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[Correlation of ultrasound and galactography in the diagnosis of nipple discharge. Preliminary results].

INTRODUCTION: Several pathologic conditions involving the breast ductal tree can cause bloody or serous nipple discharge. Galactography plays a major clinical role in identifying and localizing intraductal masses, but its sensitivity in detecting cancer is certainly suboptimal. Presently high-frequency ultrasound (US) probes allow detection and guided biopsy of intraductal lesions. We compared the specific information provided by US and galactography in the discharging breast. MATERIAL AND METHODS: Thirty-three patients with discharging breast were submitted to both diagnostic examinations. US was performed with 13 MHz scanheads both before and after galactography. Galactography was performed with 30-31 G catheters to cannulate the discharging duct. Nonionic, water-soluble, sterile contrast material was administered. Postgalactography US was performed to investigate if it could yield further information. The final diagnosis was made at histology and 2 years' instrumental follow-up. RESULTS: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were evaluated for both techniques. We considered a positive finding the detection of a lesion in general (be it papilloma, papillomatosis, or cancer), as well as the detection of carcinoma only. Sensitivity was 96% for galactography and 84% for US in the former case, versus 50% and 100%, respectively, in the latter. Postgalactography US added no major information. DISCUSSION AND CONCLUSION: US is more sensitive than galactography in cancer diagnosis and, it permits guided biopsy and preoperative localization of unpalpable ductal lesions. In our limited experience, US can be considered a complementary diagnostic tool to galactography in the discharging breast.

Adult↗

Syringomatous adenoma of the nipple.

Syringomatous adenoma of the nipple (SAN) is an extremely rare neoplasm of the breast. We present a case of 41-year-old female with a retroareolar mass in her left breast. The patient has been operated on twice and remains free of disease for 20 months after the second operation. The nosological status of SAN and its relationship to the microcystic adnexal carcinoma of the skin is discussed.

Adenoma↗

[Pigmented Paget's disease of the male nipple].

BACKGROUND: Mammary Paget's disease unfrequently occurs in males, and may be pigmented in rare instances. Differential diagnosis with malignant melanoma relies on immunohistochemical studies. CASE REPORT: A case of Paget's disease of the nipple in a 76 year-old male is reported, clinically mimicking a malignant melanoma because of massive pigmentation. Histologically, large Paget's clear cells were intermingled with numerous melanin-rich dendritic melanocytes. An underlying ductal carcinoma was found. After differential immunohistochemical staining, diagnosis of Paget's disease could be unequivocally substantiated since Paget's cells stained for epithelial markers, c-erbB-2 and hormonal receptors, whereas protein S100 and HMB45 were negative. DISCUSSION: Pigmentation in mammary Paget's disease occurs preferentially in males. Pigmentation results from numerous melanocytes with abundant melanin in close contact with Paget's cells. An increased number of melanocytes may also be observed in cutaneous metastatic breast carcinomas. It could result from a chemotactic factor produced by neoplastic cells.

Aged↗

[Electrical activity of mechanoreceptor neurons in rat mammary gland nipple skin].

Three types of the mechanosensitive units were found in the skin of the rat mammary gland nipple: receptors detecting: 1) transients, 2) velocity, 3) position and velocity. The 1st and the 2nd types were spontaneously inactive and both adapted rapidly to mechanical stimuli. The 3rd type had a spontaneous activity 1-4/sec and adapted slowly to mechanical stimuli.

Action Potentials↗

[Rare pathology of the breast: adenoma of the nipple].

Adenoma of the nipple is a benign pathology which histologically interests the epithelium of the galactophorous ducts. This pathology looks like Paget's disease both macroscopically and microscopically, therefore an exact differential histologic diagnosis is needed with the breast's carcinoma to undertake the most timely surgical therapy.

Adenoma↗

[Adenomas of the nipple].

