Imaging of the Axilla

Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. Special Imaging Considerations There are a few publications reporting on the utilization of elastography, contrast-enhanced US, photoacoustic imaging, and MRI with magnetic nanoparticles [16-18]. These advanced imaging methods are still investigational and not recommended for routine clinical use.


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis If a chest wall lesion or an axillary mass invading the chest wall is suspected, CT chest can determine if there is any adjacent bony involvement or any chest wall or pleural space involvement [23]. An axillary mass may also be an incidental imaging finding detected on a CT examination that includes the chest. In such situations, further investigation with axillary US and possible US-guided biopsy may be helpful.


Imaging of the Axilla

Imaging of the Axilla. Digital Breast Tomosynthesis Diagnostic There is insufficient data to support the use of DBT as the single initial imaging test for an axillary palpable mass, even though a portion or all of the axillary mass may be visible on DBT. If there is a personal history of breast cancer or clinical suspicion of axillary tail breast carcinoma, DBT, as an adjunct test to axillary US, can provide a global assessment of the ipsilateral breast and also assess for other suspicious findings such as microcalcifications associated with the palpable axillary mass. DBT allows better characterization of lesions and addresses some of the limitations associated with standard 2-D mammography [24-27].


Imaging of the Axilla

Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. If the unilateral axillary mass is suspicious for metastatic adenopathy from a primary breast cancer or occult breast cancer, the reported data from multicenter trials for DBT use in this population, in addition to digital mammography, was associated with an increased primary breast cancer detection rate compared with digital mammogram alone [28]. DBT, in addition to digital mammography, demonstrated best performance gains in women ages 40 to 49 years [29].


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is not beneficial for assessing an axillary mass of unknown etiology as the initial imaging assessment because of its low yield to detect an occult primary malignancy without first confirming that the unilateral axillary mass is of malignant etiology [30,31]. Less than 1% of breast cancers initially present as axillary adenopathy [32,33]. If FDG-PET/CT incidentally detects an FDG-avid lymph node, then axillary US is helpful to characterize the nodal morphology and guide biopsy, if warranted.


Imaging of the Axilla

Imaging of the Axilla. Mammography Diagnostic There is insufficient data to support the use of mammography as the initial imaging test for an axillary palpable mass, even though pathologically enlarged nodes may be seen as dense enlarged nodes or masses on the mediolateral or mediolateral-oblique projection of a mammogram. However, if there is a personal history of breast cancer or clinical suspicion of axillary tail breast carcinoma or metastatic adenopathy from a breast primary, then mammography as an adjunct test to axillary US can provide global assessment of the ipsilateral breast and identify other suspicious findings such as microcalcifications associated with the palpable mass.


Imaging of the Axilla

Imaging of the Axilla. MRI Breast MRI of the breast is not routinely performed as the initial imaging assessment for a unilateral palpable axillary mass. MRI may be helpful in defining disease extent and characterizing the breast primary if axillary US reveals adenopathy of unknown primary malignancy and the mammogram is negative for a primary breast malignancy [34,35]. MRI can also help characterize the axillary mass by determining any adjacent vascular involvement, chest wall involvement, and involvement of other axillary structures.


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi molecular breast imaging (MBI) for assessing a unilateral palpable axillary mass.


Imaging of the Axilla

Imaging of the Axilla. US Axilla Multiple studies support the use of US to characterize findings in the axilla [36,37]. The most common etiology, besides normal tissue, is adenopathy from benign or malignant disease, typically of lymphatic or mammary origin. In addition, accessory breast tissue and both benign and cancerous lesions within accessory tissue can be seen [36]. If a suspicious US finding or mass is identified, US-guided biopsy can be performed for definitive diagnosis, even if the malignancy rate may be low in a woman with palpable axillary mass and no other signs of malignancy [37].


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis There is no relevant literature to support the use of CT with or without intravenous (IV) contrast as an initial imaging test for palpable axillary mass. If systemic disease or nonmammary malignancy, such as lymphoma, is in the differential diagnosis, CT chest may be helpful to determine other areas of lymphadenopathy, as well as to assess for local bony, chest wall, or intrathoracic involvement.


Imaging of the Axilla

Imaging of the Axilla. Digital Breast Tomosynthesis Diagnostic There is insufficient data to support the use of DBT as the initial imaging test for evaluating bilateral palpable axillary masses even though a portion of the axillary region can be visualized on DBT. DBT can provide global assessment of the breasts as well as assess for microcalcifications associated with the axillary mass(es). NCCN guidelines suggest that a diagnostic mammogram and/or DBT may complement axillary US by evaluating the breast for underlying lesions in the setting of patients presenting with axillary lymphadenopathy [7,21,32].


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT as the initial imaging test for bilateral axillary adenopathy even though FDG-PET/CT can detect the axillary lymphadenopathy as well as other lymphadenopathy in the neck, chest, abdomen, and pelvis. In one series of breast cancer patients, FDG-PET/CT was significantly more accurate than US (75% versus 62%) for the detection of axillary lymph node metastases, but there was no difference in sensitivity (54% versus 38%) [38]. Incidental axillary FDG uptake on PET/CT may require further evaluation with mammography, DBT, and US, followed by possible image-guided biopsy.


Imaging of the Axilla

Imaging of the Axilla. MRI Breast MRI of the breast is not routinely performed as the initial imaging assessment for bilateral palpable axillary masses. If digital mammography or DBT is negative for a primary breast malignancy in a patient with suspicious axillary lymphadenopathy, MRI can often identify the breast primary [34,35]. In a meta-analysis of 9 retrospective studies, MRI detected an occult breast cancer in more than two-thirds of patients [39]. MRI can also help further characterize the axillary mass(es) by determining involvement of adjacent vessels, the chest wall, and other axillary structures.


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi MBI as the initial imaging of patients presenting with bilateral palpable axillary masses.


Imaging of the Axilla

Imaging of the Axilla. Variant 3: Female. Newly diagnosed breast cancer, 2 cm or less, with clinical node-negative. Initial imaging of the axilla following diagnostic mammography or DBT. Regional nodal staging is an important prognostic factor in guiding the treatment of breast cancer, which has undergone significant change over the last decade [42,43]. Historically, ALND was the standard of care for staging the nodal region and providing local control of breast cancer that has metastasized to regional nodes. The result of the Z0011 trial changed the approach to axillary disease management [5]. The Z0011 trial recruited 891 women with T1 or T2 invasive primary breast cancer and no palpable axillary adenopathy [5]. These women were randomized to SLNB versus ALND. The 10-year overall survival for Z0011 patients treated with SLNB alone was noninferior to those treated with ALND [4]. Therefore, SLNB became a safe alternative to ALND for clinically node-negative breast cancer patients, with a less invasive approach and less morbidity. In 2014, the American Society of Breast Surgeons published consensus guideline on the management of the axilla in which SLNB has replaced ALND for clinically node-negative invasive breast cancer patients [6]. It is desirable to identify those patients who can safely receive SLNB and those who we can potentially omit SLNB. However, there is no standard radiologic imaging test for this purpose and this remains an area of controversy.


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis Studies have shown that the use of advanced imaging modalities such as CT and FDG-PET/CT for staging asymptomatic women with early stage breast cancer has low yield for occult disease [44-46]. The 2020 NCCN Guidelines for Invasive Breast Cancer also suggest the use of CT with IV contrast only when there is elevated liver function tests, pulmonary or abdominal symptoms, or abnormal physical examination [7]. CT chest can visualize and assess the level I, II, and III regions of the axilla. The predictive accuracy of CT is not high enough to replace


Imaging of the Axilla

Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature to support the use of Tc-99m sestamibi MBI for staging of the axilla in breast cancer patients.


Imaging of the Axilla

Imaging of the Axilla. US Axilla Axillary US is often performed in early-stage breast cancer patients since the Z0011 trial showed that early-stage cancer and low nodal burden minimizes surgical morbidity because patients can undergo SLNB rather than ALND without compromising survival [5].


Imaging of the Axilla

Imaging of the Axilla. The other point of view supporting preoperative axillary US argues that the finding of an abnormal axillary node on axillary US followed by percutaneous biopsy confirmation would help to identify those patients with higher tumor burden [54,55], who would benefit from proceeding directly to ALND. This approach avoids the need for a


Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla second surgery. One study supporting the utilization of preoperative axillary US from a single center reported that only 3% to 5% of patients had an abnormal axillary US yet met the Z0011 criteria (ie, ALND was not necessary in these patients with preoperative abnormal axillary US). Other studies also supporting the use of preoperative axillary US even in patients who meet Z0011 criteria argue that axillary US can help identify patients with unsuspected extensive nodal disease, thereby removing them from consideration for unindicated SLNB [56-58]. Patients with negative preoperative axillary US and SLNB had fewer positive nodes, smaller nodal metastases, and lower extranodal extension on final pathology [58].


Imaging of the Axilla

Imaging of the Axilla. US-guided biopsy of any suspicious axillary node either via fine-needle aspiration (FNA) or core biopsy is commonly performed when preoperative axillary US is done. The sensitivity of US-guided biopsy is variable with a wide range of 52% to 90%, whereas the specificity is higher, ranging from 98% to 100% [59-63].


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis Even in women with clinical node-positive disease, contrast-enhanced CT is not routinely performed and is not a part of the initial staging assessment if the patient does not have any signs or symptoms of disease outside the breast. When adenopathy is seen on CT, the Hounsfield unit of the metastatic lymph node is likely higher than nonmetastatic nodes.


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is a valuable modality with potential to impact clinical management of patients with newly diagnosed locally advanced disease, monitoring treatment response in patients with known metastatic breast cancer, and for detection of recurrent disease. FDG-PET/CT is not suggested for routine systemic staging in T0 to T3, N0 to 1, M0 breast cancer patients without signs or symptoms of metastatic disease. A meta-analysis of 25 studies demonstrates the inferiority of FDG-PET/CT to SLNB for evaluation of the axilla [49].


