2018 - Cavitary Lung Disease

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[ Special Features ] 56
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Cavitary Lung Diseases 61
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8 Q1 A Clinical-Radiologic Algorithmic Approach 63
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Q38 Khalid Gafoor, DO; Shalin Patel, MD; Francis Girvin, MD; Nishant Gupta, MD, FCCP; David Naidich, MD, FCCP;
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Stephen Machnicki, MD; Kevin K. Brown, MD, FCCP; Atul Mehta, MD, FCCP; Bryan Husta, MD, FCCP;
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13 Jay Ryu, MD, FCCP; George Sarosi, MD; Tomás Franquet, MD; Johny Verschakelen, MD; Takeshi Johkoh, MD, PhD; 68
Q2 Q3 William Travis, MD; and Suhail Raoof, MD, Master FCCP
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17 Cavities occasionally are encountered on thoracic images. Their differential diagnosis is large 72
18 and includes, among others, various infections, autoimmune conditions, and primary and 73
19 metastatic malignancies. We offer an algorithmic approach to their evaluation by initially 74
20 excluding mimics of cavities and then broadly classifying them according to the duration of 75
21 clinical symptoms and radiologic abnormalities. An acute or subacute process (< 12 weeks) Q7 76
22 suggests common bacterial and uncommon nocardial and fungal causes of pulmonary 77
23 abscesses, necrotizing pneumonias, and septic emboli. A chronic process (> 12 weeks) 78
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suggests mycobacterial, fungal, viral, or parasitic infections; malignancy (primary lung cancer
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or metastases); or autoimmune disorders (rheumatoid arthritis and granulomatosis with
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polyangiitis). Although a number of radiographic features can suggest a diagnosis, their lack of Q8
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specificity requires that imaging findings be combined with the clinical context to make a
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29 confident diagnosis. CHEST 2018; -(-):---
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KEY WORDS: cavitary; cavitating infections; cavitation; focal lucencies; necrotic lesions
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33 To date, there are few specific guidelines A cavity, as defined by the Fleischner Society, 88
34 published on the optimal approach to is a gas-filled space, seen as a lucency or 89
35 cavitary lung disease.1,2 The intention of low-attenuation area, within a nodule, mass, 90
36 this review is to highlight the specific or area of parenchymal consolidation.3 It has 91
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clinical, laboratory, and radiographic a clearly defined wall > 4 mm thick.2
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features that can help guide clinicians in Although any strict definition would be
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their approach. For purposes of this report, arbitrary, we suggest that acute and subacute
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radiographic findings refer to abnormal cavities are those < 12 weeks old (according 96
42 chest imaging features seen on CT scans of to prior imaging or duration of symptoms), 97
43 the chest. and chronic cavities are > 12 weeks old. We 98
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46 ABBREVIATIONS: CNA = chronic necrotizing aspergillosis; GPA = Minneapolis VA Health Care System; Department of Radiology (Dr 101
47 granulomatosis with polyangiitis; ILD = interstitial lung disease; IPA = Franquet), Hospital de la Santa Creu i Sant Pau; Radiology (Dr Ver- Q5 102
48 invasive pulmonary aspergillosis; MAC = Mycobacterium avium schakelen), University Hospital Gasthuisberg; Radiology (Dr Johkoh), 103
complex; NTM = nontuberculous mycobacteria; RA = rheumatoid Kinki Central Hospital of Mutual Aid Association of Public School
49 arthritis Teachers; and Department of Pathology (Dr Travis), Memorial Sloan 104
50 AFFILIATIONS: From the Pulmonary Medicine Division (Drs Gafoor Kettering Cancer Center. 105
51 Q4 and Patel), Lenox Hill Hospital-Northwell Health; Department of CORRESPONDENCE TO: Suhail Raoof, MD, Pulmonary Division, 106
Radiology (Drs Girvin and Naidich), NYU—Langone Medical Center; Lenox Hill Hospital, 130 E 77th St, New York, NY 10075; e-mail: Q6
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Pulmonary, Critical Care and Sleep Medicine (Dr Gupta), University of suhailraoof@gmail.com
53 Cincinnati; Radiology (Dr Machnicki) and Pulmonary Division (Drs Copyright Ó 2018 American College of Chest Physicians. Published by 108
54 Husta and Raoof), Lenox Hill Hospital; Medicine (Dr Brown), National Elsevier Inc. All rights reserved. 109
Jewish Health; Pulmonary (Dr Mehta), Cleveland Clinic; Pulmonary/
55 DOI: https://doi.org/10.1016/j.chest.2018.02.026 110
CCM (Dr Ryu), Mayo Clinic; Infectious Diseases (Dr Sarosi),
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REV 5.5.0 DTD CHEST1599_proof 13 April 2018 10:44 am EO: CHEST-17-2419

