Endoscopic ultrasound-guided fine needle aspiration cytology of pancreatic neuroendocrine tumours: cytomorphological and immunocytochemical evaluation

OBJECTIVES: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is increasingly used in preoperative localization and diagnosis of pancreatic neoplasms including neuroendocrine tumours (NETs). The objective of the present study was to identify the cytological features of pancreatic NETs obtained by EUS-FNA. METHODS: The study group consisted of nine cases of pancreatic tumours correctly diagnosed or strongly suggestive of NETs based on EUS-FNA. Cytological smears were retrospectively reviewed. The clinical data and immunocytochemical stains applied to the cell block preparations were also reviewed and examined. RESULTS: All cases except one showed characteristic cytomorphological features sufficient for their recognition and separation from pancreatic adenocarcinoma and other lesions. The most helpful cytological features that facilitated the cytological diagnosis of NET were a richly cellular aspirate with a monotonous, poorly cohesive population of small cells with a speckled or dusty chromatin pattern and plasmacytoid morphology. The neuroendocrine differentiation of these tumours was further confirmed by immunocytochemistry. CONCLUSION: EUS-FNA is a valuable method in the recognition of pancreatic NETs. By adherence to the characteristic cytomorphological criteria of pancreatic NET together with collection of suitable material for ancillary immunocytochemical stains, cytopathologists could reach a correct diagnosis in most instances.     

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.     

Molecular diagnostics of non-small cell lung cancer using mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration

Non-small cell lung cancer is a common cancer with significant mortality. Accurate and early staging of this cancer has a significant impact on outcome. Endoscopic ultrasound-guided fine needle aspiration of involved mediastinal lymph nodes is critical for staging. Several molecular markers have been identified recently in association with non-small cell carcinoma of the lung that are promising to make early detection of metastatic disease more reliable.     

Endoscopic ultrasound-guided FNA biopsy of bile duct and gallbladder: analysis of 53 cases

OBJECTIVE: Endoscopic retrograde cholangiopancreaticography (ERCP)-guided brushing has been the standard of practice for surveillance and detection of carcinoma in the biliary tree. Few studies have evaluated the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in diagnosing clinically suspected cholangiocarcinoma. The role of this method in diagnosing clinically suspected gallbladder malignancies has not been extensively evaluated in the USA. This study investigates the role of EUS-FNA in the diagnosis of clinically suspected biliary tree and gallbladder malignancies in a large patient series. METHODS: EUS-FNAs were obtained from 46 bile duct and seven gallbladder lesions. On-site rapid interpretation was provided using air-dried Diff Quik stained smears. In addition, alcohol fixed Papanicoloau stained smears and Thin Prep preparations (Cytye Corp., Marlborough, MA, USA) were evaluated before providing a final cytological diagnosis. Tissue biopsies and/or clinical follow-up were used as the standards to determine operating characteristics for EUS-FNA. RESULTS: The mean ages for bile duct and gallbladder lesions were 66 years (range: 37-84 years), and 69 years (range 49-86 years), respectively. All cases diagnosed as suspicious/malignant on preliminary evaluation were confirmed on final cytological interpretation (27/27). The operating characteristics show that EUS-FNA is highly specific (100%) with sensitivity rates of 87% and 80% from clinically suspected malignancies of biliary tract and gallbladder, respectively. Sampling error in three cases and associated acute inflammation in two cases resulted in false-negative diagnoses. CONCLUSIONS: EUS-FNA of biliary tree and gallbladder carcinoma is highly specific and should be considered for evaluation of clinically suspicious lesions. Marked inflammation may result in false-negative diagnoses.     

Impact of cytopathologist expert on diagnosis and treatment of pancreatic lesions in current clinical practice. A series of 106 endoscopic ultrasound-guided fine needle aspirations

OBJECTIVES: To evaluate the role of a cytopathologist expert in interpreting difficult pancreatic endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in terms of impact on diagnostic yield and therapy in current clinical practice. METHODS: Retrospective study of 106 EUS-FNA performed between January 2002 and September 2004. Forty-seven cases of difficult interpretation by the local cytopathologist were mailed to an expert cytopathologist. The final diagnosis was established by histology obtained by either surgery (n=30), non-equivocal FNA (n=40) or core (n=8) biopsies, or by a mean follow-up of 14 months (n=28). RESULTS: EUS-FNA involved 68 solid lesions (SL). Specimens collected were adequate in 63%. The overall sensitivity of EUS-FNA for the diagnosis of malignancy of SL was 88% versus 72% for local cytopathologist and 89% for expert. EUS-FNA with the reevaluation by expert of 39 SL gave a therapeutic impact in 47% of SL. Thirty-eight cystic lesions (CL) were evaluated. Specimens collected were adequate for cytology in 84% of cases and for biochemistry in 79%. The sensitivity of imaging+EUS-FNA+/-biochemistry for the diagnosis of a surgical CL was 58% with a therapeutic impact in 39.5%. CONCLUSION: Pancreatic EUS-FNA is an easy technique for experienced endosonographers, which can be safely performed on an outpatient basis. The possibility of mailing difficult cases to an expert cytopathologist increases the diagnostic yield. In these circumstances, EUS-FNA has a therapeutic impact in current practice in nearly one out of two pancreatic lesions.     

Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction

H. Gerke, M. K. Rizk, A. D. Vanderheyden and C. S. Jensen
Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction
Objectives:  Endoscopic ultrasound (EUS)-guided Trucut biopsy (TCB) enables acquisition of tissue cores for histological assessment. Because of the rigid needle and the spring mechanism, tissue acquisition can be difficult from regions that require sharp angulation of the echoendoscope. Fine needle aspiration with high suction (FNAHS) has been proposed as a method to obtain histological tissue cores while affording the flexibility to obtain specimens even with extreme endoscope angulation. The objective was to compare prospectively these two methods in their ability to obtain specimens for histological assessment and in their diagnostic accuracy, including cytological diagnosis when achieved.
Methods:  Eighty lesions in 77 patients were amenable to transoesophageal, transgastric or transrectal biopsy and were randomized to TCB ( n  = 44) or FNAHS ( n  = 36). Each specimen was assessed for adequacy (scoring system where a score of 0 was no material, 1–2 was considered cytological, and 3–5 was considered histological). Follow-up information was obtained to establish a gold standard final diagnosis.
Results:  The median histological scores for FNAHS and TCB were 2 and 5, respectively. Histological cores were obtained in 95.3% of TCB, as opposed to 27.8% in the FNAHS group ( P  < 0.0001). Although the diagnostic accuracy for TCB was greater than that for FNAHS (88.3% and 77.8%, respectively), this was not statistically significant ( P  = 0.24).
Conclusion:  If histological information is required, TCB is superior to FNAHS. The difference in diagnostic accuracy did not reach statistical significance due to low numbers and the fact that FNAHS often enabled a cytological diagnosis.     

Endoscopic ultrasound-guided fine needle aspiration cytology of the pancreas: a morphological and multimodal approach to the diagnosis of solid and cystic mass lesions

Cytological evaluation of pancreatic masses and cysts is the preferred pre-operative diagnostic modality and is increasingly being performed by endoscopic ultrasound. This review focuses on the multimodal approach at the Massachusetts General Hospital that utilizes clinical, cytological, radiological and ancillary studies in rendering a final cytological 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.     

Fine needle aspiration (FNA) biopsy of orbital masses: a critical review of 51 cases

Fine needle aspiration (FNA) biopsy of orbital masses: a critical review of 51 cases
FNA biopsy of 51 orbital masses is critically reviewed. Aspiration was performed with a 23 G needle inserted by an ophthalmologist; the smears were prepared by a cytologist. Forty-two cases (83%) were correctly diagnosed as benign or malignant either with (68%) or without (15%) correct specification of the histology. There were two false-negative and seven inadequate cases. Immunocytochemical stains were performed in five cases using the following antibodies: L26 (Pan B), UCHL1 (Pan T), and immunoglobulin light chains (three cases) in order to distinguish inflammatory pseudotumours from low-grade non-Hodgkin's lymphomas. In two cases we used CAM 5.2 (a monoclonal cytokeratin cocktail) and vimentin to ascertain the epithelial origin of two metastatic tumours. In five other cases cytospins were not adequately cellular for immunocytochemistry. Insufficient material and one false-negative sample were obtained from very fibrotic lesions or from posteriorly located lesions. The results are discussed and compared with other series reported in the literature. Orbital FNA biopsy may be considered a useful tool in the diagnostic approach to orbital masses in which the relatively high number of inadequate aspirations is offset by a low cost-benefit ratio.     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

Effect of ultrasound transmission gel on ultrasound‐guided fine needle aspiration cytological specimens of thyroid

