Ako Hosono

Comparative study of FDG PET/CT and conventional imaging in the staging of rhabdomyosarcoma

ObjectiveThe current study was conducted to compare the diagnostic accuracy between 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT), and conventional imaging (CI) for the staging and re-staging of patients with rhabdomyosarcomas.MethodsThirty-five patients who underwent FDG PET/CT prior to treatment were evaluated retrospectively. CI methods consisted of 99mTc-hydroxymethylene diphosphonate bone scintigraphy, chest radiograph, whole body CT, and magnetic resonance imaging of the primary site. The images were reviewed and two boardcertified radiologists reached a diagnostic consensus. Tumor stage was confirmed by histological examination and/or follow-up examinations.ResultsInterpretation on the basis of FDG PET/CT, and CI, diagnostic accuracies of the T and N stages were similar. Using FDG PET/CT, the M stage was correctly assigned in 31 patients (89%), whereas the accuracy of CI in M stage was 63%. TNM stage was correctly assessed with FDG PET/CT in 30 of 35 patients (86%) and with CI in 19 of 35 patients (54%). The overall TNM staging and M staging accuracies of FDG PET/CT were significantly higher than that of CI (P < 0.01).ConclusionsFDG PET/CT is more accurate than CI regarding clinical staging and re-staging of patients with rhabdomyosarcomas.

Clear cell sarcoma of tendons and aponeuroses: a study of 75 patients.

Clear cell sarcoma (CCS) of tendons and aponeuroses (malignant melanoma of soft parts) is a rare melanocytic soft tissue sarcoma. The objective of this study was to determine the clinical features, prognostic factors, and optimal treatment policy for patients with this rare disease.

Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics

Purpose: We aimed to identify novel prognostic biomarkers for Ewings sarcoma by investigating the global protein expression profile of Ewings sarcoma patients. Experimental Design: We examined the proteomic profile of eight biopsy samples from Ewings 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 >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 < 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewings sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P < 0.01). Conclusions: These results establish nucleophosmin as a candidate of independent prognostic marker for Ewings sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewings sarcoma.

Peroxiredoxin 2 as a chemotherapy responsiveness biomarker candidate in osteosarcoma revealed by proteomics

Purpose: We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. Experimental design: Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2‐D DIGE consisted of 2250 protein spots. Results: Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p‐value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2‐D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. Conclusions and clinical relevance: These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.

Accuracy of 18F fluorodeoxyglucose positron emission tomography/computed tomography in staging of pediatric sarcomas.

The present study was conducted to clarify the diagnostic accuracy of 18F-fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography (PET)/computed tomography (CT) in the staging in pediatric sarcomas. Fifty pediatric patients with histologically proven sarcomas who underwent 18FDG PET/CT before treatment were evaluated retrospectively for the detection of nodal and distant metastases. Diagnostic accuracy of 18FDG PET/CT in detecting nodal and distant metastases was compared with that of 18FDG PET and conventional imaging (CI). The images were reviewed and a diagnostic consensus was reached by 3 observers. REFERENCE standard was histologic examination in 15 patients and confirmation of an obvious progression in size of the lesions on follow-up examinations. Nodal metastasis was correctly assessed in 48 patients (96%) with PET/CT, in contrast to 43 patients (86%) with PET, and 46 patients (92%) with CI. Diagnostic accuracies of nodal metastasis in 3 modalities were similar. Using PET/CT, distant metastasis was correctly assigned in 43 patients (86%), whereas interpretation based on PET alone or CI revealed distant metastasis in 33 patients (66%) and 35 patients (70%), respectively. Diagnostic accuracy of distant metastasis with PET/CT was significantly higher than that of PET (P=0.002) or CI (P=0.008). False negative results regarding distant metastasis by PET/CT in 7 patients (14%) were caused by subcentimetric lesions (n=4), bone marrow lesion (n=2), and soft tissue lesions (n=1). PET/CT is more accurate and probably more cost-effective than PET alone or CI regarding distant metastasis in pediatric sarcomas.

