Biopsy of amorphous breast calcifications: pathologic outcome and yield at stereotactic biopsy.

PURPOSE: To assess the pathologic outcome of amorphous breast calcifications and the success of stereotactic biopsy for such lesions. MATERIALS AND METHODS: From July 1995 through February 2000, biopsy of all clustered amorphous calcifications not clearly stable for at least 5 years or in a diffuse scattered distribution was recommended. Logistic regression analysis was used to stratify the risk of malignancy by patient risk factors, calcification distribution, and stability. RESULTS: Calcifications were retrieved from 150 biopsies; 30 (20%) proved malignant and included 27 ductal carcinomas in situ and three low-grade invasive and intraductal carcinomas (2-5 mm). Another 30 (20%) yielded high-risk lesions, including 21 atypical ductal hyperplasia, eight atypical lobular hyperplasia, and one lobular carcinoma in situ. In 150 lesions, stereotactic biopsy was performed on 113 and aborted in 10. Calcifications were retrieved from all 113 stereotactic biopsies. Of those with calcification retrieval, there were three histologic underestimates (accuracy, 97%). Stereotactic biopsy spared a surgical procedure in 57 (46%) of 123 patients. Needle localization was required for 23 (15%) of 150 patients due to poor conspicuity. Five (45%) of 11 biopsies performed in women with ipsilateral breast cancer showed malignancy (P = .025). When multiple lesions of amorphous calcifications were present in one breast, sampling of one reliably predicted the outcome of others. CONCLUSION: We found a substantial rate of ductal carcinoma in situ and high-risk lesions associated with amorphous calcifications. Stereotactic biopsy can be successfully performed for the majority of subtle amorphous calcifications; however, only a minority were spared a surgical procedure.

Overview of breast imaging.

In summary, it is an exciting time in breast imaging with many tools being brought to bear on an ever more common problem. The challenge for this decade will be to develop optimal cost-effective strategies to use all the tools now available with minimal discomfort and disfigurement to the patient.

Toward a standardized breast ultrasound lexicon, BI-RADS: ultrasound.

The approach outlined above for describing and reporting sonographic features of breast masses represents only the initial step in the development of a comprehensive system to enhance the accurate identification, reporting, and analysis of sonographic abnormalities of the breast. Future revisions, with validation of interobserver consistency in application of these descriptors across multiple centers, with feedback from potential users in the breast imaging community, will undoubtedly expand the utility of this effort.

Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women.

OBJECTIVE: To assess whether breast implant rupture or extracapsular silicone are associated with selected symptoms of self-reported physician-diagnosed connective tissue disease (CTD). METHODS: Women with silicone gel breast implants responded to a questionnaire that included questions on health status, satisfaction with implants, symptoms of CTD, and physician-diagnosed disease. These women then had magnetic resonance imaging (MRI) of their breasts to determine the status of the implants with respect to rupture and extracapsular silicone. RESULTS: Women with breast implant rupture diagnosed by MRI were no more likely to report a diagnosis of selected CTD than those with intact implants or those with implants of indeterminate status. Women with extracapsular silicone (silicone gel outside of the fibrous scar that forms around breast implants) were more likely to report having fibromyalgia (FM, p = 0.004) or other CTD, which included dermatomyositis, polymyositis, Hashimoto's thyroiditis, mixed CTD, pulmonary fibrosis, eosinophilic fasciitis, and polymyalgia (p = 0.008) than other women in the study. The association with FM remained statistically significant when adjusted for multiple comparisons (7 diagnoses) and implant age, implant location, or implant manufacturer (p < 0.05 in all cases), but became of borderline statistical significance when adjusted for multiple comparisons and self-perceived health status (p = 0.094) or self-perceived rupture status (p = 0.051). The association with other CTD remained statistically significant when adjusted for multiple comparisons and implant location or implant manufacturer, but became borderline or insignificant when adjusted for multiple comparisons and for implant age (p = 0.051), self-perceived health status (p = 0.434), or self-perceived rupture status (p = 0.145). Logistic regression was used to compute odds ratios of self-reported diagnoses comparing women with and without extracapsular silicone. The odds ratios were 2.8 (95% CI 1.2 to 6.3) for FM, and 2.6 (95% CI 0.8 to 8.5) for other CTD after adjustment for implant age, implant location, implant manufacturer, implant type, self-perceived health, self-perceived rupture status, and site of surgery practice. CONCLUSION: These data suggest an association between extracapsular silicone from ruptured silicone breast implants and FM. If this association persists in other studies, women with silicone gel breast implants should be informed of the potential risk of developing fibromyalgia if their breast implants rupture and the silicone gel escapes the fibrous scar capsule.

