Axillary ectopic lobular carcinoma of breast: two rare case reports.

OBJECTIVE: The presence of ectopic or supernumerary breast tissue is a rare event, related to a not complete regression of breast tissue along the milk line. Primary ectopic breast cancer of the axilla can create many difficulties in differential diagnosis with subsequent delayed specific treatments. The incidence of ectopic breast tissue is 0.2-6%, and the axilla is the most common site involved. In this tissue, the same physiologic and pathologic changes as seen in ectopic breast tissue may occur, including carcinoma formation. PATIENTS AND METHODS: Two patients (a 56 years old and 70 years old women) came to our attention for the recent development painless nodular axillary lesions, clinically characterized by an increased thickness, irregular margins and adherence to the floors below. RESULTS: Patients underwent ultrasonography (US) and mammography (MMG) revealing non-specific features of the lesions. Magnetic resonance imaging (MRI), demonstrated margins slightly irregular and a non-specific appearance of each lesion. Both patients underwent wide local excision with axillary lymph node dissection. Histological examination showed infiltrating lobular carcinomas of the breasts. CONCLUSIONS: We describe two unusual cases of ectopic axillary breast carcinoma localization. It is important a correct and fast diagnosis with a local examination, diagnostic instruments, surgical excision and histological examination.

Diagnostic accuracy of 1.5 Tesla breast magnetic resonance imaging in the pre-operative assessment of axillary lymph nodes.

The purpose of this study was to test the accuracy of 1.5 Tesla magnetic resonance imaging (1.5T MRI) in the preoperative evaluation of axillary lymph nodes in patients with invasive breast cancer. The authors retrospectively analyzed 26 patients with invasive breast cancer who had undergone sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND). All patients had been submitted to preoperative contrast enhanced breast 1.5T MRI. On the basis of lymph nodes morphological and dynamic characteristics, lymph nodes were classified as "negative" (short axis < 5 mm), "borderline" (short axis > 5 mm, absence of a hilum) or "positive" (short axis > 5 mm, absence of a hilum and also other suspicious features). The authors compared 1.5T MRI results with the outcome of histological analysis performed according to the TNM criteria; sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of 1.5T MRI were evaluated. Considering only the lymph nodes "positive", 1.5 T MRI showed: SE 37.8%, SP 99.3%, FP 0.7%, PPV 92.5%, and NPV 88.1%. However, considering also "borderline", 1.5T MRI achieved: SE 75.7%, SP 99.3%, FP 0.7%, PPV 96.1%, and NPV was 95%. Contrast enhanced breast 1.5T MRI is not yet a valid alternative to histological analysis but it is a valid tool for a preoperative study of the topography of axillary lymph nodes and has the potential to become a routine method for evaluating the metastatic lymph nodes before submission to ALND.

Apparent diffusion coefficient on 3.0 Tesla magnetic resonance imaging and prognostic factors in breast cancer.

AIM: The aim of the study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0 Tesla diffusion-weighted imaging (3T DWI) varies with the prognostic factors Ki67 and grading in invasive breast cancer. MATERIALS AND METHODS: Seventy-three patients with 75 invasive breast cancer lesions who had undergone 3.0 Tesla magnetic resonance imaging (MRI) for local staging were enrolled. All lesions were confirmed by histologic and immunohistochemical analysis. MRI included both dynamic contrast-enhanced and DWI sequences. ADC value was obtained for each lesion. Histologic tumor grade was established according to the Nottingham Grading System (NGS), while Ki67 expression was evaluated by MM1 clone IgG1 mouse anti-human monoclonal antibody. Patients were divided into the following groups: grade 1 (G1), grade 2 (G2), grade 1 plus grade 2 (G1+G2) and grade 3 (G3), and low Ki67 (< or = 14%), intermediate Ki67 (15%-30%), and high Ki67 (> or = 30%). ADC values were compared with the G and Ki67 groups. Statistical comparison was carried out using the Mann-Whitney U and the Kruskal-Wallis H test. RESULTS: ADC values were significantly higher in G3 than in G1+G2 tumors; no significant difference was observed when G1, G2, and G3 were compared. There was no statistically significant correlation between ADC values and Ki67 percentage (p > 0.05). DISCUSSION: ADC values obtained on 3T DWI correlate with low (G1+G2) and high-grade (G3) invasive breast carcinomas. CONCLUSION: ADC may be a helpful tool for identifying high-grade invasive breast carcinoma.

