Takafumi Ueda

Ossifying fibroma vs fibrous dysplasia of the jaw: molecular and immunological characterization

Ossifying fibroma and fibrous dysplasia of the jaw are maxillofacial fibro-osseous lesions that should be distinguished each other by a pathologist because they show distinct patterns of disease progression. However, both lesions often show similar histological and radiological features, making distinction between the two a diagnostic dilemma. In this study, we performed immunological and molecular analyses of five ossifying fibromas, four cases of extragnathic fibrous dysplasia, and five cases of gnathic fibrous dysplasia with typical histological and radiographic features. First, we examined the difference between fibrous dysplasia and ossifying fibroma in the expression of Runx2 (which determined osteogenic differentiation from mesenchymal stem cells) and other osteogenic markers. Fibroblastic cells in fibrous dysplasia and ossifying fibroma showed strong Runx2 expression in the nucleus. The bone matrices of both lesions showed similar expression patterns for all markers tested except for osteocalcin. Immunoreactivity for osteocalcin was strong throughout calcified regions in fibrous dysplasia, but weak in ossifying fibroma lesions. Second, we performed PCR analysis with peptide nucleic acid (PNA) for mutations at the Arg201 codon of the alpha subunit of the stimulatory G protein gene (GNAS), which has reported to be a marker for extragnathic fibrous dysplasia. All nine cases of extragnathic or gnathic fibrous dysplasia were positive for this mutation. On the other hand, none of the five cases of ossifying fibroma showed the mutation. These findings indicate that although fibrous dysplasia and ossifying fibroma are similar disease entities, especially in the demonstration of the osteogenic lineage in stromal fibroblast-like cells, they show distinct differences that can be revealed by immunohistochemical detection of osteocalcin expression. Furthermore, PCR analysis with PNA for GNAS mutations at the Arg201 codon is a useful method to differentiate between fibrous dysplasia and ossifying fibroma.

Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients.

Clear cell sarcoma (CCS) of tendons and aponeuroses (malignant melanoma of soft parts) is a rare melanocytic soft tissue sarcoma. The objective of this study was to determine the clinical features, prognostic factors, and optimal treatment policy for patients with this rare disease.

Long-term follow-up after limb salvage in skeletally immature children with a primary malignant tumor of the distal end of the femur.

BACKGROUNDnSkeletally immature children with a primary malignant tumor in the distal end of the femur are candidates for limb-salvage surgery; however, functional impairment due to subsequent limb-length discrepancy must be considered. Our aim was to evaluate the long-term clinical outcome of limb salvage in patients with a sarcoma of the distal end of the femur who were eleven years old or less, focusing on limb-length discrepancy and complications.nnnMETHODSnThe cases of forty children were retrospectively reviewed in a multicenter study based on the responses to a questionnaire. Twenty-eight patients had had endoprosthetic reconstruction, and twelve had had biological reconstruction. Functional evaluation was based on the Musculoskeletal Tumor Society scoring system, with numerical values from 0 to 5 points assigned for each of the following six categories: pain, function, emotional acceptance, use of supports, walking ability, and gait. These values were added, and the functional score was presented as a percentage of the maximum possible score. Limb-length discrepancy was measured with orthoroentgenograms. Complications and their treatment were analyzed. Patient survival and the survival of the reconstructions were analyzed with use of the Kaplan-Meier method.nnnRESULTSnSeven patients died and thirty-three remained alive, for a survival rate of 82% at ten years postoperatively. For the surviving patients, the mean follow-up periods (and standard deviations) were similar for the twenty-two who had endoprosthetic reconstruction (13.2 +/- 3.9 years) and the eleven who had biological reconstruction (10.4 +/- 4.4 years). All patients had reached skeletal maturity. The mean final functional score was 74% +/- 18% in the endoprosthetic reconstruction group and 68% +/- 17% in the biological reconstruction group (p = 0.37). For the nineteen patients who underwent limb-lengthening, the mean functional score increased significantly from 65% +/- 21% before the procedure to 81% +/- 11% after the lengthening (p = 0.0016). There were five early and twenty-eight late complications. In the endoprosthetic reconstruction group, the most frequent complications were deep infection and aseptic loosening. In the biological reconstruction group, the most frequent complications were implant breakage and nonunion. Revision surgeries were required in seventeen patients, including five who had an amputation. The rate of survival of the endoprosthetic reconstructions was 77% at five years and 51% at ten years postoperatively, whereas the rate of survival of the biological reconstructions was 46% at both five and ten years postoperatively.nnnCONCLUSIONSnEndoprosthetic or biological reconstructions as limb salvage provided good functional outcome in skeletally immature children with a malignant bone tumor of the distal aspect of the femur despite a high rate of revisions and limb-lengthening procedures.

