[Benign and malignant giant-cell rich lesions of bone: Pathological diagnosis with special emphasis on recent immunohistochemistry and molecular techniques]. / Diagnostic des lésions osseuses riches en cellules géantes : démarche diagnostique et intérêt des nouvelles techniques complémentaires immuno-histochimiques et moléculaires.

The infiltration by numerous osteoclastic giant cells is a frequent finding in bone tumors and pseudo-tumors. Pathologists must integrate clinical and radiological data to achieve a correct diagnosis in bone pathology. Benign giant-cell rich lesions of bone encompass giant cell tumor of bone, aneurysmal bone cyst, chondroblastoma, brown tumor and fibrous cortical defect/non-ossifying fibroma. Amongst malignant neoplasms, variants of conventional osteosarcoma, undifferentiated pleomorphic sarcoma, leiomyosarcoma and bone metastasis must be discussed. Recently, new diagnostic markers, antibodies for immuno-histochemistry and genetic markers, have been developed and are helpful to diagnose such lesions.

Ossifying fibromyxoid tumor: a study of 6 cases of atypical and malignant variants.

Ossifying fibromyxoid tumors (OFMT) of soft parts are rare, slow-growing tumors that have potential for local recurrence and may metastasize. While OFMT originally was considered benign, several cases of malignant OFMT have been documented. There is no universally accepted risk stratification, although this study emphasizes the importance of utilizing histology, immunohistochemistry and FISH in establishing the diagnosis. Herein, we describe six cases of atypical and malignant OFMT with differences in morphologic features, 5 of which display the proposed morphological criteria for malignancy. The patients were mostly male (M=5, F=1) with an age range of 33-69 years. The tumors arose from the extremities (3 cases), the shoulder (1 case), the head and neck area (1 case), and the paraspinal area (1 case). One tumor had high grade and overtly sarcomatous changes, while another invaded the underlying clavicle. Two cases showed cytological atypia and necrosis. Fluorescence in situ hybridization (FISH) detected rearrangement of the PHF1 gene in 5 cases. All cases were positive for EAAT4 and actin by immunohistochemistry, while negative for desmin. Three tumors were immunoreactive for S100 protein. INI-1 immunohistochemical staining was conserved in all but 2 cases in which a mosaic loss of expression was noted. All but two patients are currently alive and free of disease.

Protuberant fibro-osseous lesions of the temporal bone: two additional case reports.

The most commonly encountered fibro-osseous lesions of the skull bone are fibrous dysplasia and ossifying fibroma. Two cases of a unique "protuberant fibro-osseous lesion of the temporal bone" were first described by Selesnick and colleagues in 1999, and 2 further cases were reported in 2010 under the name "Bullough lesion". We recently found 2 new cases of this rare entity. Two Korean female patients aged 70 and 54 years presented with slow growing postauricular masses without pain or tenderness for 6 and 7 years, respectively. Computed tomography revealed a 2.9 cm calcified mass in the temporal bone of the first patient, and a 5.5 cm enhancing mass with internal cartilaginous matrix in the temporal bone of the second patient. Intramedullary or intracranial extension was not found in either case, and en bloc removals were performed. Microscopically, multiple round to oval osseous islands were scattered throughout the bland fibrous stroma in both cases. The osseous islands varied in size and were lamellar or woven, without osteoblastic rimming, and surrounded by fibroblastic bands. Neither patient has shown evidence of postoperative recurrence for 18 months. The location, histology, and clinical course of these 2 cases were identical to the 4 cases previously reported, although age and sex varied. The lesions were tested for the R201H mutation in the GNAS gene, which is present in fibrous dysplasia. No mutations were found, suggesting a different genetic background for these lesions.

Benign odontogenic tumors versus histochemically related tissues: preliminary results from mid-infrared and solid-state nuclear magnetic resonance spectroscopy.

