Most breast cancer patients with intrathoracic metastases are asymptomatic, the exception being those with significant pleural effusions. Therefore, unless pleural, parenchymal, or nodal metastases are demonstrated at initial staging, thoracic metastases are most commonly found at the time of follow-up imaging. A significant number are found on chest x-rays done for other reasons. Isolated involvement of the lung or pleural space occurs in 15% to 25% of women with metastatic breast cancer.¹

Pulmonary metastases are typically peripheral,² and, if large enough, may be discovered on preoperative chest radiographs. Because of its low cost, chest radiography may be a reasonable choice as a baseline study or in follow-up; however, the extremely low yield, false-positive results, inferior sensitivity compared with CT, and lack of data supporting an outcome benefit limit routine use in follow-up.

CT is the preferred modality for investigation of thoracic metastases. CT has proven efficacy for detecting local, regional, and distant disease. Normal-sized internal mammary nodes are not visualized on CT, so a patient in whom CT identifies a node or nodes larger than 6 mm is at risk for malignant involvement.³ Because of the recognized problem of relying on size only to diagnose disease, positron emission tomography (PET)/CT is presently considered the modality of choice for assessing internal mammary nodes (Figure 1). In women who die from disseminated breast cancer, intrathoracic nodal metastases may occur in more than 70% of patients.⁴ As with internal mammary nodes, using size as the major criterion for disease identification reduces both sensitivity and specificity. Magnetic resonance imaging (MRI) can detect most lesions larger than 5 mm, does not expose the patient to ionizing radiation, and has acceptable imaging times; however, it is generally viewed as complementary to CT, rather than as a replacement for CT (Figure 2).^5–9 Cardiac and respiratory motion, reduced sensitivity for lesions smaller than 5 mm (compared with CT), calcified metastases, and suboptimal ability to assess lymphangitic spread are recognized limitations of MRI in the thorax.¹⁰

FIGURE 1 PET/CT images from an initial staging study of a 77-year-old woman with newly identified locally advanced infiltrating ductal carcinoma (IDC). Internal mammary nodal involvement is seen on the right. Normal internal mammary lymph nodes are not usually visualized on chest CT. This enlarged node, measuring 8 mm, is readily seen on CT and is hypermetabolic on PET. Although not biopsy proven, these imaging features are strong presumptive evidence of internal mammary nodal involvement. Seven of 12 axillary nodes were involved with tumor at surgery.

FIGURE 2 A, Breast MRI of a neglected, locally advanced left breast cancer with chest wall, skin, and nipple involvement shows a lung nodule on the right, suggesting possible stage IV disease (arrow). B, Chest CT confirmed a lung nodule, with an additional tiny subpleural nodule seen on this slice as well (arrowhead).

PET using fluorodeoxyglucose (FDG), an analogue of glucose, has assumed a primary role as a whole-body survey examination in many types of cancer, including breast. PET, and more recently PET/CT, excels at identifying the metabolic status of intrathoracic nodes, including internal mammary nodes, and solitary pulmonary nodules. Metabolic changes, resulting in pathologic or increased uptake on PET scan, can occur months before changes in size or shape. Additionally, it is now well recognized that lymph nodes larger than 10 mm may be benign or reactive, and lymph nodes smaller than 10 mm may represent metastases. With one important caveat, PET does not rely on the size of a lymph node or nodule to characterize it as benign or malignant. The caveat relates to the sensitivity of the PET/CT system based on lesion size. Presently, most scanners in clinical practice are able to reliably identify hypermetabolic foci down to about 8 mm. The addition of CT capability in PET/CT combination units will in many cases further improve sensitivity by allowing relatively precise image registration. The ability to confirm hypermetabolic activity in very small lesions may complicate reliance on the standardized uptake value (SUV). This calculated value is a measure of radioactivity in a lesion divided by the average value of radioactivity in the body, corrected for body weight. Many centers use a cut-off value of 2 to 2.5 or higher to indicate malignancy, with values less than 2 as evidence for benignity. The SUV is dependent on a multitude of factors, including serum glucose at the time of FDG injection, time between injection and imaging, and lesion size. Many investigators believe that any uptake above background in small (i.e., 5 to 7 mm) lesions should be regarded as suspicious for malignancy.

