[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.

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.

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.

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.

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.

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.

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.

Bone and soft-tissue sarcoma: preoperative staging with fluorine 18 fluorodeoxyglucose PET/CT and conventional imaging.

PURPOSE: To retrospectively compare the diagnostic accuracy of positron emission tomography (PET)/computed tomography (CT), PET, conventional imaging, and combined PET/CT and conventional imaging for tumor staging of bone and soft-tissue sarcomas, by using histologic or follow-up imaging findings as the reference standard. MATERIALS AND METHODS: Institutional review board approval was received for this HIPAA-compliant study; informed consent was obtained. Integrated PET/CT was performed in 117 patients (69 male patients, 48 female patients; mean age, 42 years +/- 21 [standard deviation]; range, 9-86 years). Conventional imaging consisted of magnetic resonance imaging of the primary site, chest radiography, whole-body contrast material-enhanced CT, and bone scintigraphy. A total of four reviewers assessed all images. Overall and T staging were evaluated in 69 (59%) patients who underwent surgical removal of the primary tumors and had pathologically proved results. N and M staging were evaluated in all patients, and their reference methods were based on histologic findings (n = 101) and follow-up CT findings (n = 16). RESULTS: Interpretations based on combined PET/CT and conventional imaging findings correctly staged tumors in 60 (87%) of 69 patients, overstaged tumors in eight (12%) patients, and understaged tumors in one (1%) patient. Overall staging accuracy of combined PET/CT and conventional imaging was significantly higher than that at PET (P < .0001). Combined PET/CT and conventional imaging resulted in correct N staging in 114 (97%) of 117 patients and M staging in 109 (93%) of 117 patients. Combined PET/CT and conventional imaging helped reduce overstaging in three (4%) patients and helped change tumor diagnosis from unresectable to resectable in two (2%) patients compared with PET/CT. CONCLUSION: The combination of PET/CT and conventional imaging is accurate in preoperative staging of bone and soft-tissue sarcoma.

Favorable outcome in patients with breast cancer in the presence of pathological response after neoadjuvant endocrine therapy.

Neoadjuvant endocrine therapy (NAET) can expand the number of breast cancer patients who can be treated with breast-conserving surgery and can predict benefit from adjuvant endocrine therapy. Because no validated surrogate markers for long-term outcome have been established, we conducted prospective trials to evaluate pathological response and Ki-67 index following treatment with tamoxifen or anastrozole. The study population included postmenopausal women with operable breast tumors that were both estrogen and progesterone receptor-positive and larger than 3 cm. Response was classified as pathological response (minimal response or better) and non-response. Non-responding (25.5%, vs. response 85.9%, p=0.002), axillary node-positive (58.4% vs. node negative 100%, p=0.045), and high pretreatment Ki-67 index (41.4% vs. low Ki-67 87.1%, p=0.03) patients were significantly associated with poor 5-year relapse-free survival. Multivariate analysis of relapse-free survival indicated that pathological response was independent. Therefore, pathological response may be a favorable prognostic factor after NAET.

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.

Bilateral adrenal gland metastasis from malignant fibrous histiocytoma: value of [F-18]FDG PET-CT for diagnosis of occult metastases.

The vast majority of soft tissue sarcomas metastasize initially to the lungs. We report a 71-year-old woman with malignant fibrous histiocytoma of the right buttock and thigh that metastasized to the bilateral adrenal glands without development of pulmonary metastasis. Whole-body [F-18]FDG PET-CT showed abnormal tracer uptakes in the bilateral adrenal glands in addition to high accumulation in the primary soft tissue tumors. CT-guided needle biopsy revealed that both of the adrenal lesions were metastatic malignant fibrous histiocytoma. There was no pulmonary or other visceral metastasis. To the authors' knowledge, this is the first report of malignant fibrous histiocytoma metastatic to the bilateral adrenal glands without development of pulmonary metastases. This case illustrates the excellence of [F-18]FDG PET-CT scan for diagnosis of occult metastases from soft tissue sarcomas.

