Desmoplastic fibroma arising in the distal phalanx of the great toe: a case report.

Desmoplastic fibroma (DF) of the bone is a rare locally aggressive tumor usually occurring in adolescents and young adults. These tumors most commonly occur in the mandibles and metaphyses of long bones but are extremely rare in small bones, often resulting in diagnostic problems. The occurrence of these tumors in the foot is especially limited. We report the clinical, radiographic, and histologic features of DF arising in the distal phalanx of the great toe and a review of the published data.

SYT-SSX breakpoint peptide vaccines in patients with synovial sarcoma: a study from the Japanese Musculoskeletal Oncology Group.

In the present study, we evaluated the safety and effectiveness of SYT-SSX-derived peptide vaccines in patients with advanced synovial sarcoma. A 9-mer peptide spanning the SYT-SSX fusion region (B peptide) and its HLA-A*2402 anchor substitute (K9I) were synthesized. In Protocols A1 and A2, vaccines with peptide alone were administered subcutaneously six times at 14-day intervals. The B peptide was used in Protocol A1, whereas the K9I peptide was used in Protocol A2. In Protocols B1 and B2, the peptide was mixed with incomplete Freund's adjuvant and then administered subcutaneously six times at 14-day intervals. In addition, interferon-α was injected subcutaneously on the same day and again 3 days after the vaccination. The B peptide and K9I peptide were used in Protocols B1 and B2, respectively. In total, 21 patients (12 men, nine women; mean age 43.6 years) were enrolled in the present study. Each patient had multiple metastatic lesions of the lung. Thirteen patients completed the six-injection vaccination schedule. One patient developed intracerebral hemorrhage after the second vaccination. Delayed-type hypersensitivity skin tests were negative in all patients. Nine patients showed a greater than twofold increase in the frequency of CTLs in tetramer analysis. Recognized disease progression occurred in all but one of the nine patients in Protocols A1 and A2. In contrast, half the 12 patients had stable disease during the vaccination period in Protocols B1 and B2. Of note, one patient showed transient shrinkage of a metastatic lesion. The response of the patients to the B protocols is encouraging and warrants further investigation.

Metastatic patterns of myxoid/round cell liposarcoma: a review of a 25-year experience.

Myxoid/round cell liposarcoma (MRCL), unlike other soft tissue sarcomas, has been associated with unusual pattern of metastasis to extrapulmonary sites. In an attempt to elucidate the clinical features of MRCL with metastatic lesions, 58 cases, from the medical database of Keio University Hospital were used for the evaluation. 47 patients (81%) had no metastases, whereas 11 patients (11%) had metastases during their clinical course. Among the 11 patients with metastatic lesions, 8 patients (73%) had extrapulmonary metastases and 3 patients (27%) had pulmonary metastases. Patients were further divided into three groups; without metastasis, with extrapulmonary metastasis, and with pulmonary metastasis. When the metastatic patterns were stratified according to tumor size, there was statistical significance between the three groups (P = 0.028). The 8 cases with extrapulmonary metastases were all larger than 10 cm. Similarly, histological grading had a significant impact on metastatic patterns (P = 0.027). 3 cases with pulmonary metastatic lesions were all diagnosed as high grade. In conclusion, large size and low histological grade were significantly associated with extrapulmonary metastasis.

Anaplastic transformation of follicular thyroid carcinoma in a metastatic skeletal lesion presenting with paraneoplastic leukocytosis.

