Establishment and Characterization of a Novel Human Clear-cell Sarcoma of Soft-tissue Cell Line, RSAR001, Derived from Pleural Effusion of a Patient with Pleural Dissemination.

BACKGROUND/AIM: Clear cell sarcoma (CCS) of soft tissue is exceedingly rare and frequently exhibits aggressive behavior. Toward the goals of improving the aggressive course and poor prognosis of CCS, and establish new therapeutic methods, molecular genetic and biological characterizations of CCS are required. MATERIALS AND METHODS: A new human CCS cell line (designated RSAR001) was established from the pleural effusion of a 44-year-old man with multiple lung metastases and pleural dissemination. The cell line and its xenograft were characterized including their morphology, immunohistochemistry, cytogenetic analysis, reverse transcription-polymerase chain reaction, direct sequencing analysis, and fluorescence in situ hybridization analysis. RESULTS: The cell line has been maintained for over 12 months with more than 50 passages. RSAR001 cells exhibited a fascicular or diffuse growth pattern of short spindle- or oval-shaped cells with clear cytoplasm in heterotransplanted tumor, that was similar to the primary tumor. Immunophenotypically, RSAR001 cells in vitro and in vivo exhibited almost the same characteristics as the primary tumor. Cytogenetic analyses revealed a translocation, t(12;22)(q13;q12). Reverse transcription-polymerase chain reaction and direct sequencing analysis detected transcripts of the Ewing sarcoma breakpoint region 1-activating transcription factor 1 (EWSR1-ATF1) type 1 fusion gene. Fluorescence in situ hybridization using a break-apart probe for the EWSR1 gene on 22q12 showed a rearrangement. CONCLUSION: These findings indicate that the RSAR001 cell line harbors EWSR1-ATF1 type 1 chimeric fusion gene, which is specific to CCS. RSAR001 cells might be useful for investigating biological behaviors and developing new treatments such as molecular-targeting antitumor drugs or immunological drugs for CCS.

Missed causative tumors in diagnosing tumor-induced osteomalacia with (18)F-FDG PET/CT: a potential pitfall of standard-field imaging.

OBJECTIVE: We describe herein two tumor-induced osteomalacia (TIO) cases for whom the causative lesions, located in their popliteal fossa, that were not identified in the standard field of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT), which usually images only the head, trunk, and proximal parts of the extremities. CLINICAL PRESENTATION AND INTERVENTION: A 47 years old Japanese man with multiple pathological fractures due to osteomalacia, accompanied by muscle weakness, hypophosphatemia, and an elevation of alkaline phosphatase (ALP) was referred to our hospital. A (18)F-FDG PET/CT scan was performed, but no (18)F-FDG uptake was detected in the standard field of imaging. Magnetic resonance imaging revealed a small subcutaneous tumor (1.9×1.2×0.6cm) of the left posteriomedial knee, displaying uniform enhancement on gadolinium-enhanced T1-weighted fat-suppression imaging. The tumor was resected widely and diagnosed as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The other patient was a 31 years old Japanese woman with multiple pathological fractures, hypophosphatemia and elevated of ALP and was referred to our hospital on suspicion of TIO. Although the causative lesion was not identified in the standard field of (18)F-FDG PET/CT, (18)F-FDG uptake (SUVmax 2.9) was detected on the right knee in the additional whole-body (18)F-FDG PET/CT. Magnetic resonance imaging revealed a soft-tissue tumor (6.4×4.1×2.9cm) in the right posterior knee. Following biopsy, the tumor was marginally resected, and was pathologically diagnosed as PMTMCT. CONCLUSION: Once patients are suspected to have TIO, a whole-body nuclear imaging study such as (18)F-FDG PET/CT should be performed, in order not to miss the hidden causative tumor, especially occurring in the distal extremities.

Primary dumbbell-shaped epidural myxoid liposarcoma of the thoracic spine: A case report and review of the literature.

