Va s c u l a r a n d I n t e r ve n t i o n a l R a d i o l o g y • C l i n i c a l Pe r s p e c t i ve Fornage et al. Ultrasound-Guided FNA of IM Nodes
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Vascular and Interventional Radiology Clinical Perspective
Ultrasound-Guided Fine-Needle Aspiration Biopsy of Internal Mammary Nodes: Technique and Preliminary Results in Breast Cancer Patients Bruno D. Fornage1 Basak E. Dogan1 Nour Sneige2 Gregg A. Staerkel2
OBJECTIVE. The objective of our study was to describe our technique and preliminary results of ultrasound-guided fine-needle aspiration (FNA) of indeterminate internal mammary (IM) lymph nodes in patients with a history of breast cancer. CONCLUSION. Ultrasound-guided FNA of IM nodes is feasible and is particularly useful in the staging of breast cancer.
Fornage BD, Dogan BE, Sneige N, Staerkel GA
T
Keywords: biopsy, breast cancer, fine-needle aspiration, internal mammary nodes, lymphatic spread, staging, ultrasound DOI:10.2214/AJR.13.11148 Received April 27, 2013; accepted after revision October 10, 2013. 1 Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350, Houston, TX 77030. Address correspondence to B. D. Fornage ([email protected]). 2 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
WEB This is a web exclusive article. Supplemental Data Available online at www.ajronline.org. AJR 2014; 203:W213–W220 0361–803X/14/2032–W213 © American Roentgen Ray Society
he internal mammary (IM) lymphatic vessels and nodes, like the axillary ones, are a first-echelon nodal drainage site in breast cancer. The assessment of the IM nodal basin is beyond the reach of palpation and mammographic imaging. However, it is within the reach of the ultrasound examination of the IM chains, which was first described in the late 1980s [1] and early 1990s [2]. At our institution, we have included the systematic scanning of the ipsilateral axilla, infraclavicular region, and IM chains in the standard whole-breast examination of all patients with a history of breast cancer—in particular, when evaluating a patient with a newly diagnosed breast cancer—as part of the staging of the disease. The effect of involvement of the ipsilateral IM nodes by metastatic disease in a patient with breast cancer has been recognized for the past 2 decades, and the last two editions of the TNM staging classification of malignant tumors were revised to acknowledge the importance of this finding [3]. In some cases, pathologic confirmation of the metastatic nature of a suspicious IM node may be required by the oncologic team if that will result in an adjustment of the treatment, whether it is the institution of neoadjuvant chemotherapy that was not initially contemplated, the adjustment of the portals of radiation treatment, or the decision of a surgical excision. Although ultrasound-guided core needle biopsy is the standard for obtaining the pathologic diagnosis of a primary breast cancer, the confirmation of a metastatic lymph node is readily obtained by ultrasound-guid-
ed fine-needle aspiration (FNA) if a cytopathologist is available. This procedure is performed routinely now for the axillary nodes [2]. However, to our knowledge, ultrasoundguided FNA of the IM nodes has not yet been described in detail in the literature. In this article, we describe our technique for ultrasound-guided FNA of IM nodes and report our preliminary findings in a series of 19 cases. Materials and Methods This retrospective review included images and reports of 18 women with a history of breast cancer who had 19 IM nodes (one patient had two nodes that were sampled) initially identified as suspicious for malignancy on ultrasound. Ultrasound-guided FNA of these nodes was performed to confirm or rule out metastatic disease as part of locoregional staging. This study was approved by our institutional review board and complied with HIPAA regulations.
Ultrasound Examination Technique for the Internal Mammary Chain We used the same 13–5-MHz high-frequency linear-array broadband transducer (VFX, Siemens Healthcare) that is used for breast imaging connected to an ultrasound scanner (Elegra or Antares, Siemens Healthcare). Gray-scale imaging and color and power Doppler imaging were performed in all examinations. Longitudinal sonograms of the IM nodal chains were obtained by scanning along the edge of the sternum (Fig. 1A). Extended-FOV sonograms were particularly helpful for simultaneous visualization of the first three or four intercostal spaces and of the cross sections of the costal cartilages in a single
AJR:203, August 2014 W213
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Fornage et al. frame, thus allowing documentation of the precise location of any abnormal node (Fig. 1B). Transverse sonograms were obtained by placing the probe transversely in each intercostal space with its medial end covering the edge of the sternum (Fig. 2). Care was taken not to use real-time spatial compounding to avoid blurring of the sonograms. The focal zone was placed at the level of the target lesion. Although not a part of our standard technique, tissue harmonic imaging was used on occasion to enhance the contrast between any node and the surrounding tissues and to optimize the visualization of internal thoracic (IT) vessels, previously known as the “internal mammary vessels,” on gray-scale imaging (Fig. S3). (Fig. S3, a supplemental video, can be viewed by clicking Supplemental at the top of this article and then clicking the figure number on the Supplemental page.) The IT artery (ITA) and IT veins (ITVs) were identified on color and power Doppler ultrasound after optimization of the angle of insonation and pulse repetition frequency (PRF) of the scanner, especially on transverse sonograms when the Doppler insonation angle is close to 90˚. Spectral analysis was occasionally used to distinguish between the ITA and the ITVs (Fig. 4). Special attention was paid to the ITVs because the anatomy of the ITVs is highly variable, with the possibilities of a single ITV or two ITVs after a bifurcation at a variable level. In addition, the position of the ITVs in relation to the ITA can vary [4]. Because it is very rare in the IM nodal chains to visualize the type of normal, benign, fat-replaced echogenic node seen normally in the axilla and because normal nodes less than 3–4 mm that are often seen on MRI are too small and with insufficient contrast to be seen on ultrasound, we assumed that in a patient with breast cancer, any node visualized along the IM chain—regardless of its shape—was a potential nodal metastasis. Because the incidence of IM lymph node metastases is increased in patients with a primary tumor in the medial breast [5], the location of the primary tumor in the breast (medial quadrants, lateral quadrants, or retroareolar) was recorded. The location of the nodes in the IM chains (first through fourth intercostal spaces), the size of the node (three longest orthogonal diameters), and the location of the node in relation to the IT vessels were recorded. The overall echogenicity of the node was rated in relation to that of the costal cartilages (marked hypoechogenicity) and that of the subcutaneous fat (moderate hypoechogenicity). The presence of central or hilar echogenicity was also recorded.
W214
A
B Fig. 1—Technique for ultrasound scanning of internal mammary (IM) nodal chain. A, Technique for ultrasound scanning of IM nodal chain: Double-headed arrow on diagram shows placement of transducer to acquire longitudinal sonograms of left IM nodal chain. (Modified with permission from 3D Anatomy Images. Copyright of Primal Pictures Ltd. www.primalpictures.com) B, Normal extended-FOV longitudinal sonogram of 40-year-old woman shows cross sections of hypoechoic costal cartilages (C) and echogenic parietal pleura. No node is identified. Note that cartilages do not obscure the underlying pleura. Fig. 2—Technique for ultrasound scanning of internal mammary (IM) nodal chain. Double-headed arrow on diagram shows placement of transducer to acquire transverse sonogram of left IM nodal chain in second intercostal space. (Modified with permission from 3D Anatomy Images. Copyright of Primal Pictures Ltd. www. primalpictures.com)
Ultrasound-Guided Fine-Needle Aspiration of Internal Mammary Nodal Metastases Anticoagulation therapy was discontinued before the procedure, and the absence of any contraindication or allergy was verified and vital signs were taken by a nurse. For ultrasound-guided FNA, the transducer was placed transversely over the intercostal space
in which the suspicious node had been identified, and a lateral-to-medial approach through the pectoralis major muscle was selected (Fig. 5). A large amount of time was spent to select the optimal approach to the target, taking into account the right- or left-handedness of the operator. For instance, to approach a target in a right intercostal space, a right-handed operator had to work from
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Ultrasound-Guided FNA of IM Nodes
A
B
Fig. 4—Ultrasound anatomy of normal internal thoracic (IT) vessels in 63-year-old woman. Internal thoracic vein (ITV) lies medial to internal thoracic artery (ITA). A, Transverse color Doppler sonogram of second right intercostal space shows IT vessels anterior to parietal pleura. Spectral Doppler analysis confirms ITA. B, Transverse color Doppler sonogram of second right intercostal space shows IT vessels anterior to parietal pleura. Spectral Doppler analysis confirms ITV.
