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April 2005. A woman aged 24 years presented with symptoms related to a tumor in the fourth ventricle. Cytologically, the tumor was biphasic with areas typical of a classic ependymoma, including rosettes, and other areas containing grossly atypical giant cells. Many tumor cells were GFAP-positive and ultrastructural examination revealed microvilli and cilia. The histopathologic abnormalities place this tumor among the ependymomas. Its focal giant cell phenotype is very rare, but has been reported in 4 intracranial or filum ependymomas.

Osteoclast-like giant cell tumor of the pancreas is a very rare neoplasm, of which the histiogenesis remains controversial. A 63-yr-old woman was hospitalized for evaluation of epigastric pain. An abdominal computerized tomography revealed the presence of a large cystic mass, arising from the tail of pancreas. A distal pancreatectomy with splenectomy was performed. Histologically, the tumor was composed of mononuclear stromal cells intermingled with osteclast-like giant cells. In addition, there was a small area of moderately to well differentiated ductal adenocarcinoma. The final pathologic diagnosis was osteoclast-like giant cell tumor of the pancreas with ductal adenocarcinoma. Here, we describe the histopathological, immunohistochemical, ultrastructural and molecular biological findings of this tumor with review of the literature pertaining to this condition.

The histological, histochemical, immunohistochemical and ultrastructural features of a benign giant cell tumour (BGCT) of tendon sheaths in a 12-year-old male European lynx (Lynx lynx) are reported herein. The neoplastic mass involved the subcutaneous and inter-muscular tissues of the first, second, third and fourth digit of the left forelimb, from the phalanxes up to the carpus. The tumour appeared as a grey-whitish tissue mottled with darker areas, along with several scattered foci of orange colour. Histologically, the lesion consisted of a mixed population of numerous, multinucleated giant cells and epithelioid or spindle-shaped mononuclear cells embedded in a loose, highly vascular stroma. Neoplastic cells lined cleft formations and synovial-like projections into cystic spaces. No osteoid matrix could be detected. Haemorrhage and necrosis were also observed. The mononuclear and the giant cells were tartrate-resistant acid phosphatase and periodic acid-Schiff positive, being also immunohistochemically reactive for lysozyme and vimentin, with a few cells showing immunopositivity also for alpha-1-antitrypsin. Ultrastructurally, histiocyte-like cells, fibroblast-like cells and multinucleated giant cells were observed, but no virus-like particles could be detected in any of the above cell types. The BGCT of tendon sheaths, a fairly uncommon neoplasm in animals, has not been previously reported in the lynx.

Morphological, ultrastructural, and immunohistochemical findings of 12 diffuse type-tenosynovial giant cell tumors/pigmented villonodular synovitis are presented compared to 30 localized tenosynovial giant cell tumors (giant cell tumor of tendon sheath). Diffuse-type-tenosynovial giant cell tumor is characterized by a striking vascularisation pattern composed of densely arranged thin-walled, partly slit-like and partly hyalinized small blood vessels within the papillary synovial fronds. These vessels may show abnormal structures with incompletely arranged endothelial cells/pericytes. The fibrohistiocytic tumor cells probably cause considerable compression/distortion or destruction of the small vessels which might be responsible for an increased blood deposition and massive hemosiderosis. Accompanying multinucleated osteoclast-like giant cells seemingly are recruited from circulating blood monocytes. Microhemorrhagic foci with multinucleated giant cells could be detected in 83% of diffuse-type and 67% of localized-type tumors. Apart from the described vessels, typical morphological findings in diffuse-type tenosynovial giant cell tumors included "giant" hemosiderotic granules, (at least 2-3 times the diameter of an erythrocyte) "giant" siderophages, pseudoalveolar clefts and irregularly anastomosing synovial fronds. Neither mitotic rate nor the amount of giant cells/amount of nuclei of giant cells revealed statistically significant differences between localized-type and diffuse-type of tenosynovial giant cell tumor. Immunohistochemically, the diffuse-type exhibited focal expression of CD31 (in 75% of tumors) and calretinin (in 63%) besides CD68-staining.

Background: Osteoclast-like giant cell tumors are usually observed in osseous tissue or as tumors of tendon sheath, characterized by the presence of multinucleated giant cells and mononuclear stromal cells. It has been reported in various extraosseous sites including breast, skin, soft tissue, salivary glands, lung, pancreas, female genital tract, thyroid, larynx and heart. However, extraosseous occurrence of such giant cell tumors in the kidney is extremely rare and is usually found in combination with a conventional malignancy. De-novo primary malignant giant cell tumors of the kidney are unusual lesions and to our knowledge this is the second such case., Case Presentation: We report a rare case of extraosseous primary denovo malignant giant cell tumor of the renal parenchyma in a 39-year-old Caucasian female to determine the histogenesis of this neoplasm with a detailed literature review., Conclusion: Primary denovo malignant giant cell tumor of the kidney is extremely rare. The cellular origin of this tumor is favored to be a pluripotential mesenchymal stromal cell of the mononuclear/phagocytic cellular lineage. Awareness of this neoplasm is important in the pathological interpretation of unusual findings at either fine needle aspiration or frozen section of solid renal masses.

