lung metastases dr maria

Lung Metastases Imaging http://emedicine.medscape.com/article/358090-overview

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Lung Metastases Imaging

Author : Tanay Patel, MD; Chief Editor: Eugene C Lin, MD

Overview

Pulmonary metastasis is seen in 20-54% of extrathoracic malignancies.[1] Lungs are the

second most frequent site of metastases from extrathoracic malignancies. Twenty

percent of metastatic disease is isolated to the lungs. [1] The development of pulmonary

metastases in patients with known malignancies indicates disseminated disease and

places the patient in stage IV in TNM (tumor, node metastasis) staging systems. This

typically implies an adverse prognosis and alters the management plan. Imaging plays

an important role in the screening and detection of pulmonary metastases. Imaging

guidance is also used in histological confirmation of metastatic disease. In patients

with poor cardiorespiratory function and comorbidities, imaging-guided thermal

ablation procedures are an effective alternative to surgical resection to improve the

survival.

Chest radiography (CXR) is the initial imaging modality used in the detection of

suspected pulmonary metastasis in patients with known malignancies. Chest CT

scanning without contrast is more sensitive than CXR. For patients with bone or soft-

tissue sarcoma, malignant melanoma, and head and neck carcinoma, CT scanning of

the chest should be performed as an initial evaluation. In patients with primary renal

or testicular cancer, chest CT scanning performed should be performed based on the

presence of metastatic disease elsewhere. CT guidance is often required for obtaining

samples from a suspected metastatic disease. Several thermal ablation options are

available for treatment of pulmonary metastases, which is performed under CT

guidance.

See the images below.

1


Chest radiograph of a 58-year-old man with malignant melanoma (note surgical clips

in right lower neck) shows multiple pulmonary nodules of varying sizes consistent

with metastatic disease. There is also a small right basal effusion.

Axial CT scan in a 58-year-old man with malignant melanoma shows multiple round

nodules and masses of varying sizes in both lungs, consistent with metastases. There

are also small bilateral pleural effusions.

Volume-rendered 3-dimensional CT scan shows a metastatic mass in the trachea from

squamous cell carcinoma of the lung.

2


Ultrasound guidance used for transthoracic aspiration of malignant effusion.

Pathophysiology

Malignancies can reach the lung through 5 different pathways—hematogenous

through the pulmonary or bronchial artery, lymphatics, pleural space, airway, or direct

invasion.[2]

The most common path is the hematogenous spread, which occurs in tumors that have

direct venous drainage to the lungs. This includes cancers of the head and neck,

thyroid, adrenals, kidneys, and testes, as well as malignant melanoma and

osteosarcoma. When the primary tumor invades the venous system, tumor cells

embolize to the lungs through the pulmonary or bronchial arteries. Most of the tumor

cells that reach the pulmonary capillary and arteriolar bed perish; however, some

tumor cells pass through the vascular wall and develop parenchymal metastasis in the

alveolar space or the interstitium.

Lymphatic spread occurs to the lungs, pleura, or mediastinum. Lymphatic spread

occurs either in an antegrade fashion by lymphatic invasion through the diaphragm

and/or pleural surfaces or retrograde lymphatic spread from hilar lymph nodal

metastasis. Lymphangitic spread refers to tumor growth in lymphatic channels, which

are seen in the axial interstitium (peribronchovascular and centrilobular interstitium)

and peripheral interstitium (interlobular septa and subpleural).

The tumor initially spreads via a hematogenous route to the pulmonary arterioles and

capillaries with retrograde spread from hilar nodal metastases or upper abdominal

tumors, but subsequently extends through the vascular walls, invades the low resistant

peribronchovascular lymphatics, and spreads along the lymphatics.

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The microscopic spread of metastasis through lymphatics and perilymphatic

connective tissue is seen histopathologically in 56% of patients with pulmonary

metastasis.[3] Lymphatic spread also occurs to the mediastinal lymph nodes through the

thoracic duct, with subsequent retrograde spread to the hilar lymph nodes and then the

lungs.

Spread within the pleural space can occur by pleural invasion by a local tumor, such

as lung cancer or thymoma.

Endobronchial spread of tumor cells occurs with airway tumors. It is more common in

bronchoalveolar carcinoma, less common in other types of lung cancer, and even less

common in tracheobronchial papillomatosis.

Direct invasion of the lung occurs in tumors contiguous to the lung, including thyroid,

esophageal, mediastinal, airway, and cardiovascular structures.

Frequency

The venous return containing lymphatic fluid from body tissues flows into the lungs

through the pulmonary vascular system; thus, all tumors have the potential to involve

the lungs. Pulmonary metastasis is seen in 20-54% of extrathoracic malignancies at

autopsy. Breast, colorectal, lung, kidney, head and neck, and uterus cancers are the

most common primary tumors with lung metastasis at autopsy. Choriocarcinoma,

osteosarcoma, testicular tumors, malignant melanoma, Ewing sarcoma, and thyroid

cancer frequently metastasize to lung, but the frequency of these tumors itself is low.

Colorectal cancer, which accounts for 10% of all cancers, accounts for 15% of all

cases of pulmonary metastases.[4]

The Table illustrates the frequency of metastases in different primary malignancies.

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Table. Incidence of Pulmonary Metastases According to Site

Primary Tumor Frequency at Presentation, % Frequency at Autopsy, %

Choriocarcinoma 60 70-100

Melanoma 5 66-80

Testis, germ cell 12 70-80

Osteosarcoma 15 75

Thyroid 7 65

Kidney 20 50-75

Head and neck 5 15-40

Breast 4 60

Bronchus 30 40

Colorectal < 5 25-40

Prostate 5 15-50

Bladder 7 25-30

Uterus < 1 30-40

Cervix < 5 20-30

Pancreas < 1 25-40

Esophagus < 1 20-35

Stomach < 1 20-35

Ovary 5 10-25

Hepatoma < 1 20-60

Mortality & Morbidity

The presence pulmonary metastasis usually indicates advanced disseminated disease.

Occasionally, tumor spread can be an isolated event. The mortality depends on the

primary tumor; for example, in pancreatic and bronchogenic carcinomas, the 5-year

survival rate in patients with pulmonary metastases is less than 5%.[1]

Early diagnosis is critical in planning effective therapy in patients who can be cured.

Depending on several factors, metastasis can be resected, with 5-year survival rates up

to 30-40%.[5]

Clinical details

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While a large number of patients with pulmonary metastasis are asymptomatic at the

time of diagnosis, some patients develop symptoms such as hemoptysis, cough,

shortness of breath, chest pain, weakness, and weight loss. Particularly, patients with

lymphangitic carcinomatosis present with respiratory dysfunction, including severe

dyspnea.

Other problems to consider

The most common pattern of pulmonary metastasis is the presence of multiple, well-

defined nodules. Differential diagnoses for multiple pulmonary nodules include

infections (eg, histoplasmosis, coccidioidomycosis in endemic areas, cryptococcal and

nocardial infections as opportunistic infections in immunocompromised patients,

septic emboli, abscess, paragonimiasis, hydatid), granulomatous diseases (eg,

tuberculosis, sarcoidosis), and vascular/collagen-vascular diseases (eg, Wegener

granulomatosis, rheumatoid arthritis).

Differential diagnoses for other patterns are discussed in detail in Radiography and CT

Scan.

Intervention

In specific circumstances, histopathological samples are required from the lung lesion.

A few such scenarios include (1) atypical imaging findings; (2) the development of a

solitary pulmonary nodule in a patient with known malignancy; (3) pulmonary

metastasis without a known primary source; (4) assessment of response to therapy,

particularly in nodules that are unchanged in size, but no positron emission

tomography (PET) activity suggestive of sterilized metastasis.

Tissue sampling can be performed by transthoracic needle aspiration, transthoracic

needle biopsy, transbronchial needle aspiration and biopsy, or minimally invasive

video-assisted surgical methods.

Peripheral nodules are sampled using transthoracic aspiration/biopsy using CT

guidance, provided they are not crossing major vascular structures or fissures. Central

nodules and nodules involving airways are sampled using transbronchial needle

aspiration and biopsy. Smaller nodules are now being sampled using state-of-the-art

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techniques such as electromagnetic-guided navigation bronchoscopy, usually with CT

virtual bronchoscopic guidance. With an electromagnetic navigation system, a

bronchoscopic probe sensor is placed within the electromagnetic field created around

the chest. Real-time position is generated and superimposed on previously acquired

thin CT images to navigate to the lesion.

Biopsy or fine-needle aspiration (FNA) is typically performed under CT guidance.

Full descriptions of the procedure and its complications are beyond the scope of the

article.

The definitive treatment for pulmonary metastases from extrathoracic malignancies is

surgical resection (pulmonary metastasectomy). Surgery is performed if the primary

tumor is controlled, if no extrathoracic lesions are present, if it is technically

resectable, and if general and functional risks are tolerable.

The 5-year overall survival rate for patients with pulmonary metastasectomy is 15-

48%, compared with 13% for patients without the procedure.[5] The mean survival is

12-18 months. Survival has been shown to better in patients with a fewer number of

metastases. However, pulmonary metastasectomy can be performed only in 25-50% of

patients, owing to the presence of multiple metastatic lesions or the presence of

comorbid conditions, including poor respiratory function or refusal to have surgery.[6]

Recurrence after pulmonary metastasectomy also limits further surgical options.

In patients who are not in adequate physical condition to undergo pulmonary

metastasectomy, alternative options available include stereotactic radiosurgery and

thermal ablation procedures. Thermal ablation procedures induce coagulation necrosis

of tumor cells and are typically performed with CT guidance. These include

radiofrequency ablation (RFA), microwave ablation, laser ablation, and cryoablation.

The primary goal of all these tumor ablation procedures is to eradicate all the

malignant cells along with a margin of normal tissue, but cause minimal damage to

normal lung disease. By doing this, adequate tumor control is achieved and survival is

prolonged. The main advantage of thermal ablation procedures is selective and limited

damage of lung tissue to minimally impact pulmonary function.