A. Lalzad, D. Ristitsch, W. Downey, A. F. Little and M. E. Schneider‐Kolsky
Effect of ultrasound transmission gel on ultrasound‐guided fine needle aspiration cytological specimens of thyroid Objective: To investigate prospectively the diagnostic impact of ultrasound coupling gel on thyroid specimens obtained under ultrasound guidance. Methods: Patients presenting for ultrasound‐guided fine needle aspiration (USG‐FNA) of the thyroid were invited to participate in the study. Four specimens per nodule were collected: two using chlorhexdine wash and two using sterile, colourless ultrasound gel as couplant according to routine protocol. All slides were analysed in a blinded fashion by two senior cytologists for the presence or absence of ultrasound gel‐induced artefacts. The presence of gel‐induced artefacts between the two groups was analyzed using Pearson’s chi‐square test. Kappa statistics were used to measure the inter‐rater agreement between the cytologists. Results: Twenty thyroid nodules comprising 80 specimen slides were collected. On slides collected with gel, cytological artefacts were detected in 60–65% of cases compared with 10–15% of cases without gel (P < 0.001). The inter‐rater agreement between the two observers was very good (κ = 0.84). Two of the 14 patients required repeat FNA due to non‐diagnostic cytology results caused by inadequate sampling and gel‐induced artefacts. Conclusions: Clinical cytopathologists, radiologists and sonographers should be aware of the potential for ultrasound gel to cause significant artefacts on cytological specimens. Our findings suggest that staff involved in USG‐FNA cytology should remove the gel carefully before taking the aspirate.     

Fine needle aspiration (FNA) biopsy of primary cutaneous meningioma: report of two cases

Two cases of primary cutaneous meningioma are described. A male and a female patient, aged 56 and 61 years, respectively, presented each with a solitary subepidermal nodule. The initial diagnosis was established in both patients by application of FNA biopsy. The subsequent histologic examination confirmed the cytologic diagnosis. Extensive investigation of the patients by computed tomography (CT) and nuclear magnetic resonance imaging (MRI) scans failed to reveal any primary meningioma of the neuraxis. Neurologic examination and routine laboratory test results were all normal. The microscopic features, immunocytological study and histology, which all gave a similar pattern to that seen in intracranial meningiomas, are discussed. Distinction from other cutaneous lesions that may be considered in the differential diagnosis is made. A brief review of the literature is also presented.     

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA): experience of an academic centre in the USA

S. Zhang, D. V. S. DeFrias, R. Alasadi and R. Nayar
Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA): experience of an academic centre in the USA Objectives: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) has become widely accepted as an effective modality for obtaining tissue for primary diagnosis and staging. We have been using EUS‐FNA since July 2001 and herein we summarize our experience over a 5‐year period. Methods: A computer‐based search for in‐house EUS‐FNA was performed in the pathology database from July 2001 to October 2006. To calculate the sensitivity, specificity and accuracy of EUS‐FNA, the cytology diagnosis was compared with the surgical follow‐up. Results: A total of 951 EUS‐FNAs were performed during the study period and included 279 pancreatic solid lesions, 186 pancreatic cyst lesions, 249 lymph node aspirations, 111 gastrointestinal (GI) tract submucosal lesions, and 126 miscellaneous lesions. EUS‐FNA had a very high sensitivity and accuracy for solid pancreatic lesions (94.7 and 97.7%, respectively), low sensitivity and accuracy but high specificity (47, 64.8 and 95%, respectively) for cystic lesions. Cyst fluid carcinoembryonic (CEA) levels were significantly higher in mucinous neoplasms than non‐neoplastic cysts. EUS‐FNA also had very high sensitivity and specificity for detecting metastatic carcinoma in lymph nodes (95 and 100%, respectively). GI submucosal spindle cell tumours were further classified with immunohistochemical stains performed either on a cell block or a core biopsy obtained via EUS guidance. Conclusions: EUS‐FNA has a very high sensitivity and accuracy for pancreatic solid lesions, but the sensitivity for cystic lesions is generally low. Cyst fluid chemical analysis for CEA is helpful, but the overlap between mucinous neoplasm and non‐neoplastic cysts is significant. Recognizing GI contamination is important and immunohistochemical stains are useful for GI submucosal spindle cell lesions.     

Fine needle aspiration in plastic surgery outpatients: a retrospective study

A survey suggested that fine needle aspiration cytology of masses in plastic surgery outpatient clinics was suboptimal. A cytopathologist gave training in the technique and the effectiveness of this intervention was audited. A total of 236 aspirates were taken from 147 patients in the earlier time period and 215 from 149 in the later period. The overall inadequate aspirate rate remained constant at 43%. The most common reasons for poor aspirates were excess blood, unrepresentative adipose tissue and insufficient cellular material. When the specimen was adequate after training, the sensitivity and specificity of the investigation were 96% and 100%, respectively. We present methods for sample optimization. Alternative strategies may be to limit aspiration to one clinician or to refer the patient to a cytopathologist experienced in the technique.     