Background: We report a case of malignant fibrous histiocytoma, giant cell type (MFHGC), of the breast. A review of the literature failed to reveal cytology-based reports on this entity. The cytologic similarity of breast MFHGC on fine needle aspiration biopsy (FNAB) to other malignant breast neoplasms, including carcinoma with osteoclastlike giant cells, metaplastic carcinoma and breast sarcomas, as well as benign reactive processes, makes the recognition of this tumor challenging., Case: A 72-year-old woman presented with a 5-month history of an enlarging breast mass. FNAB of the mass showed a hypercellular smear composed of cohesive, branching clusters of spindle cells with ovoid, focally hyperchromatic nuclei and inconspicuous nucleoli. Interspersed osteoclastlike giant cells, some associated with clusters of spindle cells, were uniformly seen throughout the smear. The background was hemorrhagic, with cellular debris and occasional spindle cells and lymphocytes. No ductal epithelial or myoepithelial cells were seen. An incisional biopsy was performed, followed by radical mastectomy. The histologic examination was diagnostic of MFHGC. The diagnosis was supported by immunohistochemical and electron microscopic studies., Conclusion: MFHGC, also called primary giant cell tumor of soft tissues, is composed of a mixture of histiocytes, fibroblasts and bland-appearing osteoclastlike giant cells with a multinodular growth pattern. Although MFHGC rarely occurs in the breast and the definitive diagnosis is difficult based on cytology alone, the diagnosis can be considered when a cytologic examination reveals a hypercellular, spindle cell smear with osteoclastlike giant cells in the absence of ductal epithelial or myoepithelial cells.

Giant cell fibroblastoma (GCF) is a rare soft tissue tumor most often discovered during the first two decades of life. We present a case of a 3-year-old boy with a history of a recurrent lesion in the knee, the tumor growth progressively and enlarged to 2.1 cm in the previous two years before diagnosis. It involved the subcutaneous tissue, had infiltrative borders and extended into the superficial dermis. The tumor was surgically excised with free margins. There was no evidence of local recurrence, and a metastatic workup was negative after 10 years of follow up. We review herein the clinicopathologic features, histogenesis, differential diagnosis and relationship to dermatofibrosarcoma protuberans (DFSP).

Two cases of the diffuse type of giant-cell tumor of the tendon sheath (GCTTS) are described. Both tumors arose in the vicinity of large joints of the lower extremity, showing similar clinical and radiological features. Histologically, a proliferation of polygonal mononuclear cells was seen, together with osteoclastlike giant cells, foam cells, and siderophages. The tumors were poorly delineated, displaying an infiltrative pattern into the neighboring soft tissues. Immunohistochemically, strong expression of vimentin, neuron-specific enolase, A1-antitrypsin, and CD68 was found in both mono- and multinucleated tumor cells. At the ultrastructural level, mononuclear cells revealed a diverse morphology, displaying features of histiocytelike and fibroblastlike cells, with the former being more numerous. Scarce neurosecretorylike granules, made up of electrondense membrane-bound material, were found in the cytoplasm of the mononuclear cells. Cytogenetic analysis of one case shows the presence of a clonal population with 47 chromosomes and two different translocations, t(2;3) and der(8) t(8;12). Present findings provide further support regarding the neoplasic nature of this tumoral entity.

Aims: To document the clinical, light microscopic, immunohistochemical and ultrastructural features of four cases of extra-orbital giant cell angiofibromas., Methods and Results: Sections of formalin-fixed paraffin-embedded specimens were studied by haematoxylin and eosin, reticulin and immunohistochemical stains. Electron microscopy was carried out in two cases on tissue fixed in formalin. The age of the patients ranged from 30 to 41 years. Two patients presented with a soft tissue swelling in the left groin, one patient had a left axillary soft tissue lump and one patient presented with a parotid lump. All lesions were well circumscribed and contained variably cellular and vascularized tissue composed of round to spindle cells with a patternless arrangement, scattered multinucleate giant cells and pseudovascular spaces conforming to the description of giant cell angiofibroma. Mononuclear and multinucleate tumour cells were both positive for vimentin and CD34; one tumour exhibited focal S100 protein and GFAP positivity. Both of the tumours examined by electron microscopy showed fibroblastic features, but in addition one contained cells having Schwannian features. All four patients were well without recurrent disease on follow-up (average 25 months)., Conclusion: Giant cell angiofibroma shares many features with solitary fibrous tumour and giant cell fibroblastoma and shows a wider distribution than initially recognized. Rarely, Schwannian differentiation may be observed in these tumours.