BACKGROUND: Anaplastic transformation of differentiated thyroid carcinoma (DTC) is a rare event with a poor clinical outcome. It usually occurs in the primary site or in regional lymph nodes, but rarely in distant metastatic lesions. SUMMARY: A 55-year-old woman with persistent pain in the left hip joint visited our hospital. She had a history of DTC that had been surgically removed 12 years earlier. Clinical images showed a tumorous mass in the left pelvis, indicative of bone metastasis. The patient underwent surgery to remove the tumor and remained stable until local recurrence was found 5 weeks after the surgery. The patient subsequently underwent radiation therapy; however, she died of respiratory failure due to lung metastases 2 months after the surgery for the recurrent lesion. The surgical specimens were diagnosed as anaplastic thyroid carcinoma, indicating that anaplastic transformation of thyroid follicular carcinoma occurred in the metastatic skeletal lesion. In addition, the patient had an unusually high white blood cell count throughout the course. Based on elevated serum granulocyte colony-stimulating factor (G-CSF) levels and positive immunostaining for G-CSF in the surgical specimens, the patient was diagnosed with paraneoplastic leukocytosis. CONCLUSION: To our knowledge, this is the first case of anaplastic transformation of DTC arising in a metastatic bone lesion described in the literature. In addition, the present case also exhibited severe leukocytosis accompanied by elevated serum G-CSF levels. Clinicians should be aware of the possibility of this occurring in their patients with DTC, as this development calls for a rapid change from observational follow-up to aggressive treatment.

Possible clinical significance of serum soluble interleukin-2 receptor level in primary bone lymphoma: two case reports.

In two patients with primary bone lymphoma (PBL) treated in our clinic, serum levels of soluble interleukin-2 receptor (sIL-2R) reflected the clinical course. In both cases, sIL-2R levels were high before treatment and normalized with the therapeutic effects of chemotherapy, coinciding with the changes in lactate dehydrogenase levels and radiographic findings. Adding to the recently reported results of the diagnostic ability of sIL-2R in PBL, our case study highlights the clinical significance of serum sIL-2R levels as a tumor marker in PBL cases.

Natural evolution of desmoplastic fibroblastoma on magnetic resonance imaging: a case report.

INTRODUCTION: Desmoplastic fibroblastoma (collagenous fibroma) is a recently described tumor thought to arise predominantly from subcutaneous tissue or skeletal muscle. The natural evolution of this tumor on magnetic resonance imaging has never been described, to the best of our knowledge. We herein report a case of desmoplastic fibroblastoma arising in the thigh and show the longitudinal magnetic resonance imaging findings. CASE PRESENTATION: A 60-year-old Japanese man presented with swelling of the medial side of his right thigh, and he complained of nighttime pain and slight tenderness. Magnetic resonance imaging demonstrated a 4 × 4 cm mass in the right thigh. Open biopsy was performed. The mass was diagnosed histologically as a benign fibrous tumor, and we maintained follow-up without surgical therapy. After one year, magnetic resonance imaging showed an increase in tumor size to 4 × 5 cm, but the histologic findings were the same as those obtained one year earlier. Resection was performed with narrow surgical margins. Pathologic diagnosis was desmoplastic fibroblastoma. Two years after surgery, the patient is free from pain and shows no signs or symptoms of recurrence. CONCLUSION: The natural evolution of desmoplastic fibroblastoma is characterized by no changes in patterns on magnetic resonance imaging despite increasing size. This finding is clinically helpful for distinguishing desmoplastic fibroblastoma with increasing pain from the desmoid tumor.

Prognostic significance of HLA class I expression in Ewing's sarcoma family of tumors.

BACKGROUND: Ewing's sarcoma family of tumors (ESFT) is one of the most malignant groups of tumors in young people. Human leukocyte antigen (HLA) class I displays endogenously processed peptides to CD8+ T lymphocytes and has a key role for host immune surveillance. In ESFT, the investigation concerning both HLA class I expression and T-cell infiltration has yet to be reported. METHODS: Biopsy specimens from 28 ESFT patients were evaluated by immunohistochemistry with the anti-HLA class I monoclonal antibody (mAb) EMR8-5 and anti-CD8 mAb, respectively. RESULTS: Expression of HLA class I was negative in 10 tumors and down-regulated in 22 tumors. The status of CD8+ T cell infiltration was closely associated with the expression levels of HLA class I. ESFT patients with down-regulated or negative expression of HLA class I showed significantly poorer survival than the rest of the patients. CONCLUSIONS: Our results suggested that CD8+ T cell-mediated immune response restricted by HLA class I might play an important role in immune surveillance of ESFT, and we revealed for the first time that the status of HLA class I expression affects the survival of the patients with ESFT.

Gene expression profiling of synovial sarcoma: distinct signature of poorly differentiated type.

