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1.  Imaging Findings of Invasive Micropapillary Carcinoma of the Breast 
Journal of Breast Cancer  2012;15(1):57-64.
Purpose
The purpose of this study is to evaluate imaging and histopathologic findings including the immunohistochemical characteristics of invasive micropapillary carcinoma (IMPC) of the breast.
Methods
Twenty-nine patients diagnosed with IMPC were included in the present study. Mammographic, sonographic, and magnetic resonance imaging (MRI) findings were analyzed retrospectively according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings were also evaluated. Microscopic slides of surgical specimens were reviewed in consensus by two pathologists with a specialty in breast pathology.
Results
Most IMPCs presented as a high density irregular mass with a non-circumscribed margin associated with microcalcifications on mammography, as an irregular hypoechoic mass with a spiculated margin on ultrasound, and as irregular spiculated masses with washout patterns on MRI. PET-CT showed a high maximum standardized uptake value (SUVmax) (mean, 11.2). Axillary nodal metastases were identified in 65.5% of the patients. Immunohistochemical studies showed high positivities for estrogen receptor and c-erbB-2 (93.1% and 51.7µ, respectively).
Conclusion
Even though the imaging characteristics of IMPCs are not distinguishable from typical invasive ductal carcinomas, this tumor type frequently results in nodal metastases and high positivities for both estrogen receptor and c-erbB-2. The high SUVmax value that is apparent on PET-CT might be helpful in the diagnosis of IMPC.
doi:10.4048/jbc.2012.15.1.57
PMCID: PMC3318175  PMID: 22493629
Breast; Carcinoma; Magnetic resonance imaging; Mammography; Ultrasound
2.  Pure and Mixed Tubular Carcinoma of the Breast: Mammographic and Sonographic Differential Features 
Korean Journal of Radiology  2007;8(2):103-110.
Objective
We wanted to evaluate the mammographic and sonographic differential features between pure (PT) and mixed tubular carcinoma (MT) of the breast.
Materials and Methods
Between January 1998 and May 2004, 17 PTs and 14 MTs were pathologically confirmed at our institution. The preoperative mammography (n = 26) and sonography (n = 28) were analyzed by three radiologists according to BI-RADS.
Results
On mammography, a mass was not detected in eight patients with PT and in one patient with MT (57% vs. 8%, respectively, p = 0.021), which was statistically different. The other findings on mammography and sonography showed no statistical differences between the PT and MT, although the numerical values were different. When the lesions were detected mammographically, an irregularly shaped mass with a spiculated margin was more frequently found in the MT than in the PT (100% vs. 83%, respectively, p = 0.353). On sonography, all 28 patients presented with a mass and most lesions showed as not being circumscribed, hypoechoic masses with an echogenic halo. Surrounding tissue changes and posterior shadowing were more frequently found in the MT than in the PT (75% vs. 50%, respectively, p = 0.253, 58% vs. 19%, respectively, p = 1.000). An oval shaped mass was more frequently found in the PT than in the MT (44% vs. 25%, respectively; p = 0.434).
Conclusion
PT and MT cannot be precisely differentiated on mammography and sonography. However, the absence of a mass on mammography or the presence of an oval shaped mass would favor the diagnosis of PT. An irregularly shaped mass with surrounding tissue change and posterior shadowing on sonography would favor the diagnosis of MT and also a less favorable prognosis.
doi:10.3348/kjr.2007.8.2.103
PMCID: PMC2626773  PMID: 17420627
Breast neoplasms, diagnosis; Breast, US; Breast, mammography; Breast, biopsy
3.  Invasive ductolobular carcinoma of the breast: spectrum of mammographic, ultrasound and magnetic resonance imaging findings correlated with proportion of the lobular component 
SpringerPlus  2013;2:621.
Purpose
The aim of this study was to describe the imaging features of patients with invasive ductolobular carcinoma of the breast in comparison with the proportion of the lobular component.
Materials and methods
We retrospectively reviewed mammographic, sonographic and MRI records of 113 patients with proven ductolobular carcinoma diagnosed between January 2008 and October 2012 according to the BI-RADS ® lexicon, and correlated these to the proportion of the lobular component.
Results
At mammography the most common finding (62.9%) for invasive ductolobular carcinoma was an irregular, spiculated and isodense mass. On ultrasound an irregular and hypoechoic mass, with spiculated margins and posterior acoustic shadowing was observed in 46.8% of cases. Isolated mass and mass associated with non-mass like enhancement (NMLE) were the most common findings by MRI (89.4%). Washout pattern in delayed phase was seen in 61.2% and plateau curve was more frequently observed in patients with larger lobular component. Additional malignant findings (multifocality, multicentricity and contralateral disease) did not correlate significantly with the proportion of the lobular component.
Conclusion
Invasive ductolobular carcinoma mainly presents as an irregular, spiculated mass, isodense on mammography and hypoechoic with posterior acoustic shadowing. On MRI it is usually seen as an isolated mass or as a dominant mass surrounded by smaller masses or NMLE. Washout is the most ordinary kinetic pattern of these tumors. In general, the imaging characteristics did not vary significantly with the proportion of the lobular component.
doi:10.1186/2193-1801-2-621
PMCID: PMC3858590  PMID: 24340243
Breast carcinoma; Lobular; Ductal; Mammography; Ultrasonography; Magnetic resonance imaging
4.  Correlation between mammographic and sonographic findings and prognostic factors in patients with node-negative invasive breast cancer 
The British Journal of Radiology  2011;84(997):19-30.
Objectives
The purpose of this study was to correlate sonographic and mammographic findings with prognostic factors in patients with node-negative invasive breast cancer.
Methods
Sonographic and mammographic findings in 710 consecutive patients (age range 21–81 years; mean age 49 years) with 715 node-negative invasive breast cancers were retrospectively evaluated. Pathology reports relating to tumour size, histological grade, lymphovascular invasion (LVI), extensive intraductal component (EIC), oestrogen receptor (ER) status and HER-2/neu status were reviewed and correlated with the imaging findings. Statistical analysis was performed using logistic regression analysis and intraclass correlation coefficient (ICC).
