Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone.

Giant cell tumor of the bone (GCTOB) is a primary bone tumor that occurs mainly in young adults and is capable of locally aggressive growth. Its histologic appearance can resemble a number of benign and malignant tumors but no useful diagnostic marker is known currently. To identify diagnostic markers for this tumor, global gene expression profiling using cDNA microarray was performed on 6 fresh-frozen GCTOB, 3 aneurysmal bone cysts, 4 fibrous dysplasias and 12 giant cell tumors of tendon sheath/diffuse-type giant cell tumors. Unsupervised hierarchical clustering separated the tumors based on their histopathologic types, and significance analysis of microarray identified several genes including TP73L (encoding the p63 protein) that are significantly highly expressed in GCTOB relative to these other tumors. The diagnostic utility of p63 was subsequently confirmed using anti-p63 antibody on a series of 26 GCTOB, 25 aneurysmal bone cysts, 15 chondroblastomas, 13 giant cell reparative granulomas, 13 chondromyxoid fibromas, 4 brown tumors, 4 fibrous dysplasias, 53 giant cell tumors of tendon sheath/diffuse-type giant cell tumors and 385 additional mesenchymal tumors in tissue microarrays. Strong p63 nuclear staining was present in 18 of 26 (69%) GCTOB, 3 of 15 (20%) chondroblastomas and in 1 of 25 (4%) aneurysmal bone cysts while none of the other tumors commonly considered in the differential diagnosis of GCTOB showed any detectable p63 staining. Strong p63 staining is rare in bone and soft-tissue tumors in general. In contrast to the pattern of p63 staining, the majority of the chondroblastomas (70%) demonstrated S-100 immunoreactivity while only a minority of the GCTOB (8%) was immunoreactive for S-100. These findings altogether show that p63 can be used as a diagnostic marker to aid the clinical diagnosis of GCTOB.     

Fibro-osseous pseudotumor of digits - Expanding the spectrum of clonal transient neoplasms harboring USP6 rearrangement

Fibro-osseous pseudotumors of the digits (FOPD) is a rare self-limiting lesion composed of bland looking hypercellular fibrous tissue and bone.USP6 rearrangement is a consistent genetic finding in aneurysmal bone cyst, nodular fasciitis, myositis ossificans and giant cell lesions of small bones.We report herein the occurrence of USP6 rearrangement in fibro-osseous pseudotumors of the digits using fluorescence in situ hybridization analysis (FISH).Of the five patients included, three were female and two were male. The age ranged from 33 to 72 years (mean 48 years). Lesions arose in the palm (n = 2), thenar (n = 1), middle finger (n = 1) and great toe (n = 1). All patients underwent resection.Four cases (80%) harbored USP6 rearrangements showing that fibro-osseous pseudotumors of digits belongs to the spectrum of clonal transient neoplasms including aneurysmal bone cyst, nodular fasciitis, myositis ossificans and giant cell lesion of small bones.     

Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.

Aneurysmal bone cyst and giant cell tumor of bone are relatively rare bone tumors that sometimes coexist. We examined the karyotypes of 3 aneurysmal bone cysts, 12 giant cell tumors, and 3 combined lesions. All aneurysmal bone cysts showed involvement of chromosome segments 17p11-13 and/or 16q22. In addition, in 1 of the 3 giant cell tumors with secondary aneurysmal bone cyst, both chromosome bands were rearranged as well, albeit not in a balanced translocation. Seven out of 12 giant cell tumors were characterized by telomeric associations. One giant cell tumor showed a dup(16)(q13q22), suggesting the presence of a (minor) secondary aneurysmal bone cyst component, despite the absence of histological proof. Our results, combined with literature data further substantiate that segments 16q22 and 17p11-13 are nonrandomly involved in at least some aneurysmal bone cysts, irrespective of subtype (primary, secondary, intra/extraosseous, solid or classic). These findings strongly suggest that some aneurysmal bone cysts are true neoplasms. In addition, telomeric associations are the most frequent chromosomal aberrations in giant cell tumor of bone, the significance of which remains elusive. In combined giant cell tumor/aneurysmal bone cyst each component seems to retain its own karyotypic abnormality.     

