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Histopathological analysis is the current gold standard in breast cancer diagnosis and management, however, as imaging technology improves, the amount of potential diagnostic information that may be demonstrable radiologically should also increase. We aimed to evaluate the potential clinical usefulness of 3-D phase-contrast micro-computed tomography (micro-CT) imaging at high spatial resolutions as an adjunct to conventional histological microscopy. Ten breast tissue specimens, 2 mm in diameter, were scanned at the SYRMEP beamline of the Elettra Synchrotron using the propagation-based phase-contrast micro-tomography method. We obtained $1.2~\mu \text{m}$ pixel size images, which were analyzed and compared with corresponding histological sections examined under light microscopy. To evaluate the effect of spatial resolution on breast cancer diagnosis, scans with four different pixel sizes were also performed. Our comparative analysis revealed that high-resolution images can enable, at a near-histological level, detailed architectural assessment of tissue that may permit increased breast cancer diagnostic sensitivity and specificity when compared with current imaging practices. The potential clinical applications of this method are also discussed.

The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

Rationale and Objectives This study employs clinical/radiological evaluation in establishing the optimum imaging conditions for breast cancer imaging using the X-ray propagation-based phase-contrast tomography. Materials and Methods Two series of experiments were conducted and in total 161 synchrotron-based computed tomography (CT) reconstructions of one breast mastectomy specimen were produced at different imaging conditions. Imaging factors include sample-to-detector distance, X-ray energy, CT reconstruction method, phase retrieval algorithm applied to the CT projection images and maximum intensity projection. Observers including breast radiologists and medical imaging experts compared the quality of the reconstructed images with reference images approximating the conventional (absorption) CT. Various radiological image quality attributes in a visual grading analysis design were used for the radiological assessments. Results The results show that the application of the longest achievable sample-to-detector distance (9.31 m), the lowest employed X-ray energy (32 keV), the full phase retrieval, and the maximum intensity projection can significantly improve the radiological quality of the image. Several combinations of imaging variables resulted in images with very high-quality scores. Conclusion The results of the present study will support future experimental and clinical attempts to further optimize this innovative approach to breast cancer imaging.

The aim of this study was to highlight the advantages that propagation-based phase-contrast computed tomography (PB-CT) with synchrotron radiation can provide in breast cancer diagnostics. For the first time, a fresh and intact mastectomy sample from a 60 year old patient was scanned on the IMBL beamline at the Australian Synchrotron in PB-CT mode and reconstructed. The clinical picture was described and characterized by an experienced breast radiologist, who underlined the advantages of providing diagnosis on a PB-CT volume rather than conventional two-dimensional modalities. Subsequently, the image quality was assessed by 11 breast radiologists and medical imaging experts using a radiological scoring system. The results indicate that, with the radiation dose delivered to the sample being equal, the accuracy of a diagnosis made on PB-CT images is significantly higher than one using conventional techniques.

The successful introduction of trastuzumab and other novel tyrosine kinase inhibitors (TKI) for treatment of HER2-positive breast carcinoma has resulted in lengthened survival for affected patients. In the context of this increased survival time, it has since emerged that patients who would otherwise have succumbed to the systemic progression of their disease have an increased propensity to develop metastases within the central nervous system (CNS) when compared with their HER2-negative counterparts.1 Recent literature shows that these metastatic deposits respond poorly to TKI therapy, most likely due to their inability to penetrate the blood brain barrier.2 We write to inform you of the first known reported case documenting a HER2-positive breast carcinoma metastasising to an intracranial meningioma, without evidence of additional CNS involvement. This report serves to highlight our increasing understanding of the pathogenesis of brain metastasis, and how this growing knowledge should …

In situ localisation of follicular lymphoma (ISLFL) is an emerging diagnostic concept, with only a small volume of cases reported in the literature. We present two cases of diffuse large B-cell lymphoma (DLBCL), in lymph node (patient A) and oral mucosa (patient B), each harbouring concurrent ISLFLand discuss the morphological, immu-nohistochemical and molecular features of this diagnosis. Biopsies from these patients showed partial tissue effacement by DLBCL, with unexpanded, reactive follicles present in adjacent parenchyma. Immunohistochemistry showed strong CD10 and bcl-2 posi-tivity in some of these seemingly benign follicles, in keeping with ISLFL. In patient B, DLBCL and ISLFLcomponents were separately submitted for gene rearrangement studies, which showed no immunoglobulin heavy chain monoclonality (Fr3 V and conserved J regions) in either component, but did reveal positive result for Bcl-2/IgH t(14;18) gene rearrangement in both the DLBCL and ISLFLcomponents. Usually discovered incidentally during immunohistochemical investigation, ISLFLhas been found in association with synchronous follicular lymphoma and a range of other lymphoma types. In addition, ISLFLhas also been demonstrated in patients without any overt lymphoid malignancy. These two cases highlight the histological and immunohistochemical features of ISLFLand raise the discussion of potential molecular pathogenesis along with questions about the prognosis and appropriate treatment of affected patients.

We present a unique autopsy case of a 61-year-old female with concurrent renal and multi-focal pulmonary angiomyolipomata (AML) in the setting of pulmonary lymphangioleiomyomatosis (LAM), and in the absence of documented tuberous sclerosis. There are no previously reported cases of pulmonary AML in the setting of LAM. The patient had undergone single lung transplantation 12 months prior to presenting with severe acute fibrinoid organising pneumonia in her donor lung. Despite full treatment she died 3 months following admission. Imaging revealed multiple tumours in the right kidney and left retroperitoneum, consistent with large angio-myolipomata. A left nephrectomy for a ‘benign tumour’ was performed 45 years previously. Limited post-mortem examination of the native lung revealed marked cystic change and two 3 mm homogenous yellow parench-ymal nodules. Histological examination showed cystic dilatation and a patchy proliferation of interstitial human melanoma black 45 (HMB45)-positive spindled cells consistent with LAM. The nodules were well-circumscribed, composed of mature adipocytes, small blood vessels and bland spindled cells with occasional epithelioid forms exhibiting positive staining with HMB45, smooth muscle actin and myosin, consistent with a diagnosis of AML. On review, these lesions were not seen on repeated antemortem imaging. This case illustrates that pulmonary lesions morphologically and immunohistochemically identical to AML can rarely co-exist with LAM and renal AML, and that they may be small, multiple and undetectable by imaging. We recommend that all lungs with known or suspected LAM be carefully examined for such lesions.