The patient is a 45-year-old man who presents with syncope and hypotension. He had undergone resection of a meningioma 3 weeks prior to presentation.
Figure 1. Chest Radiographic Findings
Frontal chest radiograph shows bilateral, lower-lobe predominant, wedge-shaped, subpleural opacities without evidence of air bronchograms. No evidence of effusion is present.
What is the differential diagnosis?
Figure 2. CT Scan Findings
Thoracic CT performed using a protocol designed for the evaluation of suspected pulmonary embolism shows a main pulmonary arterial filling defect, consistent with a saddle embolism.
Click here to see a comparable image of a gross specimen.
Figure 3. CT Scan Findings
Image photographed in lung windows shows subpleural, wedge-shaped opacities consistent with pulmonary infarction (Hampton's hump on the radiograph). The opacity in the right middle lobe demonstrates cavitation, implying that embolization may have occurred over a period of time since the patient's neurosurgical procedure.
Figure 4. Slice of Lung from Another Patient
An embolus (arrow) is present in the artery to a basal segment of the lower lobe. A large hemorrhagic infarct with cavitation is present distally.
Find the cavitated area of the infarct.
Scroll down after answering the questions.
Discussion: Acute Pulmonary Venous Thromboembolism
Venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and resultant pulmonary embolism (PE), is a common disease with substantial morbidity and mortality . For those who survive the initial embolic event, the risk of mortality from subsequent emboli is high, especially for the elderly and those with cancer or cardiovascular disease . Because anticoagulation therapy has been demonstrated to lower the mortality related to PE, early, accurate diagnosis is crucial. Further, because anticoagulation is associated with risk of major bleeding, as well as thrombocytopenia, treatment should be limited to patients with confirmed VTE. For these reasons strategies for the evaluation of patients with suspected VTE require high sensitivity and specificity. Diagnostic imaging has assumed a central role in the evaluation of patients with suspected VTE, but controversy regarding the most appropriate methods to investigate these patients still exists .
Clinical Aspects: DVT is caused by injury to endothelium, circulatory stasis, or hypercoagulable states, the last including anti-thrombin, protein C or S deficiency; activated protein C resistance; or the prothrombin mutation G20210A . Risk factors (including leg fractures, knee or hip replacement, other major surgery, congestive heart failure, and malignancy), which vary in degree, may occur singly or in combination . One quarter to 1/2 of patients have no known risk factors [1,3]. DVT may remain silent or present with non-specific pain, swelling, warmth, and erythema [2,4]. VTE is thought to begin as thrombi in the deep calf veins, which may spread proximally . Symptomatic proximal DVT is associated with PE in about 1/2 of cases . Like DVTs, the symptoms and signs of PE, which include dyspnea, pleurisy, and tachypnea, are non-specific . Recently, a negative result on a sensitive test for D-dimers (increased in fibrinolytic states following thrombosis) has been shown in the emergency room/outpatient setting to exclude VTE in patients with a low pretest probability of disease, thereby decreasing the need for invasive tests [6,7].
Imaging and Deep Venous Thrombosis
Over the years, several methods have been employed to diagnose DVTs, including contrast venography, impedance plethysmography, and radionuclide imaging . The traditional gold standard, contrast venography, has the disadvantage of being an invasive procedure that may, in a small number of patients, induce the formation of DVT. Currently, lower extremity compression ultrasonography, coupled with duplex and color Doppler ultrasound, is usually the examination of choice for the assessment of suspected symptomatic lower extremity DVT .
Lower extremity compression ultrasound is at least 89% sensitive for the detection of symptomatic proximal (i.e., within the deep femoral and popliteal veins) DVT compared to contrast venography . The sensitivity of compression ultrasound, with or without duplex and color Doppler, for the detection of symptomatic calf vein thrombosis is substantially less, varying from 73 to 87% . Therefore, it has been suggested that a negative lower extremity ultrasound examination should be repeated in several days to detect venous thrombosis that may have propagated into the proximal deep venous system . See the article by Wells, et al. for diagnostic algorithms .
Imaging and Acute Pulmonary Embolism: Chest Radiography
Imaging for suspected PE often begins with chest radiography; radiographs are commonly obtained to exclude diagnoses that may clinically simulate acute PE, such as pneumothorax, pneumonia, and pulmonary edema. Chest radiography is usually abnormal in the setting of acute PE, although usually nonspecifically so. Such nonspecific findings include atelectasis, pleural effusion, and mild diaphragmatic elevation. Chest radiographic findings that may specifically suggest acute PE include enlargement of the pulmonary arteries, oligemia, and wedge-shaped peripheral pulmonary consolidations, the last indicating pulmonary infarction , although much of the opacity may be caused by rapidly-regressing hemorrhage and edema surrounding a very small infarct (see under Pathology).
