Diagnostic value of unusual gross appearance of aspirated material from endoscopic ultrasound-guided fine needle aspiration of pancreatic and peripancreatic cystic lesions

OBJECTIVE: To evaluate the diagnostic value of the gross appearance of aspirated material from endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic orperipancreatic cystic lesions. STUDY DESIGN: This study focuses on nonneoplastic (peri)-pancreatic cystic lesions on EUS-FNA. Eight cases were identified with distinct gross appearances of aspirated material by the authors' experience and by computerized review. Gross observations are evaluated together with clinical data, radiologic findings, laboratory markers and cytologic and surgical microscopy findings. RESULTS: Aspiration of cystic lesions often results in nonspecific cytologic findings. Gross and microscopic appearance of aspirated material can provide valuable information. We divide findings of 8 cystic lesions into 3 different patterns according to their gross appearance at on-site EUS-FNA: Pattern 1, 2 cases of biloma; Pattern 2, 1 case of lymphoepithelial cyst with sebaceous differentiation; Pattern 3, 3 cases of regular lymphoepithelial cysts and 2 cases ofpancreatic pseudocyst. CONCLUSION: The full value of FNA is achieved only with the integrated approach, including the gross appearance of the cytology specimens. Certain unusual gross appearances of the aspirated material can add valuable information toward a pathologic diagnosis.     

Fine needle aspiration cytology and immunocytochemistry in a case of intrathoracic thyroid goiter

Fine needle aspiration (FNA) was performed in the case of a patient with an anterior mediastinal mass. Examination of the smears revealed individual and groups of benign nondiagnostic cells. Surgical removal and histologic examination indicated that the mass was a true intrathoracic thyroid goiter. Subsequent immunocytochemical studies on the FNA smears showed thyroglobulin in the cytoplasm of the aspirated cells. The cytologic findings are presented; while not diagnostic of a thyroidal origin in this case, they serve as a reminder of the wide range of cytologic appearances of colloid nodules and goiters. This case will hopefully heighten the awareness of cytologists and other physicians to the consideration of the possibility of intrathoracic goiter in the differential diagnosis of mediastinal lesions seen in fine needle aspirates.     

Serial fine needle cytology in the diagnosis of esophageal cancer

OBJECTIVE: To describe a method of registering local spread of cancer in the esophageal wall through serial endoscopic fine needle aspiration (FNA), to evaluate FNA as a diagnostic tool as compared to histologic biopsies and brush cytology, and to investigate cytologic appearances of aspirates and correlate them with survival STUDY DESIGN: Fifty-two patients with esophageal cancer were investigated with serial FNA every second centimeter from the upper esophageal sphincter aborally down to the level of macroscopic tumor. Histologic biopsies and brush cytologies were then performed. RESULTS: Of investigated cases, 33% showed malignant or suspect malignant cells from macroscopic tumor, at > or = 4 cm orally, as did 3 of 12 patients at 14 cm. FNA was more sensitive than brush cytology in establishing the diagnosis. A high ratio between the numbers of benign and malignant cells in aspirates from gross tumor tissue correlated with shorter survival (P < .03). CONCLUSION: Serial FNA can demonstrate local microscopic tumor spread in the wall of the esophagus in vivo in esophageal cancer patients. FNA is also a useful adjunct in establishing the diagnosis. Finally, evaluations of tumor cytology may have prognostic value.     

Posters. P1 A 2‐year audit of thyroid fine needle aspiration cytology

Introduction Fine needle aspiration (FNA) cytology of the thyroid is a well‐established test in the clinical work‐up of patients with solitary nodules of the thyroid. Thyroid FNA does however have limitations and audit of diagnostic performance is important. Methods The histopathology archives of the Royal Victoria Hospital were searched for all thyroid resections and the histopathological diagnosis was correlated with the pre‐operative cytological diagnosis, where available. Special emphasis was placed on the accuracy of tumour diagnosis. Results A total of 173 cases were identified during the 2‐year period, of these 93 had available pre‐operative FNA. A total of 57 tumours were identified. A small number (six of 57) of significant discrepancies were identified. These included a malignant lymphoma diagnosed as Hashimoto's thyroiditis, a metastasis which the FNA had suggested was a medullary carcinoma and an insular carcinoma diagnosed as medullary carcinoma on FNA. False positives included a colloid cyst diagnosed as suspicious of malignancy and a cytological diagnosis of papillary carcinoma not confirmed on histology. Discussion At present, the majority of thyroid FNAs in our clinics are performed by surgeons and material is not routinely available for immunocytochemistry. In spite of these limitations, there were few major discrepancies. These might be reduced if pathologist aspirators were able to perform FNAs and collect material for further studies, where necessary. This would allow identification of medullary carcinomas and malignant lymphomas. Conclusion FNA of thyroid lesions is a useful investigation in our clinical setting, however, some areas of potential for improvement have been identified.     

