Breast density: why all the fuss?

The term "breast density" or mammographic density (MD) denotes those components of breast parenchyma visualised at mammography that are denser than adipose tissue. MD is composed of a mixture of epithelial and stromal components, notably collagen, in variable proportions. MD is most commonly assessed in clinical practice with the time-honoured method of visual estimation of area-based percent density (PMD) on a mammogram, with categorisation into quartiles. The computerised semi-automated thresholding method, Cumulus, also yielding area-based percent density, is widely used for research purposes; however, the advent of fully automated volumetric methods developed as a consequence of the widespread use of digital mammography (DM) and yielding both absolute and percent dense volumes, has resulted in an explosion of interest in MD recently. Broadly, the importance of MD is twofold: firstly, the presence of marked MD significantly reduces mammographic sensitivity for breast cancer, even with state-of-the-art DM. Recognition of this led to the formation of a powerful lobby group ('Are You Dense') in the US, as a consequence of which 32 states have legislated for mandatory disclosure of MD to women undergoing mammography. Secondly, it is now widely accepted that MD is in itself a risk factor for breast cancer, with a four-to sixfold increased relative risk in women with PMD in the highest quintile compared to those with PMD in the lowest quintile. Consequently, major research efforts are underway to assess whether use of MD could provide a major step forward towards risk-adapted, personalised breast cancer prevention, imaging, and treatment.

Clinical performance of Siemens digital breast tomosynthesis versus standard supplementary mammography for the assessment of screen-detected soft-tissue abnormalities: a multi-reader study.

AIM: To compare the diagnostic accuracy of standard screening images plus single-view digital breast tomosynthesis (DBT), using Siemens DBT equipment, with standard screening images plus supplementary mammographic views in non-calcific, screen-detected mammographic abnormalities. MATERIALS AND METHODS: Participants were unselected women aged 50-69 years recalled within a population-based European breast screening programme for assessment of soft-tissue mammographic abnormalities. Supplementary mammographic views (SMVs) and DBT were performed in all cases. A range of equipment was used for screening and supplementary mammography, but all DBT examinations were performed using the Siemens Mammomat Inspiration. A retrospective multi-reader study including 238 cases for whom either histology or at least 2 years' follow-up was available was performed with eight suitably accredited UK breast screening personnel reading all cases under both conditions, with temporal separation. Readers were blinded to case outcomes and findings from other examinations. Diagnostic accuracy using receiver operating characteristic (ROC) analysis was compared between screening plus SMV images and screening plus DBT images. The study was powered to detect a 3% inferiority margin in diagnostic accuracy between methods. RESULTS: The final sample with complete data available for analysis included 195 benign cases (1,560 reads) and 35 malignant cases (280 reads). The DBT method yielded a slightly higher area under the curve (AUC) value than the SMV method (0.870 versus 0.857), but the difference was not statistically significant (p=0.4890), indicating that the methods have equivalent accuracy. CONCLUSION: Siemens DBT demonstrates equivalent diagnostic accuracy according to ROC curve analysis when used in place of SMVs in screen-detected soft-tissue mammographic abnormalities.

Acute pancreatitis: a comparison of intervention rates precipitated by early vs guideline CT scan timing.

AIM: To assess whether computed tomography (CT) examination earlier in acute pancreatitis (AP) precipitates any surgical or radiological intervention. MATERIALS AND METHODS: A single-centre retrospective cohort study comparing intervention rates in AP precipitated by early (<6 day of admission, n=100) and UK guideline (≥6 day of admission, n=103) CT examinations. RESULTS: No intervention was precipitated by performing CT before the sixth day of admission in AP. A statistically significant larger number of interventions were precipitated when CT was performed on the sixth day or later (p<0.05). Of note, this study was conducted using day of admission, rather than day of symptom onset. Six patients underwent repeat CT examination in the same admission after an early CT examination. CONCLUSION: Performing CT before the sixth day of admission does not lead to earlier intervention. Such early examinations waste resources and may offer false reassurance to clinicians.

Accuracy of non-operative identification of the sentinel lymph node using combined gamma and ultrasound scanning.