Fine-needle aspiration biopsy of nonpalpable breast lesions in a multicenter clinical trial: results from the radiologic diagnostic oncology group V.

PURPOSE: To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine-needle aspiration biopsy (FNAB) in the diagnosis of nonpalpable breast lesions. MATERIALS AND METHODS: At 18 institutions, 442 women who underwent 22-25-gauge imaging-guided FNAB were enrolled. Definitive surgical, core-needle biopsy, and/or follow-up information was available for 423 (95.7%) of these women. The reference standard was established from additional clinical and imaging information for an additional six (1.4%) women who did not undergo further histopathologic evaluation. The FNAB protocol was standardized at all institutions, and all specimens were reread by one of two expert cytopathologists. RESULTS: When insufficient samples were included in the analysis and classified as positive, the sensitivity and specificity of FNAB were 85%-88% and 55.6%-90.5%, respectively; accuracy ranged from 62.2% to 89.2%. The diagnostic accuracy of FNAB was significantly better for detection of masses than for detection of calcifications (67.3% vs. 53.8%, P =.006) and with US guidance than with stereotactic guidance (77.2% vs. 58.9%; P =.002). CONCLUSION: FNAB of nonpalpable breast lesions has limited value given the high insufficient sample rate and greater diagnostic accuracy of other interventions, including core-needle biopsy and needle-localized open surgical biopsy.

Atypical lobular hyperplasia or lobular carcinoma in situ at core-needle breast biopsy.

PURPOSE: To review outcomes of lesions diagnosed at core-needle breast biopsy as atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: Results from 1,400 consecutive core-needle breast biopsies were reviewed. Twenty-five (1.8%) biopsy samples with the diagnosis of lobular neoplasia (15 with ALH and 10 with LCIS) adjacent to or in a targeted benign lesion were found. Lesions were excised (n = 15) or followed up (n = 10) at least 22 months. RESULTS: Of the 15 lesions with ALH, 13 (87%) were adjacent to (n = 12) or associated with (n = 1) microcalcifications, and two (13%) were in masses. Six lesions with residual calcifications were excised. One lesion was diagnosed as ductal carcinoma in situ (DCIS), and five were benign (residual ALH was seen in four). One excised mass showed residual ALH. Six lesions were gone at follow-up, one cluster of microcalcifications was decreased in size, and one fibroadenoma with ALH was stable. Of the 10 lesions with LCIS, seven (70%) were adjacent to (n = 6) or associated with (n = 1) microcalcifications, and three (30%) were in or adjacent to masses. Five lesions with LCIS and residual microcalcifications were excised. Three yielded atypical ductal hyperplasia (ADH); one, residual LCIS; and one, ALH. Three masses with LCIS were excised. One showed residual LCIS; one, a papilloma with adjacent LCIS; and one, a fibroadenoma with LCIS in it. One cluster of microcalcifications was gone at follow-up, and one was stable. CONCLUSION: After a diagnosis of lobular neoplasia at core biopsy, residual microcalcifications are viewed in the context of a patient at higher risk of cancer. Of 11 lesions with residual microcalcifications, three (27%) were ADH and one (9%) was DCIS.