Biologic characterization of human bone tumors IX. Occurrence of macrophages

Fifty bone tumors were investigated using immunohistological methods for an assessment of the amount and nature of macrophage infiltration. Polyclonal antibodies against lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsin were used as markers, besides certain monoclonal antibodies against blood monocytes and mature tissue macrophages. Particularly high macrophage infiltration was found in malignant fibrous histiocytomas, giant cell-containing osteosarcomas, giant cell tumors of bone, and aneurysmal bone cysts. Moderate infiltrates were seen in some highly malignant osteosarcomas, in fibrosarcoma, and in chondroblastoma. A low macrophage content was observed in some osteosarcomas, in Ewing's sarcomas, chordomas, fibrous dysplasias, aggressive fibromatoses, and cartilage tumors. Osteoclast-like giant cells showed distinctly positive reactions with the monoclonal antibody against mature tissue macrophages. In fibrohistiocytic tumors (MFH, giant cell tumor, non-ossifying fibroma) only macrophages gave positive reactions with those antibodies, whereas the reaction of spindle-shaped tumor cells was always negative. These results strongly indicate that the macrophages found in bone tumors (including those of fibrohistiocytic type) result from reactive infiltration. The autochthonous tumor cells are most probably derived from local mesenchymal cells, and are thus cytogenetically unrelated to the infiltrating macrophages.     

Pattern of primary tumors and tumor-like lesions of bone in children: retrospective survey of biopsy results

Background: Although primary bone tumors are relatively uncommon, they constitute the most important tumors in patients less than 20 years. We aimed to determine the frequencies of primary bone tumors and tumor-like lesions of bone and the anatomical sites of their occurrence. Methods: A retrospective review of histopathology reports of all bone specimens received in a private pathology laboratory in Istanbul between 2009 and 2015. Results: A total of 57 patients (aged 5 to 18 years) with a mean of 13.12 years were studied. Thirty five patients (61.4%) were males and 22 (38.6%) were females. Fifty five (94.4%) of the tumors were benign. Osteochondroma was the commonest tumor accounting for 31 cases (54.3%) followed by osteoid osteoma, 9 cases (15.7%). Chondrosarcoma observed in two patients and Ewing sarcoma in one patient as malignant tumors. Of the 57 bone tumors 13 (22.8%) occurred in the upper extremities, while 44 (77.2%) were in the lower extremities. Proximal humerus was the most commonly involved site in upper extremity tumors, with osteochondromas representing the most frequent type of tumor (4 patients; 7%). In the lower extremities again osteochondromas were the most common type of tumor (8 cases, 14%), with the femur being the most common site of involvement (18 patients, 31.5%). Of the patients with tumor-like lesions; four patients had fibrous dysplasia, 4 patients had non-ossified fibromas, 4 patients had simple bone cysts and 3 had aneurismal bone cyst. Conclusion: This study showed that primary bone tumors were mainly benign, settled predominantly in the lower extremities mostly in the femur with a male preponderance. Osteochondroma was the most common benign bone tumor. We didn’t observed osteosarcoma, which is the most frequent malignant bone tumor.     

Aneurysmal bone cyst,a study of ultrastructure and malignant transformation

Summary Four cases of aneurysmal bone cyst, of which one became malignant 7 years after irradiation, were studied by electron microscopy. The aneurysmal bone cyst was composed of four different types of stromal cells — fibroblasts, myofibroblasts, osteoblasts, and histiocytes — and osteo-clastlike multinucleated giant cells. The surface of blood spaces was devoid of specialized endothelium, which may explain the presence of large quantities of extravasated erythrocytes. Some histiocytes contained siderosomes. The malignant lesion consisted of two main types of stromal cells, of which one had electron lucent and the other electron dense cytoplasm. The stromal cells produced osteoid and the tumour was regarded as an osteosarcoma. The multinucleated giant cells resembled those observed in aneurysmal bone cysts, but the nuclei seemed to be more often spherical. It is concluded that irradiation of the aneurysmal bone cyst may cause sarcomatous transformation in a cell capable of producing osteoid.     

