Vertebrobasilar infarction related to giant cell (temporal) arteritis: case report.

An 84-year-old male with a 3-month history of headache and elevated C-reactive protein levels was admitted for biopsy of the superficial temporal artery, which led to the diagnosis of giant cell arteritis (GCA). Two days after prednisolone therapy was initiated, the patient began to experience transient vertigo attacks. Two days later, dysarthria, left-sided hemiparesis, right abducens palsy, and horizontal nystagmus developed. Magnetic resonance (MR) imaging disclosed fresh infarctions in the vertebrobasilar territory. Since the patient became drowsy because of brainstem compression and hydrocephalus due to cerebellar swelling, emergency suboccipital decompression surgery and ventricular drainage were performed. Subsequently, the patient's consciousness levels improved. MR angiography revealed right vertebral artery (VA) occlusion and left VA stenosis due to arteritis. Ischemic stroke is a serious though relatively rare complication of GCA. Similar cases have been reported, in which ischemic stroke developed despite or possibly due to steroid therapy. To our knowledge, this is the first description of vertebrobasilar infarction associated with GCA in the Japanese population. The merits and potential demerits of steroid therapy are briefly discussed.

[A case of papillary renal cell carcinoma type 2 resistant to sunitinib responded to second line therapy with axitinib].

According to previous studies, papillary renal cell carcinoma (pRCC) type 2 is known to have a poor prognosis, especially in cases with metastases. We report a case of pRCC that responded well to axitinib administered as second line therapy. The patient was a 52-year-old woman who presented at our hospital with an incidental tumor on the left kidney. She underwent laparoscopic radical nephrectomy, and the pathological diagnosis was pRCC type 2, grade 3 pT1b. Multiple lung and bone metastases were observed following the four months, and histological findings of lung metastases was metastatic RCC. Although sunitinib was administered as first line therapy, tumor progression was observed after the first cycle of treatment. Therefore, axitinib (10 mg/day) was administrated as second-line therapy and was gradually increased to 14 mg/day. Five months after the administration of axitinib, the maximum tumor diameter of the lung metastases reduced by 83%. At present, eight months have passed since the start of axtinib administration, but the response was still maintained and the adverse events were generally tolerable.

Laparoscopic resection for torsion of an omental lipoma presenting as an acute abdomen in a 5-year-old girl.

Primary tumors of the greater omentum are rare. We report a case of a 5-year-old girl presenting with an acute abdomen who had omental torsion caused by a giant lipoma of the greater omentum, which was diagnosed by a computed tomography scan. Laparoscopy revealed a yellow tumor of the greater omentum with a smooth surface. Tumor excision and partial omentectomy was performed to treat the torsion, and the tumor was retrieved through a 4-cm-wide abdominal incision. Macroscopically, the specimen was 80 × 60 × 25 mm in size and 74.8 g in weight, and histopathological findings were consistent with the diagnosis of lipoma. The present case highlights the possible use of laparoscopic surgery for removing large abdominal lipomas, thus avoiding the drawbacks of laparotomy in terms of postoperative pain and prolonged hospital stay.

p53 expression in pretreatment specimen predicts response to neoadjuvant chemotherapy including anthracycline and taxane in patients with primary breast cancer.

While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p＝0.045) and histological grade 3 (p＝0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.

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.

Secernin-1 as a novel prognostic biomarker candidate of synovial sarcoma revealed by proteomics.

We aimed to develop prognostic biomarkers for synovial sarcoma employing a proteomic approach. We examined the proteomic profile of synovial sarcoma using two-dimensional difference gel electrophoresis (2D-DIGE). We identified 20 protein spots whose intensity was statistically different (p<0.01) between a group of eight patients who were alive and continuously disease-free for over five years and a group of five patients who died of the disease within two years post diagnosis. Mass spectrometric protein identification demonstrated that these 20 spots corresponded to 17 distinct gene products. Three of the 20 spots corresponded to secernin-1 and had higher intensity in the good prognosis group. The prognostic performance of secernin-1 was further examined immunohistochemically in 45 synovial sarcoma cases. The 5-year survival rate was 77.6% and 21.8% for patients with secernin-1 positive and negative primary tumors respectively (p=0.0015). The metastasis-free survival was significantly higher in the patient group with high secernin-1 expression compared to that with low expression (p=0.0012). Uni- and multivariate analyses revealed that secernin-1 expression was a powerful prognostic factor compared to other clinico-pathological parameters examined. These results indicate that secernin-1 may be used as a biomarker to predict the overall and metastasis-free survival in synovial sarcoma patients.

