Application of the probabilistic approach to reporting breast fine needle aspiration in males

OBJECTIVE: To apply the probabilistic approach to a series offine needle aspiration (FNA) samples of male breast lesions and determine the accuracy and reproducibility of this method of reporting in men. STUDY DESIGN: All male breast surgical specimens with a preoperative breast FNA at our institution from 1994 to 2005 were identified. The FNAs were blindly reviewed by 2 groups of observers and classified in 1 of 5 categories using published reporting guidelines: positive, suspicious, atypical, proliferative without atypia and unremarkable. The histologic and cytologic diagnoses were correlated. The interobserver variation was determined. RESULTS: A total of 138 FNAs were performed for 123 male patients. Histologic correlation was available for 23 satisfactory FNAs. A total of 11 of 11 carcinomas (100%) were classified as positive, suspicious or atypical. Of 12 benign masses, 11 (91.6%) were classified as proliferative without atypia or unremarkable. One case of gynecomastia was classified as atypical by 1 observer but deemed not atypical with consensus review. The kappa statistic for benign and atypical/suspicious/malignant categories was 0.90. CONCLUSION: Based on this series, the probabilistic approach can be applied to the reporting of FNAs of male breast lesions. Gynecomastia may result in an atypical cytologic diagnosis.     

Statistical approach to fine needle aspiration diagnosis of breast masses

A statistical algorithm was used for recursively partitioning a consecutive series of 37 benign and 69 malignant fine needle aspirates to produce a decision tree for diagnosing breast masses. Optimal separation between benign and malignant cytology was accomplished by evaluating clump characteristics when clumps were present and evaluating cell integrity when clumps were absent. The 1.5% false-negative and 9.7% false-positive rates obtained through this scheme are better than those reported for most series.     

Triple test approach to inadequate fine needle aspiration biopsies of palpable breast lesions.

OBJECTIVE: To perform a retrospective study evaluating the triple test for inadequate fine needle aspiration (FNA) biopsies of palpable breast lesions with a two-year clinical follow-up. STUDY DESIGN: All aspirates were reviewed and assessed for cellular adequacy in a one-year period. Specimen adequacy was based on the most stringent criteria, the presence of six or more epithelial cell clusters composed of at least six cells each. In all cases, clinical and radiologic results were reviewed and compared with the histologic outcome. RESULTS: Aspirates from 61 of 263 (23%) patients with palpable breast lesions that yielded nondiagnostic results were examined. The study showed a misdirected FNA rate of 21% and a misinterpreted rate of 1.6%. The other 77% of cases had benign surgical biopsies and/or clinical follow-up. Three of 61 (4.9%) cases with nondiagnostic smears were found to have cancer; two were inadequate due to misdirected aspirates, and one was misinterpreted microscopically. All cancer cases underwent surgical removal of the mass as a result of clinical or radiologic suspicion. CONCLUSION: We recommend utilizing the three diagnostic parameters of cytology, clinical findings and radiology, the "triple test," to achieve the best diagnostic accuracy in breast FNAs and to enhance patient management.     

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.     

Choriocarcinoma metastatic to the breast diagnosed by fine needle aspiration.

Fine needle aspiration (FNA) was used to study nodules in the left breast of a patient with a previous history of uterine choriocarcinoma. The FNA smears contained numerous malignant mononucleated cells and multinucleated giant cells. The cytologic diagnosis was metastatic choriocarcinoma, which was confirmed by histologic study of excised tissue. That diagnosis would have been difficult to make cytologically if the previous history had not been known; the differential diagnosis of multinucleated giant cells in an aspirate from a breast mass is discussed.     

