Application of the probabilistic approach to reporting breast fine needle aspiration in males

OBJECTIVE: To apply the probabilistic approach to a series offine needle aspiration (FNA) samples of male breast lesions and determine the accuracy and reproducibility of this method of reporting in men. STUDY DESIGN: All male breast surgical specimens with a preoperative breast FNA at our institution from 1994 to 2005 were identified. The FNAs were blindly reviewed by 2 groups of observers and classified in 1 of 5 categories using published reporting guidelines: positive, suspicious, atypical, proliferative without atypia and unremarkable. The histologic and cytologic diagnoses were correlated. The interobserver variation was determined. RESULTS: A total of 138 FNAs were performed for 123 male patients. Histologic correlation was available for 23 satisfactory FNAs. A total of 11 of 11 carcinomas (100%) were classified as positive, suspicious or atypical. Of 12 benign masses, 11 (91.6%) were classified as proliferative without atypia or unremarkable. One case of gynecomastia was classified as atypical by 1 observer but deemed not atypical with consensus review. The kappa statistic for benign and atypical/suspicious/malignant categories was 0.90. CONCLUSION: Based on this series, the probabilistic approach can be applied to the reporting of FNAs of male breast lesions. Gynecomastia may result in an atypical cytologic diagnosis.     

Positive predictive value of fine needle aspiration cytology of breast lesions

The predictive value of fine needle aspiration (FNA) was assessed in 1,181 consecutive cases of breast lesions in which cytologic abnormalities were reported. The positive predictive value (PPV) of an FNA cytologic report of atypia, suspicious or positive was 0.49, 0.95 or 0.996, respectively. In the presence of a suspicious/positive report by both physical examination and mammography, the PPV of a cytologic report of suspicious was 0.99. The PPV was directly correlated with age, partly due to the incidence of fibroadenomas among younger patients; fibroadenomas were present in 53 of 146 cases with a false FNA report of atypia, in 10 of 19 cases with a false FNA report of suspicious and in 2 of 2 cases with a false FNA report of positive. Overall, 93 cases reported as benign by physical examination and mammography were biopsied on the basis of the FNA cytologic report; cancers were diagnosed in 33 of these 93 cases (6 cancers among 42 women less than 40 years old and 27 cancers among 51 women greater than 39 years old). The widespread use of FNA cytology to study breast lesions is thus recommended, without regard to patient age and even in the presence of clinically benign findings, since the increase in the rate of cancer detection is worth the excess of unnecessary biopsies. The predictive value of a positive report of FNA cytology, or even of a suspicious report in the presence of clinical suspicion, is so high that an intraoperative frozen section biopsy might be spared in such cases.     

Fine needle aspiration of poorly defined indurated and well-defined breast lesions: a cytopathologic comparative study

OBJECTIVE: To compare the cytologic findings and diagnoses of breast fine needle aspiration (FNA) samples of well-defined lesions (WDL) with those of poorly defined indurated lesions. STUDY DESIGN: We examined 371 consecutive breast FNA specimens obtained without diagnostic image guidance. Fifty-eight lesions were described by the examining pathologists as PDILs, and the remaining 313 lesions were described as WDLs. RESULTS: Compared with WDLs, PDILs were more likely to yield hypocellular specimens deemed unsatisfactory for diagnostic evaluation (37.9% vs. 14.1%). However, a substantial number of atypical, suspicious for malignancy and malignant cases (12.1%, 5.2%, and 13.8%, respectively) were identified with PDILs. In addition, benign diagnoses were more frequently rendered with aspirates of WDLs, compared with PDILs (47.9% vs. 31.0%). In our study, FNAs of PDILs were more often diagnostic in white women < 49 years of age and in lesions measuring > 2 cm. CONCLUSION: Given the relatively high frequency of malignant, suspicious and atypical lesions detected with PDILs, FNA is a suitable first diagnostic approach for PDILs, especially considering the relatively low cost and simplicity of FNA procedures without diagnostic imaging guidance.     

