Fumihiko Nakatani

Bizarre parosteal osteochondromatous proliferation with a t(1;17) translocation

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign lesion that tends to recur repeatedly. Histologically, BPOP contains three components (cartilage, bone, and spindle cells) in differing amounts. The histological findings of BPOP are similar to those of florid reactive periostitis (FRP) and subungual (Dupuytren’s) exostosis. Some authors have postulated that all of these conditions are reactive proliferative lesions representing different phases of reactive processes. Whether BPOP is a reactive proliferative lesion or a neoplastic lesion, however, remains controversial. Recently, a t(1;17)(q32;q21) translocation in BPOP was detected using chromosome banding and fluorescence in situ hybridization (FISH) analyses. Here, we describe a 39-year-old Japanese female with BPOP arising in the proximal phalanx of her third toe. A cytogenetic analysis revealed a t(1;17)(q42;q23) translocation. The breakpoints in this case are located close to those of previously reported cases. These results suggest that t(1;17) is a distinct translocation of BPOP and that BPOP is a neoplastic lesion, rather than a reactive proliferative process.

Myxoinflammatory fibroblastic sarcoma

Acral myxoinfl ammatory fi broblastic sarcoma (MIFS) was fi rst described in 1998 as a new entity in three independent reports by pathologists, Meis-Kindblom and Kindblom, Michal, and Montgomery et al. It occurs primarily in adults, with a peak incidence in the fourth and fi fth decades of life, and presents as a painless fi rm mass of the distal extremities, predominantly the hands and feet. Recently, proximally located MIFS has also been reported, and some authors have suggested dropping the adjective “acral” from the name of the tumor because of its possibly misleading nature. Histologically, MIFS is a poorly circumscribed and typically multinodular tumor. The most striking feature is infl ammatory infi ltration associated with a prominent myxoid matrix in variable proportions and the presence of bizarre virocyte or Reed-Sternberg-like cells and multivacuolated cells simulating lipoblasts. Surgical excision with a wide margin is considered the treatment of choice, as the tumor shows a high rate of local recurrence. Meis-Kindblom and Kindblom reported a 67% local recurrence rate within a median follow-up period of 5 years. However, the tumor is frequently diffi cult to diagnose correctly at the time of initial presentation because of its apparently benign nature, being a slowgrowing, small and painless mass in the distal extremity. As a result, there is a tendency for the tumor to be treated inadequately by referring physicians. Surgeons need to be mindful of MIFS, its nature, and the appropriate treatment necessary for this unique tumor. Case reports

PET/CT allows stratification of responders to neoadjuvant chemotherapy for high-grade sarcoma: a prospective study.

Purpose: The aim of the present study was to determine whether metabolic reduction is capable of reflecting the histopathologic response and outcome after neoadjuvant chemotherapy in patients with high-grade sarcoma. Patients and Methods: Forty-two patients with histologically proven high-grade sarcoma underwent neoadjuvant chemotherapy followed by surgical resection. Quantitative F-18 fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)/computed tomography scans were acquired before and after the first cycle and after completion of neoadjuvant chemotherapy. Standardized uptake values (SUVs) and metabolic reduction rates were compared with histopathologic response, progression-free survival, and overall survival. Results: Baseline SUVmax was 10.9 ± 3.6 (range, 3.8–19.6). Therapeutic effect resulted in 10 patients (24%) with a satisfactory response and in 32 patients (76%) with an unsatisfactory response after completion of neoadjuvant chemotherapy. The SUV decreased to 7.8 ± 3.4 after the first cycle (t1) of chemotherapy and to 5.2 ± 3.4 after completion (t2) of chemotherapy. Histopathologic response and percentage SUV (t2) reduction rate were independent predictors of progression-free survival and overall survival in the multivariate analyses. Conclusion: Metabolic reduction after neoadjuvant chemotherapy evaluated by F-18 FDG PET or computed tomography can be used for stratification of the histopathologic response in patients with high-grade sarcoma.

Prognostic Implications of Glucose Transporter Protein-1 (Glut-1) Overexpression in Bone and Soft-Tissue Sarcomas

BACKGROUND The glucose transporter protein 1 (Glut-1) overexpression is associated with poor overall survival (OS) in various malignant tumors. The aim of this study was to investigate prognostic significance of Glut-1 overexpression in patients with bone and soft-tissue sarcomas. METHODS A total of 67 patients (mean age, 43 years; range, 8-79 years) with bone and soft tissue sarcomas were analyzed. Pathologic confirmation was observed from surgical specimens in all patients. Pathologic variables including tumor differentiation, necrosis, mitotic index, MIB-1 (Ki-67) grade and Glut-1 expression were assessed. Clinical characteristics and pathologic variables were determined by Kaplan-Meyer curve of OS after treatment. RESULTS Glut-1 overexpression was found in 56 patients (83%). The patients with Glut-1 overexpression showed significantly poor OS compared with those without Glut-1 overexpression (P = 0.029). The presence of metastasis, treatment without surgical resection, tumor differentiation, necrosis, mitotic index and MIB-1 grade were also significantly negative prognostic factors. The presence of metastasis was independently associated with poor OS (P = 0.031). CONCLUSIONS Assessment of Glut-1 expression prior to treatment has a predictive potential effect in patients with bone and soft-tissue sarcomas.

