Focal and Multifocal Lung Disease Part 1

Chest physicians, when consulted, most often begin their consultation by examining the results of imaging studies—standard posteroanterior and lateral chest radiographs, computed tomography scans of the chest, or both. In doing so, they assess the differential diagnostic probabilities and possibilities on the basis of the radiographic patterns. This approach serves to focus their efforts on history taking and the physical examination, and it facilitates their defining of proper diagnostic measures, which in turn guide therapeutic and management advice. In this topic, the approach taken by chest physicians is used to discuss and categorize a wide range of lung diseases.

Assessment of Chest Radiographs

Focal and multifocal lung diseases are classified into seven categories on the basis of chest radiography and CT: (1) focal pulmonary infiltrates, (2) multifocal pulmonary infiltrates, (3) true segmental infiltrates, (4) cavitary infiltrates, (5) single small nodules, (6) large masses, and (7) multiple nodules. These radi-ographic patterns may be caused by infectious diseases; neoplas-tic diseases; or noninfectious, nonneoplastic disorders. The differential diagnoses for the seven categories are dissimilar but by no means mutually exclusive. Many diseases that usually cause focal infiltrates can produce multifocal infiltrates [see Focal Pulmonary Infiltrates, below]. Other disorders nearly always present as multiple infiltrates, and the pathology only rarely localizes to one area [see Multifocal Pulmonary Infiltrates, below]. Infiltrates that conform perfectly to the segmental anatomy of the lung usually result from an abnormality of the bronchus or pulmonary artery leading to the infiltrate [see True Segmental Infiltrates, below]. Cavitary infiltrates, single small nodules, large masses, and multiple nodules have distinct differential diagnoses.

Diagnosis of a focal or multifocal lung disorder starts with the abnormal chest radiograph or with abnormal findings on chest CT. In many instances, the chest CT scan may be abnormal when the chest radiograph is normal or shows very indistinct changes. In each category of radiographic pattern, the clinical features of the illness, the presence or absence of associated pleural or medi-astinal abnormalities, and ancillary laboratory tests all serve to narrow the differential diagnosis. In some disorders, the combined radiographic, clinical, and laboratory presentation is virtually specific. In other disorders, cytologic, histopathologic, or mi-crobiologic information is necessary to make a specific diagnosis.

Focal Pulmonary Infiltrates

When a focal infiltrate is dense, it is likely that pus, blood, water, or tissue is filling alveolar spaces. A focal infiltrate that is patchy and less dense suggests a less advanced stage of disease process. Many conditions can cause a focal infiltrate that is visible on the chest radiograph [see Table 1].

Infectious diseases

Bacterial Pneumonia

The most common cause of a focal infiltrate is bacterial pneu-monia.1 Five clinical features in combination strongly suggest the diagnosis: (1) acute onset, (2) a new or increasing infiltrate on the chest radiograph [see Figure 1a], (3) fever, (4) purulent sputum, and (5) a white blood cell count that is either high, low, or shifted to the left. Absence of one or more of these features does not eliminate the possibility of bacterial pneumonia but does increase the probability of an alternative diagnosis.

Because many different types of bacteria can cause pneumonia, a precise etiologic diagnosis cannot be made either on clinical grounds or by a chest radiograph. Positive blood cultures have near-perfect specificity but low sensitivity, whereas positive sputum cultures can only suggest a specific etiology. Streptococcus pneumoniae is the most common cause of bacterial pneumonia, accounting for perhaps 85% of all cases in otherwise healthy young adults. However, many other bacteria also cause pneumonia, with a higher incidence in patients with chronic medical conditions and advanced age. These include Haemo-philus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, and Legionella pneumophila [see 7:XX Pneumonia and Other Pulmonary Infections]. An even wider range of pathogens cause pneumonia in patients in intensive care units. These include virulent gram-negative bacilli with high potential for antibiotic resistance, such as Pseudomonas aeruginosa and Enterobacter, Serratia, and Proteus species. Other infectious causes of focal infiltrates include My-coplasma pneumoniae, Chlamydophila pneumoniae, tuberculosis (especially in patients with advanced-stage HIV infection and other immunosuppressed patients), viruses, rickettsiae, fungi, and parasites.

Neoplastic diseases

Alveolar cell carcinoma and lymphoma commonly present as focal pulmonary infiltrates, though they also cause multifocal in-filtrates. Bronchogenic lung cancer usually produces a nodule or a mass but can cause a focal dense infiltrate. The absence of fever and purulent secretions (unless there is a postobstructive pneumonia) and the longer duration of symptoms suggest a nonin-fectious cause.

Table 1 Major Causes of Focal Pulmonary Infiltrates




Bacterial pneumonia



Primary lung cancer

Alveolar cell carcinoma


Noninfectious, nonneoplastic

Radiation pneumonitis

Lipoid pneumonia

Lung contusion

Pulmonary embolism

Lobe torsion

 (a) This chest radiograph demonstrates a focal left lower lobe infiltrate caused by bacteremic pneumococcal pneumonia in a 22-year-old man. (b) A focal right upper lobe infiltrate caused by alveolar cell carcinoma is revealed in this chest radiograph of a 71-year-old woman. (c) The focal right lower lobe infiltrate in this chest radiograph is the result of lipoid pneumonia in a 68-year-old woman.