Prevalence of rupture of silicone gel breast implants revealed on MR imaging in a population of women in Birmingham, Alabama.

OBJECTIVE: Silicone gel breast implants have been reported to rupture, but the prevalence of implant rupture in an unreferred population of women is not known. The objective of this study was to assess the prevalence of implant rupture and the presence of extracapsular silicone gel in an unreferred population of women without regard to the absence or presence of any local or systemic symptoms. SUBJECTS AND METHODS: Women identified as part of a National Cancer Institute cohort study on breast implants, living in the Birmingham, AL, area were invited to undergo MR imaging of their current silicone gel breast implants at the Kirklin Clinic at the University of Alabama at Birmingham. Three radiologists independently examined and rated all MR images for signs of implant rupture and extracapsular silicone. RESULTS: A total of 344 women with silicone gel breast implants underwent MR imaging. Breast implant rupture was reported by at least two of three radiologists for 378 (55.0%) of the 687 implants in this study. Another 50 implants (7.2%) were rated as indeterminate (suspicious) for rupture. A majority of women in this study, 265 (77.0%) of 344, had at least one breast implant that was rated as ruptured or indeterminate. Radiologists also agreed that silicone gel could be seen outside the fibrous capsule that forms around the implant in 85 (12.4%) of the 687 implants affecting 73 women (21.2%). Factors that affected implant rupture were implant age and location (submuscular or subglandular). The median implant age at rupture was estimated to be 10.8 years with a 95% confidence interval of 8.4-13.9 years. CONCLUSION: The prevalence of silent or occult silicone gel breast implant rupture is higher than was previously suspected. Most women in this study had MR imaging evidence of at least one ruptured silicone gel breast implant.

Breast Imaging Reporting and Data System: inter- and intraobserver variability in feature analysis and final assessment.

OBJECTIVE: We sought to evaluate the use of the Breast Imaging Reporting and Data System (BI-RADS) standardized mammography lexicon among and within observers and to distinguish variability in feature analysis from variability in lesion management. MATERIALS AND METHODS: Five experienced mammographers, not specifically trained in BI-RADS, used the lexicon to describe and assess 103 screening mammograms, including 30 (29%) showing cancer, and a subset of 86 mammograms with diagnostic evaluation, including 23 (27%) showing cancer. A subset of 13 screening mammograms (two with malignant findings, 11 with diagnostic evaluation) were rereviewed by each observer 2 months later. Kappa statistics were calculated as measures of agreement beyond chance. RESULTS: After diagnostic evaluation, the interobserver kappa values for describing features were as follows: breast density, 0.43; lesion type, 0.75; mass borders, 0.40; special cases, 0.56; mass density, 0.40; mass shape, 0.28; microcalcification morphology, 0.36; and microcalcification distribution, 0.47. Lesion management was highly variable, with a kappa value for final assessment of 0.37. When we grouped assessments recommending immediate additional evaluation and biopsy (BI-RADS categories 0, 4, and 5 combined) versus follow-up (categories 1, 2, and 3 combined), five observers agreed on management for only 47 (55%) of 86 lesions. Intraobserver agreement on management (additional evaluation or biopsy versus follow-up) was seen in 47 (85%) of 55 interpretations, with a kappa value of 0.35-1.0 (mean, 0.60) for final assessment. CONCLUSION: Inter- and intraobserver variability in mammographic interpretation is substantial for both feature analysis and management. Continued development of methods to improve standardization in mammographic interpretation is needed.

Genetic taste markers and preferences for vegetables and fruit of female breast care patients.