Poorly differentiated type synovial sarcoma (PDSS) is a variant of synovial sarcoma characterized by predominantly round or short-spindled cell morphology. Although accumulating evidence from clinicopathologic studies suggests a strong association between this variant of synovial sarcoma and poor prognosis, little has been reported on the molecular basis of PDSS. To gain insights into the mechanism(s) that underlie the emergence of PDSS, we analyzed the gene expression profiles of 34 synovial sarcoma clinical samples, including 5 cases of PDSS, using an oligonucleotide microarray. In an unsupervised analysis, the 34 samples fell into 3 groups that correlate closely with histologic subtypes: monophasic, biphasic, and poorly differentiated types. PDSS was characterized by down-regulation of genes associated with neuronal and skeletal development and cell adhesion. Moreover, upregulation of genes on a specific chromosomal locus, 8q21.11, was identified. This locus-specific transcriptional activation in PDSS was confirmed by reverse transcriptase-PCR analysis of 9 additional synovial sarcoma samples. Our results indicate that PDSS tumors constitute a distinct group based on expression profiles.

Postoperative deep infection in tumor endoprosthesis reconstruction around the knee.

BACKGROUND: Although deep infection remains one of the most difficult complications to manage in the treatment of musculoskeletal tumor reconstructed with an endoprosthesis, limited information with respect to its incidence and risk factors has been reported. METHODS: This multicenter, retrospective, uncontrolled study reviewed the medical records of 82 patients who underwent reconstruction with an endoprosthesis or temporary spacer for bone-immature patients after resection of malignant bone tumor around the knee. Risk factors for deep infection and the impact of deep infection on prosthesis survival and oncological outcomes were analyzed. Deep infection was defined according to the Centers for Disease Control and Prevention (CDC) guidelines with minor modification. RESULTS: Deep infection occurred in 14 cases (17%), identified at a mean of 10.9 months (range <1 to 48 months) after initial surgery. Univariate analysis identified surface infection (P < 0.001) and skin necrosis (P < 0.001) as risk factors associated with deep infection. Conversely, tumor origin, chemotherapy, number of postoperative antibiotics, and length of bone resection were not associated with infection. Subclass analysis in femur cases identified a correlation between infection and the extent of partial resection of the quadriceps muscle (P = 0.04). In the multivariate analysis, surface infection represented an independent risk factor for deep infection (P = 0.03). Deep infection was a risk for endoprosthesis survival (P = 0.003) but did not affect the oncological outcome. CONCLUSIONS: A strong correlation between the condition of soft tissue and establishment of deep infection is suggested in this study. Although practical options for preventing deep infection seem limited, the present data allow a form of perioperative evaluation for patients with a higher risk of deep infection.

Alendronate inhibits growth of high-grade chondrosarcoma cells.

BACKGROUND: Conventional chemotherapy is ineffective for high-grade chondrosarcomas, highlighting the need for improved chemotherapies. Various clinical trials have been initiated using antiapoptotic agents and perifosine, and are truly in the experimental phases. Chondrosarcoma is still therefore considered a surgical disease despite its aggressive features of recurring locally and spreading to the lungs. Bisphosphonates inhibit growth of various cell types, including cancer cells and perhaps chondrosarcoma. MATERIALS AND METHODS: The effect of different concentrations of alendronate on cell proliferation, migration, apoptosis and cytoskeleton reorganization as well as on the regulation of intracellular protein expression were analyzed for the high-grade chondrosarcoma cell line CS-1. Mevalonate pathway intermediates were used in some experiments to assess mechanistic aspects. RESULTS: Alendronate decreased cell viability of CS-1 by inhibiting cell proliferation and cell migration. Alendronate-induced loss of cell viability led to a sequence of events including apoptosis and cytoskeletal rearrangements. Moreover, changes in the expression levels of various proteins involved in cell proliferation, migration, cell cycle, apoptosis and cytoskeleton reorganization were demonstrated. CONCLUSION: Alendronate exerts antiproliferative effects by perturbing various signaling pathways in CS-1 cells. These findings may lead to new treatment options for high-grade chondrosarcoma.

