Masayuki Mano

Molecular Detection of Lymph Node Metastases in Breast Cancer Patients: Results of a Multicenter Trial Using the One-Step Nucleic Acid Amplification Assay

Purpose: Accurate assessment of metastasis in sentinel lymph nodes (SLN) of breast cancer is important but involves a heavy workload for the pathologist. We conducted a multicenter clinical trial in Japan to evaluate a new automated assay system for cytokeratin 19 mRNA, the one-step nucleic acid amplification (OSNA) assay (Sysmex), to detect lymph node metastasis of breast cancer. Experimental Design: Surgically obtained axillary lymph nodes were sectioned into four pieces, two of which were examined with the OSNA assay. The other two adjacent pieces were examined with H&E and immunohistochemical staining for cytokeratin 19. Serial sections at 0.2-mm intervals were used in trial 1 to determine the specificity of the OSNA assay, and three pairs of sections cut from the sliced surfaces of the pieces were used in trial 2 to compare the accuracy of the OSNA assay with that of a routine pathologic examination for SLNs in Japan. Results: In trial 1, the sensitivity and specificity were 95.0% [95% confidence interval (95% CI), 75.1-99.9%] and 97.1% (95% CI, 91.8-99.4%), respectively, for 124 axillary lymph nodes obtained from 34 patients. In trial 2, the agreement between findings of the assay and of the pathologic examination was 92.9% (95% CI, 90.1-95.1%) for 450 axillary lymph nodes obtained from 164 patients. Conclusion: The OSNA assay can detect lymph node metastasis as accurately as can conventional pathology and thus can be an effective addition to or alternative for rapid intraoperative examination of SLNs.

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy.

In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established.

Chromosome rearrangement at 17q25 and Xp11.2 in alveolar soft‐part sarcoma

Despite the characteristic histopathologic appearance of alveolar soft‐part sarcoma (ASPS), its histogenesis remains unclear, and cytogenetic analysis of ASPS is limited to eight cases so far because of the extreme rarity of this disease.

Myoepithelioma of the lung: Report of two cases and review of the literature

Myoepithelial tumors occur mainly in the salivary glands, the sweat glands or the breast, but uncommonly in the lung. Herein, we describe two cases of myoepithelioma of the lung. Both patients were 58-year-old men, in whom the tumors were located in the right-upper bronchus and in the left-upper bronchus, respectively, with endobronchial growth pattern. Surgery was performed, but metastasis occurred into the forearm and hip muscles in the former case, and into the liver in the latter. Histologically, the tumor in the former was a spindle-plasmacytoid type, and that in the latter was a plasmacytoid type in part with squamous differentiation. Based on histochemical, immunohistochemical and ultrastructural analyses, both were compatible with myoepithelioma. The clinicopathological uniqueness of this neoplasm is discussed, together with a review of reports of this disease in the literature.

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation.

ObjectiveTo characterize the radiological and clinicopathologic features of cystic synovial sarcoma.Design and patientsSeven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed.ResultsCT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma.ConclusionAll cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging.

Clinical implications of serum C-reactive protein levels in malignant fibrous histiocytoma.

Paraneoplastic syndromes (PNSs) associated with mesenchymal tumors are uncommon. Previous reports sporadically described inflammatory PNSs with elevated serum C‐reactive protein (CRP) levels and leukocytosis in patients with inflammatory malignant fibrous histiocytoma (MFH) of soft tissue; however, the relationship between other subtypes of MFH and PNS has not been extensively investigated. Forty‐six patients with primary MFH of soft tissues who underwent radical surgery were retrospectively analyzed. These patients were divided into 2 groups according to preoperative serum CRP level: normal (<1.0 mg/dl) and elevated (≥1.0 mg/dl). The correlation between serum CRP level and several clinicopathologic factors was analyzed. Correlation between preoperative serum CRP level and metastasis‐free and overall survival was also investigated by univariate and multivariate analyses. Elevated preoperative serum CRP levels were found in 65% of patients with a mean of 3.7 mg/dl. There were statistically significant relationships regarding tumor size, depth, histologic subtypes, grade, stage and metastatic rate among normal and elevated CRP groups (p < 0.001, p < 0.02, p < 0.005, p < 0.001, p < 0.001 and p < 0.05, respectively). When the tumor was removed, the elevated CRP level subsided into the normal range and other abnormal laboratory findings diminished in all cases. In 11/14 relapsed cases that showed elevated CRP preoperatively, the serum CRP level re‐elevated with tumor relapse. The normal CRP group showed significantly more favorable prognosis than the elevated CRP group in metastasis‐free and overall survival on univariate analysis (p < 0.02, p < 0.05, respectively). Patients with MFH frequently present with an inflammatory PNS, such as elevated serum CRP level, which can be a useful marker of disease activity and a valuable prognostic indicator.

