Percutaneous biopsy

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Chapter 20 Percutaneous biopsy

Anne M. Covey, Lynn A. Brody

Biopsy Overview

Image-guided needle biopsy is the mainstay for diagnosis of nonpalpable masses almost anywhere in the body. The indications for biopsy continue to evolve, and although percutaneous biopsy of a given mass is possible, it may not be indicated (Thompson et al, 1985). As with any invasive procedure, percutaneous biopsy has associated risks that should be weighed prior to the procedure. Needle biopsy is warranted when the result of the biopsy would potentially affect patient management. These indications include confirmation of preoperative diagnosis, documentation of primary or metastatic disease in patients who are not surgical candidates, evaluation of organ dysfunction, and sampling for special studies such as receptor or gene mutation status.

Several methods are available to obtain tissue, including biopsy by percutaneous needle or by endoluminal and transvenous techniques. Needles ranging in size from 25- to 14-gauge are typically used, and outside the central nervous system, a biopsy can be obtained from almost any abnormality that can be imaged. Most needles contain an inner stylet, which is removed when the needle is appropriately positioned, immediately before obtaining the specimen; the stylet prevents the needle from coring interposed structures and accumulating nontarget material before optimal placement. Smaller “fine” needles (25 to 20 gauge) are used to obtain cytologic specimens or to obtain samples for culture or flow cytometry. Larger needles (19 to 14 gauge) are used to obtain tissue cores when histologic material is required for pathologic diagnosis or when special studies, such as immunohistochemical staining, are to be performed.

Common malignancies in which core specimens may be necessary for diagnosis include lymphoma, sarcoma, thymoma, and mesothelioma. Core material may also be required to diagnose well-differentiated hepatocellular carcinoma (HCC) or benign hepatic tumors. Tissue cores also may be required for mutational analysis in patients for whom targeted therapies are being considered. In most cases, fine needle aspirates are sufficient, and multiple immunohistochemical stains can be used on a single sample, allowing for accurate cell typing.

To increase the likelihood of a diagnostic biopsy and to minimize complications, a high-quality imaging study should be available for review both when the biopsy is being planned and when it is performed. In some cases, careful review of imaging studies may provide a definitive diagnosis, obviating the need for biopsy. Review of preprocedure imaging also influences selection of the most appropriate modality for guidance and patient positioning during the procedure, so that potential problems such as interposed lung, bowel, or blood vessels may be anticipated and avoided. In addition, knowledge of imaging findings allows for appropriate discussion of relevant risks in the informed consent. With proper preprocedure imaging, the biopsy can be planned to avoid unusual or unsustainable positions, complex needle angulation, and challenging breathing instructions.

Review of imaging studies before biopsy also facilitates targeting of the most viable area of a mass. As large masses outgrow their blood supply, they become necrotic, and diagnostic material cannot be reliably obtained in a background of necrosis. Preprocedure contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) can allow for accurate targeting of areas most likely to yield a diagnostic specimen.

Biopsy Technique

Fine Needle Aspiration

A 25- to 20-gauge needle is advanced into the target lesion, and real-time (ultrasound, fluoroscopy, or CT fluoroscopy) or interrupted imaging (conventional CT or MRI) is performed to guide and assess needle position. Coaxial techniques are sometimes useful but are generally unnecessary, but some operators are partial to this technique. Although coaxial biopsy requires the introduction of a larger needle than is used for biopsy, it has the advantage that multiple samples may be obtained without creating a new tract for each pass, and the tract can be embolized or “plugged” to prevent hemorrhage in high-risk situtations (Billich et al, 2008).

Fine needles come in a variety of tip designs. Many physicians use a Chiba-style needle, in which the needle tip and inner stylet are beveled. Our preference is a Westcott-style needle: in addition to a beveled tip, it has a notch in the sidewall of the needle just proximal to the tip; this facilitates the operator’s ability to choose more precisely the location from which the cells will be aspirated.

