Mazen Sudah

Axillary Lymph Node Biopsy in Newly Diagnosed Invasive Breast Cancer: Comparative Accuracy of Fine-Needle Aspiration Biopsy versus Core-Needle Biopsy

PURPOSE To compare the diagnostic accuracy of ultrasonographically (US)-guided fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) of the axillary lymph nodes (LNs) of patients with newly diagnosed invasive breast cancer. MATERIALS AND METHODS This prospective single-center study had institutional review board approval, and written informed consent was obtained. Between April 2011 and March 2012, 178 consecutive patients (182 axillae) were evaluated by using axillary US. Sixty-six axillae fulfilled the inclusion criteria (cortical thickness greater than 2 mm or abnormal morphologic characteristics), and patients with these axillae underwent US-guided axillary LN biopsy. Both FNAB and CNB were obtained from the same suspicious LN. Patients with biopsy-proved metastasis underwent axillary clearance, and those with a negative biopsy underwent sentinel LN biopsy with completion axillary clearance if needed. Diagnostic performance was calculated separately for US, FNAB, and CNB. Statistical differences in sensitivities were evaluated by using the McNemar test. RESULTS From the total study population, 45.6% (83 of 182 axillae) had metastases. A total of 66 axillae underwent both FNAB and CNB. The sensitivity for US was 61.4% (51 of 83 axillae), and specificity was 84.8% (84 of 88 axillae). The sensitivities for FNAB and CNB were 72.5% (37 of 51 axillae) and 88.2% (45 of 51 axillae), respectively (P = .008). Specificity for both was 100% (15 of 15 axillae). The negative predictive value for FNAB was 81.7%, and that for CNB was 91.2%. The positive predictive value was 100% for both methods. CONCLUSION When accurate preoperative staging of the axilla is needed in patients with newly diagnosed invasive breast cancer, CNB is more sensitive than FNAB.

Surgical specimen can be replaced by core samples in assessment of ER, PR and HER-2 for invasive breast cancer

Objective. To compare 14-gauge SCNB (stereotactic core needle biopsy) with surgery and to investigate tissue-heterogeneity of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth-factor receptor (HER-2) for non-palpable breast cancers. To determine the number of cores needed for assessment of these factors. Materials and methods. Cores of 41 invasive cancers were collected in three containers: the 1st into A, the 2nd and 3rd into B and subsequent cores into C. ER, PR and HER-2 were scored by immunohistochemistry and if 2+ or 3+, by chromogenic-in-situ-hybridisation (CISH) for containers and for surgical specimen. Results. Between SCNB and surgical specimen concordance was 83% (κ=0.39) for ER, 88% (κ=0.69) for PR and HER-2 and 93% (κ=0.63) for HER-2 after CISH. For the most discordant cases, status was positive in cores but negative in surgery: 5/7 for ER (p=0.459), 5/5 for PR (p=0.063), and 4/5 for HER-2 (p=0.375), after CISH 3/3 (p=0.250), but the difference was not statistically significant. Concordances between containers of cores was 100% (κ=1), 85% (κ=0.66) and 85% (κ=0.66), respectively. With more than three cores, sensitivities of 95%, 100% and 100% were reached. Conclusions. SCNB is at least as sensitive as surgery in assessment of ER, PR and HER-2. Three cores are needed for reliable assessment of HER-2 after adding CISH and more than three cores for PR, possibly due to tissue heterogeneity. For ER sensitivity remained lower, 95%, even in multiple cores, therefore ER-negative cases should be further investigated from surgical specimens.

Diffusion-Weighted Imaging in 3.0 Tesla Breast MRI: Diagnostic Performance and Tumor Characterization Using Small Subregions vs. Whole Tumor Regions of Interest

