Staging and Surveillance of Testicular Cancer. The 2021 NCCN guidelines, however, do provide an option for chest radiography for stage I pure seminoma testicular cancer patients undergoing surveillance if clinically indicated [8]. US Abdomen and Retroperitoneum US of the abdomen and retroperitoneum to detect retroperitoneal lymph node metastases is less accurate and reproducible than CT, MRI, or PET/CT [50]. US Scrotum Scrotal US does not have a role in the restaging of men with testicular cancer diagnosis established by orchiectomy unless there is concern for contralateral tumor or equivocal clinical examination [8]. Scrotal US should always be performed during the initial workup of a scrotal mass before orchiectomy to localize the tumor, plan surgery, and clear the contralateral testicle of disease [40]. After initial triage and orchiectomy, scrotal US does not have a role in the initial staging or restaging of men with testicular cancer diagnosis established by orchiectomy unless there is concern for contralateral tumor or equivocal clinical examination [8]. Variant 4: Surveillance of stage IA and IB nonseminoma testicular cancer. Diagnosed by orchiectomy. No clinical suspicion of recurrence. Bone Scan Whole Body Bone metastases from testicular cancer are uncommon. In one study, bone scan was able to detect metastases to the iliac bones ipsilateral to the testicular tumor before they were detectable by CT [12]. CT Abdomen and Pelvis CT is the reference standard imaging test used for assessing the retroperitoneum for the presence of metastatic lymphadenopathy. CT is rapid, reproducible, and provides excellent imaging assessment of the para-aortic and paracaval regions [13-15]. Challenges related to CT are that many young men have little retroperitoneal fat, which may be an impediment for readers interpreting the study, and that CT cannot detect metastatic disease in lymph nodes of normal size. Additionally, inflammatory lymph nodes cannot be differentiated from those that are enlarged from metastases [16].


Staging and Surveillance of Testicular Cancer. Lymph nodes >1 cm in short axis are highly suspicious for metastatic disease, particularly if they are located in the hilar regions of the kidney or in the para-aortic or caval areas (eg, testicular cancer landing zones). Various studies have established the accuracy of CT in detecting metastatic retroperitoneal lymph nodes from testicular cancer, which ranges from 73% to 97%, sensitivity ranges from 65% to 96%, and specificity from 81% to 100% [7,17-22]. Data also indicate that the accuracy of CT declines in patients with limited disease (eg, stage N1 and stage N2) and also if the upper limit of normal lymph node size is lowered [15,17,21]. Of note, most of these studies are relatively old and were performed using single-slice CT; however, limited newer data suggest similar accuracy using multi- slice CT compared with single-slice CT [23]. It is important to recognize that a significant percentage of metastatic lymph nodes will be <1 cm, up to 60% in one series [24]. For this reason, some authors suggest using a cut-off value of 0.7 cm to 0.8 cm in testicular cancer at the expense of reduced specificity [24,25]. These cut-off values are for the short-axis measurement when assessing the likelihood of nodal disease (N0 versus N1 disease); however, when assessing the nodal burden, the lymph nodes should be measured in long axis (eg, N1 versus N2 and N3 disease) [6,25]. Two studies have also evaluated the value of nodal craniocaudal length or volume as risk factors for recurrence in testicular cancer [26,27]. Another study comparing lymph node measurements performed by expert radiologists, other observers, and a semiautomated process showed excellent correlation between measurements, indicating that the task of actually measuring lymph nodes, which can be time consuming and tedious, could potentially be delegated or automated in the future [28].


Staging and Surveillance of Testicular Cancer. Staging and Surveillance of Testicular Cancer The use of iodinated IV contrast media, as well as oral contrast media, may aid in detection of retroperitoneal lymph nodes, clarifying the adjacent normal anatomic structures including blood vessels and the duodenum [29]. Surveillance protocols no longer include chest CT [30] and may eliminate pelvic CT, except in cases in which the pelvis is deemed high risk [53-55]. The number and frequency schedule of follow-up CT examinations of the abdomen and pelvis is variable [56]. Most recently, the 2021 NCCN guidelines recommends different intensity of follow-up for stage I pure seminoma testicular cancer and nonseminoma testicular cancer, which also depends on the presence or absence of risk factors for metastatic disease [8]. CT Chest Although CT is more sensitive than radiography for detecting recurrent disease in the chest [30,31], this added sensitivity is offset by lower specificity and a higher false positive detection rate for abnormalities that are not metastatic [32]. Detection of mediastinal and hilar lymph nodes may be aided by the use of iodinated IV contrast media [33]. In patients with thoracic symptoms, the NCCN advises the use of CT chest for follow-up of patients with nonseminoma undergoing surveillance [8]. FDG-PET/CT Whole Body FDG-PET has been used for staging and restaging patients with testicular cancer, but its incremental value in staging patients compared with CT or MRI has yet to be defined. For initial staging, PET may be slightly more sensitive than CT [34-39]. MRI Abdomen and Pelvis MRI has also been studied for staging and surveillance of testicular cancer to identify metastatic retroperitoneal lymphadenopathy [41-46]. Limited evidence from single-institution studies indicates comparable efficacy to CT for detection of retroperitoneal lymphadenopathy, notably without the need for GBCAs [41,43].


Staging and Surveillance of Testicular Cancer. A limitation of the literature regarding MRI for detection of metastatic retroperitoneal lymphadenopathy is that the studies are older and do not incorporate DWI. DWI can substantially improve identification of lymph nodes; however, it is still limited by significant overlap between benign and malignant lymph nodes [6]. A study published in 2020 showed comparable accuracy between MRI, which included DWI and omitted GBCAs, and CT for detection of metastatic retroperitoneal lymph nodes in testicular germ-cell tumors [47]. MRI Head MRI of the head is not recommended during the surveillance of pure seminoma testicular cancer unless the patient is symptomatic. Radiography Chest The 2021 NCCN guidelines recommend chest radiography for surveillance of Stage I nonseminoma testicular cancer [8]. US Abdomen and Retroperitoneum US of the abdomen and retroperitoneum to detect retroperitoneal lymph node metastases is less accurate and reproducible than CT, MRI, or PET/CT [50]. US Scrotum Scrotal US does not have a role in the restaging of men with testicular cancer diagnosis established by orchiectomy unless there is concern for contralateral tumor or equivocal clinical examination [8]. Scrotal US should always be performed during the initial workup of a scrotal mass before orchiectomy to localize the tumor, plan surgery, and clear the contralateral testicle of disease [40]. After initial triage and orchiectomy, scrotal US does not have a role in the initial staging or restaging of men with testicular cancer diagnosis established by orchiectomy unless there is concern for contralateral tumor or equivocal clinical examination [8]. Staging and Surveillance of Testicular Cancer Variant 5: Surveillance of stage IA and IB pure seminoma and nonseminoma testicular cancer. Diagnosed by orchiectomy. Suspected recurrence. Bone Scan Whole Body Bone metastases from testicular cancer are uncommon.


Staging and Surveillance of Testicular Cancer. In one study, bone scan was able to detect metastases to the iliac bones ipsilateral to the testicular tumor before they were detectable by CT [12]. CT Abdomen and Pelvis CT is the reference standard imaging test used for assessing the retroperitoneum for the presence of metastatic lymphadenopathy. CT is rapid, reproducible, and provides excellent imaging assessment of the para-aortic and paracaval regions [13-15]. Challenges related to CT are that many young men have little retroperitoneal fat, which may be an impediment for readers interpreting the study, and that CT cannot detect metastatic disease in lymph nodes of normal size. Additionally, inflammatory lymph nodes cannot be differentiated from those that are enlarged from metastases [16]. Lymph nodes >1 cm in short axis are highly suspicious for metastatic disease, particularly if they are located in the hilar regions of the kidney or in the para-aortic or caval areas (eg, testicular cancer landing zones). Various studies have established the accuracy of CT in detecting metastatic retroperitoneal lymph nodes from testicular cancer, which ranges from 73% to 97%, sensitivity ranges from 65% to 96%, and specificity from 81% to 100% [7,17-22]. Data also indicates that the accuracy of CT declines in patients with limited disease (eg, stage N1 and stage N2) and also if the upper limit of normal lymph node size is lowered [15,17,21]. Of note, most of these studies are relatively old and were performed using single-slice CT; however, limited newer data suggest similar accuracy using multi- slice CT compared with single-slice CT [23]. It is important to recognize that a significant percentage of metastatic lymph nodes will be <1 cm, up to 60% in one series [24]. For this reason, some authors suggest using a cut-off value of 0.7 cm to 0.8 cm in testicular cancer at the expense of reduced specificity [24,25].


Staging and Surveillance of Testicular Cancer. These cut-off values are for the short-axis measurement when assessing the likelihood of nodal disease (N0 versus N1 disease); however, when assessing the nodal burden, the lymph nodes should be measured in long axis (eg, N1 versus N2 and N3 disease) [6,25]. Two studies have also evaluated the value of nodal craniocaudal length or volume as risk factors for recurrence in testicular cancer [26,27]. Another study comparing lymph node measurements performed by expert radiologists, other observers, and a semiautomated process showed excellent correlation between measurements, indicating that the task of actually measuring lymph nodes, which can be time consuming and tedious, could potentially be delegated or automated in the future [28]. The use of iodinated IV contrast media, as well as oral contrast media, may aid in detection of retroperitoneal lymph nodes, clarifying the adjacent normal anatomic structures including blood vessels and the duodenum [29]. The number and frequency schedule of follow-up CT examinations of the abdomen and pelvis is variable [56]. Most recently, the 2021 NCCN guidelines recommends different intensity of follow-up for stage I pure seminoma testicular cancer and nonseminoma testicular cancer, which also depends on the presence or absence of risk factors for metastatic disease [8]. CT Chest Although CT is more sensitive than radiography for detecting recurrent disease in the chest [30,31], this added sensitivity is offset by lower specificity and a higher false positive detection rate for abnormalities that are not metastatic [32]. Detection of mediastinal and hilar lymph nodes may be aided by the use of iodinated IV contrast media [33]. Several studies indicate that chest radiography is sufficient when compared with CT for follow-up of stage I pure seminoma testicular cancers [30,32,49,54].


