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[Adjuvant treatments of early breast cancer without lymph node involvement].

Lymph node status remains the most important prognostic factor in breast cancer. However, only 70% of the node negative breast cancer patients are alive at 10 years. Several randomized trials have shown that systemic adjuvant therapy, either chemo or hormonotherapy, increases survival in these patients. A recent meta-analysis confirms these findings. In 1992, a consensus conference recommended no therapy in low risk patients (tumor size less than 1 cm), tamoxifen in good risk patients (tumor less than 2 cm, oestrogen or progesterone receptors positive, well differentiated) and chemotherapy in premenopausal or hormonotherapy in postmenopausal high risk patients (receptor-negative less than 1 cm tumor or high pathological grade).

Breast Neoplasms↗

Nuclear imaging of bone tumors: FDG-PET.

Positron emission tomography (PET) has become a very useful adjunct to anatomic imaging techniques, because it can provide an in vivo method for quantifying functional metabolism in normal and diseased tissues. Clinical trials with [(18)F] 2-deoxy-2-fluoro-D-glucose (FDG), the most commonly used radiolabeled tracer for PET imaging, has demonstrated increased accumulation of FDG in cancer tissue. FDG-PET is now widely used for the detection, differentiation, grading, staging, and monitoring of various neoplasms. However, the significance of FDG-PET in such evaluations of primary bone tumors and tumor-like lesions has not been extensively elucidated. In this article, we present recent advances in FDG-PET studies for evaluating primary bone tumors and tumor-like lesions.

Bone Neoplasms↗

Synovial sarcoma: an unexpected ultrasound finding in a post-partum patient.

A 20-year-old patient presented after an uneventful pregnancy and delivery with an asymptomatic soft-tissue mass behind her knee with the clinical features of a ganglion or Baker's cyst. An ultrasound scan demonstrated a well-defined but solid mass with prominent vascularity. The mass was noted to increase in size prior to surgery. The pathological diagnosis was that of a synovial sarcoma grade 2, a rare malignant mesenchymal neoplasm with a serious prognosis.

Adult↗

Excellent results of postoperative radiotherapy for endometrial stromal sarcoma of low-grade malignancy.

Endometrial stromal sarcoma of low-grade malignancy (ESSL) is a rare neoplasm, and neither preoperative diagnostic procedures nor standard therapy have yet been established. We treated 3 cases of ESSL in the past 27 years, and we report here one of these cases that was classified as stage III (according to the FIGO classification of endometrial carcinoma). Postoperative radiotherapy was used to treat a residual tumor, and the patient showed a complete response.

Adult↗

Low grade fibromyxoid sarcoma: report of a case with fine needle aspiration cytology and histologic correlation.

BACKGROUND: Low grade fibromyxoid sarcoma has been fully described histologically; however, the fine needle aspiration (FNA) cytologic findings are scantily defined, and the distinction from other benign and malignant soft tissue tumors can be difficult. CASE: We examined FNA cytologic material from a slowly growing, large chest wall mass in a 28-year-old woman. The surgical specimen was processed for routine histology and immunohistochemical studies. The cytologic smears were adequately cellular, showing spindly cells with uniform, elongated nuclei; small, inconspicuous nucleoli; and scanty, wispy cytoplasm associated with myxoid material. No significant nuclear pleomorphism or mitoses were noted. The excised tumor was well circumscribed, focally infiltrating the surrounding muscles. The cut surface was variable, featuring fibrous, solid, fleshy and myxoid areas. Microscopically, the solid, fibrous areas displayed increased cellularity with storiform, intersecting and parallel patterns. In the myxoid areas the cells grew in a haphazard fashion and appeared floating in abundant mucoid matrix associated with a capillary vascular network similar to the chicken-wire pattern seen in cases of myxoid liposarcoma. The tumor cells were spindly, with fusiform, uniform nuclei. Focal, moderate nuclear pleomorphism was noted. The mitotic index was low. The tumor cells were positive for vimentin, alpha-1-antitrypsin and lysozyme and negative for S-100, actin, desmin and CD34. CONCLUSION: Although low grade fibromyxoid sarcoma is a rare neoplasm, it should be recognized and distinguished from other soft tissue tumors because of its low malignant potential. The definitive FNA cytologic diagnosis can be challenging but is possible if the tumor is adequately sampled, with multiple passes from different areas. Clinical and radiologic correlations are of great help. All spindle cell tumors with myxoid changes, such as myxoid liposarcoma, myxofibrosarcoma, cellular myxoma, myxoid leiomyosarcoma and peripheral nerve sheath tumors, should be considered in the differential diagnosis. In contrast to the cytologic features, the histologic findings are characteristic and well established.