In one series of 73 patients who underwent FDG PET and CT for recurrent or metastatic disease, PET proved more sensitive (85% versus 50%) and specific (90% versus 83%) than CT. Also, PET uptake in mediastinal and internal mammary nodes was 2 times more prevalent than enlarged nodes on CT.¹¹ FDG PET has been shown to be significantly more accurate in staging the mediastinum in patients with non–small cell lung cancer, using histology as the gold standard.^12–13 Extrapolation of these data to patients with breast cancer may be problematic. It has been recognized that certain subtypes of breast cancer (e.g., invasive lobular, tubular, carcinoma in situ) show relatively low FDG uptake, resulting in reduced sensitivity compared with infiltrating ductal carcinoma (IDC) primary tumors.^14–15 Theoretically, patients whose initial staging FDG PET is negative in these tumor subtypes (especially if the primary has not been excised) may demonstrate reduced sensitivity for detection of metastases, including within the chest, on restaging studies.

Pleural involvement may be suspected based on clinical signs on physical examination or symptoms (e.g., cough, shortness of breath, pleuritic-type chest pain, orthopnea), the discovery of a pleural effusion on plain radiography or CT, or the identification of pleural abnormalities on CT or FDG PET (Figure 3). Pleural effusion is often unilateral and on the same side as the breast primary.¹⁶ The effusion can be confirmed by chest radiography, CT, or even ultrasound. Thoracentesis may be performed for both diagnostic and therapeutic purposes. If the result is nondiagnostic, or negative with a strong clinical suspicion of malignancy, consideration may be given to FDG PET imaging (preferably, PET/CT).

FIGURE 3 PET/CT axial images of a breast cancer patient with bilateral pleural metastases, more extensive on the left than the right. The pleural spaces extend far inferiorly, so that hypermetabolic pleural metastases appear to project in the periphery of the abdomen, overlapping the liver and spleen. The coronal projection image also shows a large, hypermetabolic left axillary lymph node.

FDG PET commonly identifies more pleural involvement than other imaging modalities and may be especially helpful in delineating the caudal extent of disease. The effusion itself tends to be only mildly positive on PET or frankly negative, presumably owing to the paucity of malignant cells relative to the volume of the effusion.

Many special circumstances exist with respect to the thoracic manifestations of breast cancer, reviewed in depth by Jung and associates.¹⁷ One important consideration is radiation therapy–related complications. Radiation pneumonitis typically occurs within 3 months of radiation therapy and progresses from diffuse haziness to coalescence of areas of consolidation to fibrous changes on chest x-ray or CT. Findings in the irradiated field may persist for months to years (Figure 4). Although PET/CT has demonstrated efficacy in separating scar from active tumor in many malignancies, its use following radiation therapy in the irradiated field may be problematic for months to 1 year or more. The heightened metabolic activity of activated monocytes at sites of radiation pneumonitis can last for a variable period of time, especially in the lung and with head and neck tumors. A negative FDG PET study at a site of postirradiation change on chest x-ray or CT is reassuring; however, a positive study must be interpreted with caution and reassessed or further investigated before initiation of additional tumor-targeted therapy.

FIGURE 4 Axial lung window chest CT image from a 56-year-old woman, 4 years after treatment for a high-risk IDC involving 19 of 26 lymph nodes with lumpectomy, axillary dissection, systemic chemotherapy, and radiation to the breast, axillary, and supraclavicular nodal basins, shows asymmetrical right apical radiation fibrosis. This was stable on imaging, corresponded to the radiation field, and showed stable, low-level activity on FDG PET.