Myxoid liposarcoma frequently occurs in the deep soft tissue of the extremities, particularly in the thigh. The present study describes an extremely rare case of primary dumbbell-shaped epidural myxoid liposarcoma of the thoracic spine occurring in a 22-year-old woman. Although preoperative magnetic resonance imaging findings were thought to be compatible with schwannoma, the pathological diagnosis of the resected tumor was myxoid liposarcoma. The patient underwent three courses of adjuvant chemotherapy with doxorubicin and ifosfamide, and exhibited no symptoms or signs of local recurrence or metastasis for 18 months post surgery. The present case suggests that, when radiologically diagnosing spinal epidural tumors, clinicians should consider the possibility of myxoid liposarcoma.

Functional reconstruction of the knee extension mechanism following wide resection for a prepatellar soft-tissue sarcoma: A case report.

Functional reconstruction following a wide resection for a malignant musculoskeletal tumor is often challenging, particularly for juxta-articular tumors. The current study describes a novel surgical procedure for the functional reconstruction of the knee extensor mechanism with a pedicle frozen auto-bone and -tendon graft, in a case of prepatellar clear cell sarcoma. The active range of motion of the knee was from 0-135°, and the extension muscular strength of the knee was evaluated as 5/5 by a manual muscle test at 14 months post-surgery (International Society of Limb Salvage score, 73%); this was improved compared with a similar procedure previously described by Muramatsu et al. This procedure must be considered following the wide resection of juxta-articular malignant musculoskeletal tumors.

LONG-TERM FOLLOW-UP OF FREE VASCULARIZED FIBULAR HEAD GRAFT FOR RECONSTRUCTION OF THE PROXIMAL HUMERUS AFTER WIDE RESECTION FOR BONE SARCOMA.

PURPOSE: This study investigated the shape of bone grafts and associations with upper limb function over the long term after free vascularized fibular head graft (FVFHG) for reconstruction of the proximal humerus after wide resection for bone sarcoma. METHODS: Patients comprised 3 women who had undergone FVFHG at least 5 years previously. Age at surgery was 12 years in 2 cases and 76 years in one. The mean follow-up periods were 10 years 4 months. Evaluated parameters comprised: 1) graft hypertrophy, and 2) shape of the fibular head as changes in shape of the bone graft; and 3) ISOLS score, and 4) DASH score as indicators of upper limb function. RESULTS: Rates of graft hypertrophy of the fibular shaft were -14%, -17%, and -20%, respectively, with transverse diameter decreasing in all cases. In terms of changes in shape of the grafted fibular head, transverse diameter had diminished in 2 patients (-5 mm and -2 mm), and the head had been completely resorbed in the remaining patient. Both patients in whom the fibular head remained were young, and both had good ISOLS scores >80% and good DASH scores of 5.0 and 8.3. The patient in whom the fibular head had been resorbed was elderly, with ISOLS and DASH scores of 73.3% and 34.2, respectively; comparatively poor compared with the other two. A comparison of ISOLS and DASH scores before and after fibular head resorption, however, showed no deterioration in either score. CONCLUSIONS: Long-term follow-up of humerus reconstruction by FVFHG showed no deterioration in upper limb function despite the risk of fibular head resorption. FVFHG of the proximal humerus is a reconstruction technique that can provide good long-term upper limb function.

Radiological and pathological characteristics of giant cell tumor of bone treated with denosumab.

We describe a case of giant cell tumor of the proximal tibia with skip bone metastases of the ipsilateral femur in a 20-year-old man. After the neoadjuvant treatment with denosumab, plain radiographs and computed tomography showed marked osteosclerosis and sclerotic rim formation, and 18F-FDG PET/CT showed a decreased standardized uptake value, whereas magnetic resonance imaging showed diffuse enhancement of the tumor, nearly the same findings as those at pretreatment. Pathological findings of the surgical specimen after the denosumab treatment showed benign fibrous histiocytoma-like features with complete disappearance of both mononuclear stromal cells and multinuclear osteoclast-like giant cells. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1090602085125068.

