Endoscopic ultrasound-guided fine needle biopsy in the gastrointestinal tract

INTRODUCTION — Endoscopic ultrasonography (EUS) is a combination of endoscopy and ultrasonography. EUS can be used to visualize and sample mass lesions of the pancreas, gastrointestinal tract, posterior mediastinum, and retroperitoneum. EUS has evolved from a diagnostic imaging modality to one that can also be used for invasive diagnostic and therapeutic procedures. These advances are largely due to the introduction of linear scanning instruments that are used to track a needle across an imaging plane into a target lesion. The ability of EUS to guide a needle for tissue acquisition into lesions that are too small to be identified by radiographic imaging (eg, computed tomography) or that are too well-encased by vascular structures to allow for a percutaneous approach, has secured its role in a variety of clinical settings.

EUS-guided fine needle aspiration (FNA) can be performed at the same time as the diagnostic examination and offers a diagnostic accuracy of up to 90 percent depending upon the site of the target lesion. However, EUS-FNA is associated with several limitations. It may not always be possible to assess the adequacy of sampling during the procedure, and cytologic interpretation can be hampered by the presence of blood and benign epithelial cells. Furthermore, lesions that are well differentiated or fibrotic are more difficult to diagnose using cytology alone. Finally, EUS-FNA typically yields a small sample and destroys the tissue architecture, thereby limiting diagnostic accuracy for some gastrointestinal lesions (eg, gastrointestinal stromal tumors).

Larger caliber cutting needles were designed to perform fine needle (core) biopsy that overcomes the limitations associated with FNA. These needles acquire larger tissue specimens, thereby preserving tissue architecture and permitting histologic rather than only cytologic examination. This topic will review the technique, indications, contraindications, and adverse events related to EUS-guided fine needle biopsy in the gastrointestinal tract.

A discussion on EUS-guided FNA in the gastrointestinal tract is presented separately. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract".)

Endoscopic ultrasound-guided sampling of lesions in the mediastinum is discussed separately. (See "Endoscopic ultrasound-guided sampling of the mediastinum: Technique, indications, contraindications, and complications".)

TERMINOLOGY — EUS-guided tissue acquisition can be performed with the following methods [1]:

●EUS-guided fine needle biopsy – EUS-guided fine needle biopsy refers to EUS-guided core biopsy of a lesion to obtain tissue for histology and additional studies such as immunohistologic staining.

●EUS-guided fine needle aspiration – EUS-guided fine needle aspiration refers to EUS-guided puncture of a lesion followed by aspiration of cells or fluid for cytology.

PROCEDURE

Patient preparation — The preprocedure preparation for patients undergoing EUS-fine needle biopsy (FNB) is similar to the preparation for patients undergoing upper gastrointestinal endoscopy (see "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Patient preparation'):

●Adjusting medications – Most patients do not need to discontinue aspirin or nonsteroidal anti-inflammatories when undergoing EUS-guided sampling. The management of antiplatelet and anticoagulant therapy in those undergoing endoscopy is typically individualized and managed in conjunction with the prescribing subspecialist, and is discussed separately. (See "Management of antiplatelet agents in patients undergoing endoscopic procedures" and "Management of anticoagulants in patients undergoing endoscopic procedures" and "Gastrointestinal endoscopy in patients with disorders of hemostasis".)

●Antibiotic prophylaxis – Most patients do not need prophylactic antibiotics prior to sampling solid lesions of the gastrointestinal tract, while some patients with cystic lesions require preprocedure antibiotics (eg, patients with mediastinal cysts). The indications for antibiotic prophylaxis are discussed in more detail separately. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic ultrasound'.)

Equipment

Echoendoscope — EUS is performed with an echoendoscope (an endoscope with an ultrasound transducer engineered into its tip). The echoendoscope is a flexible instrument that has a working channel and can obtain reliable images at a depth ranging from 3 to 80 mm from the transducer. Two types of echoendoscopes exist, radial and curvilinear, and the curvilinear echoendoscope is used for FNB. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract", section on 'Echoendoscope' and "Endoscopic ultrasound: Examination of the upper gastrointestinal tract", section on 'Equipment'.)

