Techniques for Endoscopic Ultrasound-Guided Fine-Needle Biopsy

Key Points

  • Although endoscopic ultrasound-guided fine-needle aspiration (EUS FNA) is very accurate, it cannot fully characterize certain neoplasms, and lack of cytology expertise may result in a limited perceived utility of endoscopic ultrasound.

  • Standard 19-G and 22-G fine-needle aspiration needles with or without high negative pressure have proven to be reliable in obtaining high-quality histologic samples in various indications.

  • The novel 19-G and 22-G ProCore needles have demonstrated a high yield in obtaining histologic samples, whereas 25-G ProCore seems unsuitable for histology.

  • Data on the newly developed 20-G ProCore, SharkCore, and Acquire needles are limited, but appear very promising.

  • In perspective, endoscopic ultrasound-guided fine-needle biopsy (EUS FNB) is expected to refine differential diagnostic capabilities, favor widespread EUS utilization, and pave the road to targeted therapies and monitoring of treatment response.


In the last decade, different techniques and specifically designed needles to acquire samples for histological evaluation have been developed. These efforts have been made in an attempt to overcome some of the limitations of endoscopic ultrasound-guided fine-needle aspiration (EUS FNA)—in particular, the need for rapid on-site evaluation (ROSE) of the collected specimens to be able to reach a diagnostic accuracy greater than 90%. However, the limited availability of ROSE throughout the world associated with the lack of cytology expertise outside high volume tertiary care centers has resulted in a limited perceived utility of EUS and has created a barrier to the dissemination of the procedure in the community and in many countries.

Recently in centers where ROSE is not available it has been recommended to perform EUS-guided fine-needle biopsy (EUS FNB) to acquire samples for histologic evaluation. This should result in a greater chance to be accurate due to the easier interpretation by the pathologists, with the additional advantage of providing tissue samples to perform ancillary tests. The latter is particularly important in view of the increasing interest in evaluating core tissue samples for molecular markers that may serve as prognostic predictors and targets for individualized chemotherapy in patients with cancer. If this will occur, diagnostic EUS will be transformed into a more therapeutic procedure performed not only to provide a diagnosis, but also to offer the best possible therapy for each individual patient.

A Tru-Cut biopsy needle dedicated for EUS-guided fine-needle biopsy (EUS FNB), the Quick-Core (Cook Medical, Bloomington, Indiana) needle, was developed but without meaningful advantages over EUS FNA. Among the newly available needles specifically designed to perform FNB, the 25-G ProCore (Cook Medical) has been found to be able to gather tissue core samples in only about 40% of the cases. Moreover, no overall clear advantages of the 22-G ProCore (Cook Medical) over standard 22-G FNA needles have been demonstrated. Finally, very promising results have been initially reported for the 19-G ProCore, but these were not followed by additional experiences. Many studies, on the other hand, have described a high accuracy of standard 19-G needles in acquiring tissue core biopsy samples for various indications. The 19-G needle, however, is not easy to use from the duodenum and is in general avoided by nonexpert endosonographers because of the fear of complications. Based on these premises, other needles for EUS FNB have been developed, the 20-G ProCore (Cook Medical), the 22- and 25-G SharkCore (Medtronic PLC, Dublin, Ireland), and the 22- and 25-G Acquire (Boston Scientific Corp., Marlborough, Massachusetts). Preliminary data on these smaller needles for both pancreatic and nonpancreatic lesions are very encouraging.

This chapter will review the EUS FNB techniques developed so far, their clinical results, their limitations, as well as their future perspectives.

Endoscopic Ultrasound-Guided Tru-Cut Biopsy

The first needle specifically developed for EUS FNB is the Quick-Core (Cook Medical), a 19-G Tru-Cut biopsy needle that is capable of collecting an 18-mm-long tissue specimen sufficient for histologic examination. This endoscopic ultrasound-guided Tru-Cut biopsy (EUS TCB) device has an outer catheter sheath, an internal 19-G cutting sheath, an 18-mm-long specimen tray, a 5-mm-long stylet tip ( Fig. 21.1 ), and a built-in spring-loaded mechanism that makes automated acquisition of biopsy specimens possible. However, various studies have proven that it has no meaningful advantages over EUS FNA and its use has been mostly abandoned.