AIM: To assess how accurately the sentinel lymph node (SLN) can be identified percutaneously, using gamma probe and ultrasound technology. MATERIALS AND METHODS: Women with breast cancer, scheduled for wide local excision or mastectomy with SLN biopsy (SLNB), were included. Peri-areolar intradermal injection of technetium-99 nanocolloid was performed on the morning of surgery and 1-2 ml of blue dye was injected in the peri-areolar region once the patient was anaesthetized. Prior to surgery, a gamma probe was used over the skin to identify any hot spot that could represent a SLN. Ultrasound, guided by the hot spot, was then used to visualize potential SLNs and guide the insertion of a localizing wire. The accuracy in localizing the SLN by preoperative gamma-probe guided ultrasonography was assessed by comparison to SLNB. RESULTS: A SLN was correctly identified and marked using gamma-probe guided ultrasonography in 44 of 59 cases (75%; 95% CI: 63-86%). CONCLUSION: This study supports the case for investigating percutaneous gamma probe and ultrasound guided interventions in the axilla in women with breast cancer, as a potential alternative to surgical SLNB.

What are the characteristics of breast cancers misclassified as benign by quantitative ultrasound shear wave elastography?

OBJECTIVES: Shear wave elastography (SWE) is a promising adjunct to greyscale ultrasound in differentiating benign from malignant breast masses. The purpose of this study was to characterise breast cancers which are not stiff on quantitative SWE, to elucidate potential sources of error in clinical application of SWE to evaluation of breast masses. METHODS: Three hundred and two consecutive patients examined by SWE who underwent immediate surgery for breast cancer were included. Characteristics of 280 lesions with suspicious SWE values (mean stiffness >50 kPa) were compared with 22 lesions with benign SWE values (<50 kPa). Statistical significance of the differences was assessed using non-parametric goodness-of-fit tests. RESULTS: Pure ductal carcinoma in situ (DCIS) masses were more often soft on SWE than masses representing invasive breast cancer. Invasive cancers that were soft were more frequently: histological grade 1, tubular subtype, ≤10 mm invasive size and detected at screening mammography. No significant differences were found with respect to the presence of invasive lobular cancer, vascular invasion, hormone and HER-2 receptor status. Lymph node positivity was less common in soft cancers. CONCLUSION: Malignant breast masses classified as benign by quantitative SWE tend to have better prognostic features than those correctly classified as malignant. KEY POINTS: • Over 90 % of cancers assessable with ultrasound have a mean stiffness >50 kPa. • 'Soft' invasive cancers are frequently small (≤10 mm), low grade and screen-detected. • Pure DCIS masses are more often soft than invasive cancers (>40 %). • Large symptomatic masses are better evaluated with SWE than small clinically occult lesions. • When assessing small lesions, 'softness' should not raise the threshold for biopsy.

Low-dose phase contrast mammography with conventional x-ray sources.

PURPOSE: To provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose. METHODS: Following the adaptation of our "edge-illumination" XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method. RESULTS: The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice. CONCLUSIONS: The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice.

Phase contrast imaging of breast tumours with synchrotron radiation.

Even though the potential of phase contrast (PC) imaging has been demonstrated in a number of biological tissue samples, the availability of free-space propagation phase contrast images of real breast tumours is still limited. The aim of this study was to obtain phase contrast images of two different pathological breast specimens containing tumours of differing morphological type at two synchrotron radiation (SR) facilities, and to assess any qualitative improvements in the evaluation and characterisation of the masses through the use of phase contrast imaging. A second aim was to assess the effects of parameters such as detector resolution, beam energy and sample-to-detector distance on image quality using the same breast specimens, as to date these effects have been modelled and discussed only for geometric phantoms. At each synchrotron radiation facility a range of images was acquired with different detectors and by varying the above parameters. Images of the same samples were also acquired with the absorption-based approach to allow a direct comparison and estimation of the advantages specifically ascribable to the PC technique.

Metastases to the breast revisited: radiological-histopathological correlation.

Metastases to the breast from extramammary tumours are infrequent. The main challenge in diagnosis is differentiating them from primary breast cancer. Radiologically this can be difficult as there are no specific imaging characteristics for metastases to the breast. Cytopathological evaluation, as well as full radiological assessment, is vital to avoid unnecessary surgery. Sources of primary tumours include a wide variety of cancers. In this pictorial review we illustrate a number of the commonest sources of primary tumours including lymphoma, lung, ovarian and cervical carcinoma, intestinal carcinoid and rare cases of Ewing's sarcoma and malignant pigmented melanocytic schwannoma (low-grade malignant melanoma).

