Katsushige Yamashiro

ErbB2 expression is correlated with increased survival of patients with osteosarcoma

Elevated ErbB2 expression and gene amplification have been shown to be associated with poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. By contrast, a previous study showed that the expression of ErbB2 declines in individual osteosarcomas as they become metastatic. In the current study, the authors determined the relation between ErbB2 status and outcome in a large number of selected patients with high‐grade osteosarcoma.

Diagnosis of Synovial Sarcoma with the Reverse Transcriptase-polymerase Chain Reaction: Analyses of 84 Soft Tissue and Bone Tumors

The chimeric transcript SYT-SSX is generated as a result of reciprocal translocation t(X;18), which is the primary cytogenetic abnormality found in, and appears to be specific for, synovial sarcoma. We performed a reverse transcriptase-polymerase chain reaction (RT-PCR) for SYT-SSX transcripts in a series of 84 tumors (61 soft tissue tumors and 23 bone tumors), including a variety of histologic types, to assess its usefulness in molecular diagnosis. Ten synovial sarcomas, three tumors initially unclassified, and one malignant peripheral nerve sheath tumor contained the chimeric transcripts. A review of the original slides and additional examination showed that a diagnosis of synovial sarcoma was appropriate for these cases. Additionally, in situ hybridization with an SSX1 probe indicated that the chimeric transcripts exist not only in the cells of special components but also in cells showing a variety of histologic patterns. Therefore, RT-PCR can be considered a useful molecular biological technique that can provide objective evidence for diagnosis of synovial sarcoma. Northern blot analysis with an SSX1 probe also detected chimeric SYT-SSX transcripts in the synovial sarcoma cases. The additional smaller bands, however, were also detected in six peripheral primitive neuroectodermal tumors (pPNETs) and one embryonal rhabdomyosarcoma. In five of these pPNETs, other bands ranging in size from 2.0 to 2.2 kb were also found, and it seems possible that these bands might represent novel karyotypic aberrations and/or splicing variants of SSX.

Extraskeletal myxoid chondrosarcoma : a multi-institutional study of 42 cases in Japan

Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm. Despite a consensus for the distinct clinicopathologic entity of EMC, its clinical features remain controversial. In addition, most studies have contained a small number of patients who underwent definitive surgical treatment.

Establishment of a new continuous clear cell sarcoma cell line. Morphological and cytogenetic characterization and detection of chimaeric EWS/ATF-1 transcripts.

Abstract Clear cell sarcoma (CCS), a rare tumour of deep soft tissues, often has a t(12; 22) (q13; q12) translocation that induces the formation of a hybrid EWS/ATF-1 gene. To investigate these alterations further, we established a new continuous cell line directly from a CCS taken from a 9-year-old girl. The cultures were characterized with respect to morphological, ultrastructural, immunohistochemical and karyotypical features and were tested by reverse transcription PCR (RT-PCR) for chimaeric EWS/ATF-1 transcripts. The continuous cell line, designated KAO, is tumorigenic in nude mice, and the resultant tumours resemble the primary CCS. The tumour cells and the cultured cells have melanosomes in their cytoplasm and are immunoreactive with the melanoma-specific antibody HMB45, but do not express S-100 protein. The cultured CCS cells have the t(12; 22)(q13; q12) translocation and express the hybrid EWS/ATF-1 gene. No transcripts of the hybrid gene were detected in a malignant cutaneous melanoma tested simultaneously. Although CCS and malignant melanoma are morphologically related, the present results suggest that their geneses differ at the chromosome and molecular levels. They also indicate that chromosome analysis and detection of fusion EWS/ATF-1 transcripts may be useful adjuvant tools for the diagnosis of CCS.

Improvement in prognosis of neuroblastoma through mass population screening

Since April 1981, the city of Sapporo, Japan, has conducted a mass screening program to measure urinary vanillylmandelic acid and homovanillylic acid using high-performance liquid chromatography. This program was expanded to the entire island of Hokkaido in October 1987. Mass screening proved beneficial, resulting in an increase in patients diagnosed with neuroblastoma under 1 year of age from 17% to 66%, an increase in stage I cases from 9% to 26%, an increase in stage III cases from 9% to 32%, and an increase in the tumor resectability rate from 15.1% to 58%. These improvements raised the 5-year survival rate for neuroblastoma from 23% to 66.7%. An additional study of these mass screening cases using Shimadas classification showed a wide range of histopathological distribution, and it demonstrated the usefulness of such a program in identifying the tumors most in need of early treatment.

