C-reactive protein in nipple aspirate fluid associated with Gail model factors.

BACKGROUND: The majority of breast cancers originate in the epithelial lining of the breast ductal system. Premalignant cell damage in this lining may produce biochemical signals that deliver inflammatory proteins to the site. The presence of C-reactive protein (CRP) in nipple aspirate fluid (NAF) may reflect an inflammatory state indicative of a premalignant breast microenvironment. This study ascertained CRP's presence in NAF and evaluated if risk factors, as identified by the Gail model, were associated with NAF CRP levels among healthy women. DESIGN: NAF CRP levels were assayed in 59 women. RESULTS: CRP was present in NAF and significantly (p = .04) and positively related to breast cancer risk as predicted by the Gail model. CONCLUSION: CRP is differentially present in NAF and varies by Gail model risk factors. CRP in NAF holds promise as a noninvasive biomarker that detects a precarcinogenic breast ductal microenvironment and may contribute to the diagnosis of breast cancer early in the course of the disease when prognosis is most favorable.

Prevalence of bacteria in the nipple discharge of patients with duct ectasia.

The aim of this study was to identify the aerobic and the anaerobic microorganisms which can be related to duct ectasia. The patients were divided into two groups. Group 1 comprised 100 patients with coloured nipple discharge (duct ectasia group), and Group 2 (the control group) was composed of 50 patients without nipple discharge. The culture media used were BHI-PRAS, blood agar, mannitol agar and MacConkey agar. There was a high frequency of bacterial growth in the two groups: 85% in Group 1 and 88% in Group 2. The most prevalent bacteria were Staphylococcus aureus and Staphylococcus epidermidis. There was a statistically significant higher rate of smokers in the duct ectasia group compared with the control group, 25 (25%) patients vs. 5 (10%), respectively (p = 0.03). These findings allow us to put forth the hypothesis that the genesis of duct ectasia may be a non-infectious inflammatory process.

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at sites typical for Borrelia burgdorferi infection.

BACKGROUND: Cutaneous manifestations of B-cell chronic lymphocytic leukemia (B-CLL) comprise a wide spectrum of clinicopathologic presentations. In some cases, onset of skin lesions is triggered by antigenic stimulation, and specific skin infiltrates at sites of previous herpes simplex or herpes zoster infection have been well documented. Specific skin manifestations of B-CLL can also be observed at sites typical for lymphadenosis benigna cutis (nipple, scrotum, earlobe), a Borrelia burgdorferi-associated cutaneous B-cell pseudolymphoma. METHODS: We studied specific skin manifestations of B-CLL arising at sites typical for B. burgdorferi-induced lymphadenosis benigna cutis, analyzing tissues for presence of B. burgdorferi DNA using the polymerase chain reaction (PCR) technique. Six patients with B-CLL (M : F = 4 : 2; mean age: 67.8) presented with specific skin lesions located on the nipple (four cases) and scrotum (two cases). RESULTS: Clinically there were solitary erythematous plaques or nodules. Histology revealed in all cases a dense, monomorphous infiltrate of small lymphocytes showing an aberrant CD20+/CD43+ phenotype. In all cases monoclonality was demonstrated by PCR analysis of the JH gene rearrangement. PCR analysis showed in four of the six cases the presence of DNA sequences specific for B.burgdorferi. CONCLUSIONS: Our study demonstrates that infection with B. burgdorferi can trigger the development of specific cutaneous infiltrates in patients with B-CLL.

Cytodiagnosis of nipple discharge: a study of 602 samples from 484 cases.

