Malignant transformation of polyostotic fibrous dysplasia with aberrant keratin expression.

Malignant transformation of fibrous dysplasia (FD) is exceedingly rare, occurring in less than 1% of all FD cases, and has been described in both monostotic and polyostotic forms of this entity. We report a case of a large proximal femur mass arising in a 45-year-old man. The biopsy revealed a high-grade pleomorphic malignancy that focally expressed multiple keratins. Based on the presence of keratin immunoreactivity, the morphologic differential diagnosis included metastatic sarcomatoid carcinoma. However, review of the clinical information revealed a history of polyostotic FD, and imaging findings were compatible with malignant transformation of FD. The resected neoplasm was biphasic and composed of areas of conventional FD admixed with a high-grade pleomorphic malignancy. Activating GNAS mutations were identified in both components. To the best of our knowledge, this is the first description of keratin expression in malignant transformation of FD.

Malignant perivascular epithelioid cell tumor (PEComa) of the femur: a case report and literature review.

BACKGROUND: We describe a case of malignant perivascular epithelial cell tumor (PEComa) arising primarily in the distal left femur of a 47-year-old male. CASE PRESENTATION: The patient presented with pain accompanied by progressive swelling of his left thigh. Computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed an osteolytic lesion. Curettage of the lesion was reported as a clear cell tumor with recommendation for exclusion of a metastatic clear cell carcinoma. However, thorough examinations did not find any primary site elsewhere, apart from the presence of bilateral pulmonary metastases. Evaluation of the submitted H & E slides identified a malignant PEComa which was further confirmed by subsequent immunohistochemical study. CONCLUSIONS: The occurrence of PEComa as a primary bone lesion is extremely rare. We present here a malignant PEComa of the distal left femur, and summarize the clinicopathological characteristics of this rare entity with literature review. VIRTUAL SLIDES: The virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5729035221600545 .

Intraosseous leiomyosarcoma arising in the epiphysis of the distal femur.

Herein, we present a rare case of intraosseous leiomyosarcoma arising in the epiphysis of the distal femur and showing unusual radiographic features. A 44-year-old man presented with a pain in the left knee joint. Computed tomography revealed an intraosseous lesion with slightly increased attenuation and a thin marginal sclerotic rim in the femoral medial condyle. The signal of the lesion was hypointense on T1-weighted magnetic resonance (MR) images and hyperintense on fat-suppressed T2-weighted MR images. After gadolinium administration, the signal of the lesion was moderately and diffusely enhanced. The histological diagnosis of leiomyosarcoma was made based on a preoperative core biopsy specimen. Microscopic examination of the resected specimen revealed an ill-defined intraosseous tumor composed of proliferated atypical and mildly pleomorphic smooth muscle cells permeating among the bone trabeculae with only focal destruction of the bone trabeculae and low mitotic activity, indicating low grade leiomyosarcoma. The bone trabeculae at the periphery of the tumor were mildly thickened and anastomosed with a rim of an increased number of osteoblasts. Systemic examination showed no tumorous lesions in other anatomical sites. Leiomyosarcomas rarely present in the bone as a diffuse intertrabecular growth, even in low grade tumors.

[Telangiectatic osteosarcoma secondary to a liposclerosing myxofibrous tumor: a case report]. / Ostéosarcome de type télangiectasique développé sur une tumeur fibromyxoïde liposclérosante : à propos d'un cas.

Malignant transformation of a fibrous dysplasia into an osteosarcoma is very rare. We report the case of an 84-year-old man with telangiectatic osteosarcoma of the upper femur arising in a previous fibrous dysplasia also known as liposclerosing myxofibrous tumor. The tumor was expressing the epithelial membrane antigen. This is the first described case of a malignant transformation into an osteosarcoma arising in a liposclerosing myxofibrous tumor. We discuss the main differential diagnosis with a review.

Clinical and pathological characteristics of giant cell angioblastoma: a case report.

Giant cell angioblastoma (GCAB) is an extremely rare soft tissue tumor of early childhood and only five cases have been described to date. As such the clinical, pathological, and prognostic features are poorly defined. We prensent here a new case of GCAB in bone of a child aged 4-years old. The lesion was composed of dense and loose cell regions. The dense regions were characterized by nodular, linear, and plexiform aggregates of oval- to spindle-shaped tumor cells around small vascular channels and interspersed with large mononuclear cells and multinucleate giant cells. The loose cell areas were characterized by distributed fibroblasts and abundant myxoid matrix, which diminished with patient age. Infiltrative growth was observed in some areas. Oval-to-spindle cells showed positivity for Vimentin, CD31 and CD34 staining, and partial positivity for smooth muscle actin. Mononuclear cells and multinucleate giant cells showed Vimentin and CD68 positivity. Seventeen months after thorough curettage of the lesion, a local recurrence was found. Based upon the clinical, histological and immunohistochemical findings, infiltrate condition, and prognosis, we classified GCAB into two subtypes. Type I does not infiltrate surrounding tissues and has good prognosis. Type II infiltrates the surrounding tissues, relapses earlier, and has worse prognosis. This report augments the limited GCAB literature to promote our understanding and guide therapy of this rare disease. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6699811297488137.

