Background Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy. Methods Thirty-six patients with untreated primary breast cancer were recruited to a window study and transcriptomic profiling of tumour samples carried out before and after metformin treatment. Results Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic level and there was a differential change in expression between two previously identified cohorts of patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation gene composite signature correlated with change in a proliferation gene signature. In vitro assays showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK activation. Conclusions We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells with implications for patient selection and drug combinations. Clinical Trial Registration NCT01266486.

Abstract Background: Despite advances in the treatment of breast cancer, there remains a significant clinical need for improved therapeutic strategies for patients with the most aggressive types of tumors. In particular, knowledge of the specific genes and pathways driving tumor growth in these patients would allow for treatment with therapeutics directed against these molecular targets. To this end, we reasoned that through the integrated analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and gene expression profiling we could understand the molecular mechanisms associated with an aggressive imaging phenotype and thus gain insight into potential therapeutic targets for these patients. Materials and Methods: We studied 61 patients with locally advanced breast cancer, for whom DCE-MRI scans and core biopsies were available prior to the start of neoadjuvant chemotherapy. To analyse the DCE-MRI data, we used Tofts' pharmacokinetic (PK) model to quantify the rate constant kep that governs the washout of contrast agent from the tumor extravascular extracellular space. We chose to focus on the PK parameter kep since our analysis showed that it can be estimated reliably from the low temporal resolution diagnostic DCE-MRI scans that are routinely performed in the clinic. We extracted mRNA from formalin fixed paraffin embedded core biopsy samples and measured gene expression using Affymetrix U133 whole genome arrays. Following normalization and pre-processing, we used significance analysis of microarrays (SAM) to determine which genes were statistically significantly correlated with median kep. Results: Using a local false discovery rate of 5% resulted in a total of 328 genes that were significantly positively correlated with median kep. These included copper transporter like solute carrier family31member2 (SLC31A2), cancer stem cell (CSC) related genes such as CD44, aldehyde dehydrogenase family 1 member A3 (ALDH1A3), and integrin alpha-6 (ITGA6), hypoxia regulated genes such as hypoxia inducible factor 1a (HIF1a), kinases such as eukaryotic translation initiation factor2-alpha kinases (EIF2AK2, EIF2AK1), and pyruvate dehydrogenase kinases (PDK1, PDK3). Discussion: Our results illustrate how functional imaging modalities such as DCE-MRI can be combined with gene expression profiling to provide insight into molecular targets that may have important therapeutic implications in breast cancer. We found that locally advanced breast cancers with high vascular permeability and/or blood flow, as quantified by the washout parameter median kep, were associated with an up-regulation of genes related to CSCs and copper metabolism, the latter of which is known to play a role in angiogenesis. In addition, up-regulation of hypoxia related genes such as HIF1a, EIF2AK1&2 and PDK1&3 may promote tumor survival and spread under stress. Our results suggest that locally advanced breast cancers with high vascular permeability and/or blood flow may benefit from therapies directed at one or more of these molecular targets. Furthermore, functional imaging with DCE-MRI may be helpful as a noninvasive means of selecting and monitoring therapy against these targets. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-01-01.

