Fine Needle Aspiration Cytology of the Breast: The Nonmalignant Categories

Currently, accurate diagnosis of breast lesions depends on a triple assessment approach comprising clinical, imaging and pathologic examinations. Fine needle aspiration cytology (FNAC) is widely adopted for the pathologic assessment because of its accurracy and ease of use. While much has been written about the atypical and maliganant categories of FNAC diagnosis, little covers the non-malignanat category which represents a sheer number in all FNAC cases. Moreover, any false-negative diagnosis of the non-malignant cases may lead to missed diagnosis of cancer. This paper aims to discuss the issues of smear adequacy, the cytologic features of benign breast lesions and the dilemma of a false-negative aspirate. Much has been suggested about the smear adequacy criterion, including quantifying epithelial clusters, whereas others advocate basing adequacy on qualitative quantum of using noncellular features of FNAC. Various benign lesions could be easily diagnosed at FNAC; however, they have cytologic features overlapped with malignant lesions. False negativity of FNAC does occur; this could be caused by either “true” false-negative cases attributed to suboptimal sampling technique, poor localization of the mass or nonpalpable lesions or “false” false-negative cases due to interpretational errors. Though false-positive cases are less commonly found, they will also be discussed briefly.

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title: Sources of diagnostic discrepancies in fine‐ needle aspiration of the breast
abstract: Fine‐needle aspiration (FNA) is a valuable technique to use in the evaluation of breast lesions; however, inadequate and discrepant diagnoses do occur. To identify the source and nature of inaccuracies related to the method we studied 39 cases in which FNA posed diagnostic problems. These problems could be attributed to sampling errors (71.8%), to the criteria of adequacy we use at our institution (2.5.6%), and to interpretation (2.6%). The nature of the breast lesion (68%) was the most common cause of inadequate sampling, followed by the experience of the aspirator (32%).

title: Accuracy of fine needle aspiration cytology from breast masses in Thailand.
abstract: To evaluate the accuracy and diagnostic performance of fine needle aspiration FNA cytology in diagnoses of breast masses.



Women who had FNA diagnoses for breast masses and underwent subsequent histopathologic evaluation during January 2003-December 2006 were accessed from the archive of the Anatomical Pathology Department of our institution. Cytologic diagnoses were classified as unsatisfactory, benign, atypical probably benign, suspicious probably malignant, and malignant, and were compared to the histopathologic diagnoses obtained from core needle biopsy, excisional biopsy, or mastectomy to give an assessment of the diagnostic performance of FNA.



A series of 190 breast masses were identified during the study period. The FNA cytological diagnosis was unsatisfactory due to inadequate specimens in eight cases (4.2%). The diagnoses in the remaining 182 cases were: benign lesions in 98 (53.9%); suspicious for malignancy in 31 (17.0%); and malignant in 53 (29.1%). From the subsequent histopathologic diagnoses, 6/98 cases of benign cytology turned out to be malignant lesions (false negatives); 22/31 cases of suspicious cytology were truly malignant while the other nine were benign; and only 1/53 with malignant cytology was benign (false positive), the lesion being a fibroadenoma . The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 91.2% (95% confidence interval (CI), 87.6%-94.8%), 92.5% (95% CI, 88.7%-96.3%), 90.2% (95% CI, 85.9%-94.5%), 88.1% (95% CI, 83.4%-92.8%) and 93.9% (95% CI, 90.4%-97.4%), respectively.



FNA cytology is highly accurate for diagnosis of breast masses. However, the clinician should correlate FNA cytological results with physical examination and imaging findings to prevent false negative and false positive events and to obtain optimal management for their patients.

title: The value of fine needle aspiration biopsy in the diagnosis and prognostic assessment of palpable breast lesions
abstract: In recent years there appears to be a growing movement toward the use of core needle biopsy (CNB) over fine needle aspiration biopsy (FNAB) for the detection of breast carcinoma. This tendency is caused in part by the idea that CNB can provide a more specific or definitive diagnosis as well as the belief that the assessment of prognostic/predictive factor is not possible or reliable on cytologic specimens. At our institution, FNAB of breast has been practiced for over 25 years with excellent cytologic–histological correlation. This practice has been beneficial not only for patients, but also for training physicians since nowadays a very small number of centers in the United States still routinely perform fine needle aspiration as a diagnostic tool in breast cases.