Selective use of electron microscopy in fine needle aspiration cytology

The utility of electron microscopy (EM) applied to fine needle aspiration (FNA) biopsy specimens was analyzed in order to determine the role and the diagnostic contribution of the EM examination. A rapid stain (Diff-Quik) was used to obtain a preliminary diagnostic impression and to assure the adequacy of the EM specimen for problematic cases. Our experience suggests that EM is being relied upon with greater frequency in the study of FNA specimens because it is an accurate and cost-effective diagnostic procedure. The use of a rapid interpretation (Diff-Quik stain) enhances the quality of the EM specimen and, as in surgical pathology, the EM examination increases the accuracy and specificity of the FNA biopsy diagnosis.     

Diagnosis of deep‐seated lymphomas by endoscopic ultrasound‐guided fine needle aspiration combined with flow cytometry

A. Stacchini, P. Carucci, D. Pacchioni, G. Accinelli, A. Demurtas, S. Aliberti, M. Bosco, M. Bruno, A. Balbo Mussetto, M. Rizzetto, G. Bussolati and C. De Angelis
Diagnosis of deep‐seated lymphomas by endoscopic ultrasound‐guided fine needle aspiration combined with flow cytometry Objective: Although endoscopic ultrasound combined with fine needle aspiration (EUS‐FNA) is rapidly becoming the preferred diagnostic approach for the sampling and diagnosis of gastrointestinal and mediastinal malignancies, there are limited data as to its use in the diagnosis of lymphoproliferative disorders. Therefore, we carried out a retrospective evaluation of the performance of EUS‐guided FNA combined with flow cytometry (FC) as a tool to improve overall sensitivity and specificity in the diagnosis of lymphoma. Methods: Of 1560 patients having EUS‐guided FNA during the period of the study, a total of 56 patients were evaluated by cytology with FC after EUS‐FNA. There was adequate material to perform FC analysis for all but one case. Results: EUS‐FNA‐FC gave a diagnosis of lymphoma in 11 cases and of reactive lymphadenopathy in 20. A specific histological type was defined by FC alone in eight cases. The remaining cases were diagnosed later by cytology and cell block sections: 13 carcinomas, nine granulomatous lymphadenopathies and one mediastinal extramedullary haematopoiesis. One case was considered only suspicious for lymphoma on cytology and FC but was not confirmed on molecular analysis and one had insufficient material for FC. Conclusions: Our results show that a combination of EUS‐FNA‐FC is a feasible and highly accurate method, which may be used for the diagnosis and subtyping of deep‐seated lymphoma, providing a significant improvement to cytomorphology alone both for diagnosis and treatment planning, as long as immunocytochemistry is available for non‐lymphoma cases.     

Renal FNA-based typing of renal masses remains a useful adjunctive modality: evaluation of 31 renal masses with correlative histology

Objectives:  Given the advances in renal imaging modalities in the recent years, a greater number of renal cell carcinomas (RCCs) with tumour size of <3 cm are being detected radiologically. Consequently, there is a pressing need for accurate typing of RCCs which, in turn, will aid in selection of cases of nephron-sparing surgery.
Methods:  A total of 31 cases of renal masses with available fine needle aspiration (FNA) material and concomitant histopathology details were retrieved. They included 27 RCCs (17 clear cells, eight papillary and two chromophobe), one oncocytoma, one liposarcoma and two benign lesions – one xanthogranulomatous pyelonephritis (XPN) and one benign cyst. Two investigators reviewed all FNA material. The degree of concordance between cytological typing and histological typing was assessed.
Results:  There was excellent agreement between the FNA typing and the final diagnosis, with correct classification in 28 of 31 cases. Among the three discordant cases, two were RCCs. The first was a papillary RCC (PRCC) that was misdiagnosed on FNA as clear cell RCC. Another case that was typed as a PRCC on final histopathology was diagnosed 'suspicious cells' on FNA. The third case was an XPN that was misdiagnosed on FNA as RCC with necrosis.
Conclusions:  There is an excellent concordance (90.3%) between the FNA diagnosis and the final histological diagnosis, especially in RCCs. There is a tendency for misdiagnosis with PRCC. Lesions with extensive necrosis and relatively insufficient diagnostic material on FNA specimens must be interpreted with caution. Better concordance might be observed with more extensive sampling.     