FNB needle — FNB or core biopsy needles have been designed to acquire larger "core" specimens that preserve tissue architecture and permit histologic evaluation and immunohistologic staining. The features of FNB needles that distinguish them from fine needle aspiration (FNA) needles include a geometric shape of the cutting tip (eg, Franseen-type needle, fork-tip needle) or a side slot (core trap) at the needle tip [2-5]. While some features of the FNB needle may vary depending on the manufacturer, the procedural techniques are generally similar among devices and comparable with FNA needles [1]. The first FNB device that was used with curvilinear echoendoscopes to obtain core biopsies was the Tru-cut biopsy needle; however, this needle device is no longer being manufactured [6].

Needles that do not have these special geometry designs or side slot features are referred to as FNA needles [1]. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract", section on 'Fine aspiration needles'.)

The FNB device uses a catheter assembly with an attached handle that secures to the working channel of the echoendoscope using a luer lock mechanism. An adjustable "screw-stop lock" is incorporated into the handle, and when unlocked, allows advancement of the needle up to 8 cm.  

The available FNB devices have a hollow core needle that ranges in size from 19 to 25 gauge and that typically uses suction to obtain a tissue specimen. Some needles also have a slot or serrated edge to enhance procurement of the biopsy specimen.

Technique — The technical procedure of EUS-FNB in the gastrointestinal tract includes examining the target lesion and surrounding structures, selecting a site for biopsy, preparing the needle device, advancing the needle to the tip of the echoendoscope, puncturing the target lesion, obtaining the biopsy specimen, and retrieving and preparing the specimen. While the technique is generally similar among FNB needle devices, reviewing the instructions provided by the needle manufacturer is an essential step.

Selecting a site for needle biopsy — Selecting a site for biopsy includes examining the target lesion and the surrounding structures with Doppler imaging to avoid blood vessels that may be located between the tip of the echoendoscope containing the needle and the target lesion.

Lesions can be approached from the esophagus, stomach, duodenum, colon, and rectum with FNB needles that are commercially available because they are sufficiently flexible to permit angulation. Use of the earlier versions of the FNB needle was generally limited to locations that did not require sharp angulation (eg, esophagus, body of the stomach).

Preparing and advancing the needle device — Prior to insertion into the echoendoscope, the FNB device is prepared by adjusting the outer sheath length of the device that is specific for the endoscope manufacturer.

After the FNB device has been prepared and the target lesion without intervening blood vessels has been identified, the FNB device is advanced through the working channel of the echoendoscope (with the endoscope's elevator in the down position). The needle is advanced until the device handle meets the insertion site of the working channel, and then the device is secured in place by using the luer lock mechanism.

Performing needle biopsy — Under direct ultrasound guidance, the needle is directed through the wall of the gastrointestinal organ (eg, stomach) nearest to the target. Next, the target lesion is punctured by advancing the needle into the lesion of interest. Occasionally, the stylet must be slightly retracted to expose the needle tip to permit entry.

The stylet is then fully withdrawn and negative pressure is applied with the syringe provided with the needle kit. Small to-and-fro movements are made with the needle while it is within the lesion to collect tissue. Although the aforementioned technique for applying negative pressure is used by most advanced endoscopists, some endoscopists prefer to use the slow-pull technique, in which the stylet is slowly withdrawn while moving the needle in a to-and-fro motion. In addition, some endoscopists do not use negative pressure when performing FNB.

The following technical tips can be helpful for obtaining a diagnostic specimen:

●Decreasing negative pressure and limiting the time that the needle is within the target lesion may reduce the likelihood of obtaining bloody samples that may be more difficult to assess histologically.

●For lesions with areas of necrosis, selecting a biopsy site that has ultrasound features suggesting a solid appearance may improve yield.

Retrieving and preparing the specimen — After the needle device containing the specimen is removed from the echoendoscope, the tissue is retrieved by advancing the stylet through the needle. Alternatively, an air-filled syringe can be used to eject the specimen into a tissue preservative solution.