Fig. 21.1

Nonhandle portion of the Tru-Cut needle demonstrating the following: outer “catheter sheath,” internal 19-G “cutting sheath” that shaves off the tissue specimen; an 18-mm-long “specimen tray,” which accommodates the tissue core; and a 5-mm-long “stylet tip.”

Adapted with permission from Levy MJ, Wiersema MJ. EUS-guided Trucut biopsy. Gastrointest Endosc 2005;62:417–26.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Using a Standard 22-Gauge Needle


In 2000, Voss and colleagues, in an attempt to overcome some of the limitations of EUS FNA, described their experience in obtaining tissue specimens from pancreatic masses using a standard 22-G FNA needle in association with high negative suction pressure by using a 30-ml syringe. They were able to gather tissue core specimens in 81% of the patients, with a diagnostic accuracy of 74%. Subsequently other groups reported their experience in using a standard 22-G FNA needle with or without high negative suction pressure to obtain samples for histologic evaluation. In particular, Larghi et al. used the Alliance II system to obtain a high steady and continuous negative suction. They named their procedure EUS-guided fine-needle tissue acquisition (EUS FNTA) to distinguish it from standard EUS FNA.

Design and Technique

The EUS FNTA technique with high negative pressure developed by Larghi et al. is performed by using the Alliance II inflation system (Boston Scientific Corp.). Once the needle is advanced into the target lesion under real-time EUS imaging, the stylet is withdrawn and the Alliance II system is attached to the proximal end of the standard 22-G FNA needle. The Alliance II system is then turned into the suction mode, and a high negative continuous pressure corresponding to the 35-mL or the 60-mL syringe is applied. The lock of the syringe is then opened to steadily and continuously apply high negative suction pressure during the to-and-fro movements of the needle inside the target lesion.


Results of studies evaluating the possibility of acquiring a tissue biopsy sample for histologic examination using a standard 22-G needle are summarized in Table 21.1 . Variable yields and diagnostic accuracies have been found in the different studies, possibly related to the different techniques used and how the samples were handled. More recently, most of the studies evaluating the capability of standard 22-G needles to acquire tissue specimens for histologic examination and to reach a definitive diagnosis have been conducted in comparison with the 22-G ProCore (Cook Medical) needles, and their results will be presented in a paragraph that follows. Briefly, standard FNA needles demonstrated a diagnostic adequacy of 75%, a diagnostic accuracy of 86%, and a rate of histologic core specimen acquisition of 78%.

TABLE 21.1

Studies Evaluating the Possibility of Acquiring a Tissue Biopsy Sample for Histologic Examination Using a Standard 22-Gauge Fine-Needle Aspiration Needle

Author (Year) No. of Patients Patient Population Yield of Core Tissue (%) Diagnostic Accuracy (%)
Voss (2000) , a 99 Pancreatic masses 81 68
Larghi (2005) , b , c 27 Solid masses 96 76.9
Iglesias-Garcia (2007) 62 Pancreatic masses 83.9 88.7
Möller (2009) 192 Pancreatic masses 86.5 71.4
Gerke (2010) , c 120 Solid masses and lymph nodes 27.8 77.8 d
Noda (2010) 32 Solid masses and lymph nodes NA 93.9
Imai (2011) 21 Autoimmune pancreatitis 100 0
Imai (2011) 64 Pancreatic cancer NA 92
Kanno (2012) 25 Autoimmune pancreatitis 80 84
Seicean (2016) 118 Pancreatic masses 94 89

a Using high negative suction pressure with a 30-mL syringe.

b Using high negative suction pressure obtained using the Alliance II inflation system.

c Results obtained with a single needle pass for tissue acquisition performed at the end of a standard fine-needle aspiration.

d Diagnostic accuracy calculated based on both histologic and cytologic specimens.