Abstract Background: Recently the FDA has withdrawn the indication for bevacizumab in metastatic breast cancer after several clinical studies failed to demonstrate an overall survival benefit. These studies however did report an increase in response rates to chemotherapy and improvement in progression free survival, suggesting a pattern of response to the drug followed by the development of resistance. We have little knowledge of the molecular mechanisms driving the development of resistance to bevacizumab. To better understand these mechanisms, we have conducted a window of opportunity study using a single cycle of bevacizumab with detailed pharmacodynamic assessments using gene expression arrays and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods: After ethical approval, 47 newly diagnosed locally advanced breast cancer patients were prospectively enrolled in this trial. Patients received single dose bevacizumab (15mg/ kg) 2 weeks prior to neoadjuvant chemotherapy and underwent core biopsies for gene expression and immunohistochemistry analysis and DCE-MRI scans before and 2 weeks after bevacizumab. 35 patients who had invasive ductal carcinoma together with good quality MRI scans and core biopsies before and after bevacizumab were included in this analysis. Pharmacokinetic (PK) modelling techniques were used to quantify PK parameters (Ktrans, kep, ve) from the DCE-MRI data. Gene expression profiling was performed using the Affymetrix Human Exon 1.0 ST arrays. Results: The majority of patients (28/35) showed a significant reduction in vessel permeability and blood flow of at least 30% following bevacizumab, with a mean decrease in the forward transfer constant (P < 0.0001) and the reverse rate constant kep (P < 0.0001). From gene expression and immunohistochemistry analyses, we identified several key metabolism-related genes that are significantly up-regulated after bevacizumab treatment, including pyruvate dehydrogenase kinase isozyme 1 (PDK1) (fig.1) and carbonic anhydrase 9 (CA9). In addition, we found a number of interesting genes that are down-regulated after bevacizumab treatment, including sulfatase-1 (SULF1), and cyclin E1 (CCNE1). Discussion: This study highlights that the combination of DCE-MRI and gene expression arrays can lead to an improved understanding of the molecular mechanisms governing response and resistance to anti-angiogenic therapy. Heterogeneity of response to bevacizumab was demonstrated, with some tumours showing increases or no change in Ktrans and others marked reductions, which may be of value in early stratification for therapy maintenance. Furthermore, the gene expression analysis showed activation of pathways, which could contribute to the development of resistance. For example, we observed significant up regulation of genes involved in regulating the switch from mitochondrial metabolism to glycolysis, such as PDK1. This suggests that using bevacizumab with the other targeted agents such as Dichloroacetate, a PDK1 inhibitor might be helpful in overcoming the development of resistance and ultimately lead to improved patient survival. Our preclinical studies strongly support this possibility. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-06-01.