Histological and Molecular Evidence of Synovial Sarcoma of Bone. A Case Report

Synovial sarcoma is a clinically and morphologically well defined soft-tissue tumor that occurs predominantly in the extremities of adolescents and young adults. It tends to arise in the vicinity of large joints, especially the knee8. This tumor was designated synovial sarcoma because of its anatomical location and its histological resemblance to normal synovial tissue. However, we do not believe that there is any convincing evidence that synovial sarcoma always originates from synovial tissue. It is possible that the lesion sometimes arises from primitive mesenchymal cells rather than from preformed synovial cells; therefore, the development of synovial sarcoma is no longer thought to require the presence of preexisting synovial tissue. To the best of our knowledge, there have been no reports of synovial sarcoma arising in bone. The reciprocal translocation t(X;18)(p11.2;q11.2) was noted in all twenty-two reported cases of synovial sarcoma that have been studied cytogenetically5,18. This translocation is considered to be specific to this tumor. Cloning of the DNA adjacent to the breakpoints of the translocation t(X;18) has shown2 that this translocation results in fusion of the SYT gene at 18q11.2 to either of two genes, SSX1 or SSX2, at Xp11.2. This rearranged configuration of DNA is transcribed to messenger RNA and is called a chimeric SYT-SSX transcript. A chimeric SYT-SSX transcript does not occur normally and thus provides a specific marker for synovial sarcoma that can be detected with reverse transcriptase-polymerase chain-reaction testing. We describe the case of a patient who had synovial sarcoma of bone that was verified by the detection of a chimeric SYT-SSX transcript. A sixty-seven-year-old man had a four-month history of pain in the right wrist when he was first seen by us. Physical examination revealed moderate swelling and a restricted range of motion of the wrist (30 …

A case of osteosarcoma arising in a solitary osteochondroma.

percent in patients with multiple osteochondromatosis (Matsuno et al. 1988). It is sometimes difficult to distinguish malignant transformation in an osteo- chondroma from other malignant tumors occurring on the surface of bone. Since the dedifferentiated chondrosarcoma (DCS) was described in detail by Dahlin and Beabout (1971), it has been given considerable attention because of its characteristic histologic features and high malignancy. DCS occurs in approximately 10 percent of the patients who have a low-grade chon- drosarcoma and histologically show chondrosarcom- atous features with additional mesenchymal components (Dahlin and Beabout 1971, McCarthy and Dorfman 1982, Capanna et al. 1988). Most

Growing teratoma syndrome of the Ovary: A case report with FDG ‐PET findings

Growing teratoma syndrome (GTS) is defined as enlarging masses during or after chemotherapy for germ cell tumors, and containing only mature teratoma components. A surgical resection is important to confirm a diagnosis and thereby result in the resection of the most appropriate therapeutic management. GTS is a rare event in association with ovarian germ cell tumors. This report presents a case of a 36‐year‐old female treated surgically for GTS found during the follow‐up after chemotherapy and the primary surgical resection of a malignant immature teratoma. Those masses showed fluorodeoxyglucose positron emission tomography positivity and elevated serum CA19‐9 prior to the second operation. The histology revealed a mature teratoma. The patient has been disease free for 6 months after the second operation.

Ultrastaging of para-aortic lymph nodes in stage IIIC1 endometrial cancer: A preliminary report

OBJECTIVE The aim of this study was to determine the rate of occult metastasis, including isolated tumor cells, in para-aortic lymph nodes of patients with stage IIIC1 endometrial cancer who underwent pelvic and para-aortic lymphadenectomy. METHODS A series of 15 patients who had undergone combined pelvic and para-aortic lymphadenectomy during the period from 2004 to 2010 and who were diagnosed as being positive for pelvic node metastasis but negative for para-aortic node metastasis were included in this study. Ultra-staging by multiple slicing, staining with hematoxylin/eosin and cytokeratin, and microscopic inspection was performed on a total of 242 para-aortic lymph nodes. RESULTS Eleven (73.3%) of the 15 patients had occult para-aortic lymph node metastasis. Two patients (13.3%) had macrometastasis and nine patients (60.0%) had isolated tumor cells. Type 2 endometrial cancer tended to have a higher rate of occult metastasis than that of type 1 cancer (90% vs. 40%, P=0.07). The rate of occult para-aortic node metastasis was not related to the number of metastatic pelvic nodes. Five patients suffered recurrence in the lung or in the intraabdomen, but lymph node recurrence was not found in any case. CONCLUSION Patients with stage IIIC1 endometrial cancer have a potentially high rate of occult para-aortic node metastasis. Local treatment of the para-aortic region should be considered in patients with stage IIIC1 endometrial cancer until effective adjuvant therapy is established.

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer

Objective The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer. Methods In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases. Results Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080). Conclusions It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.