The histological, immunohistochemical and ultrastructural features of a case of giant-cell fibroblastoma from the soft tissues of the chest wall in a 48-year-old female are described with special reference to the cell surface and matrix. Subplasmalemmal linear densities (SLDs) characterised cell surfaces, and exhibited excessive development of the dense external component: foci of identical dense material were present in the matrix. The nature of these dense foci, both the external component of the SLD and those free in the extracellular space, was investigated by light microscope immunostaining for fibronectin, laminin and collagen IV. All three proteins stained vessels. There was weaker but positive staining for tumour cell surfaces and matrix, consistent with the widely dispersed nature of the dense foci. Given their fine structural appearance, these dense foci can be referred to as granular matrices. Given also that the matrix protein immunostaining pattern is consistent with the distribution of these granular matrices as observed by electron microscopy, they may be provisionally interpreted as a kind of basement-membrane-related granular matrix. The presence of these proteins emphasises the point that, while giant-cell fibroblastoma fibroblasts lack a lamina, they nevertheless bear basement-membrane-related proteins organised, however, in a non-laminate fashion. The observations reinforce the need to qualify immunostaining results by ultrastructural investigation in order to understand the organisation of immuno-detected proteins and are discussed in terms of their diagnostic and possible biological significance.

A neoformation has been surgically withdrawn from third finger extensor tendon of the right hand of a 52 year male subject. Light (LM) and electron microscope (EM) observations from a number of tissue fragments allowed the identification of tumor nature, which appeared a giant cell tendon sheath. Moreover, some structural patterns have been described and compared to the previously reported cases. In areas of major cell density, parenchyma does not show lobular or gland-like organization; on the other hand, wide zones characterized by an amorphous matrix, progressively replacing collagen and containing elongated cells, are present. Giant multinucleated cells, mostly localized close to collagen bundles, can also be revealed. Unexpectedly, no foam cells appear and no phagocytized cell debris can be identified in giant multinucleated cells. Engulfed crystals are, differently, evidentiated by electron microscopy, both in mono- and multinucleated cell cytoplasm. Their electron density and their localization within cytoplasmic vacuoles suggest the presence of calcium. A correlation between giant cells and osteoclasts is then proposed. Multiple variously oriented centrioles support the possible mitotic genesis of multinucleated giant cells, which never show, on the other hand, fusion features. Siderosomes and residual bodies are also present. An unusual, diffuse thickening of nuclear lamina, only interrupted at nuclear pore level, is described and discussed.

Purpose: To report the clinicopathologic features of a newly recognized tumor, giant cell angiofibroma., Design: Observational case series., Main Outcome Measures: Clinical and histopathologic features of giant cell angiofibroma., Methods: Light and electron microscopy and immunohistochemistry of five cases of giant cell angiofibroma., Results: A total of five patients (4 women and 1 man) are described: two presented with a painless mass in the eyelid, two with a mass in the orbit, and one presented with a conjunctival lesion. All lesions were well demarcated with no capsule and were composed of blood vessels, a patternless spindle-shaped cell proliferation with a solid and pseudovascular appearance, and multinucleated giant cells. Both spindle-shaped and giant tumor cells were intensely positive for CD34 and vimentin., Conclusion: Giant cell angiofibroma resembles solitary fibrous tumor and giant cell fibroblastoma and should be considered in the differential diagnosis of spindle-cell tumors in the eyelid, orbit, and conjunctiva.

Multinucleated giant stromal cells (MGSC) have been described in a variety of lesions of various anatomical sites. They are generally believed to be derived from fibroblasts or myofibroblasts. Their size and bizarre appearance may lead to an erroneous interpretation of infiltrating malignant cells, but they are regarded as reactive in nature. MGSC also seem to participate in a neoplastic process and form a part of tumors called giant cell fibroblastomas (GCF). In GCF, multinucleated giant cells are sparsely scattered throughout the tumor, which is composed of loosely arranged spindle cells. Thus far, no tumor composed of MGSC entirely, to the best of the authors' knowledge, has been reported. This study involved an 80-year-old female with an omental tumor, which is believed to represent the first case of tumor of MGSC. The patient developed abdominal pain; a large abdominal tumor measuring 18 x 15 x 5 cm by computerized tomography was found located between the left lobe of the liver, the transverse colon, and the greater curvature of the stomach. Although the tumor was adherent to the above organs and infiltrating the omentum, it was resectable. Grossly, the tumor was highly vascular and the surface was shaggy with no recognizable capsule. The cut surfaces were red to tan with frequent cystic spaces containing bloody material. Microscopically, the tumor cells were large and multinucleated (2-6 nuclei) with prominent nucleoli. The cytoplasm was abundant and stained amphophilic. These tumor cells formed moderately cellular sheets filling the spaces between the varying sized vessels. There was prominent vascularity throughout the tumor. DNA study by image analysis revealed aneuploidy peaks. On immunohistochemistry, the tumor cells were strongly positive for vimentin, moderately positive for actin along the periphery of the cytoplasm, and negative for cytokeratin, EMA, myoglobin, S-100, CEA, Factor XIIIa, HMB-45, and HAM56 and KP-1. Ultrastructurally, the cytoplasm contained rich profiles of RER with scattered lysosomes. The cell borders were slightly irregular with occasional subplasmalemmal densities facing loosely arranged collagenous stroma. The light microscopic, immunohistochemical, and electron microscopic features of tumor cells were remarkably similar to MGSC. The tumor size and gross appearance suggested a malignancy, but it was a diploid tumor and the patient remains disease free 5 years after a complete resection.