Three types of human odontogenic tumors histologically classified as compound composite odontoma, ossifying fibroma, and Pindborg tumor were characterized using mid-infrared spectroscopy (mid-IR) and solid-state nuclear magnetic resonance (ssNMR). For comparison, human jawbone and dental mineralized tissues such as dentin, enamel, and dental cement were also characterized. The studies focused on the structural properties and chemical composition of pathological tissues versus histochemically related tissues. All analyzed tumors were composed of organic and mineral parts and water. Apatite was found to be the main constituent of the mineral part. Various components (water, structural hydroxyl groups, carbonate ions (CO(3)(2-)), and hydrogen phosphate ions (HPO(4)(2-))) and physicochemical parameters (index of apatite maturity and crystallinity) were examined. The highest organic/mineral ratio was observed in fibrocementoma, a finding that can be explained by the fibrous character of the tumor. The lowest relative HPO(4)(2-) content was found in odontoma. This tumor is characterized by the highest mineral crystallinity index and content of structural hydroxyl groups. The Pindborg tumor mineral portion was found to be poorly crystalline and rich in HPO(4)(2-). The relative CO(3)(2-) content was similar in all samples studied. The results of spectroscopic studies of odontogenic tumors were consistent with the standard histochemical analysis. It was shown that the various techniques of ssNMR and elaborate analysis of the mid-IR spectra, applied together, provide valuable information about calcified benign odontogenic tumors.

Expression of receptor for hyaluronan-mediated motility (RHAMM) in ossifying fibromas.

Fibro-osseous lesions of the jaw are poorly understood because of a significant overlap of clinical, radiological and histological features among the various types, though they present distinct patterns of disease progression. An ossifying fibroma is associated with significant cosmetic and functional disturbances, as it shows expansive proliferation. Thus, it is important to establish a specific marker, as well as clearly elucidate its etiology for diagnosis and proper treatment. We previously established immortalized cell lines from human ossifying fibromas of the jaw and found that they highly expressed the receptor for hyaluronan (HA)-mediated motility (RHAMM). In this study, we examined the expression of RHAMM mRNA in 65 fibro-osseous lesions, including ossifying fibroma, fibrous dysplasia and osseous dysplasia, as well as 5 normal jaws, using real-time RT-PCR and immunohistochemistry assays. RHAMM mRNA and protein expression were significantly elevated in the ossifying fibroma specimens. These results suggest that detection of upregulated RHAMM expression in an ossifying fibroma assists with differential diagnosis and has a key role in elucidation of its pathophysiology.

Ossifying fibromyxoid tumor of soft parts: a clinicopathologic, proteomic, and genomic study.

Ossifying fibromyxoid tumor (OFMTs) of soft parts is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. To better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescence in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were conducted on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 men and 17 women (median age, 52 y; range 39 to 63 y) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9), and trunk (N=5). Median tumor size was 5.4 cm (range, 1.0 to 21.0 cm). Cases were classified as typical OFMT (26 of 46, 57%), atypical OFMT (5 of 46, 11%), and malignant OFMT (15 of 46 cases, 32%). Clinical follow-up (27 cases, median 55 months' duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were as follows: S-100 protein (30 of 41, 73%), desmin (15 of 39, 38%), cytokeratin (4 of 35, 11%), EMA (5 of 32, 16%), SMA (2 of 34, 6%), INI-1 (lost in mosaic pattern in 14 of 19, 74%), EAAT4 (31 of 39, 80%), MUC4 (3 of 14, 21%), NFP (8 of 10, 80%) and CD56 (6 of 14, 43%). Gene expression profiling showed typical and malignant OFMTs to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S-100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5 of 7 (71%) cases. We conclude that malignant OFMTs exist and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a "scrambled" phenotype in OFMTs. Loss of INI-1 or other genes on 22q is likely important in the pathogenesis of these rare tumors.

Ossifying fibromyxoid tumor in the mandibular gingiva: case report and review of the literature.

BACKGROUND: Ossifying fibromyxoid tumors (OFTs) are uncommon soft tissue neoplasms. Only one case arising in the gingiva has been described. METHODS: A 21-year-old woman presented with a painless exophytic mass located in the right posterior mandibular gingiva, which was identified 6 months earlier. Radiographs showed irregular calcifications inside the lesion, discrete irregularity of alveolar bone, and integrity of buccal and lingual cortical bone. An incisional biopsy was performed based on the clinical diagnostic hypothesis of peripheral ossifying fibroma or peripheral giant cell granuloma. Microscopic features were compatible with the diagnosis of ossifying fibroma. The entire mass was excised and submitted to histopathologic and immunohistochemical analysis. RESULTS: Histopathologic analysis revealed proliferation of round to spindle-shaped cells arranged in cords and nests and embedded in a fibromyxoid matrix. An incomplete shell of bone trabeculae located beneath the fibrous pseudocapsule was observed at the periphery. Immunohistochemical analysis showed positivity for vimentin and S-100 protein and negativity for smooth muscle actin, muscle-specific actin, and glial fibrillary acidic protein. The definitive diagnosis was OFT. The patient showed no clinical signs of recurrence 7 months after surgical excision. CONCLUSIONS: OFTs located in the gingiva are extremely rare. At this site, these tumors are clinically indistinguishable from other reactive or neoplastic lesions. Although many cases present an indolent biologic behavior, the local recurrence of OFTs has been reported; therefore, long-term follow-up is mandatory.

