Occult Breast Cancer due to Multiple Calcified Hamartomas in a Patient with Cowden Syndrome.

Cowden syndrome (CS) is an autosomal dominant disorder characterized by presence of multiple hamartomas, and other benign and malignant abnormalities of the breasts, skin, thyroid, endometrium, gastrointestinal tract, and central nervous system. Hamartomas are benign, developmentally disorganized tumors that can develop in any of the above mentioned organs. The presence of massive calcifications in the breasts in very young women is an indication to perform a breast MRI to exclude a neoplasm since, like in the current case report, presence of breast calcifications may obscure a neoplasm. Although fibrocystic disease and cooccurrence of fibrocystic disease and breast cancer are much more common than CS, the presence of massive calcifications in the breasts of very young women should elicit the possibility of an underlying genetic disease. Furthermore, breast cancer and macrocephaly are considered major criteria for the diagnosis of CS and the combination of both is enough to establish the clinical diagnosis of this entity. Fibrocystic disease of the breasts and multinodular goiter are minor criteria. Family history is also important for the diagnosis of (any) hereditary disease.

Density is in the eye of the beholder: visual versus semi-automated assessment of breast density on standard mammograms.

OBJECTIVES: Visual inspection is generally used to assess breast density. Our study aim was to compare visual assessment of breast density of experienced and inexperienced readers with semi-automated analysis of breast density. METHODS: Breast density was assessed by an experienced and an inexperienced reader in 200 mammograms and scored according to the quantitative BI-RADS classification. Breast density was also assessed by dedicated software using a semi-automated thresholding technique. Agreement between breast density classification of both readers as well as agreement between their assessment versus the semi-automated analysis as reference standard was expressed as the weighted kappa value. RESULTS: Using the semi-automated analysis, agreement between breast density measurements of both breasts in both projections was excellent (ICC >0.9, P < 0.0001). Reproducibility of the semi-automated analysis was excellent (ICC >0.8, P < 0.0001). The experienced reader correctly classified the BI-RADS breast density classification in 58.5% of the cases. Classification was overestimated in 35.5% of the cases and underestimated in 6.0% of the cases. Results of the inexperienced reader were less accurate. Agreement between the classification of both readers versus the semi-automated analysis was considered only moderate with weighted kappa values of 0.367 (experienced reader) and 0.232 (inexperienced reader). CONCLUSION: Visual assessment of breast density on mammograms is inaccurate and observer-dependent.

Update on screening breast MRI in high-risk women.

Breast cancer is the most common cancer in women. One in 8 women develops breast cancer and approximately 30% of all affected women die of the disease. By performing a nationwide screening program in the Netherlands, a mortality reduction of 1.2% annually was achieved. The screening program is for women between the ages of 50 and 75 years; however, women with an increased risk for developing breast cancer are mostly younger. The role of MRI in this particular group of women has been described in different studies. MRI of the breast in this group of women has a higher sensitivity than mammography, but the highest sensitivity is reached by the combination of these two imaging modalities.

Update on screening breast MRI in high-risk women.

Breast cancer is the most common cancer in women. One in 8 women develops breast cancer and approximately 30% of all affected women die of the disease. By performing a nationwide screening program in the Netherlands, a mortality reduction of 1.2% annually was achieved. The screening program is for women between the ages of 50 and 75 years; however, women with an increased risk for developing breast cancer are mostly younger. The role of MRI in this particular group of women has been described in different studies. MRI of the breast in this group of women has a higher sensitivity than mammography, but the highest sensitivity is reached by the combination of these two imaging modalities.

The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast.

Re-excision rates after breast conserving surgery(BCS) of invasive lobular carcinoma (ILC) are high.Preoperative breast MRI has the potential to reduce re-excision rates, but may lead to an increased rate of mastectomies. Hence, we assessed the influence of preoperative breast MRI on the re-excision rate and the rate of mastectomies. We performed a retrospective cohort study of a consecutive series of patients with ILC who presented in one of two dedicated tertiary cancer centers between 1993 and 2005. We assessed the initial type of surgery(BCS or mastectomy), the re-excision rate and the final type of surgery. Patients were stratified into two groups:those who received preoperative MRI (MR? group) and those who did not (MR- group). In the MR- group, 27%of the patients underwent a re-excision after initial BCS. In the MR? group, this rate was significantly lower at 9%.The odds ratio was 3.64 (95% CI: 1.30-10.20, P = 0.010).There was a trend towards a lower final mastectomy rate in the MR? group compared to the MR- group (48 vs. 59%,P = 0.098). In conclusion, preoperative MRI in patients with ILC can reduce re-excision rates without increasing the rate of mastectomies.