Results
On mammography, non-spiculated masses with calcifications were associated with all poor prognostic factors: high histological grade, positive LVI, EIC, HER-2/neu status and negative ER. Other lesions were associated with none of these poor prognostic factors. Hyperdense masses on mammography, the presence of mixed echogenicity, posterior enhancement, calcifications in-or-out of masses and diffusely increased vascularity on sonography were associated with high histological grade and negative ER. Associated calcifications on both mammograms and sonograms were correlated with EIC and HER-2/neu overexpression. The ICC value for the disease extent was 0.60 on mammography and 0.70 on sonography.
Conclusion
Several sonographic and mammographic features can have a prognostic value in the subsequent treatment of patients with node-negative invasive breast cancer. Radiologists should pay more attention to masses that are associated with calcifications because on both mammography and sonography associated calcifications were predictors of positive EIC and HER-2/neu overexpression.
doi:10.1259/bjr/92960562
PMCID: PMC3473801  PMID: 20682592
5.  Breast cancer imaging: Mammography among women of up to 45 years 
Polish Journal of Radiology  2010;75(1):37-42.
Summary
Background:
Among women under the age of 40, screening mammography examinations are not performed routinely. An ultrasonography scan is considered to be a basic breast imaging examination among younger women. The purpose of this study was to analyze mammography images, as well as to evaluate the usefulness and role of mammography in breast cancer diagnostic processes in women of up to 45 years, based on own experience.
Material/Methods:
A retrospective analysis of mammography images, including 144 cases of breast cancer diagnosed in the group of 140 women of 45 years of age. All the patients underwent pre-treatment mammography and surgery procedure. The images were evaluated in accordance to BIRADS criteria. Lesions detectable in mammography were grouped as follows: • spiculated mass; • non-microcalcified oval/round mass; • microcalcified mass (regardless of shape); • microcalcifications; • architectural distortion; • breast tissue asymmetry.
Results:
The most common mammographic symptom was solid tumor (41%), followed by microcalcified tumors (20.8%). Clusters of microcalcifications constituted 17.4% of mammography findings. In 4.9% of mammography scans, examination did not reveal any pathological lesions.
Conclusions:
Breast cancer mammograms of women aged up to 45 years do not differ from diagnostic pictures of breast cancer in older women.
The diagnostic appearance of breast cancer in 1/3 of the patients involved microcalcifications detectable only on mammograms.
All the women with suspicion of breast cancer should have their mammography examinations performed, irrespective of ultrasonography scans.
PMCID: PMC3389859  PMID: 22802759
breast cancer; mammography; young women; microcalcifications
6.  The Role of Sonography in Patients with Breast Cancer Presenting as an Axillary Mass 
Korean Journal of Radiology  2002;3(3):189-193.
Objective
To compare sonography and mammography in terms of their diagnostic value in breast cancer cases which initially presented as an axillary mass without a palpable mass or other clinical symptoms.
Materials and Methods
Seven patients with enlarged axillary lymph nodes who first presented with no evidence of palpable breast lesions and who underwent both mammography and sonography were enrolled in this study. In six of the seven, the presence of metastatic adenocarcinoma was confirmed preoperatively by axillary needle aspiration biopsy; in four, subsequent sonographically-guided breast core biopsy performed after careful examination of the primary site indicated that primary breast cancer was present. In each case, the radiologic findings were evaluated by both breast sonography and mammography.
Results
Breast lesions were detected mammographically in four of seven cases (57%); in three of the four, the lesion presented as a mass, and in one as microcalcification. In three of these four detected cases, fatty or scattered fibroglandular breast parenchyma was present; in one, the parenchyma was dense. In the three cases in which lesions were not detected, mammography revealed the presence of heterogeneously dense parenchyma. Breast sonography showed that lesions were present in six of seven cases (86%); in the remaining patient, malignant microcalcification was detected at mammography. Final pathologic examination indicated that all breast lesions except one, which was a ductal carcinoma in situ, with microinvasion, were infiltrating ductal carcinomas whose size ranged from microscopic to greater than 3 cm. At the time of this study, all seven patients were alive and well, having been disease free for up to 61 months after surgery.
Conclusion
In women with a palpable axillary mass confirmed as metastatic adenocarcinoma, breast sonography may be a valuable adjunct to mammography.
doi:10.3348/kjr.2002.3.3.189
PMCID: PMC2713883  PMID: 12271164
Breast neoplasms, diagnosis; Breast neoplasms, radiography; Breast neoplasms, US
7.  Clinicopathological features of invasive micropapillary carcinoma of the breast 
Oncology Letters  2014;9(3):1163-1166.
The aim of the present study was to evaluate the clinical and immunohistopathological findings of invasive micropapillary carcinoma (IMPC) of the breast. In total, 25 patients were included in the present study, all of whom were diagnosed with IMPC. The mammography and ultrasound scanning (US) findings were analysed retrospectively according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. Surgical specimens obtained from the patients were microscopically reviewed in consensus by two pathologists with a specialisation in breast pathology. All the patients presented with palpable lumps in the breast, a high-density irregular mass associated with microcalcifications revealed by mammography and an irregular hypoechoic mass with a spiculated margin revealed by US. Axillary lymph node metastases were identified in 80% of the patients. Immunohistochemical studies revealed the lesions to be highly positive for the oestrogen receptor (ER) and c-erbB-2 (88% and 84%, respectively). Although no significant imaging characteristics were found to distinguish IMPC from typical invasive ductal carcinoma, IMPC resulted in nodal metastases and was highly positive for ER and c-erbB-2. This clinical significance indicates the significance of this entity being recognised by pathologists and surgeons.
doi:10.3892/ol.2014.2806
PMCID: PMC4315051  PMID: 25663874
breast carcinoma; invasive micropapillary carcinoma; immunohistochemistry
8.  Solid neuroendocrine breast carcinoma: mammographic and sonographic features in thirteen cases 
Chinese Journal of Cancer  2012;31(11):549-556.