Overexpression of cyclooxygenase-2 in malignant peripheral nerve sheath tumor and selective cyclooxygenase-2 inhibitor-induced apoptosis by activating caspases in human malignant peripheral nerve sheath tumor cells.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme in the conversion of arachidonic acid to prostanoids, and its activation is associated with carcinogenesis as well as inflammation. The antitumor effect of selective COX-2 inhibitors has been noted in various malignancies. Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue sarcoma for which effective treatments have not yet been established. The purpose of this study was to investigate a potential therapeutic role of COX-2 in MPNST. METHODS: We evaluated the expression of COX-2 in 44 cases of high-grade MPNST using immunohistochemical staining and compared the staining results with the characteristics and outcome of the patients. We also investigated the antitumor effect of etodolac, a selective COX-2 inhibitor, on MPNST cells in vitro using the MPNST cell line, FMS-1. RESULTS: Overexpression of COX-2 (≥50% positive cells) was observed in 29 cases (65.9%), was significantly associated with a poor overall survival (P = 0.0495), and was considered an independent risk factor for a poor outcome by the results of both univariate and multivariate analysis. Etodolac induced apoptosis of FMS-1 cells through the activation of caspase-8, -9, and -3. Moreover, several caspase inhibitors significantly inhibited etodolac-induced apoptosis. CONCLUSIONS: Selective COX-2 inhibitors including etodolac had an antitumor effect on MPNST cells, and their use holds promise as a novel therapeutic strategy for patients with MPNST to improve their prognoses.

Therapeutic cytodifferentiation in alveolar rhabdomyosarcoma without genetic change of the PAX3-FKHR chimeric fusion gene: a case study.

Alveolar rhabdomyosarcoma (ARMS) is a subtype of rhabdomyosarcoma and usually occurs in childhood and adolescence. ARMS is characterized by its aggressive behavior and poor prognosis. To improve the unfavorable prognosis, new therapeutic developments and the establishment of methods for precise prognostic prediction are required. We describe a case of ARMS, solid variant, which occurred in a 10-year-old boy. After chemotherapy and radiotherapy, the tumor morphologically and immunohistochemically showed marked cytodifferentiation, whereas the exact same PAX3-FKHR chimeric fusion gene transcript was detected in samples before and after treatment. The result of this study seems to indicate that therapeutic cytodifferentiation does not always correlate with genetic change and favorable prognosis in ARMS.

Remitting seronegative symmetrical synovitis with pitting edema syndrome caused by crystal-induced arthritis of the wrist: a case report.

OBJECTIVE: To describe a rare case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome caused by gouty arthritis. CLINICAL PRESENTATION AND INTERVENTION: A 76-year-old man presented with swelling and pain in the dorsum of feet and hands bilaterally. From the laboratory and radiologic findings, the diagnosis of gout-induced RS3PE syndrome was made. Conservative therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injection in the wrist joint completely and rapidly resolved all symptoms. The patient was successfully treated with oral administration of NSAIDs and a one-time intra-articular corticosteroid injection in the left wrist joint. CONCLUSION: This case demonstrated the importance of considering the possibility of crystal-induced arthritis such as gout and pseudogout, as well as malignant disease, when diagnosing the primary disease responsible for RS3PE syndrome.

Intraosseous spindle cell hemangioma of the calcaneus: a case report and review of the literature.

Spindle cell hemangioma, a rare benign tumor characterized by cavernous blood vessels and spindled areas, typically arises in the subcutis of the distal extremities, particularly the hand. The case of intraosseous spindle cell hemangioma is extremely rare, and only 1 case arises in the frontal bone has been reported previously. We describe herein a case of intraosseous spindle cell hemangioma occurring in the left calcaneus in a 65-year-old woman. The patient was successfully treated by the operation. The present case is instructive especially in the differential diagnosis of primary bone tumor structured by spindle cells, for which the possibility of spindle cell hemangioma should be considered.

A clinicopathological study of giant cell tumor of small bones.