Introduction Apparent diffusion coefficient (ADC) values are increasingly reported in breast MRI. As there is no standardized method for ADC measurements, we evaluated the effect of the size of region of interest (ROI) to diagnostic utility and correlation to prognostic markers of breast cancer. Methods This prospective study was approved by the Institutional Ethics Board; the need for written informed consent for the retrospective analyses of the breast MRIs was waived by the Chair of the Hospital District. We compared diagnostic accuracy of ADC measurements from whole-lesion ROIs (WL-ROIs) to small subregions (S-ROIs) showing the most restricted diffusion and evaluated correlations with prognostic factors in 112 consecutive patients (mean age 56.2±11.6 years, 137 lesions) who underwent 3.0-T breast MRI. Results Intra- and interobserver reproducibility were substantial (κ = 0.616–0.784; Intra-Class Correlation 0.589–0.831). In receiver operating characteristics analysis, differentiation between malignant and benign lesions was excellent (area under curve 0.957–0.962, cut-off ADC values for WL-ROIs: 0.87×10−3 mm2s-1; S-ROIs: 0.69×10−3 mm2s-1, P<0.001). WL-ROIs/S-ROIs achieved sensitivities of 95.7%/91.3%, specificities of 89.5%/94.7%, and overall accuracies of 89.8%/94.2%. In S-ROIs, lower ADC values correlated with presence of axillary metastases (P = 0.03), high histological grade (P = 0.006), and worsened Nottingham Prognostic Index Score (P<0.05). In both ROIs, ADC values correlated with progesterone receptors and advanced stage (P<0.01), but not with HER2, estrogen receptors, or Ki-67. Conclusions ADC values assist in breast tumor characterization. Small ROIs were more accurate than whole-lesion ROIs and more frequently associated with prognostic factors. Cut-off values differed significantly depending on measurement procedure, which should be recognized when comparing results from the literature. Instead of using a whole lesion covering ROI, a small ROI could be advocated in diffusion-weighted imaging.

Contrast-enhanced ultrasound -guided axillary lymph node core biopsy: Diagnostic accuracy in preoperative staging of invasive breast cancer.

OBJECTIVES To evaluate accuracy of contrast enhanced ultrasound (CEUS)-sentinel procedure followed by core biopsy (CB) and marking in patients with breast cancer. To compare the axillary metastatic tumour burden in patients with positive vs. negative CB results. METHODS Two radiologists in our tertiary care hospital performed axillary CEUS sentinel procedures on consecutive US node negative breast cancer patients. The first enhancing lymph node (LN) was core biopsied and marked with a breast coil. The results were compared to final histopathology. We analysed the diagnostic performance of CEUS CB and its ability to detect patients with higher axillary burden (>2 metastasis). RESULTS During the study period between January 2013 and December 2014, altogether 54 patients (mean age 60.4 years) were included in the statistical analysis. The sensitivity for CEUS CB was 66.7%, specificity 100%, PPV 100%, NPV 93.8% and overall accuracy 94.4%. The method correctly recognised all the axillae with higher tumour burdens (sensitivity 100%, N=3) and 59.3% of coils marking the LNs were discovered. CONCLUSION CEUS -guided axillary CB proved to be feasible and accurate procedure with moderate sensitivity and it clearly identified the higher axillary tumour burden. The coil marking of LNs as used cannot be recommended. In clinical routine, CEUS procedure might be recommended in selective patient populations.

Preoperative axillary staging with 3.0-T breast MRI: clinical value of diffusion imaging and apparent diffusion coefficient.

The axillary staging in newly diagnosed breast cancer is under major evolution. The aims of this study were to define the diagnostic performance of 3.0-T diffusion-weighted imaging (DWI) in the detection of axillary metastases in newly diagnosed breast cancer, to assess apparent diffusion coefficients (ADCs) for histopathologically confirmed metastatic lymph nodes in a clinical setting. Altogether 52 consecutive breast cancer patients underwent magnetic resonance imaging and DWI in addition to axillary ultrasound. ADCs of axillary lymph nodes were analysed by two breast radiologists and ultrasound-guided core biopsies were taken. In a separate reading by one radiologist two types of region of interests were used for a smaller group of patients. Altogether 56 axillae (121 lymph nodes) were included in the statistical analysis. Metastatic axillae (51.8%) had significantly lower ADCs (p<0.001). Mean ADCs were 0.663–0.676 x 10-3 mm2/s for the histologically confirmed metastatic LNs and 1.100–1.225 x 10-3 mm2/s for the benign. The sensitivity, specificity, and accuracy of DWI were 72.4%, 79.6%, and 75.9%, respectively with threshold ADC 0.812 x 10-3 mm2/s. Region of interest with information on the minimum value increased the diagnostic performance (area under the curve 0.794 vs. 0.619). Even though ADCs are significantly associated with histopathologically confirmed axillary metastases the diagnostic performance of axillary DWI remains moderate and ultrasound-guided core biopsies or sentinel lymph node biopsies cannot be omitted.