A case of ganglioneuroma presenting abnormal FDG uptake.

We report a case of ganglioneuroma with abnormal 18F-fluorodeoxyglucose (FDG) uptake. A 26-year-old woman presented to the hospital with a slowly growing abdominal tumor without symptoms. She was diagnosed with neuroblastoma in childhood and treated by surgery and chemotherapy. Computed tomography (CT) revealed huge retroperitoneal tumors and fused 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT image showed abnormal accumulation of FDG in tumors with maximal standardized uptake value of 2.02. Considering her past history, ganglioneuroma matured from neuroblastoma was considered, the most likely diagnosis. However, a second primary malignant tumor, such as malignant peripheral nerve sheath tumor arising in ganglioneuroma, could not be ruled out. Then, an excisional biopsy was performed and the diagnosis of mature ganglioneuroma was made. Pathological investigation may be needed to differentiate ganglioneuroma from other malignant tumors and, therefore, FDG-PET/CT findings can be helpful for biopsy planning.

CT and MRI features of low-grade fibromyxoid sarcoma in the shoulder of a pediatric patient.

We report the computed tomography (CT) and magnetic resonance imaging (MRI) features of a 10-year-old boy with low-grade fibromyxoid sarcoma (LGFMS) in the shoulder and correlate them with the clinicopathological features. LGFMS, a rare soft tissue sarcoma with bland histological features and paradoxically aggressive behavior, tends to occur in superficial regions and in children more than previously recognized. To date, few imaging studies have been reported, particularly in pediatric patients. In this case, precontrast CT showed a low- to isodensity mass and punctate calcification. On contrast-enhanced CT, heterogeneous enhancement was seen. MRI findings correlated well with the pathological features of the tumor. The myxoid area showed high signal intensity on T2-weighted MR images and heterogeneous enhancement after administration of contrast material; the hypercellular area demonstrated lower signal intensity on T2-weighted MR images and slight enhancement.

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.

Prostatic acid phosphatase is a possible tumor marker for intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (LBCL) is a rare and aggressive subtype of diffuse LBCL characterized by disseminated intravascular proliferation of neoplastic lymphocytes. Obstruction of blood flow by tumor cells in a variety of organs can cause an array of clinical changes, including alteration of the neural and spinal system and the respiratory system, as well as skin lesions. It is usually very difficult to diagnose intravascular LBCL in a patient simply from clinical symptoms or laboratory examinations. We here document our findings that serum prostatic acid phosphatase levels in both males and a female (2.2-24.0 microg/L) reflect the presence of intravascular LBCL, changing synchronously in response to chemotherapy. To determine whether prostatic acid phosphatase (PAP) might be a useful tumor marker for early diagnosis, we reviewed five intravascular LBCLs. Immunohistochemically, tumor cells in all cases were positive for anti-PAP antibody. The results were further confirmed in one case by Western-blot analysis and in another by the detection of amplified messenger RNA for PAP in microdissected tumor cells, respectively. PAP has not been detected in 17 lymphomas (diffuse LBCL, 8 cases; follicular lymphoma, 3 cases; T-cell lymphoma, 3 cases; Hodgkin lymphoma, 3 cases) by Western blot analyses. We conclude that serum PAP is a useful tumor marker for intravascular LBCL and that it deserves further investigation in this context.

[Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial pneumonia initially in the right lung after surgery lobectomy for left lung cancer].

A tumor was found in the left S10 in a chest CT scan of a 72-year-old male patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and mediastinal lymph nodes under video-assisted thoracoscopic surgery. The histopathological evaluation disclosed a well-differentiated squamous cell carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day, a severe hypoxemia (PaO2 48 mmHg) developed, and the chest CT showed diffuse ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started. However, despite this therapy, the diffuse GGO extended to both lung fields, and the patient died of respiratory failure 82 days later. The histopathology at autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of IPF/UIP could have been triggered by a high concentration of oxygen or mechanical lung injury during the patient's surgery.

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.