矢部 寛樹

Cancer polyarthritis is a very rare condition. Here, we present a case of cancer polyarthritis, who also had mononeuritis simplex as a manifestation of paraneoplastic neuralgic syndrome. A 71-year-old man, who initially presented symmetrical polyarthritis and unilateral posterior interosseous nerve palsy, was subsequently diagnosed to have gastric cancer. Total gastrectomy was performed, and his polyarthritis and the palsy simultaneously disappeared within 2 weeks after the resection. His gastric cancer was found to be metastasized to his liver 16 months after the total gastrectomy; however, the polyarthritis and the palsy did not recurrent throughout his course. The polyarthritis in this case was diagnosed as a cancer polyarthritis from its features. On the other hand, the isolated posterior interosseous nerve palsy in this case met the diagnostic criteria for paraneoplastic neurological syndrome. This case was also unique in that the manifestations of paraneoplastic syndromes did not recur even after the metastasis of the primary cancer, suggesting that some specific clones in the cancer were responsive to the manifestations of paraneoplastic syndromes. Our case suggested that relapse of the manifestations of paraneoplastic syndromes may not always herald the recurrence of primary or metastatic tumour, and other tumour markers and signs should be periodically followed to search for the recurrence of the tumours.

Spontaneous spinal epidural hematoma (SSEH) is an uncommon but clinically important disease, and delayed diagnosis of this condition can have severe consequences. General physicians should consider the possibility of SSEH when they encounter a patient with a sudden onset of unexplained cervical or back pain or subsequent radicular symptoms during anticoagulant therapy. Immediate magnetic resonance imaging is essential for early diagnosis. In this article, we present a rare case of an 80-year-old man who developed cervical SSEH during warfarin therapy.

Background: Ewing's sarcoma family of tumors (ESFT) is one of the most malignant groups of tumors in young people. Human leukocyte antigen (HLA) class I displays endogenously processed peptides to CD8+ T lymphocytes and has a key role for host immune surveillance. In ESFT, the investigation concerning both HLA class I expression and T-cell infiltration has yet to be reported. Methods: Biopsy specimens from 28 ESFT patients were evaluated by immunohistochemistry with the anti-HLA class I monoclonal antibody (mAb) EMR8-5 and anti-CD8 mAb, respectively. Results: Expression of HLA class I was negative in 10 tumors and down-regulated in 22 tumors. The status of CD8+ T cell infiltration was closely associated with the expression levels of HLA class I. ESFT patients with down-regulated or negative expression of HLA class I showed significantly poorer survival than the rest of the patients. Conclusions: Our results suggested that CD8+T cell-mediated immune response restricted by HLA class I might play an important role in immune surveillance of ESFT, and we revealed for the first time that the status of HLA class I expression affects the survival of the patients with ESFT. J. Surg. Oncol. 2011; 103: 380-385. (C) 2010 Wiley-Liss, Inc.

3カ月前から始まった手指・顔面の多発結節性皮疹と手指関節炎を主訴に来院した76歳女性．皮膚生検にて多核巨細胞の集簇を認めmulticentric reticulohistiocytosisと診断.従来有効な治療がなく急速に関節破壊に至った疾患であるが，浸潤細胞はマクロファージの形質を示し抗TNF療法が有効との報告がある．本例にインフリキシマブ投与が著効し，本症治療の第一選択肢と考えられた．<br>

In two patients with primary bone lymphoma (PBL) treated in our clinic, serum levels of soluble interleukin-2 receptor (sIL-2R) reflected the clinical course. In both cases, sIL-2R levels were high before treatment and normalized with the therapeutic effects of chemotherapy, coinciding with the changes in lactate dehydrogenase levels and radiographic findings. Adding to the recently reported results of the diagnostic ability of sIL-2R in PBL, our case study highlights the clinical significance of serum sIL-2R levels as a tumor marker in PBL cases. © 2011 S. Karger AG, Basel.

A 74-year-old woman diagnosed with Churg-Strauss syndrome (CSS) complained of difficulty in flexing her left thumb and index finger. Electromyography demonstrated isolated anterior interosseous nerve (AIN) palsy, with no other peripheral neuropathy. We diagnosed this case as spontaneous AIN palsy complicated with CSS, the first case of this kind. Surgical treatment should be considered if no sign of recovery is seen within six months of onset.

Since the term synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome was proposed by Chamot et al. (Rev Rhum Mal Osteoartic 54:187-196, 1987), clinical reviews concerning this syndrome have been mainly reported from Europe. We carried out a retrospective analysis of 11 Japanese patients with SAPHO syndrome, and reviewed the clinical features of our series in comparison with those in a European large case study. In this study the major features of SAPHO syndrome were chronic osteitis of the anterior chest wall and pustulotic arthro-ostitis with middle age onset, and mucosal lesions seemed to be a minor complication of SAPHO syndrome. The non-erosive peripheral large joints arthritis and the particular HLA types (HLA-B51, B52, or A26), which had been reported to be increased in Behcet&apos;s disease, were frequently seen in SAPHO syndrome with mucosal lesions. This study also suggests that SAPHO syndrome with mucosal lesions may be part of a broader disease spectrum including Behcet&apos;s disease.

