ShearWave™ Elastography BE1 multinational breast study: additional SWE™ features support potential to downgrade BI-RADS®-3 lesions.

PURPOSE: To determine the benefit of ShearWave™ Elastography (SWE™) in the ultrasound characterization of BI-RADS® 3 breast lesions in a diagnostic population. MATERIALS AND METHODS: 303 BI-RADS® 3 lesions (mean size: 13.2 mm, SD: 7.5 mm) from the multicenter BE1 prospective study population were analyzed: 201 (66%) had cytology or core biopsy, and the remaining 102 had a minimum follow-up of one year; 8 (2.6%) were malignant. 7 SWE features were evaluated with regard to their ability to downgrade benign BI-RADS® 3 masses. The performance of each SWE feature was assessed by evaluating the number of lesions correctly reclassified and the impact on cancer rates within the new BI-RADS® 3' lesion group. RESULTS: No malignancies were found with an E-color "black to dark blue", which allowed the downgrading of 110/303 benign masses (p < 0.0001), with a non-significant increase in BI-RADS® 3' malignancy rate from 2.6% to 4.1%. E-max ≤ 20 kPa (2.6 m/s) was able to downgrade 48/303 (p < 0.0001) lesions with a lower increase in BI-RADS® 3' malignancy rate (3.1%). No other SWE features were useful for reclassifying benign BI-RADS® 3 lesions. CONCLUSION: Applying simple reclassification rules, SWE assessment of the maximum stiffness of lesions allowed the downgrading of a sub-group of benign BI-RADS® 3 lesions. This was accompanied by a non-significant increase in the malignancy rate in the new BI-RADS® 3 class.

Can contrast-enhanced sonography distinguish benign from malignant breast masses?

BACKGROUND: We investigated whether microvascular enhancement on contrast-enhanced sonographic (CEUS) imaging can aid in distinguishing between benign and malignant lesions and correlated these findings with histopathological findings. METHOD: Fifteen patients with a palpable breast mass were recruited. Following informed consent, 4.8 mL of the microbubble contrast agent SonoVue was injected intravenously. Digital video clips of lesion enhancement were obtained and reviewed by a consultant radiologist who scored each lesion on the following characteristics: homogeneous versus heterogeneous enhancement, the presence or absence of focal defects, well- versus ill-defined margins and vascular morphology score (VMS). RESULT: Histologically there were 7 malignant and 8 benign lesions. The calculated sensitivity for CEUS in the diagnosis of malignancy was 100%, with a 37.5% specificity. There was no statistically significant difference in overall mean VMS between the malignant and benign lesions. CONCLUSION: The results of our study have not shown any additional benefit in the use of CEUS over conventional triple assessment. The positive trend seen in the higher mean VMS for the malignant tumors needs further investigation with a larger cohort of patients.

The use of breast ultrasound color Doppler vascular pattern morphology improves diagnostic sensitivity with minimal change in specificity.

PURPOSE: The aim of this study was to evaluate the use of vascular morphology, around and within the B-mode region of abnormality, for improving the diagnostic accuracy of two of the most common solid breast pathologies. MATERIALS AND METHODS: The B-mode and Doppler images of 117 breast cancers and 366 fibroadenomas and lesions with a fibroadenoma-like appearance were reviewed retrospectively and the morphology of the vascular pattern was evaluated. The ratio of external to internal color Doppler, the external vascular pattern and the connecting vessels to internal vessels were assessed and differentiated into benign and malignant vascular patterns. These patterns were correlated with the histological diagnosis. RESULTS: Vascularity was demonstrated in 95 % of cancers and in 46 % of benign lesions with a trend to increasing vascularity in cancers. This provided poor specificity for excluding cancer in fibroadenomas. Variations in vascular pattern were recorded. The observed benign vascular patterns were avascularity, vascularity in the periphery and peripheral marginal vessels connecting with internal vascularity. The observed malignant vascular patterns were radially aligned external vessels with internal vessels being more numerous than external vessels which connected to radial vessels. (Fisher exact test p < 0.0001). Analysis of the vascular morphology improved the sensitivity for identifying cancers from 97 % (B-mode) to 99 % (B-mode and color Doppler) with a minimal reduction in specificity (93.7 to 92.6 %) or accuracy (94.6 to 94.2 %). CONCLUSION: The presence of vascularity within a lesion, by itself, is no longer a good predictor of malignancy because of the increase in Doppler sensitivity associated with improvements in ultrasound technology. The color Doppler ultrasound vascular pattern morphology improves the accuracy and sensitivity of B-mode image diagnosis, breast cancers and fibroadenomas with a minimal loss of specificity. Any breast lesion with radial rather than marginal connecting vessels should be regarded with suspicion.