Fine needle aspiration cytology of medullary thyroid carcinoma: a review of 18 cases

A series of 18 consecutive medullary thyroid carcinomas (MTC) diagnosed by fine needle aspiration cytology (FNAC) is described. The most important diagnostic cytologic criteria were the dispersed cell pattern, the polygonal appearance of the cells, binucleated cells and the presence of amyloid. Other less common cytologic features are reported and the variable microscopic appearance of MTC is pointed out. The possibility that this cytologic variability of MTC may be by itself an important diagnostic feature is proposed.     

Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours

Y. Kopelman, S. Marmor, I. Ashkenazi and Z. Fireman
Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours Objective: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is performed in order to achieve a definite tissue diagnosis of pancreatic lesions. This in turn is a guide to the appropriate treatment for the patient. Tissue samples collected by the same needle for cytological preparations and cell block histological sections (often referred to as FNA‐cytology and FNA–biopsy, respectively) are handled differently. The specific contribution of each of these tests was evaluated. Methods: One hundred and two consecutive patients underwent EUS‐FNA while being investigated for pancreatic solid lesions. Diagnosis was made by cytology, cell block sections or both. The diagnosis was confirmed by clinical outcome. Results: Male/female ratio was 61/41. Mean age was 65 ± 12 years (range, 22–94). Mean lesion size was 3.1 ± 1.8 cm (range, 0.6–10 cm); 68% were >2 cm and 75% were located in the pancreatic head. The average number of needle passes was two (range, 1–4 passes). Final tissue diagnosis was malignant in 66 (65%) patients. Sensitivity, specificity and accuracy were 73%, 94% and 81%, respectively, for cytology alone, and 63%, 100% and 78%, for cell blocks alone. Eighty‐two patients (80%) had cytology and cell blocks, which matched in 64 (78%) patients. EUS‐FNA results that relied on both techniques had 84% sensitivity, 94% specificity and 88% accuracy. Cytology revealed 13 malignancies not diagnosed on cell blocks, while cell blocks revealed five malignancies not diagnosed by cytology. Malignant lesions were more common in men; they were larger in size and located in the pancreatic head. Conclusion: EUS‐FNA cytology was more sensitive than cell blocks but less specific for the diagnosis of solid pancreatic lesions. The two methods are complementary and implementing both improves the diagnostic value of EUS‐FNA.     

Carcinoid tumour of male breast diagnosed by fine needle aspiration

A primary carcinoid tumour of the breast in a 66-year-old man was diagnosed by fine-needle aspiration cytology. The nature of the lesion was proved by histochemical and immunocytochemical studies. The importance of a conclusive diagnosis is discussed and the value of immunocytochemical analysis as an aid to cytomorphologic diagnosis is demonstrated.     

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates In an attempt to improve the quality of the breast FNA specimens we instigated a continuing audit of this procedure in this hospital. All FNAs since 1990 have had the following recorded: mode of aspiration, e.g. freehand or image guided, patient presentation (screening or symptomatic), patient diagnostic category, cytological diagnosis and final histological diagnosis. Aspirator performance was assessed by means of the inadequate aspiration rate (IR) of FNAs performed on patients with a final diagnosis of cancer (FDC) and diagnostic category A patients (clinically or radiologically malignant lesions). An ongoing annual review of the performance of all the aspirators was undertaken, all of whom received individual feedback. Counselling and further training were offered where indicated by poor performance. Over the period 1990–1995 a total of 13 537 FNAs were performed by 27 aspirators. The IR on category A and FDC cases over this period was 16.0% and 18.1%. The best performance achieved by an aspirator in a calendar year was an IR of 3.6% with no inadequate specimens in either FDC or category A lesions, and the best performance over the entire period was an average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases from 12.2% to 21.7%. There was a significant improvement in individual junior aspirator performance when their first year was compared with their last year on the unit. In some cases a deterioration in intra-aspirator performance was observed, from an IR of 6% to 33%. The overall IR rate of the unit remained stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared to be largely due to a high proportion of the aspirations being performed by experienced personnel with consistent IRs. However, concealed within the overall rate there were some poor performers who benefited from counselling and/or further training. These results indicate an important role for audit in identifying poor aspirators who benefit from targeted training and advice, thereby improving the quality of FNA specimens, and ultimately patient care.