title: A retrospective study of the diagnostic accuracy of fine‐needle aspiration for breast lesions and implications for future use
abstract: In recent years, the use of fine‐needle aspiration (FNA) in the diagnosis of breast lesions has declined in many institutions. We sought to evaluate the role of FNA for breast lesions and the annual rate of the procedure at our institution over a 4½ year period (May 2002–October 2006). A total of 831 FNAs were performed, with 258 (31%) having histologic follow‐up. The number of FNAs obtained was 159 from 5/02 to 4/03, 192 from 5/03 to 4/04, 194 from 5/04 to 4/05, 191 from 5/05 to 4/06, and 95 from 5/06 to 10/06. Each case was placed into one of four categories: nondiagnostic (9%), benign (77.5%), atypical/suspicious (5.5%), or malignant (8%). Surgical tissue was available for 37% of nondiagnostic cases, 22% of benign cases, 80% of atypical/suspicious cases, and 72% of malignant cases. The overall sensitivity and specificity for FNA was 83 and 92% respectively. The overall positive and negative predictive values were 83 and 92% respectively. There were no false‐positive cases, indicating a positive predictive value of 100% for a Dx of malignancy. For cases with surgical follow‐up, the false‐negative rate was 5.4%. Although there is a national trend away from FNAs of breast lesion, this has not been the experience at our institution. Although FNA may not be ideal in the initial evaluation of suspicious lesions, we argue that FNA for clinically benign palpable lesions and recurrent carcinomas has significant value.  2008.

title: Breast cytology. Statistical analysis and cytohistologic correlations.
abstract: To analyze the sensitivity, specificity, positive and negative predictive values and the efficacy of fine needle aspiration (FNA) in our material, to investigate the influence of the histologic type and stage of carcinoma on the quality of the aspirates and on the detection rates of mammary carcinoma, and to investigate the rate of inadequate samples and the accuracy of cytologic diagnoses, with an emphasis on the rate of false positive diagnoses in benign mammary lesions.



The results of 1,472 FNAs of the breast obtained over three years were subjected to a retrospective analysis.



The cytologic diagnoses were benign in 1,003 cases (68.1%), suspicious in 49 (3.3%) and malignant in 181 (12.3%); 239 (16.2%) of the aspirates were inadequate. In 393 (26.6%) of the cases and in 85% of cytologically malignant smears, the aspirate was compared with histologic examination. The rate of false negative FNAs was 9.0%. The proportion of inadequate cases was clearly related to stage (pT): it was 9.5% in pT1, 5.0% in pT2 and 0% in pT3. Among invasive carcinomas the sensitivity was 89.9%, specificity 99.3% and overall accuracy 88.5%. Among the cases diagnosed cytologically as benign, 182 were compared with biopsies. Of these, 79.9% were true negative, 0.5% (1 case) was false positive, and 15.4% had insufficient cells for evaluation.



FNA cytology has improved decision making and the selection of patients for biopsy of mammary lesions and has contributed to saving time in the clinical management of breast lumps. In no case did FNA lead to inadequate clinical measures or other disadvantages to patients. Thus, FNA cytology is an indispensible diagnostic tool in the management of breast lesions.

title: Interinstitutional comparison of performance in breast fine-needle aspiration cytology. A Q-probe quality indicator study.
abstract: In 1989, the College of American Pathologists, Northfield, Ill, instituted a voluntary quality assurance program, called "Q-Probes," that utilized nationwide interinstitutional peer comparison. One of the anatomic pathology modules retrospectively assessed performance in fine-needle aspiration cytology (FNAC) of the breast from cytohistologic correlations that were made in 294 institutions by 988 pathologists on their own cases that were accessioned during a 6-month period. Of the 13,066 cases of FNAC, 10,751 (82%) were satisfactory for evaluation. Of these satisfactory aspirates, 3471 cases (33%) had histologic correlation, which formed the basis for determining diagnostic accuracy. Of breast aspirates, 2254 (17%) were unsatisfactory for evaluation, with the mean frequency of unsatisfactory aspirates obtained by nonpathologists (18%), ie, more than twice that of unsatisfactory aspirates obtained by pathologists (7.2%). In the diagnosis of breast cancer by FNAC, the following performance results were derived with the use of the aggregate data: 82% sensitivity of the FNAC procedure, 97% sensitivity of diagnosis, 97% specificity, 95% positive predictive value, 86% negative predictive value, and 90% efficiency. No significant difference in performance was detected when institutions were stratified by six peer group characteristics. We made the following conclusions: (1) the aggregate and median breast FNAC performance values obtained from this interinstitutional comparison of data from routine procedures performed in diverse settings in North America compared very favorably with performance from single institutions published in studies of similar design in the literature, and (2) these data may provide a reference point for participant institutions to measure future quality improvement in fine-needle aspiration of breast.