Staging and Surveillance of Testicular Cancer. However, the 2021 NCCN guidelines advise the use of chest CT in both patients with Stage I pure seminoma or nonseminoma testicular cancer with thoracic symptoms [8]. FDG-PET/CT Whole Body FDG-PET has been used for staging and restaging patients with testicular cancer, but its incremental value in staging patients compared with CT or MRI has yet to be defined. For initial staging, PET may be slightly more sensitive than CT [34-39]. Staging and Surveillance of Testicular Cancer MRI Abdomen and Pelvis MRI has also been studied for staging and surveillance of testicular cancer to identify metastatic retroperitoneal lymphadenopathy [41-46]. Limited evidence from single-institution studies indicates comparable efficacy to CT for detection of retroperitoneal lymphadenopathy, notably without the need for GBCAs [41,43]. A limitation of the literature regarding MRI for detection of metastatic retroperitoneal lymphadenopathy is that the studies are older and do not incorporate DWI. DWI can substantially improve identification of lymph nodes; however, it is still limited by significant overlap between benign and malignant lymph nodes [6]. A study published in 2020 showed comparable accuracy between MRI, which included DWI and omitted GBCAs, and CT for detection of metastatic retroperitoneal lymph nodes in testicular germ cell tumors [47]. MRI Head MRI of the head is not recommended during the surveillance of pure seminoma testicular cancer unless the patient is symptomatic. Radiography Chest In pure seminoma testicular cancer under surveillance, studies have shown that lung relapses are rarely detected by chest radiography alone, with most relapses detected by abnormal serum markers or abdominal and pelvic CT scan [57-59], calling into question the value of chest radiography in surveillance of stage I pure seminoma testicular cancer.


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child.  Introduction/Background Pneumonia is one of the most common acute infections and the single greatest infectious cause of death in children worldwide, accounting for 16% of all deaths in children under 5 years of age [1,2]. Properly recognizing, diagnosing, and treating pneumonia and its complications are of vital importance. Pneumonia can be defined clinically as the presence of fever and/or acute respiratory symptoms [3-5]. However, the clinical symptoms often lack sensitivity and specificity for the diagnosis of pneumonia [5]. Imaging plays a limited role in uncomplicated pneumonia and is primarily reserved for diagnosis of pneumonia in more severe presentations, including significant respiratory distress, hypoxemia, failed antibiotic therapy, or for suspected complications [3,6]. Resolution of radiographic findings may lag behind the clinical presentation [3,7], and imaging is not specific for the causative organism [6]. Community-acquired pneumonia in children is defined as the presence of signs and symptoms of pneumonia in a previously healthy child caused by an infection acquired outside of the hospital [3]. Hospital-acquired pneumonia is most commonly defined as pneumonia that develops after 48 hours of hospitalization that was not present at the time of admission [10]. Hospital-acquired pneumonia is the second most common nosocomial infection after bloodstream infections, and the most common of all infections acquired in intensive care units [10]. Ventilator-associated pneumonia is a subset of hospital-acquired pneumonia that occurs in mechanically ventilated children and can affect up to 12% of ventilated children [11]. A diagnosis of hospital- acquired pneumonia is based upon a new or progressive lung infiltrate along with clinical evidence that the infiltrate is of infectious origin, which includes the new onset of fever, purulent sputum, and leukocytosis [10]. The frequency of complicated pneumonia is rising [6,12].


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. Pleural effusion or empyema, pneumothorax, lung abscess, bronchopleural fistula, and necrotizing pneumonia are rare complications of community-acquired pneumonia with an incidence rate above 13% in children hospitalized with pneumonia [9,13,14]. It is estimated that Reprint requests to: publications@acr.org Pneumonia in the Immunocompetent Child 1% of children with community-acquired pneumonia develop pleural effusions and effusions that are seen in 13% to 28% of hospitalized children [9,13,14]. Parapneumonic effusions often resolve with antibiotic therapy, but large effusions and empyemas may require percutaneous aspiration, fibrinolytics, surgical drainage, or thoracoscopy [4,15-18]. Bronchopleural fistula develops as a complication of pneumonia if lung necrosis extends to the pleura. Bronchopleural fistula is associated with higher morbidity [17,19] and can be diagnosed clinically by seeing air bubbles in the chest tube drainage [19]. Recurrent pneumonia is defined as at least two episodes of pneumonia in 1 year, or three episodes ever, with radiographic clearing of parenchymal opacities between episodes. Recurrent pneumonia occurs in 7.7% to 9% of children with community-acquired pneumonia [20]. Recurrent pneumonia can be nonlocalized (different location) or localized (same location). In the immunocompetent child, the differential considerations for nonlocalized pneumonia includes aspiration, asthma, bronchiectasis, underlying pulmonary parenchymal damage (eg, history of bronchopulmonary dysplasia), and mucociliary deficiency [13,21]. The role of imaging is to identify any underlying anatomic lung abnormality such as bronchiectasis.


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. In the immunocompetent child, the main differential for localized recurrent pneumonia is localized airway narrowing from intrinsic (eg, foreign body) or extrinsic cause (eg, mass, lymphadenopathy), focal bronchiectasis, underlying congenital lung abnormality (eg, congenital pulmonary airway malformation and sequestrations), underlying pulmonary parenchymal damage (eg, with history of bronchopulmonary dysplasia), and aspiration [13,21]. All elements are essential: 1) timing, 2) reconstructions/reformats, and 3) 3-D renderings. Standard CTs with contrast also include timing issues and recons/reformats. Only in CTA; however, is 3-D rendering a required element. This corresponds to the definitions that the CMS has applied to the Current Procedural Terminology codes. Discussion of Procedures by Variant Variant 1: Child. 3 months of age and older. Immunocompetent. Suspected uncomplicated community- acquired pneumonia in a well-appearing child who does not require hospitalization. Initial imaging. Radiography Chest Chest radiographs cannot reliably distinguish viral from bacterial community-acquired pneumonia and do not reliably distinguish among the various possible bacterial pathogens [4]. Chest radiographs performed in children with suspected acute lower respiratory tract infection lead to increased use of antibiotics in a clinic or emergency department setting; however, they have not been shown to affect hospitalization rates [23]. Some of the studies in this Cochran review have minor methodological flaws; however, this is the largest available systematic review and meta-analysis [23]. Therefore, the British Thoracic Society, the Pediatric Infectious Diseases Society, and the Infectious Diseases Society of America guidelines do not recommend routine radiographs for management of uncomplicated community-acquired pneumonia in nonhospitalized patients [3,4,24].


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. CT Chest There is no relevant literature to support the use of CT as the initial imaging study in this clinical scenario. Pneumonia in the Immunocompetent Child MRI Chest There is no relevant literature to support the use of MRI as the initial imaging study in this clinical scenario. Variant 2: Child. 3 months of age and older. Immunocompetent. Community-acquired pneumonia that does not respond to initial outpatient treatment or requires hospital admission. Initial imaging. Radiography Chest Radiographs can be used to document the presence, size, and character of parenchymal infiltrates as well as to identify complications of pneumonia that may lead to interventions beyond antimicrobial agents and supportive medical therapy [3,24]. Frontal and lateral views of the chest are appropriate when evaluating for pneumonia in children with significant respiratory distress, hypoxemia, and failed antibiotic therapy, as suggested by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America [3,24,30]. Chest radiographs should be performed in select patients with prolonged fever and cough even in the absence of tachypnea or respiratory distress [3]. CT Chest There is no relevant literature to support the use of CT as the initial imaging study in this clinical scenario. MRI Chest There is no relevant literature to support the use of MRI as the initial imaging study in this clinical scenario. Variant 3: Child. 3 months of age and older. Immunocompetent. Suspected hospital-acquired pneumonia. Initial imaging. Radiography Chest Findings of new or progressive lung opacity support the diagnosis of hospital-acquired pneumonia in the appropriate clinical circumstances [10]. However, a new lung opacity in an inpatient with fever, leukocytosis, or leukopenia and purulent secretions is neither highly sensitive nor specific for hospital-acquired pneumonia [10,11].


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. CT Chest There is no relevant literature to support the use of CT as the initial imaging study in this clinical scenario. US Chest There is no relevant literature to support the use of US as the initial imaging study in this clinical scenario. MRI Chest There is no relevant literature to support the use of MRI as the initial imaging study in this clinical scenario. Variant 4: Child. Immunocompetent. Pneumonia complicated by suspected moderate or parapneumonic effusion by chest radiograph. Next imaging study. Radiography Chest Decubitus View Decubitus radiographs may be helpful to distinguish free-flowing pleural effusions from loculated collections [31]. However, radiographs can neither identify the type of fluid present nor be used to visualize the internal characteristics of the fluid [32]. In a study of adult patients, radiographs had a sensitivity of 39% and specificity of 85% compared with CT for presence of an effusion [33]. CT Chest There is limited evidence that a noncontrast chest CT is useful in this clinical scenario. Even with intravenous (IV) contrast, it may be difficult to distinguish consolidated lung from visceral pleural enhancement [34]. Contrast- enhanced CT can also be used to quantify the amount of pleural fluid and can also demonstrate pleural thickening Pneumonia in the Immunocompetent Child and enhancement that is suggestive of empyema. CT has limited ability to characterize the internal characteristics of parapneumonic effusions (eg, fibrin strands, septations, and complex fluid) [31,34-37]. US Chest US is the gold standard imaging for quantifying the size and identifying the internal characteristics of a pleural effusion. In a study of adult patients, US had a sensitivity of 92% and specificity of 93% compared with CT for presence of an effusion [33]. US can also be used to guide drainage of pleural fluid and complicated parapneumonic effusions [16,26,34,38].


