Equivocal diagnoses in breast aspiration biopsy cytology: sources of uncertainty and the role of "atypical/indeterminate" terminology.

In 1996, a National Cancer Institute committee recommended four categories as uniform terminology for breast fine-needle aspirations (FNAs): benign, malignant, suspicious/probably malignant, and atypical/indeterminate. The latter is a controversial category. This study evaluates the usefulness of the atypical/indeterminate term, and examines sources of diagnostic equivocation in breast FNA. Eight hundred and twenty-two consecutive breast FNAs were previously classified as benign, malignant, suspicious, or unsatisfactory. Two hundred and thirteen (25.9%) cases had surgical follow-up and were classified as true positive (TP), false positive (FP), true negative (TN), false negative (FN), true suspicious (TS), or false suspicious (FS). Slides from FN, FP, TS, and FS were reviewed for interpretative error, poor clarity or preservation, obscuring material, sampling error, or insufficient malignant criteria. Cases were also evaluated as to whether classification as "atypical/indeterminate" would have improved patient care. There were 21/822 (2.6%) FN, 37/822 (4.5%) TS + FS, and 0 FP diagnoses. Seventy percent of suspicious diagnoses showed cancer on follow-up. The majority of FN and suspicious cases were due to sampling problems and insufficient criteria of malignancy. None were deemed more appropriately classified as "atypical/indeterminate" All required surgical confirmation for treatment. All equivocal breast diagnoses are due to similar problems. Splitting them into "suspicious/probably malignant" and "atypical/indeterminate" would not lower the biopsy rate. A simpler three-part terminology of benign, malignant, and suspicious/equivocal, without qualification of the latter favoring benign or malignant, would provide more effective communication and appropriate follow-up. Diagn. Cytopathol. 1999;21:217-222.     

Fine-needle aspiration biopsy in the diagnosis and classification of primary and recurrent lymphoma: a retrospective analysis of the utility of cytomorphology and flow cytometry.

We retrospectively reviewed our experience with the fine-needle aspiration biopsy (FNAB) diagnosis of primary and recurrent lymphoma to assess the ability of cytomorphology with and without ancillary flow cytometry (FCM) analysis to diagnose and subclassify these tumors according to the Revised European-American Lymphoma/World Health Organization classifications. We reviewed 139 consecutive FNABS of 84 primary and 55 recurrent lymphomas. FCM was successful in 105 (75%) cases. The overall results, including cases without FCM, included 93/139 (67%) true positive, 7 (5%) false negative, and 39 indeterminate (27 [19%] suspicious and 12 [9%] atypical) diagnoses of lymphoma. In cases with FCM, there were 80/105 (77%) true positive, no false negative, and 25 indeterminate diagnoses (15 [14%] suspicious and 10 [9%] atypical). The overall results of the 84 primary lymphomas were 55 (67%) true positive, 5 (5%) false negative, and 24 indeterminate (14[16%] suspicious and 10 [12%] atypical) diagnoses for lymphoma. Of the 68 primary lymphomas analyzed with FCM, 50 [74%] were true positives, and 28 were indeterminate (11 [16%] suspicious and 7 [10%] atypical). There were no false negatives. Diagnostic accuracy varied among lymphoma subtypes. Subclassification of the positive cases were initially conclusive in only 55/93 cases (59%). However, a retrospective review of the morphologic together with FCM data in 15 of the 23 unclassified cases improved the overall subclassification of positive cases to 77%. Subclassification was best in small lymphocytic lymphoma/chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, Burkitt's lymphoma, mantle cell lymphoma, and plasmacytoma (all 100%). Subclassification was poor in marginal-zone lymphoma (33%), and initially as well in diffuse large B-cell lymphoma (62%), but it improved on review (95%), as did subclassification of follicular lymphoma (77 to 100% on review). Hodgkin's disease was recognized as malignant in only 44% of the cases (7/16) and was classified as such based on morphology alone. This review of our early efforts to diagnose and subclassify lymphoma with FNAB and FCM indicates that although a diagnosis and proper subclassification of lymphoma can be made with certainty in the majority of cases, recurrent or primary, it requires close coordination of cytomorphology and immunophenotyping data, which often comes with close cooperation of cytopathologists and hematopathologists. A mere cytological diagnosis of positive for lymphoma is no longer acceptable if FNAB is to become an independent diagnostic tool for lymphoma.     

