Survey of aspiration biopsy cytology of the breast

Based on the team approach, the Papanicolaou method, simple equipment, and special criteria of malignancy, aspiration biopsy cytology of the breast is reviewed.     

Impact of qualified (indeterminate) diagnoses on the accuracy of renal, thyroid, and breast fine-needle aspiration biopsy

A qualified (indeterminate) diagnosis (QD), such as "suggestive of malignancy," is thought to complicate patient management by heightening clinical uncertainty. We report that QDs increase the overall effectiveness of renal, thyroid, and breast fine-needle aspiration (FNA) biopsy and that the probability that a qualified diagnosis is negative (QDN) can be predicted by the formula QDN = number of QDs x (proportion of false-negative outcomes/disease prevalence expressed as a proportion). Results of renal (n = 24), thyroid (n = 163), and breast (n = 456) FNA biopsies performed from January 1992 through December 1998 were reviewed and correlated with results of tissue biopsies. For each body site, the FNA biopsies were placed into 1 of 2 diagnostic categories: unqualified diagnoses (UQDs) or QDs. Comparison of test performance characteristics for UQDs only and UQDs combined with QDs demonstrated that inclusion of UQDs increased FNA sensitivity and reduced FNA false-negative diagnoses. More important, the probability that a QD was negative could be predicted from test performance characteristics derived from UQDs.     

Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions

Fine-needle aspiration cytology (FNAC) is an established, highly accurate method for diagnosing breast lesions. However, in recent years there has been increased use of core biopsy (CB) in this setting. The aim of this study was to evaluate the accuracy of FNAC and compare the quality assessment parameters of FNAC and CB in palpable and nonpalpable breast lesions. Data regarding FNAC, CB, and excision biopsy (EB) diagnoses were retrieved from the archives of our department. A total of 4,367 FNAC samples from the years 1999-2001 was reviewed. Of these, corresponding histology results were available for 1,275 lesions, of which 1,248 were primary breast epithelial lesions (788 EB, 199 CB, 261 EB+CB). All cases were analyzed for sensitivity and specificity of FNAC. Cases with both FNAC and CB were compared and quality assessment parameters were calculated using the methodology detailed in the National Health Service Breast Screening Program guidelines. High specificity and sensitivity, as calculated for satisfactory specimens, were achieved with the use of both FNAC and CB. False-positive and false-negative diagnoses were seen in 7/404 (1.7%) and 45/635 (7.1%) of biopsy-proven specimens sampled by FNAC. The corresponding values for CB were 0% and 5.7%, respectively. Inadequate sampling (15.1%) with use of FNAC was particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. FNAC is a valuable method, although moderately less sensitive than CB. CB is the preferred method for preoperative diagnosis when sampling FNAC provides scarce material and suspicion of a fibrotic and collagenous lesion such as lobular carcinoma and radial scar arises. FNAC is most accurate when experienced cytologists are available and when immediate assessment by professionals is performed for evaluation of material adequacy, so that additional aspirations can be done when needed.     

Living with uncertainty: Equivocal Pap test results and the evolution of ASC terminology

Communication of equivocal findings and their significance has been a significant challenge related to Pap testing throughout its history. Terminology to report these findings has changed considerably to accommodate the changes in understanding of cervical neoplasia, and to accommodate new management strategies, tests, and technologies. This article reviews the evolution of terminology for equivocal Pap test findings from the original Papanicolaou classification to the current the Bethesda System 2001 atypical squamous cells terminology, the implication and use of these terms, and the changing landscape of cervical neoplasia screening, which prompted these terminology changes. Emerging issues related to improving risk stratification through the introduction of additional terms and the impact of human papillomavirus testing may alter terminology of equivocal findings in the future. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

The role of aspiration biopsy cytology in the diagnosis of pulmonary tuberculosis

The experience at one institution concerning the diagnosis of pulmonary tuberculosis by aspiration biopsy is reviewed. Twelve cases in which acid-fast bacilli were identified in pulmonary aspiration material are reported. The cytologic findings were confirmed by microbiologic culture in nine cases. The advantages of using aspiration biopsy cytology in the diagnosis of pulmonary tuberculosis are discussed. In our experience we conclude that the use of aspiration biopsy cytology in the diagnosis of pulmonary tuberculosis is not only accurate, but also offers several advantages that are important in patient care.     