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. US is superior to chest CT for effusion characterization (eg, fibrin strands, septations, and complex fluid) [31,34-36,39]. Variant 5: Child. Immunocompetent. Pneumonia complicated by suspected bronchopleural fistula by chest radiograph. Next imaging study. CT Chest CT chest without IV contrast can detect bronchopleural fistulae [45]. A direct sign on CT of a bronchopleural fistula is a fistulous tract between the bronchus or lung and pleural space. An indirect sign of a bronchopleural fistula is the presence of air bubbles beneath the bronchial stump or suspected fistula [45]. CT chest with IV contrast can show the same findings as CT chest without IV contrast [45]. Additionally, CT chest with IV contrast can show important findings, such as necrotizing pneumonia, pulmonary abscess, and empyema that may be the underlying cause of the bronchopleural fistula [13,19,35,46-48]. There is no evidence directly comparing CT chest without IV contrast and CT chest with IV contrast in diagnosis of bronchopleural fistula. US Chest There is no relevant literature to support the use of US as the initial imaging study in this clinical scenario. MRI Chest There is no relevant literature supporting the use of MRI as the initial imaging study in this clinical scenario. Variant 6: Child. Immunocompetent. Pneumonia complicated by suspected lung abscess by chest radiograph. Next imaging study. CT Chest In the context of diagnosing necrotizing pneumonia or pulmonary abscess, contrast-enhanced CT is considered the gold standard for imaging [13,19,35,46,47]. CT chest with IV contrast can also differentiate between parenchymal and pleural processes [31]. There is no literature supporting the use of noncontrast CT in the evaluation of pulmonary abscess. US Chest There is no literature that investigates the diagnostic accuracy of US in the setting of lung abscess.


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. However, there is some literature that evaluates the effectiveness of US for differentiating between lung abscess and empyema, which is the main imaging mimic. This imaging differentiation is important because treatment for these conditions is often different, with abscess often treated with antibiotics and empyema often requiring drainage and antibiotics. In a reported series of 50 and 64 patients with lung abscesses, US was 94% to 96% sensitive and 96% to 100% specific for differentiating between lung abscess and empyema [49-51]. MRI Chest There is limited evidence that MRI has similar sensitivity for abscess compared with CT [40-42]. There are some practical considerations for MRI as an initial imaging modality because clinically unstable patients can be difficult to manage in the MRI environment. If MRI is performed, IV contrast is recommended for the evaluation of lung Pneumonia in the Immunocompetent Child abscess [41]. Additionally, certain pediatric-aged patients typically require sedation, and sedation can result in atelectasis, which can make pleural effusion characterization more challenging. Variant 7: Child. 3 months of age and older. Immunocompetent. Recurrent nonlocalized pneumonia by chest radiograph. Next imaging study. CT Chest A noncontrast chest CT can be used to evaluate for an underlying pulmonary disease, such as postinfectious bronchiectasis, bronchopulmonary dysplasia, and findings such as bullae or bronchiectasis that may indicate a mucociliary deficiency [52]. There is no relevant literature regarding the use of contrast-enhanced CT in this clinical scenario. US Chest There is no relevant literature regarding the use of US as the initial imaging study in this clinical scenario. MRI Chest There is little evidence for MRI as a screening modality for causes of recurrent localized pneumonia, but it can be used to grade known or suspected disease.


Pneumonia in the Immunocompetent Child

Pneumonia in the Immunocompetent Child. In one prospective study with 50 patients with noncystic fibrosis lung disease, MRI was equivalent to CT for grading central bronchiectasis and pulmonary consolidation but performed worse than CT for peripheral lung findings and for diagnosing emphysema and bullae [53]. There is no relevant literature regarding the use of contrast-enhanced MRI in this clinical scenario. Variant 8: Child. 3 months of age and older. Immunocompetent. Recurrent localized pneumonia by chest radiograph. Next imaging study. CT Chest CT chest without IV contrast can be used to diagnose anatomical abnormalities in the immunocompetent patient that could predispose children to recurrent localized infections, such as congenital lobar overinflation [54] or foreign bodies that could cause recurrent postobstructive pneumonia [13]. CT chest without IV contrast can also be used to evaluate underlying pulmonary disease like bronchopulmonary dysplasia [52]. Similar to CT chest without IV contrast, CT chest with IV contrast can be used to diagnose anatomical abnormalities in the immunocompetent patient that could predispose children to recurrent localized infections like congenital lobar overinflation [54], foreign bodies that could cause recurrent postobstructive pneumonia [13], and underlying pulmonary disease like bronchopulmonary dysplasia [52]. CT chest with IV contrast provides benefit over CT chest without IV contrast for diagnosing conditions such as bronchial tumors, congenital pulmonary airway malformation [54-58], pulmonary sequestration [21,54,55,59-63], and bronchopulmonary foregut malformations [54,55]. CTA Chest CTA chest with IV contrast is especially helpful for presurgical planning, identifying feeding and draining vessels in patients with suspected pulmonary sequestration, and assessing for a vascular ring that may lead to tracheal narrowing [59,63]. In most cases, CTA of the chest with IV contrast is preferred over CT chest with IV contrast.


Hematuria Child

Hematuria Child.  Introduction/Background Hematuria is the presence of red blood cells in the urine, either visible to the eye (macroscopic hematuria) or as viewed under the microscope (microscopic hematuria). Detecting blood in the urine of a child may cause alarm to patients, parents, and physicians. The next step is a thorough evaluation of the urine. Tea-colored urine and hematuria accompanied by proteinuria (>2+ by dip stick), red blood cell casts, and deformed red blood cells (best seen with phase contrast microscopy) suggest a glomerular source of hematuria (eg, glomerulonephritis) [6]. The presence of white cells and microorganisms within the urine clearly indicate the possibility of a urinary tract infection, which will direct care and imaging by a different set of criteria. Evaluation for hypercalciuria (such as a spot urine calcium/creatinine ratio) and a urine culture may be indicated. When concern for chronic kidney disease exists, basic laboratory metabolic screening in the initial evaluation should include blood urea nitrogen test, a serum creatinine test, and complete blood count with platelets. If suggested by the initial clinical workup, more advanced medical assessment for various causes of glomerulonephritis and vasculitis should be performed, and an audiogram and slit lamp examinations should be performed if there is suspicion for Alport syndrome [7-13]. Isolated hematuria (nonpainful, nontraumatic) Painful hematuria In children with post-traumatic macroscopic hematuria, the role of imaging is to identify any evidence and the extent of renal or urinary tract injury. In other children, imaging has a role in identifying the cause of hematuria and to assess the size of the kidneys as an indicator of the chronicity of the renal disease and also as an assessment Reprint requests to: publications@acr.org


Hematuria Child

Hematuria Child. Discussion of Procedures by Variant Isolated Hematuria (nonpainful, nontraumatic) Asymptomatic microscopic hematuria (usually defined as five or more red blood cells per high-powered field in either 2 or 3 of 3 consecutive urine specimens [16]) is a common entity, with an incidence estimated to be 0.25% to 1.0% in children 6 to 15 years of age [3-5,7-9,11,14,15]. CT Computed tomography (CT) is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria. US US is generally not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria. Microscopic hematuria is sometimes associated with hypercalciuria [19] and hyperuricosuria, and some authors advocate renal US to evaluate for renal calculi in these patients [14,20], although others have found little value in this technique [3]. In cases of persistent unexplained microhematuria, US may be used to evaluate for occult anatomic abnormalities (cystic renal disease, nutcracker syndrome, congenital anomalies, etc), although the yield of these examinations is low [7-9,11,14,21]. Isolated microscopic hematuria is very rarely the presenting scenario of Wilms tumor [3]. IVU Intravenous urography (IVU) is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria [14,21]. MRI Magnetic resonance imaging (MRI) is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria. VCUG VCUG is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria. Voiding Urosonography Voiding urosonography is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria. Radiography Radiography (abdomen and pelvis [KUB]) is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria without proteinuria. Variant 2: Child.


Hematuria Child

Hematuria Child. Isolated microscopic hematuria (nonpainful, nontraumatic) with proteinuria. Initial imaging. While protein and blood in the urine can be harmless in some children, patients with both microscopic hematuria and leakage of protein into the urine (with or without hypertension and edema) are more likely to have glomerular renal disease and eventually develop progressive chronic kidney disease [22]. Imaging findings are usually not specific for any underlying pathology. US Kasap et al [23] showed that glomerulonephritis is a frequent cause of increased renal cortical echogenicity in childhood. The kidneys also may be enlarged in the setting of acute glomerulonephritis. In long-standing glomerular kidney disease, the kidneys may become atrophic with altered corticomedullary differentiation. Finally, US can help assess the feasibility of percutaneous kidney biopsy and aid in preprocedural planning. CT CT is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. IVU IVU is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. MRI MRI is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. Radiography Radiography (KUB) is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. VCUG VCUG is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. Voiding Urosonography Voiding urosonography is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. IVU IVU urography is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. Arteriography Arteriography is not appropriate in the initial evaluation of isolated nonpainful, nontraumatic hematuria with proteinuria. Variant 3: Child. Isolated macroscopic hematuria (nonpainful, nontraumatic). Initial imaging.