Correlation of thyroid nodule fine-needle aspiration cytology with corresponding histology at Mayo Clinic, 2001-2007: an institutional experience of 1,945 cases

Following the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference, the thyroid fine‐needle aspiration biopsy (FNAB) practice at Mayo Clinic, Rochester, Minnesota, conducted retrospective analyses correlating cytologic and histologic evaluations of thyroid nodules. Cytologic and histologic reports were retrieved for patients with thyroid nodules who underwent thyroid FNAB between January 2001 and December 2007, with subsequent surgical thyroid resection. Cases were classified by major cytologic and histologic diagnosis and specific diagnostic subcategories. Of 1,945 FNAB cytologic results, 180 (9.3%) were nondiagnostic; 512 (26.3%) were negative for malignancy; 27 (1.4%) were atypical; 729 (37.5%) were suspicious for malignancy; and 497 (25.6%) were positive for malignancy. Histology was benign in 1,179 (60.6%) and malignant in 766 (39.4%). For thyroid malignancy as the disease outcome, at cytologic thresholds of atypical, suspicious, and positive, overall sensitivity of thyroid FNAB was 94.5%, 94.1%, and 65.0%, respectively, and specificity was 46.0%, 48.3%, and 98.5%, respectively. Positive predictive value for all malignancies was 97.0%, and negative predictive value was 92.0%. When separated by specific malignant outcomes, diagnoses of papillary carcinoma, medullary carcinoma, and lymphoma had specificity of suspicious FNAB diagnoses ranging from 90.5% to 99.6%; positive predictive value ranged from 87.5% to 91.4%. For follicular or Hürthle carcinoma, suspicious FNAB diagnoses had a specificity of 52.5% and a positive predictive value of 5.9%. Sensitivity of indeterminate FNAB diagnoses ranged from 72.7% to 95.3%. For follicular or Hürthle pattern malignancies, indeterminate cytologic diagnoses should be interpreted with caution by the clinician considering surgical management. Diagn. Cytopathol. 2012;40:E27–E32. © 2010 Wiley Periodicals, Inc.     

Fine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospital

We present our experience of fine-needle aspiration (FNA) cytology of the thyroid in a community hospital setting and discuss the cancer probability of the indeterminate FNA results. There were 1,621 FNAs, 401 of which have follow-up thyroidectomies during a 10-yr period. The initial FNA diagnoses of these 401 cases were benign non-neoplastic (BNN) 159, malignant 34, atypical 33, suspicious 19, follicular neoplasm (FN) 88, follicular lesion (FL) 51, and inadequate 17. There were no false-positive cases. Cancer was found in 11 cases diagnosed as BNN (7%), 6 cases were due to sampling errors (incidental microcarcinomas), and 5 cases were due to failure to identify focal atypia in the smears of a follicular variant of papillary carcinoma. The false-negative rate was 3%, with the exclusion of cases of incidental microcarcinomas. Among the indeterminate FNA results, the follow-up operations revealed malignant tumors in 16 of 33 (48%) cases of atypical, 13 of 19 (68%) cases of suspicious, 29 of 88 (33%) cases of FN, and 7 of 51 (14%) cases of FL. Malignant tumors were also found in 2 of 17 (12%) of inadequate specimens with follow-up. When compared to the cancer rate (3%) for FNA diagnosis of BNN, the likelihood of finding cancer in the thyroidectomy is 5 times more for a FL, 11 times more for a FN, 16 times more for atypical, and 23 times more for suspicious. The sensitivity and specificity are 87 and 100%, respectively.     