The development of a solitary pulmonary nodule in patients who have been treated for breast cancer should not be assumed to be a breast recurrence without histologic proof. About half of these patients will have lung cancer, and a small percentage of cases will be benign.¹⁸ These patients are excellent candidates for PET/CT. Hypermetabolic uptake in the nodule directs the patient to tissue sampling (sometimes obviated by the finding of widespread metastases). Absent FDG uptake, as well as an otherwise negative study, may allow watchful waiting with short-term CT follow-up (e.g., 3 to 6 months). Recall the limitations of PET with respect to histology and lesion size.

Lymphangitic metastases are extremely common in women who die from breast cancer.¹⁹ CT is the imaging modality of choice for the identification of this process, which is most often bilateral (Figure 5). Findings include irregular thickening of the interlobar septa and peribronchovascular sheaths as well as thickening of the structures in the central regions of the secondary pulmonary lobules.²⁰

FIGURE 5 Axial lung window chest CT image from a 63-year-old woman with bone, thoracic, and brain metastases shows a large right pleural effusion. The lung parenchyma, particularly on the right, shows bronchovascular thickening and a finely nodular appearance of the interstitium, highly suggestive of lymphangitic tumor spread.

A 36-year-old woman was diagnosed with metastatic carcinoma to bone and the left hemithorax 4 years after mastectomy for a 1-cm left breast infiltrating lobular carcinoma. Her breast cancer was stage II, T1N1Mx, and was estrogen receptor positive and HER-2/neu 3+ positive. The patient had declined adjuvant therapy.

A left-sided pleural effusion was initially identified when the patient was evaluated for a cough 4 years after surgical treatment for breast cancer. An abnormality at T10 was noted during the same period, and biopsy confirmed metastatic breast cancer. The patient underwent thoracenteses twice of 1.5 liters of fluid, with negative cytologies. Ultimately, for management of the recurrent effusion, the patient underwent left hemithoracic thoracoscopy and thoracotomy, with drainage of the left pleural effusion, visceral and parietal pleurectomy, decortication of the left lung, and mechanical and talc pleurodesis. A pericardial effusion was also drained and a pericardial window created. Cytologies of both the pericardial and pleural fluid were positive for carcinoma, consistent with breast primary. Biopsies of the pleura, diaphragm, and pericardium confirmed metastatic carcinoma, consistent with metastatic lobular carcinoma. Evaluation of the visceral pleural specimens noted carcinoma extending into the subpleural alveolar septa.

The patient was begun on chemotherapy. Positron emission tomography (PET)/CT scans 1 and 3 months after the left pleurodesis showed similar findings, with left linear pleural space hypermetabolism (Figure 1), corresponding to the distribution of hyperdense talc on CT (Figures 2 and 3).

FIGURE 1 Three plane PET/CT images (unenhanced CT, PET, and fused PET/CT) show linear hypermetabolism in the left pleural space. On coronal slices, this is well seen at the left lung apex. Sagittal and axial images show linear hypermetabolism in the left anterior pleural reflection, anterior to the heart.

FIGURE 2 Contrast-enhanced chest CT slice through the lung apices shows linear hyperdensity along the left lateral aspect of the mediastinum (arrow).

FIGURE 3 A slice from the same contrast-enhanced chest CT, through the heart, shows residual loculated pleural fluid. Anterior to the apex of the heart, linear hyperdensity can be seen along the pleural lining, consistent with talc (arrow).

A 38-year-old woman elected to undergo prophylactic left mastectomy and bilateral transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction 10 months after finishing radiation therapy for a right stage II, T2N1, 3-cm infiltrating ductal carcinoma, estrogen receptor and progesterone receptor negative and HER-2/neu negative, with 3 of 22 involved axillary lymph nodes. She had been treated with right mastectomy with clear margins, chemotherapy with four cycles each of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) and paclitaxel (Taxol), and right chest wall, supraclavicular, and posterior axillary boost radiation therapy (see Case 18 in Chapter 3 for the presenting imaging features and staging of this patient).

Her initial staging workup had identified elevated tumor markers (CEA and CA 27.29). A PET/CT scan and enhanced diagnostic chest, abdomen, and pelvic CT scans were obtained and showed intense hypermetabolism in the known breast cancer and in a right axillary lymph node. Increased metabolic activity was also seen in a 5-mm right interpectoral (Rotter’s) lymph node.

