Takahiro Tajino

h-Caldesmon as a Specific Marker for Smooth Muscle Tumors Comparison With Other Smooth Muscle Markers in Bone Tumors

Caldesmon is a protein widely distributed in smooth and non-smooth muscle cells and is thought to regulate cellular contraction. Its isoform, high-molecular-weight caldesmon (h-CD), was demonstrated to be specific for smooth muscle cells and smooth muscle tumors of the soft tissue and to never be expressed in myofibroblasts. We performed an immunohistochemical study to examine h-CD expression in the following bone tumors: conventional and non-conventional osteosarcoma, 13; malignant fibrous histiocytoma of bone, 5; giant cell tumors of bone, 5; chondroblastoma, 3; metastatic leiomyosarcoma, 2; and rhabdomyosarcoma, 1. Frequent immunoreactivity for muscle actin (alpha-smooth muscle actin or muscle-specific actin) was seen in 11 of 13 osteosarcomas and all other tumors, whereas h-CD was expressed intensely only in 2 leiomyosarcomas. h-CD is considered a specific and useful marker to distinguish smooth muscle tumor from bone tumors with myoid differentiation.

Myofibrosarcoma of the Bone: A Clinicopathologic Study

Myofibroblastic tumors are fairly recently established soft tissue neoplasms. Although most of them appear to be benign, myofibrosarcoma of the soft tissue, seemingly their malignant counterpart, have been reported. We describe the clinicopathologic and radiologic features of four cases of myofibrosarcoma arising from the bone. All but one of the patients were women ranging in age from 60 to 71 years. Two tumors occurred in the metaphyses of distal femurs and the others arose in the iliac bones. On radiologic examination all tumors exhibited well-demarcated lytic destructive lesions without periosteal reaction. Two tumors were localized in the bone, whereas the other two extended into surrounding soft tissues. Histologically, all tumors were composed principally of a mixture of a cell-rich fascicular area and a hypocellular fibrous area. In the former area tumor cells had rather eosinophilic spindle-shaped wavy cytoplasm and were arranged in interlacing fascicles and small storiform patterns with variable numbers of inflammatory cells. Tumors occasionally showed prominent pleomorphism, and large cells with hyperchromatic nuclei were seen. In contrast, hypocellular areas had various features, including collagenous, hyalinous scar-like and rarely keloid-like areas. Focal coagulation necroses were present in all but one tumor. Immunohistochemically, the tumors were positive for vimentin, muscle actin (HHF35), alpha-smooth muscle actin, calponin, and desmin, whereas all of them were negative for high molecular weight caldesmon. On follow-up there was one fatal case with distant metastases, whereas the clinical courses of other cases after wide resection were excellent. Myofibrosarcoma of the bone has distinctive histopathologic features, which should be distinguished from those of other bone tumors with myoid differentiation.

Osteosarcomas after the age of 50: a clinicopathologic study of 64 cases--an experience in northern Japan.

Background: The clinicopathologic profile and prognostic factors of osteosarcomas after the age of 50 years have been obscure.Methods: Clinicopathologic features were analyzed in 645 patients with osteosarcoma who were registered at the Tohoku Musculoskeletal Tumor Society and National Cancer Center in Tokyo between 1972 and 2002.Results: Sixty-four patients (9.9%; 34 men and 30 women) were more than 50 years old. The most common location was the distal femur (n = 13), followed by the pelvis (n = 10), proximal femur (n = 9), and proximal fibula (n = 6). Seven (11%) patients had lung metastasis at initial presentation. On radiographs, an osteolytic appearance without periosteal reactions was a common and characteristic feature. Forty-eight tumors (75%) were classified as conventional osteosarcomas. Fourteen cases (22%) were secondary; postradiation osteosarcoma was most common in these patients, but there was no Paget’s sarcoma. At the initial presentation, misdiagnoses without biopsy were made in 15 (23%) of the 64 cases. Preoperative chemotherapy was given to 22 patients, but the effect was poor in 18 cases (82%). Fifty-four patients underwent surgery, whereas the other 10 patients were treated without surgery because of systemic or inoperable local conditions. The overall survival rate at 5 years was 55.5%. Multivariate analysis showed initial pulmonary metastasis, axial tumor location, and larger tumors as significant prognostic factors.Conclusions: In northern Japan, most patients with osteosarcoma after the age of 50 had primary osteosarcoma. Careful radiological examination and biopsy are mandatory for correct diagnosis. Current systemic chemotherapy is not effective for this age group. Alternative treatment strategies should be considered.