Accuracy of cytologic diagnoses made from touch imprints of image-guided needle biopsy specimens of nonpalpable breast abnormalities

We investigated the diagnostic utility and accuracy of touch imprints (TIs) prepared from core-needle biopsy (CNB) specimens of nonpalpable breast abnormalities. We reviewed air-dried, Diff-Quik-stained TIs prepared from 172 consecutive CNB specimens obtained with stereotactic or sonographic guidance. Using criteria established for fine-needle aspirates, TIs were categorized as benign, atypical, suspicious, malignant, or unsatisfactory (i.e., showing fewer than six benign epithelial cell clusters or cell distortion). Cytologic diagnoses of TIs were then correlated with the histologic diagnoses of corresponding CNB specimens. CNB specimens were histologically diagnosed as carcinoma (102 cases), benign (59 cases), low-grade phyllode tumor (six cases), and atypical ductal hyperplasia (five cases). TIs were cytologically diagnosed as malignant (63 cases), benign (35 cases), suspicious (19 cases), atypical (18 cases), and unsatisfactory (37 cases). Correlation of the cytologic and histologic diagnoses showed that five TIs diagnosed as benign were false-negative results for histologically diagnosed carcinomas (four cases) and phyllodes tumor (one case). False-negative results were attributed to poor representation of malignant cells. Two TIs diagnosed as suspicious were false results for two histologically diagnosed fibroadenomas. The false suspicious findings resulted from TIs with high cellularity, cytologic atypia, or no familiar (i.e., as seen on fine-needle aspirates) smear pattern. Unsatisfactory TIs were noted in both benign (44%) and malignant (11%) CNB specimens. When lesions categorized as suspicious were grouped with the malignant cases and those classified as atypical were grouped with the negative cases, TI sensitivity and specificity, were 83% and 95%, respectively. Fibroadenomas are difficult to identify on TIs and are likely to be misdiagnosed as suspicious. While high- and intermediate-grade carcinomas are easily categorized using TIs, low-grade carcinomas are best categorized as suspicious because of overlapping cytologic features with proliferative breast lesions. Increased experience with cytologic analysis of TIs improves the accuracy of cytologic diagnoses.     

A single institution experience with the new bethesda system for reporting thyroid cytopathology: Correlation with existing cytologic,clinical, and histological data

Our goal was to evaluate the Bethesda system (TBS) in comparison to the previously used system at our institution. One hundred consecutive thyroid fine needle aspirations (FNAs) and 45 consecutive indeterminate FNAs were reviewed by two cytopathology‐boarded pathologists, diagnosed based on TBS and correlated with management and follow‐up. Re‐evaluation led to a diagnosis change in 48% of cases. Thirty‐nine percent of benign cases were unsatisfactory under TBS. For malignant diagnoses the positive predictive value (PPV) was unchanged, while the negative predictive value (NPV) was slightly improved using TBS. Both the PPV and NPV were improved for actionable diagnoses. Inter‐observer variability across all categories was in moderate agreement. Clinical management of both follicular lesion (FL) and indeterminate cases ranged from none to immediate surgery. Repeat FNA resolved the diagnosis in 50% of indeterminate cases. Indeterminate cases had an overall malignancy rate of 27%; higher in pre‐ (46%) than post‐TBS cases (8%). Inter‐observer variability between the reviewing pathologists and the original pathologists for indeterminate cases was fair, and between the two reviewing pathologists was moderate. Using TBS criteria increased the unsatisfactory rate and led to improved prediction of malignancy and actionable diagnoses. The pre‐Bethesda diagnosis of FL at our institution led to inconsistent clinical management. Clinical management of patients with indeterminate diagnoses was essentially unchanged following adoption of TBS. The moderate inter‐observer agreement between the reviewing pathologists may be related to level of cytology experience, strict adherence to TBS, and the exclusive use of cytomorphology for diagnosis. Diagn. Cytopathol. 2014;42:564–569. © 2014 Wiley Periodicals, Inc.     

