Endoscopic Ultrasound–Guided Fine-Needle Aspiration: Sampling, Pitfalls, and Quality Management
2007; Elsevier BV; Volume: 5; Issue: 11 Linguagem: Inglês
10.1016/j.cgh.2007.09.011
ISSN1542-7714
AutoresPeter Kulesza, Isam A. Eltoum,
Tópico(s)Gastrointestinal Tumor Research and Treatment
ResumoEndoscopic ultrasound–guided fine-needle aspiration (EUS FNA) is an accurate and versatile technique in the diagnosis of gastrointestinal tract lesions as well as other organ sites. EUS FNA is performed ideally with cytopathologic adequacy evaluation, and diagnosis at the time of tissue procurement. In this article, we review the most relevant issues in the process of EUS FNA–based diagnostics. Specifically, we describe the technical aspects of specimen collection, processing, and appropriate selection of ancillary studies. We also illustrate the most commonly encountered diagnostic pitfalls, and methods for their avoidance. Lastly, we discuss quality management, which emphasizes the communication between the endoscopist and the pathologist. Endoscopic ultrasound–guided fine-needle aspiration (EUS FNA) is an accurate and versatile technique in the diagnosis of gastrointestinal tract lesions as well as other organ sites. EUS FNA is performed ideally with cytopathologic adequacy evaluation, and diagnosis at the time of tissue procurement. In this article, we review the most relevant issues in the process of EUS FNA–based diagnostics. Specifically, we describe the technical aspects of specimen collection, processing, and appropriate selection of ancillary studies. We also illustrate the most commonly encountered diagnostic pitfalls, and methods for their avoidance. Lastly, we discuss quality management, which emphasizes the communication between the endoscopist and the pathologist. Endoscopic ultrasound–guided fine-needle aspiration (EUS FNA) has found a wide use in most high-volume centers in the United States. EUS FNA is a simple, cost-effective, and versatile technique that has been adapted in the diagnosis of gastrointestinal tract lesions as well as other organ sites.1Erickson R.A. EUS-guided FNA.Gastrointest Endosc. 2004; 60: 267-279Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar The indications for EUS FNA are manifold, and depend on the particular radiologic and clinical presentation of the lesion.2Dewitt J. Ghorai S. Kahi C. et al.EUS-FNA of recurrent postoperative extraluminal and metastatic malignancy.Gastrointest Endosc. 2003; 58: 542-548Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar EUS FNA has a clear advantage over any other technique in cases of lesions not seen clearly by other imaging modalities.3Bardales R.H. Stelow E.B. Mallery S. et al.Review of endoscopic ultrasound-guided fine-needle aspiration cytology.Diagn Cytopathol. 2006; 34: 140-175Crossref PubMed Scopus (68) Google Scholar This includes intra-abdominal and mediastinal lymphadenopathy,4Chen V.K. Eloubeidi M.A. Endoscopic ultrasound-guided fine needle aspiration is superior to lymph node echofeatures: a prospective evaluation of mediastinal and peri-intestinal lymphadenopathy.Am J Gastroenterol. 2004; 99: 628-633Crossref PubMed Scopus (134) Google Scholar pancreatic masses,5Harewood G.C. Wiersema M.J. Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses.Am J Gastroenterol. 2002; 97: 1386-1391Crossref PubMed Google Scholar and gastrointestinal submucosal masses.6Vander Noot 3rd, M.R. Eloubeidi M.A. Chen V.K. et al.Diagnosis of gastrointestinal tract lesions by endoscopic ultrasound-guided fine-needle aspiration biopsy.Cancer. 2004; 102: 157-163Crossref PubMed Scopus (194) Google Scholar In cases in which imaging modalities (ie, computerized tomography or endoscopic retrograde cholangiopancreatography) perform as well as ultrasonography, the strongest support for EUS FNA is documented in cases in which those other biopsy techniques have failed.1Erickson R.A. EUS-guided FNA.Gastrointest Endosc. 2004; 60: 267-279Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar It is remarkable that in almost all reports of EUS FNA performed after other failed diagnostic attempts, EUS FNA was able to provide a definitive diagnosis in 80% to 95% of cases.5Harewood G.C. Wiersema M.J. Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses.Am J Gastroenterol. 2002; 97: 1386-1391Crossref PubMed Google Scholar, 7Gress F. Gottlieb K. Sherman S. et al.Endoscopic ultrasonography-guided fine-needle aspiration biopsy of suspected pancreatic cancer.Ann Intern Med. 2001; 134: 459-464Crossref PubMed Scopus (295) Google Scholar, 8Fritscher-Ravens A. Soehendra N. Schirrow L. et al.Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer.Chest. 2000; 117: 339-345Crossref PubMed Scopus (180) Google Scholar In cases of pancreatic masses EUS FNA offers superior sensitivity and specificity over endoscopic retrograde cholangiopancreatography and percutaneous computerized tomography–guided biopsy procedures,9Wakatsuki T. Irisawa A. Bhutani M.S. et al.Comparative study of diagnostic value of cytologic sampling by endoscopic ultrasonography-guided fine-needle aspiration and that by endoscopic retrograde pancreatography for the management of pancreatic mass without biliary stricture.J Gastroenterol Hepatol. 2005; 20: 1707-1711Crossref PubMed Scopus (71) Google Scholar, 10Jhala D. Eloubeidi M. Chhieng D.C. et al.Fine needle aspiration biopsy of the islet cell tumor of pancreas: a comparison between computerized axial tomography and endoscopic ultrasound-guided fine needle aspiration biopsy.Ann Diagn Pathol. 2002; 6: 106-112Abstract Full Text PDF PubMed Scopus (77) Google Scholar and cost savings from $1000 to 3000 per patient.11Chang K.J. Nguyen P. Erickson R.A. et al.The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of pancreatic carcinoma.Gastrointest Endosc. 1997; 45: 387-393Abstract Full Text Full Text PDF PubMed Scopus (538) Google Scholar, 12Erickson R.A. Garza A.A. EUS with EUS-guided fine-needle aspiration as the first endoscopic test for the evaluation of obstructive jaundice.Gastrointest Endosc. 2001; 53: 475-484Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Although few randomized studies of EUS FNA compared with other diagnostic modalities exist, the American Joint Committee on Cancer recommends EUS FNA as the primary modality in the diagnosis of pancreatic masses.13Greene F. AJCC cancer staging handbook.6th ed. Springer Verlag, New York2002Crossref Google ScholarThe Need for On-Site Evaluation and Two-Way CommunicationAlmost all centers offer cytopathologic adequacy evaluation at the time of tissue procurement, and some also offer diagnosis, performed by a cytopathologist in a manner analogous to a frozen section. The main reason for on-site evaluation is the reduction in the rate of nondiagnostic specimens. Most studies show that the on-site evaluation increases the total diagnostic yield by 10%–15%.14Erickson R.A. Sayage-Rabie L. Beissner R.S. Factors predicting the number of EUS-guided fine-needle passes for diagnosis of pancreatic malignancies.Gastrointest Endosc. 2000; 51: 184-190Abstract Full Text Full Text PDF PubMed Scopus (351) Google Scholar In a study comparing specially trained endosonographers with cytotechnologists, none were statistically equivalent to the cytotechnologist (P = .004) in adequacy assessment, and all endosonographers were inferior (P < .001) to the cytotechnologist in the preliminary diagnoses of benign vs malignant; even when best practices were followed there was a 20% nondiagnostic specimen rate if the cytopathologist (or cytotechnologist) was not present.10Jhala D. Eloubeidi M. Chhieng D.C. et al.Fine needle aspiration biopsy of the islet cell tumor of pancreas: a comparison between computerized axial tomography and endoscopic ultrasound-guided fine needle aspiration biopsy.Ann Diagn Pathol. 2002; 6: 106-112Abstract Full Text PDF PubMed Scopus (77) Google Scholar, 15Savoy A.D. Raimondo M. Woodward T.A. et al.Can endosonographers evaluate on-site cytologic adequacy? A comparison with cytotechnologists.Gastrointest Endosc. 