The ablation procedure can be repeated many times. In addition, ablation procedures

can be performed regardless of previous therapy, even in patients who have adhesions

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from previous surgeries or radiation-induced pneumonitic changes. Because of this,

ablation is often used as a salvage treatment for oligo-recurrence after surgery and

radiation.

Thermal ablation is also not an obstacle for performing concurrent or adjuvant

chemotherapy or adjuvant radiation therapy. In fact, if the tumor size is downgraded

by thermal ablation, the remaining tumor cells may become more sensitive to

chemotherapy. As a result, the combination of thermal ablation, along with

chemotherapy and other modalities, can increase the efficacy of thermal ablation

through synergistic and even additive effects.

Complications that can be seen during ablation procedure include pneumothorax,

pulmonary hemorrhage, bronchopleural fistula, pulmonary artery pseudoaneurysm,

systemic air embolism, injury of the brachial or phrenic nerve, pneumonia, needle-

tract seeding of cancer, and deterioration of interstitial pneumonia.[7]

Radiofrequency ablation

RFA operates using alternating electrical current within the radiowave frequency

(460-500 kHz). Using CT guidance, the RFA electrode is placed within the metastasis.

Electrical current is concentrated near the noninsulated tip of the electrode, and the

circuit is completed by returning to electrical ground pads in the patient’s thighs. The

aelectrical current causes agitation of ionic dipolar molecules in the surrounding tissue

and fluids. The heat is radially distributed to surrounding tissues, usually in an

ellipsoid shape with predictable distribution.

RFA has been shown to improve survival in patients with pulmonary oligometastasis

and oligo-recurrence, which means one or a few metastatic or recurrent lesions,

without and with controlled primary tumor, respectively. Several studies have been

performed using RFA on several cancers. Generally, a disease free survival of 36

months or more is considered to indicate good response.[6]

In colorectal cancers, Hiraki et al[7] demonstrated an overall survival rate of 96% at 1

year, 54% at 2 years, and 48% at 3 years. Yamakodo et al demonstrated 46% at 3

years and median survival of 60 months.[8] An absence of extrapulmonary metastasis,

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small tumor size (< 3 cm), single lung metastasis, and normal carcinoembryonic

antigen (CEA) value were good prognostic indicators.

In hepatocellular carcinoma, Hiraki et al[9] demonstrated an overall survival of 87% at

1 year and 57% at 2 and 3 years. Median and mean survival were 37.7 months and

43.2 months, respectively. Well-controlled primary cancer, an absence of intrahepatic

recurrence, Child-Pugh class A, an absence of cirrhosis or hepatitis C infection, and an

α-fetoprotein value of less than 10 ng/mL were good prognostic indicators.

In renal tumors,[10] overall survival in curative and palliative ablation groups were

shown to be 100% and 90%, respectively, at 1 year; 100% and 52% at 3 years; and

100% and 52% at 5 years.

Maximum tumor diameter is an important factor. In bone and soft tissue sarcomas, 1-

and 3-year survival rates were shown to be 92.2% and 65.2%, respectively.[11]

Microwave ablation

Microwave ablation is performed using microwave antennae and microwave

generators with power settings of 35-45 W and an ablation time of 15 ±5 minutes

under CT guidance. The efficacy of the treatment is determined by preablation tumor

size and its location in relation to the hilum. The histopathologic nature of the primary

tumor has no significant impact on the result of microwave ablation therapy.

Tumors smaller than 3 cm and peripheral lesions (ie, >5 cm from the hilum) fared

better than larger and more central lesions. With hilar lesions, the presence of large

adjacent pulmonary arteries results in a current-sink effect, which diverts the heat

current during ablation away from the core of the tumor, resulting in cooling of the

tumor. Solutions to this issue include using prolonged current application and multiple

simultaneous antennae, but these are associated with a higher risk of complications

such as hemorrhage.

Following microwave ablation, the initial CT scan may show increased tumor volume

due to edema and an inflammatory response to heat energy. However, if the tumor

size increases after 4-6 weeks, recurrence should be considered. Higher survival has

been observed in patients with tumor-free states after successful ablation compared

with patients with failed ablation.[12]

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Cryoablation

Cryoablation is performed using a cryoprobe with high-pressure argon and helium

gases for freezing and thawing on the basis of the Joule-Thomson principle. Three

freeze-thaw cycles are performed to freeze a tumor 2.5-3 cm in diameter.

Initial freezing causes an ice ball with a diameter of only 1 cm, since air prevents

conduction of low temperature and there is not enough water in the lung parenchyma.

However, after the first thawing, the induced massive hemorrhage excludes air and

results in the formation of a larger ice ball in subsequent freezing steps. During

thawing, the probe reaches a temperature of 20°C.

Cryoablation has been shown to result in 1- and 3-year progression-free intervals of

90.8% and 59%, respectively. The 3-year local progression-free interval of tumors

smaller than 15 mm in diameter was 79.8% and of tumors larger than 15 mm was 18.6

%. One- and 3-year overall survival rates were 91% and 59.6%, respectively.[13]

Laser ablation

Laser ablation is performed with a miniaturized, internally cooled applicator system,

which has an optical laser fiber with a flexible diffuser tip. Nd-YAG laser generators

are typically used. Laser ablation is performed with single or multiple applicators

under CT guidance. Wattage can be increased at 2 W/min, and a maximum energy of

14 W has been maintained for 15 minutes. The total amount of energy per tumor has

ranged from 7.4-68 W. Using laser ablation, definitive control of initial pulmonary

disease has been achieved in 45% of patients, with 1-, 2-, 3-, 4-, and 5-year survival

rates of 81%, 59%, 44%, 44%, and 27%, respectively.[14]

The advantage of laser ablation is the use of laser light and its comparably well-

studied conduction in lung tissue. Use of thin-caliber applicators and flexible fibers is

a major advantage, and the procedure is more cost effective than other ablation

techniques.

Preferred examination

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Imaging modalities available for evaluation of pulmonary metastasis include CXR,

CT scanning, MRI, scintigraphy, and PET scanning. The preferred imaging modality

depends on the biological behavior of the tumor, sensitivity and specificity of the

imaging modality, radiation dose, and cost effectiveness.

In a patient with known malignancy, CXR, with posteroanterior and lateral views, is

usually the first imaging study performed to detect pulmonary metastases. Not

uncommonly, metastases may be unexpectedly discovered on CXR performed for

some other purpose. CXR performed with dual-energy subtraction has higher

sensitivity in the detection of pulmonary metastasis by subtracting the overlying

bones. Computer-aided detection (CAD) has been used in automatic detection of small

pulmonary nodules. In a patient with known malignancy, if CXR demonstrates

multiple pulmonary nodules, further imaging is usually not necessary, unless biopsy is

planned or precise quantification of the metastatic burden is required prior to

metastasectomy or as a baseline study to assess response following chemotherapy or

radiation.

CT scanning is the most sensitive modality in the detection of pulmonary metastasis,

owing to its high spatial and contrast resolution and lack of superimposition with

adjacent structures, such as bones and vessels. Compared with CXR, CT scanning can

detect a larger number of nodules and nodules smaller than 5 mm. CT scanning can

detect 3 times as many noncalcified nodules as CXR.[15] In addition, it can detect

additional findings such as lymphadenopathy; pleural, chest wall, airway, and vascular

involvement; and upper abdominal and bony findings that may alter management. In a

patient with known malignancy, chest CT scanning is performed if CXR shows a

solitary nodule, equivocal nodule, negative findings but the extrathoracic malignancy

has high risk of lung metastasis (eg, breast, kidney, colon, bladder), or multiple

nodules (but biopsy or definitive treatment by mastectomy, chemotherapy, and

radiation is planned).

The radiation dose from frequent CT scanning can be reduced by using several dose-

reduction techniques such as low kV, low mAs, adaptive tube current modulation, and

iterative reconstruction algorithms. The sensitivity of nodule detection can be

increased by using postprocessing tools such as maximum-intensity projection (MIP)

11


or volume rendering (VR). High-resolution CT (HRCT) scanning is used for detection

of lymphangitic carcinomatosis. CT scan findings are not very specific, since nodules

can be seen in a variety of benign conditions, including granulomas, hamartomas, and

vascular abnormalities.

The American College of Radiology (ACR) recommends that CXR should be the

initial imaging modality used in the screening of pulmonary metastasis in patients

with known extrathoracic malignancy. CT scanning without intravenous contrast is

more sensitive than radiography in the detection of pulmonary metastasis. For patients

with bone and soft-tissue sarcoma, malignant melanoma, and head and neck

carcinoma, CT scanning of the chest should be performed as the primary imaging

modality. In patients with primary kidney or testicular cancers, chest CT scanning

should be performed based on the presence of metastatic disease elsewhere.[1] Detailed

guidelines for few tumors are described below. The rest of the guidelines can be seen

in the ACR article.[1]

Bone and soft-tissue sarcomas

CT scanning is the first and preferred imaging modality for screening metastases,

since aggressive resection of pulmonary metastasis is recommended for survival.

Patients with 3 or more pulmonary nodules, bilateral nodules, or large nodules are

more likely to have metastasis. Routine chest radiographs and CT scans are

recommended for the first 5 years, with radiography at each visit, chest CT scanning

every 3 months for the first year, chest CT scanning every 4 months for the second

year, chest CT scanning every 6 months for third year, and chest CT scanning once

yearly thereafter.

Renal cell cancer

Pulmonary metastasis is seen in 25-30% of patients at the initial diagnosis and in 30-

50% at later stages of renal cell carcinoma. Resection of pulmonary metastasis has

been shown to improve survival. CXR is the recommended initial screening modality.

Chest CT scanning is indicated only for (1) a solitary pulmonary nodule, (2)

symptoms of endobronchial metastasis, (3) extensive regional disease, (4) the

12


presence of other extrathoracic metastasis amenable to resection. CT scanning is not

required if CXR shows typical multiple nodules or if CXR findings are normal in a

patient with low-stage disease. Some authors advocate lifelong biannual CXR and CT

scanning.[16]

Testicular cancer

CXR is the recommended primary imaging modality for patients with negative

abdominal CT findings, and chest CT scanning is the recommended primary imaging

modality for patients with an abnormal abdominal CT scan. This recommendation is

based on studies that showed a direct correlation between abdominal CT and chest CT

findings. For those with an abnormal abdominal CT scan, chest CT scanning detected

12.5% more nodules than seen on CXR. For those with negative abdominal CT

findings, chest CT scanning did not increase the yield over CXR. In fact, the false-

positive rate in such patients is 2.3%, which results in unnecessary increased

morbidity.[17]

Malignant melanoma

The need for chest CT scanning depends on the stage of the primary tumor.