Extraarticular diffuse tenosynovial giant cell tumor is an unusual lesion the cytologic picture of which has not been discussed much in the literature. Fine needle aspiration biopsy of a nonpainful mass in the right shoulder in an 18-year-old woman revealed a highly cellular lesion consisting of polygonal cells and multinuclear giant cells with scant nuclear pleomorphism and a marked tendency toward xanthomization. Electron microscopy identified two basic cell populations among many intermediate forms: cells with scant filopodia and abundant ribosomes and cells with well-developed prolongations and numerous mitochondria, lysosomes and lipid drops. The karyotype of the tumor cells obtained from a surgically excised specimen showed a clonal population with 45, XX, t(1;2) (pter->p22::q24->pter), t(1:14)(qter->p13::q13->ter). The cytologic differential diagnosis included other tenosynovial lesions containing xanthomatous cells. Cytogenetic findings are discussed in relation to chromosomal alterations previously found in related lesions (nodular tenosynovitis and pigmented articular villonodular synovitis).

The diffuse-variant tenosynovial giant cell tumor is rare. Although it shares histologic features with the exclusively intra-articular pigmented villonodular synovitis and local tenosynovial giant cell tumor, its behavior differs dramatically, being locally very aggressive. We report a case of a diffuse-variant aggressive tenosynovial giant cell tumor that, although diploid by flow cytometry, demonstrated trisomy 7 and 5 as well as clonal rearrangements involving chromosomes 1, 3, and 15. These cytogenetic abnormalities may be markers for aggressive behavior and useful for directing treatment.

To investigate character and proliferation of tumor cells of giant cell tumor of tendon sheath (GCTTS), we studied 25 cases of GCTTS by light and electron microscopic immunohistochemistry. Mononucleated stromal cells (SC) of GCTTS could be divided into three types according to their antigenic features. The first type was the histiocytic SC expressing antigens recognized by KP1, Mac387 and Ham56. The second type was the fibroblastic SC showing fibronectin immunoreactivity. The third type was the intermediate SC expressing both KP1 and fibronectin. The presence of intermediate SC suggested that the different types of SC of GCTTS would be of common origin, i.e. from the mesenchymal cells of the synovium and represented different functional phases or phenotypic alterations. The expression of proliferating cell nuclear antigen (PCNA) was observed only in SC and occasionally, in binucleated cells, but multinucleated giant cells (GC) were negative for PCNA, suggesting that GC were non-dividing cells.

A case of malignant giant cell tumor of the tendon sheath of the right hip, which developed in a 72-year-old Japanese woman, is described. The tumor exhibited histological similarities to a benign giant cell tumor of the tendon sheath (localized nodular tenosynovitis). The resected tumor, measuring 9 x 9 x 11 cm, was located in the adductor muscle and invaded the proximal femur and acetabulum. The nodule was encapsulated with a thin membrane which was soft and gelatinous in consistency and varied in color from yellow to brown. The synovium of the hip joint was normal. The primary lesion was composed of plump polyhedral and spindle-shaped cells. The nuclei were large, irregular and hyperchromatic, and contained prominent nucleoli. A moderated number of multinucleated giant cells was scattered throughout the lesion. There was little stromal collagen. In the majority of the specimens, pseudoglandular or alveolar spaces were predominant. An ultrastructural study demonstrated three cell types: fibroblast-like, histiocyte-like and an intermediate. The patient underwent reconstructive surgery with a Dacron fabric-enveloped alumina ceramic pelvic prosthesis and total hip components after resection of the primary lesion. Unfortunately, because of a local recurrence, a hemipelvectomy was required 10 months after the initial operation. At that time the intestines were involved with the recurrent tumor, and the patient subsequently died of perforative peritonitis. An autopsy revealed distant metastases to the right pelvis, urinary bladder, right ureter, ilium, mesenterium and lungs.

Unusual crystalline cytoplasmic inclusions were encountered in tumor cells in a subependymal giant cell tumor (SEGT) in a 16-year-old girl with tuberous sclerosis. By electron microscopy, the tumor cells demonstrated typical features previously described in SEGT, including abundant dense bodies, prominent Golgi complexes, abundant mitochondria, rough and smooth endoplasmic reticulum, scattered intermediate filaments and microtubules, glycogen, and rare synaptic contacts as well as primitive intercellular junctions. The dense bodies were bound by a single membrane and were round, ovoid, irregular, or cylindric in appearance with electron-dense homogenous content or fingerprint profiles. Of note was the presence of numerous cytoplasmic rhomboidal or rectangular crystalline inclusions akin to those seen in alveolar soft part sarcoma. These inclusions measured as much as 8 microns in length and had 7-nm periodicities, often with intersecting lamellae. Rarely, the membrane-bound dense bodies showed areas of similar periodicities, indicating that the crystalline inclusions are related to and might originate from the dense bodies. While crystalline inclusions have previously been described in one patient with SEGT (Bender and Yunis, Ultrastruct Pathol 1980; 1:287-299), the inclusions in the present case were a striking feature and add to the spectrum of the ultrastructural pathology of SEGT.