title: Fine needle aspiration cytology of palpable breast lesions. Histologic subtype in false negative cases.
abstract: To evaluate the use of fine needle aspiration cytology (FNAC) in the management of benign and malignant breast disease in an outpatient breast clinic and to determine the guidelines for reporting on FNAC of breast lesions, we evaluated the test results in correlation with the histologic diagnosis.



We evaluate the test results of 669 cases of FNAC of the breast in 17 months in our outpatient breast clinic in correlation with the histologic diagnosis, histologic subtype according to the Japan Mammary Cancer Society classification and mammography results in false negative cases.



Among 669 cases, 25.3% were inadequate for cytologic diagnosis. An analysis of the results using the two-by-four contingency table, including cases with inadequate cytologic diagnosis, showed that 10.6% and 1.0% had false negative and false positive cytologic diagnoses, respectively; sensitivity and specificity were 76.9% and 91.6%, respectively. The false negative rate of 10.6% was higher than expected, and those belonged mostly to the "inadequate" cytologic diagnosis category even though they were discrete, obviously malignant masses clinically. To try to explain this, we compared the cytologic results and histologic subtype according to the Japan Mammary Cancer Society classification and the mammography results. Of 73 cases of infiltrating ductal carcinoma in which retrospective reexamination of the histology slide was possible, 27 (37.0%) were papillo-tubular type, 11 (15.1%) were solid-tubular type and 35 cases (47.9%) were scirrhous type. Although the scirrhous subtype was only 37.0% in the group in which a cytologic diagnosis of carcinoma was possible, more than two-thirds of the cases of false negative cytology were scirrhous type and had malignant mammographic findings. This finding was statistically significant.



In cases of ductal carcinoma of scirrhous subtype, the FNAC tended to be inadequate and false negative, but mammography showed better discrimination in such cases.

title: Fine needle aspiration of the breast. Importance of the aspirator.
abstract: All 503 fine needle aspirations (FNAs) of the breast performed over a three-year period at the Medical Center Hospital of Vermont were analyzed. There were 93 aspirates diagnosed as "positive," all of which were from patients eventually shown to have cancer. However, there were 38 patients with primary carcinoma in which the FNA was not diagnosed as positive, for a diagnostic failure rate of 31.4%. In order to determine the possible effect of technique as practiced by an experienced aspirator in diminishing such diagnostic failures, we compared 190 aspirates obtained by a single individual with 193 aspirates obtained by 15 individuals in the same community. For the single experienced aspirator, the technical failure rate was 9.8% whereas in the group with many aspirators it was 45.9%. This finding confirms that, although fine needle aspiration of the breast is considered easy to perform, skill on the part of the aspirator is important for satisfactory results.

title: Fine Needle Aspiration Cytology of the Breast: Factors Affecting Sensitivity
abstract: At Northampton General Hospital a pathologist takes, stains and immediately reports aspirates at a fine needle aspiration clinic which is run in conjunction with a busy surgical breast clinic. the effect of various factors on the sensitivity of the technique have been quantified. Small tumour size, certain types of tumour and lesions difficult to palpate are causes of reduced sensitivity. Acellular samples had little effect on sensitivity. In this clinic trainee aspirators achieved good results early in their experience. After one year each had improved to the level of an experienced aspirator.

title: The Uniform Approach to Breast Fine Needle Aspiration Biopsy: A Synopsis
abstract: Developed and approved at the National Cancer Institute-sponsored conference, Bethesda, Maryland, U.S.A., September 9-1 0, 1996, with representatives of the American Society of Cytopathology, Papanicolaou Society of Cytopathology, American College of Radiology, American College of 0 bstetricians & Gynecologists, American Academy of Family Physicians, Society of Surgical Oncology, College of American Pathologists, National Consortium of Breast Centers, International Academy of Cytology, American Society of Clinical Pathologists, American Cancer Society, American College of Surgeons, and the American Society for Cytotechnology.