Imaging of the Axilla

Imaging of the Axilla. MRI Breast Dynamic contrast-enhanced MRI is useful for staging prior to systemic therapy and for restaging of the axilla after systemic therapy if the preoperative axillary staging was positive [7,48]. However, most of the data focuses on the tumor within the breast and not the axillary nodes. Current standard MRI of the breast has some technical challenges that do not allow simultaneous optimal imaging of both the breast and axilla, with approximately 30% of the MRI examination excluding the axilla because of technical challenges or incomplete axillary visualization in a retrospective study of 803 newly diagnosed breast cancer patients [79]. When comparing contrast-enhanced breast MRI with noncontrast breast MRI, contrast-enhanced breast MRI is more accurate than noncontrast MRI, based on


Imaging of the Axilla

Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. a summary of 6 studies evaluating the accuracy of MRI in detecting pathologically proven positive axillary nodes [52]. In a meta-analysis of 21 eligible studies evaluating the efficacy of MRI versus FDG-PET/CT, the pooled sensitivity of MRI was significantly better (82% versus 64%, respectively), and the pooled specificity of MRI was similar (93%) [69]. A negative MRI does not exclude metastatic nodal disease on final histopathology, but a positive MRI finding suggests high tumor burden (>3 abnormal nodes) [15,69,79]. Based on the review of the literature, there was disagreement for the role of breast MRI in this clinical scenario.


Imaging of the Axilla

Imaging of the Axilla. Diffusion-weighted imaging (DWI) is a noninvasive imaging technique that does not require contrast injection, measuring the mobility of water molecules and may complement contrast-enhanced MRI. In a meta-analysis of 13 studies from a literature search of 159 articles, the apparent diffusion coefficient value of metastatic nodes are lower than nonmetastatic nodes with pooled sensitivity of 86% and specificity of 86% using a b-value of 800 [80].


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the routine use of Tc-99m sestamibi MBI for staging of the axilla in breast cancer patients.


Imaging of the Axilla

Imaging of the Axilla. US Axilla US is the most established noninvasive imaging test for assessing the axilla. Benign lymph nodes can often be differentiated from malignant nodes based on size, morphology, and vascularity, although there is a wide range of reported sensitivity and specificity for axillary US. The reported sensitivity can range from 26.4% to 94% and specificity from 53% to 98% [58,81,82]. Axillary US alone has a relatively low NPV and sensitivity to be useful as a predictor of axillary nodal burden [83,84]. When combined with needle biopsy, however, the sensitivity improves from 61% to 79% in a meta-analysis of 21 studies [54,62,85]. US-guided core needle biopsy was superior to US- guided FNA in a meta-analysis of 1,353 patients with newly diagnosed invasive breast carcinoma, with a reported sensitivity of 88% for core biopsy and 74% for FNA [86].


Imaging of the Axilla

Imaging of the Axilla. US features associated with a higher likelihood of malignancy include short-axis lymph node size >1 cm, cortical thickness of >0.3cm, and absence of a fatty hilum [87-90]. However, these imaging features are not specific enough to avoid the need for histologic sampling.


Imaging of the Axilla

Imaging of the Axilla. Since the Z0011 trial, there continues to be variability in incorporating axillary US into practice. Those in favor of performing axillary US routinely argue that >3 abnormal nodes or a positive axillary lymph node on needle biopsy warrant ALND rather than SLNB because these patients tend to have a high nodal tumor burden [58,91]. Those not in favor of performing axillary US recommend proceeding with SLNB, even if the preoperative US identify malignant-appearing lymph node(s) because the specificity of US is relatively low.


Imaging of the Axilla

Imaging of the Axilla. Variant 5: Female. Newly diagnosed breast cancer, greater than 2 cm, with clinical node-negative. Initial imaging of the axilla following diagnostic mammography or DBT. Lymph node staging is crucial in the management of breast cancer, and several multicenter trials have impacted the approach to axillary lymph node treatment in breast cancer patients. For patients with clinically node-negative disease, SLNB is an oncologically safe approach with less morbidity than ALND. The prospective IBCSG 23-01 trial of 934 patients randomized to completion of ALND (n = 465) or no ALND (n = 469), with median follow-up of 9.7 years, revealed that omitting ALND was safe, even if the sentinel nodes contained micrometastases [64]. The NSABP B-32 trial of 5,611 women randomized to SLNB alone versus axillary lymph node biopsy and ALND with follow-up of 8 years reported no statistical differences in overall survival, disease-free survival, and regional control with less postoperative morbidity in the SLNB alone group [2,3]. The Z0011 trial recruited 891 women with T1 or T2 invasive primary breast cancer and no palpable axillary adenopathy [5]. These women were randomized to SLNB versus ALND. The 10-year overall survival for patients treated with SLNB alone was noninferior to those treated with ALND. The Z0011 trial, with median follow-up of 9.3 years, also demonstrated no differences in survival between those who received ALND versus no ALND [5]. The After Mapping of the Axilla: Radiotherapy Or Surgery trial from the European Organization for Research and Treatment of Cancer with median follow-up of 10 years also showed no significant differences at 10 years for axillary recurrence or overall survival between the 2 groups [66].


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis Contrast-enhanced and noncontrast-enhanced CT studies are not typically performed for early-stage breast cancer in asymptomatic patients because asymptomatic distant disease is rare. Contrast-enhanced CT can be used if the primary breast cancer is >2 cm, there is clinical node-positive disease, the tumor demonstrates biologically


Imaging of the Axilla

Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. aggressive features on histopathology, or patients present with clinical symptoms such as elevated liver function tests [7,92]. However, findings on CT do not influence the approach for axillary surgery, reduce the number of axillary surgeries, or reduce the reoperation rate [14,47].


Imaging of the Axilla

Imaging of the Axilla. MRI Breast Dynamic contrast-enhanced MRI is not routinely performed [7,92] for staging prior to systemic therapy and for restaging of the axilla after systemic therapy if preoperative axillary staging was negative [7,48]. Current breast MRI protocols do not adequately image the breast and entire axilla in up to 30% of cases based on a retrospective study of 803 newly diagnosed breast cancer patients [79]. However, contrast-enhanced breast MRI is more accurate than noncontrast imaging with a FNR of 12% to 19% and NPV of 97% to 99% based on 6 studies designed to evaluate the accuracy of MRI in patients with histologically positive nodes [52]. In a meta-analysis of 21 eligible studies evaluating the efficacy of MRI versus FDG-PET/CT, the pooled sensitivity of MRI was significantly better (82% versus 64%, respectively), and the pooled specificity was similar (93%) [69]. A negative MRI does not exclude metastatic nodal disease on final histopathology, but a positive MRI finding suggests high tumor burden (>3 abnormal nodes) [15,69,79].


Imaging of the Axilla

Imaging of the Axilla. DWI is a noninvasive imaging technique that does not require contrast injection, measures the mobility of water molecules, and may complement contrast-enhanced MRI. In a meta-analysis of 13 studies from a literature search of 159 articles, the apparent diffusion coefficient value of metastatic nodes is lower than nonmetastatic nodes with pooled sensitivity of 86% and specificity of 86% using a b-value of 800 [80].


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the routine use of sestamibi MBI for staging of the axilla in breast cancer patients.


Imaging of the Axilla

Imaging of the Axilla. The other point of view supporting preoperative axillary US argues that the finding of an abnormal axillary node on axillary US followed by percutaneous biopsy confirmation would help to identify those patients with higher tumor burden [54,55], and these patients would benefit from proceeding directly to ALND. This approach avoids the need for a second surgery. One study, supporting the utilization of preoperative axillary US from a single center, reported that only 3% to 5% of patients had an abnormal axillary US and met the Z0011 criteria (ie, ALND was not necessary in these patients with preoperative abnormal axillary US). Other studies also supporting the addition of preoperative axillary US to the management of patients who met Z0011 criteria argue that axillary US can help identify patients with more extensive nodal disease who meet the Z0011 criteria [56-58]. Patients with negative preoperative axillary US and SLN had fewer positive nodes, smaller nodal metastases, and lower extranodal extension on final pathology [58].


Imaging of the Axilla

Imaging of the Axilla. US-guided biopsy of any suspicious axillary node either via FNA or core biopsy is commonly performed when preoperative axillary US is done. The sensitivity of US-guided biopsy is variable with a wide range of 52% to 90%, whereas the specificity is higher, ranging from 98% to 100% [59-63].


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis Contrast-enhanced CT is not routinely used to stage the axilla, even in patients with clinically positive axillary findings. While CT chest can visualize and assess the level I, II, and III regions of the axilla, the predictive accuracy of CT is not high enough to replace SLNB [50,51,95]. When adenopathy is seen on CT, the Hounsfield unit of the metastatic lymph node is likely higher than nonmetastatic nodes. Contrast-enhanced CT may be used if the primary breast cancer is >2 cm, there is clinical node-positive disease, the tumor demonstrates biologically aggressive features on histopathology, or patients present with clinical symptoms such as elevated liver function tests [7,92]. However, findings on CT do not influence the approach for axillary surgery, reduce the number of axillary surgeries, or reduce the reoperation rate [14,47]. For locally advanced breast cancer (>5 cm in size, involving skin or underlying chest wall) and local recurrence, CT may be helpful [7]. For inflammatory breast cancer, the incidence of nodal metastases at presentation is high, up to 79.8% in a SEER registry of 761 patients and 5-year survival is worse for lymph node-positive patients (49%) than node-negative patients (66%) [98]. If there is clinical suspicion of inflammatory breast cancer, contrast-enhanced CT may be helpful for staging [7].


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT may be useful in the staging of newly diagnosed advanced breast cancer given a higher likelihood of extra-axillary metastatic disease or distant disease [94,95]. It has been proposed that if a primary breast tumor is >2 cm and has a high SUVmax, there is a higher probability of axillary nodal metastases [73,99]. In addition to assisting in the staging of advanced breast cancer, FDG-PET/CT may be beneficial in staging patients with T1 stage breast cancer, particularly those with triple negative or human epidermal growth factor receptor 2 (HER2) positive breast cancer with clinical node positive disease because there is a higher prevalence of nodal disease and distant metastases [71]. In order to assess response to neoadjuvant therapy, comparing pretreatment nodal FDG uptake to subsequent midtreatment or post-treatment FDG uptake is essential and also can be used to identify those at a higher risk of recurrence [100-102].