Diagnostic dilemmas and pitfalls in ThinPrep® cytology of breast fine needle aspiration biopsy:

Fine needle aspirations (FNA) of the breast for primary diagnoses have become less popular in the USA and are usually performed for lesions with low or extremely high clinical suspicion. They are also performed for lesions in close proximity to a breast implant. Liquid‐based cytological preparations, such as ThinPrep^® (TP), provide a practical alternative to clinicians who are performing FNA. Using a selection of cases that represent challenging diagnoses, we describe common diagnostic pitfalls of breast FNA that are specifically associated with this preparation. Well known breast cytology pitfalls, such as fibroadenoma, when solely examined using a TP slide can be even more challenging since the usual stripped bipolar cells seen in the background of smeared slides, can appear singly dispersed with preserved cytoplasm, resembling carcinoma. We describe that large fragments of solid papillary carcinoma are represented by mostly singly dispersed cells with plasmacytoid features that mimic those of a lobular carcinoma. Since nuclear features are more pronounced in TP, prominent nucleoli and cytological atypia can potentially be overcalled. TP processing might also lead to clumping of epithelioid histiocytes that appear atypical, which increases the suspicion of malignancy. The presence of atypical cells in a TP slide of a peri implant seroma should always undergo additional testing, especially in patients with a prior history of breast carcinoma, to determine if it represents recurrent carcinoma or an implant associated anaplastic large cell lymphoma. Familiarity with the aforementioned artifacts associated with TP is essential to avoid diagnostic misinterpretations. Diagn. Cytopathol. 2017;45:655–661. © 2017 Wiley Periodicals, Inc.     

Needle aspiration cytology of the irradiated breast.

During a 3-year period (1987-1989), 60 fine-needle aspiration biopsies (FNAs) were obtained from new breast lesions in patients previously treated by radiation and surgery for breast carcinoma. The lesions occurred at or near the site of previous excision, 3-117 months after initiation of radiotherapy. FNAs were classified as follows: acellular (11); negative (29); atypical (13); suspicious (4); and positive (3). For statistical analysis, acellular, negative, and atypical diagnoses were considered negative findings, and suspicious and positive diagnoses were considered positive findings. On the basis of subsequent biopsy and/or patient follow-up, FNA yielded a sensitivity of 86%, a specificity of 98%, a positive predictive value of 86%, a negative predictive value of 98%, and an efficiency of 97%. Excluding cystic lesions, the most reliable criterion for distinguishing malignant from benign lesions was the abundance of epithelial cells, both singly and in large clusters. Cellular characteristics were less helpful, since nuclear atypia was seen in both benign and malignant lesions. It is concluded that (1) FNA is a reliable technique in the evaluation of the irradiated breast; (2) when performed by an experienced operator, an acellular aspirate may be interpreted as evidence against recurrent carcinoma; and (3) epithelial atypia must be interpreted with caution to avoid a false-positive diagnosis.     

Male breast lesions: gynecomastia and its distinction from carcinoma by aspiration biopsy cytology

Gynecomastia is a benign proliferative lesion of the male breast. It may present as a diffuse bilateral process or a unilateral, discrete mass, clinically suggestive of carcinoma. We examined the aspiration biopsy cytology of 50 cases of gynecomastia to define the cytologic criteria and to distinguish it from carcinoma. The parameters of cellularity, architecture, single columnar cells, naked nuclei, nuclear and cell size, nuclear and cytoplasmic characteristics, and extraneous cells were accessed. Diagnostic confusion with carcinoma may occur because of cellularity with loose groups and single cells; however, the mixed cell population, composed of cohesive sheets or groups of bland cells, bipolar naked nuclei, and single tall columnar cells, delineates gynecomastia from carcinoma of the male breast.     