Prognostic relevance of clinical symptoms in patients with spinal metastases.

Medical and surgical advances allow surgical treatment of many patients with spinal metastases. Although emerging surgical techniques facilitate stabilization of the collapsed spine, surgical candidates should be carefully selected. However, the lack of confirmed criteria to determine survival of these patients makes selection for surgery difficult. Clinical symptoms have been considered possible factors associated with prognosis, but their relevance has not been confirmed because of inadequate power for proper statistical analysis. We retrospectively reviewed 165 patients who had surgery for spinal metastases from various cancers. Clinical symptoms including pain, paresis, and walking status were recorded. Multivariate analysis indicated that the histologic type of the primary tumor was the strongest prognostic factor, followed by preoperative paresis and pain. Myeloma, thyroid cancer, renal cell cancer, breast cancer, and prostate cancer had better prognoses than other kinds of cancer. Patients without paresis before surgery had a better prognosis than patients with paresis, and patients with no pain before surgery had a better prognosis than those with pain. Preoperative walking status was not an independent prognostic factor. Level of Evidence: Therapeutic study, Level IV (case series-no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

Clinical outcome of patients with Ewing sarcoma family of tumors of bone in Japan: The Japanese musculoskeletal oncology group cooperative study

Ewing sarcoma family of tumors (ESFT) of bone is extremely rare in Japan. The objectives of the current study were to assess the clinical outcome and prognostic factors of patients with ESFT of bone in Japan and to compare them between Euro‐American and Japanese populations.

Prognostic significance of activated AKT expression in soft-tissue sarcoma.

Purpose: AKT is a serine/threonine kinase which is important in tumorigenesis. Several molecules involved in AKT pathway are dysregulated in various kinds of human cancers. Patients and Methods: Ninety-three patients (53 males and 40 females), ages ranging from 19 to 77 years (median, 57 years), with localized soft-tissue sarcomas arising in the trunk and extremities, were analyzed. Immunoperoxidase procedure (avidin-biotin complex method) was done on paraffin-embedded sections with anti–phosphorylated AKT (Thr308), anti–phosphorylated p44/42 extracellular signal–regulated kinase 1 and 2 (ERK1/2) (Thr202/Tyr204), anti–phosphorylated forkhead in rhabdomyosarcoma (FKHR) (Ser256), and anti-Ki 67 antibodies. Expression levels of phosphorylated AKT (p-AKT), phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated FKHR (p-FKHR) were categorized as either weaker (level 1) or equal to or stronger (level 2) compared with those in the endothelial cells of the same specimens. Percentage of cells showing intranuclear staining with Ki-67 was shown as the Ki-67 labeling index (LI). Cases were divided into two groups: level 1, Ki-67 LI < 20%; level 2, Ki-67 LI ≥ 20%. Results: Twenty-six (28.0%), 6 (6.5%), and 46 (44.1%) of the tumors showed level 2 expression for p-AKT, p-ERK1/2, and Ki-67 LI, respectively. Tumors with level 2 p-AKT expression showed a higher ratio of level 2 p-FKHR expression (P < 0.01). Multivariate analysis revealed p-AKT expression and Ki-67 LI to be independent prognosticators for overall survival, and p-AKT expression for disease-free survival. Conclusion: p-AKT expression level is a significant prognosticator in soft-tissue sarcoma.