title: Adequacy evaluation of fine‐needle aspiration biopsy in the breast health clinic setting
abstract: Breast health clinics (BHC) are an unfamiliar source of fine‐needle aspiration biopsies (FNABs) in the U.S. and create challenges for adequacy evaluation. The current study described the experience with breast FNAB adequacy evaluation over a 2‐year period, the issues that emerged, and the problem‐solving employed to mitigate these issues.

title: Specimen adequacy and false‐negative diagnosis rate in fine‐needle aspirates of palpable breast masses
abstract: As fine‐needle aspiration (FNA) has become a critical component of the investigation of palpable breast masses, false‐negative diagnoses have become a major concern, prompting reevaluation of the definition of specimen adequacy. Although cytopathologists agree that a number of parameters relate to the adequacy of an FNA specimen, there is no unanimity on the role of epithelial cell quantitation in the determination of an adequate FNA. To better understand the significance of epithelial cellularity, false‐negative FNA samples from palpable breast lesions were reviewed.

title: False-positive and false-negative cases of fine-needle aspiration cytology for palpable breast lesions
abstract: BackgroundFine-needle aspiration cytology (FNA) is less traumatic and technically easy to apply to small breast tumors. total of 382 cases of palpable breast lesions that had undergone fine needle aspiration and histopathologic diagnosis were reviewed with an emphasis on the rate of false positive diagnoses in benign breast lesions. diagnosis of“malignant”was made in 98 of the 382 specimens (25.6%). The predictive value for malignancy was 97.9%. The sensitivity, specificity, and accuracy of FNA were 86.3%, 98.2%, and 93.2%, respectively, when the“suspicious”group was considered positive for malignancy. The histologic subtypes of the 4 false-positive cases were epithelial proliferative lesions, ductal or lobular hyperplasia. None of these 4 cases were definitely diagnosed as“malignant”by radiological studies. Four false-negative cases by FNA were suspicious for malignancy radiologically. There was no specific pathological subtype associated with false-negative status on FNA in this study.ConclusionPalpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.

title: Three year follow-up of benign fine-needle aspiration biopsies of the breast.
abstract: Benign fine-needle aspiration, taken in context, is a reasonable alternative to open biopsy. We found a false-negative rate comparable to that for frozen section or routine histologic examination of benign surgical breast biopsies. Fine-needle aspiration must always be interpreted in context. It is never satisfactory to use this test to ignore or choose not to surgically biopsy a lump that is suspicious on clinical grounds or on the basis of other tests.

title: Calcification in breast lesions: pathologists’ perspective
abstract: Evaluation of calcification in breast lesions is a major assessment criterion for breast mammography. The morphology and distribution of the calcification are related to the histology of the lesions. Radiologically, calcifications can be divided into: benign; intermediate concern; and higher probability of malignancy according to the morphology. Different pathological entities may give rise to different calcifications. Fibrocystic changes may give rise to milk of calcium or teacup type calcification, or small calcifications occurring in a cluster. Fibroadenoma may be associated with large popcorn like calcifications, and sclerosing adenosis may have fine, punctate or granular calcifications. Fat necrosis may give rise to egg shell calcification. Precursor malignant lesions give rise to benign to indeterminate type calcifications, and may occasionally be associated with malignant type calcifications. For malignant lesions, ductal carcinoma in situ and invasive duct carcinoma may be associated with large irregular, rod or V shaped, pleomorphic or branching type calcifications that follow the distribution of the duct. Furthermore, analysis of the characteristics of the calcifications may help to predict the tumour size and grade, and presence of invasion.

title: Subclassification of benign breast disease by fine needle aspiration cytology. Comparison of cytologic and histologic findings in 265 palpable breast masses.
abstract: The cytologic and histologic features of 265 benign breast masses were analyzed in order to examine the ability of fine needle aspiration cytology to accurately subclassify benign breast lesions. Two hundred two of the masses were pure histologic examples of benign breast lesions (72 nonproliferative fibrocystic change, 27 proliferative fibrocystic change, 65 fibroadenoma, 12 abscess, 8 fat necrosis, 7 papilloma, 7 duct ectasia, 2 tubular adenoma, 1 sclerosing adenosis, 1 microglandular adenosis), and 63 masses were mixed lesions. Part I of the study consisted of retrospective comparison of the original cytologic diagnoses with the histologic diagnoses. A nonspecific descriptive diagnosis had been rendered in 135 of 265 (51%) cases, and these descriptive diagnoses corresponded to fibrocystic change in the majority of cases (70%). A specific benign cytologic diagnosis had been made in 130 of 265 (49%) cases, and overall the specific diagnosis was correct in 80% of cases. Part II of the study consisted of the semiquantitative scoring of the cytologic findings of the 202 pure examples of benign breast masses and statistical analysis of differences in the expression of cytologic features between the different types of lesions. Overall cellularity, amount of bipolar stripped nuclei, amount and architectural arrangement of epithelium, epithelial atypia/pleomorphism/nuclear overlapping and amount of apocrine metaplasia, foam cells and stroma were the cytologic parameters that were statistically significant (P < .05) in distinguishing between the cases of fibroadenoma, abscess, papilloma, fat necrosis, duct ectasia and fibrocystic change as a group. No cytologic parameter reached statistical significance in distinguishing between proliferative and nonproliferative fibrocystic change. We conclude that the majority of benign breast lesions yield characteristic cytologic findings that allow their subclassification when sufficiently sampled by fine needle aspiration. The distinction between proliferative and nonproliferative fibrocystic change is less reliable, and cytologic differences observed within this spectrum did not reach statistical significance.