The additional value of three time point color coding in dynamic contrast-enhanced MRI of the breast for inexperienced and experienced readers.

PURPOSE: To evaluate the additional value of the color coding of dynamic data using the 3TP method in the evaluation of contrast-enhanced breast MRI for readers with different levels of experience. MATERIALS AND METHODS: A total of 52 lesions were included in this study, 25 malignant and 27 benign. All lesions were evaluated by four readers on two different workstations for the evaluation of dynamic breast MRI; one displaying the subtracted images and relative enhancement versus time curves and one displaying the subtracted images together with the 3TP color coding projected onto pre-contrast T1 images. Readers with different levels of experience were used. The diagnostic performance of both workstations was evaluated using ROC curve analyses. Interobserver variations were evaluated using kappa statistics. RESULTS: All lesions were detected by all four readers on both workstations. The diagnostic performance found in the inexperienced readers improved significantly when using the 3TP evaluations (p=0.04 and p=0.03). No significant difference was found for the more experienced readers (p=0.94 and p=0.54). The level of agreement between the readers improved significantly when using the 3TP evaluation method (p=0.01). CONCLUSION: Even though the 3TP color coding did not improve the diagnostic performance of the more experienced readers, this study clearly shows its value for inexperienced readers. The use of 3TP color coding is therefore recommended for inexperienced readers.

Contrast-enhanced magnetic resonance imaging of the breast: the value of pharmacokinetic parameters derived from fast dynamic imaging during initial enhancement in classifying lesions.

The value of pharmacokinetic parameters derived from fast dynamic imaging during initial enhancement in characterizing breast lesions on magnetic resonance imaging (MRI) was evaluated. Sixty-eight malignant and 34 benign lesions were included. In the scanning protocol, high temporal resolution imaging was combined with high spatial resolution imaging. The high temporal resolution images were recorded every 4.1 s during initial enhancement (fast dynamic analysis). The high spatial resolution images were recorded at a temporal resolution of 86 s (slow dynamic analysis). In the fast dynamic evaluation pharmacokinetic parameters (K(trans), V(e) and k(ep)) were evaluated. In the slow dynamic analysis, each lesion was scored according to the BI-RADS classification. Two readers evaluated all data prospectively. ROC and multivariate analysis were performed. The slow dynamic analysis resulted in an AUC of 0.85 and 0.83, respectively. The fast dynamic analysis resulted in an AUC of 0.83 in both readers. The combination of both the slow and fast dynamic analyses resulted in a significant improvement of diagnostic performance with an AUC of 0.93 and 0.90 (P = 0.02). The increased diagnostic performance found when combining both methods demonstrates the additional value of our method in further improving the diagnostic performance of breast MRI.

Breast tumor characteristics of BRCA1 and BRCA2 gene mutation carriers on MRI.

The appearance of malignant lesions in BRCA1 and BRCA2 mutation carriers (BRCA-MCs) on mammography and magnetic resonance imaging (MRI) was evaluated. Thus, 29 BRCA-MCs with breast cancer were retrospectively evaluated and the results compared with an age, tumor size and tumor type matched control group of 29 sporadic breast cancer cases. Detection rates on both modalities were evaluated. Tumors were analyzed on morphology, density (mammography), enhancement pattern and kinetics (MRI). Overall detection was significantly better with MRI than with mammography (55/58 vs 44/57, P=0.021). On mammography, lesions in the BRCA-MC group were significantly more described as rounded (12//19 vs 3/13, P=0.036) and with sharp margins (9/19 vs 1/13, P=0.024). On MRI lesions in the BRCA-MC group were significantly more described as rounded (16/27 vs 7/28, P=0.010), with sharp margins (20/27 vs 7/28, P<0.001) and with rim enhancement (7/27 vs 1/28, P=0.025). No significant difference was found for enhancement kinetics (P=0.667). Malignant lesions in BRCA-MC frequently have morphological characteristics commonly seen in benign lesions, like a rounded shape or sharp margins. This applies for both mammography and MRI. However the possibility of MRI to evaluate the enhancement pattern and kinetics enables the detection of characteristics suggestive for a malignancy.

