Tetsuo Hotta

Tumors of peripheral nerves : correlation of symptoms, clinical signs, imaging features, and histologic diagnosis

Abstract Objective. To distinguish between benign and malignant tumors in the peripheral nerves. Design and patients. The clinical, imaging and histologic findings of 99 benign and 16 malignant tumors in the peripheral nerves were reviewed retrospectively. Results. Preoperative motor weakness was observed in only six of 99 benign tumors and was mild, while slight to severe motor weakness was present in 15 of 16 malignant lesions. Pain at rest was present in five of 99 benign tumors and in 15 of 16 malignant tumors. All benign lesions showed a smooth tumoral margin, while half the malignant lesions showed an invasive margin on CT or MRI. Thirteen of 28 benign lesions on CT and nine of 23 on MRI showed round to geographic central enhancement, but this pattern was not seen in malignant lesions. Conclusion. Absence of severe motor weakness and a central enhancement pattern strongly suggest a benign nature, while severe rest pain and invasive tumor margin suggest malignant lesions in peripheral nerve tumors.

Alveolar Soft Part Sarcoma in Japan: Multi-Institutional Study of 57 Patients from the Japanese Musculoskeletal Oncology Group

Objective: The clinical features and the management of alveolar soft part sarcoma (ASPS) are not well known. The efficacy of chemotherapy for soft tissue sarcoma, including high-dose ifosfamide and cisplatin, has not been established yet. Some reports suggest ASPS may occur primarily in bone. Methods: We report on a series of 57 patients with ASPS over 20 years. Their ages ranged from 7 to 75 years (mean 25). Results: There were 37 females and 20 males. Thirteen lesions (23%) showed bone involvement at the primary site, and 6 of them were diagnosed as bone tumors at presentation. Thirty-seven patients had distant metastases at presentation. Tumor size, bone involvement at the primary site and the presence of metastases at presentation were prognostic indicators (p < 0.05). Marginal excision with radiotherapy or wide excision without radiotherapy achieved good local control. Chemotherapy was performed in 47 patients with different regimens. Two patients treated with intra-arterial chemotherapy regimens responded partially, but intravenous chemotherapy with high-dose ifosfamide or cisplatin failed. Conclusions: ASPS can present primarily as a bone tumor. No advantage of chemotherapy with high-dose ifosfamide or cisplatin could be demonstrated.

Recurrent malignant variant of phosphaturic mesenchymal tumor with oncogenic osteomalacia.

Abstract 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.

Multiple schwannomas in the peripheral nerves

Multiple tumours of peripheral nerves are often seen in patients with neurofibromatosis of type 1 or 2. Multiple schwannomas may occur without other manifestations of neurofibromatosis. We have reviewed 12 patients with multiple schwannomas arising from peripheral lesions who did not fulfil the criteria for either type of neurofibromatosis. Four had spinal and one an intracranial lesion in addition to the peripheral tumours. Two patients had one and three café-au-lait spots, respectively, and another had a probable family history. The largest tumours were 45 to 250 mm in size. Three patients had been referred as having von Recklinghausens disease. The large size of tumours, the difficulties of histological diagnosis on biopsy, and the confusion with neurofibromatosis can lead to overtreatment. Malignant change seldom, if ever, occurs in patients with multiple schwannomas.

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.

Three Human Osteosarcoma Cell Lines Exhibiting Different Phenotypic Expressions

In an attempt to elucidate the differences in histological features and biological behavior of osteosarcomas, three human osteoblastic type osteosarcomas were studied in vitro and in nude mice. The secretory processing and extracellular fiber formation of type I collagen proved to be the most important factor in bone formation in the osteosarcomas. Alkaline phosphatase also seemed to be important. However, we were unable to find any particular protooncogene abnormalities which could have been implicated in the occurrence or biological behavior of these osteosarcomas. Acta Pathol Jpn 42: 595 603, 1992.

Expression of podoplanin in human bone and bone tumors : New marker of osteogenic and chondrogenic bone tumors

