To compare the diagnostic accuracy of computed tomography (CT), magnetic resonance (MR) imaging, and ultrasonography (US) in the detection of necrosis in metastatic cervical nodes from patients with ...head and neck squamous cell carcinoma.
Twenty-seven patients (age range, 39-85 years; mean age, 62 years) with squamous cell carcinoma in the head and neck underwent CT, MR imaging, and US. Three radiologists evaluated the images for nodal necrosis. The results of each modality were analyzed for sensitivity, specificity, and accuracy. Pathologic analysis of the surgical resection served as the reference standard. The three modalities were compared for specificity and sensitivity with the McNemar test.
Pathologic examination revealed 903 nodes, of which 89 were malignant. Of the malignant nodes, 43 were necrotic. Analysis of the detection of necrosis in the 89 malignant nodes showed an accuracy, sensitivity, and specificity of 92%, 91%, and 93% for CT; 91%, 93%, and 89% for MR imaging; and 85%, 77%, and 93% for US, respectively. All imaging modalities failed to depict necrotic areas of 3 mm or smaller in three nodes, and necrosis was missed in an additional seven nodes with US and in one node with CT. Necrosis could not be distinguished from other components of malignancy, such as viable tumor and scar tissue, in seven nodes (CT, 3; MR imaging, 5; US, 3). The sensitivity of both MR imaging and CT was significantly better than that of US (P =.0082 and P =.0339, respectively). There was no significant difference in sensitivity (P =.3173) between MR imaging and CT, or in the specificity of the three modalities.
MR imaging is comparable to CT for the detection of necrosis. The sensitivity of MR imaging and CT is better than that of US.
T2-weighted MRI shows potential in early posttreatment assessment of the primary tumor. Residual masses composed entirely of low T2-signal scar tissue suggest local control and those ≥1 cm of similar ...signal to untreated tumor suggest local failure. The purpose of this study was to investigate the diagnostic accuracy of T2-weighted MR imaging early after chemoradiotherapy for identifying primary tumor treatment failure in squamous cell carcinoma of the head and neck.
At 6 weeks after treatment, T2-weighted MR images of 37 primary tumors in 37 patients were assessed. Residual masses were divided into 3 patterns: pattern 1 = scar tissue only (flat-edged/retracted mass of low T2 signal intensity); pattern 2 = mass without features described in pattern 1 or 3; and pattern 3 = any pattern that included an expansile mass ≥1 cm of intermediate T2 signal intensity (similar grade of signal intensity to the untreated tumor). T2 patterns were analyzed for local outcome (Fisher exact test) and time to local failure (univariate and multivariate analysis of T2 pattern, age, T stage, and tumor size by use of the Cox regression model).
Residual masses after treatment were present in 34 (92%) of 37 patients. Local failures occurred in residual masses with pattern 1 in 0 (0%) of 14 patients; pattern 2 in 6 (55%) of 11 patients; and pattern 3 in 9 (100%) of 9 patients. Significant associations were found between local control and pattern 1 (P = <.0001; sensitivity, 74%; specificity, 100%; PPV, 100%; NPV, 75%; accuracy, 85%), and between local failure and pattern 3 (P = <.0001; sensitivity, 60%; specificity, 100%; PPV, 100%; NPV, 76%; accuracy, 82%). Pattern 2 showed no significant associations with local outcome. Univariate analysis of time to local failure showed that the T2 pattern was significant (P < .0001) and remained significant on multivariate analysis.
T2-weighted MR imaging is a potential tool for early posttreatment assessment of primary HNSCC treatment response. Awareness of correlation of the T2 pattern of any residual mass with treatment outcome at the primary site may contribute to patient treatment.
The wingless-type (Wnt) signalling transduction pathway is essentially a network of a number of separate but interacting pathways. Specific Wnt ligands bind to their target 'frizzled' membrane ...receptor and interfere with the multi-protein destruction complex, resulting in downstream activation of gene transcription by β-catenin. Simplistically, the multiprotein destruction complex involves Axin and APC serving as scaffolds binding both β-catenin and GSK3, to facilitate phosphorylation of β-catenin by GSK-3β. Phosphorylated β-catenin is degraded in proteasomes by the ubiquination machinery. Unphosphorylated β-catenin accumulates and associates with nuclear transcription factors leading to the eventual transcription and expression of target genes such as c-myc, c-jun, Fra and cyclin D1. There are several regulatory mechanisms for the down-regulation of the Wnt/β-catenin signal, perhaps reflecting the pivotal nature of the pathway and the detrimental consequences of inappropriate activation. There has been intense investigation into the role of Wnt genes in human cancer. Although no documentation is made of any mutation or amplification of genes encoding Wnt ligands or receptors linked to human cancer to date, several components of the Wnt pathway have been implicated in carcinogenesis, especially APC and β-catenin.