Hematuria Child

Hematuria Child. Isolated asymptomatic macroscopic hematuria is usually due to benign processes such as hypercalcuria and IgA nephropathy [4,19,24-26]. Imaging has a role to exclude nephrolithiasis, underlying urologic abnormalities, and rarely renal or bladder tumors. Voiding Urosonography While voiding urosonography is usually not indicated in the evaluation of isolated macroscopic hematuria, and there is a paucity of literature to support its use, it is likely that voiding urosonography also can be used to assess for causes of hematuria that may be detected by VCUG. CT CT is generally not indicated as a first-line test for isolated macroscopic hematuria. However, contrast-enhanced CT has a role in evaluation of renal mass diagnosed by US, and it may be considered in children with recurrent macroscopic hematuria with negative US and extensive clinical workup in the rare setting of suspected left renal vein obstruction (ie, nutcracker syndrome) [33]. Unenhanced CT may also be used to evaluate for suspected asymptomatic nephrolithiasis as a cause of hematuria in the setting of a negative US. IVU Because the incidence of upper urinary tract urothelial neoplasia is extremely rare in children, IVU is not indicated in the initial evaluation of isolated macroscopic hematuria [14,34]. MRI MR is generally not indicated as the first-line test for isolated macroscopic hematuria. In the cases of suspected renal mass or nutcracker syndrome, MRI may be of value for further diagnosis [25,27-29,33,35-41]. Arteriography/Venography Arteriography and venography have no role in the initial evaluation of isolated macroscopic hematuria. Radiography Radiography (KUB) is generally not appropriate in the initial evaluation of isolated nonpainful, nontraumatic isolated macroscopic hematuria. Radiography may have a limited role for detecting suspected asymptomatic nephrolithiasis as a cause of hematuria. Variant 4: Child. Painful hematuria (nontraumatic). Suspected urolithiasis. Initial imaging.


Hematuria Child

Hematuria Child. In the patient with abdominal pain and hematuria, the principal differential diagnosis is urolithiasis, although tumor and ureteropelvic junction (UPJ) obstruction should also be included. In young patients with genitourinary tract stone disease, the presenting symptoms may not be as classic as in adults, which in turn leads to uncertainty about the best imaging approach [42]. Interestingly, a number of pediatric patients with urolithiasis do not have hematuria [43]. While the incidence of pediatric stone disease is considerably lower than in adults, it is still commonly seen in busy pediatric practices [44]. Affected children may have a family history of nephrolithiasis or predisposing inborn metabolic disease [45,46]. While the literature provides general suggestions and guidelines, universal agreement regarding the imaging procedure of choice in suspected urolithiasis has not been reached. CT CT There is good evidence in adults that CT is the most accurate imaging modality in the identification of stones and the quantification of stone burden, with sensitivity and specificity both well above 90% [44,47-55]. With proper techniques and newer image iterative reconstruction algorithms, the CT dose can be very low and lowered to less than that of a traditional IVU [44,56,57]. Limitations of radiography (eg, small stone size, obscuration of stones by bowel contents) and US (eg, small stone size, obscuration of a portion of the kidney by bowel gas, poor sonographic window) in children do not impair CT evaluation. CT may be particularly useful in the setting of painful hematuria, a negative kidney and bladder US examination, and high clinical suspicion for urolithiasis, particularly if detection would impact treatment. US US of the kidneys and bladder has limited sensitivity in detection of renal and ureteral stones. Palmer et al [49] reported that US found 75% of all urinary tract stones, although US found only 38% of stones within the ureter.


Hematuria Child

Hematuria Child. Similarly, Oner et al [48] showed that US correctly found stones in 78% of patients, although it only found 25% of ureteral stones. The same study by Masch et al [63] showed that US has a sensitivity of only 31% for renal stone detection if an echogenic focus, posterior acoustic shadowing, and twinkling artifact are all required findings to make a diagnosis. US is still recommended by some as a first-line screening test and, if positive, can then direct patient management [48,49,64], with the caveat that a negative US does not exclude stone disease [49]. Radiography Levine et al [47] in a study of 178 adult and pediatric patients found radiographs had a 59% sensitivity for stone detection. IVU IVU is seldom indicated in children as an initial examination, although a limited study may provide information about stone position, degree of urinary tract obstruction, and movement after initial diagnosis. MRI MRI is not appropriate in the initial evaluation of painful hematuria and suspected urolithiasis. VCUG VCUG is not appropriate in the initial evaluation of painful hematuria and suspected urolithiasis. Voiding Urosonography Voiding urosonography is not appropriate in the initial evaluation of painful hematuria and suspected urolithiasis. Arteriography Renal arteriography is not appropriate in the evaluation of painful hematuria and suspected urolithiasis. 8 If the abdominal and pelvic CT is used as the criterion standard for identifying urologic trauma in children, the microscopic urinalysis has moderate discriminatory power to predict urologic injury [77]. Patients with gross hematuria and pelvic fractures are at high risk for bladder rupture [81,82]. The conventional fluoroscopic cystogram requires moving the patient to another imaging suite.


Hematuria Child

Hematuria Child. There is evidence that CT cystography (ie, CT of the pelvis performed after retrograde distention of the urinary bladder with iodinated contrast material) is an accurate method of evaluation, with the advantage that the patient need not be moved from the CT scanner [81-83]. Images are to be obtained with a contrast-filled bladder and may be obtained after drainage, although one study in adults suggests that postvoid images may be unnecessary [81]. Multiplanar reformatted images may help in diagnosis [84]. Retrograde Urethrography Patients with blood at the urethral meatus, especially if associated with pelvic fractures or straddle injury, are at risk for urethral injury and disruption. These patients should undergo retrograde urethrography prior to bladder catheter placement [76] and may warrant a cystogram to exclude concomitant bladder injury. Radiography In general, radiography is not appropriate in the initial evaluation of traumatic macroscopic hematuria. Radiographs of the pelvis may reveal pelvic fractures and, in the setting of macroscopic hematuria, raise the possibility of bladder or urethral injury. VCUG VCUG is not appropriate for the initial evaluation of traumatic macroscopic hematuria. If there is concern for urethral injury, dedicated retrograde urethrography is a more appropriate initial imaging test. If there is concern for bladder injury, dedicated CT cystography is a more appropriate initial imaging test. Voiding Urosonography Voiding urosonography is not appropriate for the initial evaluation of traumatic macroscopic hematuria. If there is concern for urethral injury, dedicated retrograde urethrography is a more appropriate initial imaging test. If there is concern for bladder injury, dedicated CT cystography is a more appropriate initial imaging test. Arteriography Arteriography is not appropriate in the initial evaluation of traumatic macroscopic hematuria.


Hematuria Child

Hematuria Child. In the setting of hemodynamic instability and renal or pelvic artery extravasation detected by CT, arteriography may be used to guide endovascular embolization. Arteriography may also be used to guide the treatment of CT-detected post- traumatic pseudoaneurysms and arteriovenous fistulas [91,92]. MRI MRI is not appropriate in the initial evaluation of traumatic macroscopic hematuria. CT (including CT cystography) Unlike in adults, no firm consensus has been reached on the best guidelines for imaging in pediatric blunt abdominopelvic trauma and microscopic hematuria [71,79]. For adult patients with isolated microscopic hematuria without coexistent injury, there is evidence that renal imaging with CT is unlikely to disclose clinically significant findings [67,70-72]. However, the evidence for that in children is limited. A study by Nguyen and Das [71] found that 12 of 32 (37.5%) with grades 2 to 5 renal injuries did not have macroscopic hematuria; 8 had microscopic hematuria, and 4 had normal urinalyses. Thus, the authors concluded that significant renal injuries can be encountered in the setting of microscopic hematuria, and the decision to perform CT should be based on history and mechanism of injury and not urinalysis alone. Children with congenital renal abnormalities (eg, UPJ obstruction), multiorgan injury, history of deceleration injury, localized flank pain, and ecchymosis should undergo CT imaging to evaluate for renal injury, even when gross hematuria is not present. Renal injury without macroscopic hematuria can also be found in a child with falling hemoglobin or a hemodynamic instability [70,72]. Microscopic hematuria has also been combined with other clinical variables to create prediction rules for identifying children with intra-abdominal injuries following blunt abdominal trauma [95]. Patients with hematuria, even microscopic, in the setting of pelvic fractures are at risk for bladder injury. Dedicated CT cystography is an accurate method of evaluation of bladder injury [81-83].