Imaging of the Axilla

Imaging of the Axilla. MRI Breast Dynamic contrast-enhanced MRI may be useful for staging prior to systemic therapy and for restaging of the axilla after systemic therapy if the preoperative axillary staging was positive [7,48]. However, most of the data focuses on the tumor within the breast and not of the axillary nodes. Current breast MRI protocols do not adequately image the entire axilla (level I, II, III) in up to 30% of cases based on a retrospective study of 803 newly diagnosed breast cancer patients [79]. However, contrast-enhanced breast MRI is more accurate than noncontrast imaging with a FNR of 12% to 19% and NPV of 97% to 99% based on 6 studies designed to evaluate the accuracy of MRI in patients with histologically positive nodes [52]. In a meta-analysis of 21 eligible studies evaluating the efficacy of MRI versus FDG-PET/CT, the pooled sensitivity of MRI was significantly better (82% versus 64%, respectively), and the pooled specificity of MRI was similar (93%) [69]. A negative MRI does not exclude metastatic nodal disease on final histopathology, but a positive MRI finding suggests high tumor burden (>3 abnormal nodes) [15,69,79].


Imaging of the Axilla

Imaging of the Axilla. DWI is a noninvasive imaging technique that does not require contrast injection, measures the mobility of water molecules, and may complement contrast-enhanced MRI. In a meta-analysis of 13 studies from a literature search of 159 articles, apparent diffusion coefficient value of metastatic nodes are lower than nonmetastatic nodes with


Imaging of the Axilla

Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. pooled sensitivity of 86% and specificity of 86% using a b-value of 800 [80]. There is insufficient data to support the use of DWI for detecting metastatic disease in axillary nodes at this time.


Imaging of the Axilla

Imaging of the Axilla. In summary, although current breast MRI protocols do not consistently image the entire axilla in patients with newly diagnosed breast cancer over 2 cm in size and clinical node-positive, breast MRI can be beneficial for evaluation of tumor within the breast and may be helpful for the axilla in some circumstances.


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for staging of the axilla in clinically node-positive breast cancer patients.


Imaging of the Axilla

Imaging of the Axilla. US Axilla Axillary US is typically performed for assessing nodal disease in patients with newly diagnosed breast carcinoma and palpable adenopathy [7,92]. In a retrospective series of 1,287 breast cancer patients who had preoperative axillary US-FNA followed by SLNB or ALND, the group with axillary US-FNA had a higher number of metastatic axillary lymph nodes than those with micro- or macrometastatic nodal disease on SLNB. This suggests that patients with US visible nodal disease, confirmed by axillary US-FNA, have more extensive nodal involvement [60]. Positive axillary US, confirmed with biopsy, helps to identify patients with higher tumor burden [54,55], and as such, these patients can proceed directly to ALND. However, axillary US is not able to detect all metastatic nodes and therefore cannot replace SLNB or ALND [58]. It is well known that negative axillary US with or without biopsy does not rule out nodal disease [58]. The sensitivity of US-guided biopsy also has variable sensitivity ranging from 52% to 90%, whereas the specificity is higher, ranging from 98% to 100% [59-63]. For many cases, axillary US can differentiate patients with high lymph node tumor burden from patients with low lymph node tumor burden, suggesting that those with positive axillary nodes on percutaneous biopsy should have ALND rather than SLNB, especially because the Z0011 criteria do not apply to patients with clinically palpable adenopathy. Axillary US features favoring nodal metastases include cortical thickness of >0.3 cm and absence of a fatty hilum, a finding with a high positive predictive value (PPV) of 90% to 93% [103-105].


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis CT allows assessment of the axillary level II and III nodal regions that are not always well visualized on US. However, there are no data to support the routine use of CT for assessing a new palpable axillary lump in breast cancer patients at midtreatment of NAC and very limited data on the use of CT for assessing nodal response. One retrospective study reviewed the pretreatment breast MRI, FDG-PET/CT, and CT imaging on 348 breast cancer patients who received NAC followed by surgery and reported that patients with higher radiological nodal stage on imaging were more likely to have node-positivity upon surgery, larger nodal metastases, and more frequent extranodal extension [108].


Imaging of the Axilla

Imaging of the Axilla. Digital Breast Tomosynthesis Diagnostic DBT allows visualization of axillary level I nodal regions but does not fully assess the axilla. Although not typically used for axillary evaluation, DBT may be helpful in evaluating for progression of the primary breast malignancy.


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT for assessing a new palpable axillary mass during midtreatment of NAC.


Imaging of the Axilla

Imaging of the Axilla. Mammography Diagnostic Similar to DBT, mammography does not visualize the entire axilla and is not useful for assessing an axillary lump. Mammography may be performed to determine if there is also progression of the primary breast carcinoma.


Imaging of the Axilla

Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. MRI Breast There is no evidence to support the use of breast MRI as the initial imaging test for assessing a new palpable axillary lump during NAC treatment. However, breast MRI may be helpful in assessing response of the primary breast tumor and associated axillary adenopathy.


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for assessing a new palpable axillary lump during midtreatment of NAC.


Imaging of the Axilla

Imaging of the Axilla. US Axilla Despite the limited literature addressing the use of axillary US for assessing a new palpable axillary lump during midtreatment, axillary US may be useful in this scenario because of its noninvasive nature. If the axillary US finding is uncertain, biopsy can be performed [86]. A small single-center study looking at the role of midtreatment axillary US in 159 patients of mixed breast cancer subtypes observed that US performed better for residual axillary nodal tumor burden than for residual index breast cancer and provided more consistent results across different cancer subtypes [109].


Imaging of the Axilla

Imaging of the Axilla. Variant 8: Female. Breast cancer, greater than 2 cm in size, clinical node-negative. Imaging of the axilla after completion of neoadjuvant chemotherapy. NAC is used to treat operable large tumors, nonoperable locally advanced tumors, and inflammatory breast cancers prior to definitive surgical management. If there is pathological response to NAC and the patient is clinically node- negative, SLNB is preferred over ALND in order to minimize morbidity. In a study of 925 patients treated with NAC, 5-year overall survival was superior for patients with pathologic complete remission of cytological proven axillary lymph node metastases (93%) compared with those without complete response (72%) [110].


Imaging of the Axilla

Imaging of the Axilla. The prognostic significance of response to NAC can vary between the primary breast tumor and the axilla and based on tumor receptor subtypes (eg, triple negative versus HER2 positive cancers) [112]. Those patients with initial node-positive breast cancer who achieve complete pathological response after NAC have similar prognoses as to those with clinical node-negativity [112]. Even though no imaging will replace SLNB or ALND for staging, the ability to assess response during or after NAC helps to predict outcomes and aids with treatment planning.


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis There is no relevant literature to support the use of contrast-enhanced or noncontrast-enhanced CT to image the axilla after completion of NAC.


Imaging of the Axilla

Imaging of the Axilla. Digital Breast Tomosynthesis Diagnostic There are no data to support the use of DBT to image the axilla after completion of NAC in patients with initial clinical node-negative disease and no new clinical concern or palpable axillary lump. For assessment of the primary breast tumor, one prospective study of 51 stage II and III breast cancer patients reported that MRI and DBT outperformed mammography and whole-breast US in the prediction of pathologic complete response [113]. However, this study cannot be extrapolated to axillary nodal disease.


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh There are limited data to support the use of FDG-PET/CT for assessing response of nodal disease from breast cancer following completion of NAC. Most studies report changes in size and SUV measurements of the index breast carcinoma or distant metastases. Four meta-analyses of FDG-PET/CT in detecting residual breast disease reported a pooled sensitivity of 81% to 84% and a specificity of 66% to 79% [114-118]. FDG-PET/CT is limited by the lack of consensus for standard criteria to measure response of the index tumor or nodal disease, and SUV measurements underestimating the amount of residual disease when the residual tumor size is small. In one meta-analysis, 4 of 19 studies reported a pooled sensitivity of 92% and an NPV of 88% in predicting regional lymph node response but the specificity was inconclusive [118]. Even though there is suggestion that the early changes in SUV may correlate


Imaging of the Axilla

Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. with NAC response, a negative FDG-PET/CT does not guarantee that the final pathology is also negative, especially if the residual tumor is of low to moderate grade [119,120]. A recent report from the National Cancer Database of 33,162 patients concluded that a breast-only response from a node-only response or both breast and nodal response had different prognoses, which also varied with tumor subtypes [112]. Given the limited data, FDG-PET/CT is not currently performed post-NAC to restage the axilla.


Imaging of the Axilla

Imaging of the Axilla. Mammography Diagnostic Mammography can reliably be used to assess response of a primary breast malignancy to NAC. However, it is less useful in assessing axillary nodal response to therapy given that the axilla is incompletely visualized.


Imaging of the Axilla

Imaging of the Axilla. MRI Breast The role of breast MRI in detecting residual tumor within the axillary lymph nodes remains questionable [121]. Based on a 26-study meta-analysis, MRI has moderate sensitivity (77%) and specificity (90%) for detecting residual disease after NAC [122,123]. Most of the literature confirms the superiority of MRI in detecting residual tumor within the breast after NAC compared with mammography, US, and physical examination [124]. However, it is not proven that preoperative MRI is associated with improved surgical outcomes or lower recurrence rates [125]. A meta-analysis of 44 studies reported MRI sensitivity for detecting residual disease in the breast was 92% and a specificity of 90% [124]. MRI also demonstrates higher accuracy in triple negative tumors and HER2-positive tumors [126-128]. The performance of MRI for the primary breast lesion cannot be extrapolated into MRI performance of the axillary nodal disease [112]. Therefore, MRI is not used routinely for predicting response of axillary nodal disease.


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for assessing response after treatment with NAC.


Imaging of the Axilla

Imaging of the Axilla. US Axilla The role of axillary US to assess the axilla after NAC remains controversial [7]. Most of the data from multicenter trials involve patients with initial clinical node-positive disease [129,130]. These studies, evaluating SLNB after NAC, report that the accuracy rates of SLNB are acceptable. With the variable sensitivity and specificity of axillary US, even in combination with percutaneous biopsy, axillary US is not able to replace SLNB. Therefore, axillary US may not assess axillary response after chemotherapy.


Imaging of the Axilla

Imaging of the Axilla. Variant 9: Female. Breast cancer, greater than 2 cm in size, clinical node-positive. Imaging of the axilla after completion of neoadjuvant chemotherapy and prior to surgery. NAC is used to treat operable large tumors, nonoperable locally advanced tumors, and inflammatory breast cancers prior to definitive surgical management. Information on the residual disease or positive axillary nodes after NAC is beneficial for the determination of the axillary surgical management and for the need of radiation therapy [7]. The guidelines define low tumor burden in the axilla as nodal disease that is image-detected disease not apparent on clinical examination; however, the imaging test is not specified in the guidelines. If there is pathological response to NAC and the patient is clinically node-negative, SLNB is preferred over ALND in order to minimize morbidity. In a study of 925 patients treated with NAC, 5-year overall survival was superior for patients with pathologic complete remission of the cytological proven axillary lymph node metastases (93%) compared with those without complete response (72%) [110].