BACKGROUND AND PURPOSE: Giant cell tumor (GCT) of the small bones (small-bone GCT) is usually rare and considered somewhat different from conventional GCT. The purpose of this study was to investigate and report the clinicopathological features of 11 cases with small-bone GCT. MATERIALS AND METHODS: Patient information was obtained with the help of questionnaires. X-rays and paraffin blocks obtained from several institutions were clinically, radiographically, and histologically evaluated. RESULTS: Small-bone GCT was observed in younger patients compared to conventional GCT; 5 of the 11 (45%) patients were below 20 years of age, whereas the corresponding figure for all GCT patients is 16% in Japan. Excessive cortical bone expansion is a special feature. There were two cases of recurrence and one case of lung metastasis; the primary lesion was in the hand for all three cases. In contrast, no primary lesion of the foot recurred or metastasized. Varying degrees of positive p63 immunostaining were observed in all examined cases (n = 9) of small-bone GCT but were negative in case of giant cell reparative granuloma (GCRG) and solid variant of aneurysmal bone cyst (ABC). One case that demonstrated high-intensity positive staining had two episodes of recurrence. CONCLUSION: Small-bone GCT tends to develop in younger patients than does conventional GCT. Primary GCTs of the hand may be biologically more aggressive than those of the feet. The p63 immunostaining may be useful not only for differential diagnosis but also for prognostication of small-bone GCT.

Primary (de novo) dedifferentiated liposarcoma in the extremities: a multi-institution Tohoku Musculoskeletal Tumor Society study of 18 cases in northern Japan.

OBJECTIVE: Dedifferentiated liposarcomas usually occur in the retroperitoneal space and relatively rarely in the extremities. METHODS: We identified 18 patients with primary dedifferentiated liposarcoma in the extremities from the files of Tohoku Musculoskeletal Tumor Society and analyzed demographics, histologic findings, treatments and prognostic factors. The average follow-up period was 58 months. RESULTS: The subjects were 12 men and 6 women with a mean age of 65 years. All tumors were in the thigh. Nine patients noticed a rapid enlargement of the long-standing tumor. Histologic subtypes of the dedifferentiated area were undifferentiated pleomorphic sarcoma (n = 12), osteosarcoma (n = 2), rhabdomyosarcoma (n = 2), leiomyosarcoma (n = 1) and malignant peripheral nerve sheath tumor (n = 1). In the patient with rhabdomyosarcoma-like dedifferentiated area, extensive necrosis was observed after the preoperative chemotherapy. One patient who underwent marginal excision developed a local recurrence, but inadequate surgical margin was not associated with a risk of local recurrence. Three patients had lung metastasis at initial presentation, and four other patients developed lung metastases during the follow-up period. The overall survival rate was 61.1% at 5 years. On univariate analyses, large size of the dedifferentiated area (>8 cm), high MIB-1-labeling index (>30%) for the dedifferentiated area and lung metastasis at initial presentation were significantly associated with poor prognosis. CONCLUSIONS: Primary dedifferentiated liposarcoma in the extremities predominantly occurred in the thigh and a rapid enlargement of long-standing tumors was a characteristic symptom. Although the local behavior of these tumors was less aggressive than that of retroperitoneal dedifferentiated liposarcomas, they had a relatively high metastatic potential.

Pseudogout of the acromioclavicular joint: report of two cases and review of the literature.

Although calcium pyrophosphate dehydrate (CPPD) deposition disease, including pseudogout, is a relatively common disease affecting the major joints, especially the knee, pseudogout in the acromioclavicular (AC) joint is very uncommon. We describe two cases of acute pseudogout attacks of the AC joint in elderly patients. Radiological findings showed chondrocalcinosis in the AC joints. Microscopically, aspirated articular synovial fluid demonstrated CPPD crystals. Conservative therapy with non-steroidal anti-inflammatory drugs completely resolved all symptoms within 1 week.

Intramuscular Castleman's disease of the deltoid: a case report and review of the literature.