Adult↗

Interdisciplinary approach to abdominal Burkitt's lymphoma.

Burkitt's lymphoma is a high-grade, rapidly growing B-cell neoplasm. It is recognized by its aggressive course, brief median survival, and low rates of long-term survival. The authors discuss the case of a patient who acutely presented with intraabdominal complications from a new onset of Burkitt's lymphoma. The clinical and pathological features, staging, treatment options, and survival data are reviewed. In addition, the role of surgical intervention is carefully analyzed.

Abdominal Neoplasms↗

Significance and problems in evaluations of pathological responses to neoadjuvant therapy for breast cancer.

Neoadjuvant therapy consists of systemic drug treatments before surgery for a primary cancer. Currently, several neoadjuvant therapy regimens for breast cancer that use various cytotoxic as well as endocrine-therapeutic and molecular-targeting agents have been performed in clinical practice and/or studies. In neoadjuvant therapy, pre-treatment pathological examination using materials obtained by a core needle biopsy (CNB) is necessary, and pathological diagnosis and evaluation of the biological status, such as hormone receptors and HER-2 over-expression are confirmed. In addition, CNB in the inter-phase of chemotherapy is also thought to be useful for assessment of therapeutic effects before regimens have been completed. After surgery, the therapeutic effects of neoadjuvant therapy have been mainly evaluated on the basis of pathological findings and a pathological complete response (pCR) is considered to be the main target of neoadjuvant therapy. Results of most of clinical studies including NSABP protocol B-18 and B-27 have confirmed the prognostic significance of pCR in neoadjuvant therapy and indicated the significance of pathological evaluation. However, universally accepted pathological response criteria have not been established, but evaluations of the main invasive tumor, intraductal components and regional lymph nodes are thought to be necessary. Additionally, evaluation of the effects below pCR also need examining in a study using a mild anti-cancer drug, such as hormone-therapeutic agent, and the survival outcomes of patients below pCR need to be examined and compared between each grade.

Breast Neoplasms↗

Reversal of multidrug-resistance using Valspodar (PSC 833) and doxorubicin in osteosarcoma.

High-grade osteosarcoma is an extremely aggressive neoplasm, where over 80% of patients present with life-threatening micrometastases at diagnosis. Systemic control of the disease is therefore critical for the treatment of these patients and neoadjuvant chemotherapy using various drugs, including doxorubicin (DXR), which has been demonstrated to be the most effective regimen. Multidrug resistance (MDR) to some anticancer agents, including DXR, mediated by the MDR1 gene product P-glycoprotein (Pgp), has been shown to be a major cause of chemotherapy failure in osteosarcoma. We analyzed the effect of a cyclosporine A derivate Valspodar (PSC 833) on MDR human osteosarcoma cells. We also evaluated Pgp expression in sporadic appendicular canine osteosarcoma. Moreover, dogs were treated with combined administration of DXR and PSC 833. Several blood samples were collected for the determination of DXR and PSC 833 levels. PSC 833 induced a complete reversal of the resistant phenotype at concentrations compatible with the clinical use. Pgp was present in 12/18 (66.6%) of the cases. At the time of DXR administration, adequate blood concentrations of PSC 833, to provide a complete MDR reversal, were obtained without clinical or laboratory findings of toxicity. Combination therapy with DXR and PSC 833 allowed a 30% decrease in DXR dose infusion with equivalent therapeutic exposure. The high incidence of Pgp expression in osteosarcoma confers to the study a rationale for an effective regimen based on down-modulation of MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Matrix gene expression pattern as indicators of the biology of cartilage-forming tumors].

