Giant epidermoid cyst penetrating the skull: a case report and literature review.

Intracranial epidermoid cyst is a rare pseudotumor of the nervous system, accounting for 0.2%-1.8% of all intracranial tumors. It is usually located in the cerebellopontine Angle or parasellar area, with insipid onset, slow growth and usually less than 2 cm in diameter. Giant epidermoid cysts that invade the bone have rarely been reported in the literature. Herein, we report a case of giant ECs extradural to the parietal bone, penetrating the skull and continuing to expand outward. In addition, a systematic search of four authoritative databases was conducted to collect the relevant reports of giant epidermoid cyst with diameter > 5cm for the first time, and to discuss the clinical and radiographic features of patients with giant epidermoid cyst and the influence of treatment options.

The character of parietal and orbital alterations in the superfamily Hominoidea (families Hominidae [exclusive of Homo] and Hylobotidae).

Parietal external surface disruption routinely referred to as porotic hyperostosis, and orbital alterations (cribra orbitalia), have been attributed to anemia-related bone marrow hyperplasia in humans. A recent study in humans identified that they were actually vascular in nature. Skeletons were examined and epi-illumination surface microscopy was performed on the parietal region and orbit of 156 Hominidae and 123 Hylobotidae to assess if these phenomena were trans-phylogenetic. Trans-cortical channels were recognized on the basis of visualized ectocranial surface defects penetrating the parietal; cribra orbitalia, by alteration of the normally smooth orbital roof appearance. Trans-cortical parietal channels, ranging in size from 20 to 100 µm, are rare in Gorilla and Pan troglodytes and absent in Pan paniscus. They are universally present in adult Pongo abeli and in Hylobatidae, independent of species. Cribra orbitalia was common in Hylobotidae, Pongo pygmaeus and P. abelii, less prevalent in adult P. troglodytes, and not recognized in any Gorilla gorilla or P. paniscus examined. The proliferative form predominated, with the exception of Hylobates concolor and muelleri, in which uncalcified vascular grooves predominated. No correlation was observed between the presence of either trans-cortical channels or cribra orbitalia and fractures, osteoarthritis, or inflammatory arthritis. Parietal alterations observed in apes are trans-cortical channels, analogous to those observed in humans, and do not represent porosity. Similarly, cribra orbitalia in apes is confirmed as vascular in nature. The proliferative form apparently represents calcification of blood vessel walls, indistinguishable from observations in humans. Predominant presence in adults rather than in juveniles suggests that both forms are acquired rather than developmental in derivation. Sex and bone alteration/disease-independence suggests that mechanical, endocrine, and inflammatory phenomena do not contribute to the development of either. Further, independent occurrence of trans-cortical channels and cribra orbitalia suggests that they do not have a shared etiology.

Primary intradiploic epidermoid cyst: A case report with literature review.

Primary intradiploic epidermoid cyst of the central nervous system (CNS) is a rare disease. More than 200 cases have been reported so far. The lesion can affect every flat bone of the cranium. The pre-operative diagnosis is always misleading. We reported a 61-year-old female with giant primary intradiploic epidermoid cyst in the parietal bone. Surgical resection was performed. The patient recovered well with no complication nor neurologic dysfunction. A literature review of the disease will also be presented here.
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Modified lateral orbitotomy with combined partial zygomatic arch and vertical ramus ostectomies for excision of a frontal and parietal bone osteoma in a dog.

OBJECTIVE: To describe modifications to the lateral orbitotomy for surgical excision of tumors affecting the frontal, parietal, palatine, or temporal bones. STUDY DESIGN: Case report. ANIMAL: A 5-year-old female spayed American pit bull terrier. METHODS: The dog presented for excision of a bone tumor affecting the right frontal and parietal bones. A modified lateral orbitotomy was performed with combined partial zygomatic arch and vertical ramus ostectomies to increase working space and allow drilling of the calvarium ventral to the mass. RESULTS: The dog tolerated the procedure well, and there were no complications from either the ostectomies or the craniectomy. Histopathological examination was consistent with complete excision of an osteoma. The dog survived 2 years with no recurrence and was euthanized due to an intestinal mass. CONCLUSION: The lateral orbitotomy approach can be modified with combined partial zygomatic arch and vertical ramus ostectomies to increase exposure and working space for resection of tumors affecting the frontal, parietal, palatine, or temporal bones.

Violence in the Early Bronze Age. Diagnosis of skull lesions using anthropological, taphonomic and scanning electron microscopy techniques.