The patient had undergone genetic testing subsequent to her diagnosis and treatment, and proved to be BRCA-1 positive. Her family history was of premenopausal breast cancer in a maternal aunt. She decided to undergo hysterectomy and oophorectomy, which was performed at the same time as prophylactic left mastectomy and bilateral TRAM flap reconstruction. Her left breast mastectomy specimen was benign.

The patient’s postoperative course was complicated by development of abdominal wound infection, requiring débridement twice of infected, necrotic tissue and intravenous antibiotic therapy. She also required anticoagulation for pulmonary embolism. (See Case 3 in Chapter 6 for imaging features of a complicated TRAM flap donor site.)

During the patient’s recovery from these procedures, she began to complain of right upper arm and shoulder pain. A lump developed under her right clavicle. She was imaged with enhanced body CT and PET/CT, which showed hypermetabolic nodal masses in the right paratracheal mediastinum and in the right infraclavicular region (Figures 1, 2, 3, and 4). These findings represented changes from prior studies, indicative of recurrent disease. Ultrasound of the right infraclavicular region identified a corresponding nodal mass (Figure 5), which was sampled with fine-needle aspiration technique, and confirmed recurrent adenocarcinoma, consistent with breast primary. To better define the extent of disease in light of the patient’s symptoms of right shoulder pain, a brachial plexus MRI was obtained (Figures 6, 7, 8, 9, 10, and 11).

FIGURE 1 Coronal PET (A) and fused PET/CT (B) images show intense hypermetabolism at the right infraclavicular level.

FIGURE 2 Coronal PET (A) and fused PET/CT (B) images show a second site of intense hypermetabolism, localizing to the right paratracheal mediastinal level.

FIGURE 3 Axial fused PET/CT image shows the two sites of hypermetabolic uptake, one at the right infraclavicular level and the other at the right paratracheal mediastinum.

FIGURE 4 Contrast-enhanced chest CT images for correlation (A above B). A, A rounded, soft tissue mass (arrow) imparts increased bulk to the right retropectoral region. B, An enlarged right paratracheal nodal mass corresponds to the PET.

FIGURE 5 Ultrasound of the right infraclavicular fullness shows a lobular nodal mass. Ultrasound-guided fine-needle aspiration confirmed metastatic adenocarcinoma.

FIGURE 6 Coronal short tau inversion recovery (STIR) (A) and T1-weighted (B) brachial plexus MRIs at the same level show the bulky right paratracheal nodal mass. Portions of the subclavian arteries are seen on these sections, accompanied by cords of the brachial plexus. Note on the T1-weighted image the symmetry of the interscalene fat triangles, through which trunks of the brachial plexus pass (asterisks).

FIGURE 7 A more anterior coronal T1-weighted image shows the subclavian veins. A nodule is seen at the level of the right subclavian vein (arrow).

FIGURE 8 Axial T1-weighted image through the infraclavicular region and superior mediastinum. The top of the bulky right paratracheal nodal mass is seen. An oval mass is seen deep to the right pectoralis major muscle on the right (arrow), which posteriorly displaces the right pectoralis minor muscle. The normal appearances of the pectoralis major and minor are well depicted on the left.

FIGURE 9 Fat-saturated, T2-weighted image, at a comparable level to Figure 7, shows hyperintensity of both the right paratracheal nodal mass and the interpectoral (Rotter’s) nodal mass. The medial aspects of both the right pectoralis major and minor muscles are also increased in signal intensity.

FIGURE 10 Sagittal MRIs of the retroclavicular components of the brachial plexus (at the level of the subclavian artery and vein, and brachial plexus cords). A, T1-weighted sagittal image. B, Matching fat-saturated, T2-weighted, sagittal image. C, T1-weighted, sagittal image, lateral to A and B. D, Matching fat-saturated, T2-weighted, sagittal image, lateral to A and B. Subclavian artery (SA) is above subclavian vein (SV). SV is anterior to the artery. In A and B, a nodule abuts the SV (asterisk). The fat around the artery is occupied by abnormal soft tissue (arrow), effacing cords of the brachial plexus. Further laterally (C and D), abnormal infiltration of the pectoralis muscle is seen anterior to the vessels (clavicle, C).