Mesenchymal cells can be characterized by the expression of specific sets of extracellular matrix (ECM) proteins. The aim of our study was to identify such expression pattern in cartilage-forming tumours in order to elucidate the biology of these neoplasms. In situ hybridisation and immunohistochemistry for various ECM components were performed on enchondromas, conventional chondrosarcomas of various grades and dedifferentiated chondrosarcomas. Chondroid areas of all investigated neoplasms showed strong expression of cartilage collagen types II and IX and aggrecan core and link protein. Focally, also the expression of other collagen subtypes such as collagen type X and collagen types I and III was observed. Non-chondroid areas of dedifferentiated chondrosarcomas lacked any expression of the cartilage-typical gene products and were instead positive for interstitial collagen types I, III, and VI. The hallmark of all investigated cartilaginous neoplasms was the expression of the chondrocyte-typical genes. Neoplastic chondrocytes showed the differentiation facettes similar to their physiological counterparts resulting in the high heterogeneity, which is characteristic for chondrogenic neoplasms. A different biology is suggested for dedifferentiated chondrosarcomas, in which the "dedifferentiated" portion is proposed to have a separate (e.g. fibroblastic) mesenchymal origin.

Bone Neoplasms↗

Induction of apoptosis in glioma cells: an approach to control tumor growth by blocking basic fibroblast growth factor autocrine loop.

Glioma is a group of neoplasms derived from neuroepithelial tissue. High grade glioma is characterized by the presence of mitotic figures and the occurrence of vascular endothelial hyperplasia. This article reviews the effects of growth factors which are secreted by glioma cells on the proliferative activity of both glioma cells and vascular endothelial cells. Among various glioma-derived growth factors, we have found that basic fibroblast growth factor (bFGF) plays an important role in determining malignant trait of human glioma via its autocrine loop. Furthermore, we discuss candidate molecular targets for the therapy of high-grade glioma by blocking the autocrine loop of bFGF.

Animals↗

Validation of the novel indices of nuclear pleomorphism, polarity and spatial distribution in the grading of urothelial carcinoma.

OBJECTIVE: To evaluate the role of the novel histomorphometric variables of pleomorphism, orientation and variability of spatial cytologic organization to objectively quantify histopathologic grade in urothelial carcinoma. STUDY DESIGN: As a validation model, we chose 51 papillary urothelial carcinomas. Thirty-six (70%) were low and 15 (29%) high grade tumors (World Health Organization grading system). Thirty-one cases (61%) were noninvasive, 12 (23%) exhibited lamina propria invasion, and 8 (16%) invaded the deep smooth muscle. Histomorphometric measurements were performed on noninvasive areas only. Pleomorphism was characterized by the anisokaryosis index (AIX), based on the autocorrelation function applied to classic nuclear shape descriptors. Additional indices of pleomorphism included standard deviations (sd) and coefficients of variation of these shape descriptors. Loss of polarity was assessed by the orientation index (ORX), based on Fourier transformation. Intraepithelial nuclear spatial distribution index (NSDX) was also computed. RESULTS: Low grade tumors exhibited less pleomorphism, higher orientation indices and a more homogeneous spatial distribution than did high grade tumors (area-AIX: P = .004, ORX: P < .0001, NSDX: P = .001). Multivariate analysis revealed the significant discriminators of grade to be nuclear size and orientation (size: max-diam, P < .0001; width: P < .0001; orientation: ORX: P < .0001). A discriminant score combining these independent variables distinguished between low and high grades in 98% of cases. The method was successfully validated using a testing sample of 40 new patients (accuracy, 94%). Lamina propria invasion was independently predicted by nuclear pleomorphism (width-sd: P = .0001, sensitivity = 64%, specificity = 91%). Muscle invasion was independently predicted by nuclear area (P < .0001) and pleomorphism (area-sd: P < .0001, max-diam-sd: P < .0001, width-AIX: P < .0001, sensitivity = 87%, specificity = 100%). CONCLUSION: These novel morphometric methods may serve as more objective methods of histopathologic grading and may contribute to the development of automated systems for quantitative grading of stratified and transitional epithelial neoplasms.

