Tumor Typing Research Articles

Bronchial Brushing Increases the Diagnostic Yield of Fiberoptic Bronchoscopy in Bronchogenic Carcinoma

Background : The importance of rapid and accurate cytopathological diagnosis in bronchial cancers is increasing due to advances in treatment modalities. Aims : We evaluated the diagnostic methods and cytologic subtypes of bronchial cancers to determine the diagnostic reliability of different bronchoscopic techniques. Material and methods: Retrospective data were obtained from the hospital files and pathological specimens of the patients with diagnosis of primary lung cancer from a period of 36 months. Cytological tumor typing was determined using histopathology of bronchoscopic forceps biopsy (FB), bronchial-bronchoalveolar lavage (BL), bronchial brushing (BB), transbronchial fine-needle biopsy. Computed tomography or ultrasonography guided transthoracic biopsy and surgical biopsies were used where the other interventional methods were inadequate for diagnosis. Results : A total of 124 patients were diagnosed during study period. 119 (96%) of them were male. The median age was 68, ranging between 36 and 88 years. Histopathologic subtypes were determined as non-small cell carcinoma (NSCC) in 104 (83.9%), squamous cell carcinoma in 64 (51.6%), adenocarcinoma in 16 (12.9%), NSCC not otherwise specified in 24 (19.3%) and small cell carcinoma in 20 (16.1%) patients. The combination of FB, BL and BB established the diagnosis of bronchogenic carcinoma in most of the cases (92.6%). Conclusions : Lung cancer is seen commonly in elderly male patients with smoking history and squamous cell carcinoma is the most common cytologic type. High diagnostic accuracy can be achieved by a combination of bronchoscopic FB, BB and BL procedures. Keywords: Bronchoscopy; Lung cancer; Bronchial brushing

Histogenesis and Natural History of Gut Neuroendocrine Tumors: Present Status

Important progress has been made during the last decade in the histopathologic characterization and overall prognostic evaluation of gut neuroendocrine tumors. However, some issues like tumor histogenesis, typing, functional characterization, and preferred site of origin deserve further clarification. This is a survey of the present status of the matter outlining some of the open points. In particular, careful comparison of normal gut endocrine cell types with related endocrine tumors so far identified shows an unexplained lack of neoplasms involving upper small intestine cells like secretin, cholecystokinin, motilin, and GIP cells, as well as the equally unexplained concentration of serotonin EC cell tumors in the ileum and appendix or of somatostatin cell tumors in the duodenal papillary region, despite their wide distribution in the normal gut, not to mention gastrinomas arising in the pancreas, normally devoid of gastrin cells. Special functional (e.g., achlorhydria-driven hypergastrinemia) or pathologic (as chronic inflammation) conditions may locally influence the proliferative and differentiation state of the endocrine cells thus promoting tumor growth. Tumor histologic structure, differentiation level, and proliferative index as well as gastrointestinal wall barriers to tumor diffusion may account for most prognostic parameters, with considerable changes, however, according to the tumor type and site. Thus, further work is needed to develop tumor- and site-adjusted prognostic parameters.

Von Hippel-Lindau Exonic Methylation Analysis Using MALDI-TOF Mass Spectrometry

Aberrant promoter methylation turns off gene expression and is involved in human malignancy. Studies show that first exon methylation has a tighter association with gene silencing compared to promoter methylation or gene mutation. However, to our knowledge the clinical importance of exonic methylation in renal cell carcinoma is unknown. We analyzed renal cell carcinoma for VHL gene exonic methylation using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In 48 institutionally banked renal cell carcinoma patient tissue samples VHL exon sequencing was done as well as methylation analysis of promoter and exon 1 by mass spectrometry or conventional bisulfite analysis. Methylated human lymphocytic DNA (0% and 100%), nontemplate distilled H2O, and the UOK121 and UOK171 human renal cell carcinoma cell lines served as assay controls. Samples were considered hypermethylated if a CpG site showed greater than 50% methylation. Nine of the 43 patient samples read by our exon 1 assay had methylated VHL exon 1 sites, including 3 showing hypermethylation. The exon 1 methylation assay was robust and reproducible. Samples with exon 1 hypermethylation showed no exonic mutations. All samples assayed at VHL exon 2 were hypermethylated. To assay renal cell carcinoma tumors for VHL methylation matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is robust and reproducible, and capable of quantifying the methylation status of individual DNA bases. Exon 1 methylation may be an alternate mechanism of VHL gene silencing in renal cell carcinoma in addition to mutation and promoter methylation. Applying this assay in patient populations may allow enhanced diagnosis or tumor typing in the future.