Metastasectomy may be the only potentially curative treatment modality in stage IV

disease, regardless of the number of lesions. Chest CT scanning is recommended to

evaluate the number of nodules and other associated disease.[1]

Head and neck carcinoma

Distant metastasis is seen in 5.5% of patients with head and neck cancers. In addition,

the risk of synchronous malignancies in head and neck cancers is 15-30%. Chest CT

scanning is an important screening examination for determining metastatic disease.

Chest CT scanning has been shown to identify malignant lesions in 25.8% of these

individuals, of which 15% have been shown to be pulmonary metastases, 5.4% are

lung cancer, and 1.1% are esophageal cancers.[18]

Treatment response

13


CT is also used in assessing response to treatment. Small changes in tumor volume

can be detected using volumetric techniques.[19]

Diagnostic studies

Histopathological samples are often required for confirming the diagnosis of

pulmonary metastasis and in select cases to identify the primary tumor. Samples can

be obtained using CT-guided transthoracic biopsy or FNA cytology. The tissue

fragments can be compared with those of the primary tumor.

Immunohistochemistry is helpful in identifying the primary tumor. Transthoracic

needle aspiration has a positive yield of 85-95% in the evaluation of pulmonary

metastasis, but the yield is lower with lymphangitic spread.

Transbronchial biopsy or navigational bronchoscopic biopsy is performed in central

lesions. Occasionally, thoracoscopic wedge resection may be essential for histological

diagnosis. Extensive immunohistochemistry reveals a final diagnosis in 50% of

patients. Additional information is provided by gene expression or reverse-

transcription polymerase chain reaction (RT-PCR).[1]

Sputum cytological analysis or bronchial brushings for malignant cells may be

positive in 35-50% of patients with pulmonary metastases. Cytologic analysis of any

pleural fluid of malignant origin may yield positive results in as many as 50% of

patients. Such analysis usually does not distinguish between primary and secondary

malignant lesions; however, this can be performed for renal and colonic primaries.

Additional workup includes hematologic studies such as complete blood cell (CBC)

count and a basic metabolic panel (BMP), which may identify abnormalities possibly

related to a paraneoplastic syndrome.[1]

Limitations of techniques

CXR may not identify small metastatic lesions and may underestimate the tumor

burden. Dual-energy subtracted radiographs are more sensitive than conventional

radiographs, owing to subtraction of overlying bony tissue. CAD has also been used

for automatic detection of pulmonary nodules. Chest tomosynthesis is another low-

dose technique with higher sensitivity that is used in the detection of lung nodules. CT

14


scanning is more sensitive, but it has high rates of false positivity. The limitations of

each technique are discussed in detail in the sections below.

Radiography

The most common radiographic pattern of pulmonary metastasis is the presence of

multiple nodules, ranging in size from 3 mm to 15 cm or more. The nodules are more

common in the lung bases (owing to higher blood flow than upper lobes) and in the

outer third of the lungs in the subpleural region. They are approximately spherical and

of varying sizes. Nodules of same size are believed to originate at the same time, in a

single shower of emboli from the primary tumor. Nodules that are smaller than 2 cm

are usually round and have smooth margins. Larger nodules are lobulated and have

irregular margins; they may become confluent with adjacent nodules, resulting in a

conglomerate multinodular mass.

Pulmonary metastatic disease has several atypical presentations. Nodules may calcify

or cavitate. Spontaneous pneumothorax is a rare presentation. A solitary pulmonary

nodule is a less common presentation of pulmonary metastasis. A miliary nodular

pattern refers to the presence of innumerable 1- to 4-mm nodules in the lungs that

resemble millet seeds (see the image below). An airspace pattern, presenting with

areas of consolidation, is another atypical presentation of metastatic disease.

Endobronchial metastasis is not directly visualized in a radiograph, but it should be in

the differential list when a patient presents with postobstructive

pneumonitis/atelectasis. Pleural metastatic disease is seen as pleural nodularities or

thickening with or without pleural effusion. Isolated pleural effusion is another type of

metastatic disease.

15


Chest radiograph in a patient with thyroid cancer shows multiple miliary metastases

Lymphangitic spread is seen on plain films as reticular or reticulonodular interstitial

markings with irregular contours, Kerley B lines (thickened interlobular septa), hilar

adenopathy, and pleural disease. Lymphangitic spread is much less commonly seen on

plain radiographs than it is at pathology. Chest radiographs have been reported as

normal in 50 % of patients who had histopathologically proven lymphangitis. [4] In

addition, the radiographic appearances of lymphangitis are very nonspecific and

radiographs are accurate in only 24% of proven cases.[2]


Chest radiograph of a 58-year-old man with malignant melanoma (note surgical clips

in right lower neck) shows multiple pulmonary nodules of varying sizes consistent

with metastatic disease. There is also a small right basal effusion.

Chest radiograph in a 62-year-old woman with malignant ovarian tumor shows

multiple predominantly peripheral metastatic nodules. There are also small bibasal

pleural effusions.

16


Chest radiograph in a 67-year-old man with a history of spindle cell sarcoma of the

thigh shows 2 large masses in the right lower lobe and the left mid lung, consistent

with cannonball metastases.

Chest radiograph in a 57-year-old woman with leiomyosarcoma of the uterus shows

multiple masses in the lungs, a large one in the medial right upper lobe and right

paratracheal region, and another one in the left suprahilar region. There is also left

basal pleural effusion with atelectasis.

17


Chest radiograph in a patient with chondrosarcoma shows calcified masses in the right

and left mid lungs and the left apical region, consistent with calcified metastasis.

Chest radiograph in a 58-year-old man with squamous cell carcinoma of the tongue

shows multiple bilateral metastatic nodules, which demonstrate cavitations, consistent

with cavitating metastases.

Chest radiograph in a patient with squamous cell carcinoma of the head and neck

shows collapse of the left upper lobe seen as hazy veil-like opacification. In addition,

18


there are multiple bilateral nodules, with cavitation of the nodules on the left,

consistent with metastatic disease.

Chest radiograph in a patient with a history of angiosarcoma of the thigh shows

sudden the development of large bilateral pneumothoraces. In addition, there is right

pleural effusion. There are multiple bilateral cystic lesions identified in both the lungs.

Posteroanterior chest radiograph in a patient with a history of bladder cancer and lung

metastasis shows a large loculated hydropneumothorax.

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Lateral chest radiograph in a patient with bladder cancer and lung metastasis shows

the presence of air-fluid levels due to hydropneumothorax.

Chest radiography in a patient with laryngeal cancer shows a solitary pulmonary

nodule in the left upper lung. This was biopsy proven to be metastasis.

Chest radiograph in a 55-year-old patient with renal carcinoma shows collapse of the

right-middle and lower lobes. Note silhouetting of the right heart border and the right

dome of the diaphragm.

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Chest radiograph in a patient with breast cancer shows volume loss of the right lung

with ipsilateral mediastinal shift. There is lobulated soft-tissue thickening of the

pleura.

Chest radiograph shows a large pleural effusion and pleural metastatic nodules in a

patient with metastatic adenocarcinoma.

Chest radiograph in a patient with prostate cancer shows bilateral pleural effusions.

There are also fine reticular changes in the lungs due to lymphangitic spread.

21


Chest radiograph in a 62-year-old patient with breast cancer shows volume loss of the

right lung. There is also diffuse reticular changes of the right lung. There are a

moderately sized right pleural effusion with atelectasis. No focal lesion is seen in the

left lung. The findings are consistent with lymphangitis carcinomatosis.

Degree of confidence

CXR is shown to have less sensitivity and specificity than CT scanning in detection of

pulmonary nodules.[15, 20] Chest radiographs are known to have low sensitivity

compared with CT scans in the detection of pulmonary metastatic nodules, especially

in primary head and neck cancers. CXR fails to depict pulmonary metastatic lesions

smaller than 7 mm, particularly those at the lung apices, bases, central locations

adjacent to heart and mediastinum, pleural surfaces, and under the ribs. Compared

with CT scanning, CXR is limited by overlapping structures and low contrast of the

nodule. Nodules may also be obscured by vascular markings or may be hidden in

areas of atelectasis or consolidation.

Of nodules smaller than 7 mm detected on CXR, 77% are calcified and are more

likely to be granulomas.[20] One study demonstrated sensitivities of 67% versus 100%,

respectively, for CXR and PET scanning in the detection of metastatic nodules. [21] In

addition, CXR also demonstrates fewer nodules than are shown with CT scanning.

Often, a solitary lesion seen with CXR is associated with multiple nodules on a CT

scan. Other causes of failure of nodule detection include incomplete visual survey or

interpretative failures.[22]

Sensitivity may be increased by using dual-energy subtraction, with which the

superimposed bony structures can be subtracted. This technique uses the differences in

the degree to which body tissues attenuate high- and low-energy photons. The

differences are used to generate tissue-selective images. Bones have higher

attenuation coefficient at lower photon and beam energy, so that structures containing

calcium can be removed from image.

Dual-energy systems can be single- or dual-exposure systems. With single-exposure

system, one radiograph is obtained by exposing 2 storage phosphor plates separated

by a copper filter. Since the front plate receives a whole-energy beam, a standard

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image is produced, whereas the copper filter filters out the lower-energy photons, so

that the back plate receives higher-energy photons. One weighted subtraction

produces a bone-selective image, whereas the different weighted subtraction produces

a soft-tissue–subtracted image. One disadvantage is a low signal-to-noise ratio.