8例动脉瘤样骨囊肿

本文报告8例动脉瘤样骨囊肿的病变部位、临床症状及X线片表现类型,着重阐述了病变特点及囊壁组织分型;讨论了本病可能是伴发于其他良性肿瘤或瘤样病变的一种疾患,指出了骨组织局部动静脉的异常或动静脉痿的形成,引起局部血液动力学改变、静脉压持续升高在发病机理上的重要地位,并讨论了鉴别诊断。     

Expression of Ia and monocyte-macrophage lineage antigens in giant cell tumor of bone and related lesions

An immunohistochemical study of six giant cell tumors of bone and eight related lesions (aneurysmal bone cyst, fibrous histiocytoma, and giant cell tumor of tendon sheath) was performed using a panel of monoclonal antibodies directed to the Ia and monocyte-macrophage lineage antigens. In all types of lesion, osteoclastlike multinucleate giant cells were negative for both types of antigen, but a proportion of mononuclear cells gave positive reactions. While the possibility that these cells are reactive cannot be excluded, in giant cell tumor and malignant fibrous histiocytoma, their frequency and their morphologic similarity to the rest of the tissue suggest that they may be an intrinsic part of the neoplasm. This finding is consistent with the presumed fibrohistiocytic nature of these tumors.     

Cytodiagnosis of benign fibrous histiocytoma of rib and diagnostic dilemma: A case report

Benign fibrous histiocytoma (BFH) of bone is rare in occurrence, and rib is an unusual site. There are limited case reports of this entity in the literature, and cytodiagnosis of this tumor is not described. A 24‐year‐old man presented with a firm mass and pain in the right lateral chest wall. Radiological investigations (plain radiograph and computed tomography) revealed a lytic bone lesion involving the 5th rib. Radiologically, giant cell tumor (GCT), BFH, and plasmacytoma were suspected. In fine‐needle aspiration cytology (FNAC), admixture of benign stromal cells and scattered osteoclast type giant cells were found in the smears. Differential diagnoses of BFH, GCT (non‐epiphyseal type), fibrous dysplasia, and aneurysmal bone cyst were made on cytology. Subsequent histologic examination confirmed the diagnosis of BFH. Cytologic diagnosis of BFH of rib is difficult as this tumor may mimic other giant cell containing tumors of bone in FNAC. The final diagnosis should always be made after correlation with histological, radiological, and clinical features. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Giant Cell Tumor of Bone: A Neoplasm or a Reactive Condition?

Giant cell tumor of bone (GCTB) is a benign but locally aggressive bone tumor of young adults. It typically presents as a large lytic mass at the end of the epiphysis of long bones. Grossly it is comprised of cystic and hemorrhagic areas with little or no periosteal reaction. Microscopically areas of frank hemorrhage, numerous multinucleated giant cells and spindly stromal cells are present. Telomeric fusions, increased telomerase activity and karyotypic aberrations have been advanced as a proof of its neoplastic nature. However such findings are not universal and can be seen in rapidly proliferating normal cells as well as in several osseous lesions of developmental and/or reactive nature, and the true neoplastic nature of GCTB remains controversial. The ancillary studies have generally not reached to the point where these alone can be taken as sole diagnostic and discriminatory criteria. While giant cells and stromal cells have been extensively studied, little attention has been paid to the overwhelming hemorrhagic component. If examined carefully intact and partially degenerated red blood cells are almost invariably seen in many giant cells as well as in the stroma. While hemorrhage in many patients may be resolved without leaving any trace over time, in some it gives rise to giant cell formation, and in others it may lead to proliferation of fibroblasts and histiocytes. At times one sees xanthomatous cells due to intracytoplasmic cholesterol deposits and sharp cholesterol clefts. Individual genetic makeup, local tissue factors as well as the amount of hemorrhage may play a key role in the final effects and outcome. Malignancy usually does not occur in GCTB and when discover, it usually represents primary bone sarcomas missed at original diagnosis. Embolization therapy to curtail hemorrhage and insertion of cement substance to support matrix are helpful in reducing recurrences. Aneurysmal bone cyst (ABC) shares many features with GCTB. There had been unique karyotypic changes in some aneurysmal bone cysts making it distinct from GCTB. However these changes may be in the endothelial cells which are quite different from stromal or giant cells. It had been concluded that the poor matrix support to the vessels may lead to frequent and profuse intraosseous hemorrhage attracting blood-derived monocytes with active conversion into osteoclasts, resulting in GCTB formation. On the other hand, dilatation of the thin-walled blood vessels results in formation of ABCs. If hemorrhagic foci are replaced by proliferation of fibroblasts and histiocytes, then a picture of fibrous histiocytic lesion is emerged. Enhanced telomerase activity and karyotypic aberrations may be necessary for rapid division of the nuclei of the giant cells in order to be able to deal with significant in situ intraosseous hemorrhage.     