Cytomorphological features of atypical teratoid/rhabdoid tumor: An account of 12 years' experience

Atypical teratoid rhabdoid tumor (AT/RT), an aggressive neoplasm mostly affecting young children, is characterized by rhabdoid cells together with epithelial, mesenchymal and primitive differentiation. Diagnosing AT/RT in intraoperative consultation and cerebrospinal fluid (CSF) samples may therefore pose problems. Fourteen immunohistochemically proven AT/RTs diagnosed between 2000 and 2012 were collected. Material consisted of squash smears prepared during intraoperative consultation (thirteen) and CSF smears (three). MGG-stained CSF smears and H&E stained squash smears were reviewed by a neuropathologist and a cytopathologist. The intraoperative diagnoses were based on squash preparations and 3 out of 13 were consistent with AT/RT, 4 were considered medulloblastoma/primitive neuroectodermal tumors (PNET), 3 were deferred to paraffin section for tumor typing, and another 3 were misdiagnosed as ependymoma, germinoma and malignant glioma. Morphological assessment of intraoperative squash preparations showed that AT/RTs can have a mixture of pseudopapillary and diffuse smearing patterns. Cytomorphologic features consisted of characteristic rhabdoid cells (8/9); primitive appearing cells with a high nuclear to cytoplasmic ratio (7/9); bi-/multinucleated cells (3/9); rare necrosis/apoptosis and mitoses. Three CSF smears showed high cellularity and inclusion-bearing large cells. These cells are characterized by reniform/oval, eccentrically placed nuclei with cytoplasmic perinuclear light stained areas which are not seen in intraoperative squash preparations. Differential diagnosis of AT/RT in cytology involves medulloblastoma/PNET, ependymoma, glioma and germinoma among all others. Overlapping features of AT/RT with entities in differential diagnosis are discussed with a special emphasis of rhabdoid cells being the strongest feature to aid in reaching the diagnosis of AT/RT.

Germ Cell Tumors of the Ovary: An Update

The field of ovarian germ cell tumors (OGCTs) has remained relatively unchanged in the last 2 decades. However, the introduction of new stem cell pluripotency markers has provided a new understanding into the identification and taxonomy of OGCT types. New data have provided new insights into unusual teratoma-associated autoimmune disorders and the origin of gliomatosis peritonei. To review the impact of new pluripotency markers in the diagnosis of malignant OGCT (MOGCT) and analyze new nomenclature proposals and clinicopathologic entities. Ovarian germ cell tumors from routine material and expert consultation files at San Cecilio University Hospital, Granada, Spain, and the relevant literature were reviewed. Although a correct diagnosis of MOGCT can often be made with histologic and classic immunohistochemical studies, the new immunohistochemical pluripotency markers give higher diagnostic accuracy. Germ cell tumors represent a caricature of the phases of normal embryonic differentiation from primordial germ and stem cells to extraembryonal and somatic tissue differentiation. Since every stage of differentiation and its related tumor type exhibit characteristic markers, the analysis of their expression facilitates tumor typing, thus complementing the use of classic antibodies. They also allow a more precise evaluation of the degree of immaturity in teratoma. The new term, primitive endodermal tumors, simplifies the understanding of the complex histology of the yolk sac tumor group, as this terminology encompasses its multiple endodermal differentiations. Recently described autoimmune encephalitis due to antibodies against the N-methyl-d-aspartate receptor has become the most frequent autoimmune disorder associated with ovarian teratoma.

Relationship between expression of mTOR and prognosis of early stage non-small cell lung cancer

To investigate the influence of mTOR expression on prognosis of early stage NSCLC. One-hundred and thirty-eight patients who underwent radical surgery for early stage NSCLC in our hospital from Janurary 2002 to December 2006 were included in this study. There were 83 males and 55 females, in an average age of 65.8 years, for both genders). The influence of age, gender, tumor typing, pathological grading, pathological staging and mTOR expression on patients' survival were analyzed by univariate and multivariate analyses. The 5-year survival rate of the 138 cases was 44.8%. Immunohistochemical examination showed that mTOR-positive cases accounted for 101 while mTOR-negative cases accounted for 37. The 5-year survival rate of mTOR-positive patients was 32.7% and that of mTOR-negative patients was 56.4% (P = 0.019). Univariate analysis showed that mTOR expression, pathological staging and N1 lymph node metastasis were identified as significant prognostic factors, and were correlated to prognosis (P < 0.05 for all). Multivaraite analysis showed that pathological staging, mTOR expression, N1 lymph node involvement were identified as independent prognostic factors for patients with early NSCLC (P < 0.05 for all). Our findings suggest that overexpression of mTOR indicates a poor prognosis for NSCLC. mTOR, pathological stage and N1 lymph node metastasis are independent prognostic factors in early stage NSCLC.