With dual-energy systems, 2 radiographs are obtained at 60 and 120 kV, with the

higher kV exposure producing a standard image. The signal-to-noise ratio of a dual-

exposure system is higher than a single-exposure system. Misregistration artifacts may

be produced due to an approximately 200-millisecond delay between the 2 exposures,

caused by cardiac, respiratory, and patient motion. Dual-energy subtraction improves

the ability to detect calcified and noncalcified nodules by reducing anatomic noise

from overlying bones. Detection of calcium improves the confidence in making a

diagnosis of a benign nodule.[23] Temporal subtraction enables easier detection of areas

that have changed between radiographs at different time points.[22]

Chest tomosynthesis is a relatively novel technique that increases the sensitivity of

radiographs. The tomosynthesis system involves an x-ray tube, flat panel detector,

computer-controlled tube mover, and special reconstruction algorithms to produce an

arbitrary number of a section of images of the chest from a single pass of the x-ray

tube. Tomographic images are obtained at lesser radiation and cost than a CT scan.

Compared with radiography, it improves detection of nodules by reducing visual

clutter from the overlying normal anatomy. Visibility of normal structures, such as

vessels and airways, is improved.[24]

However, the depth resolution of tomosynthesis is lower than that of CT owing to the

limited angle used and low radiation dose, but this is much better than with CXR. A

typical tomosynthesis obtains 60 projection images, with radiation exposure of

approximately 2 microsieverts (mSv), with a total dose of 0.12 mSv, which is 3 times

higher than with CXR (0.04 mSv) but much lesser than with CT (4 mSv).

Studies have shown higher visualization of nodules with tomosynthesis than with

radiography. For example, in the study by Vikgren et al, CXR detected only 7% of

nodules sized 4-6 mm, while tomosynthesis detected 50% of nodules.[25] Sensitivity is

increased, especially for nodules smaller than 9 mm. Increased detectability is

associated with a modest increase in radiation dose.

23


Computer-aided detection (CAD) can be used as a second reader to detect small

nodules that may be overlooked. This is useful for radiologists in training and has

been applied both for frontal and lateral radiographs.[22]

Note that these technologies may not be routinely available at all institutions.

False positives/negatives

False-positive findings can be seen because of a variety of disease processes. This

depends on the pattern of the disease. Multiple pulmonary nodules can be seen in

several other entities. Solitary pulmonary nodules can be due to primary lung cancer, a

granuloma, a hamartoma, a vascular lesion, infection, or focal fibrosis. Lymphangitis

carcinomatosis may be mistaken for pulmonary edema and fibrosis. Pulmonary

hypertension resulting from thromboembolic disease may mimic disease caused by

intravascular emboli.

False-negative findings are seen in small lesions or when nodules are obscured by

adjacent bony or vascular structures or pathological processes, such as atelectasis or

consolidation.

As a result of these limitations, several authors have disputed the role of routine CXR

in patients undergoing metastatic screening. A study showed that undiagnosed

metastasis was shown in radiographs in only 0.93 % of patients with known breast

cancer.[26] Another study showed that in localized cutaneous malignant melanoma,

although 15% had abnormal findings on initial CXR, only 0.1 % had true-positive

metastatic lesions in follow-up radiographs.[27] These false-positive findings have been

shown to increase patient anxiety.

These authors recommend that cost effectiveness may be increased by reducing the

frequency of screening in the first 2 years and limiting screening to only the first 5-10

years after diagnosis. In patients with a higher chance of pulmonary metastasis,

screening should be more frequent, and a more sensitive test, namely CT scanning, is

preferred.[1]

Computed Tomography

24


CT scanning is the modality of choice for detection and follow-up of pulmonary

metastasis, owing to its higher spatial, temporal, and contrast resolution and lack of

superimposition of adjacent structures. It has been shown to have higher sensitivity

than chest radiography (CXR) in the detection of pulmonary metastases. CT scanning

is performed using a multislice technique, and no intravenous contrast is required for

the detection of pulmonary metastases. Contrast may be useful when a nodule is

located adjacent to the hilum and mediastinum.


Axial CT scan in a 58-year-old man with malignant melanoma shows multiple round

nodules and masses of varying sizes in both lungs, consistent with metastases. There

are also small bilateral pleural effusions.

Coronal CT scan in a 58-year-old man with malignant melanoma shows multiple,

predominantly basal nodules of varying sizes, consistent with metastatic disease.

25


Axial CT scan in a 62-year-old woman with malignant ovarian tumor shows

predominantly subpleural metastatic nodules of varying sizes.

Coronal CT scan in a 62-year-old woman with malignant ovarian tumor shows

predominantly peripheral subpleural metastatic nodules of varying sizes.

Axial CT scan in a 67-year-old man with a history of spindle cell sarcoma of the thigh

shows a heterogeneously enhancing mass in the right lower lobe that is extending to

the mediastinum and into the chest wall.

The radiation dose from frequent CT scannings can be reduced by using several dose-

reduction techniques such as low kV, low mAs, adaptive-tube current modulation, and

iterative reconstruction algorithms. The sensitivity of nodule detection can be

increased by using postprocessing tools such as maximum-intensity projection (MIP)

26


or volume rendering (VR) or using cine viewing of data sets (see the images below).

High-resolution CT (HRCT) scanning is used for detection of lymphangitic

carcinomatosis. In this technique, spatial resolution is maximized by narrow

collimation (1-2 mm) and high-resolution reconstruction algorithm.

Axial maximum-intensity projection image with lung window demonstrates the

chondroid matrix, consistent with metastatic disease.

Axial maximum-intensity projection CT scan (8 mm thick) shows a small nodule in

the right apical region in a patient with colonic cancer metastasis. Detection of

metastasis early in the course of cancer is essential for treatment.

Coronal maximum-intensity projection CT scan (8 mm thick) shows the metastatic

nodule in the right apical region in a patient with colonic cancer metastasis.

27


Axial maximum-intensity projection CT scan in another patient shows the presence of

multiple small metastatic nodules.

The most common CT pattern of pulmonary metastasis is the presence of multiple

pulmonary nodules (see the images below). These nodules are in a random

distribution and are of varying sizes, owing to multiple episodes of tumor

embolization or different tumor growth rates. Nodules of the same size are believed to

be due to a shower of emboli that occurred at the same time. The margins can be

smooth or irregular and can be either well defined or ill defined. The nodule has soft-

tissue attenuation and can have a prominent pulmonary vessel heading into it, which is

called the feeding-vessel sign. They are more common in the lung bases, owing to

higher vascular supply.

CT scan in a 58-year-old man with squamous cell carcinoma of the tongue shows

multiple bilateral cavitating metastatic nodules. There is also a right pleural effusion.

28


Coronal CT image in a patient with squamous cell carcinoma of the head and neck

demonstrates multiple cavitating pulmonary metastases and left upper lobe collapse.

When the nodules are numerous, they are distributed diffusely throughout the lungs in

a random pattern without any specific anatomical distribution; when nodules are few,

they are predominantly subpleural. Multiple pulmonary nodules in a patient with

known malignancy are highly suggestive of metastasis. Of multiple pulmonary

nodules detected with CT scanning, 73% are shown to be metastases.[28] While 80-90%

of patients with multiple metastatic nodules have a history of malignancy, some do not

have a malignancy at the time of diagnosis, and, in few rare cases, the primary may

never be found.

The margins of the pulmonary metastasis are well circumscribed since histologically

the tumor cells invade perivascular interstitium and have clear, smooth margins.

However, once the tumor grows out of the vessels into the adjacent interstitium and

alveolar space and proliferates, the margins become irregular. A radiologic-pathologic

correlation study showed that well-defined, smooth-marginated metastasis

corresponded to an expanding alveolar space-filling type (eg, hepatocellular

carcinoma); poorly defined, smooth-marginated metastasis corresponded to an

alveolar cell type (adenocarcinoma); and poorly defined, irregular-marginated

metastasis corresponded to an interstitial proliferating type (squamous carcinoma or

metastases after chemotherapy). Some correlation also exists between the histological

type of primary tumor and CT appearance of a lesion margin.[4]

Because of this nonspecificity of margins, it is difficult to distinguish metastases from

other confounding lesions. For example, some metastases have smooth margins and,

hence, cannot be distinguished from benign lesions based on margins. Since some

29


metastases have irregular margins, the margins cannot be used as a factor to

differentiate primary cancer in a solitary pulmonary nodule.

The differential diagnosis for multiple pulmonary nodules includes infections (eg,

histoplasmosis, coccidioidomycosis in endemic areas, cryptococcal and nocardial

infections as opportunistic infections in immunocompromised patients, septic emboli,

abscess, paragonimiasis, hydatid), granulomatous diseases (eg, tuberculosis,

sarcoidosis), and vascular/collagen-vascular diseases (eg, Wegener granulomatosis,

rheumatoid arthritis). Appropriate clinical history and a temporal radiographic pattern

showing the evolution of ill-defined pulmonary opacities into organizing, more

circumscribed nodules as part of the healing process is the key factor differentiating

these from pulmonary metastatic disease. Follow-up CT scanning in 6 weeks to 3

months will show progression of metastatic nodules, while benign lesions show no

growth, decrease in size, or undergo complete resolution.

While these classic features are extremely helpful in narrowing the differential mainly

down to metastases, it is the atypical features of lung metastases that are difficult to

distinguish it from more benign lung pathology.

Cannonball metastasis (see the image below) refers to the presence of few, large, well-

circumscribed, and round metastatic masses. It is usually seen in metastasis from renal

carcinoma, choriocarcinoma, colon cancer, prostate cancer, or endometrial carcinoma.

Chest radiograph in a 67-year-old man with a history of spindle cell sarcoma of the

thigh shows 2 large masses in the right lower lobe and the left mid lung, consistent

with cannonball metastases.

30


Miliary nodules refer to numerous, small 1-4 mm, same-sized nodular opacities that

resemble millet seeds. Miliary metastases are seen in cancers of the thyroid

(medullary carcinoma), kidney, breast, and pancreas, as well as in malignant

melanoma, osteosarcoma, and trophoblastic disease. They are believed to be caused

from a single massive shower of tumor emboli. Miliary nodules are seen in a random

distribution within the secondary pulmonary lobule and involve the subpleural

regions. (Note that centrilobular nodules spare the subpleural regions, whereas

perilymphatic nodules involve the subpleural regions and the peribronchovascular

regions.) The differential diagnosis for miliary nodules includes granulomatous

infections such as tuberculosis, histoplasmosis, healed varicella pneumonia,

sarcoidosis, silicosis, coal worker’s pneumonoconiosis, hypersensitivity pneumonitis,

and Langerhans cell histiocytosis.