the top of the examination table, leaning over the patient’s head. This position required some minor adjustment of the respective positions of the examination bed, scanner, and slave monitor. First, the IT vessels were carefully identified using color or power Doppler ultrasound. Then, adequate local anesthetization was performed under full realtime ultrasound monitoring. A 5-cm-long 21-gauge needle and a 10-mL syringe were used to inject 3–5 mL of 1% lidocaine along the selected pathway for the FNA needle across the pectoralis major muscle. For the FNA, a 20-mL syringe and a 3.8-cmlong 20-gauge needle or a 5-cm-long 21-gauge needle were used. The needle was inserted with a very shallow angle to remain as close to parallel to the pleura as possible for maximum safety. To achieve this shallow angle, the entry site of the needle was selected at a distance of approximately 1–2 cm from the edge of the transducer. Extreme care was taken to keep the needle perfectly aligned with the scanning plane and to clearly visualize not only the needle tip but also the entire shaft of the needle at all times during its progression through the pectoralis muscle to the target (Fig. S6). The visibility of the needle was enhanced by a slight rotation movement of the needle and by positioning it so that the bevel faced upward, thereby being more echogenic. The clear visibility of the needle tip allowed the operator to keep it at a safe distance from the IM vessels and from the pleura. At times, this distance could be as short as a couple of millimeters (Fig. 7). Aspiration of cellular material from the lymph nodes was achieved by applying a moderate nega-
tive pressure (i.e., suction) manually with a single hand (the hand holding the syringe). This was done using three fingers to pull the plunger to the 1- or 2-cc mark on the syringe. Moderate suction was applied during the entire aspiration process, lasting about 20–30 seconds, during which the needle was moved to and fro and, if the size of the target permitted it, in various directions within the scanning plane (up and down) to mechanically dissociate the nodal tissue and maximize the volume of the aspirated sample. When some blood-tinged material appeared in the hub of the needle, the sampling was deemed complete; after the release of the suction, the needle-syringe assembly was pulled out. Next, the cellular aspirate was recovered from the needle. First, the needle was disconnected from the syringe; if there was obviously material in the hub of the needle, an attempt was made to recover it by gently tapping the hub against a glass slide and smearing it. Then, the standard technique of recovering the aspirate was used as follows: The plunger of the syringe was retracted, the syringe was reconnected to the needle, and the plunger was pushed to expel the material contained in the hub and shaft of the needle onto glass slides. All smears were prepared by the radiologist, and the slides were dipped in a modified Carnoy fixative solution of 83% ethanol and 17% acetic acid in preparation for Papanicolaou and DiffQuik stains. An onsite cytopathologist was available to provide a preliminary diagnosis within 15 minutes. The number of passes needed to obtain a definitive cytopathologic diagnosis was recorded. After the cytopathologist confirmed the diagnostic quality of the aspirate, the patient was reevaluat-
ed for vital signs. Because there was no skin opening other than the puncture with the 20- or 21-gauge needle, the skin was cleaned, a simple small adhesive bandage was applied to the needle’s entry site, and the patient was discharged from the clinic. The final diagnosis of malignancy was established on the basis of the cytopathologic diagnosis. Correlation was made with the histopathologic type and grade of the primary breast tumor, and the location of the primary tumor within the breast. Clinical follow-up, imaging follow-up (ultrasound or CT), or both were performed for nodes with a benign diagnosis.
Fig. 5—Ultrasound-guided fine-needle aspiration (FNA) of internal mammary (IM) node: Diagram shows lateral-to-medial insertion of needle in intercostal space for FNA of IM node that is located in second left intercostal space. (Modified with permission from 3D Anatomy Images. Copyright of Primal Pictures Ltd. www.primalpictures.com)
AJR:203, August 2014 W215
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Fornage et al.
Fig. 7—Transverse sonogram obtained during ultrasound-guided fine-needle aspiration of small internal mammary node metastasis in second left intercostal space in 90-year-old woman. Node (arrow) measures 0.8 × 0.7 × 0.4 cm and is located lateral and anterior to internal thoracic artery (ITA). Note that needle is nearly parallel to pleura to ensure maximum safety of procedure. Entire shaft of needle is visible; needle tip is seen in center of node, a few millimeters from ITA.
Results The 18 women in our series ranged in age from 33 to 90 years, with an average age of 54 ± 14 (SD) years. All had a history of ipsilateral invasive ductal cancer of the breast. The primary tumor was in the medial breast in 11, in the lateral breast in four, and retroareolar in two; the location of the primary tumor was unavailable in one patient. The tumor grade was 3 (poorly differentiated) in 10 patients, 2 (moderately differentiated) in five patients, and 1 (well differentiated) in three patients.
Ultrasound Appearances of Nodes Twelve of the 19 nodes were in the first intercostal space (seven on the left side, five on the right side), six were in the second space (four on the left side, two on the right side), and only one was in the third right space. All lesions were ovoid, with their long axis parallel to the IT vessels. The largest lesion measured 3.4 × 2.8 × 1.8 cm and the smallest, 0.8 × 0.6 × 0.5 cm. The longest diameter of the lesions ranged from 0.8 to 3.4 cm (mean ± SD, 1.4 ± 0.6 cm), and
Fig. 9—Internal mammary nodal metastasis (arrows) in second left intercostal space in 58-year-old woman. Transverse color Doppler sonogram shows that node is located medial to internal thoracic vessels. Spectral Doppler analysis confirms internal thoracic artery.
W216
Fig. 8—Small internal mammary nodal metastasis (arrows) in third right intercostal space in 56-year-old woman. Transverse power Doppler sonogram shows that node is located lateral to internal thoracic artery (ITA) and internal thoracic vein (ITV).
the shortest diameter ranged from 0.4 to 1.8 cm (mean ± SD, 0.7 ± 0.3 cm). Fifteen (79%) nodes were lateral to the IT vessels (Fig. 8), two of which also covered the vessels anteriorly. Three nodes (16%) were medial to the vessels (Fig. 9), and one node (5%) was located between the ITA and the ITV (Fig. 10). Eleven malignant nodes were markedly hypoechoic (i.e., as hypoechoic as the costal cartilages, nearly anechoic) (Fig. 11), whereas five malignant nodes were moderately hy-
Fig. 10—Small internal mammary nodal metastasis (N) in first right intercostal space in 48-year-old woman. Transverse gray-scale sonogram shows hypoechoic node between internal thoracic artery (ITA) laterally and internal thoracic vein (ITV) medially. S = lateral edge of sternum.