Touch preps can be made from the histologic core (prior to placement in formalin) and are prepared by gently touching a glass slide against the core of tissue. An onsite cytopathologist or cytotechnologist can then provide an assessment of the adequacy of sampling (ie, rapid onsite evaluation). Core samples are fixed in formalin, embedded in paraffin, and stained with hematoxylin and eosin prior to formal pathologic interpretation (picture 1).

Core samples can also be submitted in sterile saline. When the diagnosis of lymphoma is suspected, some tissue is reserved for flow cytometry which is performed on an unfixed cell suspension (eg, using Roswell Park Memorial Institute solution) or by immunohistochemistry on tissue sections. (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma", section on 'Analysis of biopsy material'.)

Post procedure care — After the procedure, patients are recovered from sedation or anesthesia. A fever after the procedure is not typical and warrants further investigation (eg, blood cultures). The equipment is cleaned per procedural protocol. (See "Preventing infection transmitted by gastrointestinal endoscopy", section on 'Overview of endoscope reprocessing'.)

CLINICAL APPLICATIONS

Diagnostic role of fine needle biopsy — EUS-fine need biopsy (FNB) is used to sample lesions within or adjacent to the gastrointestinal tract (eg, pancreatic lesions) and peri-intestinal structures (eg, lymph nodes). (See 'Lesion type' below.)

EUS-FNB may be used as a diagnostic tool in the following clinical settings:

●The suspected condition requires histologic evidence (rather than cytology only) to establish a diagnosis (eg, gastrointestinal stromal tumor) or to confirm disease progression (eg, lymph node metastasis) [7,8]. Specimens obtained with FNB generally have preserved tissue architecture that can establish a diagnosis and potentially avoid additional invasive diagnostic procedures [8-13]. As an example, in a study of 109 patients with 114 intra- or extraintestinal mass lesions and/or peri-intestinal lymph nodes, EUS-FNB yielded an adequate specimen for 112 lesions (98 percent), with a diagnostic sensitivity of 90 percent and a specificity of 100 percent for malignancy [8].

●Tissue specimens for additional testing are needed [14]. FNB typically yields an adequate amount of tissue for ancillary testing (eg, immunohistochemical or molecular genetic testing).

●Cytology from fine needle aspiration (FNA) of the lesion has been nondiagnostic [15]. In clinical practice, EUS-FNA and EUS-FNB are not regarded as competing modalities, but rather as complementary.

EUS-guided sampling with FNB technique typically requires fewer needle passes for obtaining tissue than FNA, while the overall diagnostic yield is not significantly different between the two techniques [14,16-19]. In a meta-analysis of nine studies including 576 patients undergoing EUS-guided tissue sampling of intra- and extraintestinal mass lesions or lymph nodes, diagnostic accuracy was not significantly different for FNB technique compared with FNA (86 versus 86 percent) [16]. FNB was associated with fewer needle passes compared with FNA (standardized mean difference -1.18; 95% CI -1.78 to -0.58). (See 'Lesion type' below.)

Limitations of EUS-FNB include availability of equipment and advanced endoscopy expertise, and the rare occurrence of false-negative or false-positive results that may lead to unnecessary surgery and is mostly related to interpretation of histologic material [20].

Lesion type

Gastrointestinal subepithelial lesions — Subepithelial lesions are located under the gastrointestinal mucosa and originate from the intestinal wall itself or outside the wall. We use EUS-FNB to evaluate subepithelial lesions (eg, suspected gastrointestinal stromal tumors [GISTs]), and such lesions are most commonly located in the upper gastrointestinal tract [21-23].

Data have suggested that EUS-FNB for subepithelial lesions has helped to establish the diagnosis while rates of adverse events were low. In a study including 70 subepithelial lesions in the upper gastrointestinal tract that were sampled using both FNB and FNA, EUS-FNB was associated with higher diagnostic sensitivity for malignancy (90 versus 52 percent) and higher diagnostic accuracy (83 versus 49 percent) compared with FNA [23]. Postprocedure bleeding was reported in one patient who underwent EUS-FNB and was controlled endoscopically (adverse event rate, 1 percent).