Free AccessCase of the monthLumpy breasts and headache – a crucial ultrasoundS Hinze, Y M Hart and R F AdamsS HinzeDepartment of Neurology, John Radcliffe Hospital, Oxford Radcliffe Hospitals NHS Trust, Oxford UK Search for more papers by this author, Y M HartDepartment of Neurology, John Radcliffe Hospital, Oxford Radcliffe Hospitals NHS Trust, Oxford UK Search for more papers by this author and R F AdamsOxford Breast Imaging Centre, Churchill Hospital, Oxford Radcliffe Hospitals NHS Trust, Oxford UK Search for more papers by this authorPublished Online:13 Feb 2014https://doi.org/10.1259/bjr/23418860SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail AboutA 65-year-old female was recalled to a breast assessment clinic 2 weeks after a routine screening mammogram because she had told the mammographer she had noticed a new lump in her right breast. Her mammogram showed mixed density breast tissue but no suspicious findings. The original lump had subsided since the mammogram, but she had noticed further mildly tender lumpiness developing in both breasts and a string-like thickening in her right axillary tail.On clinical examination, there was mild tender non-suspicious nodularity in both breasts, with no underlying abnormality on ultrasound. However, ultrasound revealed the palpable band in the right axillary tail to be an artery with a 24 mm segment of circumferential wall thickening (Figure 1).Figure 1 Longitudinal ultrasound image of band-like thickening in right axillary tail, showing “halo sign” (hypoechoic circumferential wall thickening representing oedema) in lateral thoracic artery. Asterisks denote lumen of artery and arrowheads denote exterior of wall. Download Figure On further questioning she reported she had been suffering from a frontal headache for 1 month and was generally feeling tired.What diagnosis could account for these signs and symptoms? What would you do next?DiagnosisGiant cell arteritis was suspected by the radiologist. Examination of the patient's temporal arteries revealed them to be nodular and mildly tender. She was referred immediately for assessment by the neurology team. Her erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were checked en route to the neurologist and were 89 mm h-1 and 23 mg l-1, respectively. She was immediately prescribed 60 mg prednisolone per day. A temporal artery biopsy the following day confirmed the diagnosis of giant cell arteritis (GCA). Her symptoms rapidly improved over the following 2 weeks, including her breast lumps.DiscussionThis patient met all five American College of Rheumatology (ACR) criteria for GCA i.e. over 50 years, new onset headache, temporal artery tenderness or decreased pulse, ESR >50 mm h-1 and positive temporal artery biopsy. The presence of 3 or more criteria yields a sensitivity of 93.5% and specificity of 91.2% [1].GCA has an insidious onset and is often diagnosed late, after major cardiovascular sequelae have occurred. There are a few reports of GCA causing breast lumps, which are usually tender [2]. In many of these cases the diagnosis was only made after, potentially unnecessary, surgical excision. Breast pain is uncommon in post-menopausal women, but in the era of “breast awareness” tender breast lumps may be the presenting symptom of some women with GCA.GCA typically affects branches of the carotid and subclavian arteries, and sometimes the aorta and femoropopliteal arteries [1]. The two main arteries supplying the breast, the lateral thoracic artery and the internal mammary artery are both branches of the subclavian artery. The lateral thoracic artery branch in this woman showed the “halo” sign, a hypoechoic circumferential wall thickening representing oedema [3].Temporal artery biopsy may be negative in patients with a clinical diagnosis of GCA owing to the segmental nature of the inflammation [1,4,5]. Ultrasonography of the temporal arteries is used in some centres as an adjunctive diagnostic method and to select a biopsy site [3]. A recent meta-analysis of temporal artery ultrasonography showed presence of the halo sign had a sensitivity of 69% and specificity of 82% when compared with biopsy. When the features of stenosis or occlusion were added in, the combined sensitivity was 88% [4]. In a few centres with expertise in temporal artery ultrasonography, it has replaced biopsy in patients with a typical presentation of GCA [3,5]. High resolution contrast-enhanced MRI has also been used to demonstrate arterial wall thickening [1,3]. Fluorodeoxyglucose positron emission tomography shows large vessel involvement which can be asymptomatic [1,3].It is important that the incidental ultrasound finding of a thickened arterial wall should lead to immediate further action. A more detailed history and examination should be sought with regards to signs and symptoms of giant cell arteritis, and inflammatory markers should be checked. Same day referral for specialist clinical assessment and treatment is required to prevent irreversible visual loss and other serious vascular sequelae [1], even if the finding is unexpected.AcknowledgmentWe would like to thank the patient for readily giving her permission to report her case. She hopes this might facilitate appropriate treatment of other women in a similar situation.Reference1 Salvarani C , Cantini F , Hunder GG . Polymyalgia rheumatica and giant-cell arteritis. Lancet 2008;372:234–45. Crossref Medline ISI, Google Scholar2 Marie I , Audeguy P , Francois A , DE Kergal F , Richard C . Giant cell arteritis presenting as a breast lesion: report of a case and review of the literature. Am J Med Sci 2008;335:489–91. Crossref Medline ISI, Google Scholar3 Blockmans D , Bley T , Schmidt W . Imaging for large-vessel vasculitis. Curr Opin Rheumatol 2009;21:19–28. Crossref Medline ISI, Google Scholar4 Karassa FB , Matsagas MI , Schmidt WA , Ioannidis JP . Meta-analysis: test performance of ultrasonography for giant-cell arteritis. Ann Intern Med 2005;142:359–69. Crossref Medline ISI, Google Scholar5 Alberts MS , Mosen DM . Diagnosing temporal arteritis: duplex vs. biopsy. QJM 2007;100:785–89. Crossref Medline ISI, Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited bySystemic vasculitis involving the breast: a case report and literature review14 March 2019 | Rheumatology International, Vol. 39, No. 8Characteristics of Systemic Diseases in the Breast: Clinical, Imaging and Pathologic Features1 September 2012 | Women's Health, Vol. 8, No. 5 Volume 84, Issue 1000April 2011Pages: 293-e88 2011 The British Institute of Radiology History RevisedSeptember 06,2010ReceivedJuly 03,2010AcceptedSeptember 20,2010Published onlineFebruary 13,2014 Metrics AcknowledgmentWe would like to thank the patient for readily giving her permission to report her case. She hopes this might facilitate appropriate treatment of other women in a similar situation.Download PDF

Neoadjuvant chemotherapy is used as the primary treatment for locally advanced breast cancer to reduce tumour size and protect against metastatic spread. Monitoring the response to chemotherapy is achieved mainly by clinical assessment, which may prove unsatisfactory. This proof-of-principle study is to determine if changes of size and texture in the elastogram can track tumour response.

