Long-term outcomes of an extracorporeal irradiated autograft for limb salvage operations in musculoskeletal tumours: over ten years' observation.

AIMS: We analyzed the long-term outcomes of patients observed over ten years after resection en bloc and reconstruction with extracorporeal irradiated autografts. PATIENTS AND METHODS: This retrospective study included 27 patients who underwent resection en bloc and reimplantation of an extracorporeal irradiated autograft. The mean patient age and follow-up period were 31.7 years (9 to 59) and 16.6 years (10.3 to 24.3), respectively. The most common diagnosis was osteosarcoma (n = 10), followed by chondrosarcoma (n = 6). The femur (n = 13) was the most frequently involved site, followed by the tibia (n = 7). There were inlay grafts in five patients, intercalary grafts in 15 patients, and osteoarticular grafts in seven patients. Functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: There were no recurrences in the irradiated autograft and the autograft survived in 24 patients (88.9%). Major complications included nonunion (n = 9), subchondral bone collapse (n = 4), and deep infection (n = 4). Although 34 revision procedures were performed, 25 (73.5%) and four (11.8%) of these were performed less than five years and ten years after the initial surgery, respectively. The mean MSTS score at the last follow-up was 84.3% (33% to 100%). CONCLUSION: Considering long-term outcomes, extracorporeal irradiated autograft is an effective method of reconstruction for malignant musculoskeletal tumours Cite this article: Bone Joint J 2019;101-B:1151-1159.

Congenital dermatofibrosarcoma protuberans with fibrosarcomatous and myxoid change.

This report describes a case of congenital dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous (FS) and myxoid areas. Immunohistochemical results showed that tumour cells in ordinary DFSP areas were diffusely positive for CD34, whereas in the FS and myxoid areas, few tumour cells were positive for this antigen. Ki-67 positive tumour cell numbers were greater in the FS (11.8%) and myxoid areas (19.8%) relative to ordinary DFSP areas (2.2%). Reverse transcription polymerase chain reaction and sequence analysis showed the presence of an identical COL1A1-PDGFB fusion transcript in ordinary DFSP (plaque-like area), FS, and myxoid areas of DFSP. These results indicate that the three components of DFSP have a common histogenesis. This study documents the first application of gene analysis involving the myxoid area of DFSP.

Extracorporeal irradiated autogenous osteochondral graft: a histological study.

We examined osteochondral autografts, obtained at a mean of 19.5 months (3 to 48) following extracorporeal irradiation and re-implantation to replace bone defects after removal of tumours. The specimens were obtained from six patients (mean age 13.3 years (10 to 18)) and consisted of articular cartilage (five), subchondral bone (five), external callus (one) and tendon (one). The tumour cells in the grafts were eradicated by a single radiation dose of 60 Gy. In three cartilage specimens, viable chondrocytes were detected. The survival of chondrocytes was confirmed with S-100 protein staining. Three specimens from the subchondral region and a tendon displayed features of regeneration. Callus was seen at the junction between host and irradiated bone.

Treatment of pathological fracture of the femur due to diffuse haemangioma in the lower limb.

We describe two patients with a diffuse haemangioma of the lower limb complicated by pathological fracture of the femoral shaft, one of whom was treated by a bone graft and immobilisation in a cast, and the other by external fixation and injection of bone marrow. A review of the literature identified difficulty in control of bleeding and obtaining bony union.

Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation.

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.

Painful Schmorl's node treated by lumbar interbody fusion.

STUDY DESIGN: A case report of painful lumbar Schmorl's node is presented. OBJECTIVE: To describe diagnostic evidence and the result of surgical treatment of a rare case of painful Schmorl's node. SETTING: Niigata, Japan. CASE REPORT: A 55-year-old housewife was diagnosed with painful Schmorl's node of L3 by discography, which depicted leakage of the contrast medium into the L3 vertebra through a disruption of the central part of the cranial end plate with concomitant back pain. Segmental fusion surgery was performed. Mechanical low back pain of the patient improved just after surgery. Histologic examination demonstrated that fibrocartilaginous tissue herniated through a disruption of the superior end plate and forced into the vertebral spongiosa. CONCLUSIONS: Painful Schmorl's node can be diagnosed by discography, which demonstrates an intravertebral disc herniation with concomitant back pain. Surgical treatment should be considered in a patient with persistent disabling back pain. When surgical treatment is indicated, eradication of the intervertebral disc including Schmorl's node and segmental fusion are preferable.

Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

Treatment of myxoid liposarcoma by marginal or intralesional resection combined with radiotherapy.

Local recurrence-free survival rate for myxoid liposarcoma (MLS) is related to negative surgical margins. The goal of surgery in the treatment of MLS is to obtain tumor-free surgical margins. When a tumor is adjacent to critical structures, wider resection, which can result in amputation, would be selected for local control. While recognizing that marginal or intralesional resection is associated with high risk of recurrence, circumstances occur that lead surgeons to conduct conservative surgery. To determine whether marginal or intralesional resection combined with radiotherapy can achieve local control, 10 cases (12 tumors) were reviewed involving MLS treated with marginal (8 tumors) or intralesional resection (4 tumors) followed by postoperative radiotherapy (50-70 Gy, average 59.2 Gy). No recurrences of MLS were observed locally at the mean follow-up of 58.1 months. The development of severe radiation-related complications was not detected. This medium follow-up study suggested that this method can achieve a high rate of local control.

Increase in serum 1,25-dihydroxyvitamin D and hypercalcaemia in a patient with inflammatory myofibroblastic tumour.

Hypercalcaemia complicates the clinical course of a substantial number of patients with advanced cancer. This report describes a patient with an inflammatory myofibroblastic tumour in soft tissue who developed an inflammatory reaction, hypercalcaemia, and a high serum concentration of 1,25 dihydroxyvitamin D. Serum concentrations of 25-hydroxyvitamin D, parathyroid hormone, and parathyroid hormone related protein were normal. Histological examination of the tumour revealed fibrosarcoma with abundant macrophage infiltration. mRNA for 25-hydroxyvitamin D-1alpha-hydroxylase was identified in the tumoral tissue. In view of this case, inflammatory myofibroblastic tumour should be added to the list of diseases that are responsible for vitamin D mediated hypercalcaemia.

Myxoid liposarcoma metastatic to the thoracic epidural space without bone involvement: report of two cases.

Myxoid liposarcoma can frequently metastasize to extrapulmonary sites. We present two cases of myxoid liposarcoma metastatic to the epidural space. Both patients complained of back pain, but plain radiography revealed no abnormality. MR imaging clearly demonstrated metastatic tumors in the epidural space, but no involvement of vertebra. When patients with myxoid liposarcoma complain of back pain, metastasis in the epidural space should be considered even in patients without bone involvement.

Presacral schwannoma with purely cystic form.

STUDY DESIGN: Case report. OBJECTIVE: To point out that presacral schwannoma can display markedly cystic degeneration. SUMMARY OF BACKGROUND DATA: Benign schwannoma sometimes displays degenerative changes, such as cyst formation, calcification, hemorrhage, and hyalinization. Usually these degenerations are partially seen in the tumors. METHODS: Medical history, physical findings, imaging features, and histologic findings were reviewed in a case with a large presacral schwannoma. RESULTS: A 62-year-old woman presented with an 18-month history of right sciatic pain. Magnetic resonance images detected a large cystic, presacral tumor. Initially the tumor was misdiagnosed as a cystic ovarian tumor. Preoperative diagnostic workup led to the diagnosis of cystic schwannoma. Intralesional curettage achieved good pain relief. CONCLUSIONS: This tumor was unusual in its totally cystic appearance and resemblance to a cystic ovarian tumor or anterior sacral meningocele. Preoperative diagnosis is important to prevent major neurologic deficit at surgery.

A PCR-ELISA assay for the detection of disseminated osteosarcoma cells in a mouse metastatic model.

Circulating tumor cells in the blood play a central role in the metastatic process. There have been no reports describing the relationship between lung metastasis and circulating osteosarcoma cells. We developed a system with a polymerase chain reaction assay based on an enzyme-linked immunosorbent assay (PCR-ELISA) to detect circulating osteosarcoma cells in a mouse metastatic model. Osf2/Cbfa1, hereafter called Osf2, a member of the runt family of transcription factors, was used as a target gene. One splicing variant of Osf2 mRNA was identified and its expression was restricted to the bones and osteosarcomas. The amount of the splicing variant of Osf2 mRNA was significantly higher in the blood of mice with metastasis than in the blood of the control group. The PCR-ELISA using Osf2 mRNA is a potential method to detect circulating osteosarcoma cells in peripheral blood.