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Ultrasound-Guided FNA of IM Nodes
Fig. 11—Internal mammary nodal metastasis from breast cancer in 44-year-old woman. Longitudinal sonogram of second right intercostal space shows markedly hypoechoic internal mammary nodal metastasis (N). Node is as hypoechoic as costal cartilage (C).
poechoic (hypoechogenicity comparable to that of subcutaneous fat). None was echogenic. Among the three benign nodes, two had the hypoechogenicity of fat (Fig. 12) and one was mildly echogenic. Two of the 16 malignant nodes had a minute amount of residual (eccentric) hilar echogenicity, and residual central echogenicity was seen in two of the three benign nodes. Only in five cases (26%), four metastases and one benign node, did color or power Doppler ultrasound reveal some internal vascularity inside the node (Fig. 13). Fine-Needle Aspiration Results A satisfactory cytologic specimen was obtained with a single 20- to 30-second pass with a 20- or 21-gauge needle in all nodes except two, in which two passes were made to confirm metastasis. All the specimens were diagnostic. FNA results revealed 16 metastases from breast cancer (Fig. 14) and benign lymphoid tissue in three cases of benign lymphadenopathy in two patients. One patient with a benign FNA result has been followed clinically for 3 years with no change in the ultrasound appearance of the node. In a second patient, who had two nodes that underwent FNA, one in the first left space and the other in the second left space, both FNAs were benign. This patient, who had a history of treated breast cancer and recently diagnosed lung cancer, underwent chemotherapy for the lung cancer. The two nodes remained stable for 2 years until one began to grow when the lung cancer recurred.
Fig. 12—Benign internal mammary node in 58-year-old woman with T1N1M0 breast cancer in lower outer quadrant of breast. Transverse gray-scale sonogram of first left intercostal space shows small flat node (arrows), which is lateral to internal thoracic vessels. Node shows hypoechogenicity similar to that of subcutaneous fat. S = lateral edge of sternum.
There were no immediate or delayed complications of the FNAs. Discussion Although the ultrasound examination of the axilla with ultrasound-guided biopsy of indeterminate axillary nodes has finally made its way into the standard ultrasound examination of patients with breast cancer, ultrasound examination of the IM nodal chains is often overlooked in the staging of disease in patients with breast cancer, and ultrasound-guided FNA of IM nodes has not been described in the literature to our knowledge. Ultrasound examination of the IM chains usually does not require special ultrasound equipment and is performed using the same high-frequency probe as the one used to scan the breast. However, in overweight patients or patients with thick muscles, it may be necessary to use a transducer of lower frequency. In individuals with a small chest or narrow intercostal spaces, a high-frequency “hockey-stick”–type transducer with a small footprint or a short-radius convex-array probe like those used for neurosonology of children might be beneficial. Although the IT vessels can sometimes be identified on gray-scale ultrasound by their characteristic motions, the use of color or power Doppler ultrasound is critical for confirming their identification before the needle biopsy and in planning the safest route for the needle. Visualization of the IT vessels on color or power Doppler imaging may also avoid the pitfall of misdiagnosing a promi-
nent or varicose ITV as a suspicious node. Power Doppler imaging is more sensitive for identifying slow or low-volume blood flow than color Doppler imaging and should be used to show the internal vascularity of the nodes whereas distinguishing between the ITV or ITVs and the ITA requires color Doppler and spectral Doppler analyses. We must stress that the PRF settings are different for the two applications and that setting the PRF at a low value to detect slow flow in the node will result in aliasing and flash artifacts in the IT vessels. Also, it may be difficult to register Doppler signals in the IT vessels because of the unfavorable insonation angle, which is often greater than 60°. Many fat-replaced echogenic nodes are normally seen in the axilla. On the contrary, such typically benign nodes are not seen along the IM chains. Although MRI can show tiny benign nodes in the range of 2–4 mm, these nodes are too small to be reliably identified on ultrasound. Therefore, it is reasonable to suspect that any visualized solid hypoechoic mass along the IT vessels in a patient with breast cancer is a metastatic node until proven otherwise. Our results show, however, that there is some overlap between the ultrasound appearances of malignant and benign nodes, although the numbers in this series are too small to draw conclusions. Although local anesthesia can be skipped when performing ultrasound-guided FNA of axillary nodes because the only sensitive anatomic component to traverse is the skin, ultrasound-guided FNA of the IM nodes re-
AJR:203, August 2014 W217
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Fornage et al.
Fig. 13—Internal mammary nodal metastasis from breast cancer in 90-year-old woman (same patient as in Fig. 7). Transverse power Doppler sonogram of second left intercostal space shows vascularity inside node.
quires local anesthetization of the pectoralis muscle with a few milliliters of 1% lidocaine [3–5]. Anesthetic administration is best performed under ultrasound guidance to ensure that the local anesthetic is deposited exactly along the projected path of the biopsy needle. Because of the presence of vital structures and the tight environment, patient safety should be the primary concern of the operator. The lateral-to-medial approach is the safest approach because the long (5-cm) needle can be inserted nearly parallel to the parietal pleura, which also results in the best visualization of the needle shaft and tip. It is important that we emphasize that the needle must be visualized during the entire procedure and not only intermittently. Any other approach (e.g., inferior-to-superior or medial-to-lateral) should be avoided because these approaches would result in a steep angle relative to the pleura and heightened risk of complications. Complications include bleeding from injury to the IM vessels and pneumothorax from pleural breaches. None occurred in our experience. Because there is no room to safely accommodate the throw of an automated large-core biopsy needle, core biopsy of the IM nodes cannot be performed with the available automated biopsy devices. Ultrasound-guided FNA is the tool of choice because of the precision with which the needle can be advanced under continuous real-time monitoring. In fact, the needle tip was often within a distance of only a few millimeters from the IT vessels or the parietal pleura.
W218
Fig. 14—Photomicrograph (Papanicolaou stain, ×40) of cytologic smear obtained from ultrasound-guided fine-needle aspiration of metastatic internal mammary node in 44-year-old woman shows abundant metastatic adenocarcinoma that has completely replaced node’s lymphoid tissue.
IM nodal metastases were most often found lateral to the IT vessels, but some were found between them or medial to them, rendering the procedure most challenging because the needle would have to pass just over the vessels. Although not encountered in this series, the possibility of nodes located not in the intercostal spaces but posterior to cartilage or even to the sternum exists. Obviously, in the latter case, the node would not even be seen on sonograms. Successfully placing the needle inside or through the target lesion is necessary but is not sufficient when performing FNA. Indeed, the most important phase of the FNA is the extraction of the cellular material. Extraction requires that the operator have expertise, especially if aspirating solid breast masses. However, aspiration of cellular material from lymph nodes—benign or malignant—is easy because of their rich cellularity. As a rule, in experienced hands, a single needle pass of 20–30 seconds’ duration can provide a sufficient sample. In this study, a single pass was sufficient in 89% of the procedures and all specimens were diagnostic. Because of limited access to the IM nodes and the risk of major complications, ultrasound-guided needle biopsy of the IM nodes should be performed only by imagers with extensive experience in interventional ultrasound and only in patients in whom the result of the procedure is expected to affect staging and clinical management. A discussion with the treating physician before the biopsy is therefore essential.
