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Keywords:

  • breast cancer;
  • lymph nodes;
  • fine-needle aspiration biopsy;
  • sentinel lymph node biopsy;
  • neoadjuvant chemotherapy

Abstract

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References

Staging of disease is routine in the evaluation of patients newly diagnosed with breast cancer. Assessment of palpable and/or nonpalpable locoregional lymph nodes is an important component of the initial staging. Ultrasound (US) is the favored imaging modality for the initial investigation of lymph nodes and results in a significant increase in the specificity of the overall evaluation when used in conjunction with fine-needle aspiration (FNA). This review provides a concise summary, based on published literature, of the current applications and future prospects of FNA biopsy of locoregional lymph nodes in the initial staging and subsequent surgical management of patients with breast cancer. Patients undergo either sentinel lymph node (SLN) biopsy or complete axillary lymph node dissection, based on whether the axillary lymph node status is determined to be negative or positive in the initial staging process. The status of lymph nodes in the supraclavicular, infraclavicular, and internal mammary regions provides more accurate staging information and also impacts subsequent surgical management. The identification and evaluation of intramammary lymph nodes can add value in the overall assessment of patients with breast cancer. The feasibility of noninvasive imaging modalities for SLN mapping in animal models has indicated a good potential for FNA biopsy in the subsequent investigation of SLNs identified noninvasively in humans. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

Staging of the malignant tumor is a routine component in the assessment of patients who are newly diagnosed with breast cancer. Breast cancer staging aids in the appropriate management of patients at each stage of disease and is useful in estimating the prognosis for a patient at a particular stage. The routine staging process includes taking a thorough history of the patient, physical examination, mammography, ultrasonography (US) of the breast and lymph node basins, computed tomography (CT) scan of the abdomen, bone scanning, and chest radiography. Cancer is assigned a clinical stage at the time of the initial diagnosis based on the findings of the physical examination, radiologic studies, and core needle biopsy (CNB) of the primary breast tumor, with or without fine-needle aspiration (FNA) biopsy or CNB of locoregional lymph nodes (ie, those in the axillary basins, supraclavicular and infraclavicular regions, and internal mammary chain). The definitive breast cancer stage is based on pathologic information obtained at the time of surgical removal of the primary tumor and regional lymph nodes.

Traditionally, breast cancer has been staged using the tumor-node-metastasis (TNM) classification system, which classifies cancer based on the size of the primary tumor, the presence and extent of regional lymph node involvement, and the presence of distant metastasis. Breast cancer staging using TNM classification has been adopted by the American Joint Commission on Cancer (AJCC); last revised in 2003, it provides guidelines for the accurate staging of any breast tumor.1, 2

Determining whether cancer has spread to locoregional lymph nodes is a critical step in the initial staging of patients with breast cancer and dictates the selection of treatment options. Physical examination alone is neither sensitive nor reliable in evaluating lymph nodes because lymph nodes with metastatic disease are often not palpable and reactive lymph nodes may be enlarged, mimicking metastasis. The false-negative rate of clinical examination of axilla for detecting metastatic lymph nodes is reported to be as high as 30% to 45% in different series.3-5 Imaging modalities can improve the sensitivity of clinical examination in assessing locoregional lymph node status in the preliminary staging process. The different types of imaging techniques available for this purpose include US, magnetic resonance imaging (MRI), CT, positron emission tomography-CT, technetium 99m sestamibi imaging, and immunoscintigraphy.6-10 In the detection of lymph node metastasis, the accuracy of high-resolution US is equal to or greater than that of other techniques. In addition, the relative ease of obtaining a tissue biopsy is a distinct advantage of US imaging of lymph nodes. Therefore, US is the favored primary imaging technique and is widely used for determining the status of locoregional lymph nodes in the initial staging of breast cancer.

Breast imaging with US has undergone a dramatic evolution in both technical advances and clinical applicability. The accuracy of preoperative US diagnosis of lymph node status has improved with the development of high-resolution and Doppler US and better definition of criteria that may indicate the presence of metastasis in the lymph nodes. US aids in the visualization of not only alterations in the size, shape, and contours of the lymph node but also changes in the cortical morphology and texture, which can reflect the presence of an underlying metastasis.