Ossifying fibromyxoid tumor of soft parts--a clinicopathologic and immunohistochemical study of 104 cases with long-term follow-up and a critical review of the literature.

Ossifying fibromyxoid tumor (OFT) is a unique soft tissue tumor of uncertain histogenesis. The majority of reported cases (approximately 220) have pursued a benign clinical course. However, recent literature has emphasized the existence of morphologically atypical and clinically malignant examples of this tumor and proposed guidelines for assessment of biologic potential. In the present study, we evaluated 104 cases of OFT from the Armed Forces Institute of Pathology, accessioned between the years 1970 and 2007. Herein, OFT was strictly defined as a tumor with lobular architecture, predominantly epithelioid cell morphology, a low level of atypia, corded and trabecular growth patterns, moderate amounts of myxocollagenous matrix, and often, focal peripheral metaplastic bone formation. Tumors that lacked conventional morphology were excluded. The exclusion group included cutaneous mixed tumors, low-grade fibromyxoid sarcomas, and extraskeletal osteosarcomas. The OFTs occurred in 64 men and 40 women with a median age of 50 years (range, 21 to 81 y). The tumor size ranged from 0.7 to 17 cm (median, 3 cm). The mitotic rate varied from 0 to 41 mitotic figures per 50 HPFs (median, 2/50 HPFs). Tumor cell nuclei typically contained small, distinct nucleoli, and necrosis was infrequent (11/104). The great majority of tumors (67/71, 94%) were positive for S100 protein, whereas only occasional examples had (focal) positivity for desmin, glial fibrillary acidic protein, and an AE1/AE3 keratin cocktail. Local recurrences were documented in 9 of 41(22%) living patients, usually 10 or more years after primary surgery, but there were no metastases. A mitotic rate of >2 mitotic figures/50 HPFs was a risk factor for local recurrence, but necrosis, tumor size, the presence of satellite nodules, and positive margins were not. When OFT is strictly defined by the criteria noted above, there is potential for local recurrence, but there seems to be little or no risk for metastasis.

Ossifying fibromyxoid tumor: invariable ultrastructural features and diverse immunophenotypic expression.

Ossifying fibromyxoid tumor (OFMT) is a rare enigmatic soft tissue tumor, the origin of which is still uncertain. The authors report on 3 cases of OFMT arising in the trunk and head and neck regions of adults. Two recurred and one was suspected to have metastasis. All tumors consisted of multiple nodules, in which round or polygonal tumor cells were arranged in sheets or cords within a fibromyxoid background. Characteristic shell-like bone tissues were recognized in all tumors. Based on the grading system proposed by Folpe et al., 2 cases were designated as malignant OFMT and 1 as typical. In addition to S-100 protein, cytokeratin and neuronal markers (neurofilament, CD56 or CD57) were detected in 1 and 2 tumors, respectively. The salient and invariable ultrastructural features included reduplicated basal laminas, which seem to be crucial for the diagnosis.

Psammomatoid ossifying fibromas: immunohistochemical analysis and differential diagnosis with psammomatous meningiomas of craniofacial bones.

OBJECTIVE: To clarify the role of immunohistochemistry in the diagnosis of psammomatoid ossifying fibroma (PSOF), conventional cemento-ossifying fibroma (COF), and psammomatous meningioma (PM) of the craniofacial skeleton. STUDY DESIGN: The histology and immunohistochemistry of 4 PSOFs, 6 COFs, and 7 PMs was studied. Antibodies included EMA, cytokeratins, smooth muscle actin (SMA), desmin, vimentin, CD34, CD10, S-100 protein, and glial fibrillary acidic protein (GFAP). RESULTS: All PSOFs showed multiple round ossicles homogeneously distributed within a fibroblastic stroma. Psammomatous meningiomas had meningothelial features. All tumors, except 1 COF, were positive for EMA. All of them expressed vimentin, and none showed cytokeratins. Staining for SMA and S-100 protein was variable. CD10 was positive in all cases except 2 meningiomas. CD34 and GFAP stained only 1 case of meningioma each. CONCLUSIONS: The diagnosis of PSOF should rest on histologic features. An incorrect diagnosis of meningioma based on the expression of EMA should be avoided.