This study aimed to determine and quantitate the mammographic and sonographic characteristics in 13 cases of solid neuroendocrine breast carcinoma (NEBC) and to analyze the association of radiological findings with the clinical and histopathologic findings. The clinical data and imaging findings of 13 female patients with histologically confirmed solid NEBC were reviewed. Imaging data were evaluated by two radiologists for a consensual diagnosis. All patients presented with one palpable mass; only 1 experienced occasional breast pain, and 5 complained of fluid discharge. In 7 patients, the masses were firm and mobile. Regional lymph node metastasis was noted in only 1 patient. For the 10 patients who underwent mammography, 6 had a mass, 1 had clustered small nodules with clustered punctuate microcalcifications, 2 had asymmetric focal density, and 1 had solitary punctuate calcification. Most of the masses had irregular shape with indistinct or microlobulated margins. For the 9 patients who underwent ultrasonography (US), 9 masses were depicted, all of which were hypoechoic, mostly with irregular shape and without acoustic phenomena. Different types of acoustic phenomena were also identified. One patient had developed distant metastases during follow-up. NEBC has a variety of presentations, but it is mostly observed on mammograms as a dense, irregular mass with indistinct or microlobulated margins. Sonographically, it typically presents as an irregular, heterogeneously hypoechoic mass with normal sound transmission. Histories of nipple discharge and calcification observed using imaging are not rare.
doi:10.5732/cjc.011.10370
PMCID: PMC3777518  PMID: 22640624
Solid neuroendocrine carcinoma of the breast; mammography; sonography
9.  Role of Computer-Aided Detection in Very Small Screening Detected Invasive Breast Cancers 
Journal of Digital Imaging  2012;26(3):572-577.
This study aims to assess computer-aided detection (CAD) performance with full-field digital mammography (FFDM) in very small (equal to or less than 1 cm) invasive breast cancers. Sixty-eight invasive breast cancers less than or equal to 1 cm were retrospectively studied. All cases were detected with FFDM in women aged 49–69 years from our breast cancer screening program. Radiological characteristics of lesions following BI-RADS descriptors were recorded and compared with CAD sensitivity. Age, size, BI-RADS classification, breast density type, histological type of the neoplasm, and role of the CAD were also assessed. Per-study specificity and mass false-positive rate were determined by using 100 normal consecutive studies. Thirty-seven (54.4 %) masses, 17 (25 %) calcifications, 6 (8.8 %) masses with calcifications, 7 (10.3 %) architectural distortions, and 1 asymmetry (1.5 %) were found. CAD showed an overall sensitivity of 86.7 % (masses, 86.5 %; calcifications, 100 %; masses with calcifications, 100 %; and architectural distortion, 57.14 %), CAD failed to detect 9 out of 68 cases: 5 of 37 masses, 3 of 7 architectural distortions, and 1 of 1 asymmetry. Fifteen out of 37 masses were hyperdense, and all of them were detected by CAD. No association was seen among mass morphology or margins and detectability. Per-study specificity and CAD false-positive rate was 26 % and 1.76 false marks per study. In conclusion, CAD shows a high sensitivity and a low specificity. Lesion size, histology, and breast density do not influence sensitivity. Mammographic features, mass density, and thickness of the spicules in architectural distortions do influence.
doi:10.1007/s10278-012-9550-y
PMCID: PMC3649063  PMID: 23131867
Breast neoplasm; Cancer detection; Computer-assisted detection
10.  Imaging features of foreign body granuloma in the lower extremities mimicking a soft tissue neoplasm 
Foreign body granuloma is a tissue reaction for retained foreign bodies after skin-penetrating trauma. Detection of retained foreign bodies can be extremely difficult when the patients present with non-specific symptoms such as pain and/or swelling without recognizing a previous trauma. We report three patients of foreign body granulomas in the lower extremities with emphasis placed on their unique clinical and radiological features. The involved sites were the foot, posterior thigh, and posterior lower leg, with wooden splinters in two patients and a fragment of tile in one. Plain radiographs could not reveal the existence of foreign bodies. Magnetic resonance imaging (MRI) showed foreign bodies as low intensities on both T1- and T2-weighted images in two patients, and the surrounding reactive lesion as low to iso intensities on T1- and high intensities on T2-weighted images in all the patients. The peripheral areas of the lesion were strongly enhanced after gadolinium injection. Ultrasound sonography could clearly visualize a foreign body as an echogenic area with posterior acoustic shadowing in one patient. The surrounding ring-like reactive lesion is easily mistaken for a soft tissue neoplasm when foreign bodies are not identified. The key to arriving at the correct diagnosis is to clarify the previous trauma and to identify foreign bodies with low signal intensities on both T1- and T2-weighted images and/or the characteristic ring-like enhancement on MRI. It is also necessary to rule out a foreign body granuloma whenever we see patients with a soft tissue tumor in the extremities, irrespective of their previous trauma history.
doi:10.1080/03009730802602455
PMCID: PMC2852748  PMID: 19242872
Extremities; foreign body; granuloma; MRI; wooden splinter
11.  Thick Slices from Tomosynthesis Data Sets: Phantom Study for the Evaluation of Different Algorithms 
PURPOSE
Tomosynthesis is a 3-dimensional mammography technique that generates thin slices separated one to the other by typically 1 mm from source data sets. The relatively high image noise in these thin slices raises the value of 1-cm thick slices computed from the set of reconstructed slices for image interpretation. In an initial evaluation, we investigated the potential of different algorithms for generating thick slices from tomosynthesis source data (maximum intensity projection—MIP; average algorithm—AV, and image generation by means of a new algorithm, so-called softMip). The three postprocessing techniques were evaluated using a homogeneous phantom with one textured slab with a total thickness of about 5 cm in which two 0.5-cm-thick slabs contained objects to simulate microcalcifications, spiculated masses, and round masses. The phantom was examined by tomosynthesis (GE Healthcare). Microcalcifications were simulated by inclusion of calcium particles of four different sizes. The slabs containing the inclusions were examined in two different configurations: adjacent to each other and close to the detector and with the two slabs separated by two 1-cm thick breast equivalent material slabs. The reconstructed tomosynthesis slices were postprocessed using MIP, AV, and softMip to generate 1-cm thick slices with a lower noise level. The three postprocessing algorithms were assessed by calculating the resulting contrast versus background for the simulated microcalcifications and contrast-to-noise ratios (CNR) for the other objects. The CNRs of the simulated round and spiculated masses were most favorable for the thick slices generated with the average algorithm, followed by softMip and MIP. Contrast of the simulated microcalcifications was best for MIP, followed by softMip and average projections. Our results suggest that the additional generation of thick slices may improve the visualization of objects in tomosynthesis. This improvement differs from the different algorithms for microcalcifications, speculated objects, and round masses. SoftMip is a new approach combining features of MIP and average showing image properties in between MIP and AV.