The impact of a false-positive MRI on the choice for mastectomy in BRCA mutation carriers is limited.

PURPOSE: To assess the false-positive rate of breast cancer surveillance by magnetic resonance imaging (MRI) in BRCA mutation carriers and the impact of an abnormal mammography or breast MRI on the patients' decision for prophylactic mastectomy. PATIENTS AND METHODS: A total of 196 BRCA mutation carriers were included with a median follow-up of 2 years (range 1-9) with annual mammography and MRI. Preference for prophylactic mastectomy was registered at first surveillance after the mutation carriership was revealed. RESULTS: In all, 41% (81 of 196) of the women had at least one positive MRI or mammography. Malignancy was detected in 17 women: 11 at surveillance, 4 at an intended prophylactic mastectomy and 2 had an interval cancer. Imaging by mammography and MRI had a sensitivity of 71% and a specificity of 90%. The probability that a positive MRI result is false positive was 83%. In the group with a prior preference for mastectomy with and without a false-positive imaging, prophylactic mastectomy was carried out in 89% and 66%, respectively (P = 0.06), in the group with prior preference for surveillance these percentages were 15% and 11%, respectively (P = 0.47). CONCLUSION: Although the rate of false-positive MRI results is high, the impact on the choice for prophylactic mastectomy is limited and is determined by the woman's preference before the establishment of a BRCA mutation.

The value of MRI compared to mammography in the assessment of tumour extent in invasive lobular carcinoma of the breast.

AIMS: Invasive lobular carcinoma of the breast (ILC) is known to be substantially underestimated by mammography, which makes correct planning of treatment difficult. MRI has been proposed as a valuable adjunct to mammography. The purpose of the current study is to evaluate its value, compare it to mammography and assess the possible causes of over- and underestimation of lesion size on MRI. METHOD: The mammograms and MRI scans of 67 consecutive patients with ILC were retrieved and re-evaluated. Size measurements were correlated to the sizes extracted from the pathology report. RESULTS: MRI measurements correlated better to pathologic size (r=0.85) than mammographic measurements (r=0.27). Underestimation of tumour size was more common on mammography (p<0.001); overestimation occurred with equal frequency (p=0.69). Overestimation on MRI, caused by non-malignant findings, was attributed to enhancing lobular carcinoma in situ. CONCLUSION: MRI is a more accurate modality for determining tumour size in patients with ILC than mammography. The typical underestimation of lesion size by mammography can be prevented with the aid of MRI, without increasing the risk of lesion overestimation.

Broncholithiasis in an immune compromised boy with disseminated Mycobacterium kansasii.

A case of broncholithiasis in a child is reported. To our knowledge, it has not been reported in children. Broncholithiasis is a condition in which a peribronchial calcified lymph node erodes into or distorts an adjacent bronchus. Symptoms of broncholithiasis include cough, recurrent episodes of fever, haemoptysis, and purulent sputum. The most common cause of broncholithiasis is Mycobacterium tuberculosis (M. tuberculosis). Here we describe a 14-year-old boy known to have disseminated Mycobacterium kansasii (M. kansasii) infection associated with hypoplastic myelodysplastic syndrome (MDS). He was presented with cough and fever. Computed tomography (CT) and bronchoscopy revealed a large calcified mass eroding in the right main bronchus. While surgical therapy was considered, haemoptysis developed and his condition deteriorated. Bone marrow puncture revealed acute myeloid leukemic transformation of the MDS. Curation was no longer possible. Post mortem examination revealed a large bronchiolith, evolving from a calcified lymph node.

[Palliation in patients with metastatic breast cancer often better with antitumour treatment than with only symptomatic treatment]. / Palliatie bij patiënten met gemetastaseerd mammacarcinoom vaak beter door antitumorbehandeling dan door alleen symptoombestrijding.

Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for uncontrolled pain due to bone metastases. Despite the fact that progressive disease was evident, a change in antitumour therapy had not been recommended. The pain control was optimised in both patients. In one patient, palliative chemotherapy was installed, combined with trastuzumab because of HER2/neu overexpression. She was still alive after one and a half year of treatment. The other patient could not adjust mentally to the fact that her palliative therapy was changed to antitumour therapy; she died one month later. It is important to be aware of the various kinds of therapy in metastatic breast cancer because palliative treatment is more than just symptomatic treatment. Systemic antitumour therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore, in patients with bone metastases, radiotherapy combined with bisphosphonates results in pain relief and can reduce skeletal complications. Because of the ensuing complexity of the treatment of metastatic breast cancer, these patients should be regularly managed by a breast-cancer care team in order to improve the quality of care.