Abstract Background: Anti-angiogenic therapy holds much promise for the treatment of breast cancer. In practice however, only a subset of patients who receive these drugs demonstrate a significant response to therapy. A key challenge therefore is to elucidate markers that are predictive of response to anti-angiogenic agents such as bevacizumab, and which would enable the selection of patients who would get the most benefit from these expensive therapies. Materials and Methods: We used high temporal resolution dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess tumor vascularity in 20 patients with primary breast cancer. Patients were imaged both before and two weeks after single dose Bevacizumab therapy (15mg/kg). Pharmacokinetic modelling techniques were used to quantify the volume transfer constant Ktrans, the rate constant kep, and the fractional volume of the extra-vascular extracellular space ve. Specifically, we used Tofts model with a population-based arterial input function (modified Fritz-Hansen) to model the contrast agent concentration time courses on a voxel-wise basis. Non-enhancing voxels were detected automatically with the use of a Bayesian noise model, and the corresponding pharmacokinetic parameter values for these voxels were set to zero. The median pharmacokinetic parameter values over the tumor volumes of interest were then computed both pre-and post Bevacizumab. Results: We found marked variation across patients in the baseline level and percentage change in median Ktrans, kep and ve following Bevacizumab. In particular, median Ktrans at baseline ranged form 0.12 to 0.88. Changes in median Ktrans varied from −97% to +19% across all patients, with an average change of −49%. Notably, we found a highly significant negative correlation (r = −0.92, P = 1e-08) between the absolute change in median Ktrans and the median Ktrans at baseline. In particular, tumors with a high median Ktrans at baseline demonstrated the greatest change in Ktrans following Bevacizumab therapy, whereas tumors with low median Ktrans at baseline demonstrated relatively little change in Ktrans. Discussion: Although Ktrans is a complex function of vessel permeability, surface area, and tumor blood flow, it has previously been demonstrated to be a reliable biomarker of response to anti-angiogenic therapy in a number of different cancers. Our results illustrate that therapy-induced changes in Ktrans can be predicted from the value of Ktrans at baseline, and hence DCE-MRI scans may enable the selection of primary breast cancer patients who show the greatest response to single-dose Bevacizumab therapy. Whether this will translate into longer term benefit and improvements in outcome for patients remains to be shown. The relationship between baseline and pre-/post-therapy change in Ktrans with the corresponding changes in gene expression is currently under study in a larger number of patients. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-02-07.

Abstract Background: Bevacizumab is an approved drug for advanced breast cancer alongside chemotherapy. To date there is no biomarker proven to be effective in patient stratification. To address this, a window of opportunity study was designed where bevacizumab is administered as a short-term first line treatment with a detailed pharmacodynamic assessment to identify the patients who are most likely to benefit from this therapy. This assessment consisted of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) and gene expression analysis. Method: This is an on going two-centre, Phase II, non-randomised study. 43 locally advanced breast cancer patients aged >18 years, with performance status 0-1 who have adequate bone marrow, renal and liver functions have been enrolled. A single infusion of bevacizumab (15mg/kg) was given prior to commencement of neoadjuvant chemotherapy. DCE-MRI and core biopsies for exon gene array analysis were performed both at baseline and 2 weeks after bevacizumab. Pharmacokinetic modelling of DCE-MRI was used to quantify the volume transfer constant Ktrans, the rate constant kep, and the fractional volume of the extra-vascular extracellular space ve. The median pharmacokinetic parameter values over the tumour volumes of interest were then computed both pre-and post-bevacizumab. Results: Our initial gene expression analysis from 21 patients showed a high variability in the response. This was true for both single gene analysis and pathway signatures. In particular the expression fold changes of hypoxia and proliferation signatures after bevacizumab ranged from a minimum of 0.6 fold decrease to a maximum of 4.3 fold increase. Interestingly, fold changes in both these signatures were significantly positively correlated (Spearman rho=0.81, P<0.001). Changes in the proliferation signature were significantly inversely correlated with changes in mean and median ve (rho=-0.57, P<0.01 in both cases). Changes in the hypoxia signature were significantly inversely correlated with changes in mean and median kep (rho=-0.48, p=0.03 and rho=-0.58, p=0.007 respectively). Significantly over-represented pathways amongst genes up-regulated after bevacizumab were T-cell activation, inflammation, PDGF and apoptosis signalling. Discussion: Our initial results provide several potentially important avenues for further research, which may be useful in the identification of new therapeutic approaches. For example, the unexpected correlation of induction of hypoxia and proliferation in the same tumours has important implications for combination therapy. Furthermore, patients whose tumours showed the largest reduction in kep, a measure of vascular leakiness, also showed the greatest increase in hypoxia. In addition, patients who experienced the largest reduction in ve showed the highest fold change in proliferation. Although these results are preliminary and will need to be confirmed at study completion, they illustrate how the integrated analysis of DCE-MRI pharmacokinetic parameters and the corresponding gene expression profiles may enable an improved understanding of the mechanisms governing response and resistance to bevacizumab. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-28.