Hematuria Child

Hematuria Child. US There is little evidence to support the use of US in the initial evaluation of traumatic microscopic hematuria. That said, renal US may be considered in cases of pediatric renal trauma that might otherwise not be imaged with CT because of low levels of hematuria to provide a screening tool for the occult vascular injury, pre-existing congenital anomaly, or the unusual major renal injury without significant hematuria. Arteriography Renal arteriography is not appropriate in the initial evaluation of traumatic microscopic hematuria. Radiography Radiography (KUB) is not appropriate in the initial evaluation of traumatic microscopic hematuria. VCUG VCUG is not appropriate in the initial evaluation of traumatic microscopic hematuria. If there is concern for urethral injury, dedicated retrograde urethrography is a more appropriate initial imaging test. If there is concern for bladder injury, dedicated CT cystography is a more appropriate initial imaging test. Voiding Urosonography Voiding urosonography is not appropriate in the initial evaluation of traumatic microscopic hematuria. If there is concern for urethral injury, dedicated retrograde urethrography is a more appropriate initial imaging test. If there is concern for bladder injury, dedicated CT cystography is a more appropriate initial imaging test. Retrograde urethrography Retrograde urethrography is not appropriate in the initial evaluation of traumatic microscopic hematuria, unless there is high clinical suspicion for urethral injury (eg, pelvic fractures or known straddle injury). IVU IVU is not appropriate in the initial evaluation of traumatic microscopic hematuria. MRI MRI is not appropriate in the initial evaluation of traumatic microscopic hematuria. Although there are references that report on studies with design limitations, 8 well-designed or good-quality studies provide good evidence.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses.  Introduction/Background Although the true prevalence of mediastinal masses is not known, a 0.9% prevalence of anterior or prevascular mediastinal masses was found among the 2,571 chest CTs of the 51% female cohort of the Framingham Heart Study, with a mean age of 59 years [1]. A 0.73% prevalence of prevascular mediastinal nodules was found on the chest CTs of a 63% male cohort (n = 56,358 participants), with a mean age of 52 years undergoing baseline low- dose chest CT for routine health surveillance [2]. A higher 4% prevalence of mediastinal masses was found on 589 CT pulmonary angiograms in a 63% female cohort with a mean age of 53 years [3]. On baseline lung cancer screening in the Early Lung Cancer Action Project, a 0.77% mediastinal mass prevalence was found in a cohort of 9,263 patients that was 51% female and had a median age of 65 years [4]. The classic imaging approach to mediastinal mass evaluation found on radiography has generally entailed a step- wise progression from chest radiography to CT [12-15] to diagnostic intervention when needed [16,17], with or without an intervening PET/CT. However, more recent recognition of the long-literature-supported ability of MRI to characterize tissue and add diagnostic specificity [18-23], prevent unnecessary biopsy and surgery [24-26], and modify and guide the approach to biopsy and surgery [27] has moved MRI into a valued position in terms of workup and triage of these lesions [28-33]. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Imaging of Mediastinal Masses OR Discussion of Procedures by Variant Variant 1: Clinically suspected mediastinal mass. Initial imaging.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. CT Chest Cross-sectional imaging can more definitively localize a lesion to a mediastinal compartment than chest radiography. Further tissue characterization of mediastinal masses beyond chest radiography is achievable by CT which can demonstrate and distinguish not only calcium and macroscopic fat but also water attenuation fluid, permitting noninvasive diagnosis of many mature teratomas [40]. Pre- and postcontrast conventional CT or dual- energy CT can show enhancing cellular components of lesions [41,42]; however, the soft-tissue contrast of CT is sometimes insufficient. For example, benign hyperattenuating thymic cysts on CT can be misinterpreted as thymomas, leading to unnecessary thymectomy [24]. Not infrequently, a mediastinal lesion is indeterminate by CT and requires further workup. CT is superior to chest radiography for detection of invasion of the mass across tissue planes, secondary to its higher contrast resolution. Invasion of adjacent large blood vessels and the chest wall is important to identify, as it is associated with a higher probability of incomplete surgical resection of primary malignant mediastinal masses [43]. In addition, it can direct surgery when still planned and, in other cases, direct toward other forms of clinical management, including neoadjuvant chemotherapy and radiation therapy. As a supplement to static assessment of tissue plane transgression, which can be difficult, dynamic CT [44] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures and confirm or exclude adherence of the mass to adjacent structures; however, dynamic MRI during free-breathing can accomplish the same task [45- 48]. MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft-tissue contrast [49-52].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. FDG-PET/CT Skull Base to Mid-Thigh Fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT offers that of conventional CT in the initial assessment of mediastinal masses [53], with the exception of its use for primary mediastinal lymphoma staging and surveillance and detection of metastatic lymphadenopathy, the latter of which is not within the scope of this topic. With regard to prevascular mediastinal masses, a negative FDG-PET/CT has been shown to be helpful in excluding malignancy; however, a positive FDG-PET/CT has little value for discrimination between benign and malignant lesions [53]. The frequent FDG-PET/CT avidity of normal and hyperplastic thymus [54] is a confounder in FDG-PET/CT assessment of the prevascular mediastinum. Benign Imaging of Mediastinal Masses thymic cysts can also be FDG-PET/CT-avid [42]. Combined use of FDG-PET/CT and dynamic contrast-enhanced (DCE) MRI has been shown to be helpful to distinguish prevascular mediastinal solid tumors from one another [55]. Higher standardized uptake values (SUVs) on FDG-PET/CT are more frequently found in high-risk thymoma, thymic carcinoma, and lymphoma than in low-risk thymoma [55-57]. Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- tissue contrast [48-52]. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, confirm or exclude adherence of the mass to adjacent structures, and observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Radiography Chest When there is a clinically suspected mediastinal mass, it is reasonable to perform a chest radiograph as an initial imaging step. Chest radiography can help localize a mass to a specific mediastinal compartment and thereby narrow the differential diagnosis [85-88]. It can also show any associated pleural, lung, and bone findings to some extent. Chest radiography offers limited assistance regarding tissue characterization of mediastinal masses, with the exception of its occasional demonstration of calcium within a lesion. US Chest There is little relevant literature to support the use of ultrasound (US) in the initial evaluation of a clinically suspected mediastinal mass. Because of the limited transthoracic sonographic window, US would not be useful to screen for a clinically suspected mediastinal mass. Transthoracic US can be used to evaluate mediastinal masses, when accessible to the sonographic window, delineating their size, location, cystic versus solid nature, relationship to important vascular structures, and vascularity, with some diagnostic potential [89]. Endoscopic US can similarly evaluate mediastinal masses when encompassed in the sonographic window [90]. The tissue characterization capability of US is inferior to MRI but not to CT. Image-Guided Transthoracic Needle Biopsy Image-guided transthoracic needle biopsy is not a form of initial imaging. Variant 2: Indeterminate mediastinal mass on radiography. Next imaging study. CT Chest Cross-sectional imaging, by its very nature, can more definitively localize a lesion to a mediastinal compartment than chest radiography. Further tissue characterization of mediastinal masses beyond chest radiography is achievable by CT, which can demonstrate and distinguish not only calcium and macroscopic fat but also water attenuation fluid, thus permitting noninvasive diagnosis of many mature teratomas [40]. Pre- and postcontrast Imaging of Mediastinal Masses