Peripheral nerve schwannoma: two cases exhibiting increased FDG uptake in early and delayed PET imaging

We present two cases of peripheral nerve schwannoma which showed an increased accumulation of 2-deoxy-[18F] fluoro-D-glucose (FDG) in the tumors on positron emission tomography (PET) imaging acquired at both 1xa0h (early phase) and 2xa0h (delayed phase) after FDG injection. FDG-PET scans were performed with a dedicated PET scanner (HeadtomeV/ SET2400xa0W, Shimadzu, Kyoto, Japan) and the PET data analyzed the most metabolically active region of interest (ROI). We set the maximum standardized uptake value (SUV max) with a cut-off point of 3.0 to distinguish benign and malignant lesions. Although the mechanism responsible for the increased FDG uptake in benign schwannomas remains unknown, we discuss our findings in the context of tumor cellularity and briefly review other studies on the subject.

Extraskeletal mesenchymal chondrosarcoma: an imaging review of ten new patients.

ObjectiveExtraskeletal mesenchymal chondrosarcoma (EMC) is a rare soft-tissue tumor that most arises in young adults. Because of its rarity, few imaging studies have been reported to date. The purpose of this study was to elucidate the imaging features of this tumor.DesignWe conducted a multi-institutional study in cooperation with five referral cancer centers in Japan. Imaging findings of ten new EMC cases, including conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI), performed at each institute, were reviewed along with clinical features.PatientsTen patients with EMC, who had been treated at each hospital from 1990 to 2001, participated in this study.Results and conclusionsSoft-tissue masses with well-demarcated, dense and granular calcification were most frequently observed on plain radiographs and CT scans. T2-weighted MR images most clearly depicted a two-component structure composed of calcified and uncalcified areas, and enhanced MRI showed inhomogeneous enhancement in both areas. Although the sensitivity and specificity of these findings are unknown, they might be characteristic and have diagnostic value for this rare tumor.

FDG-PET imaging for chronic expanding hematoma in pelvis with massive bone destruction

Chronic expanding hematoma is a rare presentation of a hematoma characterized by a persistent increase in size for more than a month after the initial hemorrhage. We present a 65-year-old man with a chronic expanding hematoma in his ilium who was receiving anticoagulant treatment. The patient had a delayed manifestation of a femoral neuropathy with massive bone destruction. 2-Deoxy-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET) imaging revealed an increased uptake in the rim of the mass in images acquired 1xa0h after FDG injection. FDG-PET scans were performed using a dedicated PET scanner (HeadtomeV/SET2400xa0W, Shimadzu, Kyoto, Japan), and the PET data for the most metabolically active region of interest (ROI) were analyzed. The maximum standardized uptake value (SUVmax) was set to a cut-off point of 3.0 to distinguish between benign and malignant lesions. The SUVmax of the patient’s lesion was 3.10, suggesting a malignant lesion. The characteristics of FDG-PET images of chronic expanding hematomas, including the uptake of FDG in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential interpretive pitfall in mimicking a sarcoma.

Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia.

Oncogenic osteomalacia, which is characterized by renal phosphate wasting, low serum 1, 25-dihydroxyvitamin D, and osteomalacia, is caused by mesenchymal neoplasms that are termed phosphaturic mesenchymal tumors (PMTs). As PMTs are usually small and lack specific histological features, the pathological identification of PMTs is difficult. Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein expressed in mineralized tissues including bone, tooth, and hypertrophic cartilage. Increased expression of DMP1 gene in PMTs has been reported by using differential cDNA screening. In the present study, DMP1 expression in PMTs and other soft tissue tumors was analyzed immunohistochemically to verify its utility in the differential diagnosis of PMTs. Anti-DMP1 polyclonal antibody was raised against the C-terminal sequence of DMP1. Three cases with PMTs and 11 other soft tissue tumors (two malignant hemangiopericytomas, three solitary fibrous tumors, three synovial sarcomas, and three malignant peripheral nerve sheath tumors) were analyzed for DMP1 expression. DMP1 expression was observed in all of the three cases with PMTs, but never found in other soft tissue tumors examined. DMP1 was detected in the extracellular matrix with myxomatous features or around capillary vessels, and in dystrophic calcified sites. Paranuclear DMP1 staining in the tumor cells was also observed. These findings indicate that DMP1 immunohistochemistry is a useful tool for identifying PMTs.