FIGURE 11 Axial fat-saturated, enhanced, T1-weighted, breath-hold, gradient echo images (A above B). A, Peripheral enhancement of a multilobular, necrotic mass is seen in the right chest wall. The epicenter is interpectoral at the Rotter’s node level. This mass extends anteriorly into the posterior pectoralis major muscle and infiltrates the pectoralis minor muscle. B, A more inferior section, showing pectoralis major and interpectoral components, with a similar enhanced appearance of the right paratracheal nodal mass.

TEACHING POINTS

The anatomy of the brachial plexus is challenging to learn. Much of the confusion arises from the multiplicity of components. A simplified approach is suggested for the imager (adapted from Castillo), concentrating on landmarks for identification of the trunks and cords.

The brachial plexus is formed from the anterior rami of C5 through T1 in most people. The anterior rami reside just beyond the neural foramen. They form the trunks, which course between the anterior and middle scalene muscles (Figure 12), above the subclavian artery. The interscalene fat pad is an important anatomic landmark to evaluate for symmetry or effacement on coronal sequences because tumors or other processes at this level will impinge on brachial plexus trunks (Figure 13). These trunks ramify to form divisions posterior to the clavicle, which run in the supraclavicular triangle above the subclavian artery. These divisions ramify again to form cords inferior to the clavicle. These cords are the infraclavicular component of the brachial plexus with which we are most concerned in breast cancer patients. (Remember: Cords are the brachial plexus component behind the clavicle.) Although breast cancer metastases can arise anywhere along the course of the brachial plexus, the critical area is in the retroclavicular region around the cords of the brachial plexus. At this level, the cords are in close proximity to the axillary artery and vein (as the subclavian artery and vein are known lateral to the first rib).

FIGURE 12 Axial T1-weighted images (A to E, from above to below), for demonstration of the anatomic landmarks used to localize the trunks of the brachial plexus. The trunks course between the anterior (colored yellow) and middle (pink) scalene muscles. The trunks are best visualized in C. No evidence of pathology is seen at these levels.

FIGURE 13 Coronal T1-weighted image, demonstrating the landmarks used to localize the position of the trunks of the brachial plexus. The anterior scalene muscles have been colored yellow, and the interscalene fat pads orange. Asymmetry of or effacement of an interscalene fat pad is an important clue to possible infiltration of the brachial plexus at the trunk level (not present here). The bulky right paratracheal nodal mass is seen.

Patients like this, with axillary nodal disease, are at a known 10% to 20% risk for recurrence at the apical axillary nodal level (axillary level III). Lymph node dissections target lymph nodes at axillary level I (lateral to pectoralis minor muscle) and level II (under the pectoralis minor muscle) and generally do not extend to encompass apical axillary nodes (level III), which lie in an infraclavicular site superior to the medial border of the pectoralis muscle. These apical axillary nodes are in continuity with supraclavicular nodes and are clustered around the axillary vessels in proximity to the cords of the brachial plexus.

This patient was known to be high risk. In addition to axillary disease, she had a PET-positive interpectoral (Rotter’s) node identified at presentation. This is not a nodal site typically addressed surgically. She received aggressive systemic therapy and underwent chest wall radiation after mastectomy.

Development of symptoms (shoulder pain) is cause for concern and appropriately should lead to further investigation for possible recurrence. In this case, the clinical picture was clouded by the imaging evaluations addressing the abdominal wall and pulmonary embolism complications of this patient’s TRAM flap surgery. CT scans were being obtained to assess these acute problems. The interpectoral nodal mass responsible for this patient’s symptoms was poorly depicted on CT. This is not surprising, given the limitations of soft tissue contrast inherent in CT. These same findings are dramatically more conspicuous with either functional imaging (PET) or better soft tissue contrast (MRI).