OBJECTIVE: To explore links between genetic responsiveness to the bitter taste of 6-n-propylthiouracil (PROP) and self-reported preferences for vegetables and fruit of female breast care patients. METHODS: PROP tasting was defined by detection thresholds and by perceived bitterness and hedonic ratings for PROP solutions. Nontasters, medium tasters, and supertasters were identified by their PROP thresholds and by the ratio of perceived bitterness of PROP to the perceived saltiness of sodium chloride solutions. Subjects rated preferences for vegetables and fruit using 9-point category scales. SUBJECTS/SETTING: A clinical sample of 170 patients with newly diagnosed breast cancer and 156 cancer-free control subjects were recruited from the University of Michigan Breast Care Center. STATISTICAL ANALYSES: Principal components factor analysis, one-way analyses of variance, and Pearson correlations and chi 2 tests were used to analyze taste and food preference data. RESULTS: Genetic responsiveness to PROP was associated with lower acceptance of cruciferous and selected green and raw vegetables (P < .05). Women who reported disliking such foods were medium tasters or supertasters of PROP. Preference ratings for fruit were unrelated to PROP taster status. APPLICATIONS/CONCLUSIONS: Women who are PROP tasters may be less likely to comply with dietary strategies for cancer prevention that emphasize consumption of cruciferous vegetables and bitter salad greens. Alternatively, PROP-sensitive women may seek to reduce bitter taste by adding fat, sugar, or salt.

Multicentric and multifocal cancer: whole-breast US in preoperative evaluation.

PURPOSE: To evaluate preoperative whole-breast ultrasonography (US) in the management of breast cancer. MATERIALS AND METHODS: The ipsilateral breast in 40 patients with known breast cancer or in whom there was high suspicion of breast cancer was evaluated with whole-breast US. Biopsy was performed on all discrete solid lesions. RESULTS: US depicted 45 (94%) of 48 invasive tumor foci and seven (44%) of 16 foci of ductal carcinoma in situ (DCIS). Mammography depicted 39 (81%) of 48 invasive tumor foci and 14 (88%) of 16 foci of DCIS. The nine (14%) of 64 malignant foci seen only at US included three infiltrating ductal carcinomas, two mixed infiltrating and intraductal carcinomas, two infiltrating lobular carcinomas, and two foci of DCIS. Two (18%) of 11 foci of infiltrating lobular carcinoma were missed at both US and mammography. Of 20 patients mammographically suspected of having unifocal disease, three (15%) required wider excision on the basis of US findings. Two additional foci were depicted only at US in one of 16 patients mammographically suspected of having multicentric or multifocal disease. Of four patients with mammographically occult disease, US correctly depicted the diffuse (n = 2) or unifocal (n = 2) extent of the cancer. CONCLUSION: Whole-breast US complements mammography in the preoperative evaluation of patients with breast cancer, particularly when breast conservation is contemplated.

The hybrid-cluster protein ('prismane protein') from Escherichia coli. Characterization of the hybrid-cluster protein, redox properties of the [2Fe-2S] and [4Fe-2S-2O] clusters and identification of an associated NADH oxidoreductase containing FAD and [2Fe-2S].

Hybrid-cluster proteins ('prismane proteins') have previously been isolated and characterized from strictly anaerobic sulfate-reducing bacteria. These proteins contain two types of Fe/S clusters unique in biological systems: a [4Fe-4S] cubane cluster with spin-admixed S = 3/2 ground-state paramagnetism and a novel type of hybrid [4Fe-2S-2O] cluster, which can attain four redox states. Genomic sequencing reveals that genes encoding putative hybrid-cluster proteins are present in a range of bacterial and archaeal species. In this paper we describe the isolation and spectroscopic characterization of the hybrid-cluster protein from Escherichia coli. EPR spectroscopy shows the presence of a hybrid cluster in the E. coli protein with characteristics similar to those in the proteins of anaerobic sulfate reducers. EPR spectra of the reduced E. coli hybrid-cluster protein, however, give evidence for the presence of a [2Fe-2S] cluster instead of a [4Fe-4S] cluster. The hcp gene encoding the hybrid-cluster protein in E. coli and other facultative anaerobes occurs, in contrast with hcp genes in obligate anaerobic bacteria and archaea, in a small operon with a gene encoding a putative NADH oxidoreductase. This NADH oxidoreductase was also isolated and shown to contain FAD and a [2Fe-2S] cluster as cofactors. It catalysed the reduction of the hybrid-cluster protein with NADH as an electron donor. Midpoint potentials (25 degrees C, pH 7.5) for the Fe/S clusters in both proteins indicate that electrons derived from the oxidation of NADH (Em NADH/NAD+ couple: -320 mV) are transferred along the [2Fe-2S] cluster of the NADH oxidoreductase (Em = -220 mV) and the [2Fe-2S] cluster of the hybrid-cluster protein (Em = -35 mV) to the hybrid cluster (Em = -50, +85 and +365 mV for the three redox transitions). The physiological function of the hybrid-cluster protein has not yet been elucidated. The protein is only detected in the facultative anaerobes E. coli and Morganella morganii after cultivation under anaerobic conditions in the presence of nitrate or nitrite, suggesting a role in nitrate-and/or nitrite respiration.