A 92-gene cancer classifier predicts the site of origin for neuroendocrine tumors

A diagnosis of neuroendocrine carcinoma is often morphologically straight-forward; however, the tumor site of origin may remain elusive in a metastatic presentation. Neuroendocrine tumor subtyping has important implications for staging and patient management. In this study, the novel use and performance of a 92-gene molecular cancer classifier for determination of the site of tumor origin are described in a series of 75 neuroendocrine tumors (44 metastatic, 31 primary; gastrointestinal (n=12), pulmonary (n=22), Merkel cell (n=10), pancreatic (n=10), pheochromocytoma (n=10), and medullary thyroid carcinoma (n=11)). Formalin-fixed, paraffin-embedded samples passing multicenter pathologist adjudication were blinded and tested by a 92-gene molecular assay that predicts tumor type/subtype based upon relative quantitative PCR expression measurements for 87 tumor-related and 5 reference genes. The 92-gene assay demonstrated 99% (74/75; 95% confidence interval (CI) 0.93–0.99) accuracy for classification of neuroendocrine carcinomas and correctly subtyped the tumor site of origin in 95% (71/75; 95% CI 0.87–0.98) of cases. Analysis of gene expression subsignatures within the 92-gene assay panel showed 4 genes with promising discriminatory value for tumor typing and 15 genes for tumor subtyping. The 92-gene classifier demonstrated excellent accuracy for classifying and determining the site of origin in tumors with neuroendocrine differentiation. These results show promise for use of this test to aid in classifying neuroendocrine tumors of indeterminate primary site, particularly in the metastatic setting.

Prospective study of the evaluation of the usefulness of tumor typing by narrow band imaging for the differential diagnosis of gastric adenoma and well-differentiated adenocarcinoma

Background and Aim: Presently, the differential diagnosis of gastric adenoma and well-differentiated adenocarcinoma by endoscopy is very difficult. We carried out magnifying endoscopy with narrow band imaging (NBI) in lesions that required discrimination between gastric adenoma and well-differentiated adenocarcinoma, and prospectively evaluated whether the tumor typing that we propose is useful for their differential diagnosis. Methods: The materials were 93 lesions that required differential diagnosis between gastric adenoma and well-differentiated adenocarcinoma among the gastric epithelial tumors for which endoscopic treatment was planned at three facilities during the 14 months between November 2008 and December 2009. According to the typing method proposed by our facility based on images of the mucosal ultrastructure and microvessels obtained by magnified endoscopy combined with NBI, type I-II and type III-V lesions were diagnosed as gastric adenoma and well-differentiated adenocarcinoma, respectively, before endoscopic treatment, and the accuracy of the diagnoses were prospectively examined by comparing them with the postoperative pathological findings. Results: Of the 93 lesions, 87 could be typed into the five types of our typing method, but six lesions could not be classified. The 87 lesions consisted of 16 type I, 12 type II, 29 type III, 27 type IV, and three type V lesions. The percentages of accurate preoperative diagnoses of types I-II as adenoma and types III-V as well-differentiated adenocarcinoma were 79% and 93%, respectively. Conclusions: The tumor typing based on NBI was useful for the endoscopic differentiation of gastric adenoma and well-differentiated adenocarcinoma.