Ultrasound-guided fine needle aspiration cytology of impalpable breast lesions in a rural setting. Comparison of cytology with imaging and final outcome

OBJECTIVE: To analyze the effectiveness of fine needle aspiration (FNA) cytology in a multidisciplinary setting in rural Australia and to compare the imaging (mammographic and ultrasound) appearances and cytomorphologic findings with the final outcome. STUDY DESIGN: Prospective analysis of ultrasound-guided FNA cytology results from 426 women, aged 40-86 years, with screening-detected mammographic abnormalities. Cases of microcalcification, assessed mainly by stereotactatic core biopsy, were not included in the study. The FNAs were performed at a rural breast screening and assessment program in New South Wales, Australia, over a three-year period between May 1993 and May 1996. RESULTS: Imaging, FNA and combined imaging and FNA results from 426 women were as follows. The imaging diagnoses included 176 (41%) benign, 34 (8%) probably benign, 17 (4%) equivocal, 104 (24%) suspicious and 95 (23%) malignant cases. The FNA findings showed 59 (14%) no epithelial cells seen (nondiagnostic), 175 (41%) benign, 36 (8%) atypical, 41 (10%) suspicious and 115 (27%) malignant. Combined imaging and cytologic results comprised 224 (52.6%) benign, 10 (2.3%) atypical/equivocal, 59 (13.9%) suspicious and 133 (31.2%) malignant cases. All the malignant cases, by combined assessment, had malignant histology, and all the benign cases behaved in a benign fashion. In 80% of the suspicious lesions, the histologic diagnosis was malignant, but only 10% of the atypical/equivocal lesions had malignant histology. The positive predictive value of diagnosis of malignancy by combined imaging and FNA was 100%, and the false negative rate was 0%. CONCLUSION: Despite the recent surge in the popularity of core biopsy, FNA cytology of impalpable, mammographically detected lesions, when practiced in a multidisciplinary setting, is an extremely accurate test with high sensitivity, specificity, predictive values and efficacy. FNA cytology of the breast is a well-tolerated, relatively noninvasive test with a very low risk of complications. The sensitivity and positive predictive values for malignant and suspicious mammographic categories are also very high.     

Improving recognition of thyroid carcinoma in rapid-consultation specimens

OBJECTIVE: To improve recognition of thyroid carcinoma in rapid consultation on Diff-Quik-stained (Fisher Diagnostics, Middletown, Virginia, USA.) fine-needle aspiration (FNA) and rapid hematoxylin-eosin (H-E)-stained intraoperative scrape preparation (ISP) specimens by assessing 3 variables (anisokaryosis, nuclear overlap [NO] and scant/absent colloid) in cases of cellular follicular lesions (CFL), an indeterminate diagnostic category. STUDY DESIGN: Thirty-seven FNAs and 28 ISPs diagnosed as CFL, with histologic follow-up, were evaluated in blinded fashion by 3 cytopathologists assessing the 3 variables. RESULTS: Over 90% of the malignant cases showed NO in both FNA and ISP, while only 22% of the benign cases did; positive and negative predictive values (PPV and NPV) were 82% and 100%. All malignant cases showed significant anisokaryosis in both FNA and ISP in contrast to 24% of benign cases; PPV and NPV were 74% and 100%. Scant/absent colloid was seen in 87% and 39% of malignancies in FNA and ISP, respectively, as compared to 55% and 20% of the benign cases. PPV and NPV were 52% and 83% in FNA and 63% and 60% in ISP, respectively. CONCLUSION: Application of these variables improves recognition of thyroid carcinoma, particularly in fine needle aspirates, while additional material may be requested. With ISP, their absence supports recommending against further surgery. Together, optimal surgical planning and outcome may be obtained.     

