In suppurative bacterial pneumonia, there is consolidation (ie, solidification) of lung parenchyma due to the accumulation of neutrophil-rich intra-alveolar exudate (Fig. 34.1). The consolidation of bacterial pneumonia is classically subclassified into two patterns: lobar pneumonia and bronchopneumonia (or lobular pneumonia).
In suppurative bacterial pneumonia, alveoli are filled with a neutrophil-rich inflammatory exudate. Although this image was taken from a case of bronchopneumonia, at high magnification distinguishing bronchopneumonia from lobar pneumonia is not possible.
In lobar pneumonia, there is consolidation of contiguous airspaces, typically an entire lobe (Fig. 34.2). Lobar pneumonia is identifiable on an x-ray by a well-circumscribed radiopacity correlating to the affected lobe. Lobar pneumonia evolves through phases of congestion, red hepatization, gray hepatization, and resolution (Fig. 34.3).
Lobar pneumonia. Shown is the cut surface of a left lung with lobar pneumonia affecting the lower lobe. The lower lobe is markedly paler than the upper lobe. On palpation, the lower lobe would be consolidated with markedly reduced or absent crepitus. From Kemp et al. Pathology: the Big Picture, McGraw-Hill; 2008.
Phases of acute pneumonia. (a) Following the congestion phase (with few neutrophils), acute pneumonia enters the red hepatization stage, with alveoli filled with neutrophils and erythrocytes. (b) Subsequently, as the gray hepatization stage evolves, neutrophils and fibrin fill the alveolar spaces. (c) Following gray hepatization, the pneumonia can resolve or, alternatively, the intra-alveolar exudate can undergo organization, in which alveoli are filled by nodules of fibroblasts, collagen, and macrophages. From Kumar et al. Robbins and Cotran Pathologic Basis of Disease, 8th ed. Saunders-Elsevier, 2010.
During the congestion phase, the affected lobe is heavy, red, and boggy; histologically, there is vascular congestion, accumulation of intra-alveolar neutrophils, and pulmonary edema. Eventually, the lungs develop the consistency of liver (hepatization). Early in hepatization, the gross appearance is red, and the microscopic morphology comprises alveoli packed with neutrophils, erythrocytes, and fibrin; fibrous or fibrinopurulent pleural exudates are common in this phase. Later in the hepatization phase, the color of the lobe becomes gray as the fibrinous inflammatory exudate persists but becomes devoid of erythrocytes. As the inflammatory reaction resolves, the consolidated exudate is digested, leaving a granular semi-solid fluid to be resorbed. Due to the availability and efficacy of antibiotic therapy, lobar pneumonia is now rare.
In bronchopneumonia, the pattern of consolidation is of noncontiguous airspaces and typically involves more than one lobe with a bronchiolocentric distribution. Grossly, the patches of consolidation are gray-red to yellow with a surrounding rim of hyperemia and edema (Fig. 34.4). Histologically, bronchopneumonia progresses through stages similar to lobar pneumonia (Fig. 34.3). Pleural involvement in bronchopneumonia is less common than in lobar pneumonia. Radiographically, bronchopneumonia is typified by multiple foci of radiopacity.
Bronchopneumonia. The cut surface of the lung shows numerous pale patches of consolidation. From Travis et al. Non-Neoplastic Disorders of the Lower Respiratory Tract. © American Registry of Pathology; 2002.
The clinical presentation of lobar pneumonia and of bronchopneumonia includes malaise, fever, and a productive cough, occasionally with pleurisy and pleural friction rub. Appropriate antibiotic therapy (Chap. 35) usually results in restoration of lung structure and function. Complications include abscess formation (see below) due to tissue destruction and necrosis, empyema (Chaps. 26 and 29), organization of the intra-alveolar exudate into solid fibrous tissue [Fig. 34.3(c)], and dissemination of the infectious organism, possibly leading to meningitis, arthritis, endocarditis, or sepsis. The mortality of patients hospitalized for bacterial pneumonia is less than 10%, with death typically related to the development of one of the aforementioned complications or due to the presence of a significant predisposition like debilitation or chronic alcoholism. There are numerous etiologies for suppurative bacterial pneumonia, many of which are briefly discussed below.
Streptococcus pneumoniae (previously Pneumococcus pneumoniae) is a gram-positive coccus; its cocci are typically paired. It is the most common cause of lobar pneumonia (>90% of cases) and is the most common cause of community-acquired acute pneumonia (15%-25% of cases). The most common microbiologic isolates are types 1, 2, 3, and 7. Of note, S. pneumoniae type 7 also causes lung abscess (see below). Staphylococcus aureus is another gram-positive coccus, but in contrast to the paired cocci of S. pneumoniae, the cocci of S. aureus are typically in "grapelike" clusters (Fig. 34.5). S. aureus typically causes bronchopneumonia with multiple abscesses (see below) but can cause lobar pneumonia. Risk factors for S. aureus pneumonia include recent measles infection in children, recent influenza infection in adults, and intravenous drug abuse.