A case of adenoma of the nipple is reported. Although this is a comparatively rare condition, knowledge of it is extremely important because clinically it simulates Paget's disease. A failure to recognise the pathology could therefore lead to mistaken diagnosis and consequent surgery which would create serious damage to the patient. According to almost all authors, it is a benign pathology and can therefore be treated with an intervention limited to removing the complete tumour. This for two reasons: the first is that if the tumour grows it can become painful, create a sense of tension and bleed in the erosive phase; the second, more important, is that malignant degeneration has been hypothesised. For these reasons it is essential to examine the other breast immediately and follow the patient over time to prevent unpleasant surprises.

Biopsy↗

Detection of 2,6-cyclolycopene-1,5-diol in breast nipple aspirate fluids and plasma: a potential marker of oxidative stress.

An high-performance liquid chromatography method with electrochemical detection was developed to quantify both 2,6-cyclolycopene-1,5-diol and lycopene in plasma and breast nipple aspirate fluids (NAF). As an example of the utility of this assay, levels in plasma and NAF of 11 women were examined and compared with levels of 8-isoprostane, a commonly used marker of lipid oxidation. Levels of 2,6-cyclolycopene-1,5-diol and 8-isoprostane were higher in NAF than in plasma, but levels of lycopene were lower in NAF than in plasma. Levels of 2,6-cyclolycopene-1,5-diol in plasma and in NAF were significantly correlated with both lycopene and 8-isoprostane levels. This is consistent with the dependence of 2,6-cyclolycopene-1,5-diol levels on both dietary intakes of lycopene and oxidative stress levels. For the correlations between NAF and plasma, lycopene levels were significantly correlated, whereas 2,6-cyclolycopene-1,5-diol levels were not, indicating that levels of 2,6-cyclolycopene-1,5-diol in NAF are difficult to predict from plasma levels. The high levels of 2,6-cyclolycopene-1,5-diol and 8-isoprostane in NAF are consistent with high levels of oxidative stress in the breast.

Adult↗

Supernumerary nipples: an overview.

Supernumerary nipples (SNs) are relatively common, minor congenital anomalies. SNs usually arise within the embryonic milk lines, but they have been known to form elsewhere. The prevalence of SNs varies, depending on the population. SNs are normally benign entities, but they are susceptible to hormonal changes and disease processes and may signify internal disease.

Congenital Abnormalities↗

Microsatellite changes in nipple aspirate fluid and breast tissue from women with breast carcinoma or its precursors.

PURPOSE: Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been identified in a variety of human cancers. The purpose of this prospective study was to determine whether (a) DNA can be isolated from nipple aspirate fluid (NAF) and PCR amplified to large fragments, (b) LOH and MSI are detectable in NAF, and (c) LOH and MSI in tissue and NAF increase with disease progression from precursor lesions to cancer. EXPERIMENTAL DESIGN: Forty-six matched samples from breast lesions, normal breast, and NAF were microdissected, and DNA was extracted. Eleven microsatellite markers from seven chromosomes that have a high frequency of LOH/MSI in breast cancer were designed and respectively amplified. RESULTS: LOH and/or MSI were identified in 22 of 46 (48%) breast lesions, including LOH in 8 of 36 (22%) proliferative/papilloma (P/Pap) and 7 of 10 (70%) cancer specimens, whereas MSI was found in 14 of 36 (39%) P/Pap and 6 of 10 (60%) cancer specimens. LOH/MSI loci in which alterations were detected in the 22 tissue specimens were PCR amplified using matched NAF DNA. LOH/MSI was detected in NAF from both P/Pap (5 of 15; 33%) and breast cancer (3 of 7; 43%) samples. CONCLUSIONS: Our findings suggest that (a) DNA from NAF, a physiological fluid collected noninvasively, can be PCR amplified and used to screen for LOH and MSI alterations that are known to be linked to breast cancer, suggesting that this methodology might prove useful for breast cancer screening, and (b) similar to findings in breast tissue, LOH and MSI alterations increase in frequency with disease progression in NAF, which suggests that NAF is a surrogate for breast tissue which has important prognostic implications.

Biomarkers, Tumor↗

The place for conservative treatment in the management of Paget's disease of the nipple.