Histological studies have described the distribution of a metastatic nodule within a

secondary pulmonary nodule. The metastatic nodule initially proliferates from tumor

emboli in the arteriole or capillary. Initially, a metastatic nodule is seen in a peripheral

portion than the centrilobular structures. Only 11-12 % were shown to be located in

the central bronchovascular bundle,[4] with 60-68% between central and perilobular

structures and 20-28% in perilobular structures. When the metastasis subsequently

grows, it appears to be connected with the bronchovascular bundle, which is called the

mass-vessel sign. Small, random metastatic nodules in secondary pulmonary lobules

are randomly distributed with no uniform relationship to secondary pulmonary lobular

structures.

Cavitation is seen in 4% of metastases (vs 9% of lung primaries).[29] Tumor necrosis

and discharge of necrotic material is thought to be the primary mechanism behind

cavitating lung metastases (excavating metastasis). These tumors initially are solid

and later become a cavitary lesion with thick and irregular walls. See the images

below.

31


Chest radiograph obtained 6 months later in the patient above shows the development

of a cavitating lesion with air-fluid levels in the left lower lobe.

CT scan 6 months later than the initial CT scan (same patient as above) shows that the

cavity has enlarged in size and has also cavitated, indicating the presence of excavated

metastasis.

Cavitation can also be caused by a check-valve mechanism of tumor infiltrating into

bronchial structures. Head and neck cancers in males and genitalia cancers in females

are the common causes. Squamous cell carcinomas are the most common (70%)

primary tumor to cause cavitation, especially seen on radiographs, although

adenocarcinomas (GI tract, breast), transitional cell tumors, and sarcomas are also

known to cavitate on CT scans. On CT scans, 10% of squamous carcinoma metastases

were shown to cavitate, while 9.5% of adenocarcinoma metastases were also shown to

cavitate.[30] Cavitation can also be seen following chemotherapy of metastatic nodules.

Cavitated metastasis usually has thick and irregular walls. Thin-walled cavities are

seen in sarcomas, which are the ones that often result in pneumothorax. See the

images below.

32


Axial CT scan in a patient with history of angiosarcoma of the thigh shows a

pneumothorax on the left. There are multiple thin-walled cystic metastatic lesions,

some of which can be clearly seen extending up to the subpleural region. The

pneumothorax is presumably caused by rupture of a cystic metastasis into the pleural

space.

Coronal CT scan in a patient with history of angiosarcoma of the thigh shows a

pneumothorax on the left. There are multiple thin-walled cystic metastatic lesions,

some of which can be clearly seen extending up to the subpleural region. The

pneumothorax is presumably caused by rupture of a cystic metastasis into the pleural

space.

The differential diagnosis for cavitating nodules includes septic emboli (eg, septic

patients, intravenous drug abusers), lung abscess, tuberculosis, angiitis, Wegener

granulomatosis, and rheumatoid nodules. Nine percent of primary lung tumors

cavitate, most commonly squamous cell cancers.

Spontaneous pneumothorax is an uncommon presentation of pulmonary metastasis.

Osteosarcoma is the most common tumor known to produce pneumothorax.

Pneumothorax has been shown in 5-7% of osteosarcoma metastasis.[31] Spontaneous

33


pneumothorax in a patient with osteosarcoma should raise suspicion of pulmonary

metastasis, which can be detected with CT scanning. Aggressive sarcomas and

nonsarcomatous tumors can also produce pneumothorax. The proposed theory behind

spontaneous pneumothorax is tumor necrosis in peripheral subpleural nodules

resulting in a bronchopleural fistula with subsequent pneumothorax. The differential

diagnosis for pneumothorax includes rupture of a subpleural bleb, trauma, mechanical

ventilation complications, and underlying lung diseases (eg, cystic fibrosis,

tuberculosis, fibrosis, sarcoidosis).

Metastasis from teratoma of the testis may show complete fibrosis or necrosis after

chemotherapy. Thin-walled air cysts, which contain no viable tumor, are present at the

site of treated metastasis. Multiple thin-walled cystic metastases are also seen in

metastasis from angiosarcoma. This is the second most common type of presentation

for angiosarcoma metastasis after multiple pulmonary nodules. Rupture of subpleural

cystic metastasis may result in pneumothorax. Proposed mechanisms for thin-walled

cysts are (1) excavation of a solid nodular lesion through discharge of necrotic tumor

material, (2) infiltration of tumor cells into walls of preexisting bulla, (3) a ball-valve

effect caused by circumferential growth of tumor around small bronchioles resulting

in bronchiolar obstruction, and (4) proliferation of tumor cells forming blood-filled

cystic spaces anastomosing the network of sinusoids.[32]

Calcification of metastatic nodule is often seen only on CT scans. Calcification is seen

in metastasis from osteosarcoma, chondrosarcoma, giant cell tumor of the bone,

mucinous adenocarcinoma, and treated metastatic choriocarcinoma. Reasons for

calcification vary but include bone formation in primary bone tumors (osteosarcoma,

chondrosarcoma), dystrophic calcification (papillary thyroid cancers, giant cell tumor

of bone, synovial sarcoma, treated metastasis), and mucoid calcification (mucinous

adenocarcinomas of the GI tract, breast, thyroid, ovary). Punctate calcification may be

seen following hemorrhagic necrosis in angiosarcoma.[32] Calcification can also be

seen following chemotherapy and radiation therapy. In osteosarcomas, dense,

eccentric calcification/ossification is seen. In rare instances, calcification may develop

at the site of pulmonary metastasis (typically from a testicular primary site) that has

vanished after chemotherapy.[30]

34


The differential diagnosis for calcified nodule includes granulomatous diseases

(tuberculosis, histoplasmosis), sarcoidosis, silicosis, coal worker’s pneumoconiosis,

and alveolar microlithiasis. CT scans cannot help differentiate calcifications or

ossifications due to metastasis from calcifications or ossifications due to other lesions.

Another atypical feature of metastatic disease is nodular density surrounded by a halo

of ground-glass attenuation or ill-defined fuzzy margins (ie, the CT halo sign). This is

seen in hypervascular primary tumors such as choriocarcinoma (parenchymal

hemorrhage), angiosarcoma (fragility of neovascular tissue resulting in rupture of

vessels), or renal carcinoma. A ruptured vessel secondary to fragile neovascular tissue

leads to hemorrhage, causing the ground-glass halo on CT scans.

The differential diagnosis for this appearance includes invasive aspergillosis,

candidiasis, tuberculoma, Wegener granulomatosis, minimally invasive

adenocarcinoma, pneumonia, eosinophilic pneumonia, abscess and lymphoma in

immunocompromised patients (due to fibrin, less dense inflammatory reaction, edema,

or less densely arranged malignant cells histopathologically), or post biopsy.

An air-space pattern is another atypical presentation of metastasis. This can be due to

lepidic growth of tumor along intact alveolar walls, which is seen in metastatic

adenocarcinoma from GI tract, ovary, or breast. Imaging features include

consolidation with air bronchography, ground-glass opacities, and air-space nodules.

Another mechanism is pulmonary infarction due to tumor embolism, which is seen in

tumors of the liver, breast, kidney, stomach, and prostate, as well as in

choriocarcinoma. The differential diagnosis for this air-space pattern includes

infections, edema, hemorrhage, organizing pneumonia, eosinophilic pneumonia,

minimally invasive adenocarcinoma, lymphoma, and sarcoidosis, among other

entities.

Tumor embolism is a less common presentation of metastatic disease. Although most

pulmonary metastases result from microscopic tumor embolization, only a few survive

to proliferate as metastases. With tumor emboli, the tumor is confined to the vascular

tree, without proliferation of metastasis into extravascular tissue. In an autopsy series,

intravascular tumor emboli have been seen in 2.4-26% of patients with solid

malignancy.[33] Tumor emboli is seen in metastasis from liver, breast, renal, gastric,

35


and prostatic cancers, as well as in sarcomas and choriocarcinomas. Tumor emboli are

seen in small or medium-sized arteries. Large tumor emboli within main, lobar, or

segmental pulmonary arterial branches are only rarely seen.

Diagnosis may be difficult to make, even with HRCT scanning. On CT scans,

multifocal dilatation and beading of the peripheral subsegmental arteries are seen due

to smaller tumor emboli. Also seen are peripheral wedge-shaped areas of infarction.

Perfusion defects can be identified with dual-source CT scanning. Occasionally, tumor

emboli may be seen within the larger pulmonary vessels.

The differential diagnosis of tumor emboli includes pulmonary thromboembolism and

pulmonary artery sarcoma. Pulmonary artery enlargement (>2.9 cm, or larger than the

ascending aorta) may be due to large tumor emboli or the development of pulmonary

hypertension from large or numerous tumor emboli.

Endobronchial metastasis is rare, seen in 2% of tumors.[30] Primaries that cause

endobronchial metastases are renal, breast, colorectal, and pancreatic cancers.

Endobronchial involvement occurs through 2 routes: (1) direct endobronchial

deposition through aspiration, hematogenous, or lymphatic spread or (2) by airway

invasion of tumor into adjacent lymph nodes/parenchyma. The endobronchial lesion,

as well as the consequences (eg, lobar atelectasis or, less commonly, complete

collapse of a unilateral lung) can be identified on CT scans. The differential diagnosis

includes primary neoplasms such as bronchogenic carcinoma, carcinoid, granulomas

such as in tuberculosis, histoplasmosis, foreign bodies, or broncholiths. See the

images below.

Axial CT scan of the same patient at a higher level shows an endobronchial mass

within the bronchus intermedius, which is the cause of the collapse of the right upper

and lower lobe.

36


Axial positron emission tomography scan of the same patient shows high uptake in the

endobronchial mass, which was proven to be endobronchial metastasis.