doi:10.1007/s10278-007-9075-y
PMCID: PMC3043718  PMID: 17955296
3D Imaging (imaging, 3-dimensional); tomography; x-ray; computed; digital mammography
12.  Automated Detection of Breast Mass Spiculation Levels and Evaluation of Scheme Performance 
Academic radiology  2008;15(12):1534-1544.
Rationale and Objectives
Although spiculation level of breast mass boundary is a primary sign of malignancy for the mass detected on mammograms, developing an automated computer scheme to detect mass spiculation level and quantitatively evaluating the performance of the scheme is a difficult task. The objective of this study is to (1) develop and test a new scheme to improve mass segmentation and detect mass boundary spiculation level, and (2) assess the scheme performance using a relatively large image dataset.
Materials and Methods
This fully-automated scheme includes three image processing steps. The first step applies the maximum entropy principle in the selected region of interest (ROI) after correcting the background-trend to enhance the initial outlines of the masses. The second step uses an active contour model to refine the initial outlines. The third step detects and identifies spiculated lines connected to the mass boundary using a special line detector. A quantitative spiculation index is computed to assess the degree of spiculation levels. To develop and evaluate this automated scheme, we selected 211 ROIs depicting masses that were extracted from a publicly available image database. Among these ROIs, 106 depict “circumscribed” mass regions and 105 involve “spiculated” mass regions. The scheme performance was evaluated using the receiver operating characteristic (ROC) analysis method.
Results
The computed area under ROC curve when applying the scheme to the dataset is 0.701 ± 0.027. By setting up a threshold at spiculation index = 5.0, the scheme achieves the overall classification accuracy of 66.4% with 54.3% sensitivity and 78.3% specificity, respectively.
Conclusions
We developed a new computer scheme with a number of unique characteristics to detect spiculated mass regions and applied a simple spiculation index to quantify mass spiculation levels. Although this quantitative index can be used to classify between the spiculated and circumscribed masses, the results also suggest that automated detection of mass spiculation levels remains a technical challenge.
doi:10.1016/j.acra.2008.07.015
PMCID: PMC2857703  PMID: 19000870
Computer-aided diagnosis; mammography; mass segmentation; mass spiculations
13.  A Case of Hypersensitivity Pneumonitis with Giant Cells in a Female Dental Technician 
Objectives
Dental technicians are exposed to methyl methacrylate(MMA) and hard metal dusts while working, and several cases of hypersensitivity pneumonitis caused by the exposure have been reported. The authors experienced a case of hypersensitivity pneumonitis in a female dental technician who had 10 years’ work experience and report the case with clinical evidence.
Method
The patient’s work, personal, social, and past and present medical histories were investigated based on patient questioning and medical records. Furthermore, the workplace conditions and tools and materials the patient worked with were also evaluated. Next, the pathophysiology and risk factors of pneumonitis were studied, and studies on the relationship between hypersensitivity pneumonitis and a dental technician’s exposure to dust were reviewed. Any changes in the clinical course of her disease were noted for evaluation of the work-relatedness of the disease.
Results
The patient complained of cough and sputum for 1 year. In addition, while walking up the stairs, the patient was not able to ascend without resting due to dyspnea. She visited our emergency department due to epistaxis, and secondary hypertension was incidentally suspected. Laboratory tests including serologic, electrolyte, and endocrinologic tests and a simple chest radiograph showed no specific findings, but chest computed tomography revealed a centrilobular ground-glass pattern in both lung fields. A transbronchial biopsy was performed, and bronchoalveolar washing fluid was obtained. Among the findings of the laboratory tests, microcalcification, noncaseating granuloma containing foreign body-type giant cells, and metal particles within macrophages were identified histologically. Based on these results, hypersensitivity pneumonitis was diagnosed. The patient stopped working due to admission, and she completely quit her job within 2 months of restarting work due to reappearance of the symptoms.
Conclusion
In this study, the patient did not have typical radiologic findings, but pathological evaluation of the lung biopsy from the bronchoscope led to the suspicion of pneumonitis. Under the microscope, the sample contained fibrotic changes in the lung, multinucleated giant cells, and particles in macrophages and was diagnosed as dental technician pneumoconiosis by the pathology. Working as a dental technician had directly exposed her to light metal dust and MMA, and her clinical symptoms and radiologic findings subsided after withdrawal from exposure to the workplace. These outcomes led to the diagnosis of hypersensitity pneumonitis due to MMA exposure and strong work-relatedness.
doi:10.1186/2052-4374-25-19
PMCID: PMC3923335  PMID: 24472630
Hypersensitivity pneumonitis; Methyl methacrylate; Occupational lung disease; Dental technician; Pneumoconiosis
14.  Cotton-ball granuloma mimicking axillary lymphadenopathy in a breast cancer patient 
Foreign body granuloma is a reaction to either a biodegradable substance or inert material. In a breast cancer patient who had undergone an excision or mastectomy with axillary clearance, a foreign body granuloma in the axilla may be misinterpreted as an axillary lymph node. We report our experience with a case of cotton-ball granuloma of the axilla in a breast cancer patient, which mimics a lymph node radiologically from the CT scan, mammogram and ultrasonography. Following biopsy and excision, the mass was diagnosed histologically as a foreign body granuloma.
doi:10.2349/biij.7.3.e19
PMCID: PMC3265191  PMID: 22279496
Foreign body granuloma; cotton-ball; axillary lymphadenopathy; breast cancer
15.  Screening Mammography for Women Aged 40 to 49 Years at Average Risk for Breast Cancer 
Executive Summary
Objective
The aim of this review was to determine the effectiveness of screening mammography in women aged 40 to 49 years at average risk for breast cancer.