Staphylococcus aureus. Shown is a Gram stain of S. aureus in culture. The cocci are arranged in grapelike clusters.
Haemophilus influenzae is a gram-negative coccobacillus that generally causes bronchopneumonia that notably in children can be complicated by empyema (Chaps. 26 and 29) and extrapulmonary infection. Risk factors for H. influenzae pneumonia include recent viral infection, cystic fibrosis, chronic bronchitis, and bronchiectasis (Chaps. 20, 22, and 38). Moraxella catarrhalis is another gram-negative coccobacillus that generally causes bronchopneumonia. Risk factors for M. catarrhalis pneumonia include old age and chronic obstructive pulmonary disease (Chaps. 20 and 22).
Klebsiella pneumoniae is the most common gram-negative bacillus (rod) causing bacterial pneumonia. The morphology is that of bronchopneumonia or lobar pneumonia as well as lung abscess formation (see below). Clinically, K. pneumoniae pneumonia has an abrupt onset with a cough productive of gelatinous sputum. Risk factors for K. pneumoniae pneumonia include debilitation, malnourishment, and alcoholism. Recovery is often complicated by abscess formation, fibrosis, and/or bronchiectasis (Chap. 20), and K. pneumoniae pneumonia has a significant mortality rate, even with therapy. Pseudomonas aeruginosa, another gram-negative bacillus, typically causes bronchopneumonia with abscess formation (see below) and, frequently, empyema (Chaps. 26 and 29). P. aeruginosa pneumonia is commonly nosocomial, and risk factors include neutropenia, extensive burn injuries, cystic fibrosis, and mechanical ventilation. Legionella pneumophila, the cause of Legionnaire disease, is a gram-negative bacillus that lives in warm water. Morphologically, Legionnaire disease is bronchopneumonia. Risk factors include old age, organ transplantation, and cardiac, renal, immunologic, or hematologic disease. Legionnaire disease is fatal in approximately 15% of cases.
Nocardia asteroides is a gram-positive, aerobic, partially acid-fast, thin, branching, filamentous bacterium (Fig. 34.6). It causes bronchopneumonia with abscess formation (see below), typically in the setting of an immunocompromised host.
The partially acid-fast nature of the thin, branching, filamentous bacterium Nocardia asteroides is shown in this image. From Travis et al. Non-Neoplastic Disorders of the Lower Respiratory Tract. © American Registry of Pathology; 2002.
Actinomyces israelii, like N. asteroides, is a gram-positive, thin, branching, filamentous bacterium (Fig. 34.7) that causes bronchopneumonia with abscess formation (see below). Unlike N. asteroides, however, A. israelii is anaerobic and is not partially acidfast. A common risk factor for A. israelii pneumonia is chronic obstructive lung disease. Actinomyces colonies are yellow, malodorous, and commonly referred to as sulfur granules, due to their morphologic similarities with elemental sulfur.
Actinomyces, shown in a tissue Gram stain, illustrates the gram-positive, filamentous, branching nature of this bacterium. From Travis et al. Non-Neoplastic Disorders of the Lower Respiratory Tract. © American Registry of Pathology; 2002.
CLINICAL CORRELATION 34.2
Sulfur granules are commonly seen within tonsillar crypts in tonsillectomy specimens. Their presence in tonsillar crypts is responsible in part for persistent malodorous breath despite teeth brushing and mouthwash usage.
The final form of acute bacterial pneumonia to be considered is aspiration pneumonia (Fig. 34.8). It differs from other forms of bacterial pneumonia in that the pneumonitis is partly chemical (due to gastric acid injury) and partly bacterial (typically mixed flora of oral cavity residents). Focal necrosis with subsequent abscess formation (see below) is common in aspiration pneumonia. Risk factors include acute alcohol intoxication, coma, anesthesia, sinusitis, gingivo-dental sepsis, and decreased or absent cough reflex.
Aspiration pneumonia. While neutrophils dominate the inflammatory response, a clue that aspiration is the etiology is the presence of foreign material (arrow) within the parenchyma. From Kemp et al. Pathology: the Big Picture, McGraw-Hill; 2008.