The purpose of this study was to describe the features of symptomatic ductal carcinoma in situ (DCIS) of the breast shown on high-resolution sonography and to correlate them with findings from ...mammography and histopathology to evaluate the prognostic ability of sonographic findings.
We retrospectively reviewed mammographic and sonographic images of 60 DCIS lesions from 55 symptomatic women. Images were reviewed by a radiologist who knew that the patients had DCIS but had no other information regarding pathology. Lesions were evaluated pathologically and classified using the Van Nuys classification system. Statistical comparisons were made using Fisher's exact test.
Of the 60 lesions, 33 were classified as Van Nuys group 1, 19 as Van Nuys group 2, and eight as Van Nuys group 3. Six (10%) of the 60 lesions were not visible on sonography, and 12 lesions (20%) were not visible on mammography. Sonography revealed a mass in 43 cases (72%), ductal changes in 14 cases (23%), and architectural distortion in four cases (7%). Eight lesions had more than one of these features. A sonographically visualized, irregularly shaped mass with indistinct or angular margins and no posterior acoustic shadowing or enhancement was associated with a high Van Nuys classification (p < 0.05). Microcalcifications were visible on sonography in 13 (22%) of the 60 lesions or on mammography in 25 lesions (42%). Both findings were associated with a high Van Nuys classification (p < 0.05).
Although sonography can reveal microcalcifications within masses, it is unreliable in depicting and characterizing the morphology and extent of microcalcifications, particularly when they are in isolation. Therefore, sonography should not be used to replace mammography but instead as an adjunctive tool to increase the sensitivity of mammography in breast diagnosis.
Background: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness ...and is aetiologically linked to a new coronavirus (SARS-CoV). Methods: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. Results: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. Conclusions: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.
To assess the clinical usefulness of localized proton (hydrogen 1) magnetic resonance (MR) spectroscopy in the characterization of contrast material-enhanced breast lesions on the basis of choline ...detection.
Examinations were performed at 1.5 T with use of a standard breast coil. Contrast-enhanced MR imaging was performed in 30 consecutive patients (mean age, 50 years; age range, 20--80 years) who had nonspecific lesions (>1.5 cm in diameter) on sonograms or mammograms. Single-voxel (1)H MR spectroscopy was performed in the enhancing lesions by using a point-resolved spectroscopic sequence with echo times of 38, 135, and 270 msec. MR spectroscopic and histopathologic findings were determined in blinded fashion and compared.
Twenty-four patients had carcinoma of the breast (tumor size, 2.0--11.2 cm; mean, 4.7 cm), and six had benign lesions (lesion size, 1.8--3.8 cm; mean, 2.7 cm). Choline was detected in 22 patients with carcinoma. Choline was not detected in five patients with benign lesions and in two patients with carcinoma. The preliminary results indicate that this technique had a sensitivity of 92%, specificity of 83%, and accuracy of 90%.
Choline can be reliably detected in less than 45 minutes in large contrast-enhanced breast lesions by using a multiecho point-resolved spectroscopic protocol. The presence of water-soluble choline metabolites obtainable with (1)H MR spectroscopy could complement MR imaging findings to improve specificity and to reduce the number of unnecessary biopsies.
To assess the relationship between breast cancer subtypes and choline detection by using in vivo proton magnetic resonance (MR) spectroscopy and to assess the feasibility of proton MR spectroscopy in ...the study of axillary lymph node metastases.
Breast and lymph node MR spectroscopy of lesions identified at contrast material-enhanced MR imaging was performed in 39 patients with breast cancer. Spectroscopic and histopathologic findings were determined and compared. The sensitivity, specificity, and accuracy of the MR spectroscopic technique in the detection of axillary lymph node metastases were determined.
There were four cases of ductal carcinoma in situ (DCIS) and 34 invasive carcinomas, including three with an extensive in situ component. Twenty-six breast lesions were positive for choline at MR spectroscopy; nine, negative; and three, failed cases (ie, determination of positive or negative for choline could not be made). No data were available for one lesion. Four of the nine negative findings were DCIS; three, infiltrating ductal carcinoma (IDC) with an extensive in situ component; and two, IDC. Fourteen axillary lymph nodes were positive for choline; 17, negative; and four, failed cases. No data were available for four nodes. Comparison of the preliminary diagnostic indexes of the MR spectroscopic technique with the ultrasonographically guided fine-needle aspiration biopsy findings in lymph nodes revealed a sensitivity of 82%, specificity of 100%, and accuracy of 90%.