Several sonographic features have been suggested to categorize a lymph node as possibly benign or metastatic. Sonographic features that suggest a benign lymph node include a predominantly hyperechoic signal due to fat replacement, the presence of a thin homogeneous symmetrical cortical rim around the hyperechoic hilar fat, and symmetrical cortical lobulations. The lymph node is categorized sonographically as suspicious or positive for metastatic disease when there is thickening or eccentric lobulation of the hyperechoic cortical rim, compression or displacement of the fatty hyperechoic hilum, or complete replacement of the hilar fat by hypoechoic tissue.11-21 Bonnema et al11 found that classifying lymph nodes with a hyperechoic pattern at the center as benign and those with a hypoechoic center or inhomogeneous architecture as malignant yielded a sensitivity of 36% and specificity of 95%. Although De Kanter et al13 also found these criteria to be helpful in detecting metastasis, they also found that 30% of lymph nodes believed to be benign using these criteria were malignant at the time of cytologic or histologic analysis. When size >5 mm was used as a criterion, Bonnema et al11 found that the sensitivity increased to 87%, with a significant reduction in specificity to 56%. Studies using in vitro sonography of isolated lymph nodes have further refined the criteria for categorizing a lymph node as possibly benign or malignant.22, 23 These studies indicate that changes in cortical morphology may precede any changes in the overall size or echogenicity of the hilum; thus, changes in cortical morphology may be at least as important as the other features alluded to by in vivo studies. Focusing on changes in cortical morphology, Bedi et al23 used in vitro sonography of 171 axillary lymph nodes, dividing the lymph nodes into 6 subgroups with a progressive increase in the probability of metastasis. Using the final correlation of sonographic features with histopathologic examination of the dissected lymph nodes that were scanned before processing, they reported that predominantly hyperechoic lymph nodes can be considered benign, whereas those with asymmetric focal hypoechoic cortical lobulation or a completely hypoechoic signal are most likely malignant. Bedi et al also pointed out that generalized cortical lobulation may produce false-negative results, and therefore should be regarded as indeterminate for metastasis.23

The criteria for the preoperative stratification of lymph nodes based on US features are not standardized, making strict comparisons between studies impossible. Alvarez et al24 performed a meta-analysis of all reported studies of sonography of axillary lymph nodes using size >5 mm or alterations in cortical morphology as criteria for labeling a lymph node as abnormal. These researchers found that sensitivity varied between 54.7% and 92.3% and specificity between 44.1% and 97.1% in studies that included palpable and nonpalpable lymph nodes. In studies of nonpalpable lymph nodes alone, sensitivity ranged from 26.4% to 87.1% and specificity from 55.6% to 98.1%. The use of different criteria and study design has resulted in mixed findings, with a wide range of results from different studies reported in the literature.

Tissue biopsy of locoregional lymph nodes that appear to harbor metastatic disease increases the specificity of physical examination during the initial staging process. FNA biopsy is widely used for this purpose. Similarly, tissue biopsy of sonographically indeterminate, suspicious, and metastatic-appearing lymph nodes provides a more definite diagnosis than sonography alone. To the best of our knowledge, there are no strict guidelines for selecting the lymph nodes for performing tissue biopsy. The majority of investigators performed FNA biopsy of lymph nodes suspected of harboring metastatic disease on sonography. Kuenen-Boumeester et al20 performed FNA biopsy of lymph nodes nearest to the breast, postulating that these lymph nodes most likely represent sentinel lymph nodes (SLNs). Some investigators have biopsied the lymph node that appeared to be the largest on US. Jain et al25 performed FNA biopsy of all lymph nodes, including benign-appearing lymph nodes. Although both FNA biopsy and CNB have been used by different investigators, FNA biopsy has most often been used for this purpose. In the very few studies that used CNB, the sensitivity and specificity were comparable to those of FNA biopsy.26-28