Carcinoma of the breast wire localisation post nuclear medicine sentinel lymph node imaging. Are radiologists receiving a significant dose?

OBJECTIVE: To assess the radiation dose received by the radiologist when performing wire localisation for axillary radio-isotope sentinel node imaging-guided biopsy in patients with impalpable breast cancers treated with breast-preserving excision. When wire placement follows radio-isotope sentinel node imaging (RSNI) the radiologist is exposed to a radiation risk that has never been previously assessed. METHODS: Radiation doses to radiologists performing ultrasound-guided localisation following nuclear medicine sentinel node imaging were measured for procedures on the day of surgery (20 MBq) and also on the day before surgery (40 MBq). These measurements were compared with theoretically calculated doses. RESULTS: Twelve patients showed comparable results between measurements and estimated doses. The mean measured dose was 1.8 muSv (estimated 1.8 muSv) for same-day and 4.8 muSv (estimated 3.4 muSv) for next-day surgery cases. At worst, radiologists who perform 36 wire localisations per year immediately following RSNI receive a radiation dose of 0.17 mSv. CONCLUSIONS: This study highlights the need to inform radiologists of the relative risk when performing pre-surgical localisation after RSNI. This risk should be justified locally in accordance with the total dose received by the localising radiologist. Particular consideration should be given to pregnant staff and the possibility of performing wire localisations before radio-isotope injection.

Colorectal breast metastases presenting with atypical imaging features.

Breast metastases from non-breast primaries are rare in female patients and exceedingly rare in male patients, with only a handful of cases described. Lymphoma, metastatic melanoma and bronchial carcinoma are the primary sites for the majority of breast metastases. Breast metastases from colorectal carcinoma have been described previously in only a small number of cases in the literature. Here, we report a further two patients with biopsy-proven colorectal carcinoma metastases to both breasts, who demonstrate contrasting unusual and atypical imaging features that have not been reported previously. In one case, the imaging appearances mimic a multifocal primary breast carcinoma. Metastatic disease in the breast is a marker for disseminated metastatic spread, with a correspondingly poor prognosis. Therefore, we review the imaging features that differentiate metastatic breast disease from multifocal breast primaries, which are important to recognize because the management options for these patients differ greatly.

Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy.

Axillary surgery for breast cancer partially obstructs lymph outflow from the arm, chronically raising the lymphatic smooth muscle afterload. This may lead to pump failure, as in hypertensive cardiac failure, and could explain features of breast cancer treatment-related lymphoedema (BCRL) such as its delayed onset. A new method was developed to measure human lymphatic contractility non-invasively and test the hypothesis of contractile impairment. 99mTc-human IgG (Tc-HIG), injected into the hand dermis, drained into the arm lymphatic system which was imaged using a gamma-camera. Lymph transit time from hand to axilla, ttransit, was 9.6+/-7.2 min (mean+/-s.d.) (velocity 8.9 cm min(-1)) in seven normal subjects. To assess lymphatic contractility, a sphygmomanometer cuff around the upper arm was inflated to 60 mmHg (Pcuff) before 99mTc-HIG injection and maintained for>>ttransit. When Pcuff exceeded the maximum pressure generated by the lymphatic pump (Ppump), radiolabelled lymph was held up at the distal cuff border. Pcuff was then lowered in 10 mmHg steps until 99mTc-HIG began to flow under the cuff to the axilla, indicating Ppump>or=Pcuff. In 16 normal subjects Ppump was 39+/-14 mmHg. Ppump was 38% lower in 16 women with BCRL, namely 24+/-19 mmHg (P=0.014, Student's unpaired t test), and correlated negatively with the degree of swelling (12-56%). Blood radiolabel accumulation proved an unreliable measure of lymphatic pump function. Lymphatic congestion lymphoscintigraphy thus provided a quantitative measure of human lymphatic contractility without surgical cut-down, and the results supported the hypothesis of lymphatic pump failure in BCRL.

A rare case of extranodal Rosai-Dorfman disease.

Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder which commonly affects the lymph nodes. Extranodal involvement along with concomitant nodal disease occurs in about 43% of cases. Isolated extranodal Rosai-Dorfman disease is relatively uncommon. We report this rare case of isolated extranodal Rosai-Dorfman disease and its ultrasound findings.

Transdermal estradiol improves bone density when used as single agent therapy for prostate cancer.