When needle position has been confirmed, the needle is attached to a disposable syringe. The plunger of the syringe is retracted to apply suction as the needle is moved back and forth within the lesion to obtain a sample. The needle is withdrawn after suction is released, and the specimen is deposited on a glass slide. Smears are made from the biopsy specimen, and these may be used for immediate analysis (e.g., Diff-Quik) or fixed in ethanol for immunohistochemical stains. In some cases, molecular studies may need to be performed on fine needle specimens, and charged slides may be used that electrostatically attract tissue and bind it to the slide. The residual material within the syringe and needle is rinsed in a cell-preserving solution for preparation of a cell block. For cases in which non-Hodgkin lymphoma is suspected, a specimen for flow cytometry may be obtained by rinsing the needle and syringe in a nutrient-rich culture medium (e.g., Roswell Park Memorial Institute medium). When infection is suspected, material can be set aside for culture.

In the ideal situation, an on-site cytopathologist or cytotechnologist can provide an immediate interpretation of the sample; this has been shown to increase the sensitivity of the biopsy, shorten the procedure time, and minimize the number of passes required to obtain a diagnostic specimen (Nasuti et al, 2002; Silverman et al, 1989).

Core Biopsy

The technique for localizing a lesion is identical for fine needle and core biopsies. To obtain a good core sample, a target lesion should be at least 1 cm in maximum dimension, but preferably 2 cm. Because of the typically larger needle size (14 to 19 gauge) used to perform a core biopsy, care should be taken to minimize the possibility of traversing medium-sized arteries, which lack the muscular wall of larger arteries and have an increased tendency to bleed; traversing the colon can result in peritonitis or abscess. Core biopsy needles come in a variety of sizes and styles, including biopsy “guns” and cutting needles that obtain histologic samples manually as the needle is passed back and forth within the lesion.

To confirm adequacy of the specimen, a touch preparation may be prepared on a glass slide for immediate evaluation by a cytopathologist or cytotechnologist. Before being placed in formalin or saline, the core of tissue is placed on a glass slide and gently moved over the slide to allow some cells to collect on the surface. In addition to the tissue sample, material is often collected at the same time that is suitable for cytology, and this increases the diagnostic yield of the procedure. Core samples are commonly placed in formalin. Occasionally, specimens may be sent “fresh” to pathology in saline or on saline-soaked gauze for special studies. Because cells placed in saline eventually undergo cell lysis related to osmotic shifts of saline into the cell, a specimen in saline needs to be fixed or frozen within a few hours to avoid deterioration of the tissue sample. Tissue also may be snap frozen for future studies. The preferred method for processing tissue may vary from institution to institution, and the preference of the pathologists reviewing the material should be determined before initiating a biopsy.

Despite the fact that more tissue is usually obtained during a core needle biopsy than with a fine needle aspiration (FNA) biopsy, the diagnostic rates for most malignancies are not necessarily higher (Longchampt et al, 2000; Stewart et al, 2002). The incremental benefit of a core biopsy in the liver is most notable in the discrimination of a well-differentiated HCC from nodular regeneration in the setting of cirrhosis and in confirmation of benign diagnoses, including hemangioma, adenoma, and focal nodular hyperplasia (Kulesza et al, 2004; Kuo et al, 2004).

Imaging Guidance

Ultrasound

Ultrasound (US; see Chapter 13) is commonly used to guide percutaneous biopsies of the liver, because it is widely available, inexpensive, and portable. US may be used at the bedside or in patients in whom CT guidance is impractical. Lesions larger than 1 cm are often visible, and US allows for real-time visualization of the needle as it courses from the skin into the lesion. This is especially helpful in small lesions that move with respiration and are difficult to target with interrupted imaging modalities. Visualization of smaller caliber needles may be difficult, and many manufacturers make needles specially designed to enhance visibility with US.

Another advantage of US guidance is the capability of multiplanar imaging. This is particularly useful in finding a route to lesions at the hepatic dome that avoids aerated lung and eliminates the risk of causing pneumothorax. Because CT provides a two-dimensional image, complex triangulation often is required to accomplish the same result. Doppler imaging is occasionally helpful in performing a biopsy by enhancing the localization of small lesions. US contrast agents may help identify the most viable regions of a tumor, and it does not use ionizing radiation—a benefit to both the patient and the operator.