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis There are no relevant data to support the use of contrast-enhanced or noncontrast-enhanced CT to image the axilla after completion of NAC.


Imaging of the Axilla

Imaging of the Axilla. Digital Breast Tomosynthesis Diagnostic There are no data to support the use of DBT to image the axilla after completion of NAC in patients with initial clinical node-positive disease pre-NAC and who have no clinical suspicion of disease progression or new axillary nodal disease. When comparing mammography to DBT, one prospective study of 51 stage II and III breast cancer patients reported that MRI and DBT outperformed mammography and whole-breast US in the prediction of pathologic complete response [113]. Unfortunately, this cannot be extrapolated to axillary nodal disease because DBT does not completely visualize the entire axilla. DBT may be useful in selected cases after NAC because it may identify response within a clipped node and provide a means for image guided localization [131].


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT is widely used to assess response to therapy, despite the lack of consensus on the criteria for determining response. The reported pooled sensitivity for FDG-PET/CT is 71% to 88% and specificity is 69% to 79.3% [117,120,132,133]. Most of the studies do not specifically report on response of the regional lymph nodes. In one meta-analysis of four studies involving 920 patients, the sensitivity of FDG-PET/CT for regional lymph node response assessment is 92% [118]. In another meta-analysis of 987 abstracts, only four were eligible for analysis, yielding a PPV between 40% and 100% [134].


Imaging of the Axilla

Imaging of the Axilla. The timing of FDG-PET/CT is critical and varies between studies, with some investigators demonstrating FDG- PET/CT has more accuracy during NAC (after first or second cycles of chemotherapy) than after NAC, whereas MRI performed better at the end of NAC [118,133]. MRI had higher sensitivity in predicting the pathologic response after NAC in 13 studies involving 575 patients, and FDG-PET/CT had a higher specificity in these same 13 studies involving 618 patients [132]. Currently, there is lack of consensus that early response detected by imaging tests translates into improved overall outcomes. A negative FDG-PET/CT during or after NAC does not necessarily correlate with final pathological node-negative disease, as demonstrated in one series of 206 patients [119].


Imaging of the Axilla

Imaging of the Axilla. SUV values may underestimate or overestimate response when the residual tumor is small. Some investigators have reported SUVmax <2.5 as negative [120], whereas others demonstrated that the change in SUV before and after NAC or change between the pre-NAC FDG-PET/CT examination and the examination performed after the first or second cycle of NAC were better predictors of response [134-136]. Despite the research, there is no accurate noninvasive test to replace SLNB or ALND at this time. However, one benefit of using FDG-PET/CT is that this examination can also evaluate other sites of metastases in a single study [102]. A search for a noninvasive restaging technique for identifying patients with axillary complete response is ongoing.


Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. MRI Breast In patients who have had axillary nodal metastatic disease diagnosed prior to NAC for breast cancer, there is little consensus on how to image the axilla subsequently. MRI has some limitations in evaluating the axilla and is unlikely to be the sole imaging test for estimating residual tumor burden preoperatively [121]. However, a combination of tests with axillary US, MRI, or FDG-PET/CT may be the future direction for clinical trials trying to answer such questions (https://clinicaltrials.gov/ct2/show/NCT03188393). At least one study suggests that measurements at 360 seconds after contrast administration provides the most accurate measurements of size, compared with the earlier phase or the later phase of the dynamic series [137].


Imaging of the Axilla

Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. Most of the literature focuses on the evaluation of response of the primary breast tumor after NAC and MRI superiority to mammogram, US, and physical examination in this setting [124].


Imaging of the Axilla

Imaging of the Axilla. The performance of MRI for the primary breast lesion cannot be extrapolated to MRI performance of the axillary nodal disease [112]. Therefore, MRI is not used routinely for predicting response of axillary nodal disease.


Imaging of the Axilla

Imaging of the Axilla. US Axilla Because of its noninvasive nature, axillary US may evaluate for residual axillary nodal disease despite its PPV of 60% to 81%, NPV of 43% to 74%, and specificity of 37% to 92% [138]. However, the sensitivity of US (71%) for prediction of residual nodal metastatic disease was higher than that of clinical examination and MRI/PET in most studies [139]. Limited data have suggested that the sensitivity of axillary US is higher for some subtypes such as triple negative breast cancer (69%) and HER2 positive breast cancer (71%) [140,141].


Imaging of the Axilla

Imaging of the Axilla. This discussion is based on the understanding that patients post-BCS or postmastectomy with reconstruction have likely already undergone a diagnostic mammogram or DBT to evaluate for or rule out in-breast recurrent disease. Therefore, the possible next imaging test or initial imaging test for the axilla are discussed below for each modality.


Imaging of the Axilla

Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. CT Chest, Abdomen, and Pelvis There are no data to support the utilization of CT for axillary node assessment in the setting of newly diagnosed in- breast recurrent disease or as the initial imaging test for the axilla. However, CT can be performed concurrently at the time of the locally recurrent breast cancer diagnosis to rule out distant metastatic disease and for pretreatment planning. CT allows visualization of any chest wall involvement as well as the relationship of the recurrent disease to regional vital structures such as axillary artery and vein [7,92,154].


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT may be ordered concurrently at the time of the locally recurrent breast cancer diagnosis to rule out distant metastatic disease and for pretreatment planning. PET/CT is helpful in identifying unsuspected regional nodal disease or distant metastases in certain situations such as in patients with locally advanced breast cancer and inflammatory breast cancer [7]. In a meta-analysis of 26 studies involving 1,752 patients with suspected recurrent breast cancer, the pooled sensitivity for FDG-PET/CT was 90% and specificity was 81%; FDG-PET/CT is more accurate than PET alone [155]. The authors noted that the studies were heterogeneous, and therefore the analysis had limitations. In-breast recurrent disease versus chest wall or nodal recurrent disease was not specified [155].


Imaging of the Axilla

Imaging of the Axilla. MRI Breast Breast MRI is a highly sensitive imaging modality for assessing disease within the breast [156,157]. There are no data to support breast MRI as the initial imaging test of the axilla in patients with newly diagnosed locally recurrent breast cancer to evaluate for additional nodal disease. The MRI may be ordered after the mammogram or DBT to evaluate additional recurrent disease or disease extent within the breast not completely seen on mammogram or DBT [158]. An observational cohort study of 13,266 women and a single-center study of 1,521 women reported higher cancer detection rate with MRI compared with mammography [156,157].


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for imaging the axilla in patients with newly diagnosed recurrent disease.


Imaging of the Axilla

Imaging of the Axilla. US Axilla US can be used to evaluate the axilla in patients with newly diagnosed recurrent breast cancer after BCS, after mastectomy, or with suspicion of recurrent nodal disease in the axilla. Diagnostic mammogram and/or DBT to evaluate for in-breast recurrent disease has also been shown to be helpful [154]. Axillary US can also provide guidance for percutaneous biopsy of any suspicious nodes because it influences potential surgical approach (SLNB versus full ALND).


Imaging of the Axilla

Imaging of the Axilla. Variant 11: Female. Suspicious axillary node on mammography or ultrasound. Next imaging study. CT Chest, Abdomen, and Pelvis CT is not frequently used to assess abnormal axillary nodes detected on US or mammography; however, it is often used to evaluate a biopsy-proven nonbreast malignant axillary node. One study with 297 patients from two centers found no change in the number of second axillary surgeries between patients who received a CT scan of their axilla versus those who did not [47]. There are little data to support the use of contrast- or noncontrast-enhanced CT for this indication if there is no clinical suspicion of additional systemic disease.


Imaging of the Axilla

Imaging of the Axilla. FDG-PET/CT Skull Base to Mid-Thigh Less than 1% of breast cancers initially present as axillary adenopathy [32,33]. Historically, mammography, US, and breast MRI have helped to identify the primary malignancy in patients with pathologic axillary adenopathy from unknown primary. However, mammography and US have relatively low sensitivity for detecting the primary breast lesion [31,159]. The addition of breast MRI has improved sensitivity [160] because MRI is able to detect the primary breast lesion in 36% to 86% of cases [39]. Although PET/CT can be helpful in identifying the site of an unknown primary, for breast cancer, there are little data to support its routine use.


Imaging of the Axilla

Imaging of the Axilla. MRI Breast Once the suspicious axillary node has been documented as metastatic nodal disease, then breast MRI can detect a mammographic or sonographic occult breast lesion with high sensitivity for detecting an in-breast lesion or confirm no breast primary [34,35]. In a meta-analysis of 8 retrospective studies involving 220 patients, MRI detects an occult breast cancer in 72% of cases with a pooled sensitivity of 90% and a specificity of 31% [39]. MRI can also help further characterize the axillary mass by evaluating its relationship to adjacent vessels, the chest wall, and other axillary structures. In a meta-analysis of 26 studies looking at the diagnostic performance of MRI in detecting


Imaging of the Axilla

Imaging of the Axilla. metastatic nodal disease, the pooled sensitivity and specificity in patients with breast cancer is 77% and 90%, respectively [123].


Imaging of the Axilla

Imaging of the Axilla. Sestamibi MBI There is no relevant literature supporting the use of Tc-99m sestamibi MBI for imaging the axilla in patients with suspicious axillary nodes detected on mammography and US.


Imaging of the Axilla

Imaging of the Axilla. US-Guided Core Biopsy Axillary Node US-guided biopsy (either core needle biopsy or FNA) may provide a diagnosis for morphologically abnormal lymph nodes detected on imaging. In a meta-analysis of 1,353 patients from 6 studies, US-guided core needle biopsy was superior to US-guided FNA in diagnosing axillary nodal metastases with reported pooled sensitivity of 88% versus 74%, respectively. Both US-guided core needle biopsy and FNA had a high specificity of 100% [86]. Complications such as pain, hematoma, and bruising were higher with core needle biopsy than FNA.


