Nipple discharge cytology in mass screening for breast cancer

Since 1977 mass screening for breast cancer has been conducted in Miyagi Prefecture, Japan; inspection, palpation and cytologic examination of any nipple discharge are part of the initial screening procedures. Among 149,681 subjects examined, 404 cancer cases and 63 papilloma cases were detected. The nipple discharges from 20,537 women were examined cytologically; of the 61 cancer cases, the smears were positive in 18 cases, suspicious in 7, negative with atypical findings in 12 and negative in 24. Ten of the cancer cases were detected exclusively by the cytologic examination of a nipple discharge. In eight of these ten cancer cases, there was no other initial evidence of the primary tumor. The cytologic diagnosis of discharges without blood from 28 cancer cases was positive or suspicious in 10 cases and negative in 18. Thirty-seven of the papilloma cases were initially detected only by the cytologic examination of a nipple discharge; neither physical examination nor mammography showed any abnormal findings.     

Fine needle aspiration cytology of "minimal" breast cancer

The value of fine needle aspiration (FNA) cytology in the diagnosis of "minimal" breast cancer was studied. Sixteen (76.2%) of 21 cases of invasive breast cancer less than 1.0 cm in diameter and 14 (73.3%) of 19 cases of noninvasive breast carcinoma were given a positive diagnosis by FNA cytology. One "suspicious" and the five false-negative diagnoses occurred in cases of invasive carcinoma; the reasons were considered to be either a faulty technique of needling the tumor or the presence of prominent fibrosis in the tumor. In noninvasive carcinoma, atypical cells were misdiagnosed in two of the five smears that had been originally reported as negative. The results of the retrospective analysis showed that FNA cytology had a higher accuracy in the diagnosis of small lesions than did radiologic and echographic criteria, and FNA cytology was thus used as the main criterion for deciding on the necessity for preoperative surgical biopsies.     

Scrape cytology assessment of margins of lumpectomy specimens in breast cancer

In cases of breast carcinoma in which only lumpectomy is performed, it is necessary to ascertain that the surgical margins were adequate, i.e., free of tumor. Since the histologic methods used for this purpose are either unreliable or very cumbersome, scrape cytology was evaluated as a method for the examination of lumpectomy margins. In 30 cases examined both cytologically and histologically, a very good correlation was found between the two methods. The scrape cytology method has the advantage of being much easier and quicker and is thus recommended for routine use.     

Aspiration cytology of breast carcinoma

In the past 12 years aspiration cytological examination was carried out in 310 cases of histologically verified breast cancer. A classification of mammary carcinomas is presented and the cytomorphological features of cells constituting the different types of tumour are described. The value of aspiration cytology in preoperative diagnosis of early cancerous proliferations is emphasized. In the light of clinical, mammographic and cytological investigations the accuracy is about 96%. The method is reliable, quick, has no hazard, and can be performed in out-patients. Its routine application is recommended to all institutions possessing adequate facilities and staff.     

Application of liquid-based preparation to fine needle aspiration cytology in breast cancer

OBJECTIVE: To examine the performance of liquid-based cytology (LBC) in breast cytology to confirm the diagnosis of carcinoma. STUDY DESIGN: Using cell clusters directly scratched from surgically removed tumor masses, we examined the immunocytochemistry, molecular biology and cytomorphology of the specimens. RESULTS: LBC was very useful for gene analysis and evaluating the immunocytochemistry. The cytologic features of LBC were slightly different from those ofa conventional aspiration cytology smear. CONCLUSION: LBC is a promising method for improving the standardization ofpreparations in breast cytology, although care should be taken to account for its characteristic cytologic features. The quantitative analysis of HER-2 mRNA correlated with the results of immunohistochemistry.     