In this paper we present the study of a skull belonging to a young male from the Italian Bronze Age showing three perimortem injuries on the frontal and parietal bones; the peculiarity of the frontal injury is represented by its singular shape, which may be indicative of the weapon that caused the lesion. The aim of the present study is to examine the traumatic evidence in relation to possible etiological factors, in order to attempt to establish if the lesion occurred peri or post-mortem, and to evaluate if these traumatic injuries could be interpreted as an evidence of interpersonal violence, by combining anthropological, taphonomic and ESEM investigations. The combination of multidisciplinary methods of study can provide important new insights into inter-personal violence.

Photobiomodulation of mesenchymal stem cells encapsulated in an injectable rhBMP4-loaded hydrogel directs hard tissue bioengineering.

Photobiomodulation (PBM) therapy displays relevant properties for tissue healing and regeneration, which may be of interest for the tissue engineering field. Here, we show that PBM is able to improve cell survival and to interact with recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate odonto/osteogenic differentiation of dental derived mesenchymal stem cells (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell carrier (Pluronic® F-127) loaded with rhBMP4 and then photoactivated. PBM improved MSCs self-renewal and survival upon encapsulation in the Pluronic® F-127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was premature and markedly improved in the photoactivated MSCs. An in vivo calvarial critical sized defect model demonstrated significant increase in bone formation after PBM treatment. Finally, a balance in the reactive oxygen species levels may be related to the favorable results of PBM and rhBMP4 association. PBM may act in synergism with rhBMP4 and is a promise candidate to direct and accelerate hard tissue bioengineering.

The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses.

OBJECTIVES: To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR). MATERIAL AND METHODS: Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis. RESULTS: Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38-42%) and newly formed bone (54-61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified. CONCLUSIONS: Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.

Intradiploic hematoma in an infant: case report and literature review.

Intradiploic hematoma is extremely rare, especially in infant patients. Less than 15 cases were reported in English literature up to now. Here, we presented another intradiploic hematoma in an infant boy without coagulopathy. A left parietal craniotomy was performed. Post-operative CT showed well-reconstructed skull.

Recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB for localized bone regeneration. Histologic and radiographic outcomes of a rabbit study.

OBJECTIVES: Improvement in localized bone regeneration is needed to avoid the use of autogenous tissue. For that purpose, the use biologic mediators was proposed. The aim was to test whether or not one of two biologic mediators, recombinant human bone morphogenetic protein-2 (rhBMP-2) or recombinant platelet-derived growth factor (rhPDGF-BB), is superior to the other and to control groups for localized bone regeneration. MATERIALS AND METHODS: Four cylinders (height: 5 mm; diameter: 7 mm) were screwed on the parietal and frontal bones at the cranium in 12 rabbits. The cylinders either received (i) deproteinized bovine bone mineral (DBBM) mixed rhBMP-2 (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB (DBBM/PDGF), (iii) DBBM (DBBM), and (iv) empty control (control). Rabbits were euthanized at 2 and 8 weeks (n = 6, respectively). Conventional histomorphometric and micro-CT analyses were performed. Parametric linear mixed models were applied for the analyses with Bonferroni correction for the multiple group comparisons. RESULTS: The area of bone regeneration (histology; AAHisto ) at 2 weeks peaked for DBBM (41.91%) with statistically significantly greater values compared to DBBM/PDGF and the control group (P < 0.05). At 8 weeks, mean AAHisto values were 96.29% (DBBM/BMP-2), 46.37% (DBBM/PDFG), 39.66% (DBBM), and 35.98% (control) (DBBM/BMP-2 vs. all groups (P < 0.05)). At 8 weeks, bone regeneration was greatest for DBBM/BMP-2 (35.62%) with statistically significant differences compared to all other groups (P < 0.05). The area of bone regeneration (micro-CT; AAm-CT ) at 2 weeks amounted to 43.87% (DBBM/BMP-2), 42.81% (DBBM/PDFG), 48.71% (DBBM), and 0.96% (control). The control group demonstrated statistically significantly less AAm-CT compared to all groups (P < 0.05). At 8 weeks, mean AAm-CT values were 63.65% (DBBM/BMP-2), 50.21% (DBBM/PDFG), 44.81% (DBBM), and 4.57% (control) (P > 0.05). CONCLUSIONS: The use of rhBMP-2 significantly enhanced bone regeneration compared to all other groups including the group with rhPDGF-BB.