Solitary pulmonary nodule (see the image below) is a less common presentation of

metastatic disease. Solitary pulmonary nodule is a round opacity that is at least

moderately well marginated and less than 3 cm in maximum diameter. [22] Solitary

pulmonary metastasis is frequent in melanoma; sarcoma; and cancers of colon, breast,

kidney, bladder, and testicle. Carcinoma of the colon, especially from the

rectosigmoid area, accounts for a third of cases with solitary pulmonary metastasis.

Metastasis accounts for 2-10% of solitary nodules.[34] The differential diagnosis is

extensive, but the most common lesions are primary lung neoplasms, granuloma,

hamartoma, and arteriovenous malformation. Granulomas (tuberculosis,

histoplasmosis) show calcification, which is usually central, diffuse, or laminated.

Hamartoma may have “popcorn” calcification, fat attenuation, or a combination.

Arteriovenous malformation has a feeding vessel.

Axial CT scan in a patient with laryngeal cancer shows a solitary pulmonary nodule in

the apicoposterior segment of the left upper lobe. This was biopsy proven to be

metastasis.

37


In a patient with known malignancy, development of a solitary pulmonary nodule is a

challenge. Distinguishing between a primary and secondary neoplasm is important,

since it has prognostic and therapeutic implications. At surgery, 0.4-9% of solitary

pulmonary nodules are likely to be metastasis in a patient with known extrathoracic

malignancy.[34] Solitary pulmonary nodules seen on radiographs have a 25% chance of

being metastasis,[30] while those seen on chest CT scans have a 46% chance of being

metastasis in a patient with known extrathoracic malignancy.[30] It should be noted that

CT scans may show additional lesions compared with a radiograph, in which case the

diagnosis becomes easier. More than one additional nodule was seen on a CT scan in

32% of patients with suspected solitary pulmonary nodule based on radiographs.[35]

The likelihood of a solitary pulmonary nodule being metastasis depends on the

histopathology of the primary tumor and age of the patient. [30] The incidence of a

second primary lung malignancy is higher than a solitary metastasis in patients with

cancers of the head and neck (8:1 ratio), bladder, breast, cervix, bile ducts, esophagus,

ovary, prostate, or stomach (3:1 ratio for all these). This likelihood also exists for

tumors of the salivary gland, adrenals, colon, kidney, thyroid, thymus, or uterus. There

is higher chance of metastasis (2.5:1) with melanoma, sarcoma, and testicular cancer.[36] In patients with melanoma or sarcoma, solitary lung metastasis is more common

than a second primary lung cancer.

No reliable imaging features help to distinguish a solitary pulmonary metastatic

nodule from primary pulmonary neoplasms. Metastatic nodules may be round or oval,

or they may have lobulated margins. Initially, it was thought that metastatic solitary

pulmonary nodules have smooth margins compared with primary lung cancers, which

can have speculated or lobulated margins. However, it is now known that margins are

not helpful in distinguishing primary and secondary tumors, since metastasis can also

have irregular, speculated margins due to a desmoplastic reaction or tumor infiltration

into the adjacent lymphatics or bronchovascular structures. Smooth borders and

lobulated margins can also be seen in benign lesions such as hamartomas. See the

images below.

38


Coronal contrast CT scan in a patient with breast cancer shows volume loss of the

right lung with multiple lobulated pleural metastatic nodules.

Axial CT scan in the same patient shows volume loss of the right lung and lobulated

pleural metastasis extending to the mediastinal pleural surface

Laminated, central, diffuse, and popcorn calcification are benign patterns, while

stippled and eccentric calcifications are considered malignant. Solitary metastases are

more common in lower lobes, while primary lung cancer is more common in upper

lobes. Attenuation measurements may be of some value. In a recent study,[37] the mean

attenuation value of pulmonary metastasis from renal cancer was found to be higher

than that of primary lung cancer nodules. The interval between appearance of initial

tumor and solitary pulmonary nodule may be useful. An interval of more than 5 years

in patients with osteosarcoma more likely represents a new primary tumor. However,

in patients with carcinoma of the breast or kidney, pulmonary metastases may occur

many years after the primary tumor is diagnosed. Biopsy is often required for

histopathological diagnosis in this scenario.

Lymphangitic carcinomatosis refers to spread of a neoplasm through the lymphatics

(see the images below). It is most commonly seen in adenocarcinomas, particularly

primary tumors of breast, lung, stomach, pancreas, uterus, rectum, or prostate. It is

39


seen in 35% of autopsies of patients with solid tumors.[2] It occurs from hematogenous

spread to the lungs, with subsequent lymphatic invasion or direct lymphatic spread

from mediastinal and hilar lymph nodes.

Axial high-resolution CT scan in another patient with renal cancer shows smooth

interlobar septal thickening in the upper lobes, right greater than left, and bilateral

pleural effusions. This was caused by lymphangitic spread. The differential diagnosis

includes edema and infection.

Coronal CT scan in the same patient with breast cancer shows smooth interlobar

septal thickening in the upper lobes, right greater than left, and bilateral pleural

effusions. This was caused by lymphangitic spread. The differential diagnosis includes

edema and infection.

Microscopically, malignant cells are seen in lymphatic cells and interlobular septa.

Edema or a desmoplastic reaction can contribute to interstitial thickening. Associated

pleural involvement is common. The imaging appearance is due to direct tumor

growth in pulmonary capillaries and lymphatics within septal interstitium. The typical

CT pattern consists of smooth, beaded, or nodular thickening of the interlobular septa.

Smooth subpleural interstitial thickening is seen as thickening of fissures. There is

40


also thickening of the axial interstitium surrounding the vessels and bronchi in

parahilar regions, resulting in peribronchial cuffing.

Nodules are seen in a perilymphatic distribution in the peribronchovascular and

subpleural regions. However, the lung architecture is preserved at the lobular level. A

nodular component from intraparenchymal extension may be associated with

lymphangitic carcinomatosis. A polygonal structure with a central dot may be seen

due to thickened interlobular septa and thickened intralobular axial interstitium by

tumor growth.

The above-mentioned findings can be bilateral and symmetrical or asymmetrical, or

diffuse or focal. Lymphangitic spread is more common in the lower lobes. In patients

with malignancies and dyspnea, diagnosis is confirmed on imaging findings, and no

further examination is indicated. Hilar lymphadenopathy and mediastinal

lymphadenopathy are present in 20-40% of patients, which may be symmetrical or

asymmetrical, and pleural effusions are present in 30-50% of patients with

lymphangitic carcinomatosis.[2]

Early diagnosis of lymphangitic carcinomatosis based on CXR findings can be

difficult, as they may be normal in 30-50% of proven cases.[2] Lymphangitic spread

can also be caused by primary tumors of the lungs, especially small cell carcinoma

and adenocarcinoma. The differential diagnosis of perilymphatic nodules includes

sarcoidosis, silicosis, coal worker’s pneumoconiosis, and amyloidosis. When the

septal thickening is smooth, the differential diagnosis includes edema, infection, and

fibrosis. An absence, distortion, or destruction of normal lung architecture at the

lobular level distinguishes lymphangitis from pulmonary fibrosis, which is associated

with architectural distortion. Although sarcoidosis has a similar appearance, with

perilymphatic nodules and nodular or beaded interstitial thickening, the degree of

septal thickening is less than that of lymphangitic spread.

Pleural metastases (see the first image below) originate from hematogenous spread to

the pleura, but occasionally they may be caused by lymphangitic spread or by direct

infiltration of chest wall, abdomen, and mediastinum or from established hepatic

metastases. Tumors that spread to the pleura are lung, breast, pancreas, and stomach.

Pleural metastases are seen as nodularities, a plaquelike formation on the pleural

41


surface with or without associated pleural effusion. Pleural metastases in contact with

the fissures and the diaphragm may be easily detected using CT scanning (see the

second and third images below). The differential diagnosis includes malignant

mesothelioma, invasive thymoma, and lymphoma.

Axial CT scan in the same patient shows volume loss of the right lung and lobulated

pleural metastasis extending to the mediastinal pleural surface

Axial CT scan of a patient with thyroid cancer shows multiple solid masses along the

right major fissure, which are metastatic. There is also right pleural effusion.

Coronal CT scan of a patient with thyroid cancer shows multiple solid masses along

the right major fissure, which are metastatic. There is also right pleural effusion.

42


Malignant pleural effusion is seen in the lung, breast, and ovaries, as well as in

lymphoma. It is seen in up to 42% of cases. There may be associated pleural

thickening and contrast enhancement.[30] See the images below.

Axial CT scan in a patient with breast cancer shows malignant effusion on the right

with multiple contrast-enhancing metastatic nodules.

Coronal CT scan in a patient with breast cancer shows malignant effusion on the right

with multiple contrast-enhancing metastatic nodules.

Dilated, tortuous, and enhancing vessels are occasionally seen within metastasis. This

is seen in very vascular primaries, particularly sarcomas such as alveolar soft-tissue

sarcoma and leiomyosarcoma.

Tracheal metastasis (see the images below) is seen either from local invasion of

tumors such as thyroid, larynx, esophagus, or lung tumors, or by hematogenous spread

of tumors, most commonly colorectal, breast, renal, sarcoma, melanoma, and

hematological malignancies such as plasmacytoma and chloroma. Typically, tracheal

metastasis is discovered 4 years after the primary tumor. The clinical presentation is

hemoptysis and coughing. CT scans shows solitary or multiple masses within the

43


trachea. The imaging appearances are nonspecific and can be seen in infections

(tuberculosis, histoplasmosis), inflammatory conditions (sarcoidosis), and neoplastic

conditions (squamous cell carcinoma, mucoepidermoid carcinoma, adenoid cystic

carcinoma). A history of extratracheal malignancy is helpful. The diagnosis can be

confirmed by biopsy. Volume-rendered images of the airway are helpful in planning

bronchoscopic biopsy.

Axial CT scan shows a large metastatic mass in the trachea from squamous cell

carcinoma of the lung.

Coronal CT scan shows a large metastatic mass in the trachea from squamous cell

carcinoma of the lung.