A histopathological study for evaluation of therapeutic effects of radiofrequency ablation in patients with breast cancer.

PURPOSE: To reveal the rate of complete therapeutic effect of radiofrequency ablation (RFA) and its correlation with tumor size by the histopathological examination of surgically resected early breast cancers. METHODS: For 28 patients who received RFA and subsequent surgical therapies for early breast cancer treatment, the effect of RFA was evaluated by both histopathological examination and nicotinamide adenine dinucleotide (NADH)-diaphorase staining of resected tumor specimens according to the criteria described by Seki et al. (this issue). The correlation of 100% RFA effect with tumor parameters including tumor size and the presence of extensive intraductal component (EIC) was examined. RESULTS: The mean size and invasive size of the primary tumors were 2.21 cm (ranging from 0.6 to 5.0 cm) and 1.44 cm (ranging from 0 to 5.0 cm), respectively. By examining hematoxylin-eosin (HE) sections, the effectiveness of RFA was found to be 100% in 16 tumors (57%). However, the effectiveness of RFA was found to be 100% in 22 cases (79%) examined by NADH-diaphorase staining of frozen sections containing part of tumorous and nontumorous tissues. The accuracy of diagnosis of complete RFA effect using NADH-diaphorase staining with reference to HE was 79% (22 of 28) with 100% (16 of 16) sensitivity and 50% (6 of 12) specificity. The rate of 100% RFA effect by HE examination was higher in EIC(-) tumors (13 of 17, 76%) than in EIC(+) tumors (1 of 9, 11%) (P = 0.0022), and was higher in tumors of ≤ 1.5 cm (10 of 11, 91%) than in tumors of >1.5 cm (6 of 17, 35%; P = 0.0034). All five tumors of ≤ 1.0 cm showed 100% RFA effect, but 3 (27%) of 11 tumors of >1.0 and ≤ 2.0 cm and 9 (75%) of 12 tumors of > 2.0 cm showed suboptimal RFA effect by HE. CONCLUSIONS: Tumor size of ≤ 1.5 cm, strictly ≤ 1.0 cm, could be an indication for RFA if a complete histological therapeutic effect is mandatory.

Radiofrequency ablation as local therapy for early breast carcinomas.

PURPOSE: To evaluate the safety and efficacy of radiofrequency ablation (RFA) as a local therapy for early breast carcinomas, we performed a phase I/II study at our institution. PATIENTS AND METHODS: Fifty patients with core-needle biopsy-proven breast carcinoma that was ≤ 3 cm in diameter on ultrasonography were enrolled in this study. Under ultrasound (US) guidance, the tumor and surrounding breast tissue were ablated with a saline-cooled RF electrode followed by immediate surgical resection. Resected specimens were examined by hematoxylin and eosin (H&E) staining and nicotinamide adenine dinucleotide (NADH) diaphorase staining to assess tumor viability. RESULTS: Forty-nine patients completed the treatment. The mean tumor size was 1.70 cm. The mean ablation time was 8.7 min using a mean power of 48.5 W. Of the 49 treated patients, complete ablation was recognized in 30 patients (61%) by H&E staining and/or NADH diaphorase staining. The NADH viability staining was available for 38 patients, and in 29 (76.3%), there was no evidence of viable malignant cells. Of the 29 treated patients with breast carcinomas ≤ 2 cm in diameter examined by pathological examination, complete ablation was achieved in 24 patients (83%). Of the 26 treated patients with breast carcinomas without an extended intraductal component (EIC) according to pathological examination, complete ablation was determined in 22 patients (85%). RFA-related adverse events were observed in five cases: two with skin burn and three with muscle burns. CONCLUSION: RF ablation is a safe and promising minimally invasive treatment for small breast carcinomas with pathological tumor size ≤ 2 cm in diameter and without EIC.

Histopathological effect of radiofrequency ablation therapy for primary breast cancer, with special reference to changes in cancer cells and stromal structure and a comparison with enzyme histochemistry.