Guided bone regeneration in osteoporotic conditions following treatment with zoledronic acid.

OBJECTIVES: To evaluate new bone formation in calvarial critical size defects (CSD) under dense polytetrafluoroethylene (d-PTFE), microporous membranes for guided bone regeneration (GBR) in healthy, osteoporotic and osteoporotic treated with zoledronic acid (ZA) rats. METHODS: Forty-eight, female, 6-month old Wistar rats were included in the study. Osteoporosis was induced by ovariectomy (OVX) and calcium-deficient diet in 32 rats. Sixteen OVX rats were treated with a single dose of Zolendronic Acid (ZA) (OZ), while 16 OVX rats received no treatment (O). The remaining 16 rats were sham-operated and used as healthy controls (C). At 6 weeks following osteoporosis induction, two 5 mm CSD were created in the parietal bones and one of them was treated with a double d-PTFE membrane. The healing periods were 30 and 60 days. New bone formation (NB) was assessed by qualitative and quantitative histological analysis. RESULTS: After 30 days of healing, NB (mean% (95% CI)) was 78.9% (21), 93.1% (9.3) and 84.2% (26.9) in the membrane treated defects and 18.8% (24.1), 27.1% (7.9) and 31% (38.8) in the untreated defects of group O, OZ and C, respectively. After 60 days of healing, NB was 78.3% (14.4), 95.8% (9) and 90.1% (26.1) in the membrane treated defects and 10.8% (17.4), 51.6% (39.4) and 15.7% (12.1) in the untreated defects of group O, OZ and C, respectively. Hierarchical analysis of variance showed that treatment with ZA (P = 0.001) and the use of membrane (P = 0.000) significantly increased new bone formation while presence of osteoporosis may have reduced new bone formation (P = 0.028). CONCLUSION: d-PTFE membranes for GBR promote bone healing in osteoporotic and healthy rats. Treatment with ZA may improve new bone formation in osteoporotic rats.

[Eosinophilic granuloma of the parietal bone of an adult patient with BRAF mutation]. / Éozinofil'naia granulema temennoi kosti s mutatsiei gena BRAF u vzroslogo patsienta.

The paper describes a case of eosinophilic granuloma of the parietal bone in a 32-year-old man. Histological examination revealed a large number of bean-shaped Langerhans cell histiocytes with lobed nuclei and nuclear grooves. The histiocytes alternated with the foci of obvious eosinophilic infiltration and with eosinophilic microabscesses. There were osteoclast-like multinucleated giant cells, bone resorption, and numerous bone rods covered with osteoblast chains. The histiocytes expressed CD1α, langerin, CD68, S100, and p53 (in 90.0% of the tumor cells). The Ki-67 proliferation index was 18.0%. A molecular genetic study identified BRAFV600E mutation (nucleotide substitution s.1799 T>A (p.V600E) in the heterozygous state). Clinical and morphological data and the results of molecular genetic studies led to the conclusion that there was eosinophilic granuloma of the right parietal bone (the unifocal form of Langerhans cell histiocytosis (LCH), type I, group A1, with the monoossal nature of lesion and with BRAFV600E mutation). In adults, this disease is extremely rare (2-5 cases of LCH per million people, bone loss in the fourth decade of life in 2.5% of the patients).

[A case report for giant cholesteatoma occurred in fronto-parietal bone].

Cholesteatoma is a destructive and expanding growth benign tumor, mainly consisting of stratified squamous epithelium. It possesses the capacity of eroding bone and can exist in a nonaggressive state, remaining undetected for years. Once cholesteatoma appeared, it grows relentlessly and threats to invade intra-temporal structures. Most cholesteatomas occurred in the petrous bone and also affected the labyrinth and middle cranial fossa. Here, we report a preliminary wrongly-diagnosed case. The patient was wrongly diagnosed as "sebaceous cyst with infection" by local hospital. The definite diagnosis was made after the surgery performed by our department, which was confirmed by pathological result. So far, there were few reports of giant cholesteatoma which occurs in fronto-parietal part of skull with bone defect.

Enlarged parietal foramina: a rare forensic autopsy finding.

Enlarged parietal foramina (EPF) are a quite rare developmental defect of the parietal bone which has to be distinguished from the normal small parietal foramina. We report a forensic case of an individual found in an advanced state of putrefaction in his own house with an undetermined cause of death. No evidence of trauma was observed, and the toxicological exam was negative. The victim was a 40-year-old man with a history of epilepsy. The large biparietal foramina, a rare anatomical variation and unusual autopsy finding, were observed at autopsy. The recognition of anatomical variations is important to avoid false interpretations and conclusions and has a significant potential as an identity factor, thus contributing to positive identification.