title: FNA of breast fibroadenoma: observer variability and review of cytomorphology with cytohistological correlation
abstract: To determine the observer variability in reporting fibroadenoma of the breast by fine needle aspiration (FNA) and to review the cytomorphological features of the lesion with cytohistological correlation.

title: Multinucleated stromal giant cells in mammary fibroepithelial neoplasms. A study of 11 patients.
abstract: Multinucleated stromal giant cells (MSGCs) found in otherwise-banal breast tissue have only rarely been mentioned in specific lesions. We describe unilateral fibroepithelial tumors with MSGCs in 11 women who were 23 to 60 years old (mean age, 42 years). The tumors ranged from 1.7 to 9.0 cm in greatest dimension (mean, 3.7 cm) and were classified on the basis of stromal cellularity, infiltration at the margin, cellular pleomorphism, and mitoses independently of MSGCs. Using these criteria, there were four fibroadenomas, one benign cystosarcoma, and four low-grade and two high-grade malignant cystosarcomas. The MSGCs had hyperchromatic or vesicular nuclei, many with clear nuclear inclusions. The nuclei were often arranged in a semicircular or florette pattern. The MSGCs, although widely distributed, tended to cluster. They accounted for most of the stromal cellularity in the fibroadenomas, numbering focally up to 10 per high-power field. The benign and low-grade malignant cystosarcomas had fewer MSGCs. The MSGCs contributed least to the cellularity in the high-grade cystosarcomas. Five patients had no further therapy. Five patients underwent wide excision and one patient had a mastectomy. Follow-up extended to 8 years (median follow-up, 4 years). There were no recurrences, and all patients were alive with no evidence of disease. The results of this study lead us to conclude that the diagnosis and grading of fibroepithelial tumors of the breast depend on the cellularity and pleomorphism of the stroma, exclusive of MSGCs. Cystosarcomas that have MSGCs do not have an especially malignant clinical course.

title: MULTINUCLEATED STROMAL GIANT CELLS IN MAMMARY PHYLLODES TUMOURS
abstract: Mammary phyllodes tumour (PT) is an uncommon fibro‐epithelial neoplasm with a prominent stromal component. We report five cases of PT (one benign, three borderline, one malignant) with giant cells in the stroma. All occurred in adults and ranged from 1.8 to 4.0 cm in size. The overall cellularity, stromal cell pleomorphism and mitotic count was higher for the malignant and borderline than the benign PT. The giant cell number ranged from 18 to 35 cells per 10 high power fields, but there was no relationship between this number and the grade of the PT. Most giant cells were subepithelial, with multiple nuclei arranged in a linear or irregular pattern, and moderate amount of cytoplasm. The immunohistochemical profile of the giant cells was similar to the stromal cells. In all cases, both giant cells and stromal cells expressed vimentin strongly but not desmin; in two cases, both cell populations expressed actin weakly. The respective percentage of giant cells and stromal cells expressing MIB1 was also similar. This suggests that these giant cells do not represent a different, more active stromal population, despite the more bizarre appearance. In view of the small number of cases, the significance of such giant cells on the prognosis of PT remains uncertain.