For more than 30 years, ventilation-perfusion scintigraphy (V/Q scan) has been the mainstay for the imaging diagnosis of acute pulmonary embolism. V/Q scanning employs an intravenously-injected radiopharmaceutical (usually technetium-99m labeled macroaggregated albumin) combined with an inhaled agent (usually xenon-133 or technetium-99m-labeled aerosols) . The injected agent produces a map of pulmonary perfusion. The inhaled agent provides a map of alveolar ventilation. Because acute PE obstructs pulmonary blood flow but (theoretically) does not affect alveolar ventilation, acute PE produces defects on the perfusion images without disturbing ventilation--the so-called "V/Q mismatch." Many other diseases may produce V/Q mismatches. Further, acute PE may occur in the absence of V/Q mismatching, so V/Q scanning is neither sensitive nor specific for the diagnosis of acute PE.
V/Q scan findings have been correlated with the results of pulmonary angiography in numerous studies. The results of these studies, the most well known of which is the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) trial, have allowed VQ scan interpretations to be categorized on the basis of the likelihood of the presence of acute PE at pulmonary angiography. Several different schemes exist, but one of the most commonly available, the PIOPED criteria, categorizes V/Q scan results as normal, low probability, intermediate probability, or high probability [2,8,9]. Because the prevalence of acute PE at angiography was 16% for low probability scan interpretations and 32% for intermediate probability scan interpretations , it has been suggested that these two scan categories be considered "nondiagnostic". Unfortunately, in the PIOPED trial, 73% of V/Q scan interpretations fell into this category . Further, the likelihood of a nondiagnostic scan interpretation rises even higher when coexistent cardiopulmonary disease is present .
Traditionally, pulmonary angiography (PA gram) has been used to evaluate patients with nondiagnostic V/Q scan results and negative lower extremity venous examinations. PA gram has been considered the gold standard for pulmonary embolism diagnosis. Although invasive, PA grams are associated with few complications and low nondiagnostic study rates. However, it has been well documented in several studies that PA grams are not requested even when indicated, resulting in the premature termination of the evaluation of suspected acute PE .
Helical CT Pulmonary Angiography
Since helical CT pulmonary angiography (HCTPA) for pulmonary embolism diagnosis was first reported in 1992, the technology has improved, now using overlapping, narrowly-collimated CT sections through the lung . It has the added benefit of accurately showing other causes of presentations simulating acute PE in cases read as negative for acute PE [2,11]. A recent study that directly compared dual-section HCTPA to pulmonary angiography showed a sensitivity of 90% and specificity of 94% .
The main controversy revolves around HCTPA's accuracy for subsegmental emboli. Isolated subsegmental emboli occur in 6% (13) to 30% of patients . The latter figure is derived from studies in which patients underwent PA gram following nondiagnostic scintigraphy, and therefore represents a biased patient population. PA gram itself is not particularly accurate for the detection of isolated subsegmental emboli: there is fairly low interobserver agreement for the diagnosis of such emboli . Whether or not isolated small emboli are clinically significant is controversial. Probably most such emboli are not clinically important, but two exceptions must be remembered.
One additional benefit of HCTPA for pulmonary embolism diagnosis is that the lower extremity venous system can be evaluated for the presence of deep venous thrombosis with the same intravenous contrast bolus used to examine the chest . Deep vein thrombi appear as low attenuation filling defects within the deep venous system. This approach allows the patient to be evaluated for venous thromboembolism and not just PE, and thereby mitigates some of the concerns over HCTPA's sensitivity for small emboli.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) with magnetic resonance angiography (MRA) is also used for the diagnosis of acute PE. Experience with MRI and MRA is limited compared to HCTPA, and examination times are longer. Further, MRI/MRA may not be performed in claustrophobic patients and patients with pacemakers. However, MRI/MRA does not employ iodinated contrast or ionizing radiation, and may be used as an alternative to HCTPA when radiation exposure must be avoided or iodinated contrast allergies are present .
Diagnostic Strategies for Patient Evaluation
The diagnostic approach to VTE is not yet standardized. A discussion of the advantages and disadvantages of angiography or HCTPA as the gold standard for diagnosis of VTE has recently been published . One example of an algorithm using clinical pretest probability of embolism, a measure of D-dimers, V/Q scan, venous ultrasound, and pulmonary angiography demonstrated safety and a decreased need for pulmonary angiography . A more comprehensive review of the evaluation of suspected PE describes diagnostic algorithms based on the degree of clinical probability of PE .