US-guided FNA of the lymph nodes is generally performed by the radiologist using a 22-gauge or 23-gauge hypodermic needle with a 10-mL syringe attached to the needle, with or without the instillation of local anesthetic in and around the lymph node of interest. There are no recommendations for optimal processing of the aspirate. Direct smears fixed in alcohol for Papanicolaou staining or air-dried for Diff-Quik staining have been used by most investigators. Conventional cytomorphologic evaluation alone was performed by all investigators for rendering a definite diagnosis of the aspirated material without the use of ancillary cytokeratin immunostaining. It is plausible that, in centers in which immediate assessment of the aspirate is not performed, the aspirated material can be used to make a cell block, cytospin, or monolayer preparation rather than many direct smears, thereby facilitating evaluation. Koelliker et al29 used Thin Prep (Hologic Inc, Bedford, Mass) and reported the utility of this technique for processing the specimen. Immediate assessment of the specimen allows for the evaluation of the quality of the aspirate proportionate to the size of the aspirated lymph node, and in cases with paucicellular aspirate, the radiologist could perform additional passes to improve the specimen quality and procure a sufficient amount of lymphoid tissue for evaluation. In addition, at the immediate diagnosis of metastatic carcinoma in 1 of many abnormal lymph nodes in a particular region, the radiologist can terminate further evaluation of the remaining sonographically abnormal lymph nodes. Inadequate sampling rates, ranging from 5% to 10%, have been reported in a few studies.18, 19, 30 These studies emphasized the value of immediate assessment to improve the adequacy of the specimen for cytologic evaluation.

The overall sensitivity of US-guided FNA biopsy for the evaluation of axillary lymph nodes in the initial staging of breast cancer ranged from 25% to 95% and specificity from 97% to 100%.24, 25, 29-41 False-positive results, ranging from 1.4% to 1.6%, have been reported only rarely.20, 30, 31 These results have been reported to occur occasionally because of interpretive errors and mistaking reactive lymphoid cells or mesothelial cells for metastatic carcinoma. The majority of cases believed to be false-positive may indeed be true‒positive cases because of complete response to neoadjuvant chemotherapy or, occasionally, failure to detect minimal volume disease on final pathologic examination. The common causes of false-negative results from US-guided FNA biopsy of locoregional lymph nodes include failure to observe all lymph nodes on US, small metastases (measuring <5 mm), involvement of few (usually 1-3) lymph nodes by metastatic disease, and interpretive errors, including failure to recognize tumor cells.12, 20 The usual pitfalls in making a diagnosis of metastatic carcinoma include mistaking reactive lymphoid cells, immunoblasts, histiocytes, dendritic reticulum cells, endothelial cells, or megakaryocytes as metastatic carcinoma. The difficulty of distinguishing histiocytes from metastatic lobular carcinoma is well known. To the best of my knowledge, the sensitivities of US-guided FNA biopsy of lymph nodes in the detection of metastatic ductal and lobular carcinomas have not been compared in any of the studies.

Current applications and future prospects of FNA biopsy of locoregional lymph nodes in the initial staging and subsequent surgical management of patients with early and advanced breast cancer are summarized below.

