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A syndrome, consisting of a congenital abnormality of the scalp, ears and nipples inherited as an autosomal dominant trait, is reported. Ten affected members of a family over five generations are recorded and the four living affected members are described in detail. A review of congenital localized aplasias of skin suggests that this may be a new syndrome.
A case is described of a man with multiple papillomas on the nipple that resembled clinically and histologically condylomata acuminata. Human papillomavirus (HPV) type 41 DNA sequences were detected in the biopsy material. There was no evidence of any immunodeficiency.
Tumours from 45 patients with Paget's disease of the nipple have been stained with antibody 21N which was raised against a peptide from the C-terminus of the predicted c-erbB-2 protein. Positive staining was observed in 41 cases (91%). In 42 cases the underlying mammary carcinoma was also available for study. In all but two cases staining was similar in the Paget's cells and the underlying carcinoma whether the latter was purely in situ ductal (35%) or in situ associated with infiltrating carcinoma (65%); the malignant cells in both components were large and pleomorphic and the in situ ductal carcinoma was of the comedo type. In the two exceptions the underlying carcinoma showed different histological features. The significance of the high levels of c-erbB-2 protein in this pattern of mammary carcinoma is considered.
A Jewish Sephardi family is reported in which 16 members are affected (15 females and 1 male) with inverted nipples. The one affected male and his brother also have gynecomastia. Under the assumption that this trait is transmitted as an autosomal dominant, linkage studies were done but were not revealing. Further family and investigative studies are needed in this disorder to understand better its pathogenesis and precise mode of genetic transmission.
The association of scalp defect, unusual ears and absence of nipples was described by Finlay & Marks as an autosomal dominant trait. We report a new case in a 23-year-old woman. Renal insufficiency and cataract seem to be frequent and must be investigated.
Patients with serous or bloody nipple discharge arising from a single duct are treated by a joint radiological/surgical approach at our institution. Two galactograms are performed; the first with contrast medium alone to identify any lesion and the second, one hour prior to surgery, using both contrast and methylene blue. This defines the area for the surgeon ensuring the involved duct is removed. Several case histories are described and the galactographic technique is detailed.
Aplasia cutis congenita (ACC) is a rare disorder characterized by localized absence of skin at birth. A subtype consisting of a solitary scalp defect in association with limb abnormalities has been described. We report a case of ACC in association with 3,4 syndactyly and supernumerary nipples with an apparent autosomal dominant inheritance pattern.
One hundred two infants and children age 3 days to 16.5 years, found to have accessory nipples (AN), were enrolled in this study. They were categorized by ethnic origin, sex, positive family history of AN, and number, site, and shape of AN, to determine factors for increased risk of anomalies of the urinary tract. Physical and ultrasound examinations of the abdomen did not reveal evidence of urinary tract malformation in any of the children. The results of this survey support the contentions that AN are not associated with urinary tract malformations, and that no further investigation is required in children with solitary AN.
Paget's disease of the breast generally affects middle-aged and older females. In the majority of cases, it is considered to be the result of epidermal spread from a contiguous mammary duct carcinoma. We report the first case in an adolescent female with an accessory nipple. The histomorphology and immunophenotypic findings support the hypothesis of in situ transformation and suggest a histologic spectrum exists in terms of cytologic atypia.
The occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB-2 oncoprotein was investigated in twenty-eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin-fixed, paraffin-embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB-2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB-2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB-2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas.
Galactography was performed in 204 women with a nipple discharge and the secretion confirmed histopathologically. All 116 intraductal tumors (papilloma, papillomatosis, carcinoma), which were associated with a serous or bloody discharge, were detected preoperatively. A palpable mass had little diagnostic significance, and exfoliative cytology was positive in only 11% (2/18) of the patients with carcinoma. The authors recommend that all patients with a spontaneous bloody or serous discharge from a single lactiferous orifice undergo galactography in addition to physical, cytological, and mammographic examination. Intraductal injection of methylene blue dye will demonstrate the affected duct system to the surgeon and can often make surgery less radical or even unnecessary.
On a mediolateral mammogram obtained during routine screening, a mass was noted deep within the breast. However, no mass could be palpated, and additional views showed no mass. Observation of the patient during imaging demonstrated the nipple of the opposite breast was inadvertently projected onto the image. Radiologists should be aware of this cause of pseudotumor of the breast.
A monofilament polypropylene guiding suture was inserted into a secreting duct in 72 female patients (aged 15-78 years) with nipple discharge. Cannulation and injection of contrast material was successful in all patients before galactography and of methylene blue dye before excision. Patients did not report discomfort, no injuries ensued, and no duct was perforated. This technique should expedite excision of a discharging duct and any lobules.
Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.