An Experimental Study of Particulate Bone Graft for Secondary Inlay Cranioplasty Over Scarred Dura.

BACKGROUND: Inlay cranioplasty in children is challenging because autologous bone is limited. Cranial particulate bone graft effectively closes defects when placed over normal dura. The purpose of this study was to determine if particulate bone graft will ossify when used for secondary cranioplasty over scarred dura. METHODS: A 17 × 17-mm critical-sized defect was made in the parietal bone of 16 rabbits. Four animals had no implant (group 1). Twelve animals had the defect remade 16 weeks postoperatively, which was managed in 2 ways: group 2 (no implant; n = 6) and group 4 (particulate bone graft; n = 6). Particulate graft was obtained using a brace and bit from the frontal bone. Computed tomography was used to determine the area of ossification and thickness of the healed graft. Eight animals previously managed with particulate bone graft over normal dura were used as an additional control (group 3). RESULTS: Critical-sized defects filled with particulate bone graft over scarred dura (group 4) exhibited superior healing of the area (83.8%; range, 73.0%-90.6%) compared to control defects over normal dura (group 1: 62.9%; range, 56.5%-73.4%) or scarred dura (group 2: 56.9%; range, 40.0%-68.3%) (P = 0.0004). Particulate bone on scarred dura exhibited less ossified area (P = 0.002), and thinner bone (0.95 mm, range, 0.71-1.32 mm) compared to defects in which graft was placed over normal dura (group 3: area, 99.2%; range, 96.8%-100%; thickness, 1.9 mm, range; 1.1-3.1 mm) (P = 0.04). CONCLUSIONS: Particulate bone graft ossifies inlay cranial defects over scarred dura although inferior to placement over normal dura. Clinically, particulate bone graft may be used for secondary inlay cranioplasty.

Cranial Fasciitis: A Systematic Review and Diagnostic Approach to a Pediatric Scalp Mass.

Cranial fasciitis is an uncommon, benign fibroproliferative condition of the scalp or skull that arises in children. Clinically, it manifests as a firm, nontender, subcutaneous, enlarging mass. The purpose of our study was to review the literature on cranial fasciitis to create a diagnostic algorithm using the latest patient at our institution as an example. The authors conducted a systematic review examining all published cases of cranial fasciitis in English literature. The authors then created a diagnostic algorithm to help distinguish cranial fasciitis from other similarly presenting cranial masses. To demonstrate this algorithm, the authors detailed the latest patient with cranial fasciitis at our institution. The authors extracted data from 53 published reports documenting 72 patients of cranial fasciitis. Our patient presented similarly to what was reported in the literature. A 7-week-old boy presented with 2 small parietal scalp masses that were noted shortly after birth. After noncontrast computed tomography imaging, the enlarging masses were resected and found to have eroded the outer cranial vault cortex. Histological analysis revealed cranial fasciitis. The differential diagnosis for an enlarging scalp mass in an infant or child is broad. Cranial fasciitis cannot be diagnosed based on clinical presentation alone. Imaging is usually employed to further characterize lesions after initial examination but histopathological analysis is essential for diagnosis. The locally invasive nature of cranial fasciitis makes it difficult to distinguish from malignant conditions such as sarcomas. However, if the diagnosis of cranial fasciitis is considered early, patients can achieve prompt clinical resolution following simple resection.

[Mother and son with enlarged parietal foramina, persistent fetal vein, and ALX4 mutation].

Enlarged parietal foramina (EPF) are rare congenital skull defects. These round or oval defects are situated on each parietal bone approximately 1 cm from the midline. Most patients with EPF have a positive family history. The condition is inherited as an autosomal dominant trait with relatively high, but not full, penetrance. Mutation in either MSX2 or ALX4 genes is associated with enlarged parietal foramina. Case 1 is a boy who was noticed to have a large anterior fontanelle, large posterior fontanelle, and widely opened sagittal suture at 2 months. During development, the anterior fontanelle and sagittal suture closed at 3 years and the posterior fontanelle subsequently divided into two foramina with ossification of the midline bridge by 4 years. The foramina were about 2.5 x 2.5 cm in diameter at 8 years. Case 2 is the 34-year-old mother of Case 1. She showed similar bone defects in her cranium, again about 2.5 x 2.5 cm in diameter. Neither patient showed any neurological symptoms. Genetic analysis revealed a mutation in the ALX4 gene in both patients, and magnetic resonance imaging showed a persistent falcine sinus and a hypoplastic straight sinus. Further evaluation revealed that the mother of Case 2 also had a mutation in the ALX4 gene, but no enlarged parietal foramina. Although high penetrance of this condition has been reported, this family suggests incomplete penetrance of this disorder.

