Chromosome analysis in 31 cases of benign and malignant breast tumors: a study in Brazil

Cultures of 31 breast tumors, being 20 carcinomas and 11 benign lesions, were cytogenetically analysed. Clonal chromosome aberrations were detected in 16 carcinomas and in 4 benign lesions. Nine carcinomas and 2 benign lesions had multiple cytogenetically unrelated and related clones, whereas a single abnormal clone was observed in 7 carcinomas and in 2 benign lesions. Polyploid clones were found in 7 carcinomas and in 2 benign lesions. The presence of clonal chromosome aberrations and polyploid cells was not associated with the clinicopathologic parameters tested. Carcinomas had more clonal changes than benign lesions (p = 0.031), showing that cytogenetic features are of diagnostic value and that different chromosome anomalies might have different pathogenetic and prognostic significance.     

Imprint cytology of core needle biopsy specimens of breast lesions. A rapid approach to detecting malignancies, with comparison of cytologic and histopathologic analyses of 173 cases

OBJECTIVE: To investigate whether imprint cytology of core needle biopsy (CNB) specimens from breast lesions is a useful method of rapidly obtaining additional diagnostic information and potentially can be used to reduce the number of biopsies needed. STUDY DESIGN: Cytologic analysis was performed on 173 breast lesions and compared with their histopathologic diagnoses (143 malignant and 30 benign). For imprint cytology, one CNB specimen was rolled between two slides and stained with Diff-Quik and Papanicolaou stain. RESULTS: The diagnostic overall accuracy of Diff-Quik stain (Papanicolaou stain) was 95.4% (95.9%), with a sensitivity of 96.5% (97.2%), specificity of 90% (90%), positive predictive value of 97.8% (97.8%) and negative predictive value of 84.3% (87.0%). There was no statistically significant difference between the stains. Histopathologic analysis had an overall accuracy of 97.7%, with a sensitivity of 97.2%, specificity and positive predictive value of 100% and a negative predictive value of 88.2%. CONCLUSION: Imprint cytology of CNBs is a sensitive method of detecting malignancies in breast tumors. Diff-Quik is a rapid and reliable approach that can reduce the number of biopsies. Inadequate and suspicious cases should be evaluated based on complementary diagnostic procedures for breast lesions.     

Ultrasonographically and stereotactically guided fine-needle aspiration cytology of non-palpable breast lesions: cyto-histological correlation

Objective:  To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine needle aspiration cytology (FNAC) for the diagnosis of non-palpable breast lesions.
Patients and methods:  From January 2002 to December 2004, 470 women with 478 mammographically detected non-palpable breast lesions had US or stereotactically guided FNAC of the breast lesion. Subsequent histological evaluation of the same lesion was performed at the Institute of Oncology Ljubljana, Slovenia. The correlation between the original cytological and histological diagnosis was assessed and the sensitivity, specificity, positive predictive value and negative predictive value were calculated.
Results:  Among US-guided FNACs, 144 (53.5%) were histologically verified benign lesions and 125 (46.5%) were carcinomas. Cytological diagnoses were: true positive (TP) in 63 cases (50.4%), suspicious in 35 (28%), false negative (FN) in eight (6.4%), and in 19 (15.2%) cases, the material was inadequate for diagnosis. In the stereotactically guided FNAC group, there were 209 women with 209 lesions, with 95 (45%) histologically proven carcinomas and 114 (55%) benign lesions. Cytological diagnoses were TP in 49 (51.6%) cases, true suspicious in 21 (22.1%), FN in nine (9.5%), and in 16 (16.8%) cases, the material was not adequate for the diagnosis.
Conclusion:  The sensitivity of 88.7% and specificity of 98.6% for US-guided FNAC and 84.5% and 100% for stereotactically guided FNAC, respectively, suggest that clinicians can rely upon cytological diagnosis for planning further management of women with non-palpable breast lesions.     

Usefulness of fine needle aspiration of the thyroid in an endemic goiter region

The accuracy of fine needle aspiration (FNA) cytology of the thyroid was addressed in 142 nodular goiters from an endemic goiter region. The aspirations and their interpretation were based on the methodology of the Karolinska Hospital. For practical purposes, the follicular lesions were divided into type I (benign), type II (atypical benign) and type III (suspicious). Excluding the follicular lesions, the cytohistologic agreement for the whole series was 87%, with a correlation of 81.5% for carcinomas. The type I and type II follicular lesions were benign on histologic grounds; 39% of the carcinomas were detected in the type III follicular lesions. The 0.7% false-positive diagnoses increased to 15% when type III follicular lesions were included. No false negatives were recorded. These observations, together with the increase of surgically resected thyroid carcinomas after FNA was accepted as a diagnostic modality, indicate that FNA biopsy of the thyroid is an accurate diagnostic method and is useful in selecting patients for subsequent surgery in areas of endemic goiter.     