Occasionally, a metastatic nodule that is seen on a CT scan may histologically contain

only necrotic nodule–viable tumor cells, with or without fibrosis. This is called

sterilized metastases. This is seen in choriocarcinoma or testicular carcinoma after

chemotherapy. Serial CT scans show no change in the size of the nodules.

Fluorodeoxyglucose (FDG) positron emission tomograph (PET) scanning may be

44


useful in such a scenario, since a previously active tumor may now have no FDG

uptake. Biological markers such as β-human chorionic gonadotrophin and α-

fetoprotein may be negative. Biopsy is often required for confirmation and for

excluding the presence of a viable tumor. Occasionally, a sterilized and viable tumor

may coexist.[30]

Another interesting scenario is when a malignant germ cell tumor converts into a

benign mature teratoma, resulting in a persistent or sometimes even enlarging mass.

Again, in this scenario, the tumor markers may be negative. Diagnosis can be

confirmed by biopsy.[30]

Even rarer is the development of thin-walled cavities, namely pulmonary lacunae that

develop at sites of germ cell tumors treated with chemotherapy. These may persist for

many years and are not malignant.

Occasionally, benign tumors may metastasize to the lung. This is seen in leiomyoma

of the uterus, hydatidiform mole of the uterus, giant cell tumor of bone,

chondroblastoma, meningioma, and pleomorphic adenoma of the salivary gland. The

radiological findings of these lesions are indistinguishable from those of metastatic

malignant lesions, with the only difference being that they show slow or no growth.

Maximum-intensity projection/volume rendering

While significant progress has been made with technological advancements resulting

in today’s multidetector CT scanning techniques, human perception errors continue to

be a significant hurdle in the detection of small intrapulmonary nodules. To that end,

there are commercially available techniques such as MIP and VR that allow

displaying a subvolume of the 3-dimensional data set. In MIP, only voxels with the

maximum intensity are displayed along a projection line from the viewer’s eye

through the 3-dimensional volume of interest. On the other hand, the VR technique

incorporates the assignment of opacity values to CT numbers, meaning high opacity

values produce an appearance similar to surface rendering and low opacity values

allow the user to “see through” structures.

A publication from 2007 directly compared MIP with VR in the detection of

pulmonary nodules. VR performed significantly better than MIP for lung nodules

45


smaller than 11 mm in diameter (P < .001) and was equivalent to MIP (P =.061) for

larger nodules. Additionally, VR was better in the detection of perihilar nodules.[38]

A study by Jankowski et al[39] showed that the sensitivity of nodule detection was

higher with MIP than with 1-mm axial images or computer-aided detection (CAD) for

all nodules (F-values=0.046). For nodules larger than 3 mm, sensitivities were higher

with 1-mm images or MIP than with CAD (P < .0001). In addition, MIP is the least

time-consuming technique, and CAD was the most time-consuming technique. MIP

and CAD reduced the number of overlooked small nodules. Using MIP reduces the

number of overlooked small pulmonary nodules, especially in the central lung and in

junior-reviewer detection of pulmonary nodules.[40]

Kawel et al[41] showed that the sensitivity of nodule detection was superior for 8-mm

MIP than for 11-mm MIP and all thicknesses of volume-rendered images, independent

of nodule localization and size.

46


Computer-aided detection

CAD has been shown to assist radiologists in the detection of pulmonary nodules.

Modern multislice CT systems are associated with huge data sets, in which small

lesions may be easily missed. A CAD system recognizes opaque lesions surrounded

by lung parenchymal attenuation as nodules. The sensitivity of a CAD system varies

from 38-95% in various studies,[42] owing to varying algorithms, CT input, and varying

populations. Nodules not surrounded by lung parenchyma are likely to be missed,

particularly in the subpleural areas, fissural areas, and costophrenic angle areas. Some

lung parenchymal nodules may also be messed. In a study by Song et al, CAD

detected an additional 5% of nodules compared with human readers.[42] However, a

high false-positive rate is a major limitation, which hinders its widespread application.

The main use of CAD is as a second reader to improve the sensitivity of the human

reader. CAD identifies nodules overlooked by radiologists. A study by Armato et al

showed that CAD detected 84% of 38 cancers missed by radiologists.[43] CAD can also

be used to determine the probabilities of malignancy. The potential exists for

integrating CT and PET data to improve characterization.[44] CAD can also measure

tumor size, tumor volume, attenuation, and enhancement characteristics. It can also

assess temporal changes in the characteristics of nodules based on CT scans obtained

at different time points. By automatically identifying corresponding CT sections, it

decreases interpreter time. Textural characteristics of the tumor may also be assessed

to determine the presence of solid components, which have a higher likelihood of

transformation into malignant nodules.[22]

A limitation is of CAD is the decreased efficiency in the detection of ground-glass

nodules.

Indications

CT scanning is not required if CXR shows multiple nodules in a patient with a known

primary malignancy. In a patient with known malignancy, chest CT scanning is

performed if (1) CXR shows a solitary nodule; (2) CXR shows an equivocal nodule;

(3) CXR findings are negative but the extrathoracic malignancy has a high risk of lung

metastasis (eg, breast, kidney, colon, bladder); or (4) CXR shows multiple nodules,

47


but biopsy or definitive treatment by mastectomy, chemotherapy, and radiation is

planned. In patients with high-risk tumors such as bone and soft-tissue sarcomas,

testicular tumors, and choriocarcinomas, CT scanning is recommended every 3-6

months for 2 years.[1]


CT scanning has much higher sensitivity than CXR in the detection of pulmonary

metastases. However, studies including that by McCormack et al showed that CT

scanning underestimated the pulmonary metastatic involvement discovered in surgery

by up to 25%.[45] Another study showed that surgery discovered 22% more malignant

nodules than those detected by helical CT scanning.[1] Hence, manual palpation is

recommended during surgery to detect subtle lesions.

CAD is also available for chest CT scanning, most often as a second look after the

radiologist has reviewed the study. It has been shown to detect 82.4% of known

pulmonary nodules.[46] Currently, these techniques are still at the developmental stage

and are used only if the image quality is good; additionally, breathing artifact is

limited with stable lung expansion.


Although CT scanning is very sensitive, the finding of a nodule is not specific. False-

positive results may be caused by hamartomas, granulomas (eg, tuberculosis,

histoplasmosis, Wegener granulomatosis), sarcoidosis, silicosis, small infarcts, small

areas of fibrosis, and intrapulmonary lymph nodes. The specificity of CT scanning

depends on the following:

Propensity of the primary malignancy to metastasize to the lung

Stage of primary malignancy

Age

Smoking history

History of prior treatment

History of granulomatous disease

Prevalence of benign nodules in the population

48


Features that are more favorable of malignancy are as follows:

Noncalcified nodule

Spherical or ovoid shape rather than linear or irregular shape

Close relationship to adjacent vessel

Lesion with decreased attenuation distally

Lesion with reticular changes

Doubling time of metastases from 2-10 months

Size is not useful in distinguishing benign and malignant nodules. Although a direct

correlation exists between nodule size and malignancy, the size should be evaluated in

the context of a known malignancy. In patients with known malignancy, it should be

noted that nodules smaller than 1 cm can also be metastasis.

A study showed that in patients with known malignancy, video-assisted thoracic

surgery showed that 84% of nodules smaller than 1 cm were malignant, of which 54%

were metastasis, 29% were new primaries, and only 18% were benign. [47] Another

study by Ginsberg et al showed that in oncologic patients undergoing video-assisted

thoracic surgery, nodules smaller than 5 mm were malignant in 42% of patients with

cancer.[48]

Lesions smaller than 7 mm cannot be characterized on CT scans, because they are not

amenable to biopsy and are not palpated at surgery.[1] Temporal assessment of nodules

is also useful in determining malignancy. However, nodule measurements have

significant interobserver and intraobserver variability, which can be reduced by

automated or semiautomated measurements. Three-dimensional volume measurement

may be more accurate and reproducible, but it is also prone to precision errors.[22]

Doubling times less than 20-30 days are suggestive of infections or rapidly growing

metastasis. Doubling times greater than 400 days are benign lesions. Nodules being

stable for at least 2 years is an indicator of benignity (with the exception of subsolid

nodules).

Nodule enhancement can be also used to distinguish benign and malignant nodules.

Thin-section CT images are obtained through the nodules before and after 1, 2, 3, and

4 minutes following administration of contrast at 2 mL/second. Enhancement of 15

HU or less is suggestive of benignity, while higher degrees of enhancement are

49


suggestive of malignancy or inflammatory. This technique has 98% sensitivity for

malignancy and 58% specificity for benignity. This technique is suitable for nodules

between 7 mm and 3 cm and for noncalcified nodules.

Peak attenuation of nodules correlates positively with microvessel density and

vascular endothelial growth factor staining on pathology. (Malignant lesions have

higher vascular endothelial growth factor expression.[49] ) With the advent of dual-

source CT scanning, simultaneous 80 kV and 140 kV images can be obtained, which

helps in identifying areas of fat, bone, soft tissue, and iodinated contrast. Virtual

unenhanced images can be generated, which then can be subtracted from contrast–

enhanced scans to evaluate areas of enhancement, yielding an estimate of tumor

perfusion.[22]

CT may miss nodules that are centrally located (either within bronchi or adjacent to

vessels), are small, have faint attenuation, are at a lower lobe location, or are adjacent

to or within parenchymal abnormalities. Sensitivity may be improved by using MIP,

VR, or cine viewing of datasets.

Magnetic Resonance Imaging

In the lungs, MRI is typically used in the evaluation of involvement of the

mediastinum and the chest wall. MRI has the advantages of no radiation or iodinated

contrast media exposure and higher soft-tissue contrast resolution, which makes it

useful patients requiring frequent follow up, especially in young and female patients.

However, MRI is not used in the evaluation of pulmonary nodules, including

metastasis, owing to several limitations and challenges. These include the following:

Lower spatial resolution

Inability to detect calcification

Motion artifacts from breathing and cardiac pulsation on sequences with lower

temporal resolution

Low proton density and very short T2* value of lung

Higher susceptibility differences between air spaces and pulmonary interstitium

Inhomogeneity of magnetic field

However, novel sequences have been developed and adapted for the lungs.