Comparison of disagreement and amendment rates by tissue type and diagnosis: identifying cases for directed blinded review

We sought to determine whether a group of cases that was relatively high in disagreements and subsequent amendments could be identified and targeted for blinded review. During a 4-year period, 8,916 surgical pathology and nongynecologic cytology cases were subjected to blinded review; of these, there were 616 disagreements (6.9%), 69 (0.8%) had subsequent amendments issued, and 33 (0.4%) represented false-negative errors of blinded review. Tissues with the highest amendment rates were breast (4.4%), endocrine (4%), gynecologic (1.8%), and cytology (1.3%). Specimen types with highest amendment rates for specimens with more than 20 cases were breast core biopsies (4.0%) and endometrial currettings (2.1%). Diagnoses were divided into negative (64.7%), malignant (21.4%), nondiagnostic (1%), defined precursor lesions (ie, atypical ductal hyperplasia, tubular adenoma) (9.8%), and atypical or "suspicious" (3.1%). Amendment rates were highest for nondiagnostic material (5%) and atypical/suspicious (2.2%). Reviewing only nondiagnostic and atypical cases would have involved reviewing only 4.0% of cases and detected 14% of amendments. Reviewing all breast, gynecologic, nongynecologic cytology, and endocrine material would have involved reviewing 26.9% of cases and detected 88% of amendments. These data can be used to define material for directed blinded review that is relatively high in potential errors.     

Fine‐needle aspiration in pediatric patients 12 years of age and younger

Fine‐needle aspiration (FNA) is a well‐established diagnostic tool in adult patients, and while in recent years it has gained popularity in the pediatric population, it is still far less universally accepted in children than in adults. A computerized search of our tertiary medical center's laboratory information system was performed for the 20‐year period from 1992 to 2012. All FNAs in children 12 years of age and younger and all related surgical pathology reports were identified. Cytologic and histologic diagnoses were stratified into six diagnostic categories—benign, atypical, suspicious, malignant, cyst contents, and nondiagnostic—and then compared to determine the utility of FNA in this patient population. Four hundred and three FNAs in 389 patients were included in this study, of which there were 288 benign (71.5%), 8 atypical (2.0%), 10 suspicious (2.5%), 42 malignant (10.4%), 12 cyst contents (3.0%), and 43 nondiagnostic (10.6%) cases. The most common benign diagnoses were reactive lymph node and inflammatory infiltrate/abscess, while the most common malignant diagnoses were leukemia/lymphoma, rhabdomyosarcoma, and neuroblastoma. Of the 127 FNAs (31.5%) with histologic follow‐up, we identified just one false positive and one false negative case. Like FNA in adults, this study shows that the technique is both sensitive (97.2%) and specific (98.5%), and has high positive predictive (97.2%) and negative predictive (98.5%) values for diagnosing malignancy in childhood. As FNA is a simpler, less invasive, and more cost‐effective procedure when compared with surgical biopsy, it represents a valuable diagnostic tool in the pediatric population. Diagn. Cytopathol. 2014;42:600–605. © 2013 Wiley Periodicals, Inc.     

Cytological results of ultrasound-guided fine-needle aspiration cytology for thyroid nodules: emphasis on correlation with sonographic findings

Purpose

To compare the cytological results of ultrasound-guided fine-needle aspiration (US-FNA) cytology of thyroid nodules to sonographic findings and determine whether US findings are helpful in the interpretation of cytological results.

Materials and Methods

Among the thyroid nodules that underwent US-FNA cytology, we included the 819 nodules which had a conclusive diagnosis. Final diagnosis was based on pathology from surgery, repeated FNA cytology or follow-up of more than one year. Cytological results were divided into five groups: benign, indeterminate (follicular or Hurthle cell neoplasm), suspicious for malignancy, malignant, and inadequate. US findings were categorized as benign or suspicious. Cytological results and US categories were analyzed.