The pathologic response of resected synovial sarcomas to hyperthermic isolated limb perfusion with melphalan and TNF-α: a comparison with the whole group of resected soft tissue sarcomas

BackgroundHyperthermic isolated limb perfusion with tumor necrosis factor-α and melphalan (TM-HILP) has been successfully used to treat limb soft tissue sarcomas (STSs) with high response rates. The data on the effectiveness of HILP-TM for the treatment of STSs are mainly based on various STS types. The aim of this study was to investigate the responses of synovial sarcomas (SS) to TM-HILP.MethodsA total of 125 TM-HILP-treated tumors (STSall), including 14 SSs, were included in the study. The tumors were subdivided into proximal and distal limb localizations. Tumor typing (using the WHO classification), resection status (using the UICC classification), and response to therapy were assessed using light microscopy. The SSs were tested for the SYT-SSX translocation using RT-PCR. The following tests were applied: a chi-squared test, a t test, and the Mann-Whitney U test.ResultsThe SSs were localized distally more often than were the STS cohort (STS−SS) (85.7% vs. 32.4%) and were smaller (5.8 cm vs. 10.7 cm). There were no differences in the responder/nonresponder ratios or the mean percentages of pathological regression between the SS and STS−SS cohorts (74.0% vs. 76.0%). A general localization-dependent difference in the tumor responses to TM-HILP could not be detected in the STSall cohort (distal, 72.0% vs. proximal, 78.0%); however, a UICC R0 status was more often observed in proximal tumors (distal, 50.0% vs. proximal, 71.4%). There was no association between the SYT-SSX type and SS responses to TM-HILP.ConclusionsBecause of the high response rates, TM-HILP is recommended for the treatment of SSs. The distal limb localization of TM-HILP-treated STSs was generally (STSall cohort) associated with fewer R0 resections.

The classification of invasive carcinoma of the breast

The classification of invasive breast carcinoma assists diagnosis, allows for comparison of different patient groups in clinical trials and facilitates epidemiological analysis. For the individual patient, accurate tumor classification informs clinical decision-making with emphasis on assessment of prognosis and treatment formulation. Tumor grade is an independent prognostic indicator and is calculated by assessing specific tumor characteristics microscopically. The Tumor Node Metastasis staging system, produced by the American Joint Committee on Cancer Union for International Cancer Control, combines information about the primary tumor size, the status of the regional lymph nodes and the presence or absence of distant metastases at diagnosis to classify disease. In recent years, the use of gene expression profiling technology has led to the development of the molecular classification of breast cancer and has highlighted the importance of hormone receptor and HER2 oncogenic pathways, with particular reference to targeted chemotherapy. Tumor typing involves the identification of ‘no special type’ carcinoma with variable clinical, histological and molecular characteristics and ‘special type’ carcinomas that are usually associated with a particular set of prognostic and predictive indices. Some special type carcinomas have unique biological features that influence diagnostic investigation and clinical management.

Brain tumor epidemiology in Austria and the Austrian Brain Tumor Registry

Cancer registries provide incidence and mortality data on patients with cancer at the population level. Cancer registration is most often restricted to the group of malignant neoplasms, whereas information on benign and intermediate tumors is generally not available. Brain tumors however differ from other sites by 1) the large spectrum of different tumor types, and 2) the exclusive localization in proximity to eloquent areas with considerable neurological comorbidity and mortality irrespective of their biological behavior. In order to obtain a comprehensive overview of the brain tumor burden, specialized brain tumor registries, which provide information on all brain tumor types, have emerged in several countries. This thesis synopsis summarizes the Austrian experience on the establishment of such a specialized brain tumor registry: the Austrian Brain Tumor Registry (ABTR). The initial steps are reported - from consensus and commitment of the Austrian Society of Neuropathology, formation of an interdisciplinary team of experts, setup of the infrastructure including data confidentiality issues, to the sustained support of the Austrian neurooncology community and major cooperation with the Austrian National Cancer Registry. ABTR differs from other registries by its scientific setting and neuropathological background warranting strong expertise in brain tumor typing and tissue-based research. Thereby, ABTR constitutes also a virtual brain tumor biobank. By having achieved these steps, first investigational results demonstrate that ABTR provides valid and accurate population-based incidence and survival data for individual brain tumor types. The exact incidence of rare tumor entities is estimated, key diagnostic criteria of newly proposed tumor entities are refined, common standards for testing of molecular markers are advocated, and medical progress via real-life outcome analyses is assessed. The diverse scientific contributions highlight the enormous scientific potential of ABTR for continued work.