Comparison of fine-needle aspiration cytology and core biopsy for diagnosis of breast cancer

Both fine-needle aspiration (FNA) cytology and core biopsy are useful in the diagnosis of breast cancer. In order to compare the sensitivities of these procedures, we reviewed 209 patients with breast cancer who had either FNA, core biopsy, or both, and also either mastectomy or lumpectomy. Sensitivities for FNA and core biopsies for diagnosing breast cancer were calculated and compared. Sensitivity for FNA or core biopsies interpreted as either atypical or malignant was 93.8% for FNA and 90.1% for core biopsy (P > 0.05). Sensitivity for FNA or core biopsies interpreted as malignant was 65.4% for FNA and 88.7% for core biopsy (P < 0.0001). Sensitivities of FNA interpreted as either atypical or malignant were 92.4% for FNA performed by pathologists and 100% for FNA by nonpathologists (P > 0.05). Sensitivities of FNA interpreted as malignant were 75.8% for FNA by pathologists and 20.0% for FNA by nonpathologists (P < 0.00001). Both FNA and core biopsies are sensitive procedures for the detection of breast cancer. There was no significant difference between sensitivity of FNA and core biopsies interpreted as either atypia or malignancy, although the sensitivity of core biopsies interpreted as unequivocal malignancy was greater than that of FNA. FNAs performed by pathologists were more sensitive than FNAs performed by nonpathologists in making an unequivocal diagnosis of breast cancer.     

Fine-needle aspiration cytology of the breast: Invasive vs. in situ carcinoma

The surgical management of invasive breast carcinoma differs from that of in situ disease. Invasive carcinoma necessitates axillary lymph node dissection, a procedure that has associated morbidity. We studied 80 cases (66 invasive, 14 in situ) of breast carcinoma that had a histological diagnosis and a preoperative fine-needle aspirate. All slides were reviewed, with 17 cytologic features assessed. We found that six of these features showed a statistically significant difference between the invasive and in situ cases. These were infiltration of fat or stroma by malignant cells (72% of invasive cases demonstrated this feature, but it was not present in any of the in situ cases, P = 0.0002), the presence of myoepithelial cells overlying clusters of tumor cells (seen in 86% of in situ tumors and 7% of invasive cases, P < 0.00001), calcification (present in 71% of in situ and 15% of the invasive group, P = 0.001), foamy macrophages (noted in 64% of in situ tumors and 16% of invasive carcinomas, P = 0.0007), intracytoplasmic vacuoles (seen in 50% of invasive cases and 21% of in situ lesions, P = 0.08), and tubules (present in 30% of invasive and 7% of in situ tumors, P = 0.10). We demonstrate that invasion can be suggested in fine-needle aspirates of carcinomas, provided that true infiltration of fibrofatty connective tissue by neoplastic cells is present. In situ disease has characteristic features, but the presence of invasion cannot be excluded, even in the presence of stromal or adipose tissue fragments without tumor infiltration.     

Determination of estrogen receptor by monoclonal antireceptor antibody in aspiration biopsy cytology from breast carcinoma

The authors evaluated the ability of a monoclonal antibody immunoperoxidase procedure (ERICA [Estrogen Receptor Immunocytochemical Assay], information from Regulatory Affairs Department, Abbott Laboratories, North Chicago, IL) to detect estrogen receptor in aspiration biopsy cytology (ABC) specimens from breast cancer routinely taken by fine-needle aspiration during office diagnostic evaluation. Results were correlated with biochemical values determined from dextran-coated charcoal (DCC) assay on tumor tissue obtained subsequently at operation. ERICA had positive results in 32 of 41 DCC-positive cases (sensitivity, 78%) and in 5 of 17 DCC-negative cases (specificity, 71%). The semiquantitative degree of ERICA positivity correlated with the concentration of estrogen receptor by DCC. Results of both assays correlated with the histologic grade of the tumor and patient age. Estrogen receptor can be determined by immunocytochemistry in ABC specimens in a community hospital. However, the sensitivity and specificity of this procedure compared with biochemical assay, and eventual response to hormonal therapy, require further investigation.     