Clinical Need
The effectiveness of screening mammography in women aged over 50 years has been established, yet the issue of screening in women aged 40 to 49 years is still unsettled. The Canadian Task Force of Preventive Services, which sets guidelines for screening mammography for all provinces, supports neither the inclusion nor the exclusion of this screening procedure for 40- to 49-year-old women from the periodic health examination. In addition to this, 2 separate reviews, one conducted in Quebec in 2005 and the other in Alberta in 2000, each concluded that there is an absence of convincing evidence on the effectiveness of screening mammography for women in this age group who are at average risk for breast cancer.
In the United States, there is disagreement among organizations on whether population-based mammography should begin at the age of 40 or 50 years. The National Institutes of Health, the American Association for Cancer Research, and the American Academy of Family Physicians recommend against screening women in their 40s, whereas the United States Preventive Services Task Force, the National Cancer Institute, the American Cancer Society, the American College of Radiology, and the American College of Obstetricians and Gynecologists recommend screening mammograms for women aged 40 to 49 years. Furthermore, in comparing screening guidelines between Canada and the United States, it is also important to recognize that “standard care” within a socialized medical system such as Canada’s differs from that of the United States. The National Breast Screening Study (NBSS-1), a randomized screening trial conducted in multiple centres across Canada, has shown there is no benefit in mortality from breast cancer from annual mammograms in women randomized between the ages of 40 and 49, relative to standard care (i.e. physical exam and teaching of breast-self examination on entry to the study, with usual community care thereafter).
At present, organized screening programs in Canada systematically screen women starting at 50 years of age, although with a physician’s referral, a screening mammogram is an insured service in Ontario for women under 50 years of age.
International estimates of the epidemiology of breast cancer show that the incidence of breast cancer is increasing for all ages combined, whereas mortality is decreasing, though at a slower rate. These decreasing mortality rates may be attributed to screening and advances in breast cancer therapy over time. Decreases in mortality attributable to screening may be a result of the earlier detection and treatment of invasive cancers, in addition to the increased detection of ductal carcinoma in situ (DCIS), of which certain subpathologies are less lethal. Evidence from the SEER cancer registry in the United States indicates that the age-adjusted incidence of DCIS has increased almost 10-fold over a 20-year period (from 2.7 to 25 per 100,000).
The incidence of breast cancer is lower in women aged 40 to 49 years than in women aged 50 to 69 years (about 140 per 100,000 versus 500 per 100,000 women, respectively), as is the sensitivity (about 75% versus 85% for women aged under and over 50, respectively) and specificity of mammography (about 80% versus 90% for women aged under and over 50, respectively). The increased density of breast tissue in younger women is mainly responsible for the lower accuracy of this procedure in this age group. In addition, as the proportion of breast cancers that occur before the age of 50 are more likely to be associated with genetic predisposition as compared with those diagnosed in women after the age of 50, mammography may not be an optimal screening method for younger women.
Treatment options vary with the stage of disease (based on tumor size, involvement of surrounding tissue, and number of affected axillary lymph nodes) and its pathology, and may include a combination of surgery, chemotherapy, and/or radiotherapy.
Surgery is the first-line intervention for biopsy confirmed tumours. The subsequent use of radiation, chemotherapy, or hormonal treatments is dependent on the histopathologic characteristics of the tumor and the type of surgery. There is controversy regarding the optimal treatment of DCIS, which is noninvasive.
With such controversy as to the effectiveness of mammography and the potential risk associated with women being overtreated or actual cancers being missed, and the increased risk of breast cancer associated with exposure to annual mammograms over a 10-year period, the Ontario Health Technology Advisory Committee requested this review of screening mammography in women aged 40 to 49 years at average risk for breast cancer. This review is the first of 2 parts and concentrates on the effectiveness of screening mammography (i.e., film mammography, FM) for women at average risk aged 40 to 49 years. The second part will be an evaluation of screening by either magnetic resonance imaging or digital mammography, with the objective of determining the optimal screening modality in these younger women.
Review Strategy
The following questions were asked:
Does screening mammography for women aged 40 to 49 years who are at average risk for breast cancer reduce breast cancer mortality?
What is the sensitivity and specificity of mammography for this age group?
What are the risks associated with annual screening from ages 40 to 49?
What are the risks associated with false positive and false negative mammography results?
What are the economic considerations if evidence for effectiveness is established?
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the International Network of Agencies for Health Technology Assessment.
Keywords used in the search were breast cancer, breast neoplasms, mass screening, and mammography.
In total, the search yielded 6,359 articles specific to breast cancer screening and mammography. This did not include reports on diagnostic mammograms. The search was further restricted to English-language randomized controlled trials (RCTs), systematic reviews, and meta-analyses published between 1995 and 2005. Excluded were case reports, comments, editorials, and letters, which narrowed the results to 516 articles and previous health technology policy assessments.
These were examined against the criteria outlined below. This resulted in the inclusion of 5 health technology assessments, the Canadian Preventive Services Task Force report, the United States Preventive Services Task Force report, 1 Cochrane review, and 8 RCTs.
Inclusion Criteria
English-language articles, and English and French-language health technology policy assessments, conducted by other organizations, from 1995 to 2005
Articles specific to RCTs of screening mammography of women at average risk for breast cancer that included results for women randomized to studies between the ages of 40 and 49 years
Studies in which women were randomized to screening with or without mammography, although women may have had clinical breast examinations and/or may have been conducting breast self-examination.
UK Age Trial results published in December 2006.