As depicted by this case presentation, the combination of PET or PET/CT and brachial plexus MRI is optimal for comprehensive imaging evaluation of the breast cancer patient manifesting symptoms of a possible brachial plexopathy.

A 64-year-old woman with stage IV breast cancer metastatic to bone developed pain in the left occipital region and numbness of the left shoulder. She had been diagnosed with infiltrating ductal carcinoma the previous year, with biopsy-confirmed bone metastases identified at the same time. She had previously been treated palliatively with radiation for right shoulder and left hip pain.

At the time of evaluation of the mild brachial plexopathy symptoms, a palpable left supraclavicular nodal mass was noted on physical examination. Fine-needle aspiration confirmed metastatic adenocarcinoma. CT and MRI of the brachial plexus confirmed stippled, nodular infiltration of the left supraclavicular triangle (Figures 1, 2, 3, 4, and 5). After progression on a trial of an experimental chemotherapeutic agent, the supraclavicular region was radiated. The supraclavicular mass decreased in size and became more mobile, and the patient’s shoulder paresthesias improved.

FIGURE 1 Contrast-enhanced soft tissue neck CT scan shows small nodules and stippled soft tissue densities effacing fat in the left supraclavicular region. SCM, sternocleidomastoid muscle; TM, trapezius muscle.

FIGURE 2 T1-weighted coronal MRI shows left supraclavicular abnormalities. In addition to a round lymph node, there is ill-defined soft tissue infiltration effacing fat.

FIGURE 3 Coronal STIR image shows hyperintense mass lesions at the left supraclavicular level.

FIGURE 4 Axial T2-weighted MRI through the supraclavicular regions shows relatively bright signal of the left soft tissue infiltrative process (asterisk). SCM, sternocleidomastoid muscle; TM, trapezius muscle.

FIGURE 5 Corresponding axial T1-weighted MRI through the same level shows the left-sided soft tissue process to abut the muscles, with loss of the intervening fat plane. SCM, sternocleidomastoid muscle; TM, trapezius muscle.

The left neck progressive disease had developed on hormonal therapy, and so chemotherapy was begun. Later the same year, the patient developed intractable nausea, vomiting, abdominal pain, and abnormal liver function tests. Abdominal ultrasound confirmed liver metastases. The patient elected hospice care.

A 42-year-old woman was found to have lung and nodal breast cancer metastases after evaluation with positron emission tomography (PET) and CT for rising tumor markers. Her diagnosis of breast cancer was 4 years before, and was stage IIB, T2N1. She underwent bilateral mastectomy and received adjuvant CMF chemotherapy and tamoxifen. Her prior medical history was notable for treatment of Hodgkin’s lymphoma at age 17 with radiation and chemotherapy.

The diagnosis of recurrent breast cancer was made by biopsy of a lung nodule, confirming malignant adenocarcinoma, consistent with breast primary. The patient was begun on a regimen of docetaxel (Taxotere) and gemcitabine (Gemzar).

A chest CT obtained just before cycle seven of chemotherapy showed that the index lung metastases were responding (Figures 1 and 2). However, new, vague, bilateral ground-glass lung opacities were noted. A drug reaction was suggested as the etiology. The patient complained of fatigue but was otherwise asymptomatic. Her tumor markers had normalized.

FIGURE 1 A, CT scan through the superior mediastinum shows paramediastinal fibrosis from prior radiation for Hodgkin’s lymphoma. The lungs at this level are clear. B, CT scan through the lower lobes shows a spiculated left lower lobe (LLL) metastasis, with localized pleural thickening.

FIGURE 2 A and B, Three months later, through comparable levels, CT scan shows new, vague increase in lung opacity diffusely. Subtle new intralobular septal thickening is present. The LLL metastasis shows marked diminution in size and volume.