title: Fine needle aspiration cytology of papillary lesions of the breast: how accurate is the diagnosis?
abstract: Cytological diagnosis of mammary papillary lesions is difficult.  To review the previous cytology diagnosis of 23 papillomas and 11 papillary carcinomas and specific cytological features that may assist in differentiating these entities.  The cytology preparations were reviewed for: (i) overall cellularity; (ii) epithelial cell ball devoid of fibrovascular cores; (iii) background single cells; and (iv) papillary fragments and their morphology.  The overall diagnostic accuracy was 59%, atypical rate was 24%, and the error (combined false positive and negative) rate was 17%. For overall cellularity, 6, 14 and 3 cases of papillomas, and 6, 3 and 2 cases of papillary carcinomas showed low, moderate and high cellularity, respectively. Cell balls were present in mild to moderate number in 20 papillomas and 10 papillary carcinomas. The background single cells were absent, or present in low or moderate to high numbers in 7, 10 and 6 papillomas, and 3, 3 and 5 papillary carcinomas, respectively. Papillary fragments were absent, or present in small, moderate or large quantities in 9, 4, 8 and 2 papillomas, and 6, 3, 1 and 1 papillary carcinomas, respectively. There was no demonstrable quantitative difference between papilloma and papillary carcinoma for all these parameters. Qualitatively, the cell balls and single cells showed a higher degree of atypia in papillary carcinoma, and the papillary fragments were more elaborate and slender.  Cytological diagnosis of papillary lesions shows a significant error rate with overlapping features. Cellular atypia and fragments with long and slender papillae with ramifying edges favour papillary carcinoma.

title: Atypia in fine needle aspirates of breast lesions
abstract: The atypical category is controversial in fine needle aspiration cytology (FNAC) of the breast; most are benign, but a significant number are malignant. To date, no morphological criterion has been found to be consistent in predicting malignancy.  To evaluate specific cytological parameters and assess their usefulness in predicting histological outcome in a cohort of atypical breast FNAC, in order to establish a set of objective criteria in defining ‘high risk’ atypical breast FNAC.  A retrospective review of 98 cases of atypical breast FNAC with histological correlation was undertaken. The cytological preparations were evaluated for cellularity, percentage of epithelial cell cluster and single epithelial cells, nuclear atypia, nucleus:cytoplasm ratio, percentage of bipolar nuclei, and the presence of stromal fragments, histiocytes and necrosis.  of 98 cases (67.35%) showed benign histology and 32 cases (32.65%) showed malignant histology. Compared with the malignant group, the benign group had significantly lower patient age (p=0.05), higher bipolar nuclei (p<0.0001), less degree of nuclear pleomorphism (p<0.0001), lower nucleus:cytoplasm ratio (p<0.0001), lower cellularity (p=0.05) and less necrosis (p<0.001). There was no difference in the percentage of epithelial clusters and single cells, or the presence of stromal fragments and histiocytes.  The presence of nuclear pleomorphism, high nucleus:cytoplasm ratio, epithelial cell atypia, low number of bipolar nuclei and necrosis are useful parameters to predict malignancy in atypical FNAC of the breast. Assessment of these factors in atypical FNAC may be helpful in predicting cancer risk and subsequent management decision making.

title: Spontaneous Infarction of an Intraductal Papilloma of the Breast: Cytological Presentation On Fine Needle Aspiration
abstract: A relatively rare case of spontaneous infarction of an intraductal papilloma of the breast is presented which was considered to be suspicious for malignancy on fine needle aspiration (FNA) cytology. the aspirate revealed several groups of atypical cells featuring a high nuclear‐cytoplasmic ratio, coarsely granular chromatin, and somewhat prominent nucleoli. There was abundant necrotic cellular debris in the background. These cellular features were considered evidence of ductal carcinoma of the breast.

title: Histologic Changes in the Breast after Fine‐Needle Aspiration
abstract: Fine-needle aspiration biopsy (FNAB) of the breast has been widely used in many centers worldwide for the initial management of patients with breast lumps. However, little has been written on the morphologic changes secondary to this commonly applied procedure. Thus we performed a retrospective study on 184 consecutive breast-excision specimens with a history of FNAB. Seventeen cases (9.2%) showed changes definitely attributable to the FNAB procedure, including three cases of near total destruction of the lesion as a result of hemorrhage (one case) or infraction (two cases), focal hemosiderin deposition (seven cases), hemorrhage with organization at the periphery (six cases), and a case of ductal papilloma showing a previously underscribed occurrence of benign epithelial implantation. The latter exhibited alarming histologic features simulating invasive carcinoma by virtue of the presence of small narrow tubules with mild cellular atypia haphazardly distributed in the fibrogranulation tissue around the papilloma; the tubules were confiremed to be benign by the presence of muscle-specific actin-positive myoepithelial cells. Other changes were possibly attributable to the FNAB procedure, including linear necrosis in the peripheral portion of the tumor (six cases), intraluminal hemorrhage in fibroadenoma (five cases), and multicentric hemorrhage in the mucinous carcinomas (four cases). We conclude that the rare occurrence of extensive tissue necrosis after FNAB can pose great difficulties in definitive diagnosis of the lesion in the subsequent excision specimen. Other changes are relatively minor, but the occurrence of benign implantation after FNAB may lead to an erroneous diagnosis of invasive carcinoma.