Early Stage Breast Cancer

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References

Initial staging of axillary lymph nodes in patients with early stage (T1 or T2) breast cancer helps the surgeon select the appropriate surgical management of axilla. Patients who have no evidence of metastatic disease in the preliminary staging process are selected for SLN biopsy, whereas those with evidence of metastatic disease undergo complete dissection of the axillary lymph nodes.42, 43 Axillary SLNs receive drainage from the breast parenchyma first and, therefore, have the highest probability of containing metastatic cells. The overall accuracy and false-negative rate of SLN biopsy performed in patients with early stage breast cancer have been validated by several large studies and range from 95% to 99% and from 8% to 12%, respectively.44-46 The pathologic status of SLNs is a sensitive and specific predictor of non-SLN status in breast cancer patients. When SLNs are found to be negative for metastasis by thorough pathologic evaluation, complete dissection of axillary lymph nodes and its associated morbidities, including lymphedema and neuropathy, can be obviated. SLNs are identified by performing a lymphoscintigram, in which radioactive technetium sulfur colloid is injected in and around the primary tumor before surgery and isosulfan blue is injected at the time of surgery to aid in the final dissection of the SLN. Detection of metastatic disease in the axillary lymph nodes during the initial staging process allows for the complete dissection of these lymph nodes at the time of primary breast surgery, thereby avoiding a staged procedure with the incurred additional operative time, cost, and effort. In addition, patients who are recognized upfront as not suitable for SLN biopsy are protected from possible anaphylactic reaction to the blue dye used for lymphatic mapping.47, 48 Cosmetic side effects, including discoloration of skin after intradermal injection of the blue dye, can also be avoided. The identification of lymph nodes harboring metastatic disease during the initial staging process can also avoid false-negative results of SLN biopsy, which may result from diversion of the lymphatic channels after blockage of the true SLN by metastatic tumor. Several studies have reported the utility of US-guided FNA biopsy for guiding surgeons in the selection of either SLN biopsy or complete axillary lymph node dissection in patients with early stage breast cancer. US-guided FNA biopsy of axillary lymph nodes with features suggesting metastasis is reported to have avoided SLN biopsy in 8% to 33% of patients with early stage breast cancer.30-40 Figure 1 is an illustration of the utility of US-guided FNA biopsy of axillary lymph nodes in a patient with early stage breast cancer. The reported false-negative rate ranges from 5% to 48%. Although the majority of studies published to date indicate that small-sized metastases accounted for the majority of the false-negative results, the mean size of the metastatic tumor missed by US-guided FNA biopsy of the lymph nodes has, to the best of my knowledge, been reported only rarely. Krishnamurthy et al40 found the mean size of metastasis to be 3.5 mm in false-negative cases of US-guided FNA biopsy of lymph nodes in patients with early stage breast cancer. US-guided FNA biopsy has high specificity and positive predictive value, thus reducing the number of unnecessary SLN procedures. Figure 2 illustrates a false-negative result of a US-guided FNA biopsy of an axillary lymph node in a patient with early stage breast cancer. The utility of FNA biopsy of axillary lymph nodes in patients with early stage breast cancer is depicted in Figure 3.

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Figure 1. (A) Ultrasound of the axilla in a patient with early stage breast cancer demonstrated an oval, hypoechoic lymph node that was categorized as indeterminate on sonographic evaluation. (B) Fine-needle aspiration biopsy of the same lymph node demonstrated a polymorphous population of lymphoid cells without any evidence of metastasis. (C) The patient underwent sentinel lymph node biopsy that was also negative for metastatic disease.

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Figure 2. (A) Ultrasound of the axilla in a patient with early stage breast cancer demonstrated an indeterminate axillary lymph node with a focal area of cortical thickening. (B) Direct smears of a fine-needle aspiration biopsy of the same lymph node demonstrated benign lymphoid tissue without any evidence of metastatic tumor. (C) The patient underwent sentinel lymph node biopsy, which demonstrated a metastatic tumor measuring 4.0 mm in greatest dimension.

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Figure 3. The utility of fine‒needle aspiration biopsy of axillary lymph nodes in patients with early stage breast cancer is shown.

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Patients Selected for Neoadjuvant Chemotherapy

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References

Neoadjuvant therapy (chemotherapy preceding therapeutic surgery) is the standard treatment plan for patients with more advanced or inoperable breast cancer.49, 50 Recently, indications for neoadjuvant therapy have expanded to include selected patients with operable and early stage disease. The neoadjuvant approach is based on the results of studies indicating that most breast tumors will decrease in size when exposed to 3 or 4 cycles of cytotoxic chemotherapy. The benefits of neoadjuvant chemotherapy for patients with locally advanced breast cancer are widely reported and include in vivo assessment of the response of the tumor to cytotoxic chemotherapy, conversion from inoperable to operable disease, and potential downsizing of large tumors, allowing breast-conserving therapy in patients who were initially believed to be unfit for such treatment.49, 50