Aspiration cytology of breast cysts

A cytologic evaluation was made of 57 samples of fluid aspirated from cystic breast masses during the past 12 years in our hospital. The cytologic diagnosis of the cyst aspirates from 17 cancer cases was positive in 10 cases, suspicious in 2 and negative in 5. No false-positive cytologic diagnosis was made in 40 cases of benign cystic disease. Blood-tinged aspirates were observed in 14 of the 17 cases of malignant cystic disease but in only 2 of 40 benign cases. Ductal cell clusters were detected in aspiration smears from 16 of the cases of malignant cystic disease and 15 of the cases of benign cystic disease. Apocrine cells were seen in the aspiration smears from 12 of the cases of benign cystic disease but in none of the aspirates from the 17 cancer cases.     

Preoperative aspiration cytology of breast tumors

During a ten-year period, 1,942 aspirations of 1,906 mammary tumors in 1,874 patients were performed before excisional biopsy or mastectomy. The cytology findings were categorized as positive (1,107 cases), suspicious (152 cases), atypical (183 cases), benign (166 cases) and unsatisfactory (298 cases). All cytologically positive cases with follow-up were confirmed histologically or by clinical observation. Follow-up showed that 96% of the cases in the suspicious category, 86% of the cases in the atypical category, 51% of the cases in the benign category and 72% of the cases in the unsatisfactory category had malignant neoplasms. Aspiration cytology diagnosed 1,031 of 1,539 primary malignant mammary neoplasms (67%) and 19 of 28 neoplasms (68%) metastatic to the breast; if unsatisfactory cases are excluded, these figures become 1,031 of 1,365 cases (75%) and 19 of 25 (76%), respectively. If those cases reported as suspicious are included with the positive cases and those reported as atypical are included with the negative cases, aspiration cytology would have a sensitivity of 84% for the presence of carcinoma, a specificity of 97% for the absence of carcinoma, a predictive value of 99% for a positive diagnosis and a predictive value of 56% for a negative diagnosis; the diagnostic efficiency would be 86%. Our findings reaffirmed that the cytologic diagnosis of mammary carcinomas is reliable but that negative or inconclusive cytologic findings should not be regarded as a definitive diagnosis if there is clinical suspicion of a malignant neoplasm.     

Fine needle aspiration cytology of the breast. Experience at an outpatient breast clinic

OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) of the breast at our institution and to perform quality assurance. STUDY DESIGN: Two hundred forty-six cases with pathologic confirmation were selected and reviewed. A pathologist performed most of the aspirations at an outpatient breast clinic. We correlated cytologic and histologic findings and evaluated the influence of the size, location, grade, and pathologic subtypes and fibrosis in breast lesions on diagnostic results. RESULTS: The likelihood ratios for malignant, suspicious, atypical, benign and unsatisfactory cytologic diagnoses were 98.71, 5.48, 1.09, 0.07 and 0.55, respectively. The absolute and complete sensitivities for malignant lesions were 64.5% and 90.3%, respectively. The specificity was 71.9%. False negative and positive rates were 4.3% and 0.7%, respectively. The predictive value for a malignant cytologic diagnosis was 98.4%. The rate of unsatisfactory samples was 9.3%. The rate of concordance between cytologic and histologic diagnosis was lower for large and diffusely growing lesions (benign and malignant), for malignancies with abundant fibrosis and of unusual types and for carcinomas of low grade. All axillary and recurrent chest wall lesions were diagnosed cytologically. Cell block sections were useful in a small number of cases. CONCLUSION: Understanding the performance and limitations of FNAC can enhance its value as a diagnostic technique in the management of breast disease.     

Aspiration cytology of tubular breast carcinoma

The cytologic features in smears of fine needle aspirates from 34 tubular breast carcinomas were studied. Uniform and bland epithelium in cohesive clusters dominated all specimens; two-thirds also showed some degree of cellular dissociation. Characteristic (but not quite pathognomonic) angular epithelial clusters with a tubular structure occurred in about 50% of the smears. Sparsely occurring atypical nuclei and/or cytoplasmic vacuoles, similar to those seen in lobular cancer, were found in half of the cases. Although a lack of myoepithelial cells was apparent in the majority of the smears, one-fourth of them showed a quite prominent myoepithelial component. Various combinations of atypical features resulted in a picture that was considered diagnostic of malignancy in 50% of the cases; the remaining specimens showed less pronounced atypia. Other pitfalls associated with the cytologic diagnosis of tubular carcinoma are discussed, and the importance of basing the management of small breast lesions on the mammographic as well as on the cytologic findings is emphasized.     

Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells

The human bitter taste receptors (T2Rs) are chemosensory receptors that belong to the G protein-coupled receptor superfamily. T2Rs are present on the surface of oral and many extra-oral cells. In humans 25 T2Rs are present, and these are activated by hundreds of chemical molecules of diverse structure. Previous studies have shown that many bitter compounds including chloroquine, quinidine, bitter melon extract and cucurbitacins B and E inhibit tumor growth and induce apoptosis in cancer cells. However, the existence of T2Rs in cancer cell is not yet elucidated. In this report using quantitative (q)-PCR and flow cytometry, we characterized the expression of T2R1, T2R4, T2R10, T2R38 and T2R49 in the highly metastatic breast cancer cell line MDA-MB-231, poorly metastatic cell line MCF-7, and non-cancerous mammary epithelial cell line MCF-10A. Among the 5 T2Rs analyzed by qPCR and flow cytometry, T2R4 is expressed at 40–70% in mammary epithelial cells in comparison to commonly used breast cancer marker proteins, estrogen receptor and E-cadherin. Interestingly, the expression of T2R4 was downregulated in breast cancer cells. An increase in intracellular calcium mobilization was observed after the application of bitter agonists, quinine, dextromethorphan, and phenylthiocarbamide that are specific for some of the 5 T2Rs. This suggests that the endogenous T2Rs expressed in these cells are functional. Taken together, our novel findings suggest that T2Rs are differentially expressed in mammary epithelial cells, with some T2Rs downregulated in breast cancer cells.     

A screening system for cervical cancer cytology.

A system for screening cervical cytological preparations is described which employs the Leitz Texture Analyzer System (E. Leitz, Rockleigh, N. J.) quantitative staining with acridine orange, and a fluorescence standard. The instrumentation scans cells on microscope slides and detects objects which it interprets to be nuclei with excess total nuclear green fluorescence intensity (Previous results employing manual measurements have indicated that normal nuclei do not produce total nuclear green fluorescence greater than a specific absolute intensity level). Detected objects are identified by visual observation. Cells (102,000) from 65 patients (29 normal, 36 abnormal) have been examined. In each abnormal sample, at least one abnormal cell was detected. In over half of the samples, three or fewer other objects (e.g. clumps of polymorphonuclear leukocytes) were detected. These are easily distinguishable from single nuclei, and could be discarded by someone with minimal cytological training.     

Papillary breast lesions diagnosed on cytology. Profile of 65 cases

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features. STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases. RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last. CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.     

High-throughput molecular analysis from leftover of fine needle aspiration cytology of mammographically detected breast cancer

We investigated whether residual material from diagnostic smears of fine needle aspirations (FNAs) of mammographically detected breast lesions can be successfully used to extract RNA for reliable gene expression analysis. Twenty-eight patients underwent FNA of breast lesions under ultrasonographic guidance. After smearing slides for cytology, residual cells were rinsed with TRIzol to recover RNA. RNA yield ranged from 0.78 to 88.40 μg per sample. FNA leftovers from 23 nonpalpable breast cancers were selected for gene expression profiling using oligonucleotide microarrays. Clusters generated by global expression profiles partitioned samples in well-distinguished subgroups that overlapped with clusters obtained using "biologic scores" (cytohistologic variables) and differed from clusters based on "technical scores" (RNA/complementary RNA/microarray quality). Microarray profiling used to measure the grade of differentiation and estrogen receptor and ERBB2/HER2 status reflected the results obtained by histology and immunohistochemistry. Given that proliferative status in the FNA material is not always assessable, we designed and performed on FNA leftover a multiprobe genomic signature for proliferation genes that strongly correlated with the Ki67 index examined on histologic material. These findings show that cells residual to cytologic smears of FNA are suitable for obtaining high-quality RNA for high-throughput analysis even when taken from small nonpalpable breast lesions.