As alluded to above, many of the causes of bacterial pneumonia can also result in the formation of a lung abscess (Fig. 34.9). Microorganisms typically cultivated from lung abscess fluid include aerobic and anaerobic streptococci, Staphylococcus aureus, many gram-negative microorganisms, and oral cavity anaerobes (eg, Bacteroides, Fusobacterium, Peptococcus). The most common cause of lung abscess is aspiration, but lung abscess can also complicate acute bacterial pneumonia due to S. aureus, K. pneumoniae, and S. pneumoniae type 3. Septic embolism, resulting from thrombophlebitis with subsequent embolism or right-sided bacterial endocarditis, can result in abscess formation, as can traumatic lung injury. Other settings in which a lung abscess may develop include spread of an infection from nearby tissue, bronchiectasis (Chap. 20), and hematogenous seeding; 10%-15% of abscesses are related to carcinoma (Chap. 31) obstructing an airway. Abscesses can be single or multiple and can affect any part of the lung, although the specific pattern of involvement offers a clue to the etiology. Aspiration-induced abscesses are usually single and on the right; abscesses following acute bronchopneumonia or in the setting of bronchiectasis are usually multiple and basal; and abscesses secondary to septic embolization or hematogenous seeding are usually multiple with a haphazard distribution. Lung abscesses range from a few millimeters in diameter to several centimeters in greatest dimension. Because of anatomic drains (ie, the airways) in the lung, abscesses may only be partially filled with pus, the remainder being air-filled. Symptoms/signs of lung abscess include cough, fever, copious and malodorous (purulent or sanguineous) sputum, fever, weight loss, and digital clubbing. Complications of lung abscess include empyema (Chaps. 26 and 29), hemorrhage, septic embolization (which can lead to brain abscess or meningitis), and reactive amyloidosis.
Lung abscess. (a) Grossly, the cut surface of the lung shows numerous abscess cavities in this example of Staphylococcus pneumonia. While the pus within a lung abscess can drain through airways, it does not always do so, as seen in the bottom left portion of (b), an example of Klebsiella pneumonia. From Travis et al. Non-Neoplastic Disorders of the Lower Respiratory Tract. © American Registry of Pathology; 2002.
In the setting of immunocompromise, a few fungi can infect the lung and induce a suppurative inflammatory reaction. Candida species occasionally infect the lung, although esophageal, vaginal, and cutaneous infections are more common. The morphology of Candida is budding yeast, frequently with pseudohyphae (Fig. 34.10). The inflammatory reaction is typically suppurative, but occasionally it can be granulomatous.
Candida albicans. Shown is C. albicans in culture using a variety of stains. The long structures are pseudohyphae. The key to distinguishing pseudohyphae from true hyphae is the "pinched" appearance connecting them (arrow).
Aspergillus species are angioinvasive molds that frequently induce thrombosis and infarction with subsequent suppuration. Morphologically, their hyphae are 5-10 μm wide, with a rather stiff appearance and a tendency toward 45-degree branching, a commonly quoted criterion that in reality has little diagnostic value (Fig. 34.11). Hematogenous spread is common, with involvement of heart valves and brain.
Aspergillus spp. are angioinvasive molds that typically cause thrombosis. (a) Numerous black-stained hyphae are within the lumen of a blood vessel and extend through its wall (top of image). (b) Hyphal morphology is apparent with stiff hyphae, easily identified septa, and a tendency toward 45-degree branching.
A less common fungal infection, mucormycosis (zygomycosis), is a clinical mimic of aspergillosis. Mucormycosis can be caused by a number of molds in the Zygomycetes class including Rhizopus (most common cause), Mucor, Rhizomucor, Absidia, and Cunninghamella. Like Aspergillus, these fungi are angioinvasive, resulting in thrombosis and infarction [Fig. 34.12(a), (b)] with subsequent suppurative inflammation. The hyphae of the Zygomycetes have few septa (although they are commonly described as aseptate), are of widely variable width with a ribbon-like appearance, and have a tendency toward 90° branching, again, a commonly quoted criterion that in reality has little diagnostic value [Fig. 34.12(c)].
Mucormycosis. (a) Grossly, the cut surface of the lung shows a wedge-shaped deep red lesion, a pulmonary infarct. (b) Associated with the infarct is thrombosis of a pulmonary arterial branch. (c) GMS staining shows hyphae consistent with molds of the class Zygomycetes. The hyphae show more variable width than Aspergillus and have a more ribbon-like appearance with rarer septa.
CLINICAL CORRELATION 34.3
Fungi can be identified by microscopic analysis of cultures. Whereas many yeasts and molds have similar appearances in tissues, there are specific morphologic features best seen in culture that can be identified. Shown in Fig. 34.13 are cultures of Mucor and Rhizopus. Rhizopus has rootlike structures (rhizoids), whereas Mucor does not.
Fungi grown in culture. (a) Mucor. (b) and (c) Photos of Rhizopus; note the rootlike rhizoids in both images. Structures such as these assist in the morphologic identification of fungi.