Podoplanin is known as a lymphatic marker because its expression is detected in lymphatic but not vascular endothelium. Podoplanin is also expressed in several normal tissues including osteocytes or osteoblasts. A systematic examination of the podoplanin expression was conducted in normal skeletal tissues and some bone tumor cell lines, and the diagnostic value determined in primary bone tumors. Podoplanin mRNA was expressed at a high level in bone marrow tissue and cartilage, and was upregulated with differentiation to osteoblasts in bone marrow cells. Strong podoplanin expression was seen in osteocytes, chondrocytes, and osteoblasts on immunohistochemistry. Podoplanin mRNA was expressed at a high level in several osteosarcoma and chondrosarcoma cell lines, whereas podoplanin was expressed at a low level in a Ewings/primitive neuroectodermal tumor cell line. In the clinical samples, osteosarcomas (22/26) expressed podoplanin at various levels. In small cell osteosarcomas (2/2), podoplanin was expressed strongly, although the tissue samples included few diagnostic osteoids. Chondrosarcomas (10/10) expressed podoplanin strongly, and chondroblastomas (5/5) expressed podoplanin moderately, while podoplanin was absent or expressed at low levels in Ewings sarcomas (0/5), chordomas (0/6) and giant cell tumors of bone (1/7). Therefore, podoplanin may be a sensitive immunohistochemical marker of osteogenic and chondrogenic bone tumors.

High-Level Expression of the Coxsackievirus and Adenovirus Receptor Messenger RNA in Osteosarcoma, Ewing’s Sarcoma, and Benign Neurogenic Tumors among Musculoskeletal Tumors

Purpose: The sensitivity of human tumor tissues to infection with recombinant adenoviruses correlates with the expression of the coxsackievirus and adenovirus receptor (CAR). CAR has been shown to function as the primary receptor for adenoviruses and to play a critical role in adenovirus entry into host cells. It is important for clinical gene therapy to determine the expression level of CAR in tumor tissues. Experimental Design: We analyzed the expression of CAR mRNA in 154 musculoskeletal tumor tissues from 154 patients and 10 normal mesenchymal tissues from 3 patients using reverse transcription-PCR and real-time quantitative PCR. An adenovirus infection assay was performed in two cell lines that were established from CAR-positive osteosarcoma tissue and CAR-negative malignant fibrous histiocytoma tissue. Results: Ninety-nine of 154 tumors were detected as CAR positive by reverse transcription-PCR. We found that the expression levels of CAR mRNA varied markedly between different tumors as determined by real-time quantitative PCR. CAR mRNA was expressed at high levels in osteosarcoma, Ewing’s sarcoma, neurofibroma, and schwannoma; at intermediate levels in exostosis, giant cell tumor, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and hemangioma; and at low levels in alveolar soft part sarcoma and desmoid. Whereas the osteosarcoma cell line that expressed a high level of CAR mRNA, like its parent tumor, had a high efficiency of adenovirus infection, the malignant fibrous histiocytoma cell line with almost undetectable expression of CAR mRNA, like its parent tumor, had a low efficiency of infection. Conclusions: Our data showed the great variations in CAR mRNA expression among human musculoskeletal tumors and mesenchymal tissues and implicated the potential usefulness of adenoviral vectors in gene therapy for osteosarcoma, Ewing’s sarcoma, neurofibroma, and schwannoma. Efficient transduction with adenovirus for gene therapy could be realized in appropriate, sensitive tumor types.

Margin-free spondylectomy for extended malignant spine tumors : Surgical technique and outcome of 13 cases

Study Design. Description of surgical technique and retrospective review of 13 cases. Objectives. To describe the surgical technique of margin-free spondylectomy and the outcome of 13 cases and to discuss the advantages and limitations of the procedure. Summary of Background Data. Recently, spondylectomy became a standard procedure by several pioneers. For extended malignant spine tumors involving pedicles or epidural space, however, performing an “en bloc” resection with a tumor-free margin remains a challenge. Methods. Our procedure consists of a combined anterior and posterior procedure with one or two stages. In the anterior procedure, tumor vertebrae are covered by the pleura or psoas muscles as a barrier. The posterior procedure includes decompression through the intact posterior elements, coverage of the tumor with all possible soft tissue barriers, and en bloc extirpation by rotating the tumor vertebrae around the spinal cord. We performed this procedure in 13 cases: 3 chondrosarcoma, 3 giant cell tumor, 1 osteosarcoma, 1 chordoma, and 5 metastases. Results. Neurologic status and pain improved in all cases except asymptomatic cases. There was no local recurrence, except in 2 cases (chondrosarcoma with extirpation of 5 vertebrae, chordoma with multiple previous surgeries). Two cases of chondrosarcoma were disease-free 14 years and 13 years after surgery, respectively. Conclusion. Although the best chance for a cure in extended malignant tumors of the spine is realized through wide resection, the procedure is not yet standardized. Margin-free spondylectomy is technically demanding, but the procedure can be used with a confidence as a more radical surgery for tumors extending to the epidural space and the unilateral pedicle. A key to success is the surgical technique, including a 360° dissection around the tumor vertebrae, instrumentation, and removal of the lesion with all possible soft tissues maintained intact to function as a barrier, like the dura mater.

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.