Magnetic resonance hysterosalpingography in the evaluation of tubal patency in infertile women: an observational study.

The purpose of this study was to evaluate the ability of magnetic resonance hysterosalpingography (MR-HSG) to demonstrate fallopian tube patency in infertile women and to improve the MR-HSG technique. Sixteen consecutive infertile women were recruited for this trial. All subjects underwent clinically indicated MR-HSG: 10-15 ml of 1:10 solution of gadolinium and normal sterile saline (0.9%) was gently hand-injected intracervically through a 7 French balloon catheter while seven consecutive flash-3D dynamic (FL 3D DY) T1-weighted MR sequences were acquired. Two readers independently assessed image quality as well as anatomic and pathologic correlations. Patient comfort was evaluated using a specific score questionnaire. MR-HSG was successfully completed in all patients. In 14/16 (87.4%) patients, MR-HSG showed bilateral tubal patency with symmetric contrast agent diffusion and a regular tubo-ovarian relationship. One patient (6.3%) with monolateral hydrosalpinx presented no contrast agent diffusion in the affected side (monolateral tubal occlusion); in another patient (6.3%) the fallopian tube was displaced upward causing loss of the tubo-ovarian anatomical relationship resulting in asymmetric and inadequate contrast agent diffusion. Eight women (50%) were found to have abnormalities on MR imaging; these abnormalities included multi follicular ovaries (5 cases 31.1%), endometrioma (1 case, 6.3%), leiomyoma (1 case/6.3%) and endometrial polyp (1 case/6.3%). The average time required for the study was 25-30 minutes. Analysis of the questionnaires administered to the patients showed that 15/16 patients (93.7%) were fully satisfied with the procedure. All examinations were judged to be of high diagnostic quality and the two readers made similar diagnoses. In conclusion, MR-HSG is a feasible, useful and well tolerated tool for the assessment of the uterus, fallopian tubes, ovaries and extra-uterine structures. MR-HSG is a new promising imaging approach to female infertility.

Insulin-like growth factor-I (IGF-1), IGF-binding protein-3 (IGFBP-3) and mammographic features.

INTRODUCTION: The IGF system has recently been shown to play an important role in the regulation of breast tumor cell proliferation. However, also breast density is currently considered as the strongest breast cancer risk factor. It is not yet clear whether these factors are interrelated and if and how they are influenced by menopausal status. The purpose of this study was to examine the possible effects of IGF-1 and IGFBP-3 and IGF-1/IGFBP-3 molar ratio on mammographic density stratified by menopausal status. PATIENTS AND METHODS: A group of 341 Italian women were interviewed to collect the following data: family history of breast cancer, reproductive and menstrual factors, breast biopsies, previous administration of hormonal contraceptive therapy, hormone replacement therapy (HRT) in menopause and lifestyle information. A blood sample was drawn for determination of IGF-1, IGFBP-3 levels. IGF-1/ IGFBP-3 molar ratio was then calculated. On the basis of recent mammograms the women were divided into two groups: dense breast (DB) and non-dense breast (NDB). Student's t-test was employed to assess the association between breast density and plasma level of IGF-1, IGFBP-3 and molar ratio. To assess if this relationship was similar in subgroups of pre- and postmenopausal women, the study population was stratified by menopausal status and Student's t-test was performed. Finally, multivariate analysis was employed to evaluate if there were confounding factors that might influence the relationship between growth factors and breast density. RESULTS: The analysis of the relationship between mammographic density and plasma level of IGF-1, IGFBP-3 and IGF-1/ IGFBP-3 molar ratio showed that IGF-1 levels and molar ratio varied in the two groups resulting in higher mean values in the DB group (IGF-1: 109.6 versus 96.6 ng/ml; p= 0.001 and molar ratio 29.4 versus 25.5 ng/ml; p= 0.001) whereas IGFBP-3 showed similar values in both groups (DB and NDB). Analysis of plasma level of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio compared to breast density after stratification of the study population by menopausal status (premenopausal and postmenopausal) showed that there was no association between the plasma of growth factors and breast density, neither in premenopausal nor in postmenopausal patients. Multivariate analysis showed that only nulliparity, premenopausal status and body mass index (BMI) are determinants of breast density. CONCLUSIONS: Our study provides a strong evidence of a crude association between breast density and plasma levels of IGF-1 and molar ratio. On the basis of our results, it is reasonable to assume that the role of IGF-1 and molar ratio in the pathogenesis of breast cancer might be mediated through mammographic density. IGF-1 and molar ratio might thus increase the risk of cancer by increasing mammographic density.