Figure 1 (a) This chest radiograph demonstrates a focal left lower lobe infiltrate caused by bacteremic pneumococcal pneumonia in a 22-year-old man. (b) A focal right upper lobe infiltrate caused by alveolar cell carcinoma is revealed in this chest radiograph of a 71-year-old woman. (c) The focal right lower lobe infiltrate in this chest radiograph is the result of lipoid pneumonia in a 68-year-old woman.

Alveolar Cell Carcinoma

Alveolar cell carcinoma may result in one or more areas of airspace opacity, presenting as an area of focal indistinct infiltrate or, sometimes, mimicking lobar pneumonia [see Figure 1b]. Chest CT often shows areas of "ground-glass opacity"; less commonly, the infiltrates are consolidative.2 Patients cough and produce mucoid sputum; a few patients produce large volumes of sputum (bronchorrhea) that in rare instances has a salty taste. Weight loss and malaise are common. Fever and chills are absent. Metas-tases are less common than with other primary lung neoplasms, and the course of the illness is longer. Alveolar cell carcinoma is not related to smoking. Diagnostic tests should begin with sputum cytology, followed by fiberoptic bronchoscopy with bron-choalveolar lavage and transbronchial biopsy or, if needed, open lung biopsy by a traditional or a video-assisted thoracoscopic approach. Localized disease can sometimes be resected; radiation therapy and chemotherapy have no important role.


Lymphoma can also produce a focal, dense consolidation. With Hodgkin disease, there may be multiple contiguous areas of tumor involvement that grow and merge, resulting in a dense infiltrate with irregular borders. Hilar and mediastinal adenopa-thy are nearly always present. Pleural effusions occur in as many as 30% of patients. Diagnostic strategies include fiberoptic bron-choscopy, aspiration biopsy of the infiltrate or of the mediastinal nodes (using needles that obtain a tissue core), mediastinoscopy, and pleural biopsy. Biopsy of associated cervical nodes or of the bone marrow is helpful in some cases. In non-Hodgkin lym-phoma, the chest radiograph may show a dense infiltrate with regular margins, similar to the infiltrate seen in bacterial pneumonia or alveolar cell carcinoma. Mediastinal and hilar node involvement may be absent. Pleural effusion occurs in one third of patients [see 12:XI Lymphomas].

Noninfectious, nonneoplastic disorders

Pulmonary embolism can cause a focal infiltrate or focal at-electasis; in other cases, the chest radiograph is normal or shows multifocal infiltrates or multiple nodules.3 Pulmonary infarcts are always based at a visceral pleural surface, including fissures [see 1:XVIH Venous Thromboembolism]. Several other noninfec-tious, nonneoplastic disorders typically present as a focal pulmonary infiltrate. In making a diagnosis, the clinical history is very important because these disorders occur in specific clinical settings.

Radiation Pneumonitis

Radiation pneumonitis follows pulmonary irradiation after a lag time that is somewhat dose dependent.4 Symptoms include nonproductive cough, dyspnea, and fever. These symptoms develop approximately 8 weeks after completion of a course of radiation therapy consisting of 4,000 cGy; they develop 1 week earlier for each additional 1,000 cGy administered.1 Chemothera-peutic agents such as dactinomycin, doxorubicin, bleomycin, and busulfan can potentiate the effects of radiation. Onset is usually subacute. There may be rales and signs of consolidation. Hy-perpigmentation of the skin overlying the irradiated lung is common but does not correlate with the severity of lung injury. Laboratory findings include leukocytosis and hypoxemia. Bron-choalveolar lavage may rule out tumor and infection—a determination that is most important in making a differential diagno-sis—and may demonstrate dysplastic type II cells, the presence of which suggests radiation injury. Lavage also reveals excess lymphocytes in both involved and uninvolved areas. Drug-induced lung injury causes similar cytopathic changes in type II cells, but usually, neutrophilic inflammation is also present.

Table 2 Major Causes of Multifocal Pulmonary Infiltrates




Bacterial pneumonia

Pneumocystis jiroveci pneumonia



Endemic fungal pneumonias

Invasive aspergillosis


Alveolar cell carcinoma


Noninfectious, nonneoplastic

Drug reactions

Simple eosinophilic pneumonia

Chronic eosinophilic pneumonia Bronchiolitis obliterans organizing pneumonia

Allergic granulomatosis and angiitis


The chest radiograph shows an infiltrate of variable density. A highly characteristic infiltrate has sharp edges and conforms exactly to the radiation port. Occasionally, high-resolution CT shows regions of air-space consolidation that are not visible on routine chest radiography. Many patients gradually improve over a few weeks. When the disease is severe, glucocorticoid therapy is often used, with uncertain benefit. Because of fever and fear of superinfection, antibacterial therapy is often given, also with uncertain benefit. Typically, the involved area of the lung scars and contracts with time, and the chest radiograph shows progressive volume loss.