Radiofrequency ablation (RFA) therapy is expected to be applicable to small breast cancers, but no criteria for its histopathological effect have yet been established. Using samples obtained from 15 patients who had undergone RFA and subsequent mastectomy, we compared the histopathological changes in the ablated area with the results of histochemical staining based on the reduction of nitroblue tetrazolium chloride (NBT) by nicotinamide adenine dinucleotide (NADH) diaphorase in frozen tissue sections, and looked for histological changes indicative of the effect of RFA on breast cancer. Grossly, the ablated area in most of the tumors was rough, gritty, less moist, and surrounded by a red congestive limbic zone. The ablated area showed no staining by the NADH diaphorase reaction, and cancer cells in the area showed marked destruction characterized by an unclear intercellular boundary, elongated eosinophilic cytoplasm, pyknotic "streaming" nuclei, and a poorly defined nuclear and cytoplasmic texture. At the same time, fibrous connective tissue also showed degenerative changes, becoming densely homogeneous with loss of its delicate wavy structure. The area in which RFA appeared to have been histopathologically effective was mostly concordant with the area in which the NADH diaphorase reaction was negative. In the periphery of the ablated area, however, cellular changes caused by RFA were less marked, although the NADH diaphorase reaction was visualized with NBT. A larger number of cases should be examined in order to establish criteria for the histopathological effect of RFA on breast cancer.

Fluorescence in situ hybridization analysis of extraskeletal myxoid chondrosarcomas using EWSR1 and NR4A3 probes.

Extraskeletal myxoid chondrosarcomas (EMCs) are characterized histologically by a cord-like or lace-like arrangement of small round cells or short spindle cells with eosinophilic cytoplasm distributed in a rich myxoid matrix. Atypical cases of EMC have also been described, with areas of poor mucus production and high cellularity and a transition to typical EMC. Most cases of EMC harbor the chromosomal reciprocal translocation t(9;22) (q22;q12) and the resultant fused gene, Ewing sarcoma region 1-nuclear receptor subfamily 4, group A, member 3 (EWSR1-NR4A3). Other translocations, such as those involving the NR4A3 gene, have also been noted, although these occur at a lower frequency. On this basis, we conducted a fluorescence in situ hybridization (FISH) analysis of 18 cases of EMC in which patients presented with typical or atypical (areas of high cellularity) histologic features of EMC. We used an EWSR1 probe and a newly prepared NR4A3 probe to evaluate the usefulness of FISH in the pathologic diagnosis of EMC. FISH analysis using the EWSR1 or NR4A3 probe showed split signals in 83% (15/18) of the cases, regardless of the presence of typical/atypical histologic features. Gene rearrangement of EWSR1 was noted in 72% (13/18) of the cases, and rearrangement of NR4A3 was noted in 61% (11/18) of the cases. The NR4A3 rearrangement was detected in 2 cases not carrying any EWSR1 rearrangement, as determined by reverse transcription-polymerase chain reaction. These results suggest that FISH analysis of formalin-fixed, paraffin-embedded specimens using EWSR1 and NR4A3 probes is useful and convenient and may provide an ancillary method for the diagnosis of EMC.

Histological differences between invasive ductal carcinoma with a large central acellular zone and matrix-producing carcinoma of the breast.

Carcinoma with a large central acellular zone (central acellular carcinoma, CAC) and matrix-producing carcinoma (MPC) have been recently noted as basal-like-type breast cancers, but the two entities are often confused. To clarify their histological differences, the histopathological sections of 15 CAC and seven MPC were examined and the following features were compared by reviewing slides: (i) mode of invasion; (ii) alteration of cancer cell adhesion in the transitional area between cellular and acellular zones; (iii) staining of the stromal matrix; (iv) lymphocyte infiltration; and (v) tumor grade. Complete agreement was required between two observers for the assessments of these features. All CAC had relatively sharp margins but showed infiltrative growth accompanied by eosinophilic intercellular matrix. In CAC there was abrupt transition between peripheral cellular and central acellular zones without alteration of cancer cell adhesion. In contrast, all MPC showed expansive growth with a well circumscribed margin, accompanied by basophilic and myxoid intercellular matrix. In MPC there was gradual transition from cellular to acellular areas with gradual loss of cancer cell adhesion. Histological grade 3 and peripheral lymphocyte infiltration were common features. It is suggested that CAC and MPC are histologically distinct entities, and that the aforementioned features are helpful for differential diagnosis.