Endosonographic findings and diagnosis of gastrointestinal subepithelial lesions including GISTs are discussed in more detail separately. (See "Endoscopic ultrasound for the characterization of subepithelial lesions of the upper gastrointestinal tract" and "Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors".)

Peri-intestinal lymph nodes — We use EUS-FNB to sample peri-intestinal lymph nodes in patients with lymphadenopathy and/or suspected lymphoma, and the diagnostic yield of FNB for lymph nodes has been generally similar to EUS-FNA [15,19,24-26]. As an example, in a study of 206 patients who underwent EUS-guided lymph node sampling, the sensitivity and diagnostic accuracy was not significantly different for EUS-FNB compared with FNA (75 versus 67 percent and 83 versus 79 percent, respectively) [25]. However, EUS-FNB was associated with higher specificity (100 versus 94 percent), while no adverse events were reported in either group.

Pancreatic lesions — EUS-FNB has been used for the following pancreatic lesions:

●Autoimmune pancreatitis – EUS-FNB has been used for evaluating patients with suspected autoimmune pancreatitis, a nonfocal benign pancreatic disease, while the role of EUS-FNA has been limited because of small specimen size and lack of tissue architecture [11,27-29]. In a systematic review of 20 studies using either FNB or FNA technique for nearly 600 tissue acquisition procedures for suspected autoimmune pancreatitis, FNB was associated with a higher diagnostic sensitivity compared with FNA (60 versus 42 percent) [29]. In addition, FNB was associated with a higher rate of obtaining an adequate specimen (97 versus 80 percent). (See "Autoimmune pancreatitis: Clinical manifestations and diagnosis".)

●Solid pancreatic lesions – EUS-FNB has been used for sampling solid pancreatic lesions located in the pancreatic head, neck, body, and tail. EUS-FNB may be particularly helpful when EUS-FNA specimens have been nondiagnostic or additional tissue studies (eg, molecular testing) are needed [14,30]. In a study including 166 patients with solid pancreatic lesions, EUS-FNB was associated with a higher diagnostic yield compared with FNA (99 versus 92 percent), while the mean number of needle passes for FNB was lower (3 versus 4 needle passes) [14]. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer" and "Endoscopic ultrasound in the staging of exocrine pancreatic cancer".)

Use of EUS-FNB for sampling solid pancreatic lesions may minimize the need for cytologic rapid onsite evaluation (ROSE) [31,32]. ROSE provides timely feedback on tissue adequacy, but it requires onsite expertise in cytopathology. In a trial including 800 patients with solid pancreatic lesions, there were no significant differences in diagnostic accuracy for patients who had EUS-FNB alone compared with EUS-FNB with ROSE (97 versus 96 percent) [32]. In addition, the mean sampling procedure time was shorter with FNB alone (12 versus 18 minutes). This study suggests that diagnostic yield with FNB alone was high because FNB provided architecturally-preserved core tissue samples for histologic analysis. However, the decision to use ROSE is individualized and is informed by multiple factors including need for molecular testing, history of nondiagnostic examination, lesion characteristics, suspected diagnosis, endosonographer experience, cytopathologist experience, and institutional protocol. (See 'Retrieving and preparing the specimen' above.)

●Cystic pancreatic lesions – We use EUS-FNB for evaluating patients with suspected pancreatic cystic neoplasms (image 1 and picture 2); however, some advanced endoscopists use EUS-guided through the needle biopsy to sample cysts that have failed previous diagnostic FNA, and this is discussed separately [11]. (See "Pancreatic cystic neoplasms: Clinical manifestations, diagnosis, and management", section on 'Cyst fluid analysis'.)

CONTRAINDICATIONS — Contraindications to EUS-fine needle biopsy include:

●Patients who cannot tolerate moderate sedation (eg, poor performance status), monitored anesthesia care, or general anesthesia. (See "Anesthesia for gastrointestinal endoscopy in adults".)

●Patients who are hemodynamically unstable.