Core needle breast biopsy in patients undergoing anticoagulation therapy: preliminary results.

OBJECTIVE: We compared complication rates of core needle breast biopsy in patients with and without concurrent anticoagulation therapy. SUBJECTS AND METHODS: Experience with 501 14-gauge and 179 11-gauge core needle breast biopsies was recorded prospectively. We performed 18 (3%) of 680 procedures on patients undergoing anticoagulation therapy. Eleven biopsies were performed in eight women treated with warfarin, one in a patient treated with heparin, and six in six women treated with aspirin. Ten biopsies were performed with sonographic guidance and a 14-gauge automated biopsy gun. Eight biopsies were performed with an 11-gauge vacuum-assisted probe and stereotactic guidance. RESULTS: Hematomas occurred in three (38%) of eight anticoagulated patients undergoing 11-gauge vacuum-assisted stereotactic biopsy, measuring 13 mm, 17 mm, and 40 mm. In patients not known to be anticoagulated, small hematomas were mammographically evident in 77 (45%) of 171 biopsies performed with an 11-gauge probe, averaging 8 mm (range, 2-17 mm); only 13 (8%) of 171 had hematomas larger than 10 mm. Small hematomas, averaging 6 mm (range, 2-12 mm) were evident mammographically in 45 (45%) of 100 stereotactic biopsies using a 14-gauge automated biopsy gun; three (3%) experienced hematomas larger than 10 mm. A 10-mm hematoma was evident during one (10%) of the 10 biopsies performed in patients undergoing anticoagulation therapy under sonographic guidance using a 14-gauge automated biopsy gun; small hematomas (mean, 10 mm) were noted during seven (2%) of 391 corresponding sonographically guided biopsies in patients not undergoing anticoagulation therapy. CONCLUSION: No patients undergoing anticoagulation therapy experienced clinically important complications; preliminary results suggest rates of hematoma formation similar to those in the control group. As such, discontinuing anticoagulation medication before core needle breast biopsy may be unnecessary when the need for biopsy is urgent.

Imaging spectrum of extracapsular silicone: correlation of US, MR imaging, mammographic, and histopathologic findings.

The appearance of free silicone at mammography, ultrasonography (US), and magnetic resonance (MR) imaging is variable. The classic appearance is dense areas of opacity on mammograms, a highly echogenic pattern with or without hypoechoic masses on US images, and foci of low signal intensity on fat-suppressed T1-weighted MR images or high signal intensity on water-suppressed T2-weighted MR images. Mammography is a reliable, cost-effective, and readily available means of demonstrating silicone. The major disadvantage of US is that its accuracy depends on the capability of the operator to recognize the abnormality. Although MR imaging outperforms US or mammography in detection of implant rupture, it is not clear that MR imaging is superior in detection of free or residual silicone. The sequelae of noncontained silicone include granuloma formation, fibrosis, and migration. After extrusion from an implant, silicone migrates primarily to local sites, such as the ipsilateral chest wall and axillary nodes. Migration of silicone into the axilla can involve the brachial plexus, resulting in neuropathy. Silicone can also migrate into more distal regions, including the arm and subcutaneous tissues of the abdominal wall. Whatever the source, silicone in breast tissue interferes with the interpretation of mammographic findings.