Four cases of Paget's disease confined to the nipple are presented. Three of them were treated conservatively by local radiotherapy and the fourth was treated by mastectomy. Histopathological examination of the breast in the last case failed to show any evidence of in situ or invasive carcinoma. The first three patients are well and without evidence of recurrence 3 to 5.5 years after treatment. Could conservative treatment in the form of local excision or radiotherapy offer an alternative to mastectomy? A discussion on the place of conservative treatment is presented.

Aged↗

Clinically silent Paget disease of male nipple.

Male breast cancer constitutes less than 1% of all breast cancer cases. Special types, such as Paget disease of the breast, are extremely rare. To our knowledge there are less than 50 cases of Paget disease of male breast described in world medical literature. Authors present pathologically proven but clinically silent case of Paget disease of the nipple in an 86-year old male with breast cancer. Literature data suggest that the prognosis of male Paget cancer is worse than in "ordinary" male breast cancer. Therefore, the histologic diagnosis of Paget disease, even in an asymptomatic male patient, may have negative prognostic value.

Aged↗

Skin-sparing and nipple-sparing mastectomy: preoperative, intraoperative, and postoperative considerations.

The last several decades have witnessed significant advances in the surgical management of breast cancer. Although many have embraced breast conservation as the procedure of choice, some patients will still opt for mastectomy for a variety of reasons. Recently, the concept of skin sparing mastectomy and immediate breast reconstruction has emerged as an option that provides excellent cosmetic results while being oncologically safe. However, this surgical approach must be considered within a multidisciplinary context, and there are a number of perioperative issues that need to be considered. In addition, newer techniques, which spare the nipple and/or areola, warrant further examination.

Breast Implants↗

Variation in estradiol, estradiol precursors, and estrogen-related products in nipple aspirate fluid from normal premenopausal women.

The purpose of the study was to measure the concentrations of estradiol, its primary precursors, and factors with which it interacts in the breast, and determine their sources of variation. Nipple aspirate fluid (NAF) was collected from premenopausal women during the mid-luteal phase of the menstrual cycle. The fluid was diluted and unconjugated steroids were extracted. Estradiol was further purified by a solvent partition into aqueous NaOH. Androgens were measured in the non-phenolic fraction. Water-soluble, conjugated steroids and proteins were measured in the aqueous residue. All analytes were measured by immunoassays. Permutation methods were used to determine the correlations over multiple periods of time. The average concentration of estradiol in NAF was 435 pmol/L after purification but was many times higher when assayed without purification. Estrone and dehydroepiandrosterone (DHEA) sulfates were present in 3.7 and 75 micromol/L concentrations, respectively, while unconjugated androstenedione and DHEA were present in nanomole per liter concentrations. Lack of the steroid sulfates in NAF in 19% of subjects had no effect on NAF estradiol levels but was associated with a 77% lower concentration of unconjugated DHEA. Progesterone was present in concentrations that were 3- to 4-fold higher than normal serum concentrations (mean: 291 nmol/L). Cathepsin D, epidermal growth factor, and interleukin 6 had average values of 3.4 microg/mL, 424 ng/mL, and 1.7 ng/mL, respectively. Correlations between breasts were between 0.57 and 0.84 for the several analytes; correlations over time ranged from 0.64 and 0.93 with estrone sulfate highest in both categories. The lower correlation between breasts than within breasts indicates that local factors play an important role in determining the levels of many of these analytes in the breast. The high stability of the concentrations of several analytes over time indicates that fluctuations in environmental factors have little immediate effect on levels in the breast, and portends their utility as surrogate breast cancer risk markers.

Adult↗

Hormones and growth factors in nipple aspirates from normal women and benign breast disease patients.