Imaging of the Axilla

Imaging of the Axilla. US-Guided Fine Needle Aspiration Biopsy Axillary Node US-guided FNA biopsy is a reliable procedure associated with minimal complications. In a meta-analysis of 31 studies, US-guided FNA improved the median sensitivity of US from 61% to 79% and specificity from 82.0% to 100% [62]. In another publication of 3,781 breast cancer patients, the sensitivity and specificity of axillary US alone were 59% and 89%, respectively. The specificity improved to 100% when axillary US was combined with FNA. FNA resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52%, 100%, 100%, 74.8%, and 80%, respectively [63]. The decision to perform FNA or core biopsy of a suspicious axillary node is not standardized and depends on provider choice and patient factors.


Imaging of the Axilla

Imaging of the Axilla. Variant 12: Female. Suspicious axillary node on any other imaging modality (excluding mammography and ultrasound). Next imaging study. Digital Breast Tomosynthesis Diagnostic When a suspicious lymph node is identified on imaging, correlation with clinical history and physical examination is essential to guide management. If a breast primary is of concern, mammography and DBT can assist in identifying the breast primary. At least one study has shown that DBT is superior to full-field digital mammography for detection of subtle architectural distortion [161].


Imaging of the Axilla

Imaging of the Axilla. Mammography Diagnostic When a suspicious lymph node is identified on imaging, other than mammography or DBT, correlation with clinical history and physical examination is essential to guide further imaging. If a breast primary is of concern, mammography and/or DBT may assist in identifying a primary breast malignancy. Mammography is not optimal for evaluating the axilla. Valente et al [162] found that mammography has a high FNR in the detection of axillary metastatic lymphadenopathy.


Imaging of the Axilla

Imaging of the Axilla. US Axilla If mammogram or DBT identifies a primary breast malignancy, then axillary US after mammogram and/or DBT may evaluate the nodal size, nodal cortical, and hilar morphology. The sensitivity and specificity for axillary US for differentiating benign from malignant nodes is variable, with reported sensitivity ranging from 26% to 94% and specificity from 53% to 98% [58]. Axillary US alone has relatively low NPV and sensitivity and therefore is not a reliable predictor of axillary nodal burden [83,84]. When combined with needle biopsy, however, the sensitivity improves from 61% to 79% in a meta-analysis of 21 studies [54,62,85].


Imaging of the Axilla

Imaging of the Axilla. Some US features that are more likely to be associated with malignancy include short-axis diameter >1 cm, cortical thickness >0.3 cm, and absence of a fatty hilum [87-90]. The absence of a fatty hilum has the highest PPV (90% to 93%) for malignancy [103,104]. A suspicious node on US warrants percutaneous biopsy because a positive axillary US helps to identify those patients at risk for higher tumor burden [54,55]. However, a negative axillary US with or without biopsy does not rule out nodal disease [58].


Imaging of the Axilla

Imaging of the Axilla. US-Guided Core Biopsy Axillary Node Based on a meta-analysis of 1,353 patients with newly diagnosed breast cancer, US-guided core needle biopsy is superior to US-guided FNA with a reported sensitivity of 88% for core biopsy and 74% for FNA [86]. The overall sensitivity of US-guided biopsy ranges from 52% to 90%, whereas the specificity ranges from 98% to 100% [59- 63].


Imaging of the Axilla

Imaging of the Axilla

Imaging of the Axilla. Imaging of the Axilla


Imaging of the Axilla

Imaging of the Axilla. US-Guided Fine Needle Aspiration Biopsy Axillary Node US-guided FNA of an axillary node is a well-tolerated low-risk procedure that can accurately confirm metastatic disease in a suspicious lymph node. Although a recent meta-analysis of 1,353 patients showed that US-guided core needle biopsy is superior to US-guided FNA [86], FNA does have a role in diagnosing patients with suspicious lymphadenopathy, especially if a patient is unable to discontinue anticoagulants. On-site cytopathologist is not a common practice even though immediate pathology assessment for inadequate sampling is very beneficial because inadequate sampling rates can occur in 5% to 10% of cases [163-165].


Imaging of the Axilla

Imaging of the Axilla. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Imaging of the Axilla

Imaging of the Axilla. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Imaging of the Axilla

Imaging of the Axilla


Nonatherosclerotic Peripheral Arterial Disease. Introduction/Background Lower-extremity vascular diseases span a diverse range of etiologies and may be autoimmune, congenital, degenerative, inflammatory, infectious, metabolic, neoplastic, or traumatic in nature. Examples of such conditions include, but are not limited to, aneurysm formation, atherosclerosis, Buerger disease, cystic adventitial disease, dissection/transection, deep vein thrombosis, external iliac artery endofibrosis (EIAE), fibromuscular dysplasia (FMD), popliteal arterial entrapment syndrome (PAES), segmental arterial mediolysis (SAM), and genetic syndromes such as Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), and vascular Ehlers-Danlos syndrome (EDS). Because of the plethora of potential underlying disease processes, imaging is often employed to secure a diagnosis and assist in guiding clinical management. Accurate vascular imaging relies upon visualization of the vessel lumen, vessel wall, and surrounding soft-tissue structures, with some modalities also offering the ability to characterize blood flow direction and velocity. Furthermore, nonvascular findings are often paramount in supporting a suspected clinical syndrome [1-4] or guiding surgical management [5-8].


Nonatherosclerotic Peripheral Arterial Disease. Guidelines proposed in this document focus on nonatherosclerotic, arterial lower-extremity vascular disease. PAES is the most common cause of surgically correctable lower-extremity vascular insufficiency in young adults and consists of anatomic and functional subtypes. Patients with PAES present with calf claudication, paresthesia, and swelling during exercise. In anatomic PAES (Types I, II, III, and V), the extravascular structures within the popliteal fossa compress the popliteal artery and/or the popliteal vein, which results in compression and stenosis or occlusion during plantar flexion. Functional PAES (Type IV) results in compression of the popliteal artery despite the presence of an anatomically normal popliteal fossa; its etiology remains unclear. Either subtype may lead to aneurysm or pseudoaneurysm formation, thrombosis or distal thromboembolism [5-8,15-19].


Nonatherosclerotic Peripheral Arterial Disease. EIAE is a rare cause of performance-limiting claudication that occurs primarily in endurance athletes. Although EIAE typically occurs in cyclists, it has been described in other groups of elite endurance athletes. Symptoms include lower-extremity weakness, thigh pain, and symptom resolution after cessation of exercise [20]. Its etiology is poorly understood and may be multifactorial. Suggested mechanisms include repeated mechanical


Nonatherosclerotic Peripheral Arterial Disease. Reprint requests to: publications@acr.org


Nonatherosclerotic Peripheral Arterial Disease. Nonatherosclerotic Peripheral Arterial Disease trauma upon the external iliac artery by a hypertrophied psoas muscle during hip flexion with subsequent arterial kinking [21] and vasospasm [22]. Arterial-brachial pressure indexes typically decrease following exercise [20].


Nonatherosclerotic Peripheral Arterial Disease. Connective tissue diseases are multisystem disorders, several of which profoundly involve the vascular system. MS is an autosomal-dominant (AD) connective tissue disorder caused by a mutation in the FBN1 gene that codes for fibrillin-1 and occurs in 1 in 20,000 individuals. The systems typically affected by MS are cardiovascular, ocular, and skeletal. MS is classically associated with aortic root aneurysms and dissection; however, the dissection flap may extend into the iliac arteries resulting in pain, pallor, paresthesias, and pulselessness [1,24]. LDS results from an AD heterozygous mutation in either of the genes that encode transforming growth factor beta. LDS has a much more aggressive clinical course than MS, with a mean survival of 26 years. Like MS, LDS is associated with aortic root aneurysm and dissection [3]. Vascular EDS, formerly known as EDS type IV, is an AD disease caused by a heterozygous mutation in the COL3A1 gene that encodes type III collagen. Vascular EDS can affect any vessel and carries a poor prognosis that is due to risk of life-threatening arterial rupture [4].


Nonatherosclerotic Peripheral Arterial Disease. SAM is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects the visceral abdominal vessels, although involvement of the iliac arteries has been reported [27]. Lysis of the medial layer of the arterial wall in SAM results in dissection, stenosis, occlusion, or aneurysm formation; it commonly presents with catastrophic hemorrhages within the abdominal cavity or retroperitoneum as a result of spontaneous aneurysm rupture [28-30].


Nonatherosclerotic Peripheral Arterial Disease. Cystic adventitial disease is a rare vascular disease predominantly affecting healthy young men with no cardiovascular risk factors. Arterial involvement is more common than venous involvement, with most cases seen involving the popliteal artery. Cystic adventitial disease affecting the lower extremity typically results in claudication or pain of sudden onset, while imaging demonstrates adventitial cysts localized to the site of symptomatology. Surgical resection is usually curative thereby obviating follow-up [31].


Nonatherosclerotic Peripheral Arterial Disease. Injury to the lower-extremity vasculature is not an uncommon occurrence in the setting of penetrating or blunt trauma. Rapid diagnostic imaging is paramount to exclude or confirm vascular injury in these potentially unstable individuals.


Nonatherosclerotic Peripheral Arterial Disease. Discussion of Procedures by Variant Variant 1: Suspected popliteal entrapment syndrome. Initial imaging. CTA Lower Extremity CT angiography (CTA), including multiplanar reformation and 3-D volume-rendered reconstructions, is helpful in depicting popliteal vascular changes (vessel deviation, stenosis, occlusion, aneurysm formation) and abnormal musculotendinous structures in the setting of PAES [5,19]. Following revascularization for PAES, CTA is recommended to assess graft patency after an abnormal ultrasound (US) [17]. The use of dynamic CTA has also been proposed for the initial workup of PAES, as images of both lower extremities can be obtained at both rest and plantar flexion in a single examination requiring only one contrast bolus [15]. However, MRA and US duplex Doppler are typically preferred because they do not require ionizing radiation.


Nonatherosclerotic Peripheral Arterial Disease. MRA Lower Extremity MR angiography (MRA) can be used to evaluate vascular abnormalities and the dynamic changes in the popliteal artery during plantar flexion [16]. MRA is typically performed as a confirmatory test after US duplex Doppler. However, many patients are unable to maintain steady forced plantar flexion throughout the duration of lengthy MR sequences, resulting in excessive motion and degradation of image quality [7,8,15]. Despite this, a recent


Nonatherosclerotic Peripheral Arterial Disease. Nonatherosclerotic Peripheral Arterial Disease


Nonatherosclerotic Peripheral Arterial Disease. study demonstrated superiority of MRA over digital subtraction angiography (DSA) in confirming PAES [6]. MRA can be particularly helpful in defining abnormal musculotendinous structures. Furthermore, the T1- weighted and T2-weighted sequences done as part of the MRA study are currently the gold standard for defining the complete anatomy of the popliteal fossa and are therefore most appropriate for determining the anatomic abnormality in suspected PAES [7,15]. MRA without intravenous (IV) contrast is typically not used because the long acquisition times required cause challenges for their performance during stress maneuvers. However, the anatomic imaging used to determine the etiology of PAES can be done without IV contrast.