Giant cell tumor of the scapula associated with secondary aneurysmal bone cyst

Giant cell tumors are distinctive neoplasms characterized by a profusion of multinucleate giant cells scattered throughout a stroma of mononuclear cells. Most giant cell tumors are found at the epiphyses of long bones, especially around the knee joint. Flat bone involvement is rare. However, a case of giant cell tumor with secondary aneurysmal bone cyst was encountered at the scapula of a 25-year-old man. Since the occurrence of a giant cell tumor with secondary aneurysmal bone cyst on flat bones (i.e., the scapula) is extremely rare, the above-mentioned case is worthy of reporting.     

髋部骨肿瘤患者行定制人工髋关节置换的体会

目的探讨定制人工髋关节假体在髋部骨肿瘤保肢术中的应用疗效。方法收集我院自1999年3月~2010年10月因髋部骨肿瘤行定制人工假体置换术病例,按照Enneking标准评价术后肢体功能,并分析术后并发症。结果本组病例中,38例获得良好随访,随访时间为14个月~8年﹙平均55个月﹚,其中髋臼9例,股骨近端29例;肿瘤类型:骨巨细胞瘤12例,软骨肉瘤4例,良性纤维组织瘤10例,骨肉瘤8例,复发性软骨瘤2例,动脉瘤性骨囊肿2例,本组病例;术后肢体功能:优﹙≥23分﹚11例,良﹙15~22分﹚19例,差﹙<15分﹚8例,平均19.8分,优良率为78.95%;1例术后出现假体脱位,成功手法复位。结论定制人工髋关节假体置换术后患者肢体功能恢复较快,是髋部骨肿瘤较为满意的一种保肢治疗方法。     

S-100 protein immunostaining in the differential diagnosis of chondroblastoma

In an effort to investigate the utility of immunostaining for S-100 protein in the differential diagnosis of chondroblastoma, the expression of S-100 protein in nine chondroblastomas was compared with that in six giant cell tumors, six aneurysmal bone cysts, four giant cell reparative granulomas, six cases of fibrous dysplasia, two cases of osteitis fibrosa cystica, two nonossifying fibromas, and one clear cell chondrosarcoma. Five enchondromas, three typical chondrosarcomas, and one mesenchymal chondrosarcoma were also included as control tumors. The proliferating stromal cells in seven of the nine chondroblastomas stained for S-100 protein, as did the lacunar chondrocytes in all of the enchondromas and chondrosarcomas and rare stromal cells in the clear cell chondrosarcoma. In contrast, none of the other tumefactive bone lesions included in this study demonstrated S-100 protein immunoreactivity. These results suggest that immunohistochemical assessment of S-100 protein may be a method for diagnostically separating chondroblastoma from pathologic entities that could be histologically confused with it in the presence of limited biopsy material. However, clear cell chondrosarcoma would appear to represent an exception to this general statement.     

Bone tumors. Their prevalence

1,200 cases of bone tumors were reviewed from the Orthopedic Hospital "Magdalena de las Salinas" between 1982 and 1989. 66.7% of them were benign tumors, 14.3% pseudotumoral lesions, 10.1% metastatic tumors, 8.6% primary malignant tumors, and 0.3% were malignant invasive tumors to bone. The most frequently found benign tumors were: osteochondroma, enchondroma and giant cell tumor; the most frequent pseudotumoral lesions were metaphyseal fibrous defects, solitary bone cysts and fibrous dysplasia; the most frequent primary malignant tumor was osteosarcoma. Prevalence, frequency, distribution, sex, most frequent ages, affected bones, multicentricity, and aggregated fractures, as well as the site of the primary lesion in metastatic and invading tumors, were similar to those reported in the classical series.     

A rare case of periosteal osteoblastoma located in the frontal cranial bone

Periosteal osteoblastoma is an extremely rare bone-forming neoplasm located on the surface of cortical bone. Of the fewer than 30 cases of periosteal osteoblastomas found in the literature, 2 have been reported to be located in cranial bone, and these have not been documented in detail with clinical history, radiographic findings, macroscopic features, and microscopic findings. Although the differential diagnoses of periosteal lesions include parosteal and periosteal osteosarcoma, periosteal chondroma and chondrosarcoma, osteochondroma, osteoid osteoma, periostitis ossificans, and myositis ossificans, an important differential diagnosis both radiologically and pathologically of such a lesion in the cranium is meningioma. We report an unusual case of periosteal osteoblastoma located in the frontal cranial bone that was radiologically consistent with a meningioma. The differential diagnosis of metaplastic meningioma with differentiation toward bone is discussed.     