Lipoid Pneumonia

Lipoid pneumonia is a noninfectious, inflammatory lung disorder caused by the aspiration of mineral oil or other oily substances. It is most common in elderly patients and others with impaired swallowing. Whether or not swallowing is impaired, lipoid pneumonia can result from the use of petroleum jelly or other oily substances applied to the lips or nose to relieve chronic dryness or mineral oil taken by mouth for relief of constipation. The most common symptom is a chronic cough, which may be caused by coexisting lung disease rather than lipoid pneumonia; fever is uncommon. Often, the disease is discovered on a routine chest radiograph that shows a focal, dense infiltrate, usually in a lower lobe or in the right middle lobe [see Figure 1c].5 The radi-ographic appearance of such an infiltrate in a relatively asymptomatic patient suggests chronic pneumonia or lung cancer. CT scanning may show an extremely low density infiltrate produced by accumulated lipid; the density typically ranges from -60 to -150 Hounsfield units (water is 0). In contrast, the density of lung cancers usually ranges from +60 to +150 Hounsfield units. Lipid-laden macrophages can be demonstrated with the oil red O stain, which colors lipid droplets bright red. The stain can be applied to bronchoalveolar lavage specimens or transthoracic aspirates. A positive test supports the diagnosis, but some caution is necessary. Endogenous lipoid pneumonia may occur distal to an obstructed bronchus, and in such cases, the lipid is derived from the breakdown of cell membranes. Thus, bronchoscopy is still needed to rule out an obstructed bronchus even after demonstration of lipid-laden macrophages by needle aspiration. A variety of other lung disorders, such as pulmonary hemorrhage and primary and metastatic cancers, can also be associated with lipid-laden macrophages. To establish the diagnosis of exogenous lipoid pneumonia, it is necessary to analyze carefully all the clinical, cy-topathologic, and radiographic findings, including the results of CT scanning. Many cases are diagnosed only after thoracotomy for resection of a presumed malignancy. The only specific therapy is avoidance of exposure to mineral oil and other lipid-con-taining agents. Lipoid pneumonia usually improves slowly after exposure to the agent is eliminated, though complete clearing of the infiltrate does not always occur.

Lung Contusion

Lung contusion is an important cause of focal, usually dense infiltrate. It results from blunt chest trauma, most often from falls or motor vehicle accidents. Usually within hours after trauma, an infiltrate develops deep beneath the impact point, representing blood and edema in the lung. Associated injuries, such as rib fractures and traumatic pneumothorax, may be present. Focal shunting through the area can cause refractory hypoxemia. If the injury is severe enough, the entire area may become necrotic and form a large cavity with irregular inner margins.

Lobe Torsion

Torsion of a lobe of the lung is rare and usually occurs postop-eratively, particularly after resection of the left upper lobe. The vascular pedicle of the remaining left lower lobe twists and is compromised, and the lobe increases in density as it fills with blood and edema fluid. The diagnosis is often made by radiography but can be difficult. The differential diagnosis includes unilateral lung infection, edema, and hemorrhage. Treatment involves surgical relief of the torsion in early cases or resection of the lobe if it is no longer viable.

Multifocal Pulmonary Infiltrates

Most disorders that cause single infiltrates can also cause multiple infiltrates [see Table 2]. Pneumococcal pneumonia and other bacterial pneumonias are occasionally multifocal [see Figure 2a]; viral pneumonias are commonly multifocal or diffuse.1 Clinical features of pneumonia with multiple infiltrates are similar to clinical features of pneumonia with one infiltrate, except that severity increases with extent of disease. Pulmonary thromboemboli can also produce multifocal infiltrates; a normal chest radiograph, unilateral or bilateral pleural effusions, and focal infiltrate or atelectasis are other possible radiographic patterns for pulmonary thromboemboli.3 Septic pulmonary emboli often cause multiple infiltrates [see Multiple Nodules and Masses, below]. Finally, sarcoidosis is perhaps the most protean of all the noninfectious and nonmalignant lung disorders [see 14:V Chronic Diffuse Infiltrative Lung Disease]. A diffuse infiltrate with or without hilar adenopathy is the usual presentation.

(a) Bacteremic pneumococcal pneumonia caused the extensive bilateral multifocal infiltrates revealed in this chest radiograph of a 27-year-old man. (b) Alveolar sarcoidosis is the cause of the extensive bilateral multifocal infiltrates shown in this chest radiograph. The patient is a 22-year-old woman. (c) Alveolar cell carcinoma often presents as multifocal infiltrates, as seen in this chest radiograph of a 65-year-old man.

Figure 2 (a) Bacteremic pneumococcal pneumonia caused the extensive bilateral multifocal infiltrates revealed in this chest radiograph of a 27-year-old man. (b) Alveolar sarcoidosis is the cause of the extensive bilateral multifocal infiltrates shown in this chest radiograph. The patient is a 22-year-old woman. (c) Alveolar cell carcinoma often presents as multifocal infiltrates, as seen in this chest radiograph of a 65-year-old man.

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