剪切波弹性成像在乳腺实性病变良恶性鉴别中的诊断价值

目的:探讨剪切波弹性成像在乳腺实性病变良恶性鉴别中的诊断价值。方法:收集2012年3月-2013年6月于我院收治的乳腺实性病变患者54例,共65个病灶,先后给予乳腺二维超声检查与剪切波弹性成像检查,采用弹性模量值与钼靶BI-RADS分级方法诊断,比较两种方法诊断的准确性。结果:良性病灶组弹性最小、最大值以及平均值、标准差与恶性病灶组比较差异具有统计学意义(P0.05);ROC曲线分析显示,在乳腺实性病变良恶性的鉴别中,弹性最大值明显优于平弹性均值;剪切波弹性成像对乳腺实性病变良恶性鉴别的敏感度、特异度、准确度、阳性预测值、阴性预测值高于二维超声技术(P0.05)。结论:剪切波弹性成像在乳腺实性病变良恶性鉴别中具有良好的诊断价值,能够提高诊断的准确性。     

Evaluating the diagnostic significance of nuclear grooves in thyroid fine needle aspirates with a semiquantitative approach

OBJECTIVE: To clarify the diagnostic significance of nuclear grooves in thyroid fine needle aspirates, to search for other associated nuclear features and to identify possible diagnostic pitfalls. STUDY DESIGN: In total, 67 fine needle aspiration cases were retrospectively reviewed for selected nuclear features, including grooves, intranuclear cytoplasmic invaginations, enlargement, pleomorphism and status of nucleoli. A semiquantitative method was used to estimate the percentage of nuclear grooves in 5 high-power fields with the most frequent nuclear grooves. RESULTS: Unequivocal intranuclear cytoplasmic invaginations were a specific diagnostic feature of papillary carcinoma. In the absence of intranuclear cytoplasmic invaginations, the presence of > or = 20% nuclear grooves was virtually diagnostic of thyroid neoplasms, predominantly papillary carcinoma. Less than 10% of nuclear grooves virtually eliminated the possibility of papillary carcinoma. However, 10-19% of nuclear grooves may be seen in papillary carcinoma and benign lesions; therefore, such cases fell into the diagnostic category of "atypical cytology" or "indeterminate" cytology. Nuclear enlargement with elongation was a readily identifiable feature usually associated with nuclear grooves. Significant pleomorphism was more commonly seen in papillary carcinoma than in benign lesions. CONCLUSION: A semiquantitative method is helpful when nuclear grooves are encountered in thyroid cytology in the absence of other diagnostic features. It can significantly improve the diagnostic specificity of nuclear grooves for papillary carcinoma.     

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

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

Analysis of fine needle aspiration cytology of the breast: a review of 1,297 cases and correlation with histologic diagnoses

OBJECTIVE: To evaluate the accuracy of fine needle aspiration (FNA) cytology of the breast and to ascertain its usefulness. STUDY DESIGN: The authors reviewed 1,297 cases of FNA cytology of the breast which were performed at Chonnam National University Hospital from 1999 to 2002. Cytologic diagnoses were compared with histologic diagnoses in 457 cases that underwent both cytologic and histologic examination. RESULTS: Of 1,297 cases, 1,201 (92.6%) were satisfactory and 96 (7.4%) unsatisfactory. Subsequent histologic examination was performed on 291 cases (29.7%) out of 981 "benign" lesions, 28 (73.7%) of 38 "suspicious," 124 (68.1%) of 182 "malignant" and 14 (14.6%) of 96 "unsatisfactory." FNA cytology revealed 77.7% sensitivity, 99.2% specificity, 98.4% positive predictive value and 88.0% negative predictive value. Diagnostic accuracy was 91.1%. Of the 291 benign cases on cytology, 35 cases were malignancy on histology. Of the 124 cases reported as malignant, 2 were benign. Interpretive error was the leading cause of false positive diagnoses. CONCLUSION: Although FNA cytology is a useful diagnostic procedure for the evaluation of breast lesions, it should be combined with other diagnostic modalities, such as physical examination, ultrasonography and mammography.     

Differential diagnosis of oncocytic lesions of the breast and thyroid utilizing a semiquantitative approach.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hürthle cell adenomas (7 cases), Hürthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and > 90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P < .005. CONCLUSION: Without the expenditures of additional time, costs or materials, this semiquantitative approach compared favorably with contemporary morphometric studies involving the differential diagnosis of oncocytic cell pathology in fine needle aspiration cytology.     