Nonatherosclerotic Peripheral Arterial Disease. Arteriography Lower Extremity Selective arteriography is regarded as the gold standard in identifying dynamic arterial deviation and/or occlusion during plantar flexion in addition to identifying vascular occlusion/stenosis, aneurysm, and thrombosis. [5,7,15]. In addition to being an invasive modality, arteriography is limited by its inability to depict extravascular anatomy. One study comparing the use of DSA and MRI in the evaluation of PAES found DSA to be nonspecific and unable to determine the etiology of patient symptoms [6], thereby obviating the need for cross-sectional imaging. Selective arteriography is therefore often used as a confirmatory modality when PAES is suspected on cross- sectional imaging or US [7,16].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity US duplex Doppler is heavily relied upon in the initial workup of PAES, where real-time visualization of flow occlusion and changes in segmental Doppler pressures upon provocative plantar flexion is crucial in confirming a suspected diagnosis [16,18]. This is extremely beneficial in the setting of functional PAES, where lack of an anatomic abnormality limits the sensitivity of cross-sectional modalities like CTA and MRA [18]. In PAES patients treated with popliteal bypass, US duplex Doppler is the first-line modality of choice in assessing graft patency; CTA, MRA, and selective arteriography are reserved for postoperative patients with abnormal US duplex Doppler examinations [17].


Nonatherosclerotic Peripheral Arterial Disease. Several studies have found the use of US in the diagnosis of PAES to be potentially problematic, as the necessary use of transducer pressure applied during the examination may result in velocity changes that are difficult to interpret [7]. Provocative maneuvers may also shift the popliteal artery out of the Doppler region of interest, giving the artifactual appearance of occlusion [7,8]. US duplex Doppler has been found to have a particularly high false-positive rate in the workup of PAES, especially in athletes [5]. MRA is recommended to confirm the etiology of PAES in patients with a positive US duplex Doppler study and in patients with a negative US duplex Doppler study with a high index of clinical suspicion.


Nonatherosclerotic Peripheral Arterial Disease. US Intravascular Lower Extremity The use of intravascular US (IVUS) has been reportedly beneficial in confirming and assessing extent of popliteal artery compression in PAES. IVUS is often used as a confirmatory modality when PAES is suspected on cross- sectional imaging. One study lauded IVUS for its ability to evaluate the arterial lumen for intimal change and potential irreparable mural damage that may be missed with conventional US [16]. In functional PAES, IVUS is beneficial in determining the magnitude of extrinsic muscular compression [16].


Nonatherosclerotic Peripheral Arterial Disease. Variant 2: Suspected external iliac artery endofibrosis. Initial imaging. CTA Lower Extremity CTA is uncommonly used in the diagnosis of EIAE and has not demonstrated diagnostic superiority to MRA combined with US [21]. CTA allows assessment of arterial kinking, arterial wall thickening, stenosis, and extent of involved arterial segment.


Nonatherosclerotic Peripheral Arterial Disease. MRA Lower Extremity The superior contrast resolution inherent to MRA allows for optimal visualization of extravascular anatomy in suspected EIAE. Like CTA, MRA allows assessment of arterial length and kinking, albeit with improved soft- tissue characterization. MRA is less sensitive than US for detecting intravascular lesions. MRA has proven useful in diagnosing EIAE when used in conjunction with US, a combination that was found to be superior or equal to CTA alone [21].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity The ability to visualize changes in both flow dynamics and vessel caliber in real time has been paramount in diagnosing EIAE in endurance athletes [21,22]. Dynamic use of US duplex Doppler and segmental Doppler pressures in both hip flexion and extension can accurately depict flow disturbance [21], while its use pre- and


Nonatherosclerotic Peripheral Arterial Disease. Nonatherosclerotic Peripheral Arterial Disease postexercise may demonstrate associated exercise-induced vasospasm [20,22]. US duplex Doppler has been found to be superior to MRA in detecting intravascular lesions; however, its sensitivity may be limited in patients with only mildly symptomatic disease [21].


Nonatherosclerotic Peripheral Arterial Disease. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of EIAE.


Nonatherosclerotic Peripheral Arterial Disease. Arteriography Lower Extremity The role of DSA in the evaluation of EIAE is not as well established. The most frequent finding of EIAE at DSA is smooth, long, and eccentric stenosis, with thrombosis and dissection present less frequently [1]. Although the external iliac artery is most frequently affected, the common iliac artery can be involved in approximately 15% of patients [32]. A benefit of arteriography, relative to other modalities, is that the pressure gradient across the narrowing can be measured at baseline as well as during various maneuvers, including following the administration of vasodilators [33]. Acquiring images during hip flexion frequently reveals a kink in the iliac arteries at the site of stenosis [32].


Nonatherosclerotic Peripheral Arterial Disease. Variant 3: Suspected or known lower-extremity inflammatory vasculitides. Initial imaging. CTA Lower Extremity While the spatial resolution of CTA is relatively high, some authors have suggested that it may not be sensitive enough to resolve the fine collateral vessels seen in thromboangiitis obliterans and other small-vessel pathologies [2]. Evaluation of subtle vascular findings may also be limited by beam hardening artifact related to adjacent bone or metal [34]. CTA is helpful in identifying vessel wall thickening, stenosis, occlusion and collaterals when large- or medium-sized vessels of the lower extremities are involved.


Nonatherosclerotic Peripheral Arterial Disease. MRA Lower Extremity MRA has lower spatial resolution than CTA, a factor that makes it less than ideal in adequately characterizing distal small vessels. Despite this, additional sequences acquired during an MRA examination may be helpful in evaluating for associated nonvascular findings, such as osteomyelitis or septic arthritis [2]. The sensitivity for detecting these soft-tissue abnormalities is greater with contrast-enhanced MRA than noncontrast-enhanced MRA.


Nonatherosclerotic Peripheral Arterial Disease. Arteriography Lower Extremity Because of its high inherent spatial resolution, selective arteriography with DSA is considered the gold standard in the diagnosis of thromboangiitis obliterans [2].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity US duplex Doppler can identify the typical corkscrew collateral vessels in the walls of the lower-extremity vessels in patients with thromboangiitis obliterans [35].


Nonatherosclerotic Peripheral Arterial Disease. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of lower-extremity inflammatory vasculitides.


Nonatherosclerotic Peripheral Arterial Disease. Variant 4: Suspected or known dissection or connective tissue lower-extremity vascular diseases. Initial imaging. CTA Lower Extremity CTA is highly recommended in the workup of MS, LDS, and vascular EDS, as it offers comprehensive whole- body imaging and high spatial resolution in a single study. This allows for evaluation of the entire vascular system and identification of typical musculoskeletal malformations that may assist in the initial diagnosis of a heritable connective tissue disease [1,3,4]. CTA is valuable for defining the true and false lumen and can be used for longitudinal follow-up. Although the initial diagnosis of these diseases is most commonly made in the pediatric population, this document addresses imaging in adults (18 years of age and older) only. Because of the high risk of vascular complications inherent to LDS and MS, CTA surveillance is recommended at least every 1 year [3] and 2 years [1], respectively.


Nonatherosclerotic Peripheral Arterial Disease. MRA Lower Extremity MRA has been suggested for evaluation of the lower extremities in patients with connective tissue disorders, such as MS, LDS, and vascular EDS. However, the lower spatial resolution inherent to MRA limits the evaluation of small arterial branches [1,2,36] compared to CTA.


Nonatherosclerotic Peripheral Arterial Disease. Nonatherosclerotic Peripheral Arterial Disease Arteriography Lower Extremity Given its invasive nature, the use of selective arteriography should be avoided in patients with congenitally weakened vessels (eg, collagen vascular diseases, such as vascular EDS) where the risk of catastrophic vascular perforation is high [1,4]. In such patients, it has been suggested that this modality only be performed if it is part of a planned interventional procedure (eg, coil embolization of remote bleeding arteries, etc) [4].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity There is no relevant literature regarding the use of US duplex Doppler in the evaluation of lower-extremity connective disease.


Nonatherosclerotic Peripheral Arterial Disease. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of lower-extremity connective disease, but the same concerns regarding arterial puncture would apply.


Nonatherosclerotic Peripheral Arterial Disease. Variant 5: Suspected or known other noninflammatory lower-extremity vascular diseases (such as fibromuscular dysplasia, segmental arterial mediolysis). Initial imaging. CTA Lower Extremity While selective arteriography is considered the gold standard in diagnosing FMD, CTA has proven helpful in the initial diagnosis and follow-up of FMD within the lower extremities [25,37]. Because of its high spatial resolution, several studies have demonstrated the superiority of CTA over MRA in visualizing vascular lesions in FMD [4,36]. Despite this, one study found CTA to have limited sensitivity in the evaluation of small vessels in patients with mild FMD [36]. CTA may be helpful in the workup of cystic adventitial disease [31]. It has also been advocated as a first-line imaging study in the diagnosis of SAM [28,29] with follow-up recommended at 1- year intervals [27].


Nonatherosclerotic Peripheral Arterial Disease. MRA Lower Extremity The improved contrast resolution inherent to MRA renders superior characterization of the extravascular soft tissues. This is of particular importance in the workup of cystic adventitial disease, where T1-weighted and T2- weighted sequences may demonstrate connections between adventitial cysts and the adjacent joint capsule. It has been recommended as the modality of choice in preoperative planning for cystic adventitial disease [31]. MRA has also been found useful for annual follow-up in SAM [27].