Statistical analysis of fine needle aspiration cytology of the breast. A review of 678 cases plus 4,265 cases from the literature

Between 1979 and 1984, 678 breast fine needle aspiration (FNA) cytologic specimens were received in our laboratory; tissue follow-up was available for 159 cases (23%). The diagnoses rendered in cases with subsequent tissue study were benign (41%), insufficient (10.5%), atypical and/or suspicious for carcinoma (10.5%) and malignant (38%). Using the tissue diagnosis as the standard, there were four false-negative cytologic results and one false-positive result. Considering only cases with a definitive diagnosis of benign or malignant, the sensitivity of cytologic interpretation for diagnosing malignancy on adequate material was 94% while the specificity was 98%; the overall efficiency of the test was thus 96%. The predictive values were 98% for a positive test and 94% for a negative test. Of the total number of submitted cases, a correct and definitive diagnosis was rendered 76% of the time. Calculation of similar statistics from six other series in which the FNA cytologic diagnoses were compared with the histologic diagnoses yielded data almost identical to our findings. The high degree of uniformity in the data indicates that these statistical parameters can be used as standards for evaluating the efficiency of breast FNA cytology.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

Renal fine needle aspiration cytology

OBJECTIVE: To audit and evaluate the pitfalls in renal fine needle aspiration (FNA) cytology. STUDY DESIGN: A retrospective analysis of 180 renal FNAs from 163 patients, encountered at Canberra Hospital, Australian Capital Territory, between June 1989 and July 1997 was undertaken. The FNA procedures had been performed by radiologists under computed tomography (CT) or ultrasound (US) guidance. The study correlated the FNA results with biopsy findings and clinical outcome. RESULTS: The initial cytologic diagnoses included 84 (47%) benign, 6 (3%) atypical, 7 (4%) suspicious, 70 (39%) malignant and 13 (7%) inadequate. Six of the 13 cytologically inadequate group, on further investigation, had malignant histology. The benign cytologic categories contained 79 benign conditions and 5 cases with a malignant outcome. The atypical cytologic group contained 5 benign and 1 malignant case. All nine cytologically suspicious cases had malignant histology. The cytologically malignant group contained 62 malignant, 7 benign and 1 patient lost to follow-up. The sensitivity was 92.5%, specificity was 91.9%, positive predictive value was 89.9%, negative predictive value was 94.0%, and efficacy of the test was 92.2%. CONCLUSION: Renal FNA can provide an accurate diagnosis in most instances; however, aspiration cytology of the kidney has limitations and pitfalls. Low grade renal cell carcinoma has to be differentiated from oncocytoma, angiomyolipoma, renal infarct and reactive conditions. Renal FNA has a high negative predictive value, which is useful in reassuring patients with radiologically and cytologically benign lesions. Negative FNA does not exclude malignancy in the presence of a radiologic suspicion.     

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.     

Cumulative sum procedure in evaluation of EUS-guided FNA cytology: the learning curve and diagnostic performance beyond sensitivity and specificity

Background: Using cumulative sum (CUSUM) chart, we address two questions: (i) Over time, how will an EUS‐FNA (endoscopic ultrasound guided fine needle aspiration) service maintain an acceptable non‐diagnostic rate defined as technical failures, unsatisfactory specimens and atypical and suspicious diagnoses? (ii) Over time, how will EUS‐FNA maintain acceptable diagnostic errors (false‐positives plus false‐negative diagnosis)? Methods: The study included all consecutive patients who underwent EUS‐FNA at our institution from July 2000 to October 2003 and were followed up until December 2004. Using a simple spread sheet, we designed CUSUM charts and used them to track trends and assess performance at a preset acceptable rate of 10% and a preset unacceptable rate of 15% for non‐diagnostic rate and diagnostic errors. We assessed all cases collectively and then in groups defined by site, size and cytopathologist. Results: Of 876 patients undergoing EUS‐FNA, 83 (9.5%) had non‐diagnostic results: 43 (51%) of these diagnoses were ‘atypical’, 27(33%) were ‘suspicious for malignancy’, eight (10%) were ‘insufficient material for diagnosis’ and five (6%) were ‘technical failure’. In 585 cases with adequate follow up, there were 26 (6.3%) diagnostic errors: three (0.5%) were false positive and 23 (3.1) were false negative. The overall CUSUM charts for both non‐diagnostic rate and for diagnostic error rate start with a small period of learning then cross to a significantly acceptable level at case numbers 121 and 97 respectively. Our diagnostic performance was better in lymph nodes than in the pancreas and other organs and was not significantly different for lesions ≤25 mm compared with lesion >25 mm in diameter. Performance was better for pathologists with prior experience than for pathologists without experience. Conclusion: In the current climate of proficiency testing, error tracking and competence evaluation, there is a great potential for the use of CUSUM charts to assess procedure failure and error tracking in quality control programs, particularly when a new procedure such as EUS‐FNA is introduced in the laboratory. Additionally, the method can be used to assess trainee competency and to track the proficiency of practicing cytologists.     