Retroperitoneal malignant peripheral nerve sheath tumor associated with scoliosis in neurofibromatosis.

Neurofibromatosis 1 is an autosomal dominant disorder characterized by distinctive clinical problems including scoliosis and malignant peripheral nerve sheath tumors. We present two cases of retroperitoneal malignant peripheral nerve sheath tumor associated with scoliosis in neurofibromatosis. Presence of spinal deformity resulted in delay of the diagnosis of the sarcoma.

Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia.

Phosphaturic mesenchymal tumor is a rare neoplasm which causes osteomalacia or rickets. The tumor typically follows a benign clinical course. Even in the rare malignant cases, local recurrence and distant metastasis are uncommon. We report on an example of a malignant phosphaturic mesenchymal tumor which recurred several times over 16 years concurrently causing hypophosphatemia, bone pain, and osteomalacia. Following each surgery, symptoms and hypophosphatemia improved. The patient died of disease 17 years after the first surgery. Histologically, the initial tumor was composed of small spindle cells with clusters of giant cells, prominent blood vessels, poorly formed cartilaginous areas, and crystalline material. Cytological atypia was minimal. Following multiple recurrences, the tumor demonstrated areas of high-grade sarcoma exhibiting marked pleomorphism, numerous mitotic figures, and p53 overexpression. This case illustrates the potential lethality of incompletely removed phosphaturic mesenchymal tumors.

Elevation of serum alkaline phosphatase in clear cell chondrosarcoma of bone.

BACKGROUND: Clear cell chondrosarcoma is a rare bone tumor, which is sometimes misdiagnosed as a different bone neoplasm. MATERIALS AND METHODS: The files of 6 patients with clear cell chondrosarcomas were reviewed. Histological slides, radiographic studies, and pre- and post-operative serum alkaline phosphatase (ALP) levels were evaluated. Molecular and histochemical analyses of ALP were documented in one case of clear cell chondrosarcoma. RESULTS: Pre-operative serum ALP levels were elevated in 3 patients, and were normal in another 3 patients. After removal of the tumors, the enzyme levels decreased in all patients and returned to normal in 3 patients, who had pre-operative high ALP levels. Enzyme histochemical and molecular analyses demonstrated that the tumor produced ALP. CONCLUSION: Clear cell chondrosarcoma produces ALP, which can be used as a tumor marker in diagnosis and follow-up.

Deep-seated segmental neurofibromatosis without café au lait spots.

Segmental neurofibromatosis is a rare disease characterized by neurofibromas with or without café au lait spots localized to one segment of the body. The majority of reported cases have had cutaneous neurofibromas, and patients with deep involvement have rarely been described. We report on two patients with deep-seated segmental plexiform neurofibromatosis and review the literature. All reviewed cases including the present two had no café au lait spots, axillary freckling, Lisch nodules, family history or malignant progression of disease. Differential diagnoses from neuro-fibromatosis 1 (von Recklinghausen disease) and malignant peripheral nerve sheath tumor are important for genetic counseling and avoiding overtreatment.

Collagenous fibroma of the arm: a report of two cases.

A recently proposed addition to fibrous tumors in soft tissue was first described as desmoplastic fibroblastoma and later renamed collagenous fibroma. This tumor is clinically and morphologically distinct and benign. However, only a few series have been reported, and the clinicopathologic features are not widely recognized. We present two cases of collagenous fibroma of the arm. Both patients presented with an enlarging, well-circumscribed and mobile soft tissue mass. Magnetic resonance imaging showed areas of low signal intensity on both T1- and T2-weighted sequences. Needle aspiration cytology revealed nondiagnostic samples because of the low cellularity of the tumors. Each of the resected tumors was composed of low-cellular spindle- to stellate-shaped cells in a fibrous matrix with clear margination. After the marginal excisions, no recurrences were observed. Clinicians should be aware of this entity to prevent overtreatment, because imaging findings and cytologic features are similar to those of desmoid tumor.