Clinicopathological features of tumors as predictors of the efficacy of primary neoadjuvant chemotherapy for operable breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NC) is standard therapy for patients with locally advanced breast cancer and is increasingly used for early-stage operable disease. Clinical and pathological responses are important prognostic parameters for NC, which aims to achieve a pathological complete response or tumor reduction to reduce the volume of subsequent breast resection. Clinicopathological markers that predict patient response to NC are needed to individualize treatment. METHODS: From 1998 to 2006, 368 patients with primary breast cancer underwent curative surgical treatment after NC (anthracycline and/or taxane without trastuzumab). We retrospectively evaluated the clinicopathological features and classification of the tumors using computed tomography (CT) before NC and analyzed the correlation with the pathological complete response (pCR) and reduction of tumor size after treatment. RESULTS: The overall response and pCR rates in these patients were 86% and 17%, respectively. In multivariate analysis, classification as a scirrhous-type tumor was an independent predictor of reduced likelihood of pCR (p=0.0115; odds ratio 0.21). For tumor reduction, histological grade 3 (p=0.0002; odds ratio 3.3) and localized tumors identified by using CT imaging (p=0.0126; odds ratio 2.4) were independent predictors in multivariate analysis. CONCLUSIONS: In this study, NC often did not result in pCR for breast cancers classified as scirrhous. Furthermore, tumor type classification using CT imaging and histological grading was effective to predict tumor reduction in response to NC that included an anthracycline and/or a taxane.

Analysis of CHOP rearrangement in pleomorphic liposarcomas using fluorescence in situ hybridization.

Pleomorphic liposarcoma (PLS) is an aggressive subtype of liposarcoma composed of high-grade sarcoma with pleomorphic lipoblasts. PLS usually exhibits a heterogeneous histology and sometimes has a myxoid or round cell area similar to myxoid/round cell liposarcomas (MLS/RCs). Using fluorescence in situ hybridization (FISH) analysis, we investigated the existence of CHOP split signals in various histological areas of PLS including the MLS/RC-like feature and also estimated the distribution of various signals with polyploidy and amplification. Moreover, to detect CHOP fusion transcripts we performed nested reverse transcription-polymerase chain reaction (RT-PCR). Seven PLSs and three MLS/RCs were selected for FISH analysis using the locus-specific indicator CHOP (12q13) dual color, break apart probe (Vysis, USA). The FISH analysis was applied to formalin-fixed, paraffin-embedded tissue sections of representative areas in all cases. Six of seven PLS cases showed the CHOP split signal ranging from 0.5% to 3% of counted nuclei, while all cases of MLS/RC exhibited CHOP rearrangement in more than 50% of counted nuclei. All cases of PLS showed a varied distribution of extra signals with polyploidy and amplification in each histological area. No CHOP fusion transcript was found in any case of PLS by nested RT-PCR. A CHOP rearrangement in PLS should be recognized only as a representative part of complex karyotypes, because the number of cells with split signals was minute compared with that of MLS/RC, and the signals were found in any area despite their histological differences. The cytogenetic background of PLS and that of MLS/RC are obviously different despite histological similarity.

Comparison among different classification systems regarding the pathological response of preoperative chemotherapy in relation to the long-term outcome.