Emboli to the lung may originate from thrombi (in leg, pelvic, or rarely arm veins, the inferior vena cava, and the heart; from around intravenous cathethers; and from infectious vegetations in the heart), tumor, amniotic fluid, bone marrow or bony fragments liberated during surgical procedures, air, or foreign intravenously-injected material. Thromboemboli, discussed here, differ from blood clots (which occur outside vessels or postmortem) in their architectural features: on section, the former have pale lines of Zahn in a dark red coagulum, and the latter settle into dark red "currant jelly" and yellowish "chicken fat" layers. With time, thrombi organize as myofibroblasts migrate from the intima to recanalize the thrombus and open the blockage to varying degrees. Often, traces of the thrombus remain as mural ridges or "violin strings" across lumens, which may cause turbulence and subsequent in-situ thrombosis.
The clinical significance depends in part on the size of the embolus . Sudden death caused by PE may often be the result of a saddle embolism, and infarction is absent. Because of the dual blood supply to the lungs, not all smaller thromboemboli cause infarction. In general, infarction does not occur with large, proximal thromboemboli. Bronchial arterial blood feeds into the distal open pulmonary artery via bronchial-pulmonary artery anastomoses. Infarcts are likely to occur when subsegmental vessels < about 3 mm in diameter are occluded. Other factors predisposing to infarction are congestive heart failure and malignancy . Cavitation ± infection, which usually develops 1 to 42 days after the appearance of the radiographic opacity, is a rare occurrence (3-7%) in infarcts .
Diagnosis: Pulmonary thromboembolism with infarction.
Follow-up: The patient was initially treated with systemic anticoagulation, not thrombolysis; the latter was avoided because of the recent neurosurgical procedure. Because he remained hemodynamically unstable, thrombolytic therapy was instituted several days later. He improved and was discharged.
References: To return to reference section after viewing abstract, click here before clicking on "abstract".
1. White R. The epidemiology of venous thromboembolism. Circulation 2003;107:I4-8. Abstract
2. Tapson V, Carroll B, Davidson B, Elliott C,
Fedullo P, Hales C, Hull R, et al. The diagnostic approach to acute
venous thromboembolism. Clinical practice guideline. American
Thoracic Society. Am J Respir Crit Care Med 1999;160:1043-1066.
Download this ATS Position Paper. See under Respiratory Diseases Adults 1999
3. Anderson F Jr, Spencer F. Risk factors for venous thromboembolism. Circulation 2003;107:I9-16. Abstract
4. Anand S, Wells P, Hunt D, Brill-Edwards P, Cook D, Ginsberg J. Does this patient have deep vein thrombosis? JAMA 1998; 279:1094-1099. Abstract
5. Kearon C. Natural history of venous thromboembolism. Circulation 2003;107:I22-30. Abstract
6. Fedullo P, Tapson V. The evaluation of suspected pulmonary embolism. N Engl J Med 2003; 349:1247-1256.
7. Wells P, Anderson D, Rodger M, Forgie M, Kearon C, Dreyer J, Kovacs G, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349:1227-1235. Abstract
8. Parker J, Coleman R, Siegel B, Sostman H, McKusick K, Royal H. Procedure guideline for lung scintigraphy: 1.0. J Nucl Med 1996; 37:1906-1910.
9. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263:2753-2759. Abstract
10. Khorasani R, Gudas T, Nikpoor N, Polak J. Treatment of patients with suspected pulmonary embolism and intermediate-probability lung scans: is diagnostic imaging underused? AJR 1997; 169:1355-1357. Abstract
11. Remy-Jardin M, Mastora I, Remy J. Pulmonary embolus imaging with multislice CT. Radiol Clin North Am 2003; 41:507-519. Abstract
12. Qanadli S, El Hajjam M, Mesurolle B, Barre O, Bruckert F, Joseph T, Mignon F, et al. Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology 2000: 217:447-455. Abstract
13. Stein P, Henry J. Prevalence of acute pulmonary embolism in central and subsegmental pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans. Chest 1997; 111:1246-1248. Abstract
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Differential Diagnosis: The differential diagnosis should include acute pulmonary embolism with pulmonary infarction, as well as septic embolization. The peripheral nature of the opacities raises the possibility of cryptogenic organizing pneumonia and chronic eosinophilic pneumonia, although the history is not suggestive of these entities. Rare considerations include vasculitides (particularly Churg-Strauss) and lymphomatoid granulomatosis.
Cavity in hemorrhagic infarct