BRAF Mutation Testing of Thyroid Fine-Needle Aspiration Specimens Enhances the Predictability of Malignancy in Thyroid Follicular Lesions of Undetermined Significance

Background/Objective: The Bethesda 2007 Thyroid Cytology Classification defines atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) as a heterogeneous category of cases that are neither convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. At our institution, we refer to these cases as 'indeterminate' and they are further subclassified into two categories. BRAF mutation occurs in 40-60% of papillary thyroid carcinoma (PTC). In this study, we examined cases in the AUS/FLUS category in correlation with BRAF mutation analysis and surgical pathology outcome. Study Design: Thyroid fine-needle aspiration (FNA) cytology specimens interpreted as 'indeterminate' were selected from our files, and available remnants of thin-layer processed specimens were used for BRAF mutation analysis. Surgical pathology reports were reviewed for the final outcomes in these patients. Results: Of the 84 indeterminate cases with BRAF mutation analysis, only 49 had follow-up with surgical intervention. Sixteen cases had BRAF mutation. All of the BRAF-positive cases had a final diagnosis of PTC. Conclusions: The sensitivity and specificity of BRAF mutation in detecting PTC in FNA specimens with indeterminate diagnosis was 59.3 and 100%, respectively, while the positive and negative predictive values were 100 and 65.6%, respectively. The limited data supports the use of BRAF mutation analysis to predict the risk of malignancy in patients with indeterminate thyroid FNAs.     

Interobserver variability in the fine needle aspiration biopsy diagnosis of follicular lesions of the thyroid gland

OBJECTIVE: To study the degree of interobserver variability in the interpretation of fine needle aspiration (FNA) biopsies of the thyroid, specifically in the categorization of follicular lesions (FLs), and to examine the accuracy of FNA diagnosis of FLs with surgical follow-up. STUDY DESIGN: Fifty cases were chosen with surgical follow-up and a cytologic diagnosis of either FL (21) or follicular neoplasms (29). Representative slides were selected for each case and circulated to 4 pathologists for review. Interobserver variability was assessed using pairwise K statistics. Accuracy of the cytologic diagnoses in predicting a nonneoplastic or neoplastic outcome was determined by measuring sensitivity and specificity. Likelihood ratios and receiver operator characteristic curves were calculated for each reviewer. RESULTS: Interobserver agreement between the 4 pathologists was fair to substantial (K scores, 0.199-0.617). The accuracy of the 4 pathologists' cytologic diagnoses in predicting the surgical outcome was 77-90% for follicular neoplasms and 53-74% for nonneoplastic diagnoses. CONCLUSION: FLs present diagnostic difficulties as to cytologic categorization. A wide range of interobserver agreement was found in this study of 4 pathologists from the same institution. Some pathologists make greater use of intermediate categories, such as FL, favor nonneoplastic, or FL, favor neoplastic, whereas others show more definitive categorization into benign and neoplastic groups.     

Fine needle aspiration of benign and malignant breast masses associated with pregnancy.