Aged↗

[Prostatic neuroendocrine cells].

From the first description of Pretl in 1944, many authors have shown different morphological and immunohistochemical studies related to prostatic neuroendocrine cells. These cells belong to a neuroendocrine system, wide disseminated network, that is found in many human tissues. They secret neuroendocrine peptides and play an important role in the glandular epithelium regulation (growing, differentiation, and exocrine secretion), in both normal and hyperplastic glands. They are also present in ordinary prostatic adenocarcinoma and in unusual small cell carcinoma. Recently, it has been suggested that prostatic neuroendocrine cells may be related to prognosis in prostatic carcinoma, particularly in cases with hormonal therapy resistant. In this study, there are 23 prostatic disorders: 11 nodular hyperplasias and 12 adenocarcinomas, and also areas of normal gland. The objective is the morphologic identification of these cells with silver impregnation technique, in normal tissue, nodular hyperplasia and adenocarcinoma. In normal gland and nodular hyperplasia, the NE cells can be seen along most of the gland or near the urethra, solitary or in small clusters. These cells are located between acinar epithelium cells and basement membrane, but they are also found within the stroma in relation to nerve endings. They characteristically contain argyrophil and argentaffin granules in the cytoplasm and exhibit cytoplasmatic processes extended to acinar or urethral lumen. Within the stroma, they are seen isolated with dendritic or ribbon-like cytoplasmatic processes. In this study, there is only one adenocarcinoma of high grade with NE cells. In this neoplasm they are increase in number, and appear isolated and more polymorphic.

Adenocarcinoma↗

Heparanase messenger RNA expression in epithelial ovarian tumor.

Endoglycosidic heparanase degrades heparan sulfate glycosaminoglycans, and may be important in cancer invasion and metastasis, although its expression in human epithelial ovarian cancer has not been characterized. Heparanase association with clinicopathological features regarding prognostic significance was examined in patients presenting with epithelial ovarian tumor. Gene expression of heparanase was assessed by reverse transcription-PCR in 5 borderline and 31 malignant epithelial ovarian tumors. Heparanase mRNA expression was high in 16 of 31 malignant epithelial ovarian tumors. In contrast, there was no specimen presenting high heparanase mRNA expression in five borderline epithelial ovarian tumors. Heparanase expression was significantly higher in tumors with massive ascites and high grade (p=0.049 and p=0.006, respectively). There was no association between heparanase expression and patient outcome. These findings provide evidence that heparanase expression may be associated with a high grade phenotype in this class of neoplasm.

Carcinoma↗

Recurrent polymorphous low-grade adenocarcinoma manifesting as a sinonasal mass: a case report.

Polymorphous low-grade adenocarcinoma (PLGA) is a malignant neoplasm that tends to follow a benign clinical course. Recurrences are uncommon. We report a case of recurrent PLGA of the paranasal sinuses that manifested as a large mass that filled the entire nasal cavity and left maxillary sinus. To our knowledge, this is the first reported case of a recurrent PLGA of the paranasal sinuses.

Adenocarcinoma↗

Polymorphous low-grade adenocarcinoma at the base of the tongue: an unusual location.

Polymorphous low-grade adenocarcinoma (PLGA) is a malignant neoplasm of low aggressiveness that occurs almost exclusively in the minor salivary glands, primarily those in the palate. We report a case of PLGA that arose in the base of the tongue and subsequently metastasized to the neck. The tumor was resected through the oral cavity with wide margins and dissection. The neck metastasis was treated with radical neck dissection and radiotherapy. The patient recovered and remained disease-free at follow-up 30 months later. This case shows that PLGA, which has a variable morphologic appearance, can occur at sites other than the salivary glands.

Adenocarcinoma↗