Tumor characteristics and detection method in the MRISC screening program for the early detection of hereditary breast cancer.

In the MRISC study, women with an inherited risk for breast cancer were screened by a 6-month clinical breast examination (CBE) and yearly MRI and mammography. We found that the MRISC screening scheme could facilitate early breast cancer diagnosis and that MRI was a more sensitive screening method than mammography, but less specific. In the current study we investigated the contribution of MRI in the early detection of breast cancer in relation to tumor characteristics. From November 1999 to October 2003, 1909 women were included and 50 breast cancers were detected, of which 45 were evaluable and included in the current study. We compared the characteristics of tumors detected by MRI-only with those of all other (non-palpable) screen-detected tumors. Further, we compared the sensitivity of mammography and MRI within subgroups according to different tumor characteristics. Twenty-two (49%) of the 45 breast cancers were detected by MRI and not visible at mammography, of which 20 (44%) were also not palpable (MRI-only detected tumors). MRI-only detected tumors were more often node-negative than other screen-detected cancers (94 vs. 59%; P=0.02) and tended to be more often

[MRI breast-cancer screening: particularly important in women at increased risk]. / Borstkankerscreening met MRI: vooral voor vrouwen met verhoogd risico.

In some women, the density of breast tissue is a limiting factor in the detection of early-stage breast cancer by palpation and mammography. This is the case in young women, for example. MRI sensitivity is not influenced by tissue density. For this reason, it would appear that young women with a genetic or familial predisposition to breast cancer would benefit from MRI screening. A series of prospective studies has shown that the sensitivity of MRI is almost twice that of mammography in these women. As a result, the disease stage in those patients screened by MRI is lower than in the patients screened by a different method. In well-defined groups MRI of the breasts may be an important additional screening tool in women at increased risk of breast cancer.

Numerous high-risk epithelial lesions in familial breast cancer.

PURPOSE: To assess the occurrence of high-risk epithelial lesions in women of breast cancer families with and without a BRCA mutation. PATIENTS AND METHODS: Prospective study of women at very high risk of breast cancer undergoing prophylactic mastectomy (68 BRCA1 mutation carriers, 14 BRCA2 mutation carriers and 24 non-BRCA mutation carriers). RESULTS: The prevalence of high-risk lesions is equal in women with a BRCA1 or a BRCA2 mutation, but is higher in non-BRCA mutation carriers: all lesions 43% versus 71% (p=0.02), atypical lobular hyperplasia 26% versus 67% (p=0.001), atypical ductal hyperplasia 17% versus 42% (p=0.01), lobular carcinoma-in situ 15% versus 29% (p=0.10) and ductal carcinoma-in situ 9% versus 17% (p=0.25). The presence of high-risk lesions is related to absence of a BRCA mutation and to age over 40 years. CONCLUSION: Women with an autosomal dominant family history for breast cancer, with and without a BRCA mutation are prone to develop high-risk epithelial lesions, especially over 40 years.

Colonic duplications: clinical presentation and radiologic features of five cases.

Diagnosis of colonic duplication can pose a potential problem even for those familiar with gastro-intestinal tract duplications in general but unaware of the condition due to its rarity and its apparently bimodal clinical presentation. In this report of five cases of surgically proven pediatric colonic duplication, we illustrate how the condition manifests clinically and describe the imaging features in an attempt to illustrate this bimodal presentation of the condition. The possible etiology, associated congenital anomalies and modes of clinical presentation are reviewed based on literature review as well as on our own experience.

Severe gastrointestinal tract bleeding in a two-month-old infant due to congenital intrahepatic arterioportal fistula.

A 2-month-old boy was referred for assessment of severe upper gastrointestinal tract bleeding and melena. On physical examination, a continuous murmur was heard over the right upper quadrant of the abdomen. A splenomegaly and dilated veins were also noted on the abdominal wall. Liver functions were normal. There was no history of trauma or jaundice. Doppler ultrasonography, magnetic resonance arteriography and angiography suggested the presence of an intrahepatic arteriovenous fistula between the phrenic artery and the portal vein. Management consisted of successful embolization by coiling of the phrenic artery. To our knowledge this is the first documented case report of a congenital fistula between the phrenic artery and the portal vein.