Limitations of US include interoperator variability and poor transmission through air and bone, which limits the visualization of some lesions. Additionally, patients who are sedated for biopsy may not be able to cooperate with breathing instructions necessary to facilitate visualization of some masses, including small lesions or those high in the hepatic dome.

Computed Tomography

CT (see Chapter 16) is a common modality for guiding percutaneous biopsies, because it provides superb anatomic detail that gives the operator the ability to plan a path from skin to lesion using the safest approach, clearly visualizing interposed structures. CT is the imaging modality of choice for biopsies of the pancreas, adrenal glands, abdominal and retroperitoneal lymph nodes, and bone and liver lesions that are not well visualized with US, or when biopsy is performed by operators who are not skilled with US. CT is also commonly used for lung lesions, although at our institution, fluoroscopy is preferred by some operators to capitalize on the real-time visualization of the target in the moving background of the lung.

Computed Tomographic Fluoroscopy

Many manufacturers now offer CT fluoroscopy as an option on diagnostic scanners. This produces CT images in near real time. It does expose the operator to ionizing radiation and requires that the operator wear lead, as with conventional fluoroscopy; but it is preferred by some physicians, owing to decreased time between needle manipulation and image availability.

Magnetic Resonance Imaging

Biopsies guided by MRI (see Chapter 17) have been made possible by the advent of open-bore MRI systems that provide access to patients during imaging and the availability of nonferrous biopsy needles and monitoring equipment. The superior contrast resolution of MR allows for targeting of lesions that are difficult to visualize with US and noncontrast CT, and the ability of MRI to image in any plane enhances the targeting of lesions that are not safe to approach or easy to access in the axial plane (Stattaus et al, 2008; Fig. 20.1). Owing to high cost and limited availability, MR-guided biopsies are generally reserved for patients whose lesion cannot be seen or targeted with US or CT. In addition, it is necessary to ensure that nonferromagnetic, MRI-compatible equipment is on hand and that the patient is able to undergo MRI.

FIGURE 20.1 Magnetic resonance (MR)-guided percutaneous liver biopsy. A, Axial T1 MR after contrast administration shows a focal lesion in segment IV in a patient with hepatitis B. B, Noncontrast computed tomography in the same patient at the same level failed to show the lesion. C, Positron emission tomography scan was positive. D, The biopsy was successfully performed using MR guidance in the sagittal plane to avoid the risk of pneumothorax. The biopsy specimen confirmed the diagnosis of hepatocellular carcinoma.

Fluoroscopy

Fluoroscopy is useful for guiding bile duct biopsies. Benign and malignant biliary strictures (see Chapter 18, Chapter 42A, Chapter 42B, Chapter 50A, Chapter 50B, Chapter 50C, Chapter 50D ) often have similar cholangiographic appearances and rarely can be distinguished based on imaging alone (Hadjis et al, 1985; Corvera et al, 2005). Lesions originating within the duct may be sampled by either an endoluminal (see Chapter 14) or a direct percutaneous approach (see Chapter 18). Percutaneous transhepatic biliary drainage allows direct access to the biliary tract for endoluminal biopsy, when satisfactory decompression of the biliary tree has been achieved. Biopsy forceps or brush-biopsy catheters can be used through the existing tract to obtain tissue samples of suspicious areas (Fig. 20.2). The sensitivity of forceps biopsy is in the range of 40% to 80%, higher than that of brush biopsy, which is in the range of 30% to 60%. Specificity for each approaches 98% (Stewart et al, 2001; Govil et al, 2002; Weber et al, 2008), and sensitivity is highest for intraductal lesions and when biopsy is done in conjunction with choledochoscopy to provide direct visualization of the lesion (Ponchon et al, 1996).

FIGURE 20.2 Biliary brush biopsy. A, Transhepatic cholangiogram shows a high bile duct stricture (arrow) in a patient with two indwelling endoscopic stents and a percutaneous biliary drainage catheter. Prior brush biopsy was nondiagnostic. B, A brush (curved arrow) was advanced to the stricture and used to obtain a specimen for cytology. The specimen was diagnostic of cholangiocarcinoma.