UDP-sugar accumulation drives hyaluronan synthesis in breast cancer

Increased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor. The content of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as compared to normal glandular tissue obtained from breast reductions. The surge of UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly, hyaluronan content did not correlate with the mRNA levels of the hyaluronan synthases (HAS1-3), thus emphasizing the role of the UDP-sugar substrates of these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs. lobular cancer subtypes. The results reveal for the first time a dramatic increase of UDP-sugars in breast cancer, and suggest that their high supply drives the accumulation of hyaluronan, a known promoter of breast cancer and other malignancies. In general, the study shows how the disturbed glucose metabolism typical for malignant tumors can influence cancer microenvironment through UDP-sugars and hyaluronan.

Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography

Objectives To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU). Methods During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test. Results Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T-MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv. Conclusions Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients. Trial Registration ClinicalTrials.gov NCT02606513

Galactography is not an obsolete investigation in the evaluation of pathological nipple discharge

Purpose To evaluate the malignancy rate and diagnostic performance of galactography in patients with pathological nipple discharge (PND) after negative clinical breast examination, mammography and ultrasound. Materials and methods We retrospectively evaluated all galactograms obtained between January 2006 and December 2014 in women with PND. Galactographic findings were classified into 6 groups according to a modified Galactogram Image Classification system (GICS) to comply with the breast imaging reporting and data system classification. Observers were blinded to the final histology and clinical outcome at the time of analysis. MRI was performed as a problem solving ancillary examination. Imaging findings, pathological diagnosis and follow-up data were evaluated. The diagnostic performance of MRI and technically successful galactography in the detection of neoplastic or risk lesions were separately calculated. Results A total of 146 patients with PND (mean age, 51.5 years; range, 17–93) were examined. Malignant lesions were detected in only 4 patients (2.7%) and risk-lesions in 5 patients (3.4%). Only one low-grade ductal carcinoma in situ was missed by galactography (GICS 1) and MRI. MRI examinations were performed in 21 (14.4%) patients; one of these patients (4.8%) had a malignant finding (GICS 0), two (9.5%) had risk-lesions (GICS 2 and 5). In the detection of neoplastic or risk lesions the sensitivity and specificity of galactography were 77.4% and 75.7% and of MRI 85.7% and 71.4%, consecutively. Conclusion The malignancy rate is negligible if clinical, mammography, ultrasound and galactography examinations are negative. Galactography remains a practical, valuable and cost-effective examination procedure. If galactography is technically unsuccessful, MRI should be considered as an additional ancillary tool to evaluate the possible etiology of symptoms, but the routine use of MRI in all patients cannot be justified.

Feasibility of mapping breast cancer with supine breast MRI in patients scheduled for oncoplastic surgery

ObjectivesTo prospectively determine the feasibility of preoperative supine breast MRI in breast cancer patients scheduled for oncoplastic breast-conserving surgery.MethodsIn addition to a diagnostic prone breast MRI, a supplementary supine MRI was performed with the patient in the surgical position including skin markers. Tumours’ locations were ink-marked on the skin according to findings obtained from supine MRI. Changes in tumours’ largest diameter and locations between prone and supine MRI were measured and compared to histology. Nipple-to-tumour and tumour-to-chest wall distances were also measured. Tumours and suspicious areas were surgically removed according to skin ink-markings. The differences between MRI measurements with reference to histopathology were evaluated with the paired-sample t test.ResultsFourteen consecutive patients, 15 breasts and 27 lesions were analysed. Compared to histology, prone MRI overestimated tumour size by 47.1% (p = 0.01) and supine MRI by 14.5% (p = 0.259). In supine MRI, lesions’ mean diameters and areas were smaller compared to prone MRI (– 20.9%, p = 0.009 and – 38.3%, p = 0.016, respectively). This difference in diameter was more pronounced in non-mass lesions (– 31.2%, p = 0.031) compared to mass lesions (– 9.2%, p = 0.009). Tumours’ mean distance from chest wall diminished by 69.4% (p < 0.001) and from nipple by 18.2% (p < 0.001). Free microscopic margins were achieved in first operation in all patients.ConclusionsSupine MRI in the surgical position is feasible and useful in the precise localisation of prone MRI-detected lesions and provides a helpful tool to implement in surgery. Supine MRI more accurately determines tumours’ size and location and might have an important role to diminish overestimations.Key Points•Breath-hold supine breast MRI is feasible using commercially available coils and sequences.•Size and area of lesions on MRI were consistently smaller when measured from the supine position as compared to the prone position.•Supine breast MRI is useful in the precise preoperative localisation of prone MRI-detected lesions.•