The significance of microbiopsies in cytological smears

The role of fine needle aspiration cytology (FNAC) in the diagnosis of malignant lesions is well documented. Conventionally obtained fine needle aspiration (FNA) smears frequently contain well preserved viable intact tissue fragments (microbiopsies). The present study was aimed at evaluating the microbiopsies and carrying out further cyto-histopathologic correlation in order to assess what additional information they could provide. A total of 116 FNA smears from clinically suspected malignant lesions were examined, of which 81 smears (70.0%) contained representative tissue fragments of the tumors. Histopathological details were available in 75 cases. Immunocytochemistry (ICC) was applied in selected smears as and when required. Tumors in which microbiopsies aided in diagnosis chiefly included soft tissue malignancies (12 cases), typed into malignant peripheral nerve sheath tumor, fibrosarcoma, spindle cell sarcoma and malignant melanoma; lung tumors (14 cases) classified as small cell carcinoma, large cell carcinoma, squamous carcinoma and adenocarcinoma; breast tumors (08 cases), typed into ductal, medullary and lobular carcinoma; and lymph node metastasis (19 cases) from primaries in lung, larynx and thyroid. The cyto-histopathologic concordance was raised from 81.2% in the absence of microbiopsies to 93.2% in their presence. FNA smears containing microbiopsies are of ample help in establishing firm diagnosis, tumor typing, and predicting possible primary sites in metastatic tumors which were not possible by cytology alone. Hence, this technique can be utilized to enhance the diagnostic accuracy of FNAC, if put into practice in evaluation of routine cytology smears, without increasing any financial burden on patients.

Assessment of Diagnostic Accuracy of Bronchoalveolar Lavage Cytology in the Diagnosis of Lung Tumors and Contribution to the Classification of Non-Small Cell Lung Cancer Entities: A Retrospective Clinocopathological Study

Background: Due to new therapeutic options in thoracic oncology, the pathological diagnosis of bronchial carcinoma has become more challenging. The majority of bronchial cancer is diagnosed from small biopsy specimens and the diagnosis often based on cytological methods. Aims: In this study, we reevaluated cytologic specimens in order to determine the diagnostic reliability of pulmonary cytopathologic techniques performed in our department. Material and methods: In our center bronchial lavage/bronchoalveolar lavage (BL/BAL) specimens are obtained both before and after forceps biopsy (FB) and subsequently processed. Retrospective data from a period of 60 months were retrieved from the institutional files. Sensitivity, specificity, as well as accuracy of cytological tumor typing were determined using histopathology of FB as gold standard. Also, the diagnostic yield of BL/BAL before and after FB was determined. Results: 678 cases were retrieved from the institutional files. The sensitivity and specificity of cytology were 83.0% and 83.4%, respectively. By FB in 3.9% of cytologically diagnosed non-small cell lung carcinomas (NSCLC) a histological assignment to a NSCLC entity was not possible. Conclusions: Cytology is a reliable diagnostic tool in the diagnosis of lung malignancies. High diagnostic accuracy is achieved by a combination of BL/BAL before and after FB. The diagnostic yield of BL/BAL after FB was significantly higher than BL/BAL before FB. Subsequent tumor typing of cytologically diagnosed NSCLC was feasible in more than 95% of cases.

Analyzing agreement patterns of intraoperative central nervous system lesion reporting according to type and grade

Background:Neuropathology centers are expected to offer a prompt and accurate intraoperative diagnosis regarding tumor/lesion type and grade on fresh unfixed tissue. Level of diagnostic accuracy according to type and grade and also, the experience at a new center has not been reported before.Aims:The aim of this study is to review the agreement patterns according to tumor/lesion type and grade between intraoperative and final histopathologic diagnosis in central nervous system (CNS) lesion samples received by a newly established neuropathology center at a tertiary care neuropsychiatric hospital.Materials and Methods:Agreement between intraoperative and final histopathologic diagnosis was classified as: (I) Grade in agreement but type not in agreement; (II) grade not in agreement but type in agreement; (III) grade and type both not in agreement; (IV) grade and type both in agreement.Statistical Analysis:Confidence interval (CI) of agreements was calculated for various categories of neoplastic as well as non-neoplastic lesions. CI was also calculated for groups where n × p and n × (1 − p) were more than 5, i.e., fulfilled the requirement of the central limit theorem.Results:On retrospective analysis of 333 cases, 284 (85.3%) cases were categorized as neoplastic while 49 (14.7%) cases were categorized as non-neoplastic. Among the neoplastic lesions agreement was seen in 237 (83.5%) cases while 47 (16.5%) cases showed disagreement. Similarly in non-neoplastic category; 46 (93.9%) cases showed agreement while 3 (6.15%) cases showed disagreement. Of the non-neoplastic lesions, one case fell into the agreement category I, 2 in category III and 46 in IV. Among neoplastic lesions, there were 21 cases in agreement category I, 17 in II, 9 in III and 237 in IV. On analyzing the accuracy of intraoperative reporting according to tumor type, the break up was: - Astrocytic: 2 (I), 16 (II), 2 (III), 86 (IV); oligodendroglial: 8 (I), 1 (II); ependymal: 2 (III), 6 (IV); embryonal: 23 (IV); cranial and spinal nerve tumors: 2 (II), 21 (IV); choroid plexus tumors: 4 (IV); meningeal tumors: 3 (I), 1 (III), 49 (IV); metastatic tumors: 3 (I), 17 (IV); cysts (tumor-like conditions): 14 (IV); neuronal and mixed neuronal glial tumors: 1 (III); malignant lymphoma: 1 (III); sellar tumors: 17 (IV); and mixed gliomas: 5 (I).Conclusions:This study identifies problem areas of CNS intraoperative reporting, in a new center, with reference to tumor typing and grading. It may forewarn upcoming centers of neuropathology about the potential problem areas of intraoperative reporting.