Exclusion Criteria
Observational studies, including those nested within RCTs
RCTs that do not include results on women between the ages of 40 and 49 at randomization
Studies in which mammography was compared with other radiologic screening modalities, for example, digital mammography, magnetic resonance imaging or ultrasound.
Studies in which women randomized had a personal history of breast cancer.
Intervention
Film mammography
Comparators
Within RCTs, the comparison group would have been women randomized to not undergo screening mammography, although they may have had clinical breast examinations and/or have been conducting breast self-examination.
Outcomes of Interest
Breast cancer mortality
Summary of Findings
There is Level 1 Canadian evidence that screening women between the ages of 40 and 49 years who are at average risk for breast cancer is not effective, and that the absence of a benefit is sustained over a maximum follow-up period of 16 years.
All remaining studies that reported on women aged under 50 years were based on subset analyses. They provide additional evidence that, when all these RCTs are taken into account, there is no significant reduction in breast cancer mortality associated with screening mammography in women aged 40 to 49 years.
Conclusions
There is Level 1 evidence that screening mammography in women aged 40 to 49 years at average risk for breast cancer is not effective in reducing mortality.
Moreover, risks associated with exposure to mammographic radiation, the increased risk of missed cancers due to lower mammographic sensitivity, and the psychological impact of false positives, are not inconsequential.
The UK Age Trial results published in December 2006 did not change these conclusions.
PMCID: PMC3377515  PMID: 23074501
16.  Contrast Limited Adaptive Histogram Equalization image processing to improve the detection of simulated spiculations in dense mammograms 
Journal of Digital Imaging  1998;11(4):193-200.
The purpose of this project was to determine whether Contrast Limited Adaptive Histogram Equalization (CLAHE) improves detection of simulated spiculations in dense mammograms. Lines simulating the appearance of spiculations, a common marker of malignancy when visualized with masses, were embedded in dense mammograms digitized at 50 micron pixels, 12 bits deep. Film images with no CLAHE applied were compared to film images with nine different combinations of clip levels and region sizes applied. A simulated spiculation was embedded in a background of dense breast tissue, with the orientation of the spiculation varied. The key variables involved in each trial included the orientation of the spiculation, contrast level of the spiculation and the CLAHE settings applied to the image. Combining the 10 CLAHE conditions, 4 contrast levels and 4 orientations gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 40 backgrounds. Twenty student observers were asked to detect the orientation of the spiculation in the image. There was a statistically significant improvement in detection performance for spiculations with CLAHE over unenhanced images when the region size was set at 32 with a clip level of 2, and when the region size was set at 32 with a clip level of 4. The selected CLAHE settings should be tested in the clinic with digital mammograms to determine whether detection of spiculations associated with masses detected at mammography can be improved.
doi:10.1007/BF03178082
PMCID: PMC3453156  PMID: 9848052
mammography; image processing; contrast limited adaptive histogram equalization; observer studies; breast cancer; spiculations
17.  Sonomammographic characteristics of invasive lobular carcinoma 
Objective
The objective of our study was to identify characteristic features of invasive lobular carcinoma on mammography and ultrasound examinations
Materials and methods
This is a retrospective multicenter study of women with biopsy-proven invasive lobular carcinoma. All patients had undergone diagnostic sonomammography. The imaging findings were identified by experienced breast imagers. Final surgical pathology results were used as the reference standard.
Results
Thirty-two women ranging in age from 42 to 63 years old (mean age, 53 years), All had biopsy-proven invasive lobular carcinomas. Common features on mammogram included dense mass followed by architectural distortion; three cases showed breast asymmetry and one case was reported as normal. On ultrasound, common features included solid mass with spiculated margins, posterior shadowing, and perpendicular to the skin.
Conclusion
Although no specific features could be linked to invasive lobular carcinoma, care should be directed to subtle signs such as architectural distortion and breast asymmetry in order not to miss any lesions. The combination of mammographic and sonographic helps to decrease the relatively high false negative diagnosis of this type of breast cancer.
Video abstract
doi:10.2147/BCTT.S34655
PMCID: PMC3846710  PMID: 24367199
mammography; ultrasound; cancer; breast
18.  A Radial Sclerosing Lesion Mimicking Breast Cancer on Mammography in a Young Woman 
Case Reports in Oncology  2012;5(1):99-103.
A spiculated mass on a mammogram is highly suggestive of malignancy. We report the case of a 32-year-old woman with a radial sclerosing lesion that mimicked breast cancer on mammography. She visited her physician after palpating a lump in her left breast. Mammography showed architectural distortion in the upper inner quadrant of the left breast. Ultrasonography showed a low echoic area with an ambiguous boundary. Core needle biopsy was performed because of the suspicion of malignancy. Histological examination did not reveal any malignant cells. After 6 months, the breast lump became larger and the patient was referred to our hospital. Mammography performed in our hospital showed a spiculated mass, and therefore mammotome biopsy was performed. Histological examination revealed dense fibroelastic stroma with a wide variety of mastopathic changes, leading to a diagnosis of a radial sclerosing lesion. One year after the biopsy, the lump on her left breast had disappeared and mammography showed no spiculated mass.
doi:10.1159/000337024
PMCID: PMC3337735  PMID: 22539921
Breast cancer; Radial sclerosing lesion; Mammography; Young women
19.  Correlation of Mammographic Calcifications with HER-2/neu Overexpression in Primary Breast Carcinomas 
Journal of Digital Imaging  2008;21(2):170-176.