2007; 65: 953-957Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Moreover, feedback provided by the cytopathologist also has impact on the final diagnosis, which requires matching of the ultimate diagnostic test to the differential diagnosis, and is a part of the live dialogue between the procuring endoscopist and the pathologist. In general, a continuous dialogue between the cytopathologist and the endoscopist is the best approach to EUS FNA diagnostics. Although we do not know the cost effectiveness of this approach, we believe that it is worthwhile despite the current low reimbursement rate. At our institution, we recently developed a decision algorithm for the management of patients suspected of having pancreatic ductal carcinoma, based on real-time, on-site cytopathologic diagnoses.16Eloubeidi M.A. Varadarajulu S. Desai S. et al.A prospective evaluation of an algorithm incorporating routine preoperative endoscopic ultrasound-guided fine needle aspiration in suspected pancreatic cancer.J Gastrointest Surg. 2007; 11: 813-819Crossref PubMed Scopus (116) Google Scholar, 17Eltoum I.A. Chen V.K. Chhieng D.C. et al.Probabilistic reporting of EUS-FNA cytology: toward improved communication and better clinical decisions.Cancer. 2006; 108: 93-101Crossref PubMed Scopus (20) Google ScholarDiagnostic AlgorithmThe algorithm used by the pathologist begins with assessing whether lesional tissue is present. This requires an average of 2 passes, and in some cases helps the endoscopist avoid areas of desmoplasia or necrosis. Subsequently, the determination is made whether the morphologic findings fit with the clinical impression and the patient's history.18Jhala N.C. Jhala D.N. Chhieng D.C. et al.Endoscopic ultrasound-guided fine-needle aspiration A cytopathologist's perspective.Am J Clin Pathol. 2003; 120: 351-367Crossref PubMed Scopus (212) Google Scholar Often, a diagnosis of malignant neoplasm is sufficient in cases of suspected recurrence, or, for example, the finding of adenocarcinoma in cases of solitary pancreatic mass, and at this point the procedure may stop. Subsequent passes are performed to either refine the morphologic diagnosis or for use in ancillary testing. The exact number of passes necessary varies greatly depending on a number of factors. Cystic and fibrotic lesions yield much less cellular material than parenchymatous ones; highly vascular lesions give progressively less diagnostic material as the number of passes increases owing to blood return. The type and diameter of the needle, whether aspiration is used as opposed to reliance on the capillary and shearing action of the needle, and, finally, the experience of the endoscopist and the pathologists all have an impact on the diagnostic yield.19Fritscher-Ravens A. Topalidis T. Bobrowski C. et al.Endoscopic ultrasound-guided fine-needle aspiration in focal pancreatic lesions: a prospective intraindividual comparison of two needle assemblies.Endoscopy. 2001; 33: 484-490Crossref PubMed Scopus (52) Google Scholar, 20Mertz H. Gautam S. The learning curve for EUS-guided FNA of pancreatic cancer.Gastrointest Endosc. 2004; 59: 33-37Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar In our experience, we found that after 5 passes the incremental diagnostic improvement of more passes was negligible.21Jhala N.C. Jhala D. Eltoum I. et al.Endoscopic ultrasound-guided fine-needle aspiration biopsy: a powerful tool to obtain samples from small lesions.Cancer. 2004; 102: 239-246Crossref PubMed Scopus (124) Google ScholarThe diagnostic features vary with the organ and the nature of the lesion being sampled. In most cases the definitive diagnosis is rendered at the time of the procedure. In difficult cases, the pathologist resorts to simple pattern recognition and classifies the neoplasm into an epithelial/epithelioid lesion, spindle-cell lesion, small round cell lesion, and so forth, and comments on the probability of malignancy. This information is necessary for subsequent processing of the specimen, and performance of ancillary studies to reach the definitive diagnosis.Ancillary StudiesEquivocal cytologic diagnoses almost always require ancillary testing. The choice of ancillary tests depends on the preliminary morphologic diagnosis: the number of passes and the processing of the sample have to be appropriate for subsequent use. Flow cytometric analysis almost always is necessary to rule out non-Hodgkin's lymphoma.22Robins D.B. Katz R.L. Swan Jr, F. et al.Immunotyping of lymphoma by fine-needle aspiration A comparative study of cytospin preparations and flow cytometry.Am J Clin Pathol. 