The impact of presurgical magnetic resonance in early breast cancer: an observational study.

The aim of this study was to evaluate the impact of presurgical breast magnetic resonance imaging (MRI) on the surgical management of selected patients with early-stage breast cancer who were candidates for BCT. The sample was built up according to the EUSOMA (European Society of Breast Cancer Specialists) recommendations enrolling women with unifocal unilateral early-stage breast carcinoma diagnosed by mammography, ultrasound (US) examination and in some cases also by histological analysis; all were scheduled for wider local excision. All eligible patients underwent presurgical breast MRI and findings were classified according to the BI-RADS system. In the presence of additional foci classified as BI-RADS 3-4, a targeted second-look US study was performed. If second-look US confirmed the presence of foci, needle biopsy was performed. Possible changes in the therapeutic approach resulting from preoperative MRI findings were decided upon by a multidisciplinary team. Outcome of histological examination of the surgical specimen and particularly analysis of tumor infiltration of the resection margins was the standard for determining the appropriateness of surgical strategy. A total of 123 patients underwent presurgical breast MRI. Additional foci were detected in 41.6% of patients, a greater local extension of the index lesion in 6.4%, whereas MRI confirmed local staging established by conventional imaging in 52%. However, 13.8% of additional foci were not confirmed by second-look and needle biopsy. More extensive surgery as a result of MRI findings was performed in 34.2%. This decision proved to be appropriate in 29.3% thus resulting in an over-treatment rate of 4.9%. Presurgical breast MRI resulted in confirmation of planned surgical strategy in 65.8% with an appropriateness rate of 54.5%. Surgical resection margins were positive for malignancy in 11.3% and repeated surgery was therefore required. Therapeutic strategy established on the basis of MRI was appropriate in 83.8% of cases. This study confirms the utility of MRI in presurgical workup of selected breast cancer patients. The results obtained suggest the importance of a sensitive tool such as MRI in the local staging of breast cancer before treatment planning.

Mammographic features in infertile women as a potential risk for breast cancer: a preliminary study.

