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.     

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.     

Quantitative image analysis of estrogen receptors in breast fine needle aspiration biopsies

OBJECTIVE: To establish whether the results of quantitative evaluation of estrogen receptors (ERs) in cytologic fine needle aspiration (FNA) biopsies of the breast are comparable to the results obtained on excised breast tumors and therefore suitable for making a clinical decision on tamoxifen treatment in women who are not candidates for surgery. STUDY DESIGN: We performed a retrospective review of 118 breast FNA specimens that were positive for adenocarcinoma cells, had adequate cell block cellularity and provided subsequent surgical resection tissue. Quantification of ERs was performed on cell block material and follow-up tissue sections by the Chromavision Automated Imaging System, San Juan Capistrano, California, U.S.A. RESULTS: Quantitative image analysis provided consistently reliable, comparable results when evaluating for the presence or absence of ERs (at a 5% staining cutoff level), with 98.3% agreement between FNA cytology and histology specimens. Quantitative measurements of FNA samples showed the best agreement with the values derived from the subsequent surgical specimens at high-end (> 85% staining) and low-end (< 10% staining) values. However, a direct linear correlation of values was not observed. In the great majority of parallel measures, ERs were either strongly positive (> 75% staining) or had a zero value, particularly in the surgical specimens, with more "in-between" values identified in FNA specimens. CONCLUSION: Quantitative image analysis of FNA of ER results are comparable to those of surgical excision specimens and can be used for therapeutic decision making. The utility and advantages of quantitative ERs by image analysis include providing the patient and physician with important early prognostic and diagnostic information before planning a surgical approach. Additionally, FNA ERs are useful in determining therapy alternatives in patients who are not surgical candidates and in evaluating the preoperative hormone status of patients receiving chemotherapy prior to surgery.     

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.     

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.     

Nucleolar morphometry in fine needle aspiration biopsies of the prostate.

OBJECTIVE: To find efficient morphometric nucleolar features for distinguishing different prostatic atypia groups in fine needle aspiration biopsies. STUDY DESIGN: A computerized interactive morphometry program was used to outline nucleoli of prostate cells. The samples were divided into three groups: group 1 (definitely benign [n = 10] and atypical but benign [n = 13]), group 2 (moderately atypical [n = 11] or highly suspicious [n = 13]) and group 3 (definitely malignant [n = 17]). RESULTS: The analysis revealed a difference in the number of nucleoli between definitely benign samples and other atypia groups but not between the latter. Nucleolar size features were best in distinguishing between atypia groups. The sample-associated mean size features were more powerful than cell group-associated size features. CONCLUSION: The sample-associated mean area, defined from cells selected by an experienced cytologist, if larger than 2 micron 2, was strongly associated with definitely malignant samples. The same was true for the largest nucleolar area if larger than 5.0 micron 2. Morphometric nucleolar size features appeared efficient in distinguishing between definitely malignant and other samples.     

Genotypic analysis of DNA isolated from fine needle aspiration biopsies

DNA was isolated from 20 fine needle aspiration (FNA) biopsies from lymphomas, hyperplastic lymph nodes and nonlymphoid malignant tumors. Small aliquots (0.2 microgram to 2.0 micrograms) of DNA from each sample were digested to completion with restriction endonuclease Eco RI and/or Bam HI and electrophoresed in 0.8% agarose minigels. DNA was transferred to a nylon filter after brief treatment in HCl and subsequent denaturation and neutralization. Filters were hybridized to radiolabeled JH, C kappa, TCR beta or bcl-2 probes to determine if these genes were in germline or rearranged configurations in each of the samples. It was possible to demonstrate rearrangement of at least one immunoglobulin gene in each of the samples diagnosed as lymphoma, while all samples derived from hyperplastic lymph nodes and nonlymphoid malignant tumors exhibited a germline pattern for each probe tested. Thus, FNA biopsies can provide suitable and sufficient DNA for genotypic analysis using molecular probes that detect gene rearrangement.     

Morphologic spectrum of hepatocellular carcinoma in fine needle aspiration biopsies

The light microscopic features of fine needle aspiration smears from 52 primary hepatocellular carcinomas were reviewed. Cytologic grading of these tumors, which indicated three grade I, 29 grade II and 20 grade III carcinomas, was compatible with grading done by histologic examination. In addition to the general cellular characteristics, other cytologic features observed in the smears included bile (48% of the cases), large cytoplasmic vacuoles (23%), small cytoplasmic vacuoles (46%), eosinophilic cytoplasmic inclusions (8%), basophilic cytoplasmic inclusions (48%) and intranuclear cytoplasmic inclusions (71%). The significance of these features is briefly discussed.     

Paratesticular adenomatoid tumors. The cytologic presentation in fine needle aspiration biopsies

Adenomatoid tumors are the most common tumors of male paratesticular tissues (epididymis, tunica or spermatic cord) and have also been described in females (uterus, fallopian tube, ovary and paraovarian tissues); fine needle aspiration (FNA) of masses in these locations is increasingly utilized as an alternative to surgical exploration in order to establish a tissue diagnosis. This paper describes the FNA cytodiagnosis of seven cases of paratesticular adenomatoid tumors. The main cytologic criteria included epithelioid sheets and multilayered clusters of monotonous cells with round or ovoid, eccentric nuclei containing small, central nucleoli. Paranuclear clearing with a pink coloration (Giemsa stain) or a clear vacuolelike area (Papanicolaou stain) and abundant cellularity with a background of naked nuclei and stromal fragments were noted. The clinical presentation and clinicohistologic follow-up of these seven cases is also described in detail. A discussion of the differential diagnosis and the expected FNA findings is provided.     