Cytochemical classification of nonpalpable breast carcinoma

A stereotaxic needle biopsy technique makes it possible to obtain diagnostic cytologic material from nonpalpable breast lesions down to sizes of 2 to 3 mm in diameter. Considering the high correlation between the type of DNA distribution pattern and patient survival demonstrated in palpable breast carcinomas, cytophotometric DNA measurements were performed on smear preparations from nonpalpable tumors. In a series of 30 consecutive nonpalpable breast carcinomas, the same types of DNA profiles as shown in palpable tumors were found. This indicates that malignancy grading of breast carcinomas by cytochemical means can be performed on stereotaxic needle biopsy material and that an improved prognostic evaluation may be expected by the use of the methods described. This should result in a better therapeutic approach to patients with nonpalpable breast tumors.     

Diagnostic value of flow cytometric DNA determination combined with fine needle aspiration biopsy in thyroid tumors

The nuclear DNA content and the numbers of cells in the S and G2M phases of the cell cycle were determined by flow cytometry (FCM) in fine needle aspirates of 187 thyroid tumors to evaluate the diagnostic value of nuclear DNA content determination in combination with aspiration cytology. DNA aneuploidy was present in 4 of 5 follicular carcinomas, 2 of 3 anaplastic carcinomas, 5 of 15 excised follicular adenomas and 2 of 20 excised adenomatous goiters; all 7 papillary carcinomas and 4 lymphomas were diploid in the aspirate. Aneuploid carcinomas had easily distinguishable S and/or G2M phases, unlike the benign aneuploid tumors. None of the histologically benign tumors or the nonexcised tumors had greater than 6% S-phase cells, and only one benign tumor had greater than 9% G2M-phase cells. In contrast, all lymphomas had greater than 10% S-phase cells and four of seven papillary carcinomas had greater than 9% G2M-phase cells. The use of FCM determination in combination with fine needle aspiration biopsy cytology improved the diagnostic potential of the latter technique.     

Aspiration biopsy cytology and special stains

Histochemical methods play a vital role in the histology laboratory. The application of histochemistry to aspiration biopsy cytology (ABC) has shown equal promise in the demonstration of distinctive intracytoplasmic and extracytoplasmic substances. In our examination of more than 8,000 fine needle aspirates, we have found that certain histochemical studies may be of special diagnostic importance. These include mucicarmine, periodic acid-Schiff, oil red O, Fontana-Masson argentaffin and Gomori's iron stains. With the exception of the oil red O stain for neutral lipids (alcohol soluble), each may be applied to the destained smear initially prepared according to the method of Papanicolaou. Modifications of these histologic stains have been made to suit the "rapid service" motto of our busy cytology laboratory.     

Nuclear image morphometry and cytologic grade of breast carcinoma

OBJECTIVE: To correlate visual cytologic grade with automated nuclear morphometry of carcinoma of the breast. STUDY DESIGN: We randomly selected 24 histologically proven infiltrating ductal carcinomas of the breast and 10 benign breast lesions (fibroadenoma). Hematoxylin-eosin-stained fine needle aspiration cytology (FNAC) smears were selected for both cytologic grade and automated image morphometry. The same hematoxylin-eosin-stained FNAC smears were studied for area, convex area, standard deviation of nuclear area, diameter, perimeter and convex perimeters of nucleus. At least 100 cells from each case were measured with an image cytometer. RESULTS: Mean nuclear area, standard deviation of nuclear area, nuclear diameter, convex area, convex perimeter and perimeter were significantly increased from benign versus grade 1 carcinomas and grade 1 versus grade 2 and 3 carcinomas (one way ANOVA test). However, there was no significant difference in grade 2 versus grade 3 carcinomas. CONCLUSION: Automated image cytometry rapidly and successfully measures various nuclear parameters. The measurement of various nuclear parameters would be helpful in future applications of automated diagnosis and grading of breast carcinomas from cytologic material.     

Cytology of argyrophilic carcinoma of the breast

Aspirations of breast lesions from 57 patients were studied by evaluating Grimelius-stained smears in order to determine the cytologic features of argyrophilic carcinoma and the reliability of argyrophilia as a characteristic of malignancy. The cytologic preparations were compared with histologic material. Sixteen benign lesions, 24 carcinomas correctly diagnosed by cytology and 5 carcinomas with technically inadequate smears were argyrophil negative. Five of 12 carcinomas with equivocal cytology were argyrophilic. There was perfect to case-to-case correlation between argyrophilia seen on histologic slides and on smears. The smears of the 5 argyrophilic carcinomas and 2 of the argyrophil-negative carcinomas with equivocal cytology shared features in common not seen in the other 50 smears: elongated cells with eccentric, round-to-oval nuclei and granular or opaque cytoplasm. These features can alert the pathologist to the possibility of malignancy in smears with equivocal cytology. A positive stain for argyrophilia will further increase the index of suspicion.     