HER-2/neu is a valuable therapeutic and prognostic marker in primary breast carcinomas. The aim of this study was to evaluate the association between mammographic calcifications and HER-2/neu overexpression in primary breast carcinomas and assess its clinical perspective. A retrospective study of 152 preoperative mammograms in patients with breast carcinoma was performed. Expression of HER-2/neu was determined by immunohistochemical staining on 152 tissues that comprised specimens of 11 ductal carcinoma in situ (DCIS) and 141 primary invasive carcinomas. Mammographic calcifications were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS), fourth edition. Calcifications were found in 73 (48.0%) out of 152 patients by mammography finding. Calcifications were more common in carcinomas with HER-2/neu overexpression (45:73, 61.6%) than in those without HER-2/neu overexpression (28:79, 35.4%; P = 0.001). Of the 73 carcinomas with calcifications on mammography, mass with spiculated margin as an associated finding of calcifications was more significantly frequent in carcinomas with HER-2/neu overexpression (15 of 45, 33.3%) than in those without HER-2/neu overexpression (2 of 28, 7.1%; P = 0.036). Fine linear morphology was more common in carcinomas with HER-2/neu overexpression (15:45, 33.3%) when compared with those without HER-2/neu overexpression (2:28, 7.1%; P = 0.036). Clustered distribution of calcifications was more common in carcinomas with HER-2/neu overexpression (26:45, 57.8%) compared with carcinomas without HER-2/neu overexpression (6:28, 21.4%; P = 0.048). Mammographic calcifications are correlated with HER-2/neu overexpression in primary breast carcinomas. Calcifications detected during screening mammography are not only of diagnostic value but of use in determining therapeutic options and prognosis.
doi:10.1007/s10278-008-9105-4
PMCID: PMC3043864  PMID: 18256879
Breast neoplasms; mammography; calcification; HER-2/neu
20.  Paget’s disease of the breast: clinical, imaging and pathologic findings: a review of 16 patients 
Objectives:
To determine the clinical, imaging and pathological findings of Paget’s disease of the breast.
Materials and methods:
Approval by Institutional Review Board was granted and informed consent was waived. Retrospective review of the pathological diagnosis of 2,361 women with breast carcinoma between January 2004 and April 2010 revealed 27 patients with Paget’s disease of the breast. The clinical, mammographic and ultrasonographic images were retrospectively reviewed.
Results:
The prevalence of Paget’s disease of the breast was 1.14% of all breast carcinoma at this institution. Of the 27 patients with Paget’s disease, only 16 had imaging studies and this group constituted the basis of this study. All 16 patients were women, with ages ranging from 36–68 years (mean age 50.31 years). Eleven patients presented with clinical findings suggestive of Paget’s disease of the breast. Seven of these 11 patients also had associated palpable mass(es). Four patients presented with a palpable mass alone and one presented with bloody nipple discharge alone. Mammography was performed in all 16 patients and ultrasonography (US) in 15 patients. Of the 16 mammographic studies, two were negative. Of the 15 US studies, three were negative. Of these three negative US studies, two also had negative mammography and one had pleomorphic microcalcifications on mammogram. US was helpful in detecting multifocality in two patients. Mammography was 100% positive in patients who presented with palpable breast mass(es) and bloody nipple discharge, but 50% positive in patients who had clinically suggestive Paget’s disease alone. Almost all patients (15/16) had underlying breast malignancies. Seven patients had multifocality or multicentricity. Modified radical mastectomy was performed in 13 patients, simple mastectomy in two, and wide local excision in one patient. Pathological findings were ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 10), metaplastic carcinoma (n = 1), invasive lobular carcinoma (ILC) (n = 1), and only Paget’s disease of the nipple without underlying breast carcinoma (n = 1).
Conclusion:
Patients with Paget’s disease of the breast have a high incidence of an underlying breast carcinoma. Most of the patients in this study presented late and were more likely to have positive mammograms. Mammography should be performed to identify the underlying breast carcinoma. Those who have only nipple areolar changes and no palpable mass have less positive mammography and less invasive carcinoma.
doi:10.2349/biij.7.2.e16
PMCID: PMC3265154  PMID: 22287988
Coronary artery disease; single photon emission computed tomography; positron emission tomography; computed tomography; diagnostic value
21.  Postoperative Aseptic Intracranial Granuloma: The Possible Influence of Fluid Hemostatics 
Case Reports in Surgery  2012;2012:614321.
Background. Numerous reports have demonstrated how postoperative intracranial granulomas can often mimic neoplasm clinically, radiologically, and even macroscopically. Herein we present an unusual case of postsurgical intracranial aseptic granuloma secondary to a chronic inflammatory reaction without any identifiable retained foreign body. Case Description. A 71-year-old patient started complaining of severe headache seven months after surgical excision of WHO Grade I right frontal falx meningioma. CT and MRI scans disclosed a contrast-enhanced lesion with diffuse mass effect in the previous surgical site. The lesion was resected; intraoperative finding and histological specimens led to the diagnosis of postoperative granuloma, likely expression of a glial reaction to the fluid absorbable hemostatics applied in the surgical site after meningioma excision. The possible granuloma-inducing materials and the timing of granuloma formation are discussed. Conclusion. A comprehensive analysis of clinical and neuroradiological data, as well as results of blood tests including positive and negative acute phase proteins, is mandatory to raise the suspicion of postoperative granuloma. The treatment options should be evaluated on a case-by-case basis, with a conservative attitude being the one of choice only for patients without progressive neurological deficit. Alternatively, aggressive surgical treatment and histopathological examination should be advocated.
doi:10.1155/2012/614321
PMCID: PMC3423776  PMID: 22924150
22.  Imaging Findings of Implanted Absorbable Mesh in Patients with Breast Partial Resection 
Yonsei Medical Journal  2008;49(1):111-118.
Purpose
The author presents imaging findings of patients that underwent partial resection of the breast followed by absorbable mesh implantation.
Materials and Methods
Ultrasonographic (n = 18) and mammographic (n = 11) images of patients that had undergone absorbable mesh implantation after breast partial resection were reviewed retrospectively. Sequential changes of the lesions were analyzed in follow-up ultrasonographic examinations, focusing on the change of the size and pattern of the lesion. The presence of a mass, asymmetry, focal asymmetry, architectural distortion, and calcification were evaluated by mammography. Pathologic findings of the implanted mesh in available cases were analyzed.