The purpose of the present study was to evaluate breast mammographic features, particularly mammographic density in a selected population of infertile women and to assess if these women should be considered at higher risk for breast cancer. The prevalence of female infertility in Western countries is approximately 10-15% and since causes affecting the female are involved in 35-40%, concerns have developed about the future health of these women, specifically whether infertility could represent a risk factor for future cancer development. Moreover, infertility is now often treated with medication and procedures that could modify the hormonal environment and be cofactors in the cellular changes towards cancer development. Mammographic breast density is a useful marker for breast cancer risk and breast density is considered one of the strongest risk factors for breast cancer. Breast density is associated with known breast cancer risk factors such as reproductive and menstrual factors including serum estrogen and progesterone concentrations. In Italy the National Federation for Breast Cancer (FONCAM) guidelines suggest the usefulness of mammography from 35 years of age for women who undergo infertility hormone therapy (FONCAM Guidelines, 2005). According to this recommendation 294 women aged > or = 35, with primary infertility, sent to our breast service before joining an IVF program were recruited and then underwent clinical examination and X-ray mammography. Women were divided into two groups: dense breast (DB) and non-dense breast (NDB). Univariate analysis was employed to evaluate if there was an association between mammographic density and other risk factors. Evaluation of mammographic features showed the presence of BI-RADs C and D in the sample of 200 (68%) patients with DB and in 94 (32%) patients with NDB BI-RADS A and B. Univariate analysis showed that there were no statistically significant differences between the groups BD and NDB as regards age at mammography, age at menarche, BMI and family history for breast cancer, while ovulatory etiology of infertility was found to be associated with high mammographic density (p < 0.05). In conclusion, bearing in mind that 68% of our study sample had high breast density, we can assume that patients with primary infertility might represent a group at high risk for breast cancer, particularly if infertility is due to an ovulatory factor. We suggest breast screening from the age of 35 in infertile patients who undergo treatment with fertility drugs in accordance with FONCAM recommendations. This might allow the identification of higher risk patients who need more closely monitored breast examinations.

Possible effects of insulin-like growth factor-I, IGF-binding protein-3 and IGF-1/IGFBP-3 molar ratio on mammographic density: a cross-sectional study.

The purpose of this study was to examine the possible effects of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio on mammographic density and assess whether this relationship was similar in subgroups of pre- and postmenopausal women. A group of 341 Italian women of childbearing age or naturally postmenopausal who had performed mammographic examination at the section of radiology of our department a maximum three months prior to recruitment were enrolled. A blood sample was drawn for determination of IGF-1, IGFBP-3 levels and IGF-1/IGFBP-3 molar ratio was calculated. On the basis of recent mammograms the women were divided into two groups: dense breast (DB) and non-dense breast (NDB). To assess the association between mammographic density and IGF-1, IGFBP-3 and Molar ratio Student's t-test was employed before and after stratified by menopausal status. The analysis of the relationship between mammographic density and plasma levels of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio showed that IGF-1 levels and molar ratio varied in the two groups resulting in higher mean values in the DB group whereas IGFBP-3 showed similar values in both groups (DB and NDB). After stratification of the study population by menopausal status, no association was found. Our study provides strong evidence of a crude association between breast density, and plasma levels of IGF-1 and molar ratio. IGF-1 and molar ratio might increase mammographic density and thus the risk of developing breast cancer.

Breast tuberculosis: rare but still present in Italy--a case of mycobacterium breast infection.

Breast tuberculosis is a rare disease in highly endemic countries, and it is even rarer in Western countries, where only occasionally the local population is affected. The rarity of the disease and particularly the lack of a typical clinical-radiological presentation may cause tuberculosis to be mistaken for breast cancer or a pyogenic abscess. The authors present a case of breast tuberculosis in a 27-year-old nulliparous woman, an Italian citizen of the Caucasian race, who has never resided in a tuberculosis endemic area. She presented with painful retroareolar and para-areolar swelling in the right breast associated with cutaneous hyperemia (without fistulization), resistant to antibiotic therapy. Histopathological examination revealed features of mastitis with epithelioid histiocytes and Langhans giant cells and was characterized by the presence of caseous necrosis which suggested tuberculous inflammation. Ziehl-Neelsen staining showed the presence of acid fast bacilli. In countries where tuberculosis is non-endemic, breast tuberculosis should always be included in the differential diagnosis in cases of inflammatory breast lesions resistant to the usual antibiotic therapies. Early recognition may prevent both clinical progression and surgical excision, as breast tuberculosis usually regresses as a response to appropriate anti-tuberculosis therapy.