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. conventional CT or dual-energy CT can show enhancing, cellular components of lesions [41,42]; however, the soft- tissue contrast of CT is sometimes insufficient. For example, benign hyperattenuating thymic cysts on CT can be misinterpreted as thymomas, leading to unnecessary thymectomy [24]. Not infrequently, a mediastinal lesion is indeterminate by CT and requires further workup. CT is superior to chest radiography for detection of invasion of the mass across tissue planes, secondary to its higher contrast resolution. Invasion of adjacent large blood vessels and the chest wall is important to identify, as it is associated with a higher probability of incomplete surgical resection of primary malignant mediastinal masses [43]. In addition, it can direct surgery when still planned, and in other cases, direct toward other forms of clinical management, including neoadjuvant chemotherapy and radiation therapy. As a supplement to static assessment of tissue plane transgression, which can be difficult, dynamic CT [44] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures and to confirm or exclude adherence of the mass to adjacent structures; however, dynamic MRI during free-breathing can accomplish the same task [45- 48]. MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft-tissue contrast [49-52]. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT offers limited additional value beyond that of conventional CT in the assessment of mediastinal masses [53], with the exception of its use for primary mediastinal lymphoma staging and surveillance and detection of metastatic lymphadenopathy, the latter of which is not within the scope of this topic.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. FDG-PET/CT has become the standard for staging and assessment of treatment response for lymphomas that are FDG-PET-avid at baseline or at the time recurrence [91-97]. A caveat is that although a negative surveillance FDG-PET/CT is reassuring of a good outcome, a positive FDG-PET/CT can be misleading, as it does not always implicate residual or recurrent lymphoma [96,98]. CT and MRI can be used for surveillance of lymphadenopathy when the metabolic activity of the lymphadenopathy is not of interest and when allowed within a clinical protocol. With regard to prevascular mediastinal masses, a negative FDG-PET/CT has been shown to be helpful in excluding malignancy; however, a positive FDG-PET/CT has little value for discrimination between benign and malignant lesions [53]. The frequent FDG-PET/CT avidity of normal and hyperplastic thymus [54] is a confounder in FDG-PET/CT assessment of the prevascular mediastinum. Benign thymic cysts can also be FDG-PET/CT-avid [42]. Combined use of FDG-PET/CT and DCE MRI has been shown to be helpful to distinguish prevascular mediastinal solid tumors from one another [55]. Higher SUVs on FDG-PET/CT are more frequently found in high-risk thymoma, thymic carcinoma, and lymphoma than in low-risk thymoma [55-57]. FDG-PET/CT appears to be more sensitive than CT alone for detection of mediastinal recurrence of thymoma [99]. Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- Imaging of Mediastinal Masses tissue contrast [48-52].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, confirm or exclude adherence of the mass to adjacent structures, and observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test. US Chest Unless a mediastinal mass found on chest radiography is deemed fully accessible by transthoracic US, there is little relevant literature to support its use as the next step. Transthoracic US can be used to evaluate mediastinal masses, when accessible to the sonographic window, delineating their size, location, cystic versus solid nature, relationship to important vascular structures, and vascularity, with some diagnostic potential [89]. Endoscopic US can similarly evaluate mediastinal masses when encompassed in the sonographic window [90]. The tissue characterization capability of US is inferior to MRI but not to CT. Image-Guided Transthoracic Needle Biopsy Image-guided transthoracic needle biopsy would seldom be performed without a preceding cross-sectional imaging study. Variant 3: Indeterminate mediastinal mass on CT. Next imaging study. FDG-PET/CT Skull Base to Mid-Thigh FDG-PET/CT offers limited additional value beyond that of conventional CT in the assessment of mediastinal masses [53], with the exception of its use for primary mediastinal lymphoma staging and surveillance and detection of metastatic lymphadenopathy, the latter of which is not within the scope of this topic. FDG-PET/CT has become the standard for staging and assessment of treatment response for lymphomas that are FDG-PET-avid at baseline or at the time recurrence [91-97].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. A caveat is that although a negative surveillance FDG-PET/CT is reassuring of a good outcome, a positive FDG-PET/CT can be misleading, as it does not always implicate residual or recurrent lymphoma [96,98]. CT and MRI can be used for surveillance of lymphadenopathy, when the metabolic activity of the lymphadenopathy is not of interest and when allowed within a clinical protocol. With regard to prevascular mediastinal masses, a negative FDG-PET/CT has been shown to be helpful in excluding malignancy; however, a positive FDG-PET/CT has little value for discrimination between benign and malignant lesions [53]. The frequent FDG-PET/CT avidity of normal and hyperplastic thymus [54] is a confounder in FDG-PET/CT assessment of the prevascular mediastinum. Benign thymic cysts can also be FDG-PET/CT-avid [42]. Combined use of FDG-PET/CT and DCE MRI has been shown to be helpful to distinguish prevascular mediastinal solid tumors from one another [55]. Higher SUVs on FDG-PET/CT are more frequently found in high-risk thymoma, thymic carcinoma, and lymphoma than in low-risk thymoma [55-57]. FDG-PET/CT appears to be more sensitive than CT alone for detection of mediastinal recurrence of thymoma [99]. Imaging of Mediastinal Masses Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- tissue contrast [48-52]. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, confirm or exclude adherence of the mass to adjacent structures, and observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. US Chest There is little relevant literature to support US of an indeterminate mediastinal mass on CT. Transthoracic US can be used to evaluate mediastinal masses when accessible to the sonographic window, delineating their size, location, cystic versus solid nature, relationship to important vascular structures, and vascularity, with some diagnostic potential [89]. Endoscopic US can similarly evaluate mediastinal masses when encompassed in the sonographic window [90]. The tissue characterization capability of US is inferior to MRI but not to CT. Image-Guided Transthoracic Needle Biopsy CT-guided percutaneous needle and core biopsy of accessible mediastinal masses has been shown to be safe and to have a good diagnostic yield, with core biopsy more effective than fine-needle aspiration. Biopsy was more frequently diagnostic for TETs than for lymphoma [101-104]. A retrospective study of 293 consecutive CT-guided mediastinal biopsies performed in 285 patients showed an overall diagnostic yield of 87% for mediastinal masses with a mean size of 5.3 cm and 57% for residual masses at the site of treated lymphoma [101]. Another retrospective study of 52 patients reported a 77% diagnostic yield for needle biopsy of mediastinal masses with a mean size of 6.9 cm [102]. When the distinction of TETs from lymphoma cannot be definitively made by imaging, image-guided biopsy has a role. PET/CT guidance for biopsy reportedly yields no diagnostic advantage [104]. When the lesion is visible within the sonographic window, transthoracic US-guided biopsy of mediastinal masses is also feasible, with color Doppler and contrast-enhanced sonographic techniques providing additional value [105-108] and with core biopsy more effective than fine-needle aspiration. Endoscopic biopsy of mediastinal masses is also feasible and effective, although not in the purview of this topic [109].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. DWI MR may be helpful in directing CT-guided biopsy toward sites of higher cellularity and diagnostic yield [110], as may DCE MRI with postprocessed subtraction. MR- guided percutaneous needle biopsy has also been shown to be safe and diagnostically accurate [111]. Radiography Chest After cross-sectional imaging has been performed for mediastinal mass evaluation, there is seldom a role for chest radiography. Variant 4: Indeterminate mediastinal mass on FDG-PET/CT. Next imaging study. CT Chest After FDG-PET/CT has been performed for mediastinal mass evaluation, there is seldom a role for chest CT. Imaging of Mediastinal Masses to CT for surveillance of treated TETs, although if there is insurmountable susceptibility artifact from sternotomy wires using fast spin-echo and other MRI techniques, alternating MRI and CT follow-up can be performed [100]. Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- tissue contrast [48-52]. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, confirm or exclude adherence of the mass to adjacent structures, and observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test. US Chest There is little relevant literature to support US of an indeterminate mediastinal mass on FDG-PET/CT. Transthoracic US can be used to evaluate mediastinal masses when accessible to the sonographic window, delineating their size, location, cystic versus solid nature, relationship to important vascular structures, and vascularity, with some diagnostic potential [89].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Endoscopic US can similarly evaluate mediastinal masses when encompassed in the sonographic window [90]. The tissue characterization capability of US is inferior to MRI but not to CT. Image-Guided Transthoracic Needle Biopsy CT-guided percutaneous needle and core biopsy of accessible mediastinal masses has been shown to be safe and to have a good diagnostic yield, with core biopsy more effective than fine-needle aspiration. Biopsy was more frequently diagnostic for TETs than for lymphoma [101-104]. A retrospective study of 293 consecutive CT-guided mediastinal biopsies performed in 285 patients showed an overall diagnostic yield of 87% for mediastinal masses with a mean size of 5.3 cm and 57% for residual masses at the site of treated lymphoma [101]. Another retrospective study of 52 patients reported a 77% diagnostic yield for needle biopsy of mediastinal masses with a mean size of 6.9 cm [102]. When the distinction of TETs from lymphoma cannot be definitively made by imaging, image-guided biopsy has a role. PET/CT guidance for biopsy reportedly yields no diagnostic advantage [104]. When the lesion is visible within the sonographic window, transthoracic US-guided biopsy of mediastinal masses is also feasible, with color Doppler and contrast-enhanced sonographic techniques providing additional value [105-108], and with core biopsy more effective than fine-needle aspiration. Endoscopic biopsy of mediastinal masses is also feasible and effective, although not in the purview of this topic [109]. DWI MR may be helpful in directing CT-guided biopsy toward sites of higher cellularity and diagnostic yield [110], as may DCE MRI with postprocessed subtraction. MR- guided percutaneous needle biopsy has also been shown to be safe and diagnostically accurate [111]. Radiography Chest After cross-sectional imaging has been performed for mediastinal mass evaluation, there is seldom a role for chest radiography.


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. FDG-PET/CT Skull Base to Mid-Thigh Unless the degree of metabolic activity of a mediastinal mass is sought and deemed capable of changing clinical management, FDG-PET/CT would be unlikely to add diagnostic information regarding a mediastinal mass beyond that offered by MRI. FDG-PET/CT offers limited additional value beyond that of conventional CT and MRI in the assessment of mediastinal masses [53], with the exception of its use for primary mediastinal lymphoma staging and surveillance and detection of metastatic lymphadenopathy, the latter of which is not within the scope of this topic. FDG-PET/CT has become the standard for staging and assessment of treatment response for lymphomas that are FDG-PET-avid at baseline or at the time recurrence [91-97]. A caveat is that although a negative surveillance FDG- PET/CT is reassuring of a good outcome, a positive FDG-PET/CT can be misleading, as it does not always implicate Imaging of Mediastinal Masses residual or recurrent lymphoma [96,98]. With regard to prevascular mediastinal masses, a negative FDG-PET/CT has been shown to be helpful in excluding malignancy; however, a positive FDG-PET/CT has little value for discrimination between benign and malignant lesions [53]. The frequent FDG-PET/CT avidity of normal and hyperplastic thymus [54] is a confounder in FDG-PET/CT assessment of the prevascular mediastinum. Benign thymic cysts can also be FDG-PET/CT-avid [42]. Combined use of FDG-PET/CT and DCE MRI has been shown to be helpful to distinguish prevascular mediastinal solid tumors from one another [55]. Higher SUVs on FDG- PET/CT are more frequently found in high-risk thymoma, thymic carcinoma, and lymphoma than in low-risk thymoma [55-57]. FDG-PET/CT appears to be more sensitive than CT alone for detection of mediastinal recurrence of thymoma [99].


Imaging of Mediastinal Masses

Imaging of Mediastinal Masses. Cross-sectional imaging by MRI remains superior to CT for detection of invasion of the mass across tissue planes, including the chest wall and diaphragm, and involvement of neurovascular structures, secondary to its higher soft- tissue contrast [48-52]. As a supplement to static assessment of tissue plane transgression, dynamic MRI [45-48] during free-breathing or cinematic cardiac gating can be performed to assess movement of the mass relative to adjacent structures, to confirm or exclude adherence of the mass to adjacent structures, and to observe diaphragmatic motion in real time [80-84]; paradoxical motion or lack of motion can indicate phrenic nerve involvement by the mediastinal mass, without the need to perform a subsequent fluoroscopic sniff test. US Chest Transthoracic US is unlikely to offer additional information regarding mediastinal mass characterization beyond that of MRI. Image-Guided Transthoracic Needle Biopsy CT-guided percutaneous needle and core biopsy of accessible mediastinal masses has been shown to be safe and to have a good diagnostic yield, with core biopsy more effective than fine-needle aspiration. Biopsy was more frequently diagnostic for TETs than for lymphoma [101-104]. A retrospective study of 293 consecutive CT-guided mediastinal biopsies performed in 285 patients showed an overall diagnostic yield of 87% for mediastinal masses with a mean size of 5.3 cm and 57% for residual masses at the site of treated lymphoma [101]. Another retrospective study of 52 patients reported a 77% diagnostic yield for needle biopsy of mediastinal masses with a mean size of 6.9 cm [102]. When the distinction of TETs from lymphoma cannot be definitively made by imaging, image-guided Imaging of Mediastinal Masses biopsy has a role. PET/CT guidance for biopsy reportedly yields no diagnostic advantage [104].


Breast Pain

Breast Pain.  Introduction/Background Breast pain is a common complaint for which patients seek medical attention, with a prevalence of up to 70% to 80% [1-5]. However, breast pain or tenderness is rarely found to result from cancer when not associated with a palpable mass or other suspicious clinical finding. Studies show that the incidence of breast cancer in patients with breast pain as their only symptom is 0% to 3.0% [6-13]. Some authors have found no increased risk of malignancy in patients with breast pain, while others have even found a decreased risk when compared to those without pain [14,15]. Breast pain should be triaged into one of two categories: pain that is not suspicious for associated malignancy versus pain that may be clinically significant. Clinically insignificant pain is cyclical (temporally associated with the menstrual cycle) or nonfocal/diffuse, either unilateral or bilateral. This type of pain is not associated with malignancy [8]. Benign causes of breast pain are numerous and include hormonal variations, larger cup size, ill- fitting or unsupportive bra, lower levels of fitness or activity, fibromyalgia, cysts, periductal mastitis, stretching of Cooper ligaments, fat necrosis, surgery, Mondor disease, diabetic mastopathy, duct ectasia, musculoskeletal disease, referred nerve root pain from degenerative spinal changes, herpes zoster, heart disease, biliary pain, and peptic ulcer [3,5,16-26]. Clinically significant pain, while still overwhelmingly due to a benign etiology, has occasionally been found to be associated with malignancy [8,9,11,12]. When malignancy related, pain tends to be well localized and persistent [27]. Therefore, breast pain is considered potentially clinically significant when it persists and is focal, defined as involving <25% of the breast and axillary tissue. Special Imaging C onsiderations Special Imaging Considerations Digital breast tomosynthesis (DBT) can address some of the limitations encountered with standard mammographic views.