Four months later, the patient noted increasing dyspnea with exertion. Her chemotherapy was interrupted and consultation with chest medicine obtained. Additional symptoms of intermittent cough and low-grade fever were noted by this time. Pulmonary function tests were abnormal, with evidence of moderate restriction and low diffusing capacity, suggesting interstitial lung disease. Bronchoscopy was performed to exclude an infectious etiology. All cultures were negative. On a chemotherapy holiday, the patient’s symptoms improved dramatically, and the ground-glass infiltrates seen on chest CT resolved (Figure 3). Repeat pulmonary function tests 3 months later showed improvement.

FIGURE 3 A and B, Six months since the CT in Figure 1, and after chemotherapy was discontinued 3 months, CT scan shows that the diffuse lung changes have resolved. The index LLL lung metastasis has grown.

A 37-year-old woman with extensive bony metastatic breast cancer known for 1 year developed increased aching, weight loss, depressed appetite, and rising tumor markers while on goserelin acetate (Zoladex), zoledronic acid (Zometa), and exemestane (Aromasin). Positron emission tomography (PET)/CT and enhanced body CT scans showed new liver metastases (see Case 2 in Chapter 9). Chemotherapy was recommended but declined. She was started on fulvestrant (Faslodex) and restaged after 2 months, at which time fatigue, shortness of breath, and rising tumor markers were noted. Repeat PET/CT and enhanced body CT scans showed progression of liver metastases, new pleural and pericardial effusions as well as pulmonary metastases, and evidence of lymphangitic spread (Figures 1, 2, 3, 4, 5). One month later, the patient was admitted with confusion, thought to be hepatic encephalopathy due to the extensive liver metastases. She died soon thereafter.

FIGURE 1 Baseline chest CT images, 7 months before identification of liver metastases. A, Axial slice through the upper lobes. B, Through the mid-thorax, at the level of the carina. C, Through the lower lobes. These images show linear, right anterior, subpleural, parenchymal consolidation (arrowheads), in a distribution compatible with radiation fibrosis from radiation therapy 4 years earlier.

FIGURE 2 Comparable levels on repeat chest CT, 7 months later. The patient was being evaluated for aching, weight loss, depressed appetite, and rising tumor markers. She had diffuse bone metastases identified 1 year earlier, and liver metastases were identified at this time. A, Axial slice through the upper lobes. B, Through the mid-thorax, at the level of the carina. C, Through the lower lobes. No pleural fluid is identified. The radiation therapy changes in the right anterior subpleural lung were again noted. No other lung parenchymal abnormalities were identified. In retrospect, very subtle ominous changes may be appreciated. The major fissure can now be visualized on these slices, and displays very subtle new nodular thickening (arrow). New subpleural interlobular pleural thickening is suggested as well, best seen on the right anteriorly in A, at the level of the prior radiation therapy change (arrowheads). Subtle nodular bronchovascular thickening is also suggested in right middle and lower bronchi visualized in C.

FIGURE 3 Comparable sections on a third chest CT, 2 months later. Liver metastases were identified on the prior study. The patient had declined recommended chemotherapy and at this point had undergone 2 months of therapy with fulvestrant (Faslodex). Progressive fatigue, shortness of breath, and rising tumor markers were noted at this time. A, Axial slice through the upper lobes. B, Through the mid-thorax, at the level of the carina. C, Through the lower lobes. Pleural effusions have developed bilaterally, right greater than left. Nodular thickening of the right major fissure is more apparent (arrow). Parenchymal findings of lymphangitic tumor are now readily apparent, especially anteriorly, right greater than left, with subpleural interlobular septal thickening and occasional tiny subpleural nodules. Bronchovascular thickening and nodularity is notable on the right centrally (A) and in the anterior right upper lobe (B).

FIGURE 4 Contrast-enhanced chest CT images (A and B, soft tissue window) from the final CT (same study as Figure 3) show bilateral pleural effusions, right greater than left. The pleura is enhancing, smoothly in some places and nodularly in others (as seen here best on the left, arrows), suggesting malignant effusions. A small new pericardial effusion is also partially visualized here.