To find out the gross and microscopic differentiating features between nipple discharges (ND) due to various breast lesions, smears of 602 ND samples from 484 cases were reviewed by one of the investigators (D.K.D.). The reviewed cytodiagnoses were as follows: benign nipple discharge (59.1%), inflammatory ND (6.5%), ?papillary lesions (2.5%), papillary lesions (20.6%), papillary lesions with atypia (3.8%), duct cells with atypia (0.2%), suspicious for malignancy (0.5%), malignant ND (1.2%), and inadequate (5.6%). Following review, samples with epithelial abnormalities (?papillary lesion, papillary lesion with and without atypia, duct cells with atypia, suspicious for malignancy, and malignancy) increased from 16.6% to 30.4% of adequate samples (P < 0.0001). 37.9% unilateral ND samples showed epithelial abnormalities, as opposed to 18.9% of bilateral ND samples (P < 0.0001). Bloodstained ND showed epithelial abnormalities in 41.5% samples, as compared to 22.1% of ND with other specified gross characteristics (P < 0.0001). The samples with epithelial abnormalities differed significantly from benign and inflammatory ND in respect of frequency of benign duct cells, duct cells with atypia, papillary clusters with or without atypia, malignant cells, columnar cells, red blood cells, inflammatory cells, and background lipid vacuoles (P < 0.01 to < 0.0001). The ND samples with suspicious and malignant cytology, besides the presence of malignant cells (P < 0.0001), differed significantly from rest of the lesions in respect of foam cells (P < 0.0001), red blood cells (P < 0.01), and inflammatory cells (P < 0.05). When compared with histopathological diagnosis in 20 cases, the benign or malignant nature of the lesion was correctly identified in ND in 80% cases. The ND cytologies in 7 histologically proved malignant cases were malignancy (3 cases), suspicious for malignancy (1 case), papillary lesion with atypia (1 case), papillary lesion (1 case), and benign ND (1 case).

Benign proliferative nipple duct lesions frequently contain CAM 5.2 and anti-cytokeratin 7 immunoreactive cells in the overlying epidermis.

Benign proliferative nipple duct lesions (PNDLs) pose a diagnostic problem for clinicians and pathologists. Clinically, they may be associated with skin changes typically present in Paget's disease of the nipple. The identification of numerous scattered cells in the epidermis that are immunoreactive for low-molecular-weight cytokeratin may lead to further confusion with Paget's disease. We studied the nipple epidermis in nine cases of PNDL and compared them with 26 histologically normal nipples from mastectomy specimens. CAM 5.2 and anticytokeratin 7 (CK7) immunoreactive cells were identified in the epidermis of seven of nine nipples associated with PNDL. The cytokeratin-positive cells appeared cytologically benign and were dispersed singly (scattered in seven of seven cases and frequent in four of seven cases) or formed small aggregates with occasional tubular structures (three of seven cases) in the basal and middle layers of the epidermis. In two of seven cases, these epidermal immunoreactive cells showed continuity with the underlying PNDL, suggesting the spread or continuation of lesional cells to the epidermis. Dispersed single immunoreactive cells were identified in small numbers (scattered) in the basal layer of the epidermis in 12 of 26 normal nipples and more frequently in 1 of 12 cases. In all cases, the intraepidermal cells were negative for carcinoembryonic antigen (CEA) and Her-2/neu. We conclude that intraepidermal CAM 5.2 and anti-CK7 immunoreactive cells, which are normally present in the nipple epidermis, may proliferate and form aggregates when there is an underlying PNDL. The presence of these cells does not imply Paget's disease when the intraepidermal cells have a bland cytologic appearance, fail to overexpress Her-2/neu, and there is no carcinoma within the PNDL or elsewhere in the breast.

Carcinoembryonic antigen estimation in nipple discharge as an adjunctive tool in the diagnosis of early breast cancer.

To assess the usefulness of carcinoembryonic antigen (CEA) estimation in nipple discharge for the detection of nonpalpable breast cancer, CEA activity in nipple discharge was measured by enzyme immunoassay using monoclonal antibody. The specificity of the antibody for breast cancer was assessed by an immunohistochemical method. Mean CEA levels in the nipple discharge from 18 patients with benign breast diseases (ten intraductal papilloma; eight fibrocystic disease) was 43 ng/ml (SD, 34 ng/ml), suggesting an upper reference limit of 100 ng/ml. Six of seven nonpalpable breast cancer patients had higher CEA levels than this tentative cutoff value, as did three of five patients with borderline lesions. The incidence of elevated CEA levels in nipple discharge correlated significantly with the incidence of intratumoral antigen expression. These results lead us to conclude that CEA measurement in nipple discharge may be a useful adjunct in the diagnosis of nonpalpable breast cancer.