Alternatively, after the biliary tree is opacified, a direct percutaneous biopsy of a bile duct lesion may be targeted with fluoroscopy using a transhepatic approach (see Chapter 18; Chawla et al, 1989). This technique is most useful for intrinsic bile duct lesions but may also be used to diagnose lesions adjacent to the bile duct. With this technique, contrast is injected into an indwelling biliary drainage catheter to delineate the targeted bile duct abnormality. A needle is advanced through the anterior abdomen to the lesion, and a specimen is obtained. Confirmation of accurate needle position is made by obtaining oblique fluoroscopic images and by real-time fluoroscopy, when the needle is seen to move the duct or the indwelling catheter or both (Fig. 20.3). Fluoroscopy also is useful to guide percutaneous biopsy of lung nodules and for nontargeted transvenous biopsies of the liver or kidney.

FIGURE 20.3 Percutaneous bile duct biopsy. A, Transhepatic cholangiogram shows a high bile duct stricture (marked by the clamp) of uncertain origin. B, Under fluoroscopic guidance, a 22-gauge needle (curved arrows) was used to target the stricture. C, Oblique imaging confirmed the position of the needle at the site of the bile duct stricture.

New Guidance Equipment

New technology is being developed that allows fusion of multiple modalities. For example, CT and MRI scans can be overlaid with real-time US images to achieve the clarity of the one imaging modality and the real-time visualization capabilities of the other. PET images (see Chapter 15) also can be fused to demonstrate sites of highest metabolic activity. Additionally, robotic guidance systems have been piloted in an effort to optimize speed and accuracy of needle placement.

Biopsy of Specific Sites

Liver Biopsy

Percutaneous liver biopsy is performed to determine the nature of focal liver masses, the cause and extent of cirrhosis, or the cause of liver dysfunction (see Chapter 64, Chapter 65, Chapter 70A, Chapter 70B ). Modern cross-sectional imaging techniques—including ultrasound, CT, and MRI—allow percutaneous biopsy of both subcentimeter and deep lesions to be performed on an outpatient basis with minimal morbidity. With current techniques, almost any liver lesion can be targeted percutaneously; most liver lesions larger than 5 mm are suitable for biopsy (Yu et al, 2001). Fine needle biopsy of liver lesions has a sensitivity of 69% to 97% (Ohlsson et al, 2002).

Focal Liver Lesions

Focal liver lesions may be solitary or multiple. For a solitary lesion, several benign conditions—cyst, hemangioma, focal nodular hyperplasia, and adenoma—often can be diagnosed confidently by high-quality cross-sectional imaging, obviating the need for biopsy (see Chapter 16, Chapter 17, Chapter 79A, Chapter 79B ; Gibbs et al, 2004; Hussain et al, 2004; Kim et al, 2004). These diagnoses should be considered in all solitary liver lesions, unless they are known to be new in the setting of a known cancer or in patients at risk for primary HCC.

HCC may also be diagnosed based on imaging and clinical criteria. In patients with cirrhosis and an arterial enhancing liver mass greater than 2 cm, an α-fetoprotein value of greater than 400, or two concordant imaging studies diagnostic of HCC, biopsy is generally unnecessary (Bruix et al, 1981). When the diagnosis of HCC is considered, and these criteria are not met, the diagnosis often can be established based on cytology alone. Smaller, encapsulated tumors are more likely to be well differentiated, and tissue cores may be required to distinguish a well-differentiated tumor from normal or cirrhotic liver. Because of the risk of tumor seeding in the biopsy tract for a lesion highly suspicious for HCC (Chaudhry et al, 2004; Perkins, 2007; Durand et al, 2007), when a curative treatment is possible, biopsy should be performed only after consultation with a hepatobiliary surgeon and after referencing the most current imaging and clinical criteria.

Multifocal solid liver lesions most commonly represent metastatic disease. In such cases, biopsy may be requested to 1) confirm the presence of metastatic disease in a patient with a known primary; 2) establish tumor type and stage simultaneously at initial presentation; 3) acquire tissue for genetic analysis, such as c-kit mutation in a patient with metastatic gastrointestinal stromal tumor; or 4) obtain histologic samples for patients undergoing experimental therapies.