Like the axillary nodes, the IM chain is a first-echelon nodal drainage site in patients with breast cancer. IM nodal metastases are more frequent in patients with medial tumors, in patients with large tumors, in young patients, and in patients with axillary involvement [5, 6]. The fact that patients with medial tumors have worse outcomes than patients with lateral tumors of similar stage suggests that IM nodal metastases are underdiagnosed and that patients with IM nodal disease are possibly undertreated. Under these circumstances, the sixth and seventh editions of the TNM staging system of the American Joint Committee on Cancer were revised to reflect the impact of a positive IM node on breast cancer stage: Category N2b was assigned in case of metastases only in clinically detected ipsilateral IM nodes and in the absence of clinically evident level I and II axillary lymph node metastases, and category N3b was given in the presence of metastases in both ipsilateral IM nodes and axillary nodes. As a result, the diagnosis of a metastatic IM node automatically categorizes a breast cancer as stage III: stage IIIA for T0–T3 and IIIB for T4 primary tumors in the absence of axillary nodal metastases and stage IIIC in the presence of axillary nodal metastases regardless of the size of the primary tumor [3, 7] (Table 1). The interest of breast surgeons in the dissection of IM nodes is not new: As early as in the 1950s and 1960s, dissection of the IM nodes became popular and was added to the Halsted’s radical mastectomy tech-
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Ultrasound-Guided FNA of IM Nodes nique to be known as “extended mastectomy.” An early large clinical trial showed no advantage of adding IM node dissection to the mastectomy in terms of survival except in women with tumors located in the medial breast and those with axillary involvement [8]. In a subsequent large single-center study involving 1119 patients treated with extended mastectomy, the overall incidence of IM nodal metastases was 19% [9]. In that study, survival was significantly affected by the presence of positive IM nodes, with the 10-year survival rate decreasing from 80.4% in patients with axillary node involvement but without IM node involvement to 30.0% in patients with involvement of both nodal basins. Intermediate survival rates of 54.6% and 53.0% were found in cases of isolated axillary and IM node involvement, respectively [9]. Those authors acknowledged the need to know the status of the IM nodes and suggested a surgical biopsy of the first intercostal space in patients at risk for IM nodal metastases; they stated that they hoped that “the research on noninvasive methods of diagnosis of internal mammary node involvement will be intensified” [9]. With the advent and routine use of lympho scintigraphy for axillary sentinel node mapping and biopsy, the interest of surgeons was revived for the surgical biopsy of the IM sentinel node shown on lymphoscintigraphy. In a series of 506 patients undergoing preoperative lymphoscintigraphy for axillary sentinel node biopsy, one or more IM sentinel nodes were found in 109 patients (22%). Such drainage to the IM nodes was more frequent when the primary tumor was in the medial breast and in younger patients. However, IM sentinel nodes could be retrieved through a parasternal intercostal incision in only 85 of the 109 patients (78%), and metastases in these sentinel nodes were observed in only 20 of the 85 patients (24%). Complications (pleural breaching or damage to the IT vessels) occurred in 10 of 109 patients (9%) [6]. Other studies have reported a range of visualized IM nodes on lymphoscintigraphy of 11–25% and successful retrieval of the sentinel IM nodes of 63–88% [10–12]. There is still debate about the clinical effect of the detection and diagnosis of an IM nodal metastasis on the patient’s treatment and prognosis. A change in management—institution or omission of radiotherapy to the IM chain, adjuvant systemic therapy, or omission of an axillary lymph node dissection—was reported in 29% of the patients in one study [12], whereas
the authors of another study found that parasternal sentinel node biopsy resulted in upstaging in only 2% of the breast cancer patients who underwent that procedure [10]. It should be remembered that because of the limitations and technical difficulties of sentinel IM node biopsy, pathologic examination will identify a metastatic node in only approximately 2–3% of the entire population undergoing this procedure [6, 10]. We expect that direct ultrasound visualization of minimally enlarged IM nodes coupled with ultrasound-guided FNA will allow the detection and diagnosis of a greater number of metastatic IM nodes of a smaller size. It should also be kept in mind that delivering a boost of radiation therapy to the IM chain is associated with a risk of inducing cardiac morbidity. As in our study, most IM nodal metastases are found in the first three intercostal spaces, which has led some authors to suggest selective irradiation of only the superior IM chain (intercostal spaces 1, 2, and 3) and exclusion of the lower spaces, thus shielding the heart [13]. However, irradiation of the IM chain should be restricted to patients with a pathologically proven IM node. This proof can now be easily obtained in a few minutes via ultrasound-guided FNA. The common thinking is that a medial tumor with an IM nodal metastasis should not be considered as associated with a worse prognosis than a lateral tumor with an axillary nodal metastasis. However, the finding of an IM nodal metastasis in addition to positive axillary nodes has a well-known substantial adverse effect on the patient’s prognosis, as reflected in the latest TNM classification. Ultrasound-guided FNA appears to be the less invasive means of detecting and confirming occult IM nodal metastases that has been long awaited to obtain the needed information on the IM lymphatic status and thereby facilitate treatment decisions. The indications for this procedure in patients with breast cancer remain to be defined in view of the implications of a positive diagnosis of metastatic disease on the patient’s management. A prospective study has been launched at our institution to study this issue. References 1. Scatarige JC, Hamper UM, Sheth S, Allen HA III. Parasternal sonography of the internal mammary vessels: technique, normal anatomy, and lymphadenopathy. Radiology 1989; 172:453–457 2. Fornage BD. Ultrasound of the breast. Ultrasound Q 1993; 11:1–39 3. Edge SB, Byrd DR, Compton CC, Fritz AG,
TABLE 1: Impact of the Presence of an Internal Mammary (IM) Node Metastasis on the Staging of Breast Cancer Stage IIIA
IIIB
IIIC
T Category N Category
M Category
T0
N2
M0
T1a
N2
M0
T2
N2
M0
T3
N1
M0
T3
N2
M0
T4
N0
M0
T4
N1
M0
T4
N2
M0
Any T
N3
M0
Note—The diagnosis of an ipsilateral IM nodal metastasis in the absence of level I and II axillary node metastases (N2b) classifies the disease as stage IIIA for T0–T3 tumors or stage IIIB for T4 primary tumors. The presence of an IM nodal metastasis in association with axillary nodes (N3b) classifies the disease as stage IIIC regardless of the size of the primary tumor [3]. aIncludes tumors with microinvasion (< 0.1 cm). Greene FL, Trotti A, eds. Breast. In: AJCC cancer staging manual, 7th ed. New York, NY: Springer, 2010:347–376 4. Loukas M, Tobola MS, Tubbs RS, et al. The clinical anatomy of the internal thoracic veins. Folia Morphol (Warsz) 2007; 66:25–32 5. Huang O, Wang L, Shen K, et al. Breast cancer subpopulation with high risk of internal mammary lymph nodes metastasis: analysis of 2,269 Chinese breast cancer patients treated with extended radical mastectomy. Breast Cancer Res Treat 2008; 107:379–387 6. Madsen E, Gobardhan P, Bongers V, et al. The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer. Ann Surg Oncol 2007; 14:1486–1492 7. Galimberti V, Veronesi P, Arnone P, et al. Stage migration after biopsy of internal mammary chain lymph nodes in breast cancer patients. Ann Surg Oncol 2002; 9:924–928 8. Lacour J, Bucalossi P, Cacers E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection: five-year results of an international cooperative study. Cancer 1976; 37:206–214 9. Veronesi U, Cascinelli N, Greco M, et al. Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes. Ann Surg 1985; 202:702–707 10. Leidenius MHK, Krogerus LA, Toivonen TS, Leppänen EA, von Smitten KA. The clinical value of parasternal sentinel node biopsy in breast
AJR:203, August 2014 W219
Fornage et al.
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
cancer. Ann Surg Oncol 2006; 13:321–326 11. Farrús B, Vidal-Sicart S, Velasco M, et al. Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan. Int J
Radiat Oncol Biol Phys 2004; 60:715–721 12. Estourgie SH, Tanis PJ, Nieweg OE, Valdés Olmos RA, Rutgers EJ, Kroon BB. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients.
Ann Surg Oncol 2003; 10:935–941 13. Marks LB, Hebert ME, Bentel G, Spencer DP, Sherouse GW, Prosnitz LR. To treat or not to treat the internal mammary nodes: a possible compromise. Int J Radiat Oncol Biol Phys 1994; 29:903–909
F O R YO U R I N F O R M AT I O N
The data supplement accompanying this web exclusive article can be viewed by clicking “Supplemental” at the top of the article.