Reconstruction modality based on the spare part concept for massive soft tissue defects following oncological hemipelvectomy.

BACKGROUND: Hemipelvectomy for massive malignancy can result in large soft tissue defects that cannot be reconstructed using conventional posterior flaps. For such cases, reconstruction methods, including a latissimus dorsi flap or a rectus abdominis myocutaneous flap, may be applied, resulting in donor site morbidity. Recent innovations in plastic surgery have resulted in the development of novel reconstruction modalities based on "the spare part concept," applying tissues from amputated limbs. METHODS: Five subjects with pelvic malignant tumors underwent hemipelvectomy with reconstruction using the spare part concept. Femoral artery-based myocutaneous flap and free fillet lower leg flap were used for three and two cases, respectively. The clinical results, including postoperative complications and oncological outcomes, were assessed. RESULTS: The mean follow-up period was 43.2 months (range 12-94 months). No local recurrence was encountered in any cases throughout follow-up. As of the final follow-up, three patients remained alive and two patients were dead due to distant metastasis. Minor postoperative infection was observed in two cases. CONCLUSIONS: The femoral artery-based myocutaneous flap and the free fillet lower leg flap are both useful, safe options for reconstruction of the large defect following extensive hemipelvectomy for malignant bone and soft tissue tumors. The present data support the continued application of these flap reconstruction techniques based on the spare part concept.

Growth suppression and apoptosis induction in synovial sarcoma cell lines by a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ).

Synovial sarcoma is a relatively common soft tissue sarcoma with an aggressive clinical course. Although surgery is currently the first treatment modality, improvement of adjuvant chemotherapy is deemed essential to improve the clinical outcome. Nuclear factor-kappaB (NF-kappaB) is constitutively activated in various cancer cells and has emerged as a potential therapeutic molecular target; however, the possible involvement of NF-kappaB in the pathology of sarcomas remains to be clarified. Herein we examined the effects of a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) on two synovial sarcoma-derived cell lines, HS-SY-II and SYO-1. The growth of both cell lines was completely inhibited by DHMEQ and apoptosis was induced at 10 microg/ml. Additionally, we found that DHMEQ showed additive effects when used in combination with other cytotoxic agents. These observations indicate that inhibition of NF-kappaB activity may serve as a potential therapeutic target for synovial sarcoma.

Clinical significance of magnetic resonance imaging in the preoperative differential diagnosis of calcifying aponeurotic fibroma.

BACKGROUND: Although the clinical and histological features of calcifying aponeurotic fibroma are well described, the magnetic resonance imaging (MRI) findings have been reported for only five cases. The purpose of this study was to describe a series of MRI findings in this rare entity to assess its utility in preoperative and differential diagnosis. METHODS: MRI findings together with the clinical signs and radiographs of six patients with pathologically proven calcifying aponeurotic fibroma were retrospectively reviewed. Distribution, morphology, margins, edematous changes, and relation to the surrounding structures together with signal intensity of each sequence of MRI were evaluated. RESULTS: MRI demonstrated subcutaneous distribution, ill-defined appearance, and a tendency to infiltrate into or adhere to the surrounding tissues. The masses were of isointensity to low intensity on T1-weighted images. T2-weighted images showed heterogeneous high signal intensity with minor areas of isointensity to low signal intensity. Postcontrast T1-weighted images demonstrated heterogeneous intense enhancement. CONCLUSIONS: MRI revealed several features that can contribute to the preoperative differential diagnosis of calcifying aponeurotic fibroma from other fibrous tumors, giant cell tumor of the tendon sheath, or soft tissue sarcoma. As a result, MRI would help orthopedic oncologists plan the surgery for this rare entity.

Association of a missense single nucleotide polymorphism, Cys1367Arg of the WRN gene, with the risk of bone and soft tissue sarcomas in Japan.