Results

Final diagnosis was concluded upon in 819 nodules based on pathology (n=311), repeated FNA cytology (n=204) and follow-up (n=304), of which 634 were benign and 185 were malignant. There were 560 benign nodules, 141 malignant nodules, 49 nodules with inadequate results, 21 with indeterminate results, and 48 that were suspicious for malignancy. The positive and negative predictive values of the US categories were 59.1% and 97.0%, and those of the cytological results were 93.7% and 98.9%. The US categories were significantly correlated with final diagnosis in the benign (p=0.014) and suspicious for malignancy (p<0.001) cytological result groups, but not in the inadequate and indeterminate cytological results groups. The false positive and negative rates of cytological results were 1.9% and 3.2%.

Conclusion

Sonographic findings can be useful when used alongside cytological results, especially in nodules with cytological results that are benign or suspicious for malignancy.     

Cytologic diagnosis of low-grade papillary urothelial neoplasms (low malignant potential and low-grade carcinoma) in the context of the 1998 WHO/ISUP classification

The 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms introduced a category called papillary neoplasm of low malignant potential (LMP) and separated it from low-grade papillary urothelial carcinoma (LGPUC), which was thought to yield abnormal cells in cytology specimens. The objective of our study was to evaluate the effectiveness of urine cytology in diagnosing these lesions. Eighty-six paired transurethral surgical biopsy and corresponding urine cytology specimens representing the spectrum of urothelial papillary lesions were examined. Consensus diagnosis on each biopsy was made, and the distribution was as follows: 16 benign urothelium, 27 LMP, 28 LGPUC, and 15 high-grade papillary urothelial carcinoma (HGPUC). This was followed by a blinded independent review of the urine cytology specimens by three observers. Each cytology case was marked as negative, atypical, suspicious, or positive for malignant cells by using previously published cytologic criteria. When the negative and atypical diagnoses were grouped together as "benign" and the suspicious and malignant diagnoses as "malignant," the detection rate of "malignancy" of the lesions was as follows: LMP, 37%; LGPUC, 25%; and HGPUC, 53%. The false positive rate was 6%, and the positive predictive value (PPV) was 94%. Detection rates of cells that were at least "atypical" were as follows: LMP, 74%; LGPUC, 79%; and HGPUC, 100%. While most of the LMP and LGPUC cases yielded cells that were at least "atypical," there was no significant difference in the distribution of cytologic diagnoses for LMP and LGPUC cases (P > 0.05). Urine cytology in the context of the 1998 WHO/ISUP classification appears to be useful as a screening tool but does not appear to discriminate LMP effectively from LGPUC.     

Follicular lesion of undetermined significance in thyroid FNA revisited

Controversy exists regarding the validity of follicular lesion of undetermined significance (FLUS), an indeterminate diagnostic category of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). According to BSRTC, FLUS carries a 5–15% risk of cancer. This study was designed to determine if cytomorphology could stratify FLUS into subgroups with different risks of malignancy. Reports of 127 consecutive FNAs reported as FLUS with subsequent tissue diagnoses were evaluated for the presence of various cytologic features and the results were correlated with histological diagnoses. FLUS cases with focal nuclear atypia (nuclear overlap/crowding, nuclear grooves/membrane irregularities, nuclear enlargement, and/or nuclear pseudoinclusions) were more frequently malignant on excision whereas those with architectural atypia (microfollicles) were more often benign on excision (P < 0.05). The presence of any one or more of these nuclear features increased the risk of carcinoma in subsequent thyroid resection. Papillary carcinomas predominated in excised FLUS cases with focal nuclear atypia whereas most FLUS with architectural atypia were adenomas or hyperplastic nodules on histological evaluation. BSRTC recommends that thyroid aspirates containing follicular cell nuclear and/or architectural atypia insufficient for a diagnosis of suspicious for follicular neoplasm, suspicious for malignancy or malignant be classified as FLUS. Our findings indicate that FLUS cases with focal nuclear atypia carry a risk for malignancy that is substantially higher than that assigned to FLUS and are best classified as suspicious. FLUS cases lacking these atypical nuclear features have a risk for malignancy that approximates the risk BSRTC has assigned to FLUS. Diagn. Cytopathol. 2014;42:18–22. © 2013 Wiley Periodicals, Inc.     