A cell line (CG-1) was established from a specimen of a 21-year-old woman with giant cell tumor of bone. Inverted-phase microscopic analysis showed that the cultured cells were spindle-shaped in appearance. Multinucleated giant cells and macrophagelike round cells characterizing the histology of giant cell tumor of bone were not found. It is believed that the spindle-shaped cells were the neoplastic element of this tumor, because they were cultured more than 40 passages over the course of one year and subsequent cytogenetic analysis with a G-band technique showed constant loss of chromosomes 14 and 19. The cell line was found to produce several cytokines: M-CSF, IFN-gamma and TNF-alpha, as demonstrated by Western blotting analysis. These cytokines are known to show chemotactic, differentiation-inducing, and activating effects on macrophages. Because it has been recently reported in the literature that there are many infiltrated macrophages in giant cell tumor of bone, and because multinucleated giant cells are formed by fusion of macrophages, the newly established cell line may prove a useful system in studying the nature of giant cell tumor of bone.

Giant cell tumor of the tendon sheath with characteristic magnetic resonance imaging findings is reported. The tumor was low intensity on T1-weighted and T2-weighted images, and showed strong homogeneous enhancement. These findings were considered to represent the pathological features of fine hemosiderin granules and collagenization.

Method: A new neoplastic cell line, UISO-GCT-1, was established from a giant cell tumor of the right tibia in an 18-year-old man. Immunohistochemical, cytogenetic, ultrastructural, and growth studies were performed., Results: Multinucleated giant cells (> 4-6 nuclei/cell) persisted in a culture relatively late in passage (passage 17), which is unique in cell lines of giant cell tumor of bone. Mononuclear and multinucleated cells in monolayer culture expressed vimentin and tartrate-resistant acid phosphatase and reacted with monoclonal antibodies to CD13 and CD68, suggesting a monocytic-macrophage origin of these cells. Mononuclear and multinuclear cells also selectively expressed high molecular weight cell membrane antigens specifically associated with soft tissue sarcomas and osteosarcomas. Karyotypically, UISO-GCT-1 cells were hypodiploid, hypotetraploid, and multiploid, with more than 200 chromosomes per mitosis present in some cells. Other chromosomal aberrations observed included ring chromosomes, double minutes, translocations, multiple fragments, and multiradials., Conclusion: Collectively, observations of this study suggest that karyotypically abnormal giant cell tumors of bone arise from a monocyte-macrophage lineage and subsequently express an antigenic profile similar to malignant mesenchymal tumors.

Enzymatic activity and cell membrane proteins were characterized in cells from five giant cell tumors of bone (GCTs). Naphthyl alpha esterase (NAE) and acid phosphatase (AP) activity was noted within both the mononuclear and multinucleated cells of each tumor. In each tumor, all mononucleated cell populations displayed tartrate-sensitive AP activity, whereas the multinucleated cell populations demonstrated variable expression of tartrate-sensitive and tartrate-resistant AP activity. Analysis of cell membrane proteins included attempts at immunodetection of mannose receptor, OKM-1 antigen (OKM-1a), colony-stimulating factor-1 receptor (CSF-1r), and platelet-derived growth factor receptor (PDGFr). None of these membrane antigens were elicited on multinucleated cells. In contrast, the mannose receptor, OKM-1a, and PDGFr all were detected on the mononucleated cells within each tumor. These data demonstrate that a population of mononucleated, not multinucleated cells, expresses features unique to mature mononuclear phagocytes and establishes the presence of a membrane receptor, PDGFr, associated with mitogenesis of mesenchymal cells.

Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (10(6)/ml) contained large amounts of IL-6 (37.9 +/- 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 +/- 11.5 ng/ml). Giant cells and stromal cells from giant cell tumors expressed IL-6 mRNA, as indicated by polymerase chain reaction analysis and in situ hybridization studies, and immunohistochemical techniques demonstrated that the giant cells expressed IL-6 receptors. The addition of a neutralizing antibody to IL-6 significantly decreased the area of dentine resorbed by purified giant cells in a dose-dependent manner, and the addition of IL-6 to cultures of purified giant cells pretreated with anti-IL-6 restored the resorbing capacity of the giant cells. These data suggest that IL-6 may act as both an autocrine and a paracrine factor for human osteoclasts and play an important role in the bone-resorbing capacity of these cells.