Inflammatory Myofibroblastic Tumor (Inflammatory Fibrosarcoma) of the Bone

Although inflammatory myofibroblastic tumors, originally described in the lung, have recently been recognized to occur in various sites, their origin in bone is exceptional. We present a case of inflammatory myofibroblastic tumor, so-called inflammatory fibrosarcoma, of the bone. The tumor occurred in the iliac bone of a 70-year-old woman. Standard radiographs and magnetic resonance imaging revealed a destructive bone tumor that expanded into the soft tissue. Although the patient underwent excision of the hemi-iliac bone, multiple pulmonary metastases were noted 1 year after the operation. On histologic examination, the tumor was found to be composed of a sarcoma-like cellular area and a hypocellular fibrous area. Inflammatory cell infiltration into the tumor was a distinctive feature and is analogous with that of conventional inflammatory myofibroblastic tumor or inflammatory fibrosarcoma of the soft tissue. This is the first report to our knowledge of an inflammatory myofibroblastic tumor of the bone with distant metastasis.

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 SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1090602085125068

Clinical Relevance of Pathological Grades of Malignant Peripheral Nerve Sheath Tumor: A Multi-Institution TMTS Study of 56 Cases in Northern Japan

BackgroundMalignant peripheral nerve sheath tumor (MPNST) is a relatively rare soft tissue tumor, and its clinical relevance of pathological grades remains obscure.MethodsFifty-six cases of MPNST identified from the files of seven oncology centers of the Tohoku Musculoskeletal Tumor Society (TMTS) and National Cancer Center were analyzed for histologic grades, demographics, treatments, and prognostic factors. The average follow-up period was 41 months.ResultsTwenty-two men and 34 women with a mean age of 45 years were involved. Forty-four (78.6%) of 56 tumors were in the lower extremity or trunk. Fifty tumors (89%) were classified as high grade, and the remaining six as low grade. Twenty-one (39.6%) of 53 patients who underwent tumor excision developed local recurrences. An axial site and inadequate surgical margin were defined as risk factors for local recurrence. The overall survival rates of the 56 patients were 55.1% at 3 years and 43.3% at 5 years. Univariate analysis of the 56 patients revealed large-sized tumors, metastasis at presentation, and histologically high grade were significantly associated with poor prognosis. Multivariate analysis revealed a large tumor and metastasis at presentation to be independent prognostic factors.ConclusionsThe current study involving 56 patients with MPNST showed the aggressive clinical behavior of the tumor. Large-sized tumors, metastasis at presentation, and high histological grade were related to poor prognosis on univariate analysis, but independency of histological grade was still obscure. In the treatment for a large and high-grade MPNST, an alternative strategy should be further considered.

Giant cell tumor of bone: Frequent actin immunoreactivity in stromal tumor cells

Although giant cell tumor (GCT) of bone is a well‐recognized neoplasm with distinctive clinical and histopathological features, the origin of tumor cells, particularly of mononuclear cells, has not yet been established. An immunohistochemicai study was carried out on 11 cases of GCT of bone to examine the cellular natures of stromal mononuclear cells. In all cases, stromal cells were positive for muscle actin (HHF35) or α‐smooth muscle actin, and in eight of 11 cases, positivist was intense and extensive. The cell margin of osteoclast‐like giant cells (OGC) was stained positively by muscle actin, In addition to Intense and diffuse positive staining of the cytoplasm for KP1 (CD68), whereas α‐smooth muscle acting exhibited a negative reaction on the OGC. In conclusion, the tumor cells with muscle actin and α‐smooth muscle actin proclivities are not rare but frequently numerous In the GCT of bone; whereas further observation Is necessary to elucidate whether the stromal cells exhibit myoflbroblastlc cell differentiation exactly.

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

BackgroundIfosfamide 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.MethodsWe retrospectively examined the incidence, severity, and risk factors of ifosfamide encephalopathy in 61 Japanese patients with bone and soft tissue sarcomas at our institution.ResultsIfosfamide 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 ≥9 g/m2. A history of cisplatin use was identified as a significant risk factor for the development of ifosfamide-induced encephalopathy.ConclusionsBecause of the risk of severe encephalopathy, we conclude that patients who have previously received cisplatin or who receive ifosfamide at doses ≥9 g/m2 require strict monitoring.

A clinicopathological study of giant cell tumor of small bones

Abstract 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.