Of 1,612 fine needle aspirates (FNA) of breast lesions performed over a seven-year period, 25 cases (1.5%) were identified as breast masses associated with pregnancy. Patients ranged in age from 16 to 46 years, with a mean of 27. Gestational age at the time of FNA ranged from three months to three months postpartum or following breast-feeding. Cytologic diagnoses of these pregnancy-associated breast masses were: galactocele (5 cases, 20%), lactating adenoma (9 cases, 36%), fibroadenoma with lactational change (7 cases, 28%), juvenile fibroadenoma with lactational change (1 case, 4%), atypical reactive duct cells with lactational change (1 case, 4%) and infiltrating duct carcinoma (2 cases, 8%). The degree of lactational change varied proportionately with gestational age. None of the 22 patients with benign cytologic diagnoses of galactocele, lactating adenoma or fibroadenoma subsequently developed carcinoma. The mean clinical follow-up for these 22 patients was 27 months. Three cases of fibroadenoma and the case of juvenile fibroadenoma were confirmed by surgical excision. Biopsy of the lesion cytologically diagnosed as atypical reactive duct cells with lactational change revealed infiltrating duct carcinoma (IDC). All three patients with IDC had involvement of multiple axillary lymph nodes, and 1 patient had widely metastatic disease. In two cases of IDC the background lactational breast epithelium exhibited marked cytologic atypia that closely resembled the IDC. Pregnancy-related cellular atypia potentially results in a false-positive diagnosis of breast carcinoma on FNA. FNA is useful in distinguishing benign breast masses of pregnancy from those with marked cytologic atypia requiring surgical biopsy and may minimize the delayed diagnosis of carcinoma associated with pregnancy.     

Value of fine needle aspiration in the diagnosis of breast lesions.

OBJECTIVE: To evaluate the accuracy values of 276 fine needle aspriations (FNA) of breast lesions with a subsequent excisional biopsy diagnosis and to make a comparison between 25 studies of the literature using the same criteria to calculate those values. STUDY DESIGN: Cytologic findings were compared with the histologic diagnosis of each mass. The correlation of results was analyzed by a decision-analysis approach, and the following values concerning diagnostic accuracy were calculated in the present study and in 25 other reports: sensitivity, specificity, positive predictive value, negative predictive value, false positive fraction and false negative fraction. To calculate those values, we eliminated unsatisfactory results and assumed that suspicious and positive cytologic findings represented carcinoma of the breast. RESULTS: Comparing our results with the means in the literature (numbers in parenthesis), FNA detected cancer with a sensitivity of 92.1% (87.7%), specificity of 98.6% (94.7%), positive predictive value of 99.4% (92.8%), negative predictive value of 82.1% (90.7%), false positive fraction of 0.6% (7.1%) and false negative fraction of 17.9% (13.4%); in 6.2% of cases the material was unsatisfactory (13.4%). CONCLUSION: All the rates varied enormously between the studies and during the past 13 years. It seems that false positive and false negative fractions tended to diminish and stabilize in more recent years, and specificity and sensitivity underwent a slight increase. The differences between the rates of those studies suggest that FNA of the breast has some unavoidable limitations.     

Value of fine needle aspiration cytology of the breast, with an emphasis on the cytodiagnosis of colloid carcinoma.

The fine needle aspiration (FNA) cytologic evaluation of 6,941 lesions of the breast was reviewed, with an emphasis on the cytodiagnosis of colloid carcinoma. The most common benign breast diseases in this series were fibroadenomas, cysts and fibrocystic conditions. All cases with an FNA diagnosis of suspicious were biopsied; a number of these were found to be carcinoma of the breast. In cases with an FNA diagnosis of carcinoma of the breast, a plan of management was immediately adopted on the basis of that diagnosis. Thirteen cases of colloid (mucinous) carcinoma of the breast were diagnosed by FNA cytology; in all, the cytodiagnosis was confirmed by the subsequent histologic diagnosis. The distinctive cytologic criteria that may be useful for making an FNA diagnosis of colloid carcinoma of the breast are discussed, and the FNA differences between the pure and mixed types of colloid carcinoma are noted.     