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.     

Fine needle aspiration cytology of cystic parathyroid lesions. A cytomorphologic overlap with cystic lesions of the thyroid

Three cases of palpable cystic parathyroid nodules examined by fine needle aspiration (FNA) cytology are reported. Two of the three aspirates were incorrectly identified as thyroid neoplasms due to the presence of papillary clusters or microfollicles and grossly golden-brown cyst fluid. Histologic examination of these two nodules revealed partially cystic parathyroid adenomas. Aspirated material from the third patient yielded clear watery fluid, which was correctly identified as consistent with a parathyroid cyst. The diagnostic difficulties in the differentiation of parathyroid adenoma from thyroid carcinoma or adenoma are discussed, as is the utilization of assays for parathyroid hormone in making the FNA diagnosis of parathyroid lesions.     

Filtration and agar embedding applied to fine needle aspirates for tumor diagnosis by electron microscopy. A combined technique.

OBJECTIVE: To develop a novel method for processing of fine needle aspirates subjected to electron microscopic (EM) study. STUDY DESIGN: Included 70 cases of poorly differentiated malignant tumors in which a definitive diagnosis was not possible on light microscopic (LM) examination and that thus required application of an ancillary technique such as FNA/EM, for diagnosis. We have established a novel method of processing, a technique of filtration through nylon mesh filters to eliminate red blood cells (RBCs) and necrotic debris, followed by agar well embedding to avoid loss of diagnostic material during processing without centrifugation at later steps after agar embedding, thus minimizing the time required for processing. It was successfully carried out in 70 cases. RESULTS: The combined technique was extremely effective in eliminating RBCs and necrotic debris. It also avoided further loss of valuable diagnostic material. An accurate diagnosis was rendered in 70 cases; that was not possible by LM alone. The whole procedure saves two to three hours of processing as centrifugation is not required after the agar embedding step. CONCLUSION: This technique was found to be cost- and time-effective, particularly suitable for developing countries, where financial resources are limited.     

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.     

Posters

Introduction  Fine needle aspiration (FNA) cytology of the thyroid is a well-established test in the clinical work-up of patients with solitary nodules of the thyroid. Thyroid FNA does however have limitations and audit of diagnostic performance is important.
Methods  The histopathology archives of the Royal Victoria Hospital were searched for all thyroid resections and the histopathological diagnosis was correlated with the pre-operative cytological diagnosis, where available. Special emphasis was placed on the accuracy of tumour diagnosis.
Results  A total of 173 cases were identified during the 2-year period, of these 93 had available pre-operative FNA. A total of 57 tumours were identified. A small number (six of 57) of significant discrepancies were identified. These included a malignant lymphoma diagnosed as Hashimoto's thyroiditis, a metastasis which the FNA had suggested was a medullary carcinoma and an insular carcinoma diagnosed as medullary carcinoma on FNA. False positives included a colloid cyst diagnosed as suspicious of malignancy and a cytological diagnosis of papillary carcinoma not confirmed on histology.
Discussion  At present, the majority of thyroid FNAs in our clinics are performed by surgeons and material is not routinely available for immunocytochemistry. In spite of these limitations, there were few major discrepancies. These might be reduced if pathologist aspirators were able to perform FNAs and collect material for further studies, where necessary. This would allow identification of medullary carcinomas and malignant lymphomas.
Conclusion  FNA of thyroid lesions is a useful investigation in our clinical setting, however, some areas of potential for improvement have been identified.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

Endoscopic ultrasound‐guided fine needle aspiration of the pancreas: cytomorphological evaluation with emphasis on adequacy assessment,diagnostic criteria and contamination from the gastrointestinal tract1