Nuclear changes in cytologic specimens obtained by CT-guided fine needle aspiration biopsies.

A light and electron microscopic study was conducted to investigate nuclear changes observed in specimens obtained from various sites by computed tomographic (CT)-guided fine needle aspiration (FNA) biopsy. These changes, which consisted of a disappearance of the nuclear chromatin and a disruption of the nuclear membrane, were found in 70% of 10 FNA specimens obtained with CT guidance, in 26% of 15 specimens obtained with fluoroscopic guidance and in 0% of 10 specimens obtained without x-ray imaging techniques. Although the number of cases studied was small and the mechanisms responsible for these changes are not clear, cytopathologists should be aware of alterations in evaluating FNA specimens obtained with the guidance of x-ray imaging techniques.     

Pulmonary fine needle aspiration biopsy. Assessing the negative diagnosis.

OBJECTIVE: To assess the significance of the "negative for malignancy" category when applied to pulmonary transthoracic fine needle aspiration biopsy (FNAB). STUDY DESIGN: Transthoracic lung FNABs diagnosed as "negative for malignancy" were identified from the files of Barnes-Jewish Hospital's South and North Campus over a period of five and nine years, respectively. Histologic correlation and clinical follow-up were obtained. RESULTS: Of the 1,181 lung FNABs performed during the study period, 108 cases (9%) had a negative cytologic diagnosis. Histologic correlation was available in 46 cases (43%), of which 23 cases had benign histologic findings, and 19 cases were malignant. Thirty-five of the 62 cases without histologic correlation had clinical follow-up consistent with a benign process. CONCLUSION: Based on the histologic correlation and clinical data available, the negative predictive value was 77%. Inadequate sampling was responsible for all false negative cytologic diagnoses in this series.     

Anaplastic Wilms' tumor. Initial diagnosis by fine needle aspiration

The diagnosis of a diffusely anaplastic Wilms' tumor in a ten-month-old child was first suggested by cytologic and histologic study of a fine needle aspirate. The mesenchymal component was predominant (75%) and exhibited some cells with hyaline, periodic acid-Schiff-positive, intracytoplasmic droplets. Foci of clear-cell carcinoma were also present. Only one case showing this histologic pattern in this unusual variant of Wilms' tumor has been reported previously.     

Secretory carcinoma of the breast. Report of a case with diagnosis by fine needle aspiration.

We report a case of secretory carcinoma of the breast in a 63-year-old woman studied by fine needle aspiration (FNA). The cytologic features included solid nests, cohesive sheets and isolated tumor cells with intracytoplasmic vacuolization and signet-ring-like forms. Although secretory carcinoma is an unusual breast tumor, especially in adults, the cellular morphology was distinctive on FNA. This could permit the preoperative diagnosis of secretory carcinoma and the planning of optimal surgical therapy prior to an intervention.     

Evaluation of fine needle aspiration of the male breast for the diagnosis of gynaecomastia

Fine needle aspiration of the male breast can present problems of diagnosis because the cytological presentation of gynaecomastia can be confused with that of adenocarcinoma. We reviewed breast aspirates from 24 male patients in order to determine the accuracy of cytology as a method of diagnosing gynaecomastia. Discrepancies were observed between the original cytology reports on one hand and the review cytology and biopsies on the other. Of the 24 aspirates from the male breast, the cytology was reported as negative in 16 cases, suspicious in three cases and malignant in five. In four cases of the negative group, a specific diagnosis of gynaecomastia was made. In two of the negative cases the subsequent biopsies revealed adenocarcinoma. Of the five cases reported on the original cytology as adenocarcinoma, two on review showed the features of florid gynaecomastia and this was confirmed on biopsy and three confirmed the initial diagnosis of adenocarcinoma. The cytological features of gynaecomastia which distinguish it from adenocarcinoma are discussed.     

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.     

Value of rapid staining and assessment of ultrasound-guided fine needle aspiration biopsies

In a series of 160 ultrasonically guided fine needle aspiration (FNA) biopsies, immediate cytologic evaluation of each specimen's adequacy was performed using a rapid staining method. The number of passes was thus limited to what was strictly necessary in order to obtain sufficient material; the average number of passes was only 1.27 per patient. The total series of FNA biopsies had a sensitivity of 95.6%, a specificity of 100% and an overall accuracy of 97.3%. In addition, the cumulative accuracy after each pass was calculated. A significant increase in diagnostic accuracy was found only after the second pass; the third and the fourth passes gave little further improvement. The results indicate that a rapid evaluation of the aspirated material during ultrasound-guided FNA biopsy can reduce the number of punctures needed per case, resulting in less discomfort and, probably, a reduced likelihood of complications for the patient. The results also suggest that a maximum of two punctures will probably yield adequate diagnostic material in most cases.     

Electron microscopy of fine needle aspiration biopsies of mediastinal and paramediastinal lesions

The ultrastructural cytologic study of fine needle aspiration (FNA) biopsies from eight cases with mediastinal and paramediastinal lesions is reported. In these cases, electron microscopy (EM) was essential in cytologically determining the correct type of the cancer cells. The results in these cases suggest that portions of FNA biopsies from deep sites, where aspiration is difficult or requires computed tomographic scanning, should be routinely processed for plastic embedding, so that EM examination can be performed if the cells are undifferentiated, scanty or poorly preserved by light microscopic examination. The proper cytologic identification of the cell might, in fact, have a major bearing on the therapeutic choices and on the prognosis.