1994; 101: 569-576PubMed Google Scholar, 23Young N.A. Al-Saleem T. Diagnosis of lymphoma by fine-needle aspiration cytology using the revised European-American classification of lymphoid neoplasms.Cancer. 1999; 87: 325-345Crossref PubMed Scopus (101) Google Scholar In these cases, 3–4 additional passes are collected into either saline if the analysis can be performed within a few hours, or preferably tissue culture medium containing fetal calf serum. It is beneficial to use heparinized collection solutions because clotting of the EUS FNA sample causes entrapment of cells in clot material, which gets filtered and discarded before flow cytometry. It is important to note that flow cytometry is not appropriate for Hodgkin's lymphoma.24Mayall F. Dray M. Stanley D. et al.Immunoflow cytometry and cell block immunohistochemistry in the FNA diagnosis of lymphoma: a review of 73 consecutive cases.J Clin Pathol. 2000; 53: 451-457Crossref PubMed Scopus (38) Google ScholarDetermination of the causative organism in suspected infection presents a challenge because of the limited amount of FNA material. Certain organisms can be identified easily using simple stains either because of their abundance, or very specific morphologic features (eg, granulomatous inflammation is detected very easily).25Stelow E.B. Lai R. Bardales R.H. et al.Endoscopic ultrasound-guided fine-needle aspiration of lymph nodes: the Hennepin County Medical Center experience.Diagn Cytopathol. 2004; 30: 301-306Crossref PubMed Scopus (26) Google Scholar Bacteria, fungal hyphae and yeast forms, and cytoplasmic and nuclear viral inclusions can be visualized in smears stained with DiffQuik or gomori methenamine silver. Mycobacteria show a negative image on Diff-Quik, however, they are difficult to detect even using acid-fast stains unless they are present in abundance. This is very common in cases of Mycobacterium avium infection in human immunodeficiency virus–positive patients, but very rare in cases of tuberculosis.26Cooksey R.C. Recent advances in laboratory procedures for pathogenic mycobacteria.Clin Lab Med. 2003; 23: 801-821Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar EUS FNA, similar to other aspiration procedures, can be used for specific organism classification and susceptibility testing if the specimen is handled properly, and submitted to the microbiology laboratory.27Powers C.N. Diagnosis of infectious diseases: a cytopathologist's perspective.Clin Microbiol Rev. 1998; 11: 341-365PubMed Google Scholar Most aerobic bacteria, fungi, and acid-fast bacilli can be recovered by resuspending the FNA material in 1 mL of sterile tryptone-soy broth as a transport medium, and using standard, organism-specific media and culture techniques subsequently.28Kulesza P. Carrol K. Microbiology laboratory procedure manual. Johns Hopkins Press, Baltimore, MD2005Google ScholarLastly, the EUS FNA material can be collected for immunohistochemistry (IHC) staining. This is by far the most common ancillary test, and is relied on heavily in diagnoses of solid tumors. The collection of material usually starts in the earliest passes by performing a needle rinse. Once the needle is withdrawn from the endoscope, the tip is placed on sterile glass slides, and the stylette is used to expel the material, typically sufficient for 2–3 slides. A syringe may be used to expel clotted material forcefully. Smears then are made, and some slides are air-dried and stained with DiffQuik to provide morphologic assessment on site. Although DiffQuik usually is sufficient for a preliminary diagnosis, it is inferior to ethanol-fixed, Papanicolaou (PAP)-stained material in nuclear detail, and fidelity of cell size. If PAP-stained slides are desired, they must be placed in 95% ethanol immediately after smearing to minimize air-drying artifacts. After the material is expelled on the slides, the needle is rinsed in sterile saline (or Hank's solution) by