Objective: Endoscopic ultrasound (EUS)‐guided fine needle aspiration (FNA) has been proved to be safe, efficient and reliable in the diagnosis of pancreatic lesions. This study evaluated specimen adequacy, diagnostic criteria of various pancreatic neoplasms and contamination from the gastrointestinal (GI) tract. Methods: EUS‐guided FNA of the pancreas and subsequent surgical resections performed at the University of California Irvine Medical Center during February 1996–October 2000 were retrospectively selected. Modified Papanicolaou staining method was used for immediate evaluation and cell block prepared. Results: A total of 267 cases were available for review, including 147 (55.1%) positive/suspicious, 10 (3.7%) atypical, 96 (36.0%) negative and 14 (5.2%) unsatisfactory cases. Eighty‐six (58.5%) positive/suspicious cases had histological confirmation and 12 (8.3%) had lymph node or distant metastases by cytology. Three atypical, two negative, and two unsatisfactory cases proved to have adenocarcinoma. Contamination from duodenum, stomach or pancreas was found in 77 positive/suspicious, three atypical and 90 negative cases. The sensitivity, specificity, diagnostic accuracy, positive and negative predictive values were 94.6%, 100%, 95.6%, 100%, 82% respectively. Conclusions: EUS FNA is efficient and accurate in the diagnosis of pancreatic neoplasms in adequate samples. Contamination from the GI tract should be well recognized to avoid misinterpretation.     

Can abundant colloid exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration? Cytohistological correlation of 127 oncocytic (Hürthle cell) lesions

Objective:  The objective of the present study was to find out whether the presence or absence of certain cytological features can exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration (FNA) to minimize unnecessary surgery. Methods:  Over a 17‐year period, 127 hypercellular, oncocyte‐exclusive, lymphocyte‐absent aspirates obtained via ultrasound‐guided FNA with on‐site assessment had histology slides for review. The presence or absence of six cytological features (microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia, transgressing blood vessels and colloid) and one histological feature (macrofollicular component) were determined for each case independently by two cytopathologists. Results:  Histology showed 12 (9.4%) cases of Hashimoto thyroiditis, 23 (18.1%) oncocytic adenomatoid nodules in nodular goitre, 66 (52.0%) oncocytic adenomas and 26 (20.5%) oncocytic carcinomas (13 minimally invasive without angioinvasion, six minimally invasive with angioinvasion, seven widely invasive). Histologically, a macrofollicular component was present in seven of 26 (26.9%) oncocytic carcinomas, including one case with abundant thin colloid. A microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia and transgressing vessels were present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. Conclusions:  A macrofollicular component is frequently present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. None of the cytological features studied, including abundant colloid, can exclude oncocytic carcinoma. Oncocytic carcinoma can only be excluded by thorough histological examination of thyroidectomy specimens. A molecular marker is needed to triage oncocytic lesions in thyroid FNA.     

Fine needle aspiration cytology in the diagnosis of sinuses and ulcers of the body surface (skin and tongue)

Both fine needle aspiration (FNA) and conventional scraping were used to obtain cytodiagnostic samples from ulcers and sinuses of the skin (18 cases) and tongue (3 cases). These included 14 cases of tuberculosis, 5 squamous-cell carcinomas and 2 cases of nonspecific infection. The FNA smears contained characteristic tuberculous granulomas or epithelioid cells in 10 of the 14 tuberculosis cases and ample diagnostic material in 4 of the 5 carcinoma cases; in contrast the scraping smears predominantly contained necrotic material on which a diagnosis was not possible. Of the 19 cases of tuberculosis and malignancy, 12 were diagnosed only by FNA, 6 were diagnosed by both methods and the FNA sample was negative while the scrape was positive in 1 case. Hence, the diagnosis was made in 18 of 19 by FNA cytology, but in only 7 of 19 cases by scraping cytology, strongly indicating the diagnostic superiority of the former in diagnosing many lesions of the body surface.     

Fine needle aspiration (FNA) of synovial sarcoma—a comparative histological–cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA‐ploidy analysis

A retrospective study of 25 FNAs (11 aspirates from primary tumours and 14 from recurrencies and metastases) from 15 synovial sarcomas was performed. The cytological findings were correlated with the histopathology and the value of immunohistochemical and electron microscopic examination as well as DNA‐ploidy and cytogenetic analysis for diagnosis were assessed. A reproducible cellular pattern with a reliable diagnosis of spindle cell sarcoma was possible provided that the aspirates were cell rich. However, a true biphasic pattern indicative of synovial sarcoma was only seen in one of the 25 specimens. Electron microscopic examination of the aspirates was a valuable adjunctive diagnostic method, whereas immunocytochemistry and DNA‐ploidy analysis were not. Immunohistochemical, electron microscopic and cytogenetic analysis were all valuable ancillary methods when performed on surgical specimens. Malignant haemangiopericytoma and fibrosarcoma were the most important differential diagnoses in the FNA specimens.     

Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: differentiation by architectural pattern

Differentiation between benign and malignant follicular lesions is one of the difficult diagnostic areas in thyroid fine needle aspiration (FNA). Nuclear criteria are usually used to distinguish between them. In this study the microarchitectural pattern of common benign follicular lesions, namely nodular hyperplasia (NH) and follicular adenoma (FA) were analysed in comparison with those of follicular variant of papillary carcinoma (FVPC) in order to aid in their differentiation. The FNA smears of histologically proven cases of FVPC, NH and FA were reviewed and compared. The microarchitectural features of FVPC, NH and FA were described. Three cytological features--multi-layered rosettes, branching monolayered sheets and balls of thick pinkish colloid--were exclusively observed in FVPC. Hyperplastic papillae with intact follicles and colloid were frequently seen in NH, 83% and 100%, respectively. Albeit less frequently, they were also noted in FVPC, 25% and 75% of cases, respectively. These overlapping features make the distinction between FVPC and NH sometimes difficult; however, assessing the smears for the specific features of FVPC may help in their differentiation. None of the aforementioned microscopic findings with the exception of the seldom presence of colloid were documented in FA. The crowded clusters of follicular cells were seen both in FA and FVPC; however, they were complex and branching in the latter and round to oval in the former. Finally, smears with good recovery of material are indispensable for the identification of these helpful microarchitectural patterns.     

Automated breast cancer diagnosis based on fine needle aspiration

OBJECTIVE: To design and analyze an automated diagnostic system for breast carcinoma based on fine needle aspiration (FNA). STUDY DESIGN: FNA is a noninvasive alternative to surgical biopsy for the diagnosis of breast carcinoma. Widespread clinical use of FNA is limited by the relatively poor interobserver reproducibility of the visual interpretation of FNA images. To overcome the reproducibility problem, past research has focused on the development of automated diagnosis systems that yield accurate, reproducible results. While automated diagnosis is, by definition, reproducible, it has yet to achieve diagnostic accuracy comparable to that of surgical biopsy. In this article we describe a sophisticated new diagnostic system in which the mean sensitivity (of FNA diagnosis) approaches that of surgical biopsy. The diagnostic system that we devised analyzes the digital FNA data extracted from FNA images. To achieve high sensitivity, the system needs to solve large, equality-constrained, integer nonlinear optimization problems repeatedly. Powerful techniques from the theory of Lie groups and a novel optimization technique are built into the system to solve the underlying optimization problems effectively. The system is trained using digital data from FNA samples with confirmed diagnosis. To analyze the diagnostic accuracy of the system > 8,000 computational experiments were performed using digital FNA data from the Wisconsin Breast Cancer Database. RESULTS: The system has a mean sensitivity of 99.62% and mean specificity of 93.31%. Statistical analysis shows that at the 95% confidence level, the system can be trusted to correctly diagnose new malignant FNA samples with an accuracy of 99.44-99.8% and new benign FNA samples with an accuracy of 92.43-93.93%. CONCLUSION: The diagnostic system is robust and has higher sensitivity than do all the other systems reported in the literature. The specificity of the system needs to be improved.     

Immunocytochemistry of fine needle aspirates. A tactical approach

To maximize the potential of immunocytodiagnosis for fine needle aspiration (FNA) samples, it is necessary to be aware of the pitfalls and limitations of these techniques and to formulate a strategy to deal with the many variables involved. Five cases are presented to illustrate some of these variables, which include determining the adequacy of the FNA specimen, selecting tactics for cytologic and immunocytochemical studies, selecting methods for processing the FNA sample, preparing smears to enrich and preserve cells of interest, selecting enzyme labeling methods to optimize sensitivity and specificity, selecting monoclonal antibodies to make the study efficient and pertinent and interpreting the study results. The adequacy of the FNA specimen could be determined by an immediate cytologic assessment of the aspirate as it was obtained. Alcohol-fixed smears and formalin-fixed tissue sections prepared from the aspirate were used for diagnosis; the immunocytochemical studies were used as a diagnostic adjunct for accurate cell identification. Immunocytochemical studies were done on air-dried cytocentrifuge smears of pre-washed cells. While both immunoperoxidase and immunoalkaline phosphatase methods were suitable, we recommend the immunoperoxidase method for the study of aspirates from nonhemopoietic tissues and the immunoalkaline phosphatase method for the study of aspirates with many blood cells present. The proper selection of monoclonal antibodies and the interpretation of the results are best made in the context of the cytologic characteristics of the FNA sample and the clinical features of the patient.