Granulocyte colony-stimulating factor-producing undifferentiated sarcoma occurring in previously fractured femur. A case report and review of the literature.

We examined the case of a 52-year-old man presenting with a sarcoma accompanied by severe leukocytosis, which developed many years after a femoral fracture. Histologic, histochemical, immunohistochemical, and ultrastructural analysis of the tumor revealed that the sarcoma could not be classified by any of the bone or soft tissue tumor classifications currently in use. The tumor cells were isolated from surgical specimens and subcultured in vitro. The concentration of granulocyte colony-stimulating factor in the culture medium was constantly elevated to considerably high levels during 20 cell passages. A genomic study using reverse transcription-polymerase chain reaction showed that the cells retained messenger RNA expression of granulocyte colony-stimulating factor. The aberrant overexpression of granulocyte colony-stimulating factor clearly represented a paraneoplastic phenomenon of the neoplastic cells.

Immunohistochemical expression of p53, MDM2, Ki-67 and PCNA in central giant cell granuloma and giant cell tumor.

Central giant cell granuloma (CGCG) is a reactive bone lesion that occurs mainly in the jaws. The giant cell tumour (GCT) is a benign locally aggressive neoplasm located near the articular end of tubular bones. Both lesions are characterised histologically by multinucleated giant cells in a background of ovoid to spindle-shaped mesenchymal cells. There is a basic question whether both lesions are separate entities or variants of the same disease. The study of cell cycle-associated proteins may give insights into clarifying such question. The expression of these proteins is also important to determine the cell cycle regulation in both tumours. The purpose of this study was to evaluate the immunohistochemical expression of p53, MDM2, Ki-67 and PCNA in CGCG and GCT. The results demonstrated that, despite the lack of p53 immunoreactivity, all the samples showed wide expression of MDM2. The percentage of Ki-67- and PCNA-positive cells in CGCG was statistically higher than that of GCT Our findings show that CGCG has a higher proliferative activity compared with that of the GCT. Our results also suggest that p53 inactivation by MDM2 expression may be involved in the pathogenesis of giant cell lesions of the jaws and long bones.

Pathologic fracture of the femur neck as first manifestation of a minute columnar cell carcinoma of the thyroid gland.

This case report concerns a 64 year-old woman who presented a pathologic fracture of the femur neck. Histologic examination of the performed bone biopsy disclosed the presence of a carcinomatous metastasis with unusual microscopic features. The site of the primary tumor could be unequivocally determined as being the thyroid gland, as immunostaining of the tumor cells showed positivity with anti-thyroglobulin. The thyroidectomy specimen weighed 149 g, was nodular and partially calcified. Exhaustive microscopic examination finally revealed the presence of a minute columnar cell carcinoma, 0.6 cm in diameter, with obvious vascular invasion. This case illustrates well 1) the usefulness of immunostaining with anti-thyroglobulin in cases of bone metastasis with unusual microscopic features and unknown primary, as well as 2) the aggressiveness of this rare type of carcinoma of the thyroid.

Malignant glomus tumor: a case report and review of the literature.

This report concerns a malignant glomus tumor, a rare soft tissue tumor that was examined immunohistochemically and ultrastructurally. It occurred in a 44-year-old male patient who had suffered from dull pain and stiffness in the right thigh for 10 months. Radiographic examination revealed a well-defined osteolytic lesion in the diaphysis of the right femur. Hypervascularity of the tumor was observed angiographically. Computed tomographic and magnetic resonance examinations showed an intramuscular mass invading the marrow space of the femur. Wide resection was performed after open biopsy. Histologically, round to polygonal tumor cells revealed a uniform appearance of round to ovoid nuclei with single large nucleoli and slightly eosinophilic cytoplasm, forming solid sheets of cells interrupted by vessels of varying size. A few mitotic figures and vascular invasion were observed. Immunohistochemically, vimentin and alpha-smooth muscle actin were stained intensely, and muscle actin was positive for tumor cells of the perivascular area. Tumor cells were negative for desmin, factor VIII-related antigen, S-100 protein, neurofilament, cytokeratin, and epithelial membrane antigen. Ultrastructurally, tumor cells were characterized by many cytoplasmic processes, pinocytotic vesicles, plasmalemmal dense plaques, and scattered microfilaments in the cytoplasm. Few cell junctions and focal basement membrane-like structures were observed. No recurrence or metastasis was noted 57 months after operation. This case was considered to be a malignant glomus tumor, that is, a glomangiosarcoma arising de novo.

[Clinicopathological analysis, immunohistochemical study and electron microscopic observation of chondroblastoma of bone].