OBJECTIVE This pilot study investigates the role of assisted-freehand ultrasound (AFUSON) elasticity imaging of the breast in assessing the contour, size and area of 23 early breast cancers by making comparison of AFUSON with the equivalent B-mode ultrasound images and gold standard histopathology slides. METHODS The B-mode, AFUSON and digitised histopathology slides of three early breast cancers were compared for contour, size and area with histopathology scans. AFUSON features that corresponded to areas of known malignant change on the histopathology slides were regarded as diagnostic. These diagnostic criteria were then applied to the B-mode and AFUSON elasticity images of all 23 breast cancers in the pilot study without having the availability of the histopathology scans for reference. Corresponding diameters were measured and the results were compared with the equivalent measurements on the scans of the histology slides. The results were tabulated in histogram form. Diagnostic confidence levels were evaluated. RESULTS Size dimension accuracy increased from 66% using B-mode alone to 82% using combined B-mode and AFUSON elasticity images. Tumour area accuracy was also increased. A small number of cases had a striking visual similarity of shape on AFUSON elasticity scans and histopathology slides. CONCLUSION In spite of the shortfalls in this study, AFUSON elasticity imaging was capable of acquiring some high-quality images that showed strong correlation between AFUSON elasticity and scans of histology slides. Further studies will be carried out to refine the technique and determine if it has a role in the diagnosis and management of breast cancer.

TPS176 Background: There are no proven biomarkers of efficacy of anti-vascular endothelial growth factor (VEGF) therapies. The vast majority of these drugs are investigated in patients with advanced cancers where multiple mechanisms of resistance are likely to have been developed. An alternative approach is to use these drugs as short-term first line treatments in combination with detailed pharmacodynamic assessments. We decided to investigate bevacizumab since it exhibits specific VEGF antagonism compared with other multi-kinase inhibitors. The aim of this study is to determine the mechanism of anti-angiogenic response and to identify the pathological characteristics of breast cancer patients most likely to be benefited from bevacizumab. Methods: This is a two-center, phase II, nonrandomized, open label, investigator-led study. This study obtained ethical approval in June 2008. A total of 40 previously untreated breast cancer patients will be enrolled consecutively. Eligibility criteria are: women who are scheduled to commence neoadjuvant chemotherapy, with age ≥18 years, performance status 0-1, who have histology proven locally advanced breast cancer (LABC), with adequate bone marrow, renal and liver functions. Patients receive a single infusion of bevacizumab (15 mg/ kg) 2-3 weeks prior to their neoadjuvant chemotherapy. Pharmacodynamic assessments include Dynamic Contrast-Enhanced (DCE), Diffusion Weighted (DW) and Blood Oxygen Level Dependent (BOLD) MRI scans, core biopsies for gene array (Affymetrix Human Exon 1.0 ST) and immunohistochemistry analysis of VEGF pathways, blood samples for proteomics, circulating endothelial cells, circulating cytokines, microparticles, plasma tumour DNA and endothelial RNA markers. Each assay is performed at baseline and 2-3 weeks following bevacizumab. The primary endpoint of the study is to correlate baseline gene expression with MRI response after one dose of bevacizumab measured at two weeks to assess whether particular patterns of gene expression relate to changes in vascular volume and permeability, as measured by MRI. The study is ongoing and has recruited 31 patients to date. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Cancer Research UK, Roche

Carcinoid tumors are known to metastasize to the breast, but their appearance can mimic a primary breast carcinoma, making biopsy essential in order to give the correct preoperative diagnosis. It has been suggested that core biopsy might precipitate a carcinoid crisis and should be avoided. We describe a case of screen-detected carcinoid tumor metastasis in the breast safely diagnosed by core biopsy and present the imaging findings, including magnetic resonance imaging and elastography. This case illustrates the importance of preoperative histologic diagnosis in enabling the appropriate surgical or medical management of these patients. Review of the literature also supports the policy that biopsy of nonhormonally active tumors may be safely performed.