W220
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Vascular and Interventional Radiology Clinical Perspective
Ultrasound-Guided Fine-Needle Aspiration Biopsy of Internal Mammary Nodes: Technique and Preliminary Results in Breast Cancer Patients Bruno D. Fornage1 Basak E. Dogan1 Nour Sneige2 Gregg A. Staerkel2
OBJECTIVE. The objective of our study was to describe our technique and preliminary results of ultrasound-guided fine-needle aspiration (FNA) of indeterminate internal mammary (IM) lymph nodes in patients with a history of breast cancer. CONCLUSION. Ultrasound-guided FNA of IM nodes is feasible and is particularly useful in the staging of breast cancer.
Fornage BD, Dogan BE, Sneige N, Staerkel GA
T
Keywords: biopsy, breast cancer, fine-needle aspiration, internal mammary nodes, lymphatic spread, staging, ultrasound DOI:10.2214/AJR.13.11148 Received April 27, 2013; accepted after revision October 10, 2013. 1 Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1350, Houston, TX 77030. Address correspondence to B. D. Fornage ([email protected]). 2 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
WEB This is a web exclusive article. Supplemental Data Available online at www.ajronline.org. AJR 2014; 203:W213–W220 0361–803X/14/2032–W213 © American Roentgen Ray Society
he internal mammary (IM) lymphatic vessels and nodes, like the axillary ones, are a first-echelon nodal drainage site in breast cancer. The assessment of the IM nodal basin is beyond the reach of palpation and mammographic imaging. However, it is within the reach of the ultrasound examination of the IM chains, which was first described in the late 1980s [1] and early 1990s [2]. At our institution, we have included the systematic scanning of the ipsilateral axilla, infraclavicular region, and IM chains in the standard whole-breast examination of all patients with a history of breast cancer—in particular, when evaluating a patient with a newly diagnosed breast cancer—as part of the staging of the disease. The effect of involvement of the ipsilateral IM nodes by metastatic disease in a patient with breast cancer has been recognized for the past 2 decades, and the last two editions of the TNM staging classification of malignant tumors were revised to acknowledge the importance of this finding [3]. In some cases, pathologic confirmation of the metastatic nature of a suspicious IM node may be required by the oncologic team if that will result in an adjustment of the treatment, whether it is the institution of neoadjuvant chemotherapy that was not initially contemplated, the adjustment of the portals of radiation treatment, or the decision of a surgical excision. Although ultrasound-guided core needle biopsy is the standard for obtaining the pathologic diagnosis of a primary breast cancer, the confirmation of a metastatic lymph node is readily obtained by ultrasound-guid-
ed fine-needle aspiration (FNA) if a cytopathologist is available. This procedure is performed routinely now for the axillary nodes [2]. However, to our knowledge, ultrasoundguided FNA of the IM nodes has not yet been described in detail in the literature. In this article, we describe our technique for ultrasound-guided FNA of IM nodes and report our preliminary findings in a series of 19 cases. Materials and Methods This retrospective review included images and reports of 18 women with a history of breast cancer who had 19 IM nodes (one patient had two nodes that were sampled) initially identified as suspicious for malignancy on ultrasound. Ultrasound-guided FNA of these nodes was performed to confirm or rule out metastatic disease as part of locoregional staging. This study was approved by our institutional review board and complied with HIPAA regulations.
Ultrasound Examination Technique for the Internal Mammary Chain We used the same 13–5-MHz high-frequency linear-array broadband transducer (VFX, Siemens Healthcare) that is used for breast imaging connected to an ultrasound scanner (Elegra or Antares, Siemens Healthcare). Gray-scale imaging and color and power Doppler imaging were performed in all examinations. Longitudinal sonograms of the IM nodal chains were obtained by scanning along the edge of the sternum (Fig. 1A). Extended-FOV sonograms were particularly helpful for simultaneous visualization of the first three or four intercostal spaces and of the cross sections of the costal cartilages in a single
AJR:203, August 2014 W213
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Fornage et al. frame, thus allowing documentation of the precise location of any abnormal node (Fig. 1B). Transverse sonograms were obtained by placing the probe transversely in each intercostal space with its medial end covering the edge of the sternum (Fig. 2). Care was taken not to use real-time spatial compounding to avoid blurring of the sonograms. The focal zone was placed at the level of the target lesion. Although not a part of our standard technique, tissue harmonic imaging was used on occasion to enhance the contrast between any node and the surrounding tissues and to optimize the visualization of internal thoracic (IT) vessels, previously known as the “internal mammary vessels,” on gray-scale imaging (Fig. S3). (Fig. S3, a supplemental video, can be viewed by clicking Supplemental at the top of this article and then clicking the figure number on the Supplemental page.) The IT artery (ITA) and IT veins (ITVs) were identified on color and power Doppler ultrasound after optimization of the angle of insonation and pulse repetition frequency (PRF) of the scanner, especially on transverse sonograms when the Doppler insonation angle is close to 90˚. Spectral analysis was occasionally used to distinguish between the ITA and the ITVs (Fig. 4). Special attention was paid to the ITVs because the anatomy of the ITVs is highly variable, with the possibilities of a single ITV or two ITVs after a bifurcation at a variable level. In addition, the position of the ITVs in relation to the ITA can vary [4]. Because it is very rare in the IM nodal chains to visualize the type of normal, benign, fat-replaced echogenic node seen normally in the axilla and because normal nodes less than 3–4 mm that are often seen on MRI are too small and with insufficient contrast to be seen on ultrasound, we assumed that in a patient with breast cancer, any node visualized along the IM chain—regardless of its shape—was a potential nodal metastasis. Because the incidence of IM lymph node metastases is increased in patients with a primary tumor in the medial breast [5], the location of the primary tumor in the breast (medial quadrants, lateral quadrants, or retroareolar) was recorded. The location of the nodes in the IM chains (first through fourth intercostal spaces), the size of the node (three longest orthogonal diameters), and the location of the node in relation to the IT vessels were recorded. The overall echogenicity of the node was rated in relation to that of the costal cartilages (marked hypoechogenicity) and that of the subcutaneous fat (moderate hypoechogenicity). The presence of central or hilar echogenicity was also recorded.
W214
A
B Fig. 1—Technique for ultrasound scanning of internal mammary (IM) nodal chain. A, Technique for ultrasound scanning of IM nodal chain: Double-headed arrow on diagram shows placement of transducer to acquire longitudinal sonograms of left IM nodal chain. (Modified with permission from 3D Anatomy Images. Copyright of Primal Pictures Ltd. www.primalpictures.com) B, Normal extended-FOV longitudinal sonogram of 40-year-old woman shows cross sections of hypoechoic costal cartilages (C) and echogenic parietal pleura. No node is identified. Note that cartilages do not obscure the underlying pleura. Fig. 2—Technique for ultrasound scanning of internal mammary (IM) nodal chain. Double-headed arrow on diagram shows placement of transducer to acquire transverse sonogram of left IM nodal chain in second intercostal space. (Modified with permission from 3D Anatomy Images. Copyright of Primal Pictures Ltd. www. primalpictures.com)
Ultrasound-Guided Fine-Needle Aspiration of Internal Mammary Nodal Metastases Anticoagulation therapy was discontinued before the procedure, and the absence of any contraindication or allergy was verified and vital signs were taken by a nurse. For ultrasound-guided FNA, the transducer was placed transversely over the intercostal space
in which the suspicious node had been identified, and a lateral-to-medial approach through the pectoralis major muscle was selected (Fig. 5). A large amount of time was spent to select the optimal approach to the target, taking into account the right- or left-handedness of the operator. For instance, to approach a target in a right intercostal space, a right-handed operator had to work from
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Ultrasound-Guided FNA of IM Nodes
A
B
Fig. 4—Ultrasound anatomy of normal internal thoracic (IT) vessels in 63-year-old woman. Internal thoracic vein (ITV) lies medial to internal thoracic artery (ITA). A, Transverse color Doppler sonogram of second right intercostal space shows IT vessels anterior to parietal pleura. Spectral Doppler analysis confirms ITA. B, Transverse color Doppler sonogram of second right intercostal space shows IT vessels anterior to parietal pleura. Spectral Doppler analysis confirms ITV.