MammoWeb continuing medical education (CME): a web-based breast imaging CME program.

The ubiquity of the world-wide web allows unique educational opportunities for continuing medical education (CME). We have designed a comprehensive breast imaging CME curriculum to permit individual physicians in their homes or offices to use personal computers to ease the burden of this process. Category 1 CME credits can be earned off-hours without having the physician travel out of town. In addition, since the course is computer-based, the overall costs to the participant are substantially reduced. The program can be updated on an ongoing basis to include new technology or to provide additional information requested by the users.

Predictive value of specimen radiography for core needle biopsy of noncalcified breast masses.

OBJECTIVE: Our objective was to determine the predictive value of specimen radiography for large core (14-gauge) needle biopsy of noncalcified breast masses. SUBJECTS AND METHODS: Eighty-four biopsies of 83 breast masses yielded 403 specimens. Specimens showing dense material on specimen radiography were predicted to be diagnostic; specimens showing intermediate- or low-density material were predicted to be nondiagnostic. Specimen radiographic and histopathologic findings were correlated for each specimen using vital dyes to mark individual specimens. RESULTS: Of the 403 specimens, 307 (76%) contained diagnostic material representative of the lesion, with a specific diagnosis achieved for 82 (99%) of 83 lesions (62 benign, 20 malignant). Of the 293 passes containing dense material, 268 (91%) proved to be diagnostic; 11 (18%) of 62 specimens containing only low-density material proved to be diagnostic. Of the 25 (9%) of 293 specimens containing radiographically dense but nondiagnostic material, 18 (72%) showed focal fibrosis and had missed the lesion; 15 (83%) of 18 such specimens were obtained in dense parenchyma. The positive predictive value of specimen radiography was 13 (100%) of 13 in fatty breasts; 77 (96%) of 80 in breasts with minimal scattered fibroglandular elements; 91 (94%) of 97 in heterogeneously dense breasts; and 35 (70%) of 50 in breasts with extremely dense parenchyma. Of the 16 lesions sampled stereotactically, specimen radiography helped assess the inadequacy of initial sampling in three (19%). In six (9%) of 68 sonographically guided biopsies, only one or two specimens could be obtained; specimen radiography helped us predict whether material was adequate for diagnosis. CONCLUSION: Radiography of core specimens obtained from noncalcified breast masses accurately reveals the adequacy of sampling unless the breast parenchyma is extremely dense. Such immediate assessment can help ensure adequate material from lesions that are difficult to biopsy and can thereby improve the diagnostic yield of large core needle breast biopsy.

Mammographic-histopathologic correlation of large-core needle biopsies of the breast.

Large-core (14g) needle biopsy (CNB) of the breast is a new diagnostic modality increasingly being used to evaluate patients with mammographic abnormalities. Two hundred twenty-four CNBs were performed on 198 patients. Surgical follow-up was available in 64 cases (28.6%). Overall concordance rate was 93.8% (60 of 64 cases). Of the four discordant cases, two were diagnosed as atypical ductal hyperplasia (ADH) on CNB; on excision, these cases showed cribriform ductal carcinoma in situ (DCIS); two remaining cases, diagnosed on CNB as ADH versus DCIS, showed invasive carcinoma (DCIS with invasive component and infiltrating cribriform carcinoma, respectively) on excisional biopsy. Malignancy, primary (52) or metastatic (5), was identified in 57 cases (25.4%); 47 of these patients underwent surgical excision, and the diagnosis was confirmed in all of these cases. Of 51 cases with radiographic evidence of microcalcifications, 48 (94%) had microcalcifications in the CNB: 30 (62.5%) were benign, 11 (22.9%) were malignant, and 7 (14.6%) were diagnosed as ADH. In the remaining three cases (1.3%), only benign breast tissue without microcalcifications was seen, and the lesion was considered to have been missed. Biopsy specimens were obtained from 173 lesions because of the presence of a mass: 125 (72.3%) were benign, 45 (26%) were malignant, and 3 (1.7%) were diagnosed as ADH. Follow-up was available in 118 patients with benign lesions: all were mammographically stable or decreased at 6 or 12 months; no follow-up was available for the remaining patients. CNB of the breast is a highly sensitive (96.9%) and specific (100%) technique for management of patients with mammographic abnormalities. The histologic findings should be correlated with the mammographic appearance, and an attempt should be made to achieve a specific diagnosis in all lesions, particularly masses. The diagnosis of ADH should always prompt excisional biopsy because of a high frequency of false-negative results caused by sampling errors or underestimation.