PURPOSE: Current androgen deprivation therapies for men with prostate cancer cause accelerated osteoporosis and a significant risk of osteoporotic fracture. We have recently shown that transdermal estradiol is an effective alternative for such patients. Here we report the impact of transdermal estradiol therapy on the bone mineral density of men with prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated with transdermal estradiol patches. Bone mineral density of the lumbar spine and the proximal femur was measured with dual-energy x-ray absorptiometry, and correlated with computerized tomography and isotope bone scan findings at 6-month intervals. RESULTS: In all measured regions bone mineral density increased with time. By 1 year mean bone mineral density +/- SEM had increased by 3.60% +/- 1.6% in the lumbar spine (p = 0.055), 2.19% +/- 1.03% in the femoral neck (p = 0.055), 3.76% +/- 1.35% in the Ward's region (p = 0.008) and 1.90% +/- 0.85% in the total hip (p = 0.031), respectively. Of 12 osteoporotic sites 4 had improvement based on World Health Organization grading. All other sites improved toward a better classification. CONCLUSIONS: Transdermal estradiol protects against bone loss in men with prostate cancer and may improve bone density in those at risk for osteoporotic fracture.

Impairment of lymph drainage in subfascial compartment of forearm in breast cancer-related lymphedema.

BACKGROUND: In arm lymphedema secondary to axillary surgery and radiotherapy (breast cancer-related lymphedema), the swelling is largely epifascial and lymph flow per unit epifascial volume is impaired. The subfascial muscle compartment is not measurably swollen despite the iatrogenic damage to its axillary drainage pathway, but this could be due to its low compliance. Our aim was to test the hypothesis that subfascial lymph drainage too is impaired. METHODS AND RESULTS: Quantitative lymphoscintigraphy was used to measure the removal rate constant (local lymph flow per unit distribution volume) for technetium-99m-human immunoglobulin G injected intramuscularly in the forearms of nine women with unilateral lymphedema. The removal rate constant was on average 31% lower in the ipsilateral swollen forearm than in the contralateral forearm (swollen arm: -0.096+/-0.041% min(-1), contralateral arm: -0.138+/-0.037% min(-1); mean+/-SD, p = 0.037). The decrease in subfascial rate constant correlated strongly with increase in arm volume (r = -0.88, p = 0.002), even though the swelling is mainly epifascial. There was no convincing evidence of dermal backflow. CONCLUSIONS: Lymph flow in the subfascial muscle compartment is decreased in breast cancer-related lymphedema. The correlation between impairment of subfascial drainage and epifascial arm swelling could be because both depend on the severity of axillary damage, or because loss of function in subfascial lymphatics impairs drainage from the epifascial to the subfascial system.

Differences in lymph drainage between swollen and non-swollen regions in arms with breast-cancer-related lymphoedema.

Recent research indicates that the pathophysiology of breast-cancer-related lymphoedema (BCRL) is more complex than simple axillary lymphatic obstruction as a result of the cancer treatment. Uneven distribution of swelling (involvement of the mid-arm region is common, but the hand is often spared) is puzzling. Our aim was to test the hypothesis that local differences in lymphatic drainage contribute to the regionality of the oedema. Using lymphoscintigraphy, we measured the removal rate constant, k (representing local lymph flow per unit distribution volume, VD), for 99mTc-labelled human immunoglobulin G in the oedematous proximal forearm, and in the hand (finger web) in women in whom the hand was unaffected. Tracer was injected subcutaneously, and the depot plus the rest of the arm was monitored with a gamma-radiation camera for up to 6 h. VD was assessed from image width. Contralateral arms served as controls. k was 25% lower in oedematous forearm tissue than in the control arm (BCRL, -0.070+/-0.026% x min(-1); control, -0.093+/-0.028% x min(-1); mean+/-S.D.; P=0.012) and VD was greater. In the non-oedematous hand of the BCRL arm, k was 18% higher than in the control hand (BCRL, -0.110+/-0.027% x min(-1); control, -0.095+/-0.028% x min(-1); P=0.057) and 59% higher than forearm k on the BCRL side (P=0.0014). VD did not differ between the hands. Images of the BCRL arm following hand injection showed diffuse activity in the superficial tissues, sometimes extending almost to the shoulder. A possible interpretation is that the hand is spared in some patients because local lymph flow is increased and diverted along collateral dermal routes. The results support the hypothesis that regional differences in surviving lymphatic function contribute to the distribution of swelling.

The value of ultrasound scanning in breast disease.

Ultrasound is the modality of choice for imaging breast masses. Most benign and malignant lesions can be accurately categorized as a result of improvements in grey scale imaging and the development of sensitive colour Doppler vascular mapping. Ultrasound contrast agents, harmonic imaging, elasticity imaging and other advances will further enhance the utility of breast ultrasound.

Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin.