title: Role of fine‐needle aspiration biopsy in breast lesions: Analysis of a series of 4,110 cases
abstract: From January of 1990 to December of 1992, 6,954 consecutive cytologic breast fine‐needle aspiration biopsies (FNAB) were performed at the Laboratory of Pathology of Sant'Anna Hospital in Turin. Of these cases 62% were solid nodes, 35% were cystic nodes, and 2.7% were nonpalpable breast lesions (stereotaxic or ultrasound guided FNAB). We verified 4,110 cases: 913 cases underwent surgery and 3,197 were evaluated clinically, and/or cytologically, and/or with mammography at least 1 yr after the first diagnosis, or checked with the database of the Tumor Registry of Turin. In our series the FNAB sensitivity was 94.6%, specificity was 99.9%, accuracy was 98.8%, inadequate samples were 6.4%, false‐negative rate was 1.4%, and false‐positive rate was 0.3%. Our results indicate that the use of cell block improves sensitivity (from 85.2 to 94.6%) and strongly reduces false‐negative results (from 3.9 to 1.4%).

title: Use of fine needle aspiration for solid breast lesions is accurate and cost-effective.
abstract: Palpable breast tumors have traditionally been diagnosed with open biopsy or core biopsy. We propose fine needle aspiration biopsy (FNA) as a reliable, cost-saving initial procedure in these patients.



Eighty-five palpable solid breast masses of the breast in 85 patients were classified by a combination of physical examination, mammography, and/or ultrasound as probably benign, indeterminate, or highly suspicious for cancer. All tumors had FNA biopsies. All patients had either a confirmatory open biopsy (55) or close clinical follow-up (30) with a mean follow-up of 29 months (range 6 to 36).



Thirty-four patients classified as clinically benign had a benign FNA biopsy. No cancers were detected in this group by either open surgical biopsy or clinical follow-up. Twenty patients were classified clinically as indeterminate. All had FNA biopsies, and 6 were either positive for cancer or suspicious for cancer. Fourteen patients had negative FNA biopsies. Five of the 6 abnormal biopsies had cancer on open biopsies. The 1 false-positive result occurred in a lactating patient. Thirty-one patients were classified clinically as highly suspicious for cancer. Twenty-three were confirmed as cancer with FNA biopsy. Eight needed open surgical biopsy to confirm cancer. All 31 patients clinically suspicious for cancer had cancer. In patients classified clinically as highly suspicious or probably benign, FNA was a reliable first diagnostic step (100% positive predictive value, 100% specificity, 87% sensitivity, and 89% negative predictive value).



Fine needle aspiration biopsy of solid palpable breast lesions should be the diagnostic procedure of choice for those patients classified clinically as probably benign or clinically as highly suspicious for cancer. Cost analysis revealed elimination of an open biopsy in such cases would save $1,100 per patient. For highly suspicious cases, a negative fine needle aspiration should not deter an open surgical biopsy. For patients classified as indeterminate, fine needle aspiration biopsy results are not reliable enough to determine treatment.

title: Accuracy of fine needle aspiration biopsy of the breast.
abstract: Fine needle aspiration biopsy (FNAB) has become a widely used and accepted procedure to detect benign and malignant lesions of the breast. In the past, highly invasive procedures were used in the investigation of suspect breast tumors. Surgical excision was the method of choice during this period often requiring hospitalization of the patient. However, the recent introduction of FNAB has allowed a less traumatic approach for such investigations. Due to pressures from Health Management Organizations (HMO's), FNAB is presently the method of choice allowing for decreased patient trauma, expense, and ability of the procedure to be performed on an outpatient basis. Although highly accepted by most clinicians, others suggest that FNAB should perform diagnostically at a level equivalent or higher than that obtainable by frozen tissue sectioning procedures. This study was designed to evaluate the diagnostic ability of FNAB. Four-hundred twenty-seven patients underwent FNAB during 1993-94 at the University of Mississippi Medical Center. Of those patients, two hundred thirty-seven also underwent corresponding surgical biopsies. Sensitivity (88%), specificity (96%), a false positive rate (4%), and a false negative rate (12%) were calculated from the data and reported. In conclusion, the diagnostic accuracy of FNAB of the breast determined in this study shows the significance of the procedure.