aspiration and expulsion. In most instances, the leftover material after slides have been made is not sufficient for IHC. Therefore, dedicated passes need to be performed. The number depends on the abundance of lesional tissue, but it is usually never less than two. This material can be collected directly into the rinse solution, usually without the need to make further slides unless localization of the lesion is difficult.The collected sample is processed to obtain a formalin-fixed, paraffin-embedded block of tissue (ie, cell block). Although this method follows typical pathology tissue processing, there are additional steps necessary because of the comparatively minute amount and the fragmented nature of the specimen. This is accomplished by centrifugation of the sample and using either an agarose gel or fibrin clot to hold the specimen together before dehydration and embedding in paraffin. The cell blocks are used to generate numerous slides, and can be used to perform immunostaining without any differences from the established protocols. However, caution has to be exercised if the EUS FNA material is collected in Cytolyt (Cytyc, Marlborough, MA) (a common fixative in the cytology laboratory) because some antigens are sensitive to alcohol-containing vs formalin fixation and can give rise to erroneous results.29Arnold M.M. Srivastava S. Fredenburgh J. et al.Effects of fixation and tissue processing on immunohistochemical demonstration of specific antigens.Biotech Histochem. 1996; 71: 224-230Crossref PubMed Scopus (93) Google ScholarDiagnostic PitfallsThe chance for misdiagnosis is highest when either the differential diagnosis includes entities with very similar morphologies, or when a distinct morphology is not expected. Often, this is reflected in the total number of passes necessary to make the diagnosis. Aside from the abundance of the lesional material, it has been shown that this number depends mainly on the differentiation of the tumor because well-differentiated lesions are more difficult to classify as malignant, and the ability to distinguish lesional tissue from background. Despite sheathing of the needle, EUS FNA introduces surrounding nonlesional tissue, which presents a diagnostic challenge and may result in misdiagnoses. Specific pitfalls depend on the anatomic location of the lesion, and the cytomorphology of tissues that are present in the sample.Esophagus and Gastroesophageal JunctionIn the upper esophagus, the pitfalls lie in the distinction between a benign ulceration and squamous cell carcinoma. The cytomorphologic appearance of a reactive process mimics carcinoma: there are atypical cells, with increased nuclear to cytoplasmic (N/C) ratios, and prominent nucleoli. The features that favor malignancy are orangephyllic keratin, and classic nuclear features of malignancy: irregular nuclear border, hyperchromasia, and overt atypia (Figure 1). In most cases, these features are best appreciated on PAP-stained, and not DiffQuik-stained, material. In the gastroesophageal junction, the differential diagnosis changes to ulceration, dysplasia, and adenocarcinoma. In these cases, the squamous metaplasia expected in ulcers cannot be distinguished from the mixture of normal, reactive squamous epithelium surrounding the glandular dysplasia. Although a core biopsy is useful to rule out an invasive lesion, there is interobserver variation in grading of the severity of dysplasia.30Montgomery E. Bronner M.P. Goldblum J.R. et al.Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.Hum Pathol. 2001; 32: 368-378Abstract Full Text Full Text PDF PubMed Scopus (682) Google Scholar Thus, the cytopathologic diagnosis should be confined to the detection of overt malignant features.MediastinumEUS FNA is used increasingly in accessing mediastinal lymph nodes for lung carcinoma staging.31Eloubeidi M.A. Tamhane A. Chen V.K. et al.Endoscopic ultrasound-guided fine-needle aspiration in patients with non-small cell lung cancer and prior negative mediastinoscopy.Ann Thorac Surg. 2005; 80: 1231-1239Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar This indication almost never presents a challenge for the pathologist, however, lung-draining lymph nodes contain dust-laden macrophages, which can be confused with metastatic melanoma (Figure 2). Primary lung masses, mediastinal neoplasms (lymphomas and germ-cell tumors), as well as nonneoplastic conditions such as foregut cysts can be accessed and sampled via EUS FNA.1Erickson R.A. EUS-guided FNA.Gastrointest Endosc. 