Acute lymphoblastic leukemia after temozolomide treatment for anaplastic astrocytoma in a child with a germline TP53 mutation

We present a case of a 12‐year‐old female with a germline TP53 mutation who presented with anaplastic astrocytoma and subsequent acute lymphoblastic leukemia (ALL) 13 months after starting treatment with temozolomide (TMZ). The patient had no family history of malignancy except her grand father and his siblings. Although alkylating agents such as TMZ are known to induce secondary hematologic malignancy, only several cases of treatment‐related acute leukemia have been reported after TMZ‐alone chemotherapy for malignant gliomas. We demonstrate a rare case of TMZ‐related ALL in a child with glioma possibly associated with a germline TP53 mutation. Pediatr Blood Cancer. 2010;55:577–579.

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma

Aims: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. Methods: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. Results: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. Conclusion: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Segregated graft-versus-tumor effect between CNS and non-CNS lesions of Ewing's sarcoma family of tumors

For patients with the localized Ewings sarcoma family of tumors (ESFT), first-line multimodal treatment, including intensive multi-agent chemotherapy, local radiation therapy and surgery, produces 70–75% of the long-term survival rate.1, 2 However, once patients relapse, there is no effective treatment that yields a 5-year survival rate exceeding 20%, even with high-dose chemotherapy (HDC) with autologous stem cell rescue.3, 4 Therefore, a new and more effective treatment approach is clearly needed for this population. Several reports have described patients with ESFT who had bone marrow metastases and underwent allogeneic SCT instead of autologous SCT,5 including a rare patient who exhibited evidence of a graft-versus-tumor (GVT) effect.6 To accumulate further knowledge, we report the case of a patient with recurrent ESFT who responded to allogeneic SCT from a sibling donor. A unique aspect of this case was that the manifestation of the GVT effect differed in different organs, with involvement of central nervous system (CNS) and non-CNS lesions. The GVT effect is rare in CNS diseases.

Intensive multimodality therapy including paclitaxel and reduced-intensity allogeneic hematopoietic stem cell transplantation in the treatment of adrenal cancer with multiple metastases

Adrenocortical carcinoma is a rare malignancy in adolescents and young adults. The prognosis of unresectable/metastatic adrenocortical carcinoma remains very poor because the rarity of the tumor has made it difficult to establish treatment guidelines, and diagnosis and the resultant treatment can be greatly delayed. We treated a 24-year-old woman who was diagnosed with adrenocortical carcinoma of the right adrenal gland which extended to the inferior vena cava. Although she underwent surgical resection of the extensive tumor as the primary treatment, the disease recurred in the lung and liver as multiple metastases shortly after surgery. She received intensive multimodality therapy, including chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen), embolization of the feeding arteries, and proton irradiation for the liver mass. Finally, she underwent reduced-intensity allogeneic hematopoietic stem cell transplantation from an HLA 1-locus-mismatched sibling donor. A prolonged survival of 39 months after the onset of the disease was achieved. Although this experience is limited, we suggest that TIP chemotherapy was effective for adrenocortical carcinoma, and a graft-versus-tumor effect after reduced-intensity stem cell transplantation may have contributed to the prolonged survival.

A retroperitoneal mass, systemic lymphadenopathy, and pulmonary nodules in a pregnant woman

A 27-year-old woman in the 18th week of pregnancy presented with a 1-week history of left supraclavicular lymphadenopathy. A sample obtained by open biopsy of a supraclavicular node was diagnosed as a malignant tumor metastasizing from another site, and the patient was referred to our hospital for further work-ups and treatment in the 22nd week of pregnancy. Computed tomography (CT) and magnetic resonance (MR) imaging were subsequently obtained for further work-ups (Figs. 1, 2). Re-evaluation of the biopsy specimen was performed (Fig. 3). In the 37th week, she had a spontaneous delivery of healthy twins. Imaging of the affected sites was performed after delivery (Fig. 4).