Neoadjuvant chemotherapy (NAC) is increasingly used for operable disease. However there are several pathological response classification systems and the correlation between the pathological response to NAC according to each system and the patient outcome is still under debate. From 1998 to 2006, 370 primary breast cancer patients underwent curative surgical treatment after NAC containing both anthracycline and taxane at the National Cancer Center Hospital. We retrospectively evaluated the clinical and pathological response using the cTMN, Fisher's, Chevailler's, and the Japanese Breast Cancer Society classification systems (JBCS) respectively, and analyzed the correlation between each pathological response and disease free survival (DFS). Ninety-five (26%) patients had tumor recurrence. The five-year DFS according to Fisher's system was pCR, 80% and pINV, 63%. The five-year DFS according to Chevallier's system was Grade 1, 83%, Grade 2, 85%, Grade 3, 62%, and Grade 4, 65%. The five-year DFS according to the JBSC system was Grade 3, 77%, Grade 2, 68%, Grade 1a, 68%, Grade 1b, 58%, and Grade 0, 52%. None of the pathological response systems reached a statistically significant difference. In the classification by the post-treatment number of metastatic axillary lymph nodes, the 5-year DFS was n = 0, 86%; n = 1-3, 64%; n = 4-9, 44%; and n > 10 positive: 25% (P < .0001). In pathologically node negative patients, there were no significant differences in the DFS among all the classification systems. All three classifications analyzed were considered inadequate as the prognostic marker of the long-term outcome after NAC and further studies are warranted to optimize the prediction.

Computed tomography and magnetic resonance imaging findings of soft tissue perineurioma.

Soft tissue perineurioma is an uncommon benign peripheral nerve sheath tumor, although it is the most common subtype of perineuriomas. We present a case of soft tissue perineurioma in the left groin of a 48-year-old man. Precontrast computed tomography showed a homogeneous hypodense mass that showed faint enhancement. The mass appeared with hypointensity on T1-weighted magnetic resonance (MR) images and heterogeneous hyperintensity on T2-weighted MR images. Slight contrast uptake was noted on enhanced T1-weighted MR images with fat suppression. Although these CT and MR imaging findings were nonspecific, the overall imaging features are similar to those of schwannomas.

Pfetin as a prognostic biomarker of gastrointestinal stromal tumors revealed by proteomics.

PURPOSE: We aimed to develop prognostic biomarkers for gastrointestinal stromal tumors (GIST) using a proteomic approach. EXPERIMENTAL DESIGN: We examined the proteomic profile of GISTs using two-dimensional difference gel electrophoresis. The prognostic performance of biomarker candidates was examined using a large-scale sample set and specific antibodies. RESULTS: We identified 43 protein spots whose intensity was statistically different between GISTs with good and poor prognosis. Mass spectrometric protein identification showed that the 43 spots corresponded to 25 distinct gene products. Eight of the 43 spots derived from pfetin, a potassium channel protein, and four of the eight pfetin spots had a high discriminative power between the two groups. Western blotting and real-time PCR showed that pfetin expression and tumor metastasis were inversely related. The prognostic performance of pfetin was also examined by immunohistochemistry on 210 GIST cases. The 5-year metastasis-free survival rate was 93.9% and 36.2% for patients with pfetin-positive and pfetin-negative tumors, respectively (P < 0.0001). Univariate and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinicopathologic variables examined, including risk classification and c-kit- or platelet-derived growth factor receptor A mutation status. CONCLUSIONS: These results establish pfetin as a powerful prognostic marker for GISTs and may provide novel therapeutic strategies to prevent metastasis of GIST.

Advantage of FISH analysis using FKHR probes for an adjunct to diagnosis of rhabdomyosarcomas.

Translocations can be detected using fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded tissues. Recently, a commercially available FKHR (13q14) dual-color, break-apart rearrangement probe has been developed. However, the advantages of using this probe have not been reported. This study demonstrated the usefulness of this probe for the clinical diagnosis of rhabdomyosarcomas (RMS). We studied 33 RMS (19 embryonal rhabdomyosarcomas [ERMS], including three sclerosing-type RMS, and 14 alveloar rhabdomyosarcomas [ARMS]). Fluorescence signals were detected for 18 of the 19 (94.7%) ERMS and 13 of the 14 (92.8%) ARMS. A split-signal pattern was detected in 12 of 13 (92.3%) ARMS but was not detected in any of the ERMS, including the three sclerosing-type RMS. Amplification and polyploidy were present in both the ERMS and the ARMS. Our FISH study highlighted the excellent performance of the presently reported commercial break-apart probe for the detection of FKHR gene rearrangements in RMS. Because amplification and polyploidy were detected in both the ERMS and the ARMS, sufficient care should be taken when counting the nuclear signals. No rearrangements of the FKHR gene were found in any of the three sclerosing-type RMS when examined using a FISH assay, supporting the hypothesis that sclerosing RMS can be included as an ERMS.