Apocrine metaplasia: mammographic and sonographic appearances.

OBJECTIVE: Our objective was to evaluate the mammographic and sonographic appearances of apocrine metaplasia and correlate imaging and histopathologic findings. MATERIALS AND METHODS: Retrospective review of 408 lesions in 318 consecutive patients undergoing core needle biopsy (n = 370) or fine needle aspiration (n = 38) revealed 46 cases of apocrine metaplasia. In 17 of these cases, apocrine metaplasia represented more than 50% of the lesion sampled; these 17 lesions formed the basis for analysis. RESULTS: On mammography, all 17 cases appeared as new or enlarging equal-density (n = 15) or low-density (n = 2) masses with an average size of 12.8 mm. Borders were microlobulated in 59% (10/17), macrolobulated in 29% (5/17), and circumscribed or oval in 12% (2/17). Sonography revealed a lobulated mass containing a cluster of small (2- to 5-mm) anechoic foci and intervening septae in 77% (10/13) of cases. A discrete hypoechoic solid component was seen in 23% of cases (3/13). Posterior acoustic enhancement was seen in 85% of cases (11/13). In 65% of lesions (11/17), we noted a decrease in size or total resolution during biopsy or fine needle aspiration. Histopathologic examination showed the typical appearance of dilated cystic acini lined by apocrine metaplastic epithelium. CONCLUSION: On mammography, the combined findings of an equal- or low-density microlobulated or lobulated mass that corresponds on sonography to a cluster of small (2- to 5-mm) anechoic foci with intervening septae should suggest the diagnosis of focal apocrine metaplasia. With radiologists' increasing experience, follow-up, rather than biopsy, of such typical-appearing lesions may be adequate.

Apparent local stability of the secondary structure of Azotobacter vinelandii holoflavodoxin II as probed by hydrogen exchange: implications for redox potential regulation and flavodoxin folding.

As a first step to determine the folding pathway of a protein with an alpha/beta doubly wound topology, the 1H, 13C, and 15N backbone chemical shifts of Azotobacter vinelandii holoflavodoxin II (179 residues) have been determined using multidimensional NMR spectroscopy. Its secondary structure is shown to contain a five-stranded parallel beta-sheet (beta2-beta1-beta3-beta4-beta5) and five alpha-helices. Exchange rates for the individual amide protons of holoflavodoxin were determined using the hydrogen exchange method. The amide protons of 65 residues distributed throughout the structure of holoflavodoxin exchange slowly at pH* 6.2 [kex < 10(-5) s(-1)] and can be used as probes in future folding studies. Measured exchange rates relate to apparent local free energies for transient opening. We propose that the amide protons in the core of holoflavodoxin only exchange by global unfolding of the apo state of the protein. The results obtained are discussed with respect to their implications for flavodoxin folding and for modulation of the flavin redox potential by the apoprotein. We do not find any evidence that A. vinelandii holoflavodoxin II is divided into two subdomains based on its amide proton exchange rates, as opposed to what is found for the structurally but not sequentially homologous alpha/beta doubly wound protein Che Y.