The triage efficacy of fine needle aspiration biopsy for follicular variant of papillary thyroid carcinoma using the Bethesda reporting guidelines

Diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) by ultrasound-guided fine-needle aspiration (FNA) is challenging. In this retrospective review, we evaluated triage efficacy (i.e., potential for triggering surgical intervention) in 44 archived FNA biopsies of surgically confirmed FVPTC obtained between December 2006 and December 2008. We compared the original FNA diagnoses with reclassified diagnoses based on 2007 National Cancer Institute (NCI)/Bethesda recommendations, and reviewed FNA cytologic features. Original FNA diagnoses included colloid nodule (7%, 3/44), atypical follicular cells (5%, 2/44), follicular lesion (11%, 5/44), follicular neoplasm (16%, 7/44), suspicious for malignancy/PTC (27%, 12/44), and papillary thyroid carcinoma (34%, 15/44). Reclassified diagnoses included indeterminate (5%, 2/44), colloid nodule (7%, 3/44), atypical cells of undetermined significance [ACUS] (7%, 3/44), Hurthle cell neoplasm (2%, 1/44), follicular neoplasm (7%, 3/44), suspicious for malignancy/PTC (25%, 11/44), and PTC (48%, 21/44). Triage efficacy was 77% (34/44) for original diagnoses versus 82% (36/44) for reclassified FNA diagnoses. We frequently observed cytologic features of PTC, such as nuclear grooves and fine chromatin; conversely, intranuclear inclusions, though present in 77% cases, were scant. Our review findings suggest that lack of characteristic cytologic features of PTC,coexistence with other thyroid lesions, and small tumor size arethe major obstacles to FNA diagnosis of FVPTC. Reclassification of thyroid FNA diagnoses does not significantly improve triage efficacy. Furthermore, FNA diagnoses of follicular neoplasm and suspicious for malignancy are valuable in patients with FVPTC because they trigger triage toward surgical intervention.     

Fibroadenoma of the breast: diagnostic pitfalls of fine-needle aspiration.

On fine-needle aspiration (FNA), fibroadenomas have a characteristic cytological appearance, although occasional cases are misinterpreted as carcinomas and vice versa. In a review of 521 breast aspirates correlated with the subsequent histology, six of 87 fibroadenomas (7%) were malignant or suspicious of malignancy on FNA (false positives). Following cytological review, four were still suspicious of malignancy because of cellular dyscohesion and prominent nucleoli, while two were fibroadenomas. On FNA, four of 145 carcinomas (3%) were diagnosed as fibroadenomas (false negatives). On review, three were malignant or suspicious of malignancy, while one was consistent with a fibroadenoma. Three false negative diagnoses were due to underappreciation of single malignant cells present between epithelial groupings typical of a fibroadenoma, while one was due to undersampling of the carcinoma. Cytologically, some fibroadenomas are sufficiently atypical that histological confirmation is necessary to exclude a malignancy. Misinterpreting carcinomas as fibroadenomas could be avoided by careful study of the morphology of isolated cells.     