A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m-labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99mTc-HIG compared with 99mTc-HSA, although ultimately, the blood recovery of 99mTc-HIG was significantly higher (P < 0.05) than that of 99mTc-HSA. Clearance rates of radioactivity from the injection site were not significantly different, however, between the two agents. In patients with PMO, web space injection of 99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for normal and swollen arms combined) than into the forearm (0.053% per minute; P < 0.05). These results suggest that (a) 99mTc-HIG is a potentially useful agent for measuring lymph flow and lymph node function; but (b) injection into the dorsum of the forearm is not a useful method of administration for these measurements; and (c) clearance rates from the injection site do not support the notion that PMO is the result of decreased lymph flow. Further studies are warranted to evaluate 99mTc-HIG as an agent for assessment of lymphatic function, especially with respect to measurement of lymph flow and possibly also for the evaluation of lymph node Fc-mediated immunocompetence.

Gynaecological cytology and pelvic ultrasonography in patients with breast cancer taking tamoxifen compared with controls.

The objective of this study was to look at the effect of tamoxifen on the endometrium by comparing gynaecological cervical and endometrial cytology in breast cancer patients on tamoxifen for 3 years compared with controls. In addition, pelvic ultrasonography was employed to detect ovarian abnormalities and to measure endometrial thickness. Patients followed-up after primary surgical therapy for breast cancer were invited for gynaecological assessment consisting of clinical examination pelvic ultrasonography and a cervical smear and endometrial sampling. The patients taking tamoxifen (n = 49) has been on adjuvant hormone therapy for a minimum of 3 years. Control patients (n = 45) were also being followed-up for breast cancer. On examination the tamoxifen patients had very similar clinical findings to the control patients with regard to the cervix (normal in 84% of tamoxifen takers compared to 87% of controls). The uterus was clinically enlarged in eight patients on tamoxifen and in none of the control patients (P = 0.006) and only one ovarian cyst was clinically detectable in a patient taking tamoxifen. Pelvic ultrasonography between the two groups of patients was not statistically different (chi 2 test) and ovarian cysts were noted in nine patients from each group (tamoxifen patients 18% vs control patients 20%, n.s.). There was a highly significant difference in endometrial thickness in premenopausal patients (9.2 mm) compared with postmenopausal patients (6.4 mm, P = 0.001). There was also a suggestion that endometrial thickness was greater in tamoxifen treated patients (P = 0.08). In general, a greater proportion of patients taking tamoxifen had cervical and endometrial cells exhibiting hyperplastic nuclei, and in endocervical smears, this difference achieved statistical significance (Mann-Whitney test, P = 0.046). These findings show that a significantly increased proportion of patients taking tamoxifen had endocervical nuclear hyperplasia, and a trend towards increased endometrial thickness. These findings confirm that tamoxifen has mild oestrogenic activity. However, the lack of any difference in the incidence of dysplasia suggests that the carcinogenic potential of tamoxifen on the uterus is very low and the beneficial effects of tamoxifen as an adjuvant therapy for breast cancer outweighs its theoretical risks.

Colour Doppler demonstrates venous flow abnormalities in breast cancer patients with chronic arm swelling.

Chronic arm oedema following breast cancer treatment is traditionally attributed to lymphatic obstruction, with venous obstruction as an infrequent complicating factor. The axillo-subclavian venous systems of 81 patients with arm swelling following breast cancer treatment were examined with colour Doppler, duplex Doppler and grey scale ultrasound. Over half (57%) had evidence of venous outflow obstruction and a further 14% had signs of venous "congestion". Only 30% of the swollen arms had normal venous outflow. The venous systems of the contralateral non-swollen arms were all normal as were both arms in 28 control patients who had similar treatment but had not developed arm swelling. These findings suggest that venous outflow obstruction is an important contributory factor in the pathophysiology of arm swelling following breast cancer treatment.

Increased arterial inflow demonstrated by Doppler ultrasound in arm swelling following breast cancer treatment.

Doppler ultrasound was used to estimate the mean arterial flow in the arms of 50 patients with arm oedema following breast cancer treatment (oedema group). They were compared with 26 treated breast cancer patients with no arm swelling (control group). Flows on the treatment side were expressed as a percentage of the flow in the contralateral normal arm. Mean percentage blood flow was 68% higher in the swollen arms than the contralateral normal arms compared to a mean increase of 38% on the breast cancer treatment side in the control group. In both groups there was a significantly higher proportion of patients with increased (> 150%) rather than decreased (< 50%) flow on the treatment side. The ratio of increased to decreased flow was 27:4 in the oedema group and 6:0 in the control group. A neurological deficit on the treatment side was associated with an increased incidence of higher flow on the same side in the oedema group. These findings demonstrate that breast cancer treatment results in a significant increase in arterial flow in the arm on the treatment side, and that this increase is even higher in those patients with swelling. Increased blood flow is likely to contribute to arm swelling. One explanation for increased flow would be neurological deficit with loss of sympathetic vasoconstrictor control.