Liver Parenchyma Biopsy

Core liver biopsy is used to grade and stage liver disease in patients with abnormal liver function studies, chronic hepatitis, and known or suspected cirrhosis (see Chapter 64, Chapter 65, Chapter 70A, Chapter 70B ). Gastroenterologists have historically performed most liver biopsies without imaging guidance; however, unusual anatomy occasionally makes imaging-guided biopsy advisable. Adequate tissue cores can be obtained with needles 20 gauge and larger, although needles 18 gauge and larger provide a more generous specimen for analysis (Guido & Ruggae, 2004; Maharaj et al, 1986).

Transvenous Biopsy

Transjugular liver biopsy is a useful alternative to percutaneous biopsy in patients with coagulopathy or when hepatic venous pressure measurements are required (Sawyerr et al, 1993; Garcia-Compean & Cortes, 2004). Although transvenous biopsy is seemingly more invasive than percutaneous biopsy, the risk of significant bleeding in coagulopathic patients is minimized using a transvenous approach, because bleeding from the biopsy site tracks back into the venous circulation and not into the abdominal cavity, as can happen with percutaneous biopsies. Proper technique to avoid puncture of the liver capsule is crucial to optimize safety.

In this technique, a venous sheath is introduced into a hepatic vein, most commonly the right hepatic vein, from a right internal jugular approach. Pressure measurements may be obtained to evaluate the source (presinusoidal, sinusoidal, or postsinusoidal) and degree of portal hypertension. A core biopsy needle or biopsy forceps is introduced through the sheath into the liver parenchyma to obtain histologic samples (Fig. 20.4). Care must be taken to avoid performing the biopsy from a peripheral approach, because this increases the risk that the liver capsule will be punctured and that peritoneal hemorrhage will result.

FIGURE 20.4 Transjugular liver biopsy. A, Right hepatic venogram through a sheath placed via the right internal jugular vein. B, A 19-gauge automated flexible biopsy needle with a 20-mm throw (arrow) is advanced through a metal cannula and directed anteriorly as the biopsy specimen is obtained.

Transvenous biopsy is only used for nontargeted parenchymal biopsy; it cannot be used for biopsy of a focal lesion. Transvenous biopsy of the kidney also has been reported and may be useful for evaluation of renal dysfunction in coagulopathic patients (Cluzel et al, 2000). This may be particularly convenient in coagulopathic patients who require both parenchymal hepatic and renal biopsies.

Biopsy of Other Organs

Adrenal Biopsy

The adrenal gland is a common site of metastatic disease. This gland also is the site of many benign neoplasms, and adenomas occur in 5% of individuals (Abecassis et al, 1985; Libe et al, 2002). Adrenal biopsy can often be avoided, as MRI can sometimes distinguish between an adenoma and a metastasis (National Institutes of Health, 2002). In some cases, the mass remains indeterminate, and biopsy is indicated. Because of the posterior approach used for all left and some right adrenal biopsies, it is common to traverse the lung, introducing the possibility of a pneumothorax. The right adrenal gland can alternatively be targeted from a lateral, transhepatic approach to eliminate the risk of pneumothorax (Fig. 20.5).

FIGURE 20.5 Adrenal biopsy. A, Transpeural biopsy of right adrenal mass (arrows). B, Transhepatic right adrenal mass (arrows) biopsy eliminates the risk of pneumothorax.

Complications of Percutaneous Biopsy

Any invasive procedure has risks. Risks of biopsy include bleeding, pneumothorax, infection, bile leak, and needle-tract seeding of tumor. The risks vary depending on the organs involved. To minimize the risk of bleeding, we advocate that all patients should have appropriate laboratory work before biopsy, including a complete blood count and coagulation profile. Although criteria differ from institution to institution and from physician to physician, a platelet count of greater than 50,000 µL and an international normalized ratio (INR) less than 1.5 are acceptable in most cases. Biopsy in thrombocytopenic patients can be performed with platelet coverage, although the decision to proceed with biopsy should be considered carefully. For patients with an elevated INR, transfusion of plasma or supplementation with vitamin K is required. Elevated partial thromboplastin time (PTT) in patients not on heparin usually is due to circulating antiphospholipid cardiolipins and is not typically clinically significant. A test of bleeding time may be performed to evaluate the significance of an elevated PTT in select patients. It is advisable to have patients stop antiplatelet medications, if possible, to minimize the risk of bleeding; however, the risk of stopping antiplatelet therapy must be weighed against the risk of bleeding from the biopsy; occasionally the balance favors performing the biopsy while the patient remains on the regular medication.