Automated breast cancer diagnosis based on fine needle aspiration

OBJECTIVE: To design and analyze an automated diagnostic system for breast carcinoma based on fine needle aspiration (FNA). STUDY DESIGN: FNA is a noninvasive alternative to surgical biopsy for the diagnosis of breast carcinoma. Widespread clinical use of FNA is limited by the relatively poor interobserver reproducibility of the visual interpretation of FNA images. To overcome the reproducibility problem, past research has focused on the development of automated diagnosis systems that yield accurate, reproducible results. While automated diagnosis is, by definition, reproducible, it has yet to achieve diagnostic accuracy comparable to that of surgical biopsy. In this article we describe a sophisticated new diagnostic system in which the mean sensitivity (of FNA diagnosis) approaches that of surgical biopsy. The diagnostic system that we devised analyzes the digital FNA data extracted from FNA images. To achieve high sensitivity, the system needs to solve large, equality-constrained, integer nonlinear optimization problems repeatedly. Powerful techniques from the theory of Lie groups and a novel optimization technique are built into the system to solve the underlying optimization problems effectively. The system is trained using digital data from FNA samples with confirmed diagnosis. To analyze the diagnostic accuracy of the system > 8,000 computational experiments were performed using digital FNA data from the Wisconsin Breast Cancer Database. RESULTS: The system has a mean sensitivity of 99.62% and mean specificity of 93.31%. Statistical analysis shows that at the 95% confidence level, the system can be trusted to correctly diagnose new malignant FNA samples with an accuracy of 99.44-99.8% and new benign FNA samples with an accuracy of 92.43-93.93%. CONCLUSION: The diagnostic system is robust and has higher sensitivity than do all the other systems reported in the literature. The specificity of the system needs to be improved.     

Melanoma metastatic to the breast: utility of fine needle aspiration and immunohistochemistry

OBJECTIVE: To describe the morphologic spectrum of metastatic malignant melanoma (MM) cells involving the breast and to explore the diagnostic utility of HMB45, Mart-1, Melan-A and T311 (antityrosinase) antibodies in fine needle aspiration material of MM metastatic to the breast. STUDY DESIGN: Cytologic material from 21 cases (18 women) was reviewed for cytomorphology (epithelioid, spindled, mixed) and immunocytochemical staining attributes for Mart-1, HMB45, T311, Melan-A and cytokeratin based on tissue availability. RESULTS: Seventeen cases (81%) demonstrated epithelioid cell morphology, with 14% exhibiting mixed and 5% spindled morphologies. All 21 cases (100%) were immunoreactive with Mart-1 antibody, with 81% (17/21) immunoreactive for HMB45. In 38% of cases there was a similar percentage of cells immunoreactive for Mart-1 and HMB45, while 48% showed a higher percentage of cells immunoreactive for MART-1 than HMB45. Immunoreactivity with T311 was seen in 8 of 11 cases tested (73%). All six cases tested (100%) were immunoreactive with Melan-A. Staining for cytokeratin was negative in all eight cases tested. CONCLUSION: Because the majority of MM metastatic to the breast shows epithelioid cell morphology, it may mimic primary breast carcinoma. Mart-1 should be part of the immunocytochemical panel utilized to confirm the diagnosis of MM metastatic to the breast.     

Carcinoid tumour of male breast diagnosed by fine needle aspiration

A primary carcinoid tumour of the breast in a 66-year-old man was diagnosed by fine-needle aspiration cytology. The nature of the lesion was proved by histochemical and immunocytochemical studies. The importance of a conclusive diagnosis is discussed and the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis is demonstrated.     

Cytological grading of breast cancer in Giemsa-stained fine needle aspiration smears

A potential cytological nuclear grading based on a semi-quantitative evaluation of three basic nuclear features, size of cell nuclei, anisonucleosis and the proportion of nucleoli-containing-nuclei, was tested on 74 Giemsa-stained fine needle aspiration of breast smears for its reliability in establishing the malignant potential of breast cancer. The prognostic impact of DNA-ploidy and S-phase fraction was also assessed. A good correlation between the three basic nuclear features, DNA-ploidy, S-phase fraction, cytological nuclear grade and histological grade, was shown. Using the cytological nuclear grade proposed, correct classification of cases between low histological grade (HG I) and high histological grade (HG II + HG III) was achieved in 79.73%. A statistically significant difference in 5-year survival rate was also observed between low malignancy grade and high malignancy grade breast cancer patients, regardless of the grading method used. DNA-ploidy and S-phase fraction were not statistically significant in establishing the malignant potential of breast cancer.     

Value of fine needle aspiration in the diagnosis of breast lesions.