We describe a rare carcinoma of the gallbladder containing osteoclast-like giant cells. Well-differentiated adenocarcinoma was found in the mucosa of the fundus, and osteoclast-like giant cells were present mainly in a haemorrhagic mass protruding from the mucosal surface. The metastatic hepatic tumour was composed chiefly, if not exclusively, of osteoclastoma-like cells, but minute carcinomatous elements were also present. There was an apparent transition between the giant cells and tubular structures in both the gallbladder tumour and hepatic tumour. However, ultrastructural study did not reveal any evidence of epithelial differentiation in the giant cells. Immunohistochemical studies suggested that the mononuclear and giant cells were mesenchymal and histiocytic in nature (vimentin and factor XIIIa positive). A few exceptional giant cells transforming from the fine tubular structure were positive for epithelial membrane antigen. In conclusion, the osteoclast-like giant cell tumour component was thought to represent mesenchymal metaplasia in pre-existent adenocarcinoma.

An in vitro tissue culture was established using a giant cell bone tumor derived from a 66-year-old female. The tumor was clinically classified as stage 2, and grade 1 histologically. Morphological observations including, in vitro growth character, histochemical and immunohistochemical staining, and ultrastructural studies, support that the giant cell originated from the mononucleated stromal cell. They do not belong to the monocyte-macrophage system. In this aggressive case, we also tried to evaluate the significance of using DNA ploidy flow cytometry, and chromosomal study in predicting its clinical outcome. The DNA ploidies of both the primary and cultured tumor cells were diploid. The chromosomal analyses revealed its chromosome number ranging from 43 to 46 with three clonal structural changes; dic (19;20) (p13;q13), dic (19;22) (q13;q13) and dic (12;?) (p13;?). As previously compared and reported, cases with marker chromosomes usually had a more aggressive clinical course than those without marker chromosomes. Instability of the terminal portion of the F- and G- chromosome groups were reported in other studies and were also detected in our case. Possible association of clinical aggressiveness with the clonal structural changes, especially dic (19;20) (p;q) and dic (19;22) (q;q), needed further investigation.

Bone tumors were categorized into alkaline phosphatase (ALPase)-positive (2 ossifying fibromas, 1 benign osteoblastoma and 16 osteosarcomas) and negative (2 chondromas, 2 chondrosarcomas, 3 non-ossifying fibromas, 2 malignant fibrous histiocytomas and 6 giant cell tumors of bone) groups. Production and distribution of matrix vesicles (MVs) in the tumor tissues were examined to clarify their role in neoplastic bone formation. Four distinct types of MV were isolated primarily in ALPase positive bone tumors: empty, amorphous, crystalline and ruptured MVs. They were formed by budding off from the cytoplasmic projections of the osteoblastic tumor cells. The significance of differences in the production rate of MVs between ALPase-positive and negative bone tumors was investigated in view of the predominantly high production of MVs in ALPase-positive bone tumors. Many more mature MVs (crystalline and ruptured) were observed in the osteoblastic lesions of osteosarcoma than in the fibroblastic and MFH-like lesions, suggesting an intimate relationship with maturation and differentiation of the osteoblastic tumor cells. The above findings indicate that production of MVs is one of the diagnostic parameters for osteoblast-derived bone tumors, as well as ALPase activity, and that vesicle-induced mineralization is a major mineralization mechanism in neoplastic bone formation.

The number of nucleolar organizer regions (NORs) in giant cell tumors of bones was measured using the one-step silver staining technique (AgNOR) with black and white photographs and semiautomatic image analysis. The purpose of the study was to determine whether this method provides useful information on the biological behavior of bone GCTs. The number of AgNORS in bone CGTs (mononuclear cells: 3.45 +/- 1.17, and multinucleate cells: 2.52 +/- 0.97) was found to be higher than in NOF cells (2.16 +/- 1.02 and 2.01 +/- 0.78) but lower than in MFH cells (4.17 +/- 1.3 and 3.86 +/- 1.24). Statistical analysis showed that differences between GCTs and MFH were highly significant for both mononuclear and multinucleate cells, whereas differences between GCTs and NOF were significant only for mononuclear cells.

The behaviour of multinucleated giant cells (GCs), obtained from a giant cell tumour of the tibia and cultured on glass coverslips or on devitalized bone slices, was studied using light and electron microscopy. Monitoring the GCs on bone slices by phase-contrast microscopy revealed that they had removed calcified bone matrix resulting in excavation of lacunae, with subsequent lateral extension and perforation of the bone slices. Electron microscopy demonstrated for the first time that the GCs responsible for exavating lacunae had two specific membrane modifications, ruffled border and clear zone, and showed basically similar cytoplasmic fine structures to those of osteoclasts. Fluorescence images of the GCs on glass and on bone after rhodamine-conjugated phalloidin staining revealed that most of the GCs had an intensely fluorescent peripheral band composed of a number of F-actin dots called podosomes. Some GCs showed unusual arrangements of podosomes suggesting abortive attempts at GC formation. We have demonstrated that the band structure of the GCs cultured on bone is intimately involved in bone resorption. Two stromal cell types could be recognized. The predominant type, which seemed to be the only neoplastic element because of its proliferative capability, showed quite different fine structural and cytoskeletal features from the GCs. The other type, which was much less frequent and seemed not to proliferate, had morphological similarities to the GCs, and seemed to be their precursor. Importantly GCs cultured on bone and the osteoclasts share common structures for adhesion to and resorption of bone, strongly supporting the view that the GCs of the giant cell tumour of bone are potentially active bone resorbers and can be regarded as osteoclasts.