FIGURE 5 A contrast-enhanced image from the same chest CT shows the pericardium distended by a moderate-sized effusion. The enhancing pericardium is visualized, evidence that this is a malignant effusion. A right pericardial lymph node is seen (arrowhead), and there is an enhancing soft tissue nodule within the pericardial fluid (arrow). The liver is heterogeneous. Liver metastases were better demonstrated on other slices (not shown). Malignant pleural effusions with enhancement of the pleura are again seen.

Her original tumor had been treated 5 years earlier and was an estrogen receptor– and progesterone receptor–positive, T1cN1b(4) infiltrating ductal carcinoma. She was treated with breast conservation and axillary dissection, with 4 of 20 lymph nodes positive and showing microscopic extracapsular extension. Additional treatment was with chemotherapy (four cycles of doxorubicin [Adriamycin] and cyclophosphamide [Cytoxan] [AC] and four of paclitaxel [Taxol]); right breast, supraclavicular, and axillary radiation therapy; and tamoxifen. Four years after the original breast cancer diagnosis and 1 year before detection of liver metastases, diffuse bone metastases were found. See Case 3 in Chapter 8 for discussion of the imaging manifestations of this patient’s bone metastases.

A 55-year-old woman with stage III breast cancer diagnosed 3 years before was noted to have rising tumor markers (CA 27.29), while finishing a delayed year of trastuzumab (Herceptin) therapy. She had been treated at another facility for a 4.5-cm, estrogen receptor– and progesterone receptor–negative, HER-2/neu positive, infiltrating ductal carcinoma, with mastectomy, chemotherapy (four cycles of doxorubicin [Adriamycin] plus cyclophosphamide [Cytoxan] [AC] and four cycles of docetaxel [Taxotere]), and radiation. Ten of 12 lymph nodes were involved. The patient presented for medical oncology second opinion 9 months after finishing primary treatment and began a year’s therapy with trastuzumab (Herceptin).

The patient’s rising tumor markers prompted a restaging workup with CT and positron emission tomography (PET). Tiny (2 to 3 mm) micronodules were noted in the right upper lobe (RUL) on chest CT. The PET scan was negative. She was evaluated by pulmonary medicine. A short interval follow-up was recommended because the patient was essentially asymptomatic, other than left knee pain.

A repeat chest CT 4 months later showed increased interstitial lung changes, and the specter of lymphangitic tumor was raised (Figures 1 and 2). Repeat PET scan showed new abnormalities, with bilateral suprahilar hypermetabolic uptake, as well as new mild, generalized, increased upper lobe activity, corresponding to the new parenchymal findings (Figure 3).

FIGURE 1 Chest CT images (A to C, from above to below) show increased parenchymal ground-glass opacity, with thickening of peripheral interlobular septa. These findings are most evident in the posterior RUL, with similar but lesser changes in the superior segment right lower lobe and posterior left upper lobe. Note subtle nodularity of prominent bronchovascular structures in the RUL. Anterolateral subpleural lung changes on the left are consistent with radiation fibrosis (arrowheads). Note prior left mastectomy.

FIGURE 2 Prior chest CT images, for comparison, 15 months (A) and 4 months (B) before. Note new prominence of RUL peripheral interstitial markings and interlobular septa. Tiny peripheral RUL subpleural micronodules are now suggested (arrow).

FIGURE 3 Coronal PET images show new bilateral perihilar hypermetabolism, with lower-level, generalized, mild increased activity of both upper lobes.

Bronchoscopy showed a normal tracheobronchial tree. RUL lavage and transbronchial biopsy confirmed metastatic breast cancer, estrogen receptor and progesterone receptor negative. Bone scan, obtained to evaluate complaints of left knee pain, showed findings suggesting hypertrophic osteoarthropathy as a possible etiology for the pain (Figure 4).

FIGURE 4 Bone scan images show a long segment of mild increased uptake at the left 11th rib level posteriorly, a pattern suspicious for metastasis. Left neck degenerative activity is similar to the PET scan findings at this level. Cortex of the left femur is unusually well seen. Given the lung findings, this could be a subtle case of hypertrophic osteoarthropathy.