Endoscopic Ultrasound Fine-Needle Biopsy Using a Standard 19-Gauge Needle


Between 2005 and 2006, two Japanese investigators first reported their experience in using a standard 19-G needle to gather core biopsy specimens for histologic examination in patients with solid pancreatic masses and with mediastinal and/or intraabdominal lymphadenopathy of unknown origin. They reported overall diagnostic accuracies of 69% and 98%, respectively. This discrepancy in the overall reported accuracy was due to the high rate of failure (five out of eight patients, 62.5%) when the sampling procedure was performed from the duodenum, as required for patients with pancreatic head and uncinate process masses.

Inspired by these very promising results and in an attempt to overcome the limitations of using a standard 19-G needle through the duodenum, we modified the technique described by Itoi et al. and by Yasuda et al. by removing the stylet before insertion of the needle into the working channel of the EUS scope in order to increase needle flexibility and improve its performance. This technique, which we continued to name EUS FNTA to distinguish it from EUS FNA, was tested in different patient populations and in some specific cases, in which a histologic sample could be more useful to reach a definitive diagnosis.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Technique

The EUS FNTA technique is performed by using a disposable standard 19-G needle. The needle is prepared before insertion into the working channel of the echoendoscope by removing the stylet and attaching to its proximal end a 10-mL syringe already preloaded with 10 mL of negative pressure ( Video 21.1 ). The needle is then advanced under EUS guidance a few millimeters inside the target lesion. After opening the lock of the syringe to apply negative pressure, two or three to-and-fro motions inside the lesion using the fanning technique are made, which together account for one needle pass. The needle is removed after closing the lock of the syringe, and the collected specimens are placed directly in formalin by flushing the needle with saline and sent for histologic examination.

Video 21.1

Technique of Endoscopic Ultrasound-Guided Fine-Needle Tissue Acquisition Using a Standard 19-G Needle


The results of all studies in which a standard 19-G FNA needle has been used to gather samples for histologic analysis, independent of the technique utilized, are summarized in Table 21.2 , and representative cases of histologic samples obtained with a standard 19-G FNA needle are presented in Fig. 21.2 . As shown in Table 21.2 , apart from the study by Itoi et al., in which a high technical failure rate was found when the procedure was performed through the duodenum, and the study by Eckardt et al. involving patients with GI subepithelial lesions, the overall technical success and yield for a tissue core in all the published studies were above 90%. Moreover, the overall diagnostic accuracy was also found to be higher than 90%, with the only exception being the study by Iwashita and colleagues, in which only patients with a pancreatic mass suspicious for autoimmune pancreatitis (AIP) were evaluated. In the latter study, despite specimens for histologic analysis being obtained in 93% of the patients, a definitive histologic diagnosis of AIP based on lymphoplasmacytic infiltration around pancreatic ducts, obliterative phlebitis, and/or positive IgG4 immunostaining could be possible in only 43% of the cases. This low diagnostic yield can be attributed to the patchy distribution of the specific histologic changes of AIP, thus rendering the amount of tissue obtained with EUS-guided biopsy insufficient to establish a definitive diagnosis. On the other hand, in all patients with available tissue, a malignant etiology could be excluded, which is extremely important in order to safely start empirical therapy for AIP with steroids.

TABLE 21.2

Studies Evaluating the Possibility of Acquiring a Tissue Biopsy Sample for Histologic Examination Using a Standard 19-Gauge Fine-Needle Aspiration Needle