A case of anaplastic, multinucleated giant cell tumor of the thyroid was studied by light and electron microscopy. The coexistence of anaplastic sarcomatous tumor and well differentiated follicular carcinoma, and the presence of desmosomes among the mononuclear cells suggested that this tumor originates in thyroid follicular cells. The multinucleated giant cells, which characterize this thyroid tumor, appeared to be formed by fusion of follicular carcinoma cells and mononuclear epithelial cells, and not by nuclear division without cytoplasmic division.

A case of neuroendocrine lung tumor located beneath the pleura in a 71-year-old woman is reported. At autopsy, the tumor was found to have metastasized to the bones and liver without involving the hilar lymph nodes. Histologically, the tumor cells at the primary site and in the liver metastasis exhibited a carcinoid-like organoid structure, whereas pleomorphic giant cells were noted in the bone metastasis. The argyrophilic tumor cells were immunoreactive for neuron-specific enolase, chromogranin A, serotonin, calcitonin, calcitonin gene-related peptide, gastrin-releasing peptide, neuropeptide Y, gastrin, pancreatic polypeptide, glicentin, the alpha-subunit of human chorionic gonadotropin, keratin, epithelial membrane antigen, Leu M1 and carcinoembryonic antigen. Electron microscopy revealed abundant neurosecretory granules in the cytoplasm. This was considered to be a rare case of neuroendocrine lung tumor showing carcinoid-like histology at the primary site and large-cell transformation in bone metastasis.

A rare, osteoclastoma-like giant cell tumor developed in the macronodular cirrhotic liver of an 87-year-old man. Histogenetically, the tumor was considered to be of reticuloendothelial cell (Kupffer cell) origin. A brief review of the literature concerning the extraosseous giant cell tumors is included in this report.

A case of basal cell epithelioma (BCE) with multiple large nuclei on the right buttock of a 69-year-old woman is reported, and the skin was studied by light and electron microscopy. This represented the only case (0.85%) of giant tumor cells with multiple nuclei among 117 patients with BCE. Ultrastructural studies revealed that giant tumor cells were not different from ordinary tumor cells of BCE, except for large convoluted nuclei. In the cytoplasms of giant tumor cells, we observed autophagic vacuoles which were derived from autophagocytosis. Scattered among the giant tumor cells, there were many degenerate tumor cells, some of which were phagocytized by giant tumor cells with multiple nuclei (referred to as macrophagocytosis). It is indicated that tumor cells have considerable phagocytic activities, and degrade the autophagic vacuoles or the degenerate tumor cells with the lysosomes. These findings suggest that the presence of the giant tumor cells with multiple nuclei does not indicate a increased malignant potential or anaplasia of the tumor, and that autophagocytosis or macrophagocytosis is a factor in initiating giant tumor cell formation.

Among the differentiated progeny of stem cells transplantable by bone marrow are osteoclasts, the multinucleate cells which are the major agents of bone resorption. Although the osteoclast is well characterized from a structural and functional standpoint, its development and origin are still far from clear. We have used monoclonal antibodies to investigate the interrelationship between osteoclasts and other haemopoietic cells in man. We have analysed the distribution of 19 granulocyte-monocyte antigens in eight reactivity clusters on the non-neoplastic osteoclasts present within nine osteoclastomas (syn. giant cell tumours of bone) and a single example of aneurysmal bone cyst. We found that osteoclasts are antigenically effete, failing to express granulocyte-monocyte, common leucocyte or other haemopoietic determinants; the only monocyte antigens detected on osteoclasts are My-7 and two closely related specificities, MCS.2 and DüHL60.4, which are also expressed by tissues outside the haemopoietic system. Our findings, taken together with recent transplantation studies, cast further doubt on the view that osteoclasts are specialized bone-resorbing macrophage-derived giant cells, and support a hypothesis that they are the end product of fusion of a hitherto unidentified circulating mononuclear cell type, the preosteoclast, which constitutes a cell lineage separate from those originating from the conventional multipotential haemopoietic stem cell, although still of bone marrow origin.

A case of osteoclast-type giant cell tumour of the pancreas is described and the features of eight other previously reported patients are reviewed. Characteristically, these neoplasms are large at presentation and show focal haemorrhage and necrosis, but seem slow to give rise to metastases. Histological examination reveals numerous osteoclast-like giant cells set in a sarcomatous stroma, the appearances being similar to those seen in giant cell tumours of bone. They are distinct from pleomorphic giant cell carcinomas of the pancreas and may have a slightly better prognosis after resection than ordinary adenocarcinomas. The histogenesis of these rare tumours is unknown.