Osteocalcin expression in primary bone tumors--in situ hybridization and immunohistochemical study.

Osteocalcin is one of the most abundant noncollagenous proteins found in adult bone. It is a highly conserved gamma-carboxyglutamic acid-containing protein that is believed to be produced exclusively by osteoblasts. In this study, intracellular and extracellular localization of osteocalcin in osteosarcoma was examined with anti-osteocalcin antibody and in situ hybridization using a synthetic oligonucleotide. Immunohistochemically, osteoblastic osteosarcomas were all positive for osteocalcin. The chondroblastic osteosarcomas were positive on the neoplastic chondrocytes. The five fibroblastic osteosarcomas out of seven were positive for osteocalcin immunostaining over the neoplastic spindle cells. Five cases of osteoblastic osteosarcomas out of seven were positive for osteocalcin in situ hybridization. Two cases of chondroblastic osteosarcomas and three cases of fibroblastic osteosarcomas were positive for in situ demonstration of osteocalcin. The malignant tumor giant cells were positive for osteocalcin immunostaining 83%. They were also positive for in situ hybridization. The benign giant cells in five giant cell tumors and five aneurysmal bone cysts were negative for osteocalcin immunostaining. The benign giant cells in three chondroblastoma and three Paget''s disease were positive for osteocalcin. In this study, the osteocalcin in situ hybridization and immunostaining has very important meaning for making differential diagnoses of, especially giant cell rich bone forming tumors.     

Myositis ossificans associated with subclinical idiopathic thrombocytopenic purpura: report of a case

A 56-year-old healthy man noticed a stony-hard mass gradually grown in his neck for more than a 6-year period. Examinations revealed 2 additional calcified masses at the esophageal hiatus and retroperitoneum. The cut-surface of the operative specimens showed fibrous and mucinous appearance with many calcified islands. Microscopically, the lesion showed a gradual transform from the central immature area with fibroblasts and mucinous matrix, to the peripheral mature area with woven bone and osteoclasts (zoning phenomenon), which was compatible with the features of mature myositis ossificans. Myositis ossificans is an isolated, benign, nonneoplastic disease typically found in adolescence, after traumatic episode. Similar lesions have been found in the major musculature of patients with increased bleeding tendency. In the present case, idiopathic thrombocytopenic purpura was found to be associated and was suggested to be involved in initiating myositis ossificans. Still, it is extremely rare to observe lesions in these sites synchronously.     

Cytogenetic and molecular cytogenetic findings in 43 aneurysmal bone cysts: aberrations of 17p mapped to 17p13.2 by fluorescence in situ hybridization.

Aneurysmal bone cyst is a benign, cystic lesion of bone composed of blood-filled spaces separated by fibrous septa. Relatively few cases of aneurysmal bone cyst have been cytogenetically characterized, yet abnormalities of the short arm of chromosome 17 appear to be recurrent. In this study, conventional cytogenetic analysis of 43 aneurysmal bone cyst specimens from 38 patients over a 12-year period revealed clonal chromosomal abnormalities in 12 specimens. Karyotypic anomalies of 17p, including a complex translocation and inversion, were identified in eight of these 12 specimens. In an effort to further define the aberrant 17p breakpoint, fluorescence in situ hybridization (FISH) analyses were performed using a series of probe combinations spanning a 5.1 Mb region between the TP53 (17p13.1) and Miller-Dieker lissencephaly syndrome (17p13.3) gene loci. These studies revealed the critical breakpoint locus at 17p13.2, flanked proximally by an RP11-46I8, RP11-333E1, and RP11-457I18 bacterial artificial chromosome (BAC) probe cocktail and distally by an RP11-198F11 and RP11-115H24 BAC and RP5-1050D4 P1 artificial chromosome (PAC) probe cocktail. Overall, abnormalities of the 17p13.2 locus were identified by metaphase and/or interphase cell FISH analysis in 22 of 35 (63%) aneurysmal bone cyst specimens examined including 26 karyotypically normal specimens. These cytogenetic and molecular cytogenetic findings expand our knowledge of chromosomal alterations in aneurysmal bone cyst, further localize the critically involved 17p breakpoint, and provide an alternative approach (ie FISH) for detecting 17p abnormalities in nondividing cells of aneurysmal bone cysts. The latter could potentially be utilized as an adjunct in diagnostically challenging cases.