Nonatherosclerotic Peripheral Arterial Disease. Arteriography Lower Extremity Because of its high inherent spatial resolution, selective arteriography with DSA is considered the gold standard in the diagnosis of FMD [25,26,36,38-40], with many authors claiming that CTA and MRA may lack the spatial resolution necessary to detect small-artery pathology [36]. Arteriography is susceptible to standing waves. Therefore, caution must be exercised to accurately distinguish standing waves from true arterial beading characteristic of FMD [15]. This modality may simultaneously be therapeutic in FMD, as angioplasty is currently the preferred treatment of choice [25,38,39]. Selective arteriography is considered the reference standard in the diagnosis of SAM while also having therapeutic potential [28].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity A recent study found US duplex Doppler to be helpful in diagnosing cystic adventitial disease, where numerous anechoic cysts are seen scattered throughout the adventitia at a site of vessel stenosis [31]. While much has been published about the use of US duplex Doppler in renal artery FMD, no literature is currently present to support its use in the diagnosis of FMD affecting the lower-extremity arteries.


Nonatherosclerotic Peripheral Arterial Disease. US Intravascular Lower Extremity IVUS has been reported to be useful in diagnosing cystic adventitial disease [31]. In FMD, other authors have concluded that IVUS is likely more accurate than other modalities in characterizing the hemodynamic severity of encountered stenosis [39,41].


Nonatherosclerotic Peripheral Arterial Disease. Variant 6: Lower-extremity vascular trauma. Initial imaging. CTA Lower Extremity CTA is considered especially important in the setting of trauma to the lower extremities. Several studies recognize its use as a first-line investigation in all patients with suspected vascular injury [42], demonstrating a sensitivity of 95% to 100% and a specificity of 87% to 100% [34,43]. Sensitivity for vascular injury in equivocal cases can be increased by using reconstructed images. The use of CTA is associated with lower morbidity than that of selective arteriography and has resulted in a precipitous decrease in negative surgical exploration rates in the post-traumatic


Nonatherosclerotic Peripheral Arterial Disease. Nonatherosclerotic Peripheral Arterial Disease


Nonatherosclerotic Peripheral Arterial Disease. patient [43]. One study has suggested that the critical time saved by CTA in diagnosing lower-extremity vascular injury translates to decreased morbidity, thereby reducing hospital costs while improving outcomes [34].


Nonatherosclerotic Peripheral Arterial Disease. MRA Lower Extremity MRA is not indicated after trauma, as long requisite imaging times are precarious in a potentially unstable patient. Underlying shrapnel or bullet fragments pose significant safety concerns within the confines of the magnetic field, in addition to degrading image quality [43].


Nonatherosclerotic Peripheral Arterial Disease. Arteriography Lower Extremity Arteriography is recommended for vascular evaluation in patients with hard signs of vascular injury requiring immediate repair [44,45]. This can be done in the operating room with a C-arm or in a hybrid suite [44,45]. Selective arteriography is invasive and unable to depict extravascular anatomy [34]. In addition, it is time- consuming and could delay treatment of other traumatic injuries. However, it accurately detects active bleeding, pseudoaneurysms, arteriovenous fistula, and vascular thrombosis. A recent retrospective review advocates the use of arteriography if CTA is equivocal [43].


Nonatherosclerotic Peripheral Arterial Disease. US Duplex Doppler Lower Extremity While portability and lack of nephrogenic contrast administration make US duplex Doppler an attractive option for evaluating the lower-extremity vessels after trauma, significant injury to the superficial soft tissues may limit its accuracy in assessing vascular integrity [43]. A recent meta-analysis reported that the post-test probability of arterial injury was 89% with a positive US and 5% with a negative US [46].


Nonatherosclerotic Peripheral Arterial Disease. US Intravascular Lower Extremity There is no relevant literature regarding the use of IVUS in the evaluation of lower-extremity vascular trauma.


Nonatherosclerotic Peripheral Arterial Disease. Summary of Recommendations Variant 1: MRA lower extremity without and with IV contrast or US duplex Doppler lower extremity or CTA lower extremity with IV contrast is usually appropriate for the initial imaging of suspected popliteal entrapment syndrome. These procedures are equivalent alternatives. Variant 2: US duplex Doppler lower extremity or MRA lower extremity without and with IV contrast or CTA lower extremity with IV contrast is usually appropriate for the initial imaging of suspected EIAE. These procedures are equivalent alternatives. Variant 3: Arteriography lower extremity or CTA lower extremity with IV contrast or MRA lower extremity without and with IV contrast is usually appropriate for the initial imaging of suspected or known lower- extremity inflammatory vasculitides. These procedures are equivalent alternatives. Variant 4: CTA lower extremity with IV contrast or MRA lower extremity without and with IV contrast is usually appropriate for the initial imaging of suspected or known dissection or connective tissue lower- extremity vascular diseases. These procedures are equivalent alternatives. Variant 5: CTA lower extremity with IV contrast or MRA lower extremity without and with IV contrast or Arteriography lower extremity is usually appropriate for the initial imaging of suspected or known other noninflammatory lower-extremity vascular diseases (such as FMD, SAM). These procedures are equivalent alternatives. Variant 6: CTA lower extremity with IV contrast is usually appropriate for the initial imaging of lower- extremity vascular trauma.


Nonatherosclerotic Peripheral Arterial Disease. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch.acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation.


Nonatherosclerotic Peripheral Arterial Disease. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www.acr.org/ac.


Indeterminate Renal Mass

Indeterminate Renal Mass. Introduction/Background Renal masses are increasingly detected in asymptomatic individuals as incidental findings. Many of these are small renal tumors that vary widely in biological aggressiveness, ranging from benign tumors to high-grade renal cell carcinomas (RCCs). An indeterminate renal mass cannot be diagnosed confidently as benign or malignant at the time it is discovered. Masses that can be definitively characterized on the first imaging test will not be discussed in this review.


Indeterminate Renal Mass

Indeterminate Renal Mass. Special Imaging Considerations Dual-energy CT and contrast-enhanced ultrasound (CEUS) are gaining traction in the characterization of indeterminate renal masses.


Indeterminate Renal Mass

Indeterminate Renal Mass. Several studies have demonstrated that dual-energy CT can improve the differentiation between nonenhancing cysts and low-level-enhancing tumors [8-11]. Dual-energy CT with reconstruction of virtual monochromatic images has been shown to decrease or overcome renal cyst pseudoenhancement [12]. Other studies have shown that dual-energy CT can differentiate between solid tumors and hyperdense cysts incidentally detected on a single-phase postcontrast CT [13-15] and can be useful when a comprehensive multiphase renal protocol CT is not available.


Indeterminate Renal Mass

Indeterminate Renal Mass. CEUS with microbubble agents is a useful alternative for characterizing renal masses, especially for patients in whom iodinated CT contrast or gadolinium-based MRI contrast is contraindicated. The microbubble agents are not excreted by the kidneys and therefore do not affect renal function. CEUS allows real-time evaluation of microvasculature and has been shown to be valuable for differentiating between cystic and solid renal lesions and for characterizing complex renal cystic lesions and indeterminate renal masses [16-18]. CEUS may result in assignment of a higher Bosniak classification compared to contrast-enhanced CT [19,20]. However, a typical CEUS examination does not result in a complete evaluation of both kidneys for additional renal masses.


Indeterminate Renal Mass

Indeterminate Renal Mass. Tc-99m sestamibi single-photon emission computed tomography (SPECT)/CT has been shown in several studies to be helpful when the diagnosis of a renal oncocytoma is suspected [21-23]. For example, in a study of 31 renal masses imaged with Tc-99m sestamibi SPECT/CT, 91.6% (11 of 12) of oncocytomas had radiotracer uptake above


Indeterminate Renal Mass

Indeterminate Renal Mass. aUniversity of California San Francisco School of Medicine, San Francisco, California. bPanel Chair, Northwestern University, Chicago, Illinois. cPanel Vice- Chair, UT Southwestern Medical Center, Dallas, Texas. dUniversity of Rochester Medical Center, Rochester, New York. eThe University of Texas MD Anderson Cancer Center, Houston, Texas. fUniversity of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; American Society of Nephrology. gUniversity of Washington, Seattle, Washington; American Urological Association. hDuke University Medical Center, Durham, North Carolina. iMayo Clinic, Rochester, Minnesota. jEmory University School of Medicine, Atlanta, Georgia. kThomas Jefferson University Hospital, Philadelphia, Pennsylvania. lCleveland Clinic, Cleveland, Ohio. mMedical University of South Carolina, Charleston, South Carolina; American Urological Association. nUniversity of Alabama at Birmingham, Birmingham, Alabama. oJohns Hopkins University School of Medicine, Washington, District of Columbia. pUniversity of Maryland School of Medicine, Baltimore, Maryland. qSpecialty Chair, University of Alabama at Birmingham, Birmingham, Alabama.


Indeterminate Renal Mass

Indeterminate Renal Mass. Reprint requests to: publications@acr.org


Indeterminate Renal Mass

Indeterminate Renal Mass

Indeterminate Renal Mass. Indeterminate Renal Mass


Indeterminate Renal Mass

Indeterminate Renal Mass. adjacent normal renal parenchyma, three hybrid tumors (mixed-type oncocytoma and chromophobe renal cancer) showed tracer uptake, one papillary RCC had a slight tracer uptake, and the remaining 11 RCC were sestamibi negative [23].


Indeterminate Renal Mass

Indeterminate Renal Mass. CT urography (CTU) is an imaging study that is tailored to improve visualization of both the upper and lower urinary tracts. There is variability in the specific parameters, but it usually involves unenhanced images followed by IV contrast-enhanced images, including nephrographic and excretory phases acquired at least 5 minutes after contrast injection. Alternatively, a split-bolus technique uses an initial loading dose of IV contrast and then obtains a combined nephrographic-excretory phase after a second IV contrast dose; some sites include arterial phase. CTU should use thin-slice acquisition. Reconstruction methods commonly include maximum intensity projection or 3-D volume rendering. For the purposes of this document, we make a distinction between CTU and CT abdomen and pelvis without and with IV contrast. CT abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts and without both the precontrast and excretory phases.


Indeterminate Renal Mass

Indeterminate Renal Mass. MR urography (MRU) is also tailored to improve imaging of the urinary system. Unenhanced MRU relies upon heavily T2-weighted imaging of the intrinsic high signal intensity from urine for evaluation of the urinary tract. IV contrast is administered to provide additional information regarding obstruction, urothelial thickening, focal lesions, and stones. A contrast-enhanced T1-weighted series should include corticomedullary, nephrographic, and excretory phases. Thin-slice acquisition and multiplanar imaging should be obtained. For the purposes of this document, we make a distinction between MRU and MRI abdomen and pelvis without and with IV contrast. MRI abdomen and pelvis without and with IV contrast is defined as any protocol not specifically tailored for evaluation of the upper and lower urinary tracts, without both the precontrast and excretory phases, and without heavily T2-weighted images of the urinary tract.