Several reports have indicated that the breast fluid obtained by nipple aspiration provides valuable biological material for inclusion in studies of breast cancer biochemical epidemiology. Breast fluids contain a variety of hormones and growth factors, often at concentrations considerably higher than those in the corresponding serum. Aspirates from benign breast disease patients have very high levels of bioactive lactogenic hormones and, to a lesser extent, immunoassayable prolactin, compared with healthy controls. A growth hormone-like protein, recognized in a radioimmunoassay but not in a growth hormone-specific immunoradiometric assay, and lacking activity in the Nb2 cell bioassay, is usually present in fluids from Finnish (low breast cancer risk) but not American (high breast cancer risk) women. Epidermal growth factor and transforming growth factor-alpha are present in breast fluids, with preliminary indications that these functionally related polypeptides occur at relatively high concentrations in benign breast disease.

Adult↗

Lack of effect of celecoxib on prostaglandin E2 concentrations in nipple aspirate fluid from women at increased risk of breast cancer.

BACKGROUND: Cyclooxygenase enzymes (COX-1, COX-2, and COX-3) convert arachidonic acid to prostaglandins, prostacyclins, thromboxanes, and other hydroxy fatty acids. Among these, prostaglandin E(2) (PGE(2)) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE(2) production in cancerous tissue. OBJECTIVE/HYPOTHESIS: We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE(2) would be secreted in breast nipple aspirate fluid (NAF), that levels in NAF would be higher than in corresponding plasma, and that celecoxib would decrease PGE(2) levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma. SPECIFIC AIM: To determine if PGE(2) concentrations in NAF and plasma decrease after a 2-week course of celecoxib and then return to baseline 2 weeks after stopping the medication (washout). STUDY DESIGN: NAF and plasma were collected before celecoxib treatment, 2 weeks after taking celecoxib, and 2 weeks after washout. Each woman served as her own control. RESULTS: PGE(2) concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE(2) levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE(2) concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE(2) concentrations after celecoxib administration. CONCLUSIONS: PGE(2) can be measured in NAF. PGE(2) levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE(2) concentrations in NAF and plasma.

Adult↗

Erosive adenomatosis of the nipple: histology, immunohistology, and differential diagnosis.

Erosive adenomatosis of the nipple (EAN) is a complex benign mammary proliferation that has a variety of histologic appearances. All forms of this lesion are thought to be composed of two apparent cell types: epithelial luminal cells and basal myoepithelial cells. A panel of immunohistochemical reagents was employed to determine whether this divergence of differentiation could be confirmed immunohistochemically. It included antibodies against cytokeratin (CK), vimentin (VIM), glial fibrillary acidic protein (GFAP), and muscle-specific actin (MSA); the latter three markers are associated with myoepithelial differentiation. EAN was also assessed with reagents directed at carcinoembryonic antigen (CEA) and collagen type IV (CIV). Basal glandular cells in EAN homogeneously expressed CK and MSA. They also were positive for VIM in 10 cases, and for GFAP in three. Luminal glandular cells in EAN expressed CK uniformly and CEA focally. Lesional glands were surrounded by a concentric layer of CIV. The authors conclude that two cell types are indeed demonstrable immunohistochemically in EAN, one of which has myoepithelial features. CEA may be expressed by this lesion despite its innocuous biological nature, and constituent glands synthesize basement membrane proteins in a pattern that is characteristic of benign mammary proliferations. Differential diagnosis between EAN and invasive carcinoma of the breast may be facilitated by immunohistologic evaluation, but the latter modality of study is not capable of distinguishing between EAN and other benign proliferative mammary lesions.

Adenoma↗

Position of heart in relation to sternum and nipple line at various ages.

Frontal X-ray pictures of 210 healthy children from birth to twelve years of age with radio-opaque markers at sternal ends and both nipples were reviewed. The position of centre of cardiac silhouette was correlated with sternal areas and internipple line. The heart was found to descend with age, its centre lying beneath mid-sternum during first six months of life and beneath lower sternum after infancy (p less than 0.001). The position did not vary with age in relation to internipple line (p greater than 0.05). In 77.6% of all children, it was below the internipple line and in 22.4% above or at the internipple line. Because of the erratic relationship of cardiac centre with internipple line, the latter should not be considered a landmark for cardiac position. External cardiac massage should be applied in relation to sternum and at different locations according to the age. Sites for optimal compression have been suggested. No sexual dimorphism was observed.

Anthropometry↗