Three similar and unique, predominantly osteolytic lesions are reported in young patients between the ages of 4 and 19 years. Progressive back pain and neurologic deficits were the principal clinical features. The initial roentgenographic impression was that of a malignant tumor either primary or metastic. Despite incomplete resections of a firm, intraosseous and extradural tumor, healing has occurred during the follow-up interval with one interim exception. A spindle-cell stroma containing a variable number of giant cells was the consistent microscopic finding. Ultrastructural studies of one case revealed that the mononuclear spindle cells and giant cells contained cytoplasmic microfilaments similar to those of the myofibroblast. The possible relationship of this tumor to nodular fasciitis and desmoplastic fibroma is hypothesized in the light of the role of the myofibroblast in the fibromatoses and nodular fasciitis.

Giant cell tumors are benign neoplasms of unknown etiology that have a histologically distinctive, multinucleated giant cell tumor associated. Microscopic evaluation is essential for accurate diagnosis. The treatment of choice is total surgical excision.

An attempt has been made of cryopreservation of tissue fragments from 6 GCTB surgical specimens. They have been kept in 10% DMSO or 15% glycerol medium and stored in liquid nitrogen for periods up to 180 days. Tumor cellular components survive the process of slow freezing and rapid thawing as cellular growth is successful in subsequent culture. Though certain reversible ultrastructural changes have been detected, no apparent distinction could be found in microscopic morphology, motility, growth behavior and LDH isozyme pattern between cultured cells of the cryopreserved fragments and those of the fresh ones. Electron microscopy shows that DMSO exceeds glycerol in protecting the ultrastructure of the cells. Slow cooling and rapid thawing is recommended because ice-crystals form in the intercellular space, which causes only light damage to the cells.

A case of malignant phyllodes tumor of the breast with unique multinucleated giant cells is reported. The possible nature of the giant cells is discussed briefly. The existence of such giant cells makes judgement of the tumor difficult, so that diagnosis must also be based on other histological criteria of malignancy.

A malign giant cell tumor of the soft parts is reported and the specific localization of the hand is pointed out; on this basis, a possible connection or a common origin is discussed and the latest literature reviewed.

Three cases of malignant giant cell tumors were studied by light microscope and electron microscope. Light microscopic observation revealed three different types of tumor cells, namely, malignant stromal cells, fibrosarcomatous cell and osteosarcomatous cells. Electron microscopic observation revealed that fibrosarcomatous cells had ultrastructure similar to that of malignant stromal cells. Both types of cells showed nuclear pseudo-inclusions (NPI), and well developed organellae related to matrix synthesis in the cytoplasm. Polysaccharide staining of the same cells revealed positive products in the cytoplasm. Osteosarcomatous cells showed irregular nuclei which contained NPI and well developed r-ER. The cells were located in the non-calcified matrix which consisted of collagen fibers. No alkaline phosphatase activity was observed in this area. These facts suggest that: (1) malignant stromal cells and fibrosarcomatous cells synthesize collagenous stroma as normal fibroblasts do, and (2) osteosarcomatous cells are devoid of the ability to promote matrix calcification.

Six cases of osteosarcoma, 5 cases of chondrosarcoma, and 6 cases of giant cell tumor of bone were studied by electron microscopy. The cells comprising osteosarcoma were basically osteoblasts and in addition to them, malignant chondrocytes, myofibroblasts and undifferentiated cells. The ratio of number of these cells were variable according to the portions designated microscopically as osteoblastic, chondroblastic and fibroblastic. Previous ultrastructural studies on osteosarcoma have scarcely revealed the presence of myofibroblasts. It is likely that osteosarcoma arises from undifferentiated mesenchymal cells capable of differentiating into various cells such as osteoblasts, chondroblasts, and fibroblasts; especially capable of differentiating into osteoblasts. On the other hand, chondrosarcoma was composed of the cells in the series of maturation from undifferentiated cells to chondrocytes. In high-grade malignant cases, glycogen particles and rough endoplasmic reticulum became less conspicuous, and occasionally malignant multinucleated cells were seen. In one case, endoplasmic reticular inclusions which were thought to be viral nucleocapsid by some authors were found. They, however, seemed to be formed by condensation of intracisternal granular material secreted by the rough endoplasmic reticulum. The cells comprising giant cell tumor of bone were multinucleated giant cells and stromal cells classified into four types. In a malignant case, giant cells showed no remarkable morphological change while stromal cells underwent an atypical change. This finding suggests that the mononuclear stromal cells are the principal tumor cells and the establishment of histological grading should mainly depend on the atypism of stromal cells. The tumor is likely to originate from undifferentiated mesenchymal cells which have the tendency of histiocytic and fibroblastic differentiation. The morphogenesis of multinucleated giant cells is not clarified in this study. Although the possibility that stromal cells are the origin of giant cells is still remained, it could also be speculated that giant cells are somehow related to immune response to the tumor having macrophage-related origin.