Results
Ultrasonograms revealed a well-encapsulated anechoic lesion with (pattern 1, n = 11) or without (pattern 2, n = 5) internal isoechoic nodular portion, and a hyperechoic mass-like lesion without anechoic portion (pattern 3, n = 2). The mean length of the longest diameter decreased gradually as determined in follow-up examinations (3 months, 6.12 ± 2.599 cm; 6 months, 5.08 ± 2.105 cm; 12 months, 3.26 ± 2.206 cm). In mammograms, a mass (n = 4) was noted at the surgical site and focal asymmetry, overlapping with the postoperative change, was seen in the remaining seven cases. Pathologic findings of two cases revealed foreign body reaction.
Conclusion
Ultrasonography of the patients that underwent breast partial resection followed by absorbable mesh implantation showed a well-encapsulated cyst at the surgical site that gradually decreased in follow-up examinations. Adjunctive ultrasonography combined with mammography would be recommended in postoperative follow-up examinations.
doi:10.3349/ymj.2008.49.1.111
PMCID: PMC2615257  PMID: 18306477
Absorbable implants; surgical mesh; breast; ultrasonography; mammography
23.  Supplementary Screening Sonography in Mammographically Dense Breast: Pros and Cons 
Korean Journal of Radiology  2010;11(6):589-593.
Sonography is an attractive supplement to mammography in breast cancer screening because it is relatively inexpensive, requires no contrast-medium injection, is well tolerated by patients, and is widely available for equipment as compared with MRI. Sonography has been especially valuable for women with mammographically dense breast because it has consistently been able to detect a substantial number of cancers at an early stage. Despite these findings, breast sonography has known limitations as a screening tool; operator-dependence, the shortage of skilled operators, the inability to detect microcalcifications, and substantially higher false-positive rates than mammography. Further study of screening sonography is still ongoing and is expected to help establish the role of screening sonography.
doi:10.3348/kjr.2010.11.6.589
PMCID: PMC2974219  PMID: 21076583
Breast screening; Screening ultrasound; Breast cancer
24.  Characterization of Mammographic Masses Based on Level Set Segmentation with New Image Features and Patient Information 
Medical physics  2008;35(1):280-290.
Computer-aided diagnosis (CAD) for characterization of mammographic masses as malignant or benign has the potential to assist radiologists in reducing the biopsy rate without increasing false negatives. The purpose of this study was to develop an automated method for mammographic mass segmentation and explore new image based features in combination with patient information in order to improve the performance of mass characterization. Our previous CAD system, which used the active contour segmentation, and morphological, textural, and spiculation features, has achieved promising results in mass characterization. The new CAD system is based on the level set method, and includes two new types of image features related to the presence of microcalcifications with the mass and abruptness of the mass margin, and patient age. A linear discriminant analysis (LDA) classifier with stepwise feature selection was used to merge the extracted features into a classification score. The classification accuracy was evaluated using the area under the receiver operating characteristic curve. Our primary data set consisted of 427 biopsy-proven masses (200 malignant and 227 benign) in 909 regions of interest (ROIs) (451 malignant and 458 benign) from multiple mammographic views. Leave-one-case-out resampling was used for training and testing. The new CAD system based on the level set segmentation and the new mammographic feature space achieved a view-based Az value of 0.83±0.01. The improvement compared to the previous CAD system was statistically significant (p=0.02). When patient age was included in the new CAD system, view-based and case-based Az values were 0.85±0.01 and 0.87±0.02, respectively. The performance of the new CAD system was also compared to an experienced radiologist’s likelihood of malignancy rating. When patient age was used in classification, the accuracy of the new CAD system was comparable to that of the radiologist (p=0.34). The study also demonstrated the consistency of the newly developed CAD system by evaluating the statistics of the weights of the LDA classifiers in leave-one-case-out classification. Finally, an independent test on the publicly available digital database for screening mammography (DDSM) with 132 benign and 197 malignant ROIs containing masses achieved a view-based Az value of 0.84±0.02.
PMCID: PMC2728555  PMID: 18293583
computer-aided diagnosis; mammography; breast masses; level set; segmentation; classification
25.  Medical and Surgical Treatment of Idiopathic Granulomatous Lobular Mastitis: A Benign Inflammatory Disease Mimicking Invasive Carcinoma 
Journal of Breast Cancer  2012;15(1):119-123.
Purpose
Idiopathic granulomatous lobular mastitis (IGLM) is a rare chronic inflammatory disease of the breast with obscure etiology that mimics invasive carcinoma both clinically and radiologically. The treatment of IGLM remains controversial. The aim of proper management is to use a combination of medical and surgical treatment of this benign condition to achieve a good cosmetic result and low recurrence rate.
Methods
A retrospective analysis of 19 patients with IGLM is performed based on the findings of clinical, radiological, and pathological examinations. The results of two treatments are presented: medical treatment with oral corticosteroids, and consecutive surgical excision after a follow-up period of 20 months (range, 6-75 months).
Results
The majority of patients treated in this paper were young (mean, 34 years) parous women with a history of hormonal medication use. The main clinical finding is large, irregular, and painful mass. Hypoechoic lobulated, irregular tubular or oval shaped masses had been imaged by ultrasound. Mammographic findings were an ill-defined mass, enlarged axillary lymph nodes, asymmetric density, and architectural distortion. Diagnoses of IGLM had been established by cytological or histological examination. Symptoms subside and inflammatory changes regressed with medical treatment. The remaining lesions were excised by consecutive breast conserving surgery. The disease recurred in one patient during the follow-up period.
Conclusion
IGLM is an inflammatory breast disease found in young women who present with a large painful irregular mass, which mimics carcinoma, as a physical change. Breast imaging modalities are not helpful to differentiate IGLM from invasive cancer. The correct diagnosis is established by cytological or histological examination. Medical treatment with corticosteroids provides significant regression of the inflammatory disease, allowing more conservative surgery. Consecutive surgical excision of the remaining lesions with good cosmetic results provides definitive treatment and reduces the risk of recurrence.
doi:10.4048/jbc.2012.15.1.119
PMCID: PMC3318163  PMID: 22493638
Breast; Carcinoma; Corticosteroid; Mastectomy; Mastitis

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