Cytomorphology of gastrointestinal stromal tumor: diagnostic role of aspiration cytology, core biopsy, and immunochemistry

Gastrointestinal stromal tumors (GISTs) comprise a heterogeneous group of neoplasms of the gastrointestinal tract previously referred to as leiomyomas, leiomyosarcomas, or schwannomas. GISTs derive from the interstitial cell of Cajal and, in addition to variable expression of smooth muscle and neural markers, they characteristically express CD34 and CD117. To our knowledge, the cytologic appearance of gastric neoplasms designated as GISTs has never been reported. We illustrate the fine-needle aspiration (FNA) cytology findings of a gastric stromal tumor having spindle cells with delicate cytoplasm and prominent nuclear palisading. Consistent core biopsy and immunochemistry findings further supported the diagnosis of GIST. Pathologic evaluation of the resected tumor confirmed the cytologic diagnosis. In the appropriate clinical and radiologic setting, a confident diagnosis of GIST can be established by FNA cytology and core biopsy. The roles of immunochemical stains and other ancillary techniques in reaching the correct diagnosis are addressed.     

The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions

AIMS: To investigate the role of needle core biopsy (NCB) in the preoperative assessment of impalpable breast lesions, mainly derived from the NHS Breast Screening Programme (NHSBSP) and to assess our own modifications to a suggested system for the classification of breast NCBs. METHODS: The NCB, fine needle aspiration cytology (FNAC), and radiology scores from 298 women with non-palpable breast lesions presenting between January 1997 and December 1998, together with the open biopsy results (where available) were collated and analysed. RESULTS: The mean follow up period was 15.8 months (range, 5-28). The 298 NCB specimens were categorised as follows: unsatisfactory/non-representative (B1; n = 61; 20.5%), benign but uncertain whether representative (B2r; n = 52; 17.4%), benign (B2; n = 103; 34.6%), lesions possibly associated with malignancy but essentially benign (B3a; n = 9; 3.0%), atypical epithelial proliferations (B3b; n = 10; 3.4%), suspicious of malignancy (B4; n = 7; 2.3%), and malignant (B5; n = 56; 18.7%). Excision biopsy was performed in 43 cases within the B1 (n = 19), B2r (n = 8), B2 (n = 8), and the B3a (n = 8; data unavailable in one case) categories, revealing malignancy in 18 (42.8%) cases and in 65 cases within the B3b, B4, and B5 categories, revealing malignancy in 64 cases (98.5%). The sensitivity of NCB for malignancy was 87.7%, with a specificity and positive predictive value of 99.3% and 98.5%, respectively. FNAC had an inadequacy rate of 58.7%, a complete sensitivity of 34.5% and a specificity of 47.6%. CONCLUSIONS: This study confirms the value of NCB in the preoperative assessment of impalpable breast lesions. Two new categories are suggested for the NCB classification; category B2r for benign breast tissue where representativeness is uncertain, and the subdivision of category B3 into B3a for benign lesions potentially associated with malignancy (for example, radial scars and intraduct papillomas) and B3b for more worrisome atypical epithelial proliferations. These will aid the accurate audit of NCB and identify more clearly the intellectual pathway leading to a particular assessment.     