the top of the examination table, leaning over the patient’s head. This position required some minor adjustment of the respective positions of the examination bed, scanner, and slave monitor. First, the IT vessels were carefully identified using color or power Doppler ultrasound. Then, adequate local anesthetization was performed under full realtime ultrasound monitoring. A 5-cm-long 21-gauge needle and a 10-mL syringe were used to inject 3–5 mL of 1% lidocaine along the selected pathway for the FNA needle across the pectoralis major muscle. For the FNA, a 20-mL syringe and a 3.8-cmlong 20-gauge needle or a 5-cm-long 21-gauge needle were used. The needle was inserted with a very shallow angle to remain as close to parallel to the pleura as possible for maximum safety. To achieve this shallow angle, the entry site of the needle was selected at a distance of approximately 1–2 cm from the edge of the transducer. Extreme care was taken to keep the needle perfectly aligned with the scanning plane and to clearly visualize not only the needle tip but also the entire shaft of the needle at all times during its progression through the pectoralis muscle to the target (Fig. S6). The visibility of the needle was enhanced by a slight rotation movement of the needle and by positioning it so that the bevel faced upward, thereby being more echogenic. The clear visibility of the needle tip allowed the operator to keep it at a safe distance from the IM vessels and from the pleura. At times, this distance could be as short as a couple of millimeters (Fig. 7). Aspiration of cellular material from the lymph nodes was achieved by applying a moderate nega-
tive pressure (i.e., suction) manually with a single hand (the hand holding the syringe). This was done using three fingers to pull the plunger to the 1- or 2-cc mark on the syringe. Moderate suction was applied during the entire aspiration process, lasting about 20–30 seconds, during which the needle was moved to and fro and, if the size of the target permitted it, in various directions within the scanning plane (up and down) to mechanically dissociate the nodal tissue and maximize the volume of the aspirated sample. When some blood-tinged material appeared in the hub of the needle, the sampling was deemed complete; after the release of the suction, the needle-syringe assembly was pulled out. Next, the cellular aspirate was recovered from the needle. First, the needle was disconnected from the syringe; if there was obviously material in the hub of the needle, an attempt was made to recover it by gently tapping the hub against a glass slide and smearing it. Then, the standard technique of recovering the aspirate was used as follows: The plunger of the syringe was retracted, the syringe was reconnected to the needle, and the plunger was pushed to expel the material contained in the hub and shaft of the needle onto glass slides. All smears were prepared by the radiologist, and the slides were dipped in a modified Carnoy fixative solution of 83% ethanol and 17% acetic acid in preparation for Papanicolaou and DiffQuik stains. An onsite cytopathologist was available to provide a preliminary diagnosis within 15 minutes. The number of passes needed to obtain a definitive cytopathologic diagnosis was recorded. After the cytopathologist confirmed the diagnostic quality of the aspirate, the patient was reevaluat-
ed for vital signs. Because there was no skin opening other than the puncture with the 20- or 21-gauge needle, the skin was cleaned, a simple small adhesive bandage was applied to the needle’s entry site, and the patient was discharged from the clinic. The final diagnosis of malignancy was established on the basis of the cytopathologic diagnosis. Correlation was made with the histopathologic type and grade of the primary breast tumor, and the location of the primary tumor within the breast. Clinical follow-up, imaging follow-up (ultrasound or CT), or both were performed for nodes with a benign diagnosis.
Fig. 5—Ultrasound-guided fine-needle aspiration (FNA) of internal mammary (IM) node: Diagram shows lateral-to-medial insertion of needle in intercostal space for FNA of IM node that is located in second left intercostal space. (Modified with permission from 3D Anatomy Images. Copyright of Primal Pictures Ltd. www.primalpictures.com)
AJR:203, August 2014 W215
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Fornage et al.
Fig. 7—Transverse sonogram obtained during ultrasound-guided fine-needle aspiration of small internal mammary node metastasis in second left intercostal space in 90-year-old woman. Node (arrow) measures 0.8 × 0.7 × 0.4 cm and is located lateral and anterior to internal thoracic artery (ITA). Note that needle is nearly parallel to pleura to ensure maximum safety of procedure. Entire shaft of needle is visible; needle tip is seen in center of node, a few millimeters from ITA.
Results The 18 women in our series ranged in age from 33 to 90 years, with an average age of 54 ± 14 (SD) years. All had a history of ipsilateral invasive ductal cancer of the breast. The primary tumor was in the medial breast in 11, in the lateral breast in four, and retroareolar in two; the location of the primary tumor was unavailable in one patient. The tumor grade was 3 (poorly differentiated) in 10 patients, 2 (moderately differentiated) in five patients, and 1 (well differentiated) in three patients.
Ultrasound Appearances of Nodes Twelve of the 19 nodes were in the first intercostal space (seven on the left side, five on the right side), six were in the second space (four on the left side, two on the right side), and only one was in the third right space. All lesions were ovoid, with their long axis parallel to the IT vessels. The largest lesion measured 3.4 × 2.8 × 1.8 cm and the smallest, 0.8 × 0.6 × 0.5 cm. The longest diameter of the lesions ranged from 0.8 to 3.4 cm (mean ± SD, 1.4 ± 0.6 cm), and
Fig. 9—Internal mammary nodal metastasis (arrows) in second left intercostal space in 58-year-old woman. Transverse color Doppler sonogram shows that node is located medial to internal thoracic vessels. Spectral Doppler analysis confirms internal thoracic artery.
W216
Fig. 8—Small internal mammary nodal metastasis (arrows) in third right intercostal space in 56-year-old woman. Transverse power Doppler sonogram shows that node is located lateral to internal thoracic artery (ITA) and internal thoracic vein (ITV).
the shortest diameter ranged from 0.4 to 1.8 cm (mean ± SD, 0.7 ± 0.3 cm). Fifteen (79%) nodes were lateral to the IT vessels (Fig. 8), two of which also covered the vessels anteriorly. Three nodes (16%) were medial to the vessels (Fig. 9), and one node (5%) was located between the ITA and the ITV (Fig. 10). Eleven malignant nodes were markedly hypoechoic (i.e., as hypoechoic as the costal cartilages, nearly anechoic) (Fig. 11), whereas five malignant nodes were moderately hy-
Fig. 10—Small internal mammary nodal metastasis (N) in first right intercostal space in 48-year-old woman. Transverse gray-scale sonogram shows hypoechoic node between internal thoracic artery (ITA) laterally and internal thoracic vein (ITV) medially. S = lateral edge of sternum.