Expression of SSX genes in human osteosarcomas

Norifumi NAKA*, Nobuhito ARAKI, Hirofumi NAKANISHI, Kazuyuki ITOH, Masayuki MANO, Shingo ISHIGURO, Diederick R.H. DE BRUIJN, Akira MYOUI, Takafumi UEDA and Hideki YOSHIKAWA Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan Department of Human Genetics, University Medical Center, Nijmegen, the Netherlands Department of Orthopaedics, Osaka University Medical School, Osaka, Japan

Ipsilateral adrenal involvement from renal cell carcinoma: retrospective study of the predictive value of computed tomography

OBJECTIVES To compare the radiologic evidence of adrenal involvement on computed tomography (CT) with pathologic reports and to assess the accuracy of CT in the diagnosis of adrenal involvement with renal cell carcinoma. METHODS Between January 1992 and June 2000, we treated 229 patients with renal cell carcinoma. In this study, we retrospectively analyzed 73 patients who had been examined by CT before surgery and had undergone radical nephrectomy, including removal of the ipsilateral adrenal gland. The abnormal integrity of the adrenal glands on CT and the pathologic adrenal involvement of renal cell carcinoma were demonstrated by a radiologist and pathologist, respectively. RESULTS The blinded review by a radiologist of the CT results of 73 patients with renal cell carcinoma identified a normal appearance of the ipsilateral adrenal gland in 54 patients (74%), none of whom had pathologic evidence of malignant involvement. The adrenal gland was diagnosed as abnormal on CT in 19 patients (26%), including enlargement in 7 patients, nodule formation in 7, and an irregular surface in 8. Two of these 19 patients had adrenal involvement. Both were staged at T3M1, and their primary tumors were large, measuring more than 10 cm. In this study, CT demonstrated 100% sensitivity, 76% specificity, 11% positive predictive value, and 100% negative predictive value for ipsilateral adrenal involvement of renal cell carcinoma. CONCLUSIONS Normal adrenal images on CT could exclude adrenal involvement by renal cell carcinoma. However, radical nephrectomy, including removal of the ipsilateral adrenal gland, should be performed in patients with large tumors.

Renal angiomyolipoma with minimal fat

Abstract We report here two patients with angiomyolipoma with minimal fat, who were treated by radical nephrectomy, with a diagnosis of renal cell carcinoma. The tumors in these two patients were hyperattenuated on unenhanced computed tomography (CT) images, but did not show fat components, and were moderately enhanced on contrast-enhanced CT images. The tumor in one patient was homogeneously hypointense on T2-weighted magnetic resonance (MR) images, enhanced during the early phase on dynamic MR images, and, further, showed abundant pulsatile blood vessels on color Doppler examination. These imaging findings of renal tumors suggested the possibility of angiomyolipoma with minimal fat; accordingly, when imaging results suggest this possibility, further careful sampling to identify minimal fat components must be performed by thin-section unenhanced CT.

Immature tumor angiogenesis in high-grade and high-stage renal cell carcinoma.

OBJECTIVES To investigate the correlation between pathologic findings and maturation of the tumor neovasculature of renal cell carcinoma by immunohistochemical studies. METHODS Formalin-fixed and paraffin-embedded specimens from 25 randomly selected patients with renal cell carcinoma were stained with mouse monoclonal antibodies, anti-human CD31, anti-alpha smooth muscle actin (alphaSMA), and anti-human calponin by the indirect immunoperoxidase method. The microvessels were counted in six areas with the higher number of microvessels in each patient at 200x magnification (0.255 mm2 per area). RESULTS The number of CD31-positive microvessels in grade 3 tumors was significantly lower than those in grade 1 or 2 tumors (P = 0.003222 and P = 0.043217, respectively). The CD31-positive microvessel counts of those of higher stage, tumor size greater than 4.5 cm, or non-clear cell type were significantly lower than tumors of lower stage, size less than 4.6 cm, or clear cell type. In the grade 3 tumors, the expression ratio of the number of alphaSMA-positive microvessels to the number of CD31-positive microvessels was significantly decreased compared with grade 1 or 2 tumors (P = 0.000011 and P = 0.000000, respectively). The expression of calponin in the tumor neovasculature was not observed. The expression ratios of the number of alphaSMA-positive microvessels to the number of CD31-positive microvessels in higher stages, larger tumor sizes, or non-clear cell types were significantly decreased. CONCLUSIONS The tumor neovasculature of high-grade and high-stage tumors was immature. These results imply that high-grade tumors of renal cell carcinomas may be susceptible to antiangiogenesis therapy inducing apoptosis of immature tumor vessels.