"Missed" diagnoses of phyllodes tumor on breast biopsy: pathologic clues to its recognition

Fibroadenoma and phyllodes tumors of the breast exhibit a continuum of pathologic features. We examined phyllodes tumors initially called fibroadenoma for features that may accurately classify the tumor as phyllodes tumor on the first biopsy specimen. The phyllodes tumors initially called fibroadenoma for features that may accurately classify the tumor as phyllodes tumors on the first biopsy specimen are examined. Fifteen patients with phyllodes tumors were studied, initially called FA or another term short of PT. These tumors were compared with 16 true fibroadenomas, all with needle-core biopsy followed by excision. Resected phyllodes tumors were larger on average than fibroadenoma, 6.8 cm (range = 1.7-16.2 cm) versus 2.6 cm (range = 1.0-4.8 cm). In needle-core biopsy cases, sampling was limited, even in large breast masses. p53 and cleaved caspase-3 were noncontributory. Ki-67 showed higher proliferation indices in phyllodes tumors versus fibroadenoma (4.8% vs 0.6%). Features suggesting phyllodes tumors include tissue fragmentation, increased stromal cellularity especially around glands, stromal overgrowth, and increased mitoses. Increased sampling of a large tumor will likely yield more correct diagnoses.     

Aspiration biopsy cytology of papillary carcinoma of the breast.

The fine-needle aspirates of two cases of noninfiltrating papillary carcinoma (PC) and three examples of early invasive PC of the breast were examined. In three cases in which the tumors displayed cuboidal or polygonal cells the aspirates showed papilla-like clusters of tumor cells with relatively "strong" cellular cohesiveness. Single and small aggregates of tumor cells as well as hemosiderin-laden or foamy macrophages were also present. Aspirates from the two PCs predominantly consisting of tall columnar epithelial cells revealed only monolayered and multilayered epithelial fragments with folding in one case. In the other case large epithelial fragments and small tight clusters of polygonal tumor cells were present. No bipolar nuclei of myoepithelial cells were identified in all cases. No specific cellular features permitting the differentiation between noninfiltrating and early invasive breast PCs were identified in this small series. Staining for carcinoembryonic antigen using the peroxidase-antiperoxidase technique was performed on aspiration smears of three cases. It revealed a positive cytoplasmic reaction in two cases.     

Carcinoma of the breast in a fibroadenoma: diagnosis by fine-needle aspiration cytology.

A case of carcinoma of the breast concurrent with a fibroadenoma in a 49-yr-old female is described in which the diagnosis was made on fine-needle aspiration cytology. Reports of such an occurrence are few, and to our knowledge none has previously documented the cytologic findings in detail.     

Fine-needle aspiration cytology of metastatic neoplasms in the breast

Twenty cases of metastatic neoplasms in the breast were identified in a series of 1,034 fine-needle aspirations (FNAs) of the breast, of which 389 were malignant. Patients with breast carcinomas in whom metastasis to the contralateral breast developed were excluded from this study. This series consisted of 17 women and 3 men, ranging in age from 28 to 63 years (mean, 49 years). The tumors included oat cell carcinoma (three), melanoma (three), ovarian serous carcinoma (one), bronchogenic adenocarcinoma and squamous carcinoma (four and two, respectively), lymphoma (two), carcinoid (two), transitional cell carcinoma (one), plasma cell myeloma (one), and rhabdomyosarcoma (one). In two patients, the breast mass was the first manifestation of an extramammary cancer (two adenocarcinoma of the lung). Eleven patients died of disseminated cancer shortly after the breast metastasis was diagnosed. In most cases, the aspirates displayed the cytologic features characteristic of the primary tumors, thereby establishing the metastatic nature of the neoplasm. In four cases (two carcinoids, one myeloma, and one rhabdomyosarcoma), the cytologic features were difficult to differentiate from a primary breast carcinoma; however, the final diagnosis was established by electron microscopic examination and immunocytochemical studies on the aspirates. One case (adenocarcinoma of the lung) was misdiagnosed as primary breast carcinoma on both FNA and mastectomy specimen. Because metastatic neoplasms in the breast may mimic primary breast tumors, the authors recommend the following: (1) Evaluation of FNA of breast should be done with complete knowledge of the patient's clinical history. (2) The possibility of metastasis should be suspected in lesions with unusual cytologic patterns. (3) Ancillary studies on FNA can be helpful in interpreting selected cases.