Breast Pain

Breast Pain. In addition to planar images, DBT allows for creation and viewing of thin-section reconstructed images that may decrease the lesion-masking effect of overlapping normal tissue, and reveal the true nature of potential false positive findings without the need for recall. While there is no specific literature assessing its use in evaluation of breast pain, DBT can be useful in the diagnostic setting, improving lesion characterization [28-31] in noncalcified lesions, when compared to conventional mammographic workup. The following discussion is for cases of isolated breast pain without other symptoms. In cases where the pain is associated with other symptoms, for example, lump or nipple discharge, pain should be considered a secondary symptom and the workup should follow the ACR Appropriateness Criteria recommendations for that additional symptom. aEmory University Hospital, Atlanta, Georgia. bPanel Vice-Chair, NYU Clinical Cancer Center, New York, New York. cGeorge Washington University Hospital, Washington, District of Columbia. dRoper St. Francis Physician Partners Breast Surgery, Charleston, South Carolina; American College of Surgeons. eNorthwestern University Feinberg School of Medicine, Chicago, Illinois; American College of Physicians. fNew York University School of Medicine, New York, New York. gThe University of Texas MD Anderson Cancer Center, Houston, Texas. hNew York University School of Medicine, New York, New York. iAlpert Medical School of Brown University, Providence, Rhode Island. jBeth Israel Deaconess Medical Center, Boston, Massachusetts. kH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. lBeth Israel Deaconess Medical Center, Boston, Massachusetts. mWomen and Infants Hospital, Providence, Rhode Island; American Congress of Obstetricians and Gynecologists. nMecklenburg Radiology Associates, Charlotte, North Carolina. oDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York.


Breast Pain

Breast Pain. pPerelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania. qPanel Chair, Emory University Hospital, Atlanta, Georgia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document. Reprint requests to: publications@acr.org Breast Pain Discussion of Procedures by Variant Discussion of Procedures by Variant Variant 1: Female with clinically insignificant breast pain (nonfocal [greater than one quadrant], diffuse, or cyclical) without other suspicious clinical finding. Any age. Initial imaging. Mammography There is very limited literature specifically evaluating the use of imaging in patients with nonfocal or cyclical breast pain. In a retrospective review of 236 patients with breast pain, authors found no mammographic or sonographic correlate in the 10 patients who had cyclical breast pain [8]. Given that this type of breast pain is not associated with malignancy, the use of mammography beyond the usual screening recommendations is not expected to result in increased cancer detection. Some argue that imaging may be helpful in order to reassure the patient of the absence of malignancy [14,32]. One study found patients with breast pain reported a decreased level of pain and anxiety after sonography [33]. However, the assumption that negative imaging reassures the patient or clinician is challenged by a retrospective cohort study that found that imaging women with breast pain at the time of the initial clinical visit increased the odds of subsequent clinical visits [34]. DBT DBT There is no relevant literature regarding the specific use of DBT in the evaluation of nonfocal or cyclical breast pain.


Breast Pain

Breast Pain. US Breast There is scant literature specifically evaluating the use of ultrasound (US) imaging in patients with nonfocal or cyclical breast pain. In a retrospective review of 236 patients with breast pain, authors found no mammographic or sonographic correlate in the 10 patients who had cyclical breast pain [8]. A prospective study of 76 patients younger than age 30 who presented with cyclical breast pain as their only complaint and underwent US found no malignancy [35]. A limitation of this study was the lack of follow-up. MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of nonfocal or cyclical breast pain. Sestamibi MBI There is no relevant literature regarding the use of molecular breast imaging (MBI) in the evaluation of nonfocal or cyclical breast pain. Variant 2: Female with clinically significant breast pain (focal and noncyclical). Age less than 30. Initial imaging. Mammography There is little in the literature specifically evaluating the use of mammography in patients less than 30 years of age who have focal and noncyclical breast pain. Because of greater breast density, mammography is known to be less accurate than US in evaluating symptomatic women less than 30 years of age [36]. DBT DBT There is no relevant literature regarding the use of DBT in the evaluation of focal and noncyclical breast pain in patients less than 30 years of age. US Breast US Breast The literature regarding the efficacy of US in evaluation of breast pain is somewhat limited by lack of age-group- specific results. Most authors have found that cancer is a rare cause of focal, clinically significant breast pain [12,35], and that US has a high negative predictive value (NPV), sensitivity, and specificity for evaluation of breast pain.


Breast Pain

Breast Pain. Leddy et al [11] performed a retrospective review of 257 patients who underwent US after presenting with focal breast pain and found cancer in 1.2% of patients, with a sensitivity of 100%, specificity of 92.5%, positive predictive value of 13.6%, and NPV of 100%. Loving et al [37] found a 100% NPV and sensitivity in their retrospective study of 830 patients less than 30 years of age with focal breast signs or symptoms (not limited to but including breast pain). Some authors suggest that, despite the low incidence of malignancy, US may be useful in that it could potentially find treatable causes of breast pain, such as cysts [9]. On the other hand, a prospective, observational follow-up study of 987 patients with breast pain alone found benign findings in 8.6% of cases, which consisted mostly of Breast Pain small cysts [14]. The authors argued that in the absence of a palpable abnormality, any cyst that may be found by US would be unlikely to be large enough to cause pain or benefit from aspiration. MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of focal and noncyclical breast pain. Sestamibi MBI There is no relevant literature regarding the use of MBI in the evaluation of focal and noncyclical breast pain. Variant 3: Female with clinically significant breast pain (focal and noncyclical). Age 30 to 39. Initial imaging. Mammography Though the incidence is low, mammography may be used to exclude malignancy in cases of focal and noncyclical breast pain. Mammography was found to have a high sensitivity (100%) and NPV (100%) in a retrospective review of 206 patients with focal breast pain [11]. While this study found specificity to be slightly lower at 87.6%, another retrospective study of focal, noncyclical pain calculated a specificity of mammography of 97% for nondense breasts and 96% for dense breasts [9].


Breast Pain

Breast Pain. Additionally, Tumyan et al [38] in a retrospective study of mammography in combination with US found a NPV of 100%, though the study was limited by a significant number of patients being lost to follow-up. DBT DBT While there is no literature specifically evaluating the use of DBT in the workup of focal and noncyclical breast pain, DBT can be useful in the diagnostic setting. It is known to improve lesion characterization in noncalcified lesions and cancer detection when compared to conventional mammographic workup [28-30,39-41]. US Breast While there are few studies evaluating US independently of mammography in the setting of focal and noncyclical breast pain, the existing literature suggests that US may be useful to exclude malignancy in these cases. A retrospective review of 110 cases of focal breast pain evaluated by US found no imaging abnormality in 85 cases (77.3%) [12] and there were no malignancies. In 15 cases (13.6%), cysts were identified, and 3 patients (2.7%) had solid masses, all of which were benign. Fluid collections and edema were seen in the remaining cases. Several studies have evaluated the usefulness of US in addition to mammography in cases of focal, noncyclical breast pain and concluded that in the setting of a negative mammogram, US may not be indicated, especially in patients with nondense breasts. A retrospective study of 206 patients with focal breast pain as their only symptom evaluated with US after a mammogram found that US resulted in 8 additional biopsies and 14 additional 6-month follow-up examinations without detecting any additional cancers [11]. Another retrospective study found 76 imaging abnormalities in 413 cases of focal pain, with 46 (61%) seen on US alone, for a specificity of 82%. While there were no malignancies, US found a benign lesion in 40 of 56 cases in which mammography was negative in patients with dense breasts and found a benign lesion in 6 of 20 cases with a negative mammogram and nondense breasts.


Breast Pain

Breast Pain. The specificity of US was 95% for nondense breasts and 87% for dense breasts [9]. Some authors suggest that, despite the low incidence of malignancy, US may be useful in that it could potentially find treatable causes of breast pain, such as cysts [9]. On the other hand, a prospective, observational follow-up study of 987 patients with breast pain alone found benign findings in 8.6% of cases, which consisted mostly of small cysts [14]. The authors argued that in the absence of a palpable abnormality, any cyst that may be found by US would be unlikely to be large enough to cause pain or benefit from aspiration. MRI Breast MRI Breast There is no relevant literature regarding the use of MRI in the evaluation of focal and noncyclical breast pain. Sestamibi MBI Sestamibi MBI There is no relevant literature regarding the use of MBI in the evaluation of focal and noncyclical breast pain. Variant 4: Female with clinically significant breast pain (focal and noncyclical). Age greater than or equal to 40. Initial imaging. Mammography Though the incidence is low, mammography may be used to exclude malignancy in cases of focal and noncyclical breast pain. Mammography was found to have a high sensitivity (100%) and NPV (100%) in a retrospective review of 206 patients with focal breast pain [11]. While this study found specificity to be slightly lower at Breast Pain 87.6%, another retrospective study of focal, noncyclical pain calculated a specificity of mammography of 97% for nondense breasts and 96% for dense breasts [9]. Additionally, Tumyan et al [38] in a retrospective study of mammography in combination with US found a NPV of 100%, though the study was limited by a significant number of patients being lost to follow-up. A mammogram should be obtained if the patient has not undergone mammography within the last 3 to 6 months.