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Ultrasound-Guided FNA of IM Nodes
Fig. 11—Internal mammary nodal metastasis from breast cancer in 44-year-old woman. Longitudinal sonogram of second right intercostal space shows markedly hypoechoic internal mammary nodal metastasis (N). Node is as hypoechoic as costal cartilage (C).
poechoic (hypoechogenicity comparable to that of subcutaneous fat). None was echogenic. Among the three benign nodes, two had the hypoechogenicity of fat (Fig. 12) and one was mildly echogenic. Two of the 16 malignant nodes had a minute amount of residual (eccentric) hilar echogenicity, and residual central echogenicity was seen in two of the three benign nodes. Only in five cases (26%), four metastases and one benign node, did color or power Doppler ultrasound reveal some internal vascularity inside the node (Fig. 13). Fine-Needle Aspiration Results A satisfactory cytologic specimen was obtained with a single 20- to 30-second pass with a 20- or 21-gauge needle in all nodes except two, in which two passes were made to confirm metastasis. All the specimens were diagnostic. FNA results revealed 16 metastases from breast cancer (Fig. 14) and benign lymphoid tissue in three cases of benign lymphadenopathy in two patients. One patient with a benign FNA result has been followed clinically for 3 years with no change in the ultrasound appearance of the node. In a second patient, who had two nodes that underwent FNA, one in the first left space and the other in the second left space, both FNAs were benign. This patient, who had a history of treated breast cancer and recently diagnosed lung cancer, underwent chemotherapy for the lung cancer. The two nodes remained stable for 2 years until one began to grow when the lung cancer recurred.
Fig. 12—Benign internal mammary node in 58-year-old woman with T1N1M0 breast cancer in lower outer quadrant of breast. Transverse gray-scale sonogram of first left intercostal space shows small flat node (arrows), which is lateral to internal thoracic vessels. Node shows hypoechogenicity similar to that of subcutaneous fat. S = lateral edge of sternum.
There were no immediate or delayed complications of the FNAs. Discussion Although the ultrasound examination of the axilla with ultrasound-guided biopsy of indeterminate axillary nodes has finally made its way into the standard ultrasound examination of patients with breast cancer, ultrasound examination of the IM nodal chains is often overlooked in the staging of disease in patients with breast cancer, and ultrasound-guided FNA of IM nodes has not been described in the literature to our knowledge. Ultrasound examination of the IM chains usually does not require special ultrasound equipment and is performed using the same high-frequency probe as the one used to scan the breast. However, in overweight patients or patients with thick muscles, it may be necessary to use a transducer of lower frequency. In individuals with a small chest or narrow intercostal spaces, a high-frequency “hockey-stick”–type transducer with a small footprint or a short-radius convex-array probe like those used for neurosonology of children might be beneficial. Although the IT vessels can sometimes be identified on gray-scale ultrasound by their characteristic motions, the use of color or power Doppler ultrasound is critical for confirming their identification before the needle biopsy and in planning the safest route for the needle. Visualization of the IT vessels on color or power Doppler imaging may also avoid the pitfall of misdiagnosing a promi-
nent or varicose ITV as a suspicious node. Power Doppler imaging is more sensitive for identifying slow or low-volume blood flow than color Doppler imaging and should be used to show the internal vascularity of the nodes whereas distinguishing between the ITV or ITVs and the ITA requires color Doppler and spectral Doppler analyses. We must stress that the PRF settings are different for the two applications and that setting the PRF at a low value to detect slow flow in the node will result in aliasing and flash artifacts in the IT vessels. Also, it may be difficult to register Doppler signals in the IT vessels because of the unfavorable insonation angle, which is often greater than 60°. Many fat-replaced echogenic nodes are normally seen in the axilla. On the contrary, such typically benign nodes are not seen along the IM chains. Although MRI can show tiny benign nodes in the range of 2–4 mm, these nodes are too small to be reliably identified on ultrasound. Therefore, it is reasonable to suspect that any visualized solid hypoechoic mass along the IT vessels in a patient with breast cancer is a metastatic node until proven otherwise. Our results show, however, that there is some overlap between the ultrasound appearances of malignant and benign nodes, although the numbers in this series are too small to draw conclusions. Although local anesthesia can be skipped when performing ultrasound-guided FNA of axillary nodes because the only sensitive anatomic component to traverse is the skin, ultrasound-guided FNA of the IM nodes re-
AJR:203, August 2014 W217
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Fornage et al.
Fig. 13—Internal mammary nodal metastasis from breast cancer in 90-year-old woman (same patient as in Fig. 7). Transverse power Doppler sonogram of second left intercostal space shows vascularity inside node.
quires local anesthetization of the pectoralis muscle with a few milliliters of 1% lidocaine [3–5]. Anesthetic administration is best performed under ultrasound guidance to ensure that the local anesthetic is deposited exactly along the projected path of the biopsy needle. Because of the presence of vital structures and the tight environment, patient safety should be the primary concern of the operator. The lateral-to-medial approach is the safest approach because the long (5-cm) needle can be inserted nearly parallel to the parietal pleura, which also results in the best visualization of the needle shaft and tip. It is important that we emphasize that the needle must be visualized during the entire procedure and not only intermittently. Any other approach (e.g., inferior-to-superior or medial-to-lateral) should be avoided because these approaches would result in a steep angle relative to the pleura and heightened risk of complications. Complications include bleeding from injury to the IM vessels and pneumothorax from pleural breaches. None occurred in our experience. Because there is no room to safely accommodate the throw of an automated large-core biopsy needle, core biopsy of the IM nodes cannot be performed with the available automated biopsy devices. Ultrasound-guided FNA is the tool of choice because of the precision with which the needle can be advanced under continuous real-time monitoring. In fact, the needle tip was often within a distance of only a few millimeters from the IT vessels or the parietal pleura.
W218
Fig. 14—Photomicrograph (Papanicolaou stain, ×40) of cytologic smear obtained from ultrasound-guided fine-needle aspiration of metastatic internal mammary node in 44-year-old woman shows abundant metastatic adenocarcinoma that has completely replaced node’s lymphoid tissue.
IM nodal metastases were most often found lateral to the IT vessels, but some were found between them or medial to them, rendering the procedure most challenging because the needle would have to pass just over the vessels. Although not encountered in this series, the possibility of nodes located not in the intercostal spaces but posterior to cartilage or even to the sternum exists. Obviously, in the latter case, the node would not even be seen on sonograms. Successfully placing the needle inside or through the target lesion is necessary but is not sufficient when performing FNA. Indeed, the most important phase of the FNA is the extraction of the cellular material. Extraction requires that the operator have expertise, especially if aspirating solid breast masses. However, aspiration of cellular material from lymph nodes—benign or malignant—is easy because of their rich cellularity. As a rule, in experienced hands, a single needle pass of 20–30 seconds’ duration can provide a sufficient sample. In this study, a single pass was sufficient in 89% of the procedures and all specimens were diagnostic. Because of limited access to the IM nodes and the risk of major complications, ultrasound-guided needle biopsy of the IM nodes should be performed only by imagers with extensive experience in interventional ultrasound and only in patients in whom the result of the procedure is expected to affect staging and clinical management. A discussion with the treating physician before the biopsy is therefore essential.