BACKGROUND: Recent guidelines suggest that chemoprevention with tamoxifen may be appropriate for women who have a 5-year risk of breast cancer greater than 1.66% calculated using the Gail model. OBJECTIVES: To determine whether nipple aspirate fluid (NAF) cytology combined with the Gail model provides breast cancer risk assessment that is superior to either method alone. METHODS: Prospective observational cohort of 6,904 asymptomatic women. Breast cancer cases were identified through follow-up with the women and linkage to cancer registries. We used proportional hazards modeling to recalculate the coefficients for the predictor variables used in the Gail model. NAF cytology was added to create a second model. The two models were compared using the concordance statistic (c-statistic). RESULTS: During 14.6 years of follow-up, 400 women were diagnosed with breast cancer. There were 940 (14%) women with hyperplasia and 109 (1.6%) women with atypical hyperplasia found in NAF. Adding NAF cytology results to the Gail model significantly improved the model fit (P < 0.0001). The c-statistic for the Gail model was 0.62, indicating only modest discriminatory accuracy. Adding NAF cytology to the model increased the c-statistic to 0.64. NAF cytology results had the largest effect on discriminatory accuracy among women in the upper third of Gail model risk. The relative incidence for the highest quintile of risk score compared with the lowest quintile was 7.2 for the Gail model and 8.0 for the model including NAF cytology. CONCLUSION: NAF cytology has the potential to improve prediction models of breast cancer incidence, particularly for high-risk women.
BACKGROUND: Concentrations of estrogen and progesterone within the breast could provide a better reflection of breast cancer risk than levels in the circulation. We developed highly sensitive immunoassays for multiple steroid hormones and proteins in the nipple aspirate fluid (NAF), which can be obtained noninvasively with a simple suction device. Previous studies showed that NAF hormone levels are strongly correlated between breasts and within a single breast over time and are predictably related to hormone replacement therapy or use of oral contraceptives. This study evaluates the relationship of NAF estrogen and progesterone levels to those in serum and saliva, the relationship of NAF estradiol to androgenic and estrogenic precursors in NAF, and the relationship of NAF hormone levels to those of response proteins such as cathepsin D and epidermal growth factor (EGF). METHODS: Normal premenopausal women collected saliva daily and donated blood and NAF in the midluteal phases of menstrual cycles at intervals of 0, 4, 12, and 15 months. Analytes were measured by immunoassays after solvent fractionation. Log-transformed values were fit to repeated measures analysis of covariance models to ascertain associations between analytes. RESULTS: Small nonsignificant associations were found between NAF and serum or salivary estradiol. However, progesterone in NAF was significantly associated with progesterone in serum and saliva (R=0.18 and 0.32, respectively). Within NAF, the estradiol precursors estrone sulfate, androstenedione, and dehydroepiandrosterone were significantly associated with estradiol concentration (P<0.06), and a multiprecursor model explained the majority of variance in NAF estradiol (model R(2)=0.83). Cathepsin D and EGF in NAF could not be predicted from serum or salivary steroid measurements; however, both could be predicted from estradiol and its precursors in NAF (model R(2)=0.70 and 0.93, respectively). CONCLUSIONS: By showing consistent associations between estradiol and its precursors and response proteins, these data provide support for the biological validity of NAF hormone measurements and for the importance of steroid interconversion by aromatase and sulfatase within the breast. The low correlation between estrogen levels in NAF and those in serum or saliva suggests that the degree of association between estrogen or its androgen precursor levels and risk of breast cancer observed in epidemiologic studies using serum estimates might be highly attenuated.
PURPOSE: To establish a comprehensive proteomic approach for biomarker discovery and validation in breast fluid. EXPERIMENTAL DESIGN: A total of 95 specimens from three institutions were used including 10 nipple aspiration fluid (5 stage I/II cancerous breasts and 5 age-matched healthy controls), 42 ductal lavage fluid from 14 patients with unilateral stage I/II cancer (25 from 9 cancerous breasts and 17 from 7 contralateral breasts), and 42 ductal lavage fluid from 14 high-risk women (multiple ducts repeated lavage). Differentially expressed protein/peptides were discovered by proteomic analysis of training sample, using ProteinChip arrays and surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry, and validated on independently collected testing samples. After protein identification, ELISA was done to confirm the SELDI findings. RESULTS: We were able to obtain reproducible protein profiles using minimal amount of protein (1 mug) by applying an optimized chip protocol and SELDI. We were able to select cancer-associated biomarkers despite large individual variability by applying both unsupervised and supervised cluster analysis. Furthermore, we were able to train and test candidate biomarkers on independently collected samples and identified one component of a multimarker panel as human neutrophil peptides 1 to 3. CONCLUSIONS: Breast fluid is a rich source of breast cancer biomarkers. In combination with high-throughput novel proteomic profiling technology and multicenter study design, markers that are highly specific to breast cancer can be discovered and validated. Our observations also suggest that persistent elevation of human neutrophil peptide in high-risk women may imply early onset of cancer not yet detectable by current detection method. Proof of this hypothesis requires follow-up on a larger study population.
A case of cutaneous leiomyoma of the male nipple is reported. This is the second case reported by dermatologists to the best of our knowledge.