Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review.

Clear cell sarcoma is an uncommon sarcoma which rarely occurs as a primary tumour in the gastrointestinal tract (CCS-GIT). It shares common molecular genetic abnormalities with the more recently described entity, malignant gastrointestinal neuroectodermal tumour (GNET) but is distinguished by its morphological and immunohistochemical findings. The exact nosological relationship between these tumours continues to be debated. In this review, we present two cases of these rare neoplasms from our files and perform a statistical comparison of all published cases to determine if significant differences exist in their clinicopathological features and biological behaviour. Thirteen cases of CCS-GIT and 58 of GNET were included. CCS-GIT occurred more commonly in males (84.6% vs 46.6%, p = 0.01) and in an older age group (median 57 vs 33 years, p < 0.01). There was no significant difference in their location in the gastrointestinal tract, median tumour size and proportion of cases with an EWSR1-ATF1 vs EWSR1-CREB1 fusion. Median survival for CCS-GIT was 13.5 months and for GNET, 9.5 months (p = 0.78). There was no significant difference in the Kaplan-Meier survival curves for either time to first metastasis (p = 0.88) or overall survival (p = 0.18), including after controlling for tumour size using regression models. Our analysis confirms that aside from morphological variations between these tumours, they also exhibit epidemiological and clinical differences. Despite the prevalent perception that GNET is associated with a more aggressive clinical course, our findings indicate that there is no significant difference in their biological behaviour, although both clearly share a bleak prognosis. Further experience is awaited to determine optimal treatment strategies and whether CCS-GIT and GNET would differ in their response to various therapies.

MDM2/CDK4 gene amplification in large/deep-seated 'lipomas': incidence, predictors and clinical significance.

This study of 140 cases assessed the incidence of MDM2/CDK4 gene amplification in lipomatous neoplasms with histological features of a lipoma but which were of clinical concern due to large size (≥50 mm) and/or deep-seated (subfascial) location. Univariate and multivariate statistical analyses were used to identify clinical, radiological and pathological predictors of gene amplification. Differences in local recurrence rates between amplified and non-amplified cases were assessed using survival analysis. The findings indicate that the incidence of MDM2/CDK4 amplification in this setting is low at 5% (95%CI 1.4-8.6%). Variables associated with amplification on univariate analysis were tumour site (thigh, p = 0.004), size (>100 mm, p = 0.033) and presence of equivocal atypia (p = 0.001). Independent predictors on multivariate analysis were size (OR 3.9, 95%CI 1.4-11.3, p = 0.012) and presence of equivocal atypia (OR 12.5, 95%CI 1.9-80.3, p = 0.008). There was no significant difference in local recurrence rates between amplified and non-amplified cases (p = 0.461) based on a median follow-up time of 31 months. Assessment for MDM2/CDK4 amplification, therefore, should be considered in 'lipomas' which are >100 mm in size, show equivocal atypia and arise in the thigh. However, the clinical significance of gene amplification in this setting is unclear and requires confirmation in larger studies.

Ultrasound-guided optical coherence tomography needle probe for the assessment of breast cancer tumor margins.

OBJECTIVE: The purpose of this study was to evaluate a new imaging technique for the assessment of breast cancer tumor margins. The technique entails deployment of a high-resolution optical imaging needle under ultrasound guidance. Assessment was performed on fresh ex vivo tissue samples. CONCLUSION: Use of the ultrasound-guided optical needle probe allowed in situ assessment of fresh tissue margins. The imaging findings corresponded to the histologic findings.

Assessing HER2 amplification in breast cancer: findings from the Australian In Situ Hybridization Program.

In August 2006, the Australian government approved subsidized trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, and it was mandated that HER2 testing should be performed using in situ hybridization (ISH) rather than immunohistochemistry (IHC). Here we review results of the first regulated, nationwide program to provide HER2 ISH testing for all newly diagnosed breast cancer patients, with a particular emphasis on cases where IHC and ISH results were discordant. Data from all laboratories participating in the program were collated. Cases with an equivocal ISH test result [by chromogenic ISH (CISH) or silver ISH (SISH)] were tested centrally by fluorescence ISH. Most laboratories also performed HER2 IHC, and 200 cases with discordant IHC and ISH results were selected for further analysis in a central laboratory. A total of 26 laboratories were involved and 53,402 tests were reported. Over a 4-year period the HER2 positivity rate decreased for primary cancers from 23.8 to 14.6 %, but remained relatively constant for samples from metastases. Average ISH reporting times were <5 days for all yearly reporting periods. Test-repeat rates decreased for CISH (8.9-3.6 %) and SISH (13.7-8.4 %). Only 12 of 196 cases remained discordant after retesting in a central laboratory. These findings demonstrate the successful implementation of a regulated, national program that continues to collect data on HER2 status. The results also highlight the differences in IHC interpretation between local laboratories and a central, more experienced, laboratory. This model could be used to establish future biomarker-testing programs in other countries.

Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography.

We report the use of optical coherence tomography (OCT) to determine spatially localized optical attenuation coefficients of human axillary lymph nodes and their use to generate parametric images of lymphoid tissue. 3D-OCT images were obtained from excised lymph nodes and optical attenuation coefficients were extracted assuming a single scattering model of OCT. We present the measured attenuation coefficients for several tissue regions in benign and reactive lymph nodes, as identified by histopathology. We show parametric images of the measured attenuation coefficients as well as segmented images of tissue type based on thresholding of the attenuation coefficient values. Comparison to histology demonstrates the enhancement of contrast in parametric images relative to OCT images. This enhancement is a step towards the use of OCT for in situ assessment of lymph nodes.

Ependymomas with neuronal differentiation: a morphologic and immunohistochemical spectrum.

The category of mixed glioneuronal tumors of the CNS is rapidly losing its definition as encompassing tumors composed of histologically distinct neuron variants and glia. We encountered five ependymomas with neuronal differentiation seen in two by histology, in two by immunohistochemistry alone, and in one by electron microscopy. Antibodies against GFAP, S-100 protein, neurofilament protein, chromogranin, synaptophysin, Neu-N, and EMA were applied. Ultrastructural studies were also performed. In addition, 33 randomly selected ependymomas of various histologic types were screened for these same antigens. Cases 1 and 2 were anaplastic and showed clearly defined neuropil islands or pale islands as in nodular desmoplastic medulloblastoma, respectively. The tumors affected a 16-year-old male and a 5-year-old female and involved the right frontoparietal lobe and fourth ventricle, respectively. The islands were positive for synaptophysin and Neu-N (cases 1 and 2), and chromogranin (case 1). Cases 3-5, as well as 7 of the 33 screened ependymomas, showed a suggestion of neuronal differentiation by immunohistochemistry alone, including immunoreactivity for Neu-N (n = 8), synaptophysin (n = 4), neurofilament protein (n = 4), and chromogranin (n = 2). Five tumors each were WHO grade II and III. Electron microscopy performed on the two cases with neuronal islands demonstrated microtubule bundles and dense core granules (case 1) and poorly differentiated cells with high nuclear/cytoplasmic ratios, with intermediate filament accumulation and rare cilia (case 2). Cases identified by immunohistochemistry or electron microscopy demonstrated dense core granules (n = 5) and aligned microtubules (n = 3). Neuronal differentiation occurs in ependymomas but is less frequently definitive (histologic, ultrastructural) than merely a limited immunohistochemical finding. The clinical significance of these observations is unknown but deserves further exploration.