A series of 73 cases of chondroblastoma of bone, a rare benign tumor, was subjected to clinicopathological analysis, 50 cases of it were studied by immunohistochemistry and affinity histochemistry and 3 cases were observed by electron microscopy. In this series, chondroblastomas were found nearly in patients of all age groups, with the peak incidence occurring in the second decade of life. The lesions were more commonly located in long bone metaphyseal portion, especially in the upper end of femur and the head and neck of femur. It was easily misdiagnosed as giant cell tumor of bone, chondroma, and osteochondroma by clinic and radiography. There was gradual transition from a few chondroblasts to a small focus of clear cells in 3 cases, therefore, chondroblastoma may transform into clear cell chondrosarcoma by anaplastic change of chondroblast, which is one of malignant chondroblastomas. Our immunohistochemistry and affinity histochemistry results supported the point of view of chondroblast originated from epiphyseal chondrocytes. Immunohistochemical assessment of S-100 protein may be one useful parameter for differentiating chondroblastoma from giant cell tumor of bone and aneurysmal bone cyst ultrastructurally, chondroblasts had characteristic lobulated nuclei, compact zones under nuclear membrane, and microvilli on cells surface. In most cells, the Golgi apparatus and RER were inconspicuous without.

[Osteosarcoma cell immunophenotype and heterogeneity].

48 cases of osteosarcoma, including 18 cases of osteoblastic type, 16 of fibroblastic type and 14 of chondroblastic type, were studied in accordance with Dahlin's classification. All specimens were stained with 11 specific markers using immunohistochemical ABC methods. Positive immunostaining for BMP was found in all of these cases. The results showed 48 vimentin positive cases, 46 actin positive cases, 5 keratin positive cases and 4 desmin positive cases. Neither cytokeratin nor EMA was identified in any of the cases. Positive reactions to S-100 protein, collagen type IV, UEA-1 and factor XIII were observed in 26, 20, 36 and 13 of the cases respectively. The results of this study confirm that osteosarcoma possesses the unique multidirectional differentiation potential toward osteoblastic, chondroblastic, myofibroblastic, fibrohistiocytic and epithelial cells, and also indicate that immunophenotypic analysis is useful for the diagnosis, differential diagnosis and classification of the tumor cells of osteosarcoma.

Chemotherapeutic effect on osteosarcoma on basis of collagen analysis: a proposal of the induction of osteosarcoma differentiation.

The authors studied effect of chemotherapy on osteosarcoma by collagen analysis. As a result of this case study we propose the induction of osteosarcoma differentiation by chemotherapy. Treatment of a conventional osteosarcoma with two intra-arterial infusions of cisplatin and the T-12 protocol of Rosen resulted in sclerotic changes and good margination accompanied by the disappearance of the soft-tissue component from the X-rays. More than 90% tumour destruction was histologically demonstrated; tumour bone and osteoid increased after the chemotherapy, and the viable area of the tumour resembled an osteoblastoma. Before the chemotherapy, immunolocalization determined collagen types I and V to be diffusely present in the bone and osteoid. After the chemotherapy, the antibody to type I collagen was diffusely present, but the antibody to type V collagen occurred only on the surface of the increased bone and osteoid as in normal bone. When osteosarcoma cells were treated in vitro with methotrexate or cisplatin, collagen production increased significantly. It is thus believed that tumour cells were directly stimulated with these chemotherapeutic agents to produce collagen. The findings suggested that some anticancer agents might not only be cytotoxic to but also differentiate osteosarcoma cells.

Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone.

Alterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewing's sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giant-cell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.

Primitive neuroepithelial tumors with vermiform processes (filiform neuroepithelial tumors). Immunocytochemical and ultrastructural study of 2 cases.

Two unique, poorly-differentiated neuroepithelial tumors are described, one in a 35-year-old woman with an anterior mediastinal tumor and one in a 71-year-old woman with a left femoral mass. Immunocytochemical stains demonstrated Neuron specific enolase in both tumors and Chromogranin in one. Electron microscopy showed the cells of both neoplasms to contain abundant, thick, vermiform, organelle-free processes, previously described solely in large cell lymphomas. Rare dense-core granules were present, and very few processes were suggestive of neurites. These observations enlarge the spectrum of poorly differentiated neuroepithelial tumors.

Giant cell tumors of bone containing large amounts of hemosiderin: MR-pathologic correlation.

We present three giant cell tumors of bone that contained large amounts of hemosiderin and compare their MR appearance with intraoperative findings and histological characterization. Histologically, hemosiderin was found in multinucleated giant cells, mononuclear stromal cells, and xanthoma cells. All cases showed markedly decreased signal areas on both T1- and T2-weighted MR imaging due to hemosiderin deposition; this made evaluation of the integrity of the adjacent cortices difficult. In one case, extraosseous tumor extension appeared as a signal void area on MR imaging. Findings on immunohistochemical studies suggested the giant cells may have a histiocytic nature. Because the tumor cells themselves have a phagocytic nature, the decreased signal areas in and around giant cell tumors should be regarded as active tumor tissues in delineating the tumor on MR imaging.