Purpose: We aimed to identify novel prognostic biomarkers for Ewing&apos;s sarcoma by investigating the global protein expression profile of Ewing&apos;s sarcoma patients. Experimental Design: We examined the proteomic profile of eight biopsy samples from Ewing&apos;s sarcoma patients using two-dimensional difference gel electrophoresis. Three patients were alive and continuously disease-free over 3 years after the initial diagnosis (good prognosis group) and five had died of the disease within 2 years of the initial diagnosis (poor prognosis group). Results: The protein expression profiles produced using two-dimensional difference gel electrophoresis consisted of 2,364 protein spots, among which we identified 66 protein spots whose intensity showed &gt;2-fold difference between the two patient groups. Mass spectrometric protein identification showed that the 66 spots corresponded to 53 distinct gene products. Pathway analysis revealed that 31 of 53 proteins, including nucleophosmin, were significantly related to bone tissue neoplasms (P &lt; 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewing&apos;s sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P &lt; 0.01). Conclusions: These results establish nucleophosmin as a candidate of independent prognostic marker for Ewing&apos;s sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewing&apos;s sarcoma.

We describe two patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-ostitis) syndrome who presented some of the classic features of Behcet's disease. The first case is a man diagnosed as SAPHO at 74 years old. His major complaint is pain and swelling of the bilateral sterno-clavicular region for more than 14 years. Another conspicuous complication was bilateral glaucoma and episodes of iritis were recognized during the follow-up period. The second case is a 65-year-old woman, who first consulted us with right knee pain. As she had a past history of palmoplantar pustulosis and anterior chest pain, her sterile knee arthritis was diagnosed as SAPHO. She also had been suffering from recurrent oral aphthous ulceration since 6 months before visiting our hospital. Considering the clinical courses of our two cases and a review of five previously reported cases, these conditions may imply that classic features of Behcet's disease are minor complications of SAPHO syndrome. Human leukocyte antigen typing and frequent association of sacroiliitis in our cases and in the review of the literature for SAPHO syndrome with some of the classic features of Behcet's disease may indicate this condition to be a closely related disease with seronegative spondylo-arthritis.

Ewing's sarcoma family of tumors (ESFT) is comprised of highly malignant bone and soft tissue tumors in children and young adults. Despite intensive treatments for patients with ESFT, disease which presents with metastatic spread or relapses after primary treatment remains incurable in the majority of cases, indicating the importance of efforts to develop new treatment modalities, including immunotherapy. The present study was designed to examine the expression profile of papillomavirus binding factor (PBF), which we previously defined as an osteosarcoma-associated antigen, and its prognostic significance for patients with ESFT. Biopsy specimens from 20 ESFT were stained with an anti-PBF antibody. Survival was estimated using Kaplan-Meier plots and the prognostic significance of several variables, including the expression status of PBF, on disease-free and overall survival was determined by univariate analysis using the log-rank test. Of 20 specimens, 18 (90%) reacted positively to the anti-PBF antibody. Fifteen specimens (75%) were graded as PBF overexpression. Of the I I variables analyzed, stage III disease, inadequate surgical margins and PBF overexpression were significantly associated with decreased disease-free and overall survival. None of the other variables, including age, gender, origin of tumor, tumor site or levels of LDH, ALP, CRP and ESR, showed any significant association. These findings indicate that the overexpression of PBF is a factor indicative of poor prognosis in ESFT. PBF may also serve as a putative target antigen in immunotherapy for patients with ESFT that have a poor prognosis and PBF overexpression.

Ewing sarcoma is a malignant bone and soft tissue tumor of children and young adults, which is known to be highly aggressive and invasive. It expresses specific chimeric genes (EWS-FLI-1, EWS-ERG, EWS-ETV1. and EWS-E1AF), the 3' portions of which are all members of the ETS family. ETS-related proteins, such as FLI-1. ERG, and E1AF, transactivate the promoters of matrix metalloproteinase (MMP) genes. which play important roles in the processes of invasion and metastasis. Therefore. we hypothesize that the Ewing sarcoma-specific chimeric genes also transactivate the MMP genes, contributing to the tumor's invasiveness and propensity for metastasis. To verify this hypothesis, we investigated the expression of MMPs in eight Ewing sarcoma cell lines. Surprisingly, MMP-1 and MMP-3 were not expressed at all in any of the cell lines. MMP-9 was expressed in four out of the eight cell lines, and MMP-2 and MT1-MMP in all of the cell lines. Ewing sarcoma-specific chimeric genes have been shown to transactivate the promoter of the MMP-1 gene by the reporter assay, and bind to the putative recognition sites in the MMP regulatory elements by the gel shift assay. However, an in vivo formaldehyde cross-linking study revealed that the chimeric protein did not bind to the predicted ETS recognition sites in the regulatory elements of the MMPs. These results indicate that the absence of the MMP expression in the tumor cells is at least in part due to the loss of accessibility of the ETS recognition sites in the regulatory elements of the MMP genes. Therefore, we should be careful before theorizing simply that a putative binding site is essential for the transcription of critical genes, since the binding of this fusion protein was found to be modulated in tumor cells in this study. (C) 2002 Elsevier Science (USA). All rights reserved.

Ewing's sarcoma, one of the most malignant tumors of children and young adults, expresses specific chimeric genes, e.g. EWS-FL1-1, EWS-ERG, EWS-ETV1 and EWS-FEV. In this paper, we extensively characterized a new fusion gene, EWS-E1AF by means of whole cDNA sequencing, RNA blot analysis, DNA blot analysis and chromosomal analysis, and showed it to be available for the diagnosis of Ewing's sarcoma and to participate in the oncogenesis of Ewing's sarcoma, Furthermore, we conducted a genetic analysis of Ewing family tumors in conjuction with immunohistochemical analysis and ultrastructural analysis. Our results demonstrate some limitations of both genetic analysis and histopathological analysis, and establish the relationship between neurogenic phenotypes and chimera genes.