Fine needle aspiration of breast lesions in women aged 30 and under

Fine needle aspiration (FNA) biopsies of 1,598 breast masses were performed between 1983 and 1989, and of them, 48 were from women aged 30 and under for whom a cytologic diagnosis was made by FNA and histologic follow-up was available. In 37 (77%) of the cases, both the cytologic and histologic diagnoses were benign. Fibroadenoma (20/37) and fibrocystic changes (14/37) were the most common benign lesions aspirated. Eight (17%) FNAs showed cytologic atypia. Four of these atypical lesions proved to be benign (two fibroadenomas, two fibrocystic changes). Epithelial proliferation in fibroadenomas and fibrocystic changes and cellular stroma in a fibroadenoma mimicking phylloides tumor were the causes of atypia in these biopsies. Four of the eight atypical lesions were shown to be carcinoma at biopsy (three infiltrating duct, one atypical medullary). Low cellularity, epithelial cohesiveness mimicking a fibroadenoma and background lactational changes in a pregnant patient were the causes of the atypical, rather than unequivocally malignant, diagnoses in these cases. In three patients (6%), a diagnosis of carcinoma was made by FNA and confirmed histologically (all were infiltrating duct carcinoma). Although most breast masses in women aged 30 and under are benign, cytologic atypia in a breast fine needle aspirate in this age group warrants a surgical biopsy. Clinical follow-up alone may be appropriate for young women with clinically nonsuspicious breast masses without cytologic atypia.     

Accuracy of cytologic interpretation of pancreatic neoplasms by fine needle aspiration and pancreatic duct brushings

OBJECTIVE: To investigate the accuracy of fine needle aspiration (FNA) specimens and pancreatic duct brushings in the detection of pancreatic lesions and to compare the results with follow-up biopsy and/or surgical interpretation. STUDY DESIGN: We reviewed a total of 57 specimens (37/20), 37 FNA specimens and 20 pancreatic duct brushings, from 45 patients treated at Froedtert Memorial Lutheran Hospital, affiliated with the Medical College of Wisconsin, Milwaukee, over a 4-year period. The FNA and brushing samples were categorized as follows: positive for malignancy (21/3 = 24), suspicious for malignancy (8/7 = 15) and atypical (8/10 = 18). The results were then correlated with the tissue diagnosis. RESULTS: The 24 cytologic samples positive for malignancy included 23 (20/3) pancreatic ductal carcinoma (CA) and 1 (1/0) neuroendocrine CA; in the suspicious category, 11 (6/5) were pancreatic ductal CA; 2 (0/2) mucinous neoplasms and (2/0) neuroendocrine neoplasms; in the atypical category; 2 (2/0) suggestive of mucinous neoplasia, 1 (1/0) suggestive of serous neoplasia and 9 (2/7) favor reactive; and 6 (3/3) without further categorization. Tissue diagnoses were available in 26 cases: 12 (10/2) cases positive for malignancy, 8 (5/3) suspicious for malignancy and 6 (5/1) atypical. The 12 cytologically positive cases confirmed by histology showed 10 ductal CA, 1 neuroendocrine CA and 1 negative. All 8 cases (100%) suspicious for malignancy revealed positive results, including 5 ductal CA, 1 neuroendocrine neoplasm, 1 mucinous cystic neoplasm and 1 lymphoma. Of the 6 atypical lesions, 1 showed ductal CA, 2 mucinous cystic neoplasm and 3 chronic pancreatitis. CONCLUSION: Pancreatic FNA and duct brushings [table: see text] are accurate methods in identifying pancreatic lesions, particularly ductal CA. Accuracy can be improved in the case of mucinous and other lesions with adequate cellularity of the smear and recognizing the limitations of brush samples in the case of mucinous cystic lesions. False negative results may occur in cases of poor representation of malignant cells or poor sampling.     

Endoscopic ultrasound-guided fine needle aspiration of the pancreas. Diagnostic utility and accuracy

OBJECTIVE: Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) is regarded as a safe and reliable procedure for diagnosing and staging of pancreatic neoplasms. This study retrospectively evaluated both the diagnostic utility and accuracy of pancreatic EUS-FNABs and potential cytologic pitfalls when using Diff-Quik stain for on-site evaluation. STUDY DESIGN: Pancreatic EUS-FNABs performed between 1995 and 1998 were identified from the files of the Department of Pathology. All patients were studied via a linear-array ultrasound endoscope with an FNAB device. Immediate evaluation of the specimen by a pathologist using air-dried slides and Diff-Quik stain was done on all cases. An average of five passes (range, three to nine) were performed. Five cytologic categories were identified: nondiagnostic, benign, atypical, suspicious and malignant. EUS disease staging, histologic correlation and clinical follow-up were reviewed. RESULTS: Sixty-nine consecutive pancreative FNABs were evaluated in the study period. The patients comprised 38 females and 31 males with a mean age of 65 years (range, 36-83). Histologic correlation was available on 40 patients, and follow-up was available on the remaining 29. The cytologic diagnoses included: 31 malignant, 8 suspicious, 6 atypical, 20 benign and 4 nondiagnostic. Forty-three cases were true positive, 9 were true negative, 2 were false positive, and 11 were false negative. The overall sensitivity was 80% and specificity was 82%. CONCLUSION: The study showed that cytologic evaluation of pancreatic EUS-FNABs has 80% sensitivity and 82% specificity. False negative diagnosis was usually due to sampling error. A nondiagnostic cytologic diagnosis should be rendered in the absence of adequate sampling of a lesion. On-site cytologic evaluation of EUS-FNABs aids in guaranteeing specimen adequacy, and the pathologist should be trained to evaluate Diff-Quik-stained samples.     