Automated analysis of rat breast tumors. Comparison of four methods

Chemically-induced malignant rat breast tumors pose diagnostic dilemmas since the majority are well-differentiated, noninvasive papillary lesions that are barely distinguishable from benign papillary lesions. This study compared several automated modalities to see which best separated benign from malignant breast tumors. Thirty-three carcinogen-induced rat breast tumors (13 adenomas, 10 papillary carcinomas and 10 invasive carcinomas) were evaluated by static (image) cytometry (ICM) of integrated optical density, by flow cytometry (FCM) and by two automated morphometric protocols, contextual analysis and single-gland analysis. DNA ploidy analysis, by either ICM or FCM, did not discriminate between the benign and malignant tumors. Contextual analysis correctly identified 11 of 13 benign and 17 of 20 malignant lesions (P less than .01). Single-gland analysis correctly identified all 13 benign and 17 of 20 malignant lesions (P less than .01). No method distinguished invasive from noninvasive carcinomas. The data suggest that architectural features are more important than nuclear features in differentiating benign from malignant rat breast tumors.     

Diagnostic pitfalls in fine needle aspiration cytology of atypical apocrine metaplasia in a breast lesion. A case report

BACKGROUND: Apocrine metaplastic cells are frequently encountered in fine needle aspirates of breast lesions. Atypical apocrine metaplastic cells with signet ring features can also occur, and their presence may present a diagnostic dilemma in the differentiation of benign versus malignant lesions. CASE: A fine needle aspirate of a 2.5 x 1.0-cm, subareolar mass in a 47-year-old female showed atypical cells with signet ring morphology. Also present were clusters of cells that were enlarged and showed nuclear atypia, prominent nucleoli and cytoplasmic granules. Papillary cohesive clusters of ductal cells were also identified. The fine needle aspiration diagnosis was mucinous carcinoma. The nodule was excised, and the histologic diagnosis was sclerosing ductal papilloma with atypical apocrine metaplasia. CONCLUSION: Atypical apocrine cells can be misinterpreted as mucinous carcinoma or usual duct adenocarcinoma on fine needle aspiration cytology. We present clues that may help in rendering the correct interpretation.     

Diagnostic Efficacy of Cell Block Immunohistochemistry,Smear Cytology,and Liquid-Based Cytology in Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Lesions: A Single-Institution Experience

Background

The diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology varies widely depending on the treatment method of the specimens. The present study aimed to evaluate the diagnostic efficacy of cell block (CB) immunohistochemistry, smear cytology (SC), and liquid-based cytology (LBC) in patients with pancreatic lesions without consulting an on-site cytopathologist.

Methods

This study prospectively enrolled 72 patients with pancreatic lesions. The EUS-FNA specimens were examined by SC, LBC, and CB immunohistochemistry. The diagnostic efficacy of the 3 methods was then compared. Patients’ final diagnosis was confirmed by surgical resection specimens, diagnostic imaging, and clinical follow-up.

Results

Our results included 60 malignant and 12 benign pancreatic lesions. The diagnostic sensitivity (90%), negative predictive value (66.7%), and accuracy (91.7%) of CB immunohistochemistry were significantly higher than those of SC (70.0%, 30.0%, and 75.0%, respectively) and LBC (73.3%, 31.6%, and 77.8%, respectively) (all P<0.05). The combination of CB and SC, or CB and LBC, did not significantly increase the efficacy compared to CB immunohistochemistry alone.

Conclusion

Our findings suggest that in the absence of an on-site cytopathologist, CB immunohistochemistry on EUS-FNA specimens offers a higher diagnostic efficacy in patients with pancreatic lesions than does SC and LBC.     

p53 mutations as tumor markers in fine needle aspirates of palpable breast masses

OBJECTIVE: Mutations in p53 exons 5-8 are found in 40-50% of breast carcinomas. We performed a retrospective analysis of p53 mutations in fluid-based, archival fine needle aspirates (FNAs) of breast masses to determine their potential diagnostic utility as breast tumor cell markers. STUDY DESIGN: Residual, fluid-based, archival FNAs of 27 breast masses were retrospectively evaluated by polymerase chain reaction (PCR), single-strand conformational polymorphism analysis (SSCP) and sequencing for p53 exons 5-8. Results were compared with the morphologic diagnoses and genotyping of available excisional biopsy tissue. RESULTS: Six of the twenty-seven cases were found to have a clonal mutation in p53; all six mutated cases showed carcinoma on subsequent excisional biopsy. Definitive cytologic diagnosis of cancer had been possible in only four of the six cases. Identical mutations were found in the excised carcinomas in the five cases with available tissue. None of the 14 aspirates with benign cytology had detectable mutations in p53. CONCLUSION: p53 Mutational analysis by PCR/SSCP/sequencing deserves to be critically studied as a diagnostic criterion in patients with indeterminate or suspicious cytology. Validation studies should be performed to test p53 mutations as molecular diagnostic markers in breast cytology specimens.     

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.