Differential distribution of glycosaminoglycans in human cementifying fibroma and fibro-osseous lesions.

OBJECTIVE: Differential diagnosis of cementifying fibroma, ossifying fibroma and fibrous dysplasia by histological evaluation is often difficult. The aim of this study was to examine the immunoreactivities for keratan sulfate (KS) and chondroitin-4-sulfate (C4S) glycosaminoglycans of the histological samples obtained from mandibles of patients with these diseases. MATERIALS AND METHODS: The samples were collected from three patients with cementifying fibroma, two with ossifying fibroma and three with fibrous dysplasia and were subjected to immunohistochemical analyses. RESULTS: The results demonstrated that a significant immunoreactivity for KS was found in lacunae housing cells in the cementum-particles of cementifying fibromas, while both ossifying fibromas and fibrous dysplasias showed no significant immunoreactivity for KS. For C4S, while the former showed little immunoreactivity, the latter two cases exhibited intensive immunostaining in the pre- and poorly mineralized matrices. CONCLUSIONS: These results suggest that cementifying fibromas could be distinguished from these fibro-osseous tumors by using immunohistochemical analysis for KS and C4S.

Ossifying fibromyxoid tumor of soft parts: report of a case with novel cytogenetic findings.

A slowly growing tumor of the left thenar region in a 40-year-old man had the classic features of an ossifying fibromyxoid tumor of soft parts, including an incomplete shell of lamellar bone; a center composed of nodular aggregates of small spindled, oval, and stellate cells in abundant myxoid stroma; and strong expression of vimentin, S-100, and neuron-specific enolase by the tumor cells. Clonal chromosomal abnormalities included loss of a chromosome 6, extra material of unknown origin attached to the long arm of chromosome 12, and an unbalanced translocation involving the short arm of a chromosome 6 and the long arm of a chromosome 14. The karyotype was interpreted as 45,XY, der(6;14)(p10;q10),add(12)(q24.3). The chromosomal abnormalities suggest osteochondroblastic rather than neuronal or schwannian lineage.

[Ossifying fibromyxoid tumor of soft parts: a clinicopathological analysis of eight cases].

OBJECTIVE: To study the morphological characteristics and immunophenotype of ossifying fibromyxoid tumor of soft parts (OFT) with a discussion of its histogenesis. METHODS: The clinical, pathological and immunohistochemical features of 8 cases of OFT were evaluated. RESULTS: All 8 cases were middle to old aged patients, ranged from 43 -- 78 years (mean 63 years). Clinically, the majority presented as slowly growing painless masses that located in subcutis of the proximal extremities. Histologically, the tumor was characterized by the following three unique features which have diagnostic value. (1) The tumor was well circumscribed and encapsulated with an incomplete bony shell composed of metaplastic bone within the capsule in most cases; (2) The tumor parenchyma consisted of lobules of variable size and cellularity. The tumor cells within each lobule were rounded to short spindled with pale-staining or eosinophilic cytoplasm; (3) The tumor cells arranged in nests, cords, or laciform pattern, and were embedded in a characteristic fibromyxoid to collagenized stroma. Immunohistochemically, all 7 cases tested were positive for vimentin and NSE, while 6 cases expressed S-100 protein and 2 cases expressed desmin. Follow-up information showed recurrences in two patients 2 and 15 years after local excision. CONCLUSIONS: OFT is a distinctive soft tissue tumor of potentially low-grade malignancy which occurred predominantly in middle to old aged patients. The characteristic bony shell, the unique cytological appearance and arrangement of the cells are pathognomonic features of OFT. Our immunohistochemical result supported a Schwann-cell origin.

Recurrent ossifying fibromyxoid tumour of soft parts. Immunohistochemical profile and ultrastructure.

Growing bulk of evidence supports a view that ossifying fibromyxoid (OFMT) tumor histogenetically belongs to tumors derived from peripheral nerve sheath. Its precise cellular ancestor is disputable nevertheless the Schwann cell should be considered as a first candidate. Clinical behavior of this rare and usually benign neoplasm can probably vary from benign to even truly malignant, though the latter possibility is extremely rare. We present a case of recurrent OFMT located subcutaneously in the medial aspect of the knee in 66-year-old male. Macroscopically, microscopically, and immunohistochemically both primary and recurrent tumors were almost identical. Tumors were entirely negative for S-100 protein and strongly positive for neuron specific enolase. However, electron microscopy did not reveal any traces of basal lamina. Apparent lack of vascularization of tumor tissue may play an important role in the morphogenesis of OFMT.