Role of repeat fine-needle aspiration biopsy (FNAB) in the management of thyroid nodules

The purpose of the present study was to determine the role of repeat fine-needle aspiration biopsy (FNAB) in the evaluation of thyroid nodules initially classified as "nondiagnostic" due to limited cellularity or as "indeterminate for neoplasm." We reviewed a cohort of 431 patients (352 females, 79 males; average age 50 yr); 237 patients were classified as "nondiagnostic" due to limited cellularity and 194 as "indeterminate for neoplasm" over a 3-yr period (1999-2002). Repeat FNAB under ultrasound guidance was performed in 226 patients (226/431, 52%); surgical pathology results were available in 101 patients. Repeat FNAB diagnoses were: benign 70 (31%), follicular/Hürthle cell neoplasm 62 (27%), suspicious for papillary carcinoma 25 (12%), malignant 17 (7%), and nondiagnostic 52 (23%) cases. Surgical follow-up was available in 101 (45%) patients; malignancy was identified in 50 (49%) patients. The malignancy rate was 51% and 48% in cases in which initial FNAB was nondiagnostic and indeterminate for neoplasm, respectively. There were no false-positives and all malignant cases undergoing surgery were found to be malignant. This study demonstrates that repeat FNAB is warranted in patients with thyroid nodules diagnosed on initial FNAB as nondiagnostic and indeterminate for neoplasm since it can yield a definitive diagnosis in the majority of cases with an overall malignancy rate of 49%.     

Significance of the diagnostic categories “atypical” and “suspicious for malignancy” in the cytologic diagnosis of solid pancreatic masses

Endoscopic ultrasound guided (EUS) fine‐needle aspiration (FNA) investigation of solid pancreatic lesions has been shown to have good sensitivity and specificity. Many lesions can be definitely classified as benign or malignant but some can only be cytologically classified as “atypical” or “suspicious for malignancy”. Risk for malignancy in these indeterminate categories has not been well categorized. The cytology records of four University Medical centers were searched for all EUS guided FNAs of solid pancreatic lesions. All cases with a diagnosis of “atypical”, or “suspicious for malignancy” were selected for analysis when histologic biopsy or over 18 months clinical follow‐up was available. Two hundred and ninety‐two cases with a diagnosis of “atypical” or “suspicious for malignancy” and adequate follow‐up were obtained from the combined data of the four institutions. The percentage malignant for the categories “atypical” and “suspicious for malignancy” were 79.2 and 96.3%, respectively. If the category “atypical” was classified as benign and “suspicious for malignancy” was classified as malignant, the resulting positive predictive value was 96.3 (95% CI: 92.6–98.5) and the negative predictive value 20.8 (95% CI: 13.4–30.0). The categories of “atypical” and “suspicious for malignancy” stratify risk for malignancy in a fashion, which may aid in patient counseling and selection of follow‐up protocols. Classification of “suspicious for malignancy” as malignant optimizes diagnostic sensitivity and specificity. Diagn. Cytopathol. 2014;42:292–296. © 2014 Wiley Periodicals, Inc.     

Discrepancy analysis, communication, and feedback for cytotechnologist quality improvement of nongynecologic cytopathology

The Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) detail the requirements for the cytotechnologist (CT) who evaluates gynecologic cytopathology specimens. However, the role of the CT in nongynecologic cytopathology is not clearly defined. Furthermore, non gynecologic cytopathology cases are diverse and the screening, interpretative, and diagnostic issues may be quite different from the gynecologic cases. At our institution, the CT and pathologist review nongynecologic cytopathology cases. Since CLIA '88 does not require the CT to screen nongynecologic cytopathology cases, there are few guidelines for quality assessment or quality improvement for the CT regarding nongynecologic cytopathology cases. To provide better understanding of the expectations of the CT and the needs of the pathologist, we developed a system comparing the CT's interpretation to the pathologist's interpretation as a means for enhanced communication and feedback. Using our Laboratory Information System (LIS), we generate a daily report that lists all cases with discrepancy in diagnoses between the CT and pathologist. The general supervisor reviews this report for diagnostic discrepancy in each case. To determine the degree of discrepancy, numerical values are assigned to each primary interpretation. Minor discrepancies are defined as differences less than +/-2.0. Major discrepancies are defined as differences greater than or equal to +/-2.0. For the entire laboratory, the overall percentage of concordant cases was consistently above 80% for each of the 6 mo analysis. Regarding the monthly discrepancies, the proportion of minor discrepancies ranged from 11.09% to 15.44% and the proportion of major discrepancies ranged from 1.40% to 3.56%. The frequency distribution of discrepancies by degree approximates a normal (Gaussian) curve and serves as baseline information that may be used for comparison when there are changes in practice or personnel. The CTs attend slide review sessions conducted by the general supervisor for discussion of cases with major discrepancies. The discrepancy data from individual CTs are useful in counseling and recommending areas for improvement. As the CT and pathologist work cooperatively and in tandem, our system allows for a mechanism by which the expectations and needs of pathologist are communicated to the CT more effectively. We believe our process is a fundamental step in improving CT performance in Nongynecologic cytopathology and keeps the CT informed of complexities of nongynecologic cytopathology.     