Negative predictive value of pulmonary fine needle aspiration cytology.

Percutaneous fine needle aspiration (FNA) for cytologic examination is an accepted and reliable technique for diagnosing neoplasia. It is less useful, however, in excluding that diagnosis. We performed a retrospective analysis of a consecutive series of pulmonary FNA specimens at Memorial Sloan-Kettering Cancer Center to determine the negative predictive value (NPV) of this technique in the setting of a large cancer hospital. Fifty-seven cases were studied. Six cases (10.5%) were initially diagnosed as negative but acellular and were not further analyzed, and another 6 were lost to follow-up; 24 cases (42.1%) were subsequently confirmed negative by tissue or clinical follow-up, and 21 of the cases (36.8%) were proven positive for malignancy by repeat aspiration, tissue diagnosis or clinical means. Of these 21 cases, 1 was misdiagnosed as negative, and review demonstrated malignant cells on the slide; 3 of the 21 cases should have been initially rejected as unsatisfactory, and 18 of the 21 contained material sufficient for a cytologic diagnosis but not representative of the lesion. On follow-up the false-negative cases showed primary adenocarcinoma, epidermoid carcinoma, lymphoma, metastatic breast carcinoma and metastatic sarcoma. Specific benign diagnoses were made on the initial cytologic preparation in three cases. No benign tumors were found. The NPV in our series was 53.3%, comparable to values in previous reports. The single largest factor contributing to false-negative diagnoses is sampling error, and we recommend repeat aspiration when no specific benign diagnosis is made. In addition, we suggest that the diagnoses of negative for malignant cells and insufficient for diagnosis or acellular be considered separate categories.     

Surgical Utility of Afirma: Effects of High Cancer Prevalence and Oncocytic Cell Types in Patients with Indeterminate Thyroid Cytology

ObjectiveThe Afirma Gene Expression Classifier (GEC) molecular marker assay was developed for the purpose of improving surgical decision-making with indeterminate fine-needle aspiration (FNA) biopsies of thyroid nodules. In this paper, we analyze the performance of the GEC over 27 months in a community hospital-based thyroid surgery practice.MethodsWe began using GEC and Thyroid Cytopathology Partners (TCP) exclusively for thyroid FNA analysis in January 2011, shortly after the Afirma GEC became commercially available. In this paper, we focus on patients with indeterminate FNA results and the outcomes of GEC analysis, with particular attention paid to the calculation of the negative predictive value (NPV) of the Afirma test.ResultsWe performed 645 FNAs in 519 patients over 27 months. Overall, 58 FNAs (9%) were read as indeterminate, with 36 of these classified as suspicious by GEC (62%), 20 characterized as GEC benign (34%), and 2 determined to be inadequate due to low mRNA content. Of the 36 suspicious GEC patients, 30 underwent thyroidectomy, and 21 of the 30 had malignant final pathology. Of the 20 benign GEC patients, 5 underwent thyroid surgery, and 2 were discovered to have malignancies. The NPV for the Afirma GEC in our practice environment was 89.6%.ConclusionIn a practice with a high incidence of thyroid cancer in patients with indeterminate FNAs (33% for our practice), the NPV of the Afirma GEC test may not be as robust as suggested in the existing literature. (Endocr Pract. 2014;20:364-369)