How significant is detection of ductal carcinoma in situ in a breast screening programme?

PURPOSE: To compare the histological grades of screen detected and non-screen detected ductal carcinoma in situ (DCIS) and to identify any differences that might support the contention that DCIS found by breast screening represents an over-diagnosis. The aim was also to establish whether any particular mammographic features of DCIS can be used to predict tumour grade reliably. MATERIALS AND METHODS: Biopsy proven cases of DCIS (n=153) were reviewed with respect to grade and subdivided into high, intermediate and low grades using the Van Nuys classification. A more aggressive subset of DCIS (microinvasive and interval cancers) were similarly analysed. Mammograms were reviewed with regard to abnormal features and distribution, and the appearances correlated with grade. RESULTS: Fifty-four percent (53/98) of screen detected and 62% (34/52) of non-screen detected DCIS were high grade. The rest were equally intermediate and low grade, with no statistical difference between the two groups. Eighty-four percent of the aggressive subset of tumours were high grade. Micro-calcification was present in 90% and in 10% there were soft tissue changes alone. Seventy-six percent of linear branching calcification was associated with high grade DCIS. Only 13% of high grade DCIS demonstrated punctate micro-calcification; however, 38% of cases of punctate micro-calfication were associated with high grade tumours and there was a great deal of overlap between the groups. CONCLUSION: Most cases of DCIS in both screen and non-screen detected groups were high grade. Only one in five was low grade. Analysis of the aggressive subgroup underlines the significance of high grade DCIS. Mammographic patterns are not always reliable in the prediction of tumour grade. The detection of DCIS in screening programmes is important and should not be regarded as over-diagnosis.

Correlation between ultrasound characteristics, mammographic findings and histological grade in patients with invasive ductal carcinoma of the breast.

AIM: To investigate the relationship between ultrasound characteristics, mammographic findings and histological grade in cases of invasive ductal carcinoma which produce a mass on ultrasound. MATERIAL AND METHODS: A retrospective review was performed of the imaging findings in 120 patients diagnosed with invasive ductal carcinoma of the breast between January 1996 and December 1997. Imaging findings were correlated with the histological grade of tumour. RESULTS: High-grade tumours were significantly larger both on ultrasound and mammography (P < 0.016). A spiculated margin on mammogram was documented in 72% of low-grade tumours compared with only 24% of high-grade tumours (P = 0.001). Twenty-two per cent of low-grade tumours had a poorly defined margin on mammography compared with 66% of high-grade tumours (P = 0.001). At ultrasound, 16% of high-grade tumours (95% confidence limits 7-29%) had a well-defined margin. Acoustic enhancement was seen in 36% of high-grade tumours compared with only 9% of low and intermediate-grade tumours (P = 0.003): 22% of all tumours showed acoustic enhancement. Acoustic shadowing was seen in 71% of low-grade tumours compared with only 28% of high-grade tumours (P = 0.003). Malignant-type microcalcification was seen on mammogram in 6% of low-grade tumours compared with 31% of high-grade tumours (P = 0.045). CONCLUSION: The classical appearance of a malignant breast mass as a spiculated mass on mammogram associated with acoustic shadowing on ultrasound is more typical of a low-grade tumour. In comparison, high-grade tumours are more likely to demonstrate posterior acoustic enhancement, and a proportion has a well-defined margin on ultrasound. Therefore, high-grade invasive ductal carcinoma may paradoxically display similar imaging features to a benign breast mass.

Primary breast cancer: mammographic changes after neoadjuvant chemotherapy, with pathologic correlation.