title: Analysis of morphologic patterns of fine‐needle aspiration of the breast to reduce false‐negative results in breast cytology
abstract: The identification of specific morphologic diagnostic criteria is of paramount importance to optimize the accuracy of fine‐needle aspiration cytology (FNAC) and to reduce the rate of false‐negative results. In the current study, the authors reviewed a consecutive series of false‐negative findings observed in the study center to define the presence and degree of cytologic abnormalities. False‐negative cases were randomly mixed with true‐negative cases and were reviewed by a panel of expert readers in a blinded fashion. The main objective of the current study was to identify a morphologic pattern that may permit the reduction of false‐negative findings while maintaining the specificity of FNAC.

title: Diagnosing breast lesions by fine needle aspiration cytology or core biopsy: which is better?
abstract: Fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) are widely used in diagnosing breast lesions, with both achieving high sensitivity and specificity. Whether FNAC or CNB is better remains highly controversial. In this review, the advantages and disadvantages of each of these methods are discussed, especially in relation to specific problematic groups of breast lesions. In general, CNB has a slight advantage with lower inadequate and suspicious rates, allowing easier grade assessment and ancillary testings (hormome receptors, HER2) in cases of cancers. FNAC cannot reliably predict invasion in a malignant aspirate, whereas CNB, although useful in confirming invasion in carcinomas, has a much lower efficacy in predicting invasion when only in situ carcinoma is detected. The other problematic areas are papillary breast lesions and fibroepithelial lesions, notably phyllodes tumors. In papillary lesions, FNAC diagnosis is inaccurate, but with CNB, one can confidently diagnose papillary lesion, although there is still significant false positive and false negative rates, even with immunohistochemistry. For fibroepithelial lesions, using either FNAC or CNB to differentiate between a phyllodes tumor from fibroadenoma is also inaccurate. As management of breast diseases necessitates the triple approach (clinical, imaging and pathological), an awareness of the limitations of these very useful diagnostic modalities by all specialists is prudent, especially when dealing with these specific groups of breast lesions.

title: Rate of insufficient samples for fine‐needle aspiration for nonpalpable breast lesions in a multicenter clinical trial
abstract: Radiologic Diagnostic Oncology Group 5 is a multicenter clinical trial designed to evaluate fine‐needle aspiration (FNA) of nonpalpable breast lesions performed by multiple operators using the same protocol.

title: Ultrasound-guided fine-needle aspiration of nonpalpable breast lesions. Cytologic and histologic findings.
abstract: Between 1989 and 1992, 651 nonpalpable breast lesions in 586 patients were aspirated using the ultrasound-guided technique at M.D. Anderson Cancer Center. Cytologic diagnoses were as follows: malignant, 167; suspicious, 30; benign, 211; cysts, 168; atypical ductal hyperplasia, 4; and insufficient for diagnosis, 71. In all cystic and most benign lesions, fine-needle aspiration (FNA) confirmed the benign clinical findings, and surgery was not performed. Of the 483 solid lesions, 254 were subsequently treated surgically, either because of suspicious mammographic or sonographic findings or because of positive or suspicious cytologic findings. The cytologic diagnoses in these cases were as follows: 132 (52%) malignant, 65 (25%) benign, 26 (10%) suspicious, 4 (2%) atypical, and 27 (11%) insufficient for diagnosis. The sensitivity of ultrasound-guided FNA for the diagnosis of malignant lesions was 91%, specificity 77%, and overall accuracy 84%. There were four (2%) false-negative results. Diagnostic failures were attributed to the small size of the lesions, histologic type, and inexperience in localization and cytologic interpretation of tubular carcinoma. One (1%) false-positive diagnosis was made (atypical ductal hyperplasia misdiagnosed as carcinoma). The authors' findings indicate that ultrasound-guided FNA offers a reliable and simple alternative to open biopsy of nonpalpable breast lesions. The efficacy of this technique depends primarily on accurate localization of the biopsy needle and on skillful cytologic interpretation of certain breast lesions.