Like the axillary nodes, the IM chain is a first-echelon nodal drainage site in patients with breast cancer. IM nodal metastases are more frequent in patients with medial tumors, in patients with large tumors, in young patients, and in patients with axillary involvement [5, 6]. The fact that patients with medial tumors have worse outcomes than patients with lateral tumors of similar stage suggests that IM nodal metastases are underdiagnosed and that patients with IM nodal disease are possibly undertreated. Under these circumstances, the sixth and seventh editions of the TNM staging system of the American Joint Committee on Cancer were revised to reflect the impact of a positive IM node on breast cancer stage: Category N2b was assigned in case of metastases only in clinically detected ipsilateral IM nodes and in the absence of clinically evident level I and II axillary lymph node metastases, and category N3b was given in the presence of metastases in both ipsilateral IM nodes and axillary nodes. As a result, the diagnosis of a metastatic IM node automatically categorizes a breast cancer as stage III: stage IIIA for T0–T3 and IIIB for T4 primary tumors in the absence of axillary nodal metastases and stage IIIC in the presence of axillary nodal metastases regardless of the size of the primary tumor [3, 7] (Table 1). The interest of breast surgeons in the dissection of IM nodes is not new: As early as in the 1950s and 1960s, dissection of the IM nodes became popular and was added to the Halsted’s radical mastectomy tech-
AJR:203, August 2014
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
Ultrasound-Guided FNA of IM Nodes nique to be known as “extended mastectomy.” An early large clinical trial showed no advantage of adding IM node dissection to the mastectomy in terms of survival except in women with tumors located in the medial breast and those with axillary involvement [8]. In a subsequent large single-center study involving 1119 patients treated with extended mastectomy, the overall incidence of IM nodal metastases was 19% [9]. In that study, survival was significantly affected by the presence of positive IM nodes, with the 10-year survival rate decreasing from 80.4% in patients with axillary node involvement but without IM node involvement to 30.0% in patients with involvement of both nodal basins. Intermediate survival rates of 54.6% and 53.0% were found in cases of isolated axillary and IM node involvement, respectively [9]. Those authors acknowledged the need to know the status of the IM nodes and suggested a surgical biopsy of the first intercostal space in patients at risk for IM nodal metastases; they stated that they hoped that “the research on noninvasive methods of diagnosis of internal mammary node involvement will be intensified” [9]. With the advent and routine use of lympho scintigraphy for axillary sentinel node mapping and biopsy, the interest of surgeons was revived for the surgical biopsy of the IM sentinel node shown on lymphoscintigraphy. In a series of 506 patients undergoing preoperative lymphoscintigraphy for axillary sentinel node biopsy, one or more IM sentinel nodes were found in 109 patients (22%). Such drainage to the IM nodes was more frequent when the primary tumor was in the medial breast and in younger patients. However, IM sentinel nodes could be retrieved through a parasternal intercostal incision in only 85 of the 109 patients (78%), and metastases in these sentinel nodes were observed in only 20 of the 85 patients (24%). Complications (pleural breaching or damage to the IT vessels) occurred in 10 of 109 patients (9%) [6]. Other studies have reported a range of visualized IM nodes on lymphoscintigraphy of 11–25% and successful retrieval of the sentinel IM nodes of 63–88% [10–12]. There is still debate about the clinical effect of the detection and diagnosis of an IM nodal metastasis on the patient’s treatment and prognosis. A change in management—institution or omission of radiotherapy to the IM chain, adjuvant systemic therapy, or omission of an axillary lymph node dissection—was reported in 29% of the patients in one study [12], whereas
the authors of another study found that parasternal sentinel node biopsy resulted in upstaging in only 2% of the breast cancer patients who underwent that procedure [10]. It should be remembered that because of the limitations and technical difficulties of sentinel IM node biopsy, pathologic examination will identify a metastatic node in only approximately 2–3% of the entire population undergoing this procedure [6, 10]. We expect that direct ultrasound visualization of minimally enlarged IM nodes coupled with ultrasound-guided FNA will allow the detection and diagnosis of a greater number of metastatic IM nodes of a smaller size. It should also be kept in mind that delivering a boost of radiation therapy to the IM chain is associated with a risk of inducing cardiac morbidity. As in our study, most IM nodal metastases are found in the first three intercostal spaces, which has led some authors to suggest selective irradiation of only the superior IM chain (intercostal spaces 1, 2, and 3) and exclusion of the lower spaces, thus shielding the heart [13]. However, irradiation of the IM chain should be restricted to patients with a pathologically proven IM node. This proof can now be easily obtained in a few minutes via ultrasound-guided FNA. The common thinking is that a medial tumor with an IM nodal metastasis should not be considered as associated with a worse prognosis than a lateral tumor with an axillary nodal metastasis. However, the finding of an IM nodal metastasis in addition to positive axillary nodes has a well-known substantial adverse effect on the patient’s prognosis, as reflected in the latest TNM classification. Ultrasound-guided FNA appears to be the less invasive means of detecting and confirming occult IM nodal metastases that has been long awaited to obtain the needed information on the IM lymphatic status and thereby facilitate treatment decisions. The indications for this procedure in patients with breast cancer remain to be defined in view of the implications of a positive diagnosis of metastatic disease on the patient’s management. A prospective study has been launched at our institution to study this issue. References 1. Scatarige JC, Hamper UM, Sheth S, Allen HA III. Parasternal sonography of the internal mammary vessels: technique, normal anatomy, and lymphadenopathy. Radiology 1989; 172:453–457 2. Fornage BD. Ultrasound of the breast. Ultrasound Q 1993; 11:1–39 3. Edge SB, Byrd DR, Compton CC, Fritz AG,
TABLE 1: Impact of the Presence of an Internal Mammary (IM) Node Metastasis on the Staging of Breast Cancer Stage IIIA
IIIB
IIIC
T Category N Category
M Category
T0
N2
M0
T1a
N2
M0
T2
N2
M0
T3
N1
M0
T3
N2
M0
T4
N0
M0
T4
N1
M0
T4
N2
M0
Any T
N3
M0
Note—The diagnosis of an ipsilateral IM nodal metastasis in the absence of level I and II axillary node metastases (N2b) classifies the disease as stage IIIA for T0–T3 tumors or stage IIIB for T4 primary tumors. The presence of an IM nodal metastasis in association with axillary nodes (N3b) classifies the disease as stage IIIC regardless of the size of the primary tumor [3]. aIncludes tumors with microinvasion (< 0.1 cm). Greene FL, Trotti A, eds. Breast. In: AJCC cancer staging manual, 7th ed. New York, NY: Springer, 2010:347–376 4. Loukas M, Tobola MS, Tubbs RS, et al. The clinical anatomy of the internal thoracic veins. Folia Morphol (Warsz) 2007; 66:25–32 5. Huang O, Wang L, Shen K, et al. Breast cancer subpopulation with high risk of internal mammary lymph nodes metastasis: analysis of 2,269 Chinese breast cancer patients treated with extended radical mastectomy. Breast Cancer Res Treat 2008; 107:379–387 6. Madsen E, Gobardhan P, Bongers V, et al. The impact on post-surgical treatment of sentinel lymph node biopsy of internal mammary lymph nodes in patients with breast cancer. Ann Surg Oncol 2007; 14:1486–1492 7. Galimberti V, Veronesi P, Arnone P, et al. Stage migration after biopsy of internal mammary chain lymph nodes in breast cancer patients. Ann Surg Oncol 2002; 9:924–928 8. Lacour J, Bucalossi P, Cacers E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection: five-year results of an international cooperative study. Cancer 1976; 37:206–214 9. Veronesi U, Cascinelli N, Greco M, et al. Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes. Ann Surg 1985; 202:702–707 10. Leidenius MHK, Krogerus LA, Toivonen TS, Leppänen EA, von Smitten KA. The clinical value of parasternal sentinel node biopsy in breast
AJR:203, August 2014 W219
Fornage et al.
Downloaded from www.ajronline.org by 158.121.247.60 on 08/21/14 from IP address 158.121.247.60. Copyright ARRS. For personal use only; all rights reserved
cancer. Ann Surg Oncol 2006; 13:321–326 11. Farrús B, Vidal-Sicart S, Velasco M, et al. Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan. Int J
Radiat Oncol Biol Phys 2004; 60:715–721 12. Estourgie SH, Tanis PJ, Nieweg OE, Valdés Olmos RA, Rutgers EJ, Kroon BB. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients.
Ann Surg Oncol 2003; 10:935–941 13. Marks LB, Hebert ME, Bentel G, Spencer DP, Sherouse GW, Prosnitz LR. To treat or not to treat the internal mammary nodes: a possible compromise. Int J Radiat Oncol Biol Phys 1994; 29:903–909
F O R YO U R I N F O R M AT I O N
The data supplement accompanying this web exclusive article can be viewed by clicking “Supplemental” at the top of the article.
W220
AJR:203, August 2014