2004; 60: 267-279Abstract Full Text Full Text PDF PubMed Scopus (144) Google ScholarFigure 2(A) Benign macrophages in mediastinal lymph node smear. The cells are large, with kidney bean-shaped nuclei, and numerous pigment granules in the cytoplasm. There is a background of small lymphocytes (DiffQuik, 400×). (B) Malignant melanoma. The malignant cells have plasmacytoid morphology, round nuclei with prominent nucleoli, and very delicate cytoplasmic granularity. There is no evidence of melanin pigment (DiffQuik, 400×). Color version of this figure available at www.cghjournal.org.View Large Image Figure ViewerDownload Hi-res image Download (PPT)StomachGastric epithelial lesions usually follow the typical morphology seen in the excisional specimens, and do not present specific diagnostic challenges if the radiologic presentation is typical. The difficulty arises if the lesion cannot be diagnosed as mucosal or submucosal. EUS FNA sampling can result in fragments of the thick gastric muscularis present in the specimen (Figure 3). If there are no other morphologic features to account for the lesion, the presence of smooth muscle cells on the on-site evaluation raises the differential diagnosis of spindle-cell neoplasm. This differential includes gastrointestinal stromal tumor (GIST), leiomyoma, Schwannoma, and solitary fibrous tumor; malignant entities usually are too atypical to be included. GIST usually is cellular, solitary fibrous tumor and Schwannoma are very rare, and often can be ruled out morphologically (Figure 3). The distinction between smooth muscle wall and leiomyoma cannot be made morphologically, however, a clinical and radiologic correlation on-site is sufficient to determine if the cytologic material accounts for the lesion. Ancillary testing by IHC almost always is essential. Table 1 summarizes the most commonly used stains.32Friedman D. ImmunoQuery. http://www.ipox.org; Last accessed July 2007.Google ScholarFigure 3(A) Gastric wall smooth muscle. There are numerous elongated nuclei within dense, strongly staining matrix (DiffQuik, 400×). (B) Schwannoma: there is a vague pallisading arrangement of the nuclei (DiffQuik, 400×). (C) GIST. The smear is uniformly cellular (DiffQuik, 100×).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 1Immunohistochemical Characteristics of Spindle Cell NeoplasmsIHCGISTSFTSchwannomaLeiomyomaS-100NegativeNegativeStrongly positiveNegativec-kitPositiveNegativeNegativeNegativeCD 34Often positiveStrongly positiveRarely positiveNDCD 99PositiveStrongly positiveNDRarely positiveSmooth muscle markersaIncluded H-caldesmon, smooth muscle myosin heavy chain, and smooth muscle actin.Occasionally positiveRarely positiveNegativeAlways positiveND, not determined; SFT, solitary fibrous tumor.a Included H-caldesmon, smooth muscle myosin heavy chain, and smooth muscle actin. Open table in a new tab Pancreas/Biliary TreeDuctal pancreatic adenocarcinomas and cholangiocarcinomas share some of the morphologic characteristics that make them difficult to diagnose as malignant. This particularly applies to well-differentiated lesions, which tend to lack hyperchromasia, have modestly increased N/C ratios, and show minimal architectural disorder of epithelial fragments (Figure 4). The differential diagnosis includes reactive epithelial changes, which almost always are seen in patients with history of stenting or prior instrumentation of the area. Although stent atypia shows more prominent nucleoli, and less single cells on smear slides, the features are overlapping. In most cases, an increased number of passes is necessary, and is used exclusively for morphologic evaluation because no ancillary test can detect malignant transformation. Chronic pancreatitis often is difficult to distinguish