Histological Subtypes of Brain Tumor

Background: A brain tumor is an intracranial solid neoplasm which involves varied types of cells. Management strategies and prognosis of tumor depends on the combination of factors like the type and grade of tumor, its location, size and state of development. So definite typing of brain tumor by histological examina­tion is essential for appropriate treatment. Methods: This cross-sectional study was carried out from May 2011 to June 2012 in Delta Hospital Limited, Dhaka, Bangladesh. A total of 65 brain tissue biopsy samples were collected irrespective of age and sex along with patients’ clinical diagnoses, CT scan or MRI report, and operative findings and histological diagnosis were done. The frequency and proportion were calculated using SPSS 12.0 for Windows. Results: Majority (38.5%) of the study subjects belonged to 40–49 years of age group with male predominance (63.1%). Astrocytoma comprised the largest group (27.7%) and majority of the tumors were in spinal region (23.1%). Conclusions: It is concluded from this study that among the different varieties of brain lesions astrocytoma is the most common one and the location of tumor is more common in spinal region with male predominance between the age group of 40–49 years confirmed by biopsy and histopathology along with CT or MRI. DOI: http://dx.doi.org/10.11566/cmoshmcj.v12i1.20 Chatt Maa Shi Hosp Med Coll J 2013; 12(1): 9-11

Abstract P5-01-16: Value of ultrasonography appearance of breast mass in prediction of histologic type

Abstract Objective to determine the relationship of sonographic features to the histological typing and grading of breast mass. Methods: 292 breast masses were prospectively evaluated with ultrasonography. Sonographic features included irregular shape, microlobulation, spiculated margin, halo, posterior attenuation, microcalcification, ductal distortion. Lesion morphology was analyzed and correlated with histopathologic results, which included tumor typing and grading. Then we make a retrospective analysis and evaluation of patients scanned completely by qualitative and semi-quantitative methods. All patients have signed the informed consent form before the test, together with the recognition of the Ethics Committee. Resuls: Among these masses, there are breast cancer accounted for 45.89% (134/292), A rounded or lobular mass was strongly associated with ductal carcinoma in situ(DCIS), poorly differential invasive ductal carcinoma(IDC), or some of the specific invasive cancer. Mastitis accounted for 8.22% (24/292), fibroadenoma accounted for 43.84% (128/292), and phyllodes tumor accounted for 2.05% (6/292). In 134 breast cancer cases, 92.70% (127/134)have obviously sonographic features with justled growth was found around the turmor with lamellar necrosis in different extents and lympholeukocytic infiltration, microlobulation, speculated margin, halo, posterior attenuation, microcalcification, ductal distortion, with justled growth was found around the turmor, neoplastic cell array showed as massive nest, patchy and satin ribbon structure, and the membrane of tumor cells was unsharpness with less cytoplasma, round or oval nucleus, great heteromorphism, higher karyoplasmic ratio and common nuclear mitotic figures. Other 7 cases with fibrous tissue hyperplasia under microscope show a regular shape. In fibroadenoma, phyllodes tumor and mastitis team, they shows unobviously sonographic features and the cell morphology contrast with breast cancer are quite different. Conclusions:Ultrasonography appearance of breast masses is related to pathologic characteristics and can be a predictor of histopathologic pattern preoperatively. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-16.