Role of breast magnetic resonance imaging (MRI) in patients with unilateral nipple discharge: preliminary study.

PURPOSE: This study was performed to assess the role of magnetic resonance imaging (MRI) in patients with unilateral nipple discharge. MATERIALS AND METHODS: Forty-four patients with bloody or serosanguineous nipple discharge and negative mammographic findings (35/44 cases) underwent MRI for evaluation of breast ducts. Ultrasonography, negative in 18 patients, identified 26 cases of ductal ectasia (12 simple, nine with solid intraductal echoes and wall thickening, five with inhomogeneous parenchyma). Galactography was negative in three patients and positive in nine. Nineteen patients were followed up by clinical examination, ultrasonography, and cytological evaluation of nipple discharge (6-12 months); three patients underwent excisional biopsy, ten core biopsy and 12 cytological biopsy (followed by excisional biopsy). RESULTS: MRI identified 25 enhancing lesions Breast Imaging Reporting and Data Systems (BI-RADS) 3 or 4) and confirmed the galactographic findings (ductal ectasia, intraluminal filling defects). Five papillomatoses appeared as patchy, homogeneous enhancing areas, 15 intraductal papillomas as areas with well-defined margins and type II time-intensity curves, and two atypical ductal hyperplasias as diffuse nodular enhancement. One micropapillary ductal carcinoma in situ (DCIS), one papillary carcinoma and one infiltrating ductal carcinoma (IDC) were visualised as two segmental areas of enhancement and one mass-like enhancement with poorly defined margins (BI-RADS 4). The follow-up was negative, showing no pathological enhancement (BI-RADS 1) in 12 patients and benign enhancement (BI-RADS 2) in seven. CONCLUSIONS: Breast MRI can be considered a valuable examination in the diagnosis of suspected ductal disease and an alternative to galactography when the latter cannot be used.

Tamoxifen in women with breast cancer and mammographic density.

PURPOSE OF INVESTIGATION: To evaluate the effect of tamoxifen on mammographic density using a qualitative and a semiquantitative method. METHODS: Mammograms from 148 women treated for breast cancer before and after surgery were reviewed: 68 were administered tamoxifen; 80 did not receive tamoxifen. The mammograms were classified in one of the four BIRADS density categories by two radiologists blinded to the treatment and by a computer-assisted method after digitizing images. RESULTS: At mammographic one-year-follow-up density was reduced in both groups and remained stable in the following years. A comparison of mammograms performed before surgery and after one year showed a statistically significant difference in density reduction between the tamoxifen and the non-tamoxifen-treated group. Good agreement was obtained between the qualitative and semiquantitative method. CONCLUSION: Breast density reduction observed in women treated with tamoxifen may help in the detection of small tumors in dense breasts by means of reducing the masking effect of parenchyma.

Diagnostic utility of combined ultrasonography and mammography in the evaluation of women with mammographically dense breasts.

PURPOSE: To assess the diagnostic utility and additional cost of combined breast ultrasonography and mammography in the evaluation of asymptomatic women with mammographically dense breasts. MATERIALS AND METHODS: Of 5108 asymptomatic women, who underwent mammography, 1754 had dense breasts (BI-RADS 3 or 4) and negative mammographic outcome. They were divided in 4 subgroups according to their age (<40 yrs; 40-49 yrs; 50-59 yrs; >59 yrs). Breast ultrasonography was performed immediately after mammography. Lesions detected at ultrasonography were examined cytologically/histologically. Mammograms from women, who were diagnosed carcinoma at ultrasonography, were reviewed by an external radiologist. Costs per diagnosed carcinoma and per examined woman were calculated on the basis of current regional charges. RESULTS: Mammographies (5108) were performed, 67 cancers were detected (cancer detection rate 13.1‰): mammography identified 55 carcinomas and ultrasonography performed in women with dense breasts identified 12 cancers (17.9% of all cancers detected, overall cancer detection rate 6.8‰). Ultrasonography identified a benign condition in 1567 out of 1754 women (89.3%) (in 925 absence of focal lesions; 438 simple cysts; 56 ductal ectasia; 148 benign solid lesions); 97 complex cysts, 52 lesions that could not be differentiated as liquid or solid lesions, and 38 solid lesions suspicious for malignancy in the remaining 187 out of 1754 patients (10.7%). Cytology/histology confirmed carcinoma in 12 women (overall biopsy rate 26.2‰, benign biopsy rate 19.4‰). The additional costs were: € 6,123.45 per detected cancer, € 41.89 per examined woman. CONCLUSION: Breast ultrasonography immediately after mammography in women with dense breasts is useful to avoid diagnostic delays and inconvenient medico-legal implications even though this procedure involves increased costs.