Bone and soft tissue sarcomas (BSTSs) are rare malignant tumors of mesenchymal origin. Although BSTSs frequently occur in some hereditary cancer syndromes with germline mutations of DNA repair genes, genetic factors responsible for sporadic cases have not been determined. In the present study we undertook a case-control study and analyzed possible associations between the susceptibility to BSTS and the single nucleotide polymorphisms (SNPs) in DNA repair genes. Genomic DNAs extracted from case and control peripheral blood leukocytes were genotyped by pyrosequencing. For candidate polymorphisms, we chose 50 non-synonymous missense SNPs, which we have previously been identified by resequencing 36 DNA repair genes among the Japanese population. In the first screening, we analyzed 240 cases and 685 controls and selected six SNPs at the significance level of P < 0.1 (Fisher's exact test). The six SNPs were further analyzed in the second genotyping on an additional set of 304 cases and 834 controls. In the joint analysis (the first and second genotyping combined) of 544 cases and 1378 controls, Cys1367Arg of the WRN gene was found to be a protective factor of BSTS (odds ratio = 0.66, 95% confidence interval = 0.49-0.88, P = 0.005). An exploratory subgroup analysis without multiple comparison adjustment suggested that the WRN-Cys1367Arg SNP is associated with soft tissue sarcomas, sarcomas with reciprocal chromosomal translocations and malignant fibrous histiocytoma.

Overexpression of papillomavirus binding factor in Ewing's sarcoma family of tumors conferring poor prognosis.

Ewing's sarcoma family of tumors (ESFT) is comprised of highly malignant bone and soft tissue tumors in children and young adults. Despite intensive treatments for patients with ESFT, disease which presents with metastatic spread or relapses after primary treatment remains incurable in the majority of cases, indicating the importance of efforts to develop new treatment modalities, including immunotherapy. The present study was designed to examine the expression profile of papillomavirus binding factor (PBF), which we previously defined as an osteosarcoma-associated antigen, and its prognostic significance for patients with ESFT. Biopsy specimens from 20 ESFT were stained with an anti-PBF antibody. Survival was estimated using Kaplan-Meier plots and the prognostic significance of several variables, including the expression status of PBF, on disease-free and overall survival was determined by univariate analysis using the log-rank test. Of 20 specimens, 18 (90%) reacted positively to the anti-PBF antibody. Fifteen specimens (75%) were graded as PBF overexpression. Of the 11 variables analyzed, stage III disease, inadequate surgical margins and PBF overexpression were significantly associated with decreased disease-free and overall survival. None of the other variables, including age, gender, origin of tumor, tumor site or levels of LDH, ALP, CRP and ESR, showed any significant association. These findings indicate that the overexpression of PBF is a factor indicative of poor prognosis in ESFT. PBF may also serve as a putative target antigen in immunotherapy for patients with ESFT that have a poor prognosis and PBF overexpression.

Clinical outcome of patients with Ewing sarcoma family of tumors of bone in Japan: the Japanese Musculoskeletal Oncology Group cooperative study.

BACKGROUND: 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. METHODS: The authors conducted a retrospective analysis of 243 patients who were treated for ESFT of bone in Japan between 1981 and 2003. Local therapy was surgery in 35% of patients, surgery combined with radiotherapy in 40% of patients, radiotherapy alone in 22% of patients, and no local treatment in 3% of patients. All but 3 patients received various regimens of multidrug chemotherapy. RESULTS: The median patient age was 16 years. The primary disease sites were the trunk in 53% of patients and the extremities in 47% of patients. Forty-one patients had metastases at presentation. The median follow-up was 66 months. A univariate survival analysis demonstrated that patients who had metastases at presentation, primary site in the trunk, age >or=16 years, tumor size >or=10 cm, tumor that responded poorly to induction chemotherapy, and local treatment with radiotherapy alone had a significantly worse event-free survival (EFS). A multivariate analysis further verified that the former 3 factors were significant adverse prognostic factors. Of 201 patients with localized disease, 45 patients who received current chemotherapy regimens that included ifosfamide and etoposide had a significantly better 5-year EFS rate (67.6%) compared with other patients. CONCLUSIONS: The clinical outcome of patients with localized ESFT of bone in Japan has improved markedly with the use of current chemotherapy regimens that include ifosfamide and etoposide and has become comparable to the outcomes observed in other major series of Euro-American patients. The prognostic factors are also almost identical.