Indeterminate Renal Mass

Indeterminate Renal Mass. OR Discussion of Procedures by Variant Variant 1: Indeterminate renal mass. No contraindication to either iodinated CT contrast or gadolinium- based MR intravenous contrast. Initial imaging. Arteriography Kidney Cross-sectional imaging has replaced arteriography for the evaluation of indeterminate renal masses. There is no relevant literature regarding the use of arteriography in the evaluation of an indeterminate renal mass.


Indeterminate Renal Mass

Indeterminate Renal Mass. Although CT with and without IV contrast is optimal for evaluation of indeterminate renal masses, CT without IV contrast can provide some information. For example, homogenous renal masses measuring <20 HU or >70 HU [1,2] or lesions containing macroscopic fat can be characterized as benign lesions on noncontrast CT. Other studies have also shown that dual-energy CT can differentiate between solid tumors and hyperdense cysts incidentally detected on a single-phase postcontrast CT [13-15] and can be useful when a comprehensive multiphase renal protocol CT is not available.


Indeterminate Renal Mass

Indeterminate Renal Mass


Indeterminate Renal Mass

Indeterminate Renal Mass. Cystic Renal Masses The Bosniak CT classification system for cystic renal masses encompasses the spectrum from simple renal cyst to cystic RCC, with the likelihood of malignancy increasing with the complexity of the mass [28,29]. Because the presence of any enhancing nodules, walls, or thick septa within a cystic mass is key to determining the probability of malignancy using the Bosniak classification, CT without and with IV contrast is usually necessary for evaluating these lesions. One retrospective study of 156 Bosniak IIF lesions showed that 10.9% of the lesions progressed to malignancy between 6 months and 3.2 years [30]. Another retrospective study of 69 Bosniak IIF lesions and 144 Bosniak III lesions showed malignancy rates of 25% and 54%, respectively [31]. In one study of 312 prospectively classified Bosniak lesions, the malignancy rate at pathology was 38% for Bosniak IIF, 40% for Bosniak III, and 90% for Bosniak IV renal lesions [32].


Indeterminate Renal Mass

Indeterminate Renal Mass. Oncocytoma is another benign tumor that mimics RCC, and to date there are no specific CT features to reliably differentiate between the two [37]. Enhancement pattern on multiphasic CT has been used to subtype RCC. In a retrospective study of 298 cases of RCC and oncocytoma evaluated with 4-phase CT, multiphasic enhancement threshold helped to discriminate clear-cell RCC from oncocytoma with an accuracy of 77%, clear-cell RCC from papillary RCC with an accuracy of 85%, and clear-cell RCC from chromophobe RCC with an accuracy of 84% [38]. However, no prospective studies have validated the reported enhancement threshold, and accuracies of 77% to 85% may not be sufficient to change clinical management.


Indeterminate Renal Mass

Indeterminate Renal Mass. CTU While there is no literature specifically evaluating the performance of CTU for indeterminate renal masses, CTU may be useful in this context. CTU that includes the acquisition of both unenhanced and nephrographic phase images would be expected to provide the same information as CT abdomen without and with IV contrast. The excretory phase images from CTU may provide additional information for differentiating between intrarenal urothelial carcinoma from centrally located RCC [39].


Indeterminate Renal Mass

Indeterminate Renal Mass. MRI Abdomen MRI is frequently used to characterize renal lesions. In one retrospective study of 120 patients, the specificity of MRI was significantly higher than that of CT in diagnosing RCC (68.1% versus 27.7%), whereas their sensitivities


Indeterminate Renal Mass

Indeterminate Renal Mass. Ho et al [51] showed that the optimal percentage of enhancement threshold for distinguishing cysts from solid tumors on MRI was 15%. Hecht et al [52] reported that both quantitative and qualitative methods are sensitive in the detection of enhancement in a renal lesion on MRI and that subtracted images enable accurate assessment of tumor enhancement for intrinsically hyperintense lesions using qualitative methods.


Indeterminate Renal Mass

Indeterminate Renal Mass. Although MRI without and with IV contrast is optimal for renal lesion characterization, MRI without IV contrast can also provide diagnostic information. For example, simple cystic lesions, or even those with thin septations, can often be characterized on noncontrast T2-weighted imaging based on their homogeneous and very high T2 signal intensity. To differentiate between hemorrhagic or proteinaceous cyst and RCC, a retrospective study shows that homogenous high T1 signal intensity lesions with smooth borders and lesion to renal parenchyma signal intensity ratio of >1.6 predicted the lesion as a benign cyst [53]. Another study of 144 T1-hyperintense lesions demonstrated that diffuse and marked T1-hyperintensity achieved accuracies of 73.6% to 79.9% for the diagnosis of T1- hyperintense cysts [54]. An angular interface with the renal parenchyma on T2-weighted imaging has been shown to be 78% sensitive and 100% specific for differentiating benign exophytic renal masses from malignant masses [55]. Diffusion-weighted imaging, although less accurate than contrast-enhanced MRI, may have some ability to differentiate solid RCC from oncocytomas and characterize the histologic subtypes of RCC [56]. New and specialized MRI sequences have been proposed for the purposes of characterizing the vascularity of renal lesions in patients with renal dysfunction. For example, one small study of 17 renal lesions used arterial spin labeling to detect blood flow in renal masses, which correlated with malignancy [57].


Indeterminate Renal Mass

Indeterminate Renal Mass. Cystic Renal Masses In a study of 69 cystic renal masses evaluated using the Bosniak classification with CT and MRI, there was CT and MRI agreement in 56 of 69 lesions (81%) and disagreement in 13 of 69 lesions (19%) [29]. CT and MRI were felt to be similar in evaluation of most renal cystic mass lesions. However, MRI may depict additional findings, such as an increase in number of septa, septal or wall thickness, and enhancement. Such findings would result in MRI upgrading cystic lesions and thus might alter patient management [29]. Another study of 33 cystic lesions imaged with both 1.5T and 3.0T MRI showed that there is a greater tendency to upgrade cyst complexity and Bosniak cyst category at 3.0T than at 1.5T and thus suggested that serial follow-up of cystic renal lesions be performed at constant field strength [58].


Indeterminate Renal Mass

Indeterminate Renal Mass. Solid Renal Masses Other than AMLs with macroscopic fat, MRI cannot yet reliably differentiate benign from malignant renal tumors. However, several MRI features have been reported to be useful for suggesting types of solid renal tumors. In one multiparametric MRI study, lipid-poor AMLs were characterized by higher T1 signal intensity and lower T2 signal intensity compared to normal renal cortex and by greater arterial-to-delayed enhancement ratio than RCC [59]. Another study showed that the combination of low T2 signal and signal drop on chemical-shift imaging is specific for lipid-poor AMLs but lacks sensitivity, and the combination of low T2 signal intensity and high area under the contrast-enhanced MRI curve is sensitive and specific for lipid-poor AMLs [60]. Although both papillary RCC and lipid-poor AMLs can have low signal intensity on T2-weighted images, the presence of intratumoral hemorrhage seen on T1-weighted images was suggested to be a specific feature of papillary RCC [61]. Nonetheless, MRI findings of lipid-poor AMLs overlap with various RCC subtypes and remain difficult to prospectively diagnose [60].


Indeterminate Renal Mass

Indeterminate Renal Mass. Indeterminate Renal Mass diagnostic algorithm had diagnostic accuracy of 81% (88 of 109) and 91% (99 of 109) in the diagnosis of clear-cell RCC and papillary RCC, respectively, while achieving moderate to substantial inter-reader agreement among 7 radiologists [64].


Indeterminate Renal Mass

Indeterminate Renal Mass. MRU There is no relevant literature regarding the use of MRU in the evaluation of indeterminate renal masses.


Indeterminate Renal Mass

Indeterminate Renal Mass. Radiography Intravenous Urography There is no relevant literature regarding the use of IV urography (IVU) in the evaluation of indeterminate renal masses.


Indeterminate Renal Mass

Indeterminate Renal Mass. US Abdomen with IV Contrast CEUS using microbubble agents is emerging as a useful way to characterize previously indeterminate renal lesions [16-18]. In a study of 1,018 indeterminate renal lesions, CEUS had a per patient sensitivity of 100% (126 of 126 patients), specificity of 95% (132 of 139 patients), positive predictive value of 94.7% (126 of 133 patients), and negative predictive value of 100% (132 of 132 patients) for classifying benign versus malignant renal masses [16]. In that study, any echogenic masses with enhancement equal to or greater than normal renal cortex and wash-out, and any masses with blood flow, were considered malignant. In another study, CEUS successfully classified 95.7% (90 of 94) previously indeterminate lesions and has an accuracy of 90.2% (37 of 41 lesions) when compared with the reference standard, including histopathology and follow-up [18]. In the subgroup analysis, CEUS was definitive for 94.4% (17 of 18) of cases referred because of equivocal enhancement at CT [18]. In that same study, CEUS was able to classify lesions in 100% (10 of 10) of the cases in which the lesions were indeterminate on prior MRI [18]. Another study of CEUS in 83 CT indeterminate renal masses reported that the accuracy of characterization by CEUS was 95.2% compared with 42.2% using unenhanced US [17].


Indeterminate Renal Mass

Indeterminate Renal Mass. Studies have shown CEUS to be more sensitive than contrast-enhanced CT in characterizing cystic renal masses [19,65]. In a study of 31 cystic renal masses evaluated by both CT and CEUS using the Bosniak classification, 26% of the lesions were upgraded by CEUS [19]. In a prospective CEUS study of 94 solid renal lesions excluding lipid- rich AML, hypovascularity of small solid renal masses relative to the cortex in the arterial phase has 100% specificity for detecting malignancy, especially for detecting papillary RCC [66]. Quantitative analysis of CEUS has also been reported to be useful to stratify RCC and benign renal tumors [67,68].


Indeterminate Renal Mass

Indeterminate Renal Mass. Variant 2: Indeterminate renal mass. Contraindication to both iodinated CT and gadolinium-based MR intravenous contrast. Initial imaging. Arteriography Kidney Cross-sectional imaging has replaced arteriography for the evaluation of indeterminate renal masses. There is no relevant literature regarding the use of arteriography in the evaluation of indeterminate renal masses. Arteriography typically requires IV administration of iodinated contrast.