Choline is consistently detected in IDC. DCIS and IDC with an extensive in situ component are likely to be negative for choline at MR spectroscopy. In vivo proton MR spectroscopy of axillary lymph nodes in patients with breast cancer is feasible and has encouraging preliminary results.
Proton MR spectroscopy is a recently described technique with high sensitivity and specificity for differentiating breast carcinoma from benign lesions. We evaluated the possible relationship between ...spectroscopy results and the tumor proliferative index, angiogenesis, and HER2/neu oncogene overexpression. SUBJECTS AND METHODS. We prospectively evaluated 19 breast carcinomas, 21 benign breast lesions (including 18 fibroadenomas, one fibrocystic change, one hamartoma, and one papilloma), and six phyllodes tumors (four benign, two of borderline malignancy) using proton MR spectroscopy. All lesions were larger than 1.5 cm. Tumor Ki-67 proliferative index, tumor angiogenesis, and HER2/neu oncogene overexpression were evaluated by immunohistochemistry of the histologic material.
Spectroscopy findings were positive in 17 (89%) of 19 carcinomas but negative for all benign lesions and phyllodes tumors (sensitivity, 89%; specificity, 100%). Significantly higher levels were obtained for all biologic parameters in carcinomas compared with benign lesions and phyllodes tumors. HER2/neu oncogene overexpression was present in 37% of carcinomas but not in other lesions. The two false-negative findings of breast carcinoma showed similar Ki-67 proliferative index and microvessel density compared with the remaining carcinomas, but both cases were negative for HER2/neu overexpression.
Proton MR spectroscopy is useful in the in vivo characterization of breast masses when the lesion exceeds 1.5 cm in maximal dimension. Spectroscopy is unable to reveal benign breast lesions and phyllodes tumors of benign and borderline malignancy. We suggest that a false-negative spectroscopic result may be related to an absence of HER2/neu overexpression in carcinoma of the breast.
Abstract
Background: Aberrant signaling via the PI3K pathway is a common alteration in breast cancer (BC), with frequent activating mutations in the PIK3CA gene helical (exon 9) and catalytic (exon ...20) domains. These mutations occur across all BC subtypes with an overall incidence of 36%, with the highest frequency (∼45%) in luminal A/ER+ tumors. Lobular phenotype is common among luminal A tumors. We examined associations between lobular histology and molecular features among BC samples submitted for comprehensive molecular analyses for The Cancer Genome Atlas (TCGA).
Design: Experts in breast pathology reviewed digital slides of breast cancer samples submitted for comprehensive molecular profiling to the TCGA. Tumors were graded, subtyped and scored for additional histopathologic features. We tested pairwise associations between lobular features and components of grade, PAM50-derived molecular subtype and mutational status for BRAC1/2, PIK3CA, TP53 and CDH1 by performing Chi-Square analysis for comparisons with a categorical variable and the Mann-Whitney test for comparisons with an ordinal variable
Results: A total of 1132 images were scored from 589 unique cases in TCGA. For cases with multiple scorers (43% of cases), we summarized scores by taking the median (for ordinal variables) or the consensus diagnosis (for categorical variables). A total of 567 cases had a consensus diagnosis for lobular features, all of which had pathological information on components of histologic grade and 540 of which had data for TP53, CDH1, and PIK3CA mutations. 110/567 (19%) of cases were classified as invasive lobular or invasive mammary carcinoma with lobular features. The lobular cases had significantly less nuclear pleomorphism (p = 3.3 e -12), lower mitotic index (p = 3.4e-16), less tubule formation (p = 3.9e-8), increased association with lobular carcinoma in situ (p < 2.2 e-16), decreased stromal inflammation (p = 1.5e-7), and decreased necrosis (p = 4.4e-11) compared with cases without lobular features. Cases with lobular features were highly enriched for CDH1 mutations with 19% of cases with lobular features having CDH1 mutations, compared with only 1% of cases without lobular features (p = 2.4 e-14). The lobular features cases were more likely to have PIK3CA mutations (p = 0.01), with 33% of the lobular features cases having PIK3CA mutations, compared with 21% of the non-lobular cases. The lobular features cases were less likely to have TP53 mutations (p = 0.02), with 13% of lobular features cases having TP53 mutations as compared with 24% of the non-lobular feature cases. Lobular status was associated with PAM50 molecular subtype (Chi-square p = 0.002) with the lobular cases significantly less likely to be basal molecular subtype and more likely to be Luminal-A.
Conclusions: PIK3CA mutations are enriched in invasive lobular carcinomas and invasive mammary carcinomas with lobular features. These associations point to the possibility that PIK3CA mutations as well as CDH1 alterations are important drivers of invasive lobular carcinomas.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-05-10.
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