50


Findings

MRI sequences that have been evaluated in the evaluation of pulmonary nodules

include the following[50] :

T2-weighted half-Fourier acquisition single-shot turbo spin-echo (HASTE)

Three-dimensional gradient-related echo (eg, volume-interpolated breath-hold

[VIBE])

T1-weighed

T2-weighted

Short-tau inversion recovery (STIR) sequences[51]

Diffusion-weighted imaging (DWI)

Dynamic contrast-enhanced (DCE) sequences

Metastatic nodules have low- or intermediate-signal intensities on T1-weighted

images and slightly higher intensity on T2-weighted spin-echo or turbo spin-echo

sequences. T1-weighted, T2-weighted, and STIR sequences can help distinguish

neoplasms from other lesions, such as tuberculoma, bronchocele, mucin-containing

tumors, hamartoma, and aspergilloma, but differentiating a benign from malignant

lesion is not easy with MRI.[51]

HASTE sequence is favored owing to higher T2 relaxivity and a higher signal for

neoplastic lesions relative to the air-filled low signal of lungs. Vessels are seen as flow

voids. The sensitivity of HASTE for nodules of 6-10 mm has been shown to be

95.7%,[52] while the sensitivity for nodules smaller than 3 mm is 73%.[53]

Although HASTE has the lowest motion artifact, breath-hold T2-weighted turbo spin-

echo sequences have been shown to detect more lesions than HASTE.[54] Three-

dimensional gradient echo sequences such as VIBE MRI sequences are also good in

detecting pulmonary nodules. Although multidetector CT scanning is better than MRI

at detecting 1- to 3-mm nodules, one can argue that these nodules are not significant in

a low-risk population, while MRI is a good alternative to multidetector CT scanning

for the detection of nodules larger than 5 mm.[54]

DCE MRI and parameters such as maximal enhancement ratio and slope of contrast

uptake with three-dimensional gradient-echo sequences can be used to distinguish

51


malignant from benign nodules with a sensitivity, specificity, and accuracy of 100%,

70%, and 95%, respectively.[55] However, it is not possible to distinguish malignancy

and active infection, a problem similar to positron emission tomography (PET)

scanning. Kono et al[56] showed an early peak pattern of enhancement in malignancy

and active infection.

Higher signal is seen on DWI sequences and low signal on apparent diffusion

coefficient (ADC), owing to increased cellularity, high tissue disorganization, and

extracellular space tortuosity. However, higher signal is also occasionally seen in

granulomas, inflammatory nodules, and fibrous nodules.

DCE MRI has the capability of distinguishing benign and malignant pulmonary

nodules based on the presence of tumor angiogenesis, tumor interstitial spaces,

fibrosis, scarring, and necrosis. Malignant pulmonary nodules have homogeneous

contrast enhancement, but at different levels of T1-weighted images after contrast

media, compared with benign nodules.


MRI has lower sensitivity than CT in the detection of metastatic pulmonary nodules.

Using turbo spin-echo, the sensitivity of MRI was 84% compared with CT scanning

and only 36% for nodules smaller than 5 mm.[57] With STIR, the sensitivity was 72%

for nodules larger than 5 mm.[54]


False-positive findings may be seen with MRI owing to diaphragmatic motion,

especially in the lower lobes. Small nodules near the diaphragm may be missed

because of respiratory motion, resulting in false-negative findings. Lesions may also

be missed because of lower spatial resolution and motion artifacts, either from

breathing or cardiac pulsation.

52


Ultrasonography

Ultrasound has only a very limited role in the evaluation of pulmonary metastases.

Ultrasound may be used in aspiration of pleural effusions to detect malignant cells and

to obtain a biopsy specimen from pleural nodules (see the image below). Parenchymal

lesions in subpleural regions may undergo biopsy using ultrasound guidance.

Endoscopic ultrasound with bronchoscopy is used in the evaluation and biopsy of

pulmonary nodules and mediastinal and hilar lymph nodes.

Ultrasound guidance used for transthoracic aspiration of malignant effusion.

Nuclear Imaging

The primary scintigraphic modality used in the evaluation of pulmonary metastasis is

fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET).

FDG is a glucose analogue. One of the important biochemical alterations in a cancer

cell is the increased rate of glycolysis that results in increased cellular glucose uptake.

This principle is used in the detection of neoplastic lesions.


CT scan in a patient with squamous carcinoma of the tonsil shows a 2.5-cm lesion in

the left lower lobe.

53


Positron emission tomography in the same patient (with squamous carcinoma of the

tonsil) shows high fluorodeoxyglucose uptake in the nodule, which was shown by

biopsy to be metastatic.

Axial positron emission tomography scan of the same patient shows high uptake in the

endobronchial mass, which was proven to be endobronchial metastasis.

FDG-PET increases the specificity of nodules based on their metabolic activity. It

works well with extrathoracic primaries such as bone and soft-tissue sarcomas,

malignant melanomas, and head and neck cancers. However, it is not the study of

choice when the primary tumor is renal cell carcinoma or testicular cancer, for which

it receives an American College of Radiology (ACR) appropriateness criteria of 1 and

3, respectively, equating to “usually not appropriate”.[1] This is related to the poor

FDG avidity of these tumors.

Another application of FDG-PET is in differentiating benign and malignant nodules,

especially in solitary pulmonary nodules. PET scanning has been shown to have a

sensitivity of 96% and specificity of 88% in diagnosing a nodule as malignant.[58] The

positive predictive value is lower owing to false positives caused by

54


infection/inflammation. The negative predictive value and sensitivity are lower owing

to lower spatial resolution.

It is also important to note that PET scanning has very poor sensitivity in the detection

of nodules smaller than 1 cm. Hence, a negative FDG-PET scan does not exclude

metastatic disease, owing to an absence of uptake in lesions smaller than 1 cm and in

non–FDG-avid primaries. Specificity is also affected secondary to false-positive

results from non-neoplastic inflammatory processes. In a study on head and neck

cancers, PET-positive lesions were seen in 27% of patients; however, 83% of these

lesions were shown to be benign, indicating a low specificity.[59]

With improved technology, evaluation of nodules as small as 7 mm is possible. New

developments, such as the development novel radiotracers and delayed imaging, can

further refine the role of FDG-PET scanning in the workup of lung nodules and

cancer.[60, 61, 62, 63]

PET scanning versus CT scanning alone

Several studies have evaluated the benefits of PET versus standard CT in the

screening of pulmonary metastases. For nodules larger than 1 cm, in head and neck

cancers, there was no statistical difference between PET and CT. [64] However for

nodules smaller than 1 cm, high-resolution CT (HRCT) is more sensitive in evaluating

pulmonary metastasis than PET. One study by Krug et al showed that using PET may

help in avoiding 20% of futile surgeries in patients who were thought to be free of

metastasis.[65] However, this study is limited because it was based on data published

from other studies.

Other isotopes

Several other isotopes have potential applications in the evaluation of pulmonary

metastasis. Technetium (Tc) 99m–methoxyisobutylisonitrile (Tc-MIBI) scintigraphy

has been shown to detect 92% of metastatic lesions in patients with melanoma. [66]

Indium (In)-111–labelled monoclonal antibody (CCR 086) has been shown to detect

colorectal metastasis as small as 1 cm.[67] Bone scintigraphy with99 Tc methylene

diphosphonate (Tc-MDP) can be used to detect osteosarcoma metastasis.[67]

55


Fluorobenzamide (FBZA) coupled with FDG can be used in the detection of melanin-

producing tumors.[68]


Most false-negative FDG-PET results are caused by micrometastases and lesions

smaller than 10 mm. In addition, some pulmonary lesions are not FDG avid, such as

renal and testicular cancers. CT scanning is equivalent to or more sensitive than FDG-

PET scanning for detecting small pulmonary lesions.


Physiologic variants, benign tumors, and inflammatory diseases may all cause

increased uptake of FDG and mimic malignant disease.

Angiography

Angiography is not extensively used in the evaluation of pulmonary metastasis.

In tumor embolism, pulmonary angiography may show delayed filling of segmental

arteries, pruning and tortuosity of third- to fifth-order vessels, and subsegmental

filling defects.[30] See the image below.

Coronal MR angiography in a patient with renal carcinoma shows tumor emboli in

segmental branches of pulmonary arteries.

Angiographic embolization may be used in metastatic tumors presenting with massive

hemoptysis, for which bronchial artery embolization may stop bleeding.

Contributor Information and Disclosures

56


Author

Tanay Patel, MD Resident Physician in Diagnostic Radiology, Department of

Radiology, University Hospitals Case Medical Center

Tanay Patel, MD is a member of the following medical societies: American College of

Radiology, American Society of Neuroradiology, and Radiological Society of North

America

Disclosure: Nothing to disclose.

Coauthor(s)

Prabhakar Rajiah, MD, MBBS, FRCR Assistant Professor, Department of

Radiology, University Hospitals of Cleveland

Prabhakar Rajiah, MD, MBBS, FRCR is a member of the following medical societies:

American Roentgen Ray Society, European Society of Radiology, Indian Radiology

and Imaging Association, North American Society for Cardiac Imaging, Radiological

Society of North America, Royal College of Radiologists, Society for Cardiovascular

Magnetic Resonance, and Society of Cardiovascular Computed Tomography


Specialty Editor Board

W Richard Webb, MD Professor, Department of Radiology, University of

California, San Francisco, School of Medicine


Robert M Krasny, MD Resolution Imaging Medical Corporation

Robert M Krasny, MD is a member of the following medical societies: American

Roentgen Ray Society and Radiological Society of North America


57


Chief Editor

Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac

Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical

Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College

of Nuclear Medicine, American College of Radiology, Radiological Society of North

America, and Society of Nuclear Medicine


Additional Contributors

Isaac Hassan, MB, ChB, FRCR, DMRD Former Senior Consultant Radiologist,

Department of Radiology, St Bernard's Hospital

Isaac Hassan, MB, ChB, FRCR, DMRD is a member of the following medical

societies: American Roentgen Ray Society and Royal College of Radiologists

58


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