Determining the status of locoregional lymph nodes contributes to the accurate staging of the cancer before the initiation of neoadjuvant chemotherapy and provides a baseline for evaluating response in lymph nodes proven to contain metastases. In addition, the status of locoregional lymph node involvement at presentation is prognostic of treatment failure. Patients with documented lymph node disease before systemic therapy are reported to have the highest recurrence rates, and lack of a response to chemotherapy is a statistically significant predictor of distant failure.54 Many reports have described the role of US-guided FNA biopsy of axillary lymph nodes in directing the surgical treatment of patients with early stage breast cancer; however, only a few reports have illustrated its utility in patients selected to receive neoadjuvant chemotherapy. Khan et al51 reported the value of a comprehensive approach to staging, including the evaluation of axillary and nonaxillary lymph nodes (including supraclavicular, infraclavicular, and internal mammary chain lymph nodes), before neoadjuvant chemotherapy.51 Although preneoadjuvant lymph node staging cannot determine the full extent of axillary lymph node disease, it provides useful information for medical oncologists in planning chemotherapy regimens.

To the best of our knowledge, only a few other reports to date have indicated the value of the initial staging of the axillary lymph nodes and its impact on subsequent axillary intervention after the completion of chemotherapy.52-56 Patients who are negative for lymph node metastasis in the initial staging process may be candidates for SLN biopsy, and patients with documented metastasis may be candidates for complete dissection of axillary lymph nodes after the completion of chemotherapy. Figure 4 illustrates the utility of US-guided FNA of axillary lymph nodes in the initial staging of a patient with advanced breast cancer. Whereas the majority of published data regarding SLN biopsy and neoadjuvant chemotherapy have reported on the accuracy of lymphatic mapping performed after the completion of systemic therapy, few groups have reported the utility of SLN biopsy before the initiation of chemotherapy in patients who are determined to be free of lymph node disease by US, with or without FNA biopsy of suspicious and indeterminate lymph nodes.54, 55 The rationale for performing SLN biopsy before chemotherapy is to determine axillary lymph node status more accurately than would be possible from US-guided biopsy alone, which can aid in the subsequent management of axilla after the completion of chemotherapy. The utility of FNA biopsy of axillary lymph nodes in patients selected for neoadjuvant chemotherapy is depicted in Figure 3.

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Figure 4. (A) Ultrasound of the axilla in a patient with locally advanced cancer demonstrated a large, hypoechoic lymph node that was categorized as malignant on sonographic evaluation. (B) Direct smears demonstrated metastatic disease. (C) The patient received neoadjuvant chemotherapy and subsequently underwent axillary lymph node dissection. Note the presence of residual tumor amid areas of sclerosis, indicating a partial response to chemotherapy.

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Evaluation of other lymph node regions, such as the supraclavicular, infraclavicular, and internal mammary chains, in addition to the axillary basins, allows for a more thorough evaluation of lymph node status in the initial staging process of patients who are selected for neoadjuvant chemotherapy. In the sixth edition of the AJCC staging system, metastasis in ipsilateral infraclavicular lymph nodes and axillary lymph nodes is staged as N3a, that in internal mammary lymph nodes and axillary lymph nodes is staged as N3b, and metastasis in supraclavicular lymph nodes is staged as N3c. Rare reports have indicated the utility of determining the status of these lymph nodes in the initial staging process. The relatively low fat content in lymph nodes at these sites makes US evaluation of their status, with or without FNA biopsy, very suitable for evaluation. Newman et al56 evaluated the significance of the involvement of infraclavicular (level III axillary contents) adenopathy identified by US, with or without FNA biopsy, in a series of patients with locally advanced breast cancer who were receiving preoperative chemotherapy. These authors reported that infraclavicular lymph node involvement as detected by US indicated a significantly worse survival rate. They found that the disease-free and overall 5-year survival rates for patients with suspected infraclavicular adenopathy was significantly worse than for patients without this feature (50% vs 68% and 58% vs 83%, respectively). Nearly one-third of patients with locally advanced breast cancer will have involved infraclavicular lymph nodes, which indicates a significantly adverse prognosis. In addition, preoperative identification of infraclavicular lymph node involvement necessitates a level III axillary lymph node dissection during definitive surgery after neoadjuvant chemotherapy. Figure 5 illustrates the results of an investigation of the infraclavicular region in a patient with advanced breast cancer. With rapid advancements in the development of novel systemic therapy regimens, it will become increasingly important to identify patients who face the highest risk of disease recurrence and risk of failure to respond to systemic therapy. The utility of the assessment of lymph node involvement in regions other than axillary lymph node basins is evolving and is routinely evaluated in some if not all centers involved in the comprehensive care of patients with breast cancer.