Ossifying fibromyxoid tumor of soft parts: a report of 17 cases with emphasis on unusual histological features.

Ossifying fibromyxoid tumor of soft parts is an unusual benign neoplasm, with a tendency for local recurrence. Its typical microscopic appearance is that of a multinodular proliferation of round to spindle shaped cells separated by fibrous bands in which bone formation is often seen. Herein, we present the clinicopathologic features of 17 examples of this tumor with particular emphasis on some unusual histopathologic features that may place pitfalls in the diagnosis of this tumor, including satellite micronodules, mucinous microcysts, absence of myxoid areas, crush artifact, multiple microcalcifications, epidermoid cysts, atypical chondroid differentiation with binucleate lacunar cells, pericytic growth pattern, and malignant change. Awareness of these unusual morphologic features should lead to a search for areas displaying the more typical features of ossifying fibromyxoid tumor to arrive at a correct diagnosis.

Ossifying fibromyxoid tumor of the retroperitoneum.

A case of ossifying fibromyxoid tumor (OFMT) in an unusual site, the retroperitoneum, in a 71 year old Japanese man is reported. The well demarcated tumor contained a large amount of mature bony tissue within the tumor. The tumor cells were round to spindle-shaped, and showed a high cellularity in some areas and were loosely arranged in other areas. Although the majority of tumor cells expressed vimentin, neuron specific enolase and Leu-7, there were no tumor cells positive for S-100 protein, myogenic or epithelial markers. We would like to emphasize that tumors classified as OFMT contain a wide spectrum of histologic features and heterogeneity.

Ossifying subcutaneous tumor with myofibroblastic differentiation: a variant of ossifying fibromyxoid tumor of soft parts?

Immunohistochemical, ultrastructural, and flow cytometric studies were performed on an ossifying soft-tissue tumor, presumed to be a variant of ossifying fibromyxoid tumor of soft parts, which was located in the subcutis of the left buttock of a 76 year old Japanese woman. Histologically, this was a benign-looking spindle, oval, or round cell lesion, having a fibrous capsule with a discontinuous rim of bone as seen in typical cases. However, this lesion was also characterized by a high degree of cellular proliferation in storiform and whorl arrangements, extensive ossification, osteoid and metaplastic bone formation and absence of myxoid features. In an immunohistochemical study using formalin-fixed, paraffin-embedded sections, many tumor cells expressed vimentin, S-100 protein, Leu-7, neuron specific enolase, and desmin. Ultrastructurally, this neoplasm consisted of fibroblast-like cells and myofibroblast-like cells. This tumor had an aneuploid DNA content. No recurrence has been observed for 16 months. These results suggest that the neoplastic cells may show the phenotypic expressions of myofibroblast and also osteogenic differentiation.

Ossifying fibromyxoid tumor of soft parts: a morphological and immunohistochemical study.

A case is presented of ossifying fibromyxoid tumor of soft parts (OFMTSP) which occurred in the left cheek of a 59 year old Chinese woman. Histologically, the tumor was located in the subcutis with a fibrous pseudocapsule that contained discontinuous rims of mature trabecular bone. The tumor cells were small, round to ovoid with a uniform, round nucleus and a pale or slightly eosinophilic cytoplasm. Most of the cells were arranged in a random manner, some in a vague lace-like pattern. Mitotic figures were extremely rare. The stroma appeared fibromyxoid with scattered foci of mucinous lakes. Immunohistochemically, most of the neoplastic cells displayed immunoreactivities for S-100 protein, S-100 protein alpha, vimentin and alpha-smooth muscle actin; many tumor cells were positive for desmin. The tumor also showed stromal immunoreactivity for type IV collagen and was negative for cytokeratins, epithelial membrane antigen, glial fibrillary acidic protein, neurofilaments, muscle-specific actin, Leu-7, myelin-basic protein, osteocalcin and melanoma-specific antigen. The immunophenotypes expressed by the present OFMTSP seem to reflect two lineages of neoplastic cell differentiation, that is of nerve sheath and of smooth muscle; at the present stage, it is premature to diagnose this lesion as either nerve sheath or smooth muscle tumor.