PURPOSE:To evaluate the diagnostic accuracy of percutaneous image-guided cutting-needle biopsy of pleural thickening in the presence of a suspected malignant pleural effusion.MATERIALS AND METHODS:Thirty-three adult patients with diffuse or focal pleural thickening (median, 1.0 cm; range, 0.2-6.0 cm), pleural effusion, and suspected pleural malignancy underwent percutaneous image-guided cutting-needle biopsy. Biopsy guidance was performed with computed tomography in 24 patients and ultrasonography in nine patients. A final diagnosis of benign or malignant disease was established with radiologic and clinical follow-up findings and with other histologic or cytologic findings, when available.RESULTS:A correct histologic diagnosis of malignant disease was made in 21 of 24 patients (sensitivity, 88%; specificity, 100%), including 13 of 14 patients with mesothelioma (sensitivity, 93%). A correct histologic diagnosis of benign pleural disease was made in nine patients. Positive and negative predictive values for malignant disease were 100% and 75%, respectively. The overall accuracy was 91%. Complications comprised a chest wall hematoma in one patient.CONCLUSION:Image-guided percutaneous cutting-needle biopsy of pleural thickening in the presence of a pleural effusion is a safe procedure, with an overall accuracy of 91% in the diagnosis of malignancy.

STUDY OBJECTIVES:Pleural fluid cytology and non-image-guided Abrams or Cope biopsies have sensitivities of approximately 30% for detecting malignant mesothelioma, and thoracoscopic biopsy has a sensitivity of approximately 90%. The difference between these two probably relates to obtaining adequate tissue. The use of immunohistochemical stains allows a firm diagnosis to be made from relatively small samples. This study explores whether percutaneous image-guided cutting needle biopsy (CNB) combined with immunohistochemistry is accurate in diagnosing pleural thickening due to mesothelioma.DESIGN:Retrospective review of image-guided CNB of pleural thickening performed on consecutive patients over 7 years by a single radiologist.SETTING:Teaching hospital chest radiology department.PATIENTS:Twenty-one adult patients with a final diagnosis of malignant mesothelioma were identified from 53 consecutive patients who underwent percutaneous image-guided CNB. All 21 patients had pleural thickening identified on contrast-enhanced CT, and all had a final histologic diagnosis of mesothelioma confirmed by postmortem examination or thoracoscopy.INTERVENTIONS:Fourteen-gauge and 18-gauge cutting needles were used. Biopsy guidance was by ultrasound in 6 patients and by CT in 15 patients.MEASUREMENTS AND RESULTS:A correct histologic diagnosis of malignant mesothelioma was made by CNB in 18 patients (86% sensitivity and 100% specificity). Complications included one chest wall hematoma and a small hemoptysis. Four patients with a pleural thickness of < or = 5 mm underwent biopsy, and all specimens were diagnostic for mesothelioma.CONCLUSIONS:Image-guided percutaneous CNB of pleural thickening is a safe procedure, with 86% sensitivity for detecting malignant mesothelioma. Pleural thickening of < or = 5 mm may be successfully sampled.

Most patients referred for lung biopsy have a focal lesion that is likely to be a carcinoma, and fine needle aspiration is usually sufficient to confirm the diagnosis. When non-carcinomatous disease is suspected, tissue architecture is important and potential diagnostic techniques include percutaneous cutting needle biopsy (CNB). We retrospectively reviewed 37 CNBs performed for clinically suspected non-carcinomatous disease; recording the biopsy result, final diagnosis, radiological nature of the pulmonary abnormality, distance from the pleura of the lesion biopsied and biopsy complications. 9 patients had a single pulmonary nodule/mass; 13 had multiple nodules/masses; 8 had a lobar consolidation/mass; and 7 had multifocal consolidation. The lesion abutted the pleura in 31 cases, lying within 1 cm in the other 6 cases. The minor complication rate was 14%, with no major complications. Specific malignant diagnoses were made in 9 patients, and specific benign in 23, in all of whom clinicoradiological follow-up was concordant. CNB did not yield a specific diagnosis in five patients, including two lymphomas and one case of unsuspected tuberculosis in which the sample was not cultured. The overall accuracy of CNB was 32/37 (86%). CNB is a safe and accurate means of achieving a tissue diagnosis for patients with peripheral pulmonary parenchymal disease thought not to represent carcinoma.