Cytologic endometrial surveillance in tamoxifen-treated women.

The authors report the results of a study conducted on 136 patients affected by breast cancer under treatment with tamoxifen at a daily dose of 20 mg who underwent a strict follow-up including endometrial surveillance. The cytologic evaluation of the endometrium was performed on smears obtained by the endocyte sampling. The results were in accordance with what is reported in the literature. Forty cases presented with hyperplasia which was atypical in two cases. Only in one case did histology show a well differentiated adenocarcinoma. In 25 cases the endometrium resulted to be proliferative in accordance with the effect of tamoxifen, while the remaining 67 cases were atrophic. The investigation was not possible in four cases due to stenosis. In our study the endocyte sampler resulted to be an economic, simple and painless cytologic device, suitable for clinical use because of its low incidence of false positives.

[Clinical aspects of breast cancer in the aged woman]. / Aspetti clinici del carcinoma mammario nella donna anziana.

In Italy breast cancer mortality is constantly increasing in women over 70 years of age. The retrospective analysis of the cases observed at the "Senology Center" of the II Institute of Obstetrics and Gynecology (University "La Sapienza" of Rome) shows when compared to the group of women under age of 40 a higher number of advanced cases. This delayed diagnosis needs a most radical treatment and adjuvant therapies (i.e. chemotherapy) that cannot often be carried out because of general problems. Therefore, elderly women should be sensibilized to undergo periodical and regular sanitary inspection.

An overview of adolescents breast disorders.

Our investigation has confirmed the low incidence of mammarian pathology in adolescents and the near absence of malignant neoplastic pathology. Programs of breast control in this age can be valid only by aiming at health education prevention and correction of eventual risk factors. The group of adolescents studied by us has allowed us to define the most frequent pathology as the functional one, that is, mastodinia, and among the organic cases single or multiple fibroadenomas are the most frequent lesions. An exact diagnostic profile is necessary in order to reassure the patient in cases of absence of pathology, or to schedule a follow-up or to program an eventual surgical and/or medical treatment.

[Randomized study of the use of synthetic diosmin in premenstrual and vascular dysplastic mastodynia]. / Studio randomizzato sull'impiego della diosmina sintetica nella mastodinia displasica premestruale e vascolare.

The antalgic effect of synthetic diosmin in 120 patients suffering from vascular and premenstrual mastodynia is studied compared to the same number of non-treated cases. The therapy has been carried out for one consecutive year. For the same period the course of the painful symptomatology, both in the cases treated and in the controls, has been checked. For the treated cases a significant decrease of the painful symptomatology has been obtained and this decrease was maintained.

[Typology and etiopathogenesis of breast pain]. / Tipologia ed etiopatogenesi del dolore mammario.

Although mammary pain is the most common reason prompting women to seek breast examination, it is considered to unimportant to be fully investigated and often treatment is extremely superficial. A projected investigation of the natural history of mammary pain through examination of the symptomatology of the commonest forms is considered to be necessary for accurate diagnosis, itself indispensable for effective treatment.