The cell block for body cavity fluids: do the results justify the cost?

We reviewed retrospectively reports on cytologic smears and cell blocks from body cavity fluids received in our department over a 12-mo period. In order to evaluate the usefulness of the two modalities independently, all available slides were studied with the reviewers blinded to the original diagnoses, history, and appearances on corresponding cytology/cell block. Of 524 cytology samples, 283 had cell blocks, of which 263 were available for comparative cytologic and histologic review. Twenty-four cases based on the original reports and 22 cases in the review had diagnoses with major discrepancies between the cell block and cytology. On original reports, cytology favored malignancy in 21 cases in which the cell block was benign, with one false suspicious cytology. In three cases, the cell block was suspicious/positive (two false suspicious cell blocks), but cytology was negative/atypical. In the review diagnoses, there were also 21 cases of suspicious/positive cytology (one false suspicious cytology) and negative/atypical cell blocks. In only one case did the cell block favor malignancy when cytology was benign (a false suspicious cell block). Review of Medicare data indicated that the physician's fee charged for these 283 cell blocks would range from about $7,000 to $28,000 to detect one additional malignancy. We conclude that the routine use of cell blocks is not a cost-effective method of detecting malignancy in body cavity fluids. We advise that samples be refrigerated or be kept fixed. If immunoperoxidase studies are desired following cytologic evaluation, they may be performed subsequently on fresh smears or a cell block.     

Fine-needle aspiration of the breast: A review of 1,995 cases with emphasis on diagnostic pitfalls

Between 1985 to 1989, 1, 95 fine-needle aspirations of palpable breast lesions were performed at our institution. In all cases, the aspirates were procured by cytopathologists using 22- or 23-gauge needles. Direct smears were immediately stained with Diff-Quik and Papanicolaou and assessed for specimen adequacy (criteria as followed in this institution). Tissue follow-up was available in 1,117 cases. The cytologic diagnoses rendered in these cases were: malignant, 690 cases (60.2%); suspicious for carcinoma, 49 cases (4.3%); benign, 343 cases (29.9%), and insufficient specimen, 35 cases (3.1%). There were 28 false-negative and 2 false-positive results. Considering only cases definitively diagnosed as benign or malignant, the sensitivity was 96%, specificity 99%, positive predictive value 99%, negative predictive value 94%, and overall efficiency 97%. Of those specimens considered suspicious, only 11 cases (22%) were proved not to be malignant after excisional biopsy. These were three fibroadenomas, three ductal hyperplasias, two adenosis tumors, two mucocele-like lesions, and one nipple adenoma. The two lesions that resulted in true false-positive diagnoses were an apocrine cyst with atypia and sclerosing adenosis with radial scar. The clinical and cytologic features of the benign conditions that resulted in false suspicious and positive diagnoses and those features that distinguish them from carcinoma are presented.     

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.     

Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48 %) were classified as malignant and 9 cases (1.49 %) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76 %). There were 26 (4.3 %) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95 %). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.