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Figure 5. (A) Ultrasound of the infraclavicular region in a patient with locally advanced breast cancer illustrated a hypoechoic lymph node that was categorized as suspicious on sonographic evaluation. (B) Direct smears of a fine-needle aspiration of the lymph node demonstrated metastatic carcinoma. The patient received neoadjuvant chemotherapy and underwent complete axillary lymph node dissection, including removal of infraclavicular lymph nodes. (C) An illustration of 1 of the infraclavicular lymph nodes with large areas of sclerosis without any evidence of metastatic tumor is shown, indicating a complete response to chemotherapy.

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Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References

Intramammary lymph nodes (IMLNs) are defined as lymph nodes surrounded by breast tissue and are encountered in 1% to 28% of patients.57-59 Low-lying axillary lymph nodes or deep pectoral lymph nodes can be mistaken for IMLNs. IMLNs are a potential site for the regional spread of breast cancer. Although IMLNs can occur anywhere in the breast parenchyma, they are usually identified in the upper outer quadrant of the breast.59 The clinical importance of IMLN metastasis has not received adequate attention. Current breast cancer staging considers an IMLN with metastatic disease as an axillary lymph node, leading to a lymph node stage of N1 (provided the size of metastasis is >0.2 mm), even if the axillary lymph nodes are proven to be negative for metastatic disease. US is more sensitive than mammography in the detection of metastasis in IMLNs. Evaluation of IMLNs not only provides staging information in both early and advanced stage breast cancer but also localizes these lymph nodes for subsequent final histopathologic examination of the mastectomy/segmental mastectomy specimen. A preoperative diagnosis of metastatic IMLN by US-guided FNA biopsy warrants inclusion of the lymph node in the surgically excised tissue for patients undergoing breast-conserving surgery. Rarely, the identification of metastasis in an IMLN may lead to detection of occult or recurrent breast cancer. Edeiken-Monroe et al60 have reported the usefulness of sonography and US-guided FNA biopsy for the preoperative assessment of IMLNs in patients with breast cancer. The most consistent sonographic features associated with IMLN metastases were a reduction in the volume of central echogenic hilum and marked hypoechogenicity of the IMLN cortex.

The management of axillary lymph nodes in patients with IMLN metastasis is controversial. The controversy lies in whether an IMLN testing positive for metastasis warrants a complete dissection of axillary lymph nodes, similar to a positive axillary lymph node, or whether the axillary lymph nodes can be spared.59, 61-65 Irrespective of the controversy regarding the management of axillary lymph nodes in patients with an IMLN metastasis, the preoperative identification of IMLNs by US imaging and the investigation of these lymph nodes by US-guided FNA biopsy may be meaningful for the subsequent care of patients with breast cancer.

Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References

There is currently a great deal of interest in exploring noninvasive methods for the accurate identification and investigation of metastatic disease in SLNs for axillary lymph node staging in breast cancer. A combination of the radioactive colloid and blue dye methods that is currently used to identify SLNs in patients with breast cancer suffers from some limitations. The radioactive colloid method requires special facilities for handling radioactive isotopes and suffers from the low spatial resolution of the Geiger counters used for noninvasive SLN identification. In addition, this method takes approximately 24 hours for lymph node uptake because of the large size of the tracers (typically 100-200 nanometers) and may cause radiation damage to the connective tissues of the skin. The method using blue dye, such as isosulfan blue or methylene blue, requires surgery for visual identification of lymph nodes with uptake of the blue dye. Noninvasive, nonionizing, and high-resolution mapping of SLNs in conjunction with minimally invasive methods, such as FNA biopsy, for the detection of metastatic tumors is currently being actively investigated in a few preclinical studies. One such technique, photoacoustic tomography, is an emerging hybrid technology that is proving to be excellent for noninvasive imaging of biologic tissues, offering not only a good spatial resolution but also high soft-tissue contrast.66-69 This technique is highly sensitive to endogenous and exogenous optical contrast and provides good ultrasonic spatial resolution. In addition, because this imaging system uses diffusive photons, it can achieve up to a 50-mm imaging depth in biologic tissues with satisfactory spatial resolution, which is very suitable for the noninvasive identification of axillary SLNs. Photoacoustic imaging (PI) systems are nonionizing and relatively inexpensive, have a higher sensitivity than MRI, and have the potential to be readily and easily adapted to clinical practice. PI has been used successfully for the in vivo identification of SLNs in animal models using different types of contrast agents with high contrast-to-noise ratios and good resolution. These contrast agents are used as nanoparticles because of their widely tunable properties, such as sizes, shapes, and composition that enhance the contrast for optical imaging in the noninvasive identification of SLNs. Pramanik et al67 have demonstrated the utility of single-walled carbon nanotubes as a contrast agent for the noninvasive identification of SLNs using PI in a rat model.67 The advantage of this agent is reported to be the broad absorption spectrum, which provides a wide range of light wavelengths for imaging. Near-infrared gold nanocages were used by Song et al68 for SLN mapping using the PI modality.68 These authors point out that both of these contrast agents can be further functionalized by bioconjugation with specific targeting molecules, thereby allowing molecular imaging for the detection of metastatic tumor in SLNs. The PI techniques hold promise for translation to humans for the noninvasive identification of SLNs; in conjunction with FNA biopsy, PI can potentially avoid the currently practiced invasive technique of SLN biopsy. Currently, this imaging system is limited by its slow scanning speed. However, using a higher pulse repetition frequency laser and a US array system could accelerate acquisition of signals, improving the feasibility of real-time PI for clinical use.

Conclusions

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References

In summary, FNA biopsy of locoregional lymph nodes plays an important role in the initial staging of breast cancer. Sonographic evaluation of lymph nodes, with or without associated FNA biopsy of indeterminate, suspicious, or metastatic lymph nodes, increases the sensitivity and specificity of the evaluation in patients with early and advanced stage breast cancer. In both groups, the evaluation of axillary lymph nodes can influence surgical management of the axilla. In addition, in patients with advanced stage disease, the detection of metastatic disease in lymph nodes not only provides staging information but also provides an opportunity to evaluate the tumor's response to treatment during the course of neoadjuvant chemotherapy. Currently, comprehensive evaluation of locoregional lymph nodes in patients newly diagnosed with breast cancer is routinely practiced in several comprehensive cancer centers.

Advances in imaging modalities, such as PI, hold promise for the noninvasive identification of SLNs in patients with breast cancer. FNA biopsy is well suited as a minimally invasive technique for the investigation of SLNs identified noninvasively by such newly emerging technology. In addition, if molecular imaging of SLNs becomes feasible after successful bioconjugation of contrast agents with specific targeting molecules for imaging of metastatic tumor, FNA biopsy can be useful for confirming the presence of metastatic tumor in the targeted areas.

References

  1. Top of page
  2. Abstract
  3. Early Stage Breast Cancer
  4. Patients Selected for Neoadjuvant Chemotherapy
  5. Preoperative Identification and Detection of Metastatic Tumors in Intramammary Lymph Nodes
  6. Prospects for Use of FNA Biopsy in Staging Axillary Lymph Nodes
  7. Conclusions
  8. Acknowledgements
  9. Conflict of Interest Disclosures
  10. References
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