Differences in the developmental origins of the periosteum may influence bone healing.

BACKGROUND AND OBJECTIVE: The jaw bone, unlike most other bones, is derived from neural crest stem cells, so we hypothesized that it may have different characteristics to bones from other parts of the body, especially in the nature of its periosteum. The periosteum exhibits osteogenic potential and has received considerable attention as a grafting material for the repair of bone and joint defects. MATERIAL AND METHODS: Gene expression profiles of jaw bone and periosteum were evaluated by DNA microarray and real-time polymerase chain reaction. Furthermore, we perforated an area 2 mm in diameter on mouse frontal and parietal bones. Bone regeneration of these calvarial defects was evaluated using microcomputed tomography and histological analysis. RESULTS: The DNA microarray data revealed close homology between the gene expression profiles within the ilium and femur. The gene expression of Wnt-1, SOX10, nestin, and musashi-1 were significantly higher in the jaw bone than in other locations. Microcomputed tomography and histological analysis revealed that the jaw bone had superior bone regenerative abilities than other bones. CONCLUSION: Jaw bone periosteum exhibits a unique gene expression profile that is associated with neural crest cells and has a positive influence on bone regeneration when used as a graft material to repair bone defects. A full investigation of the biological and mechanical properties of jaw bone as an alternative graft material for jaw reconstructive surgery is recommended.

The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

OBJECTIVES: Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. MATERIAL AND METHODS: Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. RESULTS: Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). CONCLUSION: These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery.

Histomorphometric and microtomographic evaluation of the effects of hyperbaric oxygen and systemic ozone, used alone and in combination, on calvarial defect healing in rats.

PURPOSE: The aim of this study was to compare the efficacy of hyperbaric oxygen and systemic ozone, used separately and in combination, on the healing of bone defects. MATERIAL AND METHODS: Sixty male Wistar rats were divided into 4 groups (n = 15) according to treatment (control, hyperbaric oxygen [HBO], ozone [O], and HBO plus O [HBO-O]) and divided further into 3 subgroups according to day of sacrifice (postsurgical days 5, 15, and 30). Surgery was performed under general anesthesia to create a critical-size bone defect (5 mm in diameter) in the cranium. After sacrifice, microtomographic images of all samples were recorded, and histomorphometric analysis was performed. RESULTS: Histologic and radiologic measurements showed that the values of all experimental groups were higher than those of the control group. Histologic scores for all experimental groups were statistically higher than those for the control group day 30 (O, P = .045; HBO, P = .049; HBO-O, P = .042). Histologic scores also were statistically higher for the HBO group on day 5 (P = .045) and day 15 (P = .009) compared with the control group. Microtomographic scores were higher for the experimental groups than for the control group, with statistically significant differences for group O on day 5 (P = .033) and day 30 (P = .0045) and for group HBO on day 15 (P = .005). Histologic and radiologic analyses showed positive correlations. CONCLUSION: Within the limitations of this study, the use of hyperbaric oxygen and ozone, separately and in combination, were shown to be effective in increasing bone healing. Combined usage was no more effective in stimulating bone healing than separate usage.

Benign fibrous histiocytoma of parietal bone: case report and review of the literature.

A benign fibrous histiocytoma with primary site of origin in the parietal bone has not yet been reported in the literature. We report here a case concerning a 12-year-old girl with a 14-month history of an enlarging parietal bone mass. The tumor was excised after removal of the cortical bone and resection of the tumor surrounding the cortical bone erosion using pre-plasticity titanium repair. Both postoperative histopathological examination and immunohistochemical analysis were consistent with a benign fibrous histiocytoma. No clinical or computed tomography (CT) radiological signs of tumor recurrence and/or metastasis were observed at 12 months. Although a primary benign fibrous histiocytoma of the parietal bone is a rare tumor, it should be considered as a potential diagnosis for any cranial tumor. Surgical intervention is the most effective treatment technique for a benign fibrous histiocytoma.