Use of Vascularized Free Fibular Head Grafts for Upper Limb Oncologic Reconstruction

Background: Transfer of a vascularized fibular graft is the method of first choice for reconstruction of defects of long bones. In particular, the vascularized fibula head graft is preferred for patients with bone defects of the upper limb involving the distal radius or the proximal humerus. The aim of the present study was to analyze the operative results, complications, and postoperative function after vascularized fibula head graft transfer and the indications for this procedure. Methods: From 1998 through 2008, vascularized fibula head graft transfer was performed in eight patients to reconstruct bone defects following resection of tumors of the upper limb. The primary site of the tumor was the proximal humerus in four patients and the distal radius in four patients. The postoperative course of the transferred bone was examined, and functional results were evaluated. Results: All vascularized fibula head grafts were transferred successfully. During the follow-up period, absorption of the transferred fibula head was not observed. The mean overall functional rating of the reconstructed shoulder joint was 70 percent. The range of motion of the reconstructed wrist joint showed no specific patterns, and instability of the wrist joint was observed in only one case. Conclusions: The authors believe that the vascularized fibula head graft transfer is a safe and reliable method for reconstructing the upper limb, especially for patients with a defect of the distal radius or the proximal humerus. This procedure is also useful for pediatric patients, in whom bone growth is expected after transplantation, and for salvage procedures after reconstructive materials of an artificial joint have failed.

Association of a missense single nucleotide polymorphism, Cys1367Arg of the WRN gene, with the risk of bone and soft tissue sarcomas in Japan

Bone and soft tissue sarcomas (BSTSs) are rare malignant tumors of mesenchymal origin. Although BSTSs frequently occur in some hereditary cancer syndromes with germline mutations of DNA repair genes, genetic factors responsible for sporadic cases have not been determined. In the present study we undertook a case‐control study and analyzed possible associations between the susceptibility to BSTS and the single nucleotide polymorphisms (SNPs) in DNA repair genes. Genomic DNAs extracted from case and control peripheral blood leukocytes were genotyped by pyrosequencing. For candidate polymorphisms, we chose 50 non‐synonymous missense SNPs, which we have previously been identified by resequencing 36 DNA repair genes among the Japanese population. In the first screening, we analyzed 240 cases and 685 controls and selected six SNPs at the significance level of P < 0.1 (Fishers exact test). The six SNPs were further analyzed in the second genotyping on an additional set of 304 cases and 834 controls. In the joint analysis (the first and second genotyping combined) of 544 cases and 1378 controls, Cys1367Arg of the WRN gene was found to be a protective factor of BSTS (odds ratio = 0.66, 95% confidence interval = 0.49–0.88, P = 0.005). An exploratory subgroup analysis without multiple comparison adjustment suggested that the WRN‐Cys1367Arg SNP is associated with soft tissue sarcomas, sarcomas with reciprocal chromosomal translocations and malignant fibrous histiocytoma. (Cancer Sci 2008; 99: 333–339)

Solitary intramuscular myxoma with monostotic fibrous dysplasia as a rare variant of Mazabraud’s syndrome

The rare coexistence of intramuscular myxoma (IM) and fibrous dysplasia (FD) is known as Mazabraud’s syndrome. IM tends to occur multifocally and is associated most frequently with polyostotic FD in Mazabraud’s syndrome. We present an extremely rare combination of a solitary IM and monostotic FD as a variant of Mazabraud’s syndrome, and discuss the importance of recognizing this rare coexistence for appropriate management of the patient.

An Analysis of Factors Related to Recurrence of Myxofibrosarcoma

OBJECTIVE Myxofibrosarcoma is clinically characterized by a high frequency of local recurrence after surgery. To improve the clinical outcome of patients with myxofibrosarcoma, it is imperative to control any postsurgical local recurrence. METHODS In this study, we performed a retrospective clinicopathologic analysis of 100 consecutive patients with myxofibrosarcoma to identify factors related to poor prognosis. All of the patients had been diagnosed, and had undergone surgery at the National Cancer Center Hospital between 1999 and 2008. RESULTS At the initial visit to our hospital, 64 patients had primary myxofibrosarcoma, whereas 36 had undergone primary unplanned resection at other facilities. Of the 36 patients, 11 consulted our hospital before recurrence and 25 did so after recurrence. A histologically positive margin after surgery was evident in 28% of the cases overall. The estimated 5-year recurrence-free survival rate was 74.8%. Univariate analysis showed that primary unplanned resection at another facility (P = 0.0001) and a histologically positive margin (P = 0.0224) were significant predictors of local recurrence. When these two factors were subjected to multivariate analysis, only primary unplanned resection at another facility was significantly correlated with the estimated recurrence-free survival rate (P = 0.0011). Primary unplanned resection was also significantly related to the 5-year disease-free survival rate (P = 0.0401). CONCLUSIONS Our findings indicate that primary unplanned resection at a non-referral hospital is the most important risk factor related to poor prognosis of myxofibrosarcoma. Accurate diagnosis and adequate initial surgery are most important factors for improving the clinical outcomes of myxofibrosarcoma.

Treatment of bone and soft-tissue sarcoma patients in Japan: The distribution of patients and medical specialties by cancer topography and treatment modality.

e22544Background: Sarcoma clinical guidelines often emphasize the evaluation of patients by an expert multidisciplinary team, and thus in many countries, care is centralized to treatment centers. However, there are no standard guidelines for referrals of sarcoma patients in Japan, and the overall picture of where and by whom they are treated has never been systematically investigated. Methods: We used hospital-based cancer registry and health claims data of sarcoma patients diagnosed in Japan in 2012 and 2013. We analyzed the distribution of patients across hospitals and the extent of centralization of care across treatment modality and cancer topography. Results: We identified 1032 bone and 7257 soft-tissue sarcoma (STS) patients who were newly diagnosed in 2012 and 2013. Bone sarcomas occurred in the limbs in 55% of the patients, with 73% treated by orthopedic surgeons. Care was weakly centralized to 9 high-volume hospitals ( > 10 new cases per year) and 120 hospitals with 1-9 new cases. Care was greatl...