (extent of the) inflammatory reaction and its consequences.

Malignant fibrous histiocytoma (giant cell type) of soft parts in the abdominal mammary region of a female Ankara (Angora) cat

The present report describes a giant cell type of malignant fibrous histiocytoma (MFH), diagnosed in soft parts of the right abdominal mammary region, in an 11-year old, 8 kg, nulliparous female Ankara (Angora) cat diagnosed in soft parts of the right abdominal mammary region. The tumor, surgically excised from the abdominal region, had a flexible consistency with ulcerated overlying skin. The tumor was elliptical (8.0 cm × 7.0 cm × 5.0 cm) with a necrotic area of 3.0 cm × 1.5 cm × 1.0 cm in the middle of the cut surface. Microscopically, the tumor was subcutaneous and unencapsulated. Tumor cells were comprised of a mixture of fibroblast-like spindle and histiocytic-like cells with a pale pink cytoplasm. Cells were oval or elongated with a round, large nucleus, and small single nucleoli. In addition, an abundant number of multi-nucleated giant cells were observed. In some fields, there was a dense collagen connective tissue, foci of cartilaginous, bony metaplasia, and hemorrhage surrounding necrosis.

Macrophages in Langerhans cell histiocytosis are differentiated toward M2 phenotype: Their possible involvement in pathological processes

Although numerous macrophages are found in the lesions of Langerhans cell histiocytosis (LCH), their activation phenotypes and their roles in the disease process have not been clarified. Paraffin-embedded LCH samples were examined on immunohistochemistry and it was found that CD163 can be used to distinguish infiltrated macrophages from neoplastic Langerhans cells (LC). The number of CD163-positve macrophages was positively correlated with the number of multinucleated giant cells (MGC), indicating that most MGC are derived from infiltrated macrophages. A significant number of CD163-positive macrophages were positive for interleukin (IL)-10 and phospho-signal transducer and activator of transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This indicates that these macrophages are polarized to anti-inflammatory macrophages of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was considered to responsible for inducing M2 differentiation of infiltrated macrophages. The number of CD163-positive macrophages in different cases of LCH varied, and interestingly the density of CD163-positive macrophages was inversely correlated with the Ki-67-positivity of LC. Although the underlying mechanism is not fully elucidated, macrophage-derived IL-10 was considered to be involved in the suppression of tumor cell proliferation via activation of STAT3.

Proposed histological progression of the Spirocerca lupi-induced oesophageal lesion in dogs

This study aims to outline the histological progression of the Spirocerca lupi nodule from infection to neoplastic transformation. Sixty-two spirocercosis-induced nodules, 42 non-neoplastic and 20 neoplastic, were stained with HE. Ten non-overlapping high power fields per nodule were examined and non-neoplastic and neoplastic nodules were compared. Inflammation was scored 0–3 and revealed a score of 1.91 ± 0.52 in the non-neoplastic and 0.97 ± 0.5 in the neoplastic cases ( p < 0.01). In most non-neoplastic cases the inflammatory infiltrate was lymphoplasmacytic and in the neoplastic cases neutrophils predominated. Necrosis was scored 0–3 and revealed a score of 0.88 ± 0.41 in the non-neoplastic and 1.47 ± 0.5 in the neoplastic cases ( p < 0.01). The average number of mitoses over 10 high power fields per nodule was 1.31 ± 1.55 in the non-neoplastic compared to 42.85 ± 30.79 in the neoplastic cases ( p < 0.01). The average number of multinucleated giant cells over 10 high power fields per nodule was 0.9 ± 1.45 in the non-neoplastic compared to 13.9 ± 14.66 in the neoplastic cases ( p < 0.01). In the non-neoplastic cases, collagen, immature fibroblasts and fibroblast activation (excessively plump euchromatic nuclei with single or multiple prominent nucleoli) were scored 0–3 and a combined score, fibroblasts + activation score − collagen was calculated. The non-neoplastic cases were divided into a combined score of ≤1 ( n = 15) or >1 ( n = 27). The 2 groups had similar scores for inflammation and necrosis, but were significantly different ( p < 0.01) in mitotic index (0.26 ± 0.46 vs. 1.89 ± 1.65) and number of multinucleated cells (0 vs. 1.4 ± 1.6). These results indicate 2 stages in the non-neoplastic nodules: early inflammation, characterized by fibrocytes and abundant collagen, and a pre-neoplastic stage, characterized by activated fibroblasts and reduced collagen.

A Quantitative Evaluation of Inflammatory Cells in Human Temporomandibular Joint Tissues From Patients With and Without Implants

Previous studies made only qualitative assessments of immune cell responses to temporomandibular joint (TMJ) implant wear debris. The aim of this study was to perform a quantitative comparison of inflammatory cell types in TMJ tissues with implant wear debris, TMJ tissues with a history of disc pathology without implant debris, and TMJ tissues from normal control subjects. TMJ tissues were collected from the following 3 groups of subjects: 1) individuals with failed TMJ implants (implant group, n = 10), 2) patients with TMJ disc pathology but no history of implant placement (nonimplant surgery group, n = 10), and normal cadaveric tissues with no history of surgery (control group, n = 10). Tissue sections (5 microm) from all subjects were stained with hematoxylin-eosin, after which cell counts were done for 2 types of inflammatory cells: multinucleated giant cells and lymphocytes. Mean inflammatory cell counts from the 3 groups were compared by use of a 1-way analysis of variance procedure and Bonferroni adjustment to maintain an overall type I error rate of .05. Implant group tissues contained significantly more inflammatory cells than tissues from the nonimplant surgery and control groups (P < .0001). Multinucleated giant cells were only present in implant group tissues. Although the high number of multinucleated giant cells present in the implant group obscured a total count of lymphocytes for that group, lymphocyte cell counts were still significantly greater (P < .005) in implant group tissues than in tissues from the other 2 groups. Our data provide quantitative confirmation that the presence of Proplast-Teflon implant (Vitek, Houston, TX) wear debris is associated with a significant increase in the number of local multinucleated giant cells and lymphocytes.

Two Cases of Bovine Sarcoma in Clinically Long-Standing Lesions

Histopathological examination of clinically long-standing lesions with durations of one year or more in the extremities of two cattle revealed the presence of sarcomas with distant metastases. In case 1, neoplastic cells were fusiform to pleomorphic, stained for no specific differentiation markers, and diagnosed as undifferentiated sarcoma. Neoplastic growth in case 2 was composed of spindle to histiocytoid cells and a significant number of multinucleated giant cells, both of which were immunoreactive to histiocyte markers, and diagnosed as giant cell malignant fibrous histiocytoma. Neoplastic cells of both cases were immunohistochemically positive for nitric oxide-related antigens, which were recognized as markers of inflammation-induced carcinogenesis in human and laboratory animals.