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.     

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.     

Is a five‐category reporting scheme for thyroid fine needle aspiration cytology accurate? Experience of over 18 000 FNAs reported at the same institution during 1998–2007

S. Piana, A. Frasoldati, M. Ferrari, R. Valcavi, E. Froio, V. Barbieri, C. Pedroni and G. Gardini Is a five‐category reporting scheme for thyroid fine needle aspiration cytology accurate? Experience of over 18 000 FNAs reported at the same institution during 1998–2007 Objective: Fine needle aspiration (FNA) has long been recognized as an essential technique for the evaluation of thyroid nodules. Although specific cytological patterns have been recognized, a wide variety of reporting schemes for thyroid FNA results have been adopted. This study reports our experience with a five‐category reporting scheme developed in‐house based on a numeric score and applied to a large series of consecutive thyroid FNAs. It focuses mainly on the accuracy of thyroid FNA as a preoperative test in a large subset of histologically distinct thyroid lesions. Methods: During the 1998–2007 period, 18 359 thyroid ultrasound‐guided FNAs were performed on 15 269 patients; FNA reports were classified according to a C1–C5 reporting scheme: non‐diagnostic (C1), benign (C2), indeterminate (C3), suspicious (C4), and malignant (C5). Results: Non‐diagnostic (C1) and indeterminate (C3) FNA results totalled 2 230 (12.1%) and 1 461 (7.9%), respectively, while suspicious (C4) and malignant (C5) results totalled 238 (1.3%) and 531 (2.9%), respectively. Histological results were available in 2 047 patients, with thyroid malignancy detected in 840. Positive predictive value of FNA was 98.1% with a 49.0 likelihood ratio (LR) of malignancy in patients with a C4/C5 FNA report. Conclusions: This five‐category scheme for thyroid FNA is accurate in discriminating between the virtual certainty of malignancy associated with C5, a high rate (92%) of malignancy associated with C4, and a 98% probability of a histological benign diagnosis associated with C2. Further sub‐classifications of C3 may improve the accuracy of the diagnostic scheme and may help in recognizing patients eligible for a ‘wait and see’ management.     

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.     

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.     

Endoscopic ultrasound-guided tissue sampling by combined fine needle aspiration and trucut needle biopsy: a prospective study

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has a diagnostic accuracy of 70-90%, depending on the site under evaluation. In order to improve EUS-guided tissue sampling a novel 19-gauge trucut-type needle has been designed to obtain core biopsies during EUS. We prospectively evaluated the safety and accuracy of EUS-FNA alone versus combined EUS-FNA and trucut needle biopsy (TNB) in patients referred to our Unit over a 3-year period. PATIENTS AND METHODS: A total of 159 patients underwent EUS-FNA alone (lesions<2 cm) or the combination of both sampling modalities (lesions>or=2 cm). The adequacy of sampling, sensitivity, specificity and overall accuracies of EUS-FNA or EUS-TNB alone and combined EUS-FNA/TNB were determined. RESULTS: Adequate samples were obtained by EUS-FNA, EUS-TNB and EUS-FNA/TNB in 91%, 88% and 97% of patients, respectively. From the pancreas (n=83), adequate samples were obtained by FNA in 94% and by TNB in 81%, compared with 87% and 92% from non-pancreatic sites (n=76), respectively. The combination of both techniques resulted in more adequate samples from non-pancreatic cases than EUS-FNA alone (P=0.044). The specificity was 100%. Overall accuracy for EUS-FNA alone was 77%, for EUS-TNB alone 73% and for EUS-FNA/TNB 91% (P=0.008). For pancreatic sampling, the accuracy of EUS-FNA alone was 77%, for EUS-TNB alone 56% and for EUS-FNA/TNB 83%. For non-pancreatic sampling, the accuracy for EUS-FNA alone was 78%, for EUS-TNB alone 83% and for EUS-FNA/TNB 95% (P=0.006). The complication rate was 0.6%. CONCLUSIONS: Combined EUS-FNA/TNB for lesions>or=2 cm improves adequacy of sampling and diagnostic accuracy compared with either technique alone and is safe.     

Lymphangioma of the pancreas: a multimodal approach to pre‐operative diagnosis

Background: Lymphangioma of the pancreas is an extremely rare benign tumour of lymphatic origin, with only four cases diagnosed by EUS‐FNA reported to date. Methods and materials: Five cases of either cytologically or histologically diagnosed pancreatic lymphangioma with pre‐operative cytological analysis by EUS‐FNAC were reviewed. Results: All patients were female, with a mean age of 56.4 years. By imaging, the cystic lesions ranged in size from 2 to 7 cm (mean 4.5 cm) and were mainly located in the head of the pancreas. All cysts had thin walls and no cyst demonstrated a mural nodule. Diagnosis based on imaging features was benign in all cases due to the absence of high‐risk features. Four samples were sent for biochemical analysis, which showed low CEA levels (range, <0.5–19.4 ng/ml; mean, 5.45 ng/ml) and CA 19.9 and CA 72.4 levels within normal range. All cyst fluids showed numerous small lymphocytes with no atypia; no epithelial cells were present, including no gastrointestinal contamination. Flow cytometry in two cases showed T lymphocytes with a mature phenotype. Surgical resection in two patients confirmed the cytological diagnosis. Benign clinical follow‐up was available in three patients at 2, 3 and 3.5 years. Conclusion: A multimodal approach to cytological diagnosis (combining clinical, radiological and cyst fluid gross, biochemical and cytological characteristics) can lead to the diagnosis of this cystic neoplasm and distinguish it from other more common cysts in the pancreas, potentially avoiding the need for unnecessary surgery.     

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.     

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.     

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.