from adenocarcinoma both radiologically and morphologically. Furthermore, desmoplasia and inflammatory infiltrate almost invariably accompanies adenocarcinoma. Unlike on a frozen section of intact tissue, on smear slides the malignant and benign components become intermixed. Thus, the architectural information that makes the definitive diagnosis possible (ie, relative positions of atypical but reactive cells vs malignant cells) is not available. Most pathologists focus on overt nuclear atypia, and marked anisonucleosis within an intact epithelial fragment (Figure 4). Other solid lesions, such as acinar cell carcinoma, neuroendocrine tumors, and others, have more characteristic morphologies, and do not present great difficulties, especially if adequate material is available for IHC.Figure 4(A) Reactive ductal epithelium. There is mild disorganization of the epithelial architecture, uniform nuclear enlargement, and almost all cells show prominent nucleoli (PAP, 400×). (B) Well-differentiated pancreatic adenocarcinoma. Although the epithelial architecture is almost normal, the cells are beginning to lose polarity, the nucleoli are markedly pronounced, and there is some anisonucleosis. There is a background of necrotic debris and neutrophils which may be seen in benign and malignant lesions. (C) Pancreatic adenocarcinoma. The cells show overt malignant features: extreme nuclear enlargement, prominent anisonucleosis within the epithelial fragment, and marked nuclear membrane irregularity (PAP, 600×). Color version of these figures available at www.cghjournal.org.View Large Image Figure ViewerDownload Hi-res image Download (PPT)The cytopathologic diagnosis of cystic mucinous neoplasms, including intraductal papillary mucinous neoplasm of the pancreas, rests on the finding of mucinous epithelial fragments (Figure 5). This is problematic because nonlesional, epithelial contaminants are unavoidable in EUS FNA, and are admixed to the sample of the lesion. The contaminants originate from the duodenal and gastric mucosa. Of the two, the duodenal mucosa is easier to distinguish; it has occasional goblet cells, and an extremely regular honeycomb pattern (Figure 5). Gastric mucosa shows accentuated polarization, and may show more cytologic atypia, such as nuclear enlargement (Figure 5).Figure 5(A) Intraductal pancreatic mucinous neoplasm. The epithelial fragment shows cells with clearly delineated mucin-containing vacuoles (DiffQuik, 400×). (B) Duodenal mucosa. The cells are arranged in a perfectly regular honeycomb pattern, with goblet cells appearing as cleared spaces (DiffQuik, 400×). (C) Gastric mucosa. The edge of the fragment shows prominent polarization of the epithelium, and mucous-containing cells (PAP, 400×). Color version of these figures available at www.cghjournal.org.View Large Image Figure ViewerDownload Hi-res image Download (PPT)LiverThe challenges in liver diagnoses are similar in EUS FNA as in other methods; however, EUS FNA is more likely to require material for IHC. This is particularly necessary in cases of poorly differentiated lesions, which present the differential diagnosis of high-grade hepatocellular carcinoma or adenocarcinoma (Figure 6). Although it is common for hepatocellular carcinoma to not have detectable serum α-fetoprotein level, the tissue markers usually are preserved, and are possible to detect by IHC.Figure 6(A) Hepatocellular carcinoma. The smear shows cohesive clusters of markedly atypical cells. There are no features indicative of hepatocytic origin (PAP, 200×). (B) Cholangiocarcinoma. The cells are tightly clustered, with increased N/C ratios and nuclear enlargement (DiffQuik, 400×). Color version of this figure available at www.cghjournal.org.View Large Image Figure ViewerDownload Hi-res image Download (PPT)RectumThe diagnosis of adenocarcinoma of the rectum can be complicated by very rare, gender specific findings. Depending on the particular approach taken by the endoscopist, the EUS FNA sample in men inadvertently may include seminal vesicle cells. These cells show characteristic atypia, whic
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