Author (Year) No. of Patients Patient Population Technical Success (%) Yield (%) Diagnostic Accuracy (%)
Itoi (2005) , a 16 Pancreatic masses 81 68.8 68.8
Yasuda (2006) 104 Mediastinal and/or abdominal lymphadenopathy 100 100 98.1; 88 accuracy in subclassification of lymphoma
Iwashita (2008) 41 Mediastinal lymphadenopathy suspicious for sarcoidosis 100 95.1 95.1
Larghi (2011) , b , c 120 Heterogeneous patient population 99.2 96.7 93.2;
Larghi (2012) , c 30 Pancreatic masses suspicious for nonfunctional neuroendocrine neoplasia 100 93.3 93.3
Iwashita (2012) 44 Pancreatic masses suggestive of autoimmune pancreatitis 100 93 43.2
Yasuda (2012) 152 Mediastinal and/or abdominal lesions suspicious for lymphoma 97 97 93.4; 95 accuracy in subclassification of lymphoma (142 patients)
Varadarajulu (2012) 38 Pancreatic masses/subepithelial lesions 100 94.7 94.7
Stavropoulos (2012) , d 22 Patients with abnormal liver tests undergoing endoscopic ultrasound to rule out biliary obstruction 100 91 91
Eckardt (2012) 46 Gastric subepithelial lesions NA 59 52
Larghi (2014) , e , c 121 GI Subepithelial lesions 99.2 93.4 93.4
Diehl (2015) 110 Abnormal liver tests or hepatic disease 100 98 98
Iwashita (2015) 111 Patients with solid lesions 99 79 f 95 g

a All failures occurred when sampling was performed from the duodenum.

b Consecutive patients with subepithelial lesions, esophagogastric wall thickening, mediastinal and abdominal masses/lymphadenopathy of unknown origin, pancreatic body or tail lesions after a negative FNA were included in the study.

c The endoscopic ultrasound-guided fine-needle tissue acquisition technique was used.

d Adequate specimen defined as a length of 15 mm with the presence of at least 6 portal tracts.

e All procedures were performed using the forward-viewing endoscopic ultrasound scope.

f Reported as percentage of all passes.

g Only diagnostic accuracy for malignancy is reported.

Fig. 21.2

Representative cases of specimens obtained by EUS FNTA. (A, B) Mediastinal lymph node: (A) abundant tissue fragments, at higher magnification (B) showing caseous material and polynucleated giant cells consistent with a tubercular granuloma, as also later confirmed by polymerase chain reaction (PCR) methods; H&E. (C–E) Body-tail of the pancreas: (C, D) multiple large tissue fragments of a well-differentiated, nonfunctioning, neuroendocrine tumor, with a typical trabecular structure, low-grade histology void of necrosis and mitotic figures (D), and chromogranin A expression at immunohistochemistry (E); (C, D) H&E; (E) immunoperoxidase. (F–H) Perigastric lesion: (F), abundant, large fragments of neoplastic tissue with solid structure, in the absence of necrosis, composed of regular, fused cells with mild atypia (G) intensely immunoreactive for c-Kit (H), consistent with gastrointestinal stromal tumor; (F, G) H&E, (H) immunoperoxidase.

From Larghi A, Verna EC, Ricci R, et al. EUS-guided fine-needle tissue acquisition by using a 19-gauge needle in a selected patient population: a prospective study. Gastrointest Endosc 2011;74:504–10.

In another study involving patients with suspected nonfunctional neuroendocrine tumors, comparison between the ki-67 index determination on biopsy specimens and on surgical specimens using a cutoff of greater than 5% to define G2 tumors found an agreement in all patients. Moreover, in patients with GI stromal tumors, Ricci et al. were able to perform genetic analysis for diagnostic and prognostic purposes, allowing optimization of chemotherapy for initially unresectable cases, where neoadjuvant therapy may be an option.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Using ProCore Needles


Although the Quick-Core needle failed to reach widespread use due to the technical difficulty associated with its utilization and the relative lack of advantages over standard FNA needles, the same manufacturer developed a new needle with a different design, the ProCore needle. To meet most of the needs of EUS-guided FNB, three needle sizes have been initially developed: 19 G, 22 G, and 25 G ( Fig. 21.3 ). Moreover, more recently a 20-G needle with a different design has become available ( Fig. 21.4 ).

Fig. 21.3

Novel 19-G, 22-G, and 25-G ProCore needles with reverse bevel technology for acquisition of tissue samples.

Permisson for use granted by Cook Medical, Bloomington, Indiana.

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Feb 19, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on Techniques for Endoscopic Ultrasound-Guided Fine-Needle Biopsy
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