OBJECTIVE: To evaluate the accuracy values of 276 fine needle aspriations (FNA) of breast lesions with a subsequent excisional biopsy diagnosis and to make a comparison between 25 studies of the literature using the same criteria to calculate those values. STUDY DESIGN: Cytologic findings were compared with the histologic diagnosis of each mass. The correlation of results was analyzed by a decision-analysis approach, and the following values concerning diagnostic accuracy were calculated in the present study and in 25 other reports: sensitivity, specificity, positive predictive value, negative predictive value, false positive fraction and false negative fraction. To calculate those values, we eliminated unsatisfactory results and assumed that suspicious and positive cytologic findings represented carcinoma of the breast. RESULTS: Comparing our results with the means in the literature (numbers in parenthesis), FNA detected cancer with a sensitivity of 92.1% (87.7%), specificity of 98.6% (94.7%), positive predictive value of 99.4% (92.8%), negative predictive value of 82.1% (90.7%), false positive fraction of 0.6% (7.1%) and false negative fraction of 17.9% (13.4%); in 6.2% of cases the material was unsatisfactory (13.4%). CONCLUSION: All the rates varied enormously between the studies and during the past 13 years. It seems that false positive and false negative fractions tended to diminish and stabilize in more recent years, and specificity and sensitivity underwent a slight increase. The differences between the rates of those studies suggest that FNA of the breast has some unavoidable limitations.     

Positive predictive value of fine needle aspiration cytology of breast lesions

The predictive value of fine needle aspiration (FNA) was assessed in 1,181 consecutive cases of breast lesions in which cytologic abnormalities were reported. The positive predictive value (PPV) of an FNA cytologic report of atypia, suspicious or positive was 0.49, 0.95 or 0.996, respectively. In the presence of a suspicious/positive report by both physical examination and mammography, the PPV of a cytologic report of suspicious was 0.99. The PPV was directly correlated with age, partly due to the incidence of fibroadenomas among younger patients; fibroadenomas were present in 53 of 146 cases with a false FNA report of atypia, in 10 of 19 cases with a false FNA report of suspicious and in 2 of 2 cases with a false FNA report of positive. Overall, 93 cases reported as benign by physical examination and mammography were biopsied on the basis of the FNA cytologic report; cancers were diagnosed in 33 of these 93 cases (6 cancers among 42 women less than 40 years old and 27 cancers among 51 women greater than 39 years old). The widespread use of FNA cytology to study breast lesions is thus recommended, without regard to patient age and even in the presence of clinically benign findings, since the increase in the rate of cancer detection is worth the excess of unnecessary biopsies. The predictive value of a positive report of FNA cytology, or even of a suspicious report in the presence of clinical suspicion, is so high that an intraoperative frozen section biopsy might be spared in such cases.     

Telecytologic diagnosis of breast fine needle aspiration biopsies. Intraobserver concordance

OBJECTIVE: To determine the intraobserver concordance between telecytologic and glass slide diagnosis of breast fine needle aspirates. STUDY DESIGN: Twenty-five cases, originally received in consultation, were each examined by three cytopathologists. An average of seven compressed digital images per case were presented, together with a brief clinical history, using the http protocol and an internet browser. RESULTS: Agreement between the telecytologic and glass slide diagnosis ranged from 80% to 96%. Nevertheless, two cases that had been unequivocally diagnosed as malignant based upon video images were considered to be benign by the same pathologist when reviewing the glass slides. Both diagnostic confidence and self-concordance were higher for one pathologist having significant previous video microscopy experience. CONCLUSION: Although intraobserver concordance between telecytologic and glass slide diagnoses of breast fine needle aspirates is high, refinement of existing criteria for diagnosis of malignancy, taking account of the particular limitations associated with telecytologic diagnosis, may be prudent prior to widespread use of telecytology for fine needle aspiration evaluation.     

Papillary neoplasms of the breast: clues in fine needle aspiration cytology

Papillary neoplasms of the breast include a wide spectrum of mammary lesions. The differential diagnosis of benign and malignant lesions can be problematic not only cytologically, but also histopathologically. Aspiration smears can demonstrate that cytological differentiation is feasible. A retrospective study of 30 cases of papillary tumour of the breast, 15 papillary carcinomas and 15 papillomas, was performed to find the cytological differences between the pathologies. Cytological samples of papillary carcinomas were characterized by an abundance of cellular material, three-dimensional papillary clusters without fibrovascular connective tissue cores, small papillae arranged in cell balls, tall columnar cells and isolated naked nuclei. Numerous haemosiderin-laden macrophages were seen. There were no eosinophilic bipolar cytoplasmic granules, bipolar naked nuclei or apocrine metaplasia. In the papillomas there was less material; the papillae had cohesive stalks surrounded by columnar cells in a honeycomb pattern. We also found fewer small papillae and isolated columnar cells. In addition, the presence of apocrine metaplasia and bipolar naked nuclei was noted. We suggest that papillary carcinoma of the breast can be diagnosed by cytology and differentiated from papilloma.