Multimodal nonlinear microscopic investigations on head and neck squamous cell carcinoma: Toward intraoperative imaging

Prognosis and appropriate treatment of head and neck squamous cell carcinoma (HNSCC) depend on the tumor type routinely derived by invasive histopathology. A promising noninvasive alternative is nonlinear optical imaging, which is capable of in vivo tissue visualization for tumor typing and grading. Thin tissue sections from 3 patients aged 56 to 60 years presenting advanced carcinoma of the hypopharynx, larynx, and left tonsil were investigated by coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and 2 photon excited fluorescence (TPEF) to study the morphochemistry of the tissues. Morphologic alterations of prognostic significance, such as cell density, nuclear to cytoplasm ratio, and keratinization as well as the underlying compositional changes during malignant transformation were determined, such as the distributions of lipids, collagen, and autofluorophors. Nonlinear imaging provides a noninvasive optical biopsy of the epithelial layer comparable to staining microscopy. By integration into an operational microscope, routine screening of suspicious lesions and surgical guidance can be realized.

Molecular characterization of central neurocytomas: Potential markers for tumor typing and progression

Central neurocytomas (CNs) are rare intraventricular tumors presenting a favorable prognosis after surgery. Their transcriptomic profile is poorly characterized. We performed a microarray transcriptomic study to search for molecular markers that might improve diagnostic accuracy. Microarray analysis was performed on five CNs (3 primary and 2 recurrent CNs) using CodeLink human whole genome bioarrays, and the gene expression in CNs was compared with that in four pineal parenchymal tumors, consisting of two pineocytomas (PCs) and two pineoblastomas (PBs), other periventricular tumors which may present neuronal differentiation. We identified genes that were highly expressed in CNs compared to normal brain and might be candidates for the molecular typing of CNs. Several genes are part of the Wnt/β-catenin and sonic hedgehog signaling pathways or mainly linked to calcium function or maintenance of neural progenitors. Moreover, several genes are overexpressed in both CNs and PCs and/or PBs such as INSM1 and NEUROD4, involved in neural or neuroendocrine differentiation. The overexpression of eight candidate genes in CNs (CHRDL2, IGF2, KiSS-1, CAL2, NTS, NHLH1, RGS16 and SCGN) was confirmed by real-time RT-PCR. Of the genes overexpressed in the recurrent CNs compared to the primary CNs, AQP5, KiSS-1, FZD7, AURKB, UBE2C and PTTG1 are genes which may be involved in tumor progression. Our study shows the potential involvement of various genes in the pathogenesis of CNs. These genes could be potential candidate markers for improving the characterization of CNs and some could be involved in CN tumorigenesis.

Metabolomics of human breast cancer: new approaches for tumor typing and biomarker discovery

Breast cancer is the most common cancer in women worldwide, and the development of new technologies for better understanding of the molecular changes involved in breast cancer progression is essential. Metabolic changes precede overt phenotypic changes, because cellular regulation ultimately affects the use of small-molecule substrates for cell division, growth or environmental changes such as hypoxia. Differences in metabolism between normal cells and cancer cells have been identified. Because small alterations in enzyme concentrations or activities can cause large changes in overall metabolite levels, the metabolome can be regarded as the amplified output of a biological system. The metabolome coverage in human breast cancer tissues can be maximized by combining different technologies for metabolic profiling. Researchers are investigating alterations in the steady state concentrations of metabolites that reflect amplified changes in genetic control of metabolism. Metabolomic results can be used to classify breast cancer on the basis of tumor biology, to identify new prognostic and predictive markers and to discover new targets for future therapeutic interventions. Here, we examine recent results, including those from the European FP7 project METAcancer consortium, that show that integrated metabolomic analyses can provide information on the stage, subtype and grade of breast tumors and give mechanistic insights. We predict an intensified use of metabolomic screens in clinical and preclinical studies focusing on the onset and progression of tumor development.

Sa1630 A Prospective, Multicenter Study of the Evaluation of the Usefulness of Tumor Typing by Narrow Band Imaging for the Differential Diagnosis of Gastric Adenoma and Well-Differentiated Adenocarcinoma

Sa1630 A Prospective, Multicenter Study of the Evaluation of the Usefulness of Tumor Typing by Narrow Band Imaging for the Differential Diagnosis of Gastric Adenoma and Well-Differentiated Adenocarcinoma