The risk of significant bleeding after liver biopsy is less than 1% (Piccinino et al, 1986; Riemann et al, 2000). In most cases, the bleeding is self-limited, and conservative management comprising observation and hydration is sufficient. In patients with more significant bleeding, hepatic angiography and potential embolization of an injured artery may be required (Fig. 20.7). Some authors advocate placing absorbable gelatin sponge (Gelfoam) pledgets in the biopsy tract through the needle after core biopsy, but this has not been shown definitively to decrease the risk of major bleeding (Hatfield, 2008).

FIGURE 20.7 Hemorrhage complicating liver biopsy. A, Contrast-enhanced computed tomographic scan 5 days after liver biopsy shows a large subcapsular hematoma (arrow) with active extravasation of contrast from the liver mass (curved arrow). B, Angiography shows active extravasation (curved arrow) from peripheral segment VIII artery that was successfully embolized with stainless steel coils (C; arrow).

Pain out of proportion to imaging findings after liver biopsy may be due to bile peritonitis (Ruben & Chopra, 1987). Care should be taken to minimize needle passes through the gallbladder, cystic duct, or dilated bile ducts. If the gallbladder is inadvertently punctured, it should be aspirated as completely as possible before removing the needle. Bile leaks resulting in discernible collections are rare after liver biopsy in the absence of downstream biliary obstruction.

Adrenal masses and lesions in the dome of the liver often require an approach for biopsy that crosses the lung base, putting patients at risk for pneumothorax. The two most common complications after lung biopsy include hemoptysis and pneumothorax (Westcott et al, 1997). Hemoptysis occurs in up to 30% of lung biopsies and is usually self-limited, but it can be frightening to the patient. Pneumothorax occurs in 20% to 30% of patients after biopsy and requires placement of a chest tube in approximately 6% of cases. The risk of pneumothorax is typically related more to patient than technical factors, although depth of the target lesion, number of pleural surfaces transgressed, and patient positioning (prone positioning decreases the risk of pneumothorax) have been shown to affect the likelihood. Elderly patients and patients with underlying chronic obstructive pulmonary disease are more prone to developing a pneumothorax requiring treatment (Covey et al, 2004). A symptomatic or enlarging pneumothorax is treated with a small-bore chest tube (generally 8 to 12 Fr) and occasionally necessitates hospital admission.

Hemorrhagic pericardial tamponade is a rare, potentially life-threatening complication after mediastinal biopsy (Kucharczyk et al, 1982). Although hypoxemia may be a feature, this complication can be distinguished from iatrogenic pneumothorax clinically by the development of hypotension with narrowing of the pulse pressure and diminished amplitude of the electrocardiogram complex on the monitor. The diagnosis can be confirmed immediately by scanning the heart and pericardium, and it can be treated by directly placing a drainage catheter into the pericardial space.

Needle-tract seeding after percutaneous biopsy is a worrisome complication. The interval between biopsy and appearance of a tract metastasis is 6 to 24 months (Kosugi et al, 2004; Schotman et al, 1999). The risk overall is likely greater than reported, but current understanding is that the risk in HCC is in the range of 2% to 3% (Perkins, 2007; Stigliano et al, 2007). Although the incidence is relatively small, the possibility of rendering a patient ultimately incurable because of tract or peritoneal seeding should be considered in the risk/benefit analysis for each patient. For this reason, some surgeons do not advocate percutaneous biopsy for patients with potentially resectable lesions highly suspicious for malignancy (Cha et al, 2002; Al-Leswas et al, 2008); this sentiment is particularly strong among transplant surgeons in regard to patients with HCC or other malignant disease undergoing evaluation for a new liver graft (see Chapters 97D and 97E).