PURPOSE: To correlate changes depicted at mammography during neo-adjuvant chemotherapy for operable breast carcinoma with subsequent pathologic status. MATERIALS AND METHODS: Patients (n = 107) underwent mammography before and after neoadjuvant chemotherapy, prior to surgery. Four retrospectively determined grades of response at mammography included complete, mammographic (decreased size and/or density), stable disease, or progressive disease. RESULTS: In 95 fully assessable patients, grade of response to chemotherapy was complete in eight (9%), mammographic in 78 (82%), stable disease in seven (7%), and progressive disease in two (2%). Before and after treatment, respectively, 64 (67%) and 20 (21%) masses were greater than 2 cm in bidimensional diameter. Response was not complete in any of the 44 (46%) cases of microcalcifications. At histologic examination after surgery in 95 fully assessable patients, five of eight patients with complete response were found to have residual tumor (three with an invasive component); eight were found to have no residual tumor (response in three was complete; in four, mammographic; and in one, stable disease). CONCLUSION: Whereas mammograms in most patients showed some response to chemotherapy, prediction of pathologic outcome was not possible.

Posterior urethral valves in male infants and newborns: detection with US of the urethra before and during voiding.

PURPOSE: To document the appearance and width of the posterior urethra with transperineal ultrasound (US) before and during voiding in male infants and newborns with posterior urethral valves. MATERIALS AND METHODS: Thirty-three patients with bilateral hydronephrosis underwent prospective transabdominal and transperineal US. RESULTS: Fifteen patients had proved posterior urethral valves (obstructed group); 18 patients had no obstruction (unobstructed group). In the obstructed group, the median posterior urethral width was 4.5 mm before and 10.0 mm during voiding. In the unobstructed group, the median posterior urethral width was 1.0 mm (P = .046) before and 4.0 mm (P < .001) during voiding. Bladder wall thickness was 3.0-7.6 mm (obstructed group) and 2.0-5.0 mm (unobstructed group; P < .001). With a posterior urethral diameter of at least 6 mm during voiding as a criterion for transperineal US diagnosis of obstruction, sensitivity was 100%; specificity, 89%; and positive predictive value, 88%. CONCLUSION: Transperineal voiding US is noninvasive and useful in diagnosing posterior urethral valves.

Posterior urethral diverticula: a complication of surgery for high anorectal malformations.

We describe five boys, all of whom presented with urinary tract infection or acquired urinary incontinence some years after surgery for a high anorectal malformation (ARM). All were found to have a posterior urethral diverticulum thought to represent the remains of the original rectourethral fistula accompanying the high rectal atresia. Excision of the diverticula resulted in complete relief of symptoms. The clinical features and radiological appearances of the diverticula are described. A urethral diverticulum is one treatable cause of urinary symptoms in children with high anorectal malformations, and should be considered when symptoms recur late after definitive surgical correction of the malformation.

Normal pelvic lymph nodes: evaluation with CT after bipedal lymphangiography.

PURPOSE: To establish guidelines to determine the normal size of pelvic lymph nodes by correlating computed tomographic (CT) and lymphangiographic data. MATERIALS AND METHODS: Forty men in whom stage I testicular tumors were being treated underwent CT scanning 3-4 months after undergoing lymphangiography. The site, size, and number of nodes at CT scanning were documented. Maximum short-axis diameter (MSAD) was measured at four anatomic sites in the pelvis. Results were analyzed with histograms, and median and percentile values were calculated. RESULTS: There were 187 nodes measured in 27 men before lymphangiography. There were 1,801 nodes measured in 40 patients after lymphangiography. Median MSAD values at CT after lymphangiography were 5 mm or less; fewer than 2% of nodes had an MSAD greater than 10 mm. CONCLUSION: Almost all normal pelvic nodes are less than 10 mm MSAD, depending on the site. The low sensitivity of CT in depicting metastases to the pelvic lymph nodes might be improved by adopting upper limits of normal that reflect this size.

Directional atherectomy in the treatment of anastomotic neointimal hyperplasia associated with prosthetic arterial grafts: technique and preliminary results.

The development of anastomotic neointimal hyperplasia is a common cause of late prosthetic arterial bypass graft failure. The cost and morbidity of graft failure are high, hence the widespread use of graft surveillance programmes in order to detect graft-related stenoses before they progress to occlusion. However, the optimal treatment of stenoses secondary to neointimal hyperplasia is not clear, with a number of authors reporting poor results with both balloon angioplasty and surgical revision. We report our early experience with the Simpson atherectomy catheter in the treatment of anastomotic neointimal hyperplasia associated with prosthetic arterial grafts at eight sites in seven patients. A high technical success rate may be expected and further long-term studies of this mode of treatment are indicated.