Breast Pain

Breast Pain. DBT DBT While there is no literature specifically evaluating the use of DBT in the workup of focal and noncyclical breast pain, DBT can be useful in the diagnostic setting and is known to improve lesion characterization in noncalcified lesions when compared to conventional mammographic workup [28-30]. US Breast While there are few studies evaluating US independently of mammography in the setting of focal and noncyclical breast pain, the existing literature suggests that US may be useful to exclude malignancy in these cases. A retrospective review of 110 cases of focal breast pain evaluated by US found no imaging abnormality in 85 cases (77.3%) [12], and there were no malignancies. In 15 cases (13.6%), cysts were identified, and of those, 3 patients (2.7%) had solid masses, all of which were benign. Fluid collections and edema were seen in the remaining cases. Several studies have evaluated the usefulness of US in addition to mammography in cases of focal, noncyclical breast pain and concluded that in the setting of a negative mammogram, US may not be indicated, especially in patients with nondense breasts. A retrospective study of 206 patients with focal breast pain as their only symptom evaluated with US after a mammogram, found that US resulted in 8 additional biopsies and 14 additional 6-month follow-up examinations without detecting any additional cancers [11]. Another retrospective study found 76 imaging abnormalities in 413 cases of focal pain, with 46 (61%) seen on US alone, for a specificity of 82%. While there were no malignancies, US found a benign lesion in 40 of 56 cases in which mammography was negative in patients with dense breasts and found a benign lesion in 6 of 20 cases with a negative mammogram and nondense breasts. The specificity of US was 95% for nondense breasts and 87% for dense breasts [9]. Some authors suggest that, despite the low incidence of malignancy, US may be useful in that it could potentially find treatable causes of breast pain, such as cysts [9].


Abnormal Liver Function Tests

Abnormal Liver Function Tests.  Introduction/Background Liver function tests are often obtained as part of standard laboratory panels in asymptomatic and symptomatic patients. Alteration in the biochemical markers of hepatocyte damage or bile flow indicate hepatobiliary insult rather than a measurement of liver function. Routine liver chemistries include alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. On the contrary, albumin and prothrombin time are actual markers of hepatocellular synthetic function. The severity of abnormal aminotransferase can be classified as 1) mild: <5 times the upper reference limit, 2) moderate: 5 to 10 times the upper reference limit, or 3) severe: >10 times the upper reference limit. Moderate and severe are discussed collectively as significant clinical overlap exists between these 2 categories. Pathologically increased levels of ALP may occur in cholestatic liver disease, which can show elevated ALP with or without elevated bilirubin. Cholestasis can be due to obstruction of biliary outflow or impairment in bilirubin uptake. If abnormal ALP levels are seen without impairment of other liver enzymes, the etiology is suspected to be cholestatic in origin. If ALP is elevated in isolation, a confirmation with gamma-glutamyl transpeptidase (GGT) or fractionated ALP isoenzyme helps to differentiate hepatic from nonhepatic etiologies, such as bone disease. GGT can be elevated in nonhepatic diseases such as myocardial infarction, renal failure, diabetes, pulmonary, and pancreatic disorders; therefore, it is not used in isolation to assess for liver disease when other liver function tests are normal [1]. Bilirubin is produced by the breakdown of heme. Following conjugation within the liver to increase water solubility, bilirubin is excreted into bile. Conjugated (direct) bilirubin is rapidly excreted in the alimentary tract; thus, bilirubin amounts are negligible in serum in healthy individuals.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. A rise in levels of conjugated bilirubin in the serum is an indicator of impaired liver excretion. Conjugated hyperbilirubinemia can occur because of impaired bilirubin transport into the intrahepatic bile ducts or downstream obstruction of the biliary tract from intrinsic or extrinsic causes. aUniversity of Arizona, Banner University Medical Center, Tucson, Arizona. bUniversity of Alabama Medical Center, Birmingham, Alabama. cPanel Chair, Johns Hopkins University School of Medicine, Baltimore, Maryland. dDuke University Medical Center, Durham, North Carolina. eOregon Health & Science University, Portland, Oregon. fPerelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania; American Association for the Study of Liver Diseases. gUniversity of Alabama at Birmingham, Birmingham, Alabama, Primary care physician. hUniversity of Connecticut, Farmington, Connecticut. iUniversity of Alabama at Birmingham Medical Center, Birmingham, Alabama. jJohns Hopkins Bayview Medical Center, Baltimore, Maryland; Commission on Nuclear Medicine and Molecular Imaging. kNorthShore University HealthSystem, Evanston, Illinois. lNew York University Langone Medical Center, New York, New York. mUniversity of Cincinnati Medical Center, Cincinnati, Ohio. nCleveland Clinic, Cleveland, Ohio; American College of Physicians, Hospital Medicine. oJohns Hopkins Hospital, Baltimore, Maryland. pSpecialty Chair, Virginia Commonwealth University Medical Center, Richmond, Virginia. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Abnormal Liver Function Tests


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Serum unconjugated (indirect) bilirubin can be increased in hemolysis or Gilbert syndrome, which is diagnosed when unconjugated hyperbilirubinemia is the only abnormal liver function test and conjugated bilirubin and complete blood count are normal. OR Discussion of Procedures by Variant Variant 1: Abnormal liver function tests. Hepatocellular predominance with mild aminotransferase increase. Initial imaging. Hepatocellular predominant liver chemistry is seen when aminotransferases are elevated much higher than ALP (cholestatic-pattern). Hepatocellular injury causes the release of ALT and AST in serum. Increase in ALT (mild or moderate to severe) is directly linked to hepatocyte injury. In addition to fatty liver disease, other causes of rising ALT include acute or chronic viral hepatitis, acute Budd-Chiari syndrome, ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins, autoimmune, alpha1-antitrypsin deficiency, and Wilson disease. AST levels are also increased in fatty liver disease and cirrhosis. However, if the aminotransferase rise is predominantly AST, nonhepatic causes (hemolysis, myopathy, thyroid disease, exercise) should also be considered. Common causes of mild increases in aminotransferases are nonalcoholic fatty liver disease (NAFLD) and alcohol- induced liver disease; uncommon causes include drug-induced liver injury, hepatitis B, hepatitis C, and hereditary hemochromatosis. Rare causes are alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. The 2 most common causes of fatty liver disease are NAFLD and alcohol-induced steatosis/steatohepatitis. Excessive intake of alcohol results in alcohol-induced fatty liver disease. The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease and <1 in metabolic disease-related fatty liver. Alcohol-induced liver disease is caused by excess alcohol consumption, whereas the nonalcoholic variant is related to insulin resistance and the metabolic syndrome.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. NAFLD is the most common liver disease in first world countries, with a prevalence of 20% to 30% in the general population; however, this increases to 70% with obesity and 90% with diabetes mellitus. NAFLD is a spectrum of fat deposition and hepatic inflammation followed by fibrosis due to metabolic insults. Simple hepatic steatosis can be seen in 70% to 75% of cases without cellular insult. Nonalcoholic steatohepatitis (NASH) can be found in 25% to 30% of cases with hepatocyte injury and inflammation due to lipid; these entities, simple hepatic steatosis and NASH, can coexist. Progressive insults with inflammation can result in fibrosis leading to cirrhosis and hepatocellular carcinoma [4,5]. US Abdomen Ultrasound (US) is useful as a first-line investigation tool for mild increase in liver enzymes. US has been used world-wide to screen for both alcohol-induced liver disease and NAFLD. US has the benefit of being noninvasive and is an accurate method to detect steatosis [6,7]. US can be successfully diagnose hepatic lipid content of >33% but can be unreliable with mild fatty infiltration, with an 84.8% sensitivity and a 93.6% specificity with US in moderate and sever hepatic fat deposition (defined as >30% by histology) [8,9]. Both sensitivity and specificity declined to 53.3% to 65% and 77% to 81.2%, respectively, when mild steatosis was included with moderate and severe degrees of steatosis. It is noteworthy that sonographic specificity further deteriorates with confounding factors such as inflammation or fibrosis within the liver parenchyma [8,10,11]. Estimation of hepatic steatosis on conventional US is subjective and challenged by inter- and intraobserver variability. Normal liver shows echogenicity similar to or just higher than normal renal cortex. Fatty infiltration Abnormal Liver Function Tests increases the echogenicity of the liver parenchyma.


Abnormal Liver Function Tests

Abnormal Liver Function Tests. Hepatic steatosis can be graded as mild, moderate, and severe: 1) mild: mild diffuse increase in liver echogenicity and clear definition of the diaphragm and intrahepatic vessel walls; 2) moderate: mild diffuse increase in liver echogenicity and obscuration of the diaphragm and intrahepatic vessel walls; and 3) severe: marked increase in liver echogenicity leading to nonvisualization of diaphragm and intrahepatic vessel walls [12]. Instead of qualitative assessment of liver and kidney parenchyma, quantitative grading can be done to obtain hepatorenal index. Mancini et al and Webb et al have shown an excellent correlation of mild steatosis quantified on hepatorenal index to fat fraction on MR spectroscopy and liver biopsy, with the area under the curve measuring up to 99.2% and 99.6%, respectively. The hepatorenal index is independent of confounding factors including high body mass index, inflammation, or fibrosis [13,14]. US Abdomen with IV Contrast Cocciolillo et al [15] showed hepatic blood flow derangements in the portal vein and liver parenchyma using contrast-enhanced US (CEUS). The percentage of maximal contrast activity, regional blood volume (cubic centimeters) and regional blood flow (cubic centimeters per second) was reduced in NASH and NAFLD compared with controls. CEUS can be added to conventional US and US shear wave elastography; however, there is no evidence in the current literature to support the use of CEUS in this clinical scenario. US Duplex Doppler Abdomen Duplex Doppler may be added as adjunct to conventional US B-mode images. The normal triphasic flow pattern in right hepatic vein flow may become monophasic following intrahepatic fat deposition or, occasionally, by inflammatory or fibrotic changes [16]. Tarzamni et al [17] found an increase in the arterial resistive index and no change in pulsatility index and portal venous velocity in patients with NAFLD with favorable response to treatment.