Castleman's disease (CD), a rare benign disease characterized by lymphoid hyperplasia, typically arises in the mediastinum as a solitary tumor. We describe herein a rare case of intramuscular CD occurring in the left deltoid in a 28-year-old woman. The present case is instructive in the differential diagnosis of primary soft tissue tumors, for which the possibility of CD should be considered.

Ifosfamide encephalopathy associated with chemotherapy for musculoskeletal sarcomas: incidence, severity, and risk factors.

BACKGROUND: Ifosfamide encephalopathy is a central nervous system toxicity that occurs in patients treated with ifosfamide. Although it has been reported in European and American patients with various carcinomas, there have been no published reports regarding ifosfamide encephalopathy in Asian patients with bone and soft tissue sarcomas. METHODS: We retrospectively examined the incidence, severity, and risk factors of ifosfamide encephalopathy in 61 Japanese patients with bone and soft tissue sarcomas at our institution. RESULTS: Ifosfamide encephalopathy occurred in 17 of 61 patients (31.2%) to whom ifosfamide was administered and in 29 of 214 ifosfamide treatment courses (13.6%). The most common symptoms of encephalopathy were "confusion," "somnolence," and "mood alteration - agitation." Severe encephalopathy occurred only in patients who received ifosfamide at doses >or=9 g/m(2). A history of cisplatin use was identified as a significant risk factor for the development of ifosfamide-induced encephalopathy. CONCLUSIONS: Because of the risk of severe encephalopathy, we conclude that patients who have previously received cisplatin or who receive ifosfamide at doses >or=9 g/m(2) require strict monitoring.

Establishment and characterization of a novel human malignant peripheral nerve sheath tumor cell line, FMS-1, that overexpresses epidermal growth factor receptor and cyclooxygenase-2.

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. We established a new human MPNST cell line (designated FMS-1) from MPNST of the right brachial plexus of a 69-year-old woman with NF1. The cell line has been maintained for >24 months with >100 passages. FMS-1 cells showed a fibrosarcoma-like or epithelioid pattern in the heterotransplanted tumor, compared with a fascicular growth pattern of short-spindle tumor cells in the primary tumor. Immunophenotypically, FMS-1 cells showed almost the same characteristics as the primary tumor. Cytogenetic and molecular analyses revealed a deletion in exons 5-8 of the p53 gene. Epidermal growth factor receptor (EGFR) and cyclooxygenase (COX)-2 were expressed in FMS-1 cells. To improve the highly aggressive course and poor prognosis and establish new therapeutic methods, molecular genetic and biological characterizations of MPNST are required. Thus, FMS-1 cells might be useful for investigating biological behaviors and developing new molecular-targeting antitumor drugs for MPNST expressing EGFR or COX-2.

Fibronexus in low-grade myofibrosarcoma: a case report.

Fibronexus (fibronexus junction) has been thought to be a characteristic ultrastructural feature of myofibroblasts, but it is controversial as to whether fibronexus is a characteristic of various myofibroblastic tumors. We report here a case of low-grade myofibrosarcoma with fibronexus arising in the right arm of an 80-year-old man. Histologically, the tumor was composed of relatively uniform and slender spindle cells arranged in fascicles. The nuclei with fusiform and tapered shapes were mildly hyperchromatic, but never exhibited pleomorphism. Mitotic figures were common, but no atypical mitosis was identified. At the tumor periphery, tumor cells had invaded into the surrounding skeletal muscle tissue. Tumor cells were positive diffusely for alpha-smooth muscle actin and less intensely for desmin, but were negative for h-caldesmon and S-100 protein. Ultrastructurally, tumor cells had well developed cytoplasmic organelles and varying amounts of peripheral or subplasmalemmal bundles of thin myofilaments with focal density. In addition, well formed, long fibronectin fibrils adjacent to the cell surface and fibronexus contacting intracellular myofilaments were easily identified. We believe that fibronexus is a useful ultrastructural feature for differentiating myofibrosarcoma from other myogenic sarcomas.