●Patients with gastrointestinal obstruction (eg, duodenal stricture due to a lesion in the head of the pancreas) may undergo EUS but imaging may be limited to the areas proximal to the level of obstruction. However, the lesion may still be accessible for FNB.

●Lack of a biopsy needle path to the target lesion that avoids vascular structures.

●Patients with abnormal coagulation studies (platelet count ≤50,000/microL or international normalized ratio >1.5).

ADVERSE EVENTS — Endoscopic ultrasound (EUS) and EUS-guided sampling are generally safe procedures. Some complications are due to the effect of procedural sedation, while others are due to the endoscopy itself or the sampling procedure. In a series of 247 patients who underwent EUS-fine needle biopsy (FNB), the overall complication rate was 2 percent (eg, minor bleeding, pneumonia, mucosal tear), and no deaths were reported [13].

Endoscopy related — Complications associated with EUS may be due to the gastrointestinal endoscopy itself (without FNB) and/or the associated sedation and anesthesia (eg, hypotension) [33]. These complications are discussed in more detail separately. (See "Adverse events related to procedural sedation for gastrointestinal endoscopy in adults" and "Overview of upper gastrointestinal endoscopy (esophagogastroduodenoscopy)", section on 'Complications'.)

Fine needle biopsy-related — Reported complications of FNB are generally uncommon and include:

●Bleeding (usually minor, hemorrhage requiring transfusion is rare) [10,13,34-36].

●Pancreatitis after sampling the pancreatic parenchyma or a pancreatic lesion [14,36,37].

●Abdominal pain (usually minor and transient) [38,39].

●Infection such as pneumonia (rare) [13].

●Needle tract seeding of malignant cells (rare) [40].

SUMMARY AND RECOMMENDATIONS

●Background – Endoscopic ultrasonography (EUS) is a combination of endoscopy and ultrasonography. EUS can be used to visualize and sample lesions of the pancreas, gastrointestinal tract, posterior mediastinum, and retroperitoneum. EUS has evolved from a diagnostic imaging modality to one that can also be used for invasive diagnostic and therapeutic procedures. (See 'Introduction' above.)

EUS-guided tissue acquisition can be performed with the following methods (see 'Terminology' above):

•EUS-guided fine needle biopsy – EUS-guided fine needle biopsy (EUS-fine needle biopsy [FNB]) refers to EUS-guided core biopsy of a lesion to obtain tissue for histology and additional studies such as immunohistologic staining.

•EUS-guided fine needle aspiration – EUS guided fine needle aspiration (EUS-fine needle aspiration [FNA]) refers to EUS-guided puncture of a lesion followed by aspiration of cells or fluid for cytology.

●Technique – The technical procedure of EUS-FNB in the gastrointestinal tract includes examining the target lesion and surrounding structures, selecting a site for biopsy, preparing the needle device, advancing the needle to the tip of the echoendoscope, puncturing the target lesion, obtaining the biopsy specimen, and retrieving and preparing the specimen. (See 'Technique' above.)

●Clinical applications – EUS-FNB is used to sample lesions within or adjacent to the gastrointestinal tract (eg, subepithelial lesions, pancreatic lesions) and peri-intestinal structures (eg, lymph nodes). EUS-FNB may be used as a diagnostic tool in the following clinical settings (see 'Clinical applications' above):

•The suspected condition requires histologic evidence to establish a diagnosis

•Tissue specimens for additional testing (eg, molecular testing) are needed

•Cytology from FNA of the lesion has been nondiagnostic

●Contraindications – There are few contraindications to EUS-guided sampling which are most commonly related to the upper endoscopy itself including hemodynamic instability, inability to tolerate anesthesia/sedation, and possibly gastrointestinal obstruction. (See 'Contraindications' above.)

●Adverse events – EUS and EUS-guided sampling are generally safe procedures, and complications are infrequently reported. Some complications are due to the effect of procedural sedation (eg, hypotension), while others are due to the endoscopy itself or the sampling procedure (eg, bleeding, pancreatitis). (See 'Adverse events' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael J Levy, MD (deceased), who contributed to earlier versions of this topic review.