111 derived the definition of “chronic” from the US National rapidly evolving cavity (< 12 weeks) strongly suggests 166
112 Q10 Center for Health Statistics, which defines a chronic an acute infectious cause. In contrast, cavities with a 167
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condition as one lasting 12 weeks (3 months) or longer.4 more chronic or indolent evolution (> 12 weeks)
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Before we delve deeper into a discussion about cavitary suggest chronic infections, autoimmune conditions, or
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lung disease, it is important to discuss conditions that malignancy. However, there may be significant overlap Q11
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mimic cavities. These include cysts, emphysema, in temporal evolution of cavitary disease processes,
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infected bullae, and cystic bronchiectasis. depending in part on the patient’s immune status and 173
119 comorbidities. 174
It is also helpful to recognize the chest imaging findings
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that can guide clinicians to a particular diagnosis. For Step 1: Are We Dealing With True Cavities?
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example, multiple peripheral nodules in varying stages
122 True cavities must be differentiated from their mimics, 177
of cavitation (Fig 1) indicae septic emboli, pulmonary
123 such as cystic disease, emphysema, infected bullae, and 178
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Langerhans cell histiocytosis, or possible infarction. 179
cystic bronchiectasis. The definitions and radiologic
125 Bronchiectasis and accompanying peripheral small 180
appearances of these mimics that distinguish them from
126 airways disease (Fig 2) typically indicate widespread 181
cavities are summarized in Table 1.5-8 Q12
127 chronic infection. Halo (Fig 3) and reversed halo (Fig 4) 182
128 signs often are seen in association with various Step 2: Assess Disease Duration 183
129 rheumatologic diseases, infections (including fungal), 184
Use the patient’s history and previous chest images to
130 septic emboli, pulmonary infarcts, and malignancies, 185
estimate disease duration. If the estimated disease
131 especially metastatic disease with hemorrhage such as 186
duration suggests an acute or subacute process
132 choriocarcinoma. An irregular internal wall (Fig 5) is 187
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(< 12 weeks), see step 3. If it is more than 12 weeks, 188
seen more frequently in malignant cavitary lesions. see step 4.
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Linear outer border, associated bronchial wall
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thickening, satellite nodules, consolidation, and ground- Step 3: Acute and Subacute Cavities (< 12 Weeks
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glass opacities are associated more commonly with in Duration)
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138 benign cavitary lesions. Although the differential diagnosis of an acute or 193
139 subacute cavity is wide, the first step is to rule out recent 194
140 Algorithmic Approach infection. Clinical features suggesting infection include 195
141 fever, chills, and cough.9 Laboratory values that suggest 196
In our algorithmic approach (Fig 6), we begin with
142 an acute bacterial infection include sputum cultures 197
ensuring that the lesions visible on CT scans are cavitary
143 demonstrating respiratory pathogens, elevated white 198
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lesions. It is important to distinguish these lesions from 199
blood cell count with shift to the left, and elevated
145 mimics of cavitary lesions. We emphasize accompanying 200
procalcitonin C levels. For fungal infections, blood
146 radiologic features that may point toward specific 201
cultures, b-D-glucan level, galactomannan level, as well
147 causes. In addition, we discuss how acuity or chronicity 202
as measurements of specific fungal antigens in the blood
148 of cavitation, clinical features, and other laboratory 203
and urine, may be important. Cavitary Mycobacterium
149 indexes influence the likelihood of diagnosis. 204
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tuberculosis can manifest acutely; however, it is more 205
Comparison with prior imaging, when available, is
151 likely to have a chronic manifestation and is discussed 206
helpful in gauging the tempo of the disease process—a
152 later. Common infectious causes, including bacterial 207
153 lung abscesses, necrotizing pneumonias, septic emboli, 208
154 and acute fungal infections, are described here and 209
155 summarized in Table 2. 210
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Bacterial Pathogens: Lung abscesses are pus- 212
158 containing necrotic lesions of the lung parenchyma 213
159 that show an air-fluid level at chest imaging. Microbial 214
160 cultures performed from lung abscesses usually 215
161 demonstrate multiple pathogens.10-12 These include 216
162 microaerophilic streptococci and viridans streptococci, 217
163 Q24 Figure 1 – Axial CT scan obtained in a 55-year-old man with a skin which were considered the most common.13 However, 218
164 abscess leading to methicillin-resistant Staphylococcus aureus bacter- 219
emia and septic emboli. There are multiple nodules in varying stages of studies from Japan and Taiwan have implicated both
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cavitation. Streptococcus species and Klebsiella pneumoniae as the
2 Special Features [ -#- CHEST - 2018 ]

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239 Figure 2 – A-B, Axial CT scans (A, B) obtained in a 52-year-old man with culture-positive Mycobacterial tuberculosis. Thick-walled cavity and 294
240 multiple tree-in-bud opacities appear posteriorly in the apical segment of the right upper lobe. 295
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242 most frequent causes of cavitary disease, suggesting level, erythrocyte sedimentation rate, and procalcitonin 297
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that the bacteriologic aspects of cavity formation may C level.10 Radiographically, a lung abscess appears as a
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be changing.13,14 Less frequently isolated organisms cavity with thick walls, irregular luminal margins and
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include Staphylococcus aureus, Pseudomonas outer borders and typically demonstrates an air-fluid
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aeruginosa, Haemophilus influenzae (type B), level (Fig 7). Lung abscesses are usually unilateral and 302
248 Acinetobacter species, Escherichia coli, and Legionella solitary and predominantly occur in the posterior 303
249 species. Contributing clinical factors are alcoholism, segments of the upper lobes and superior segments of 304
250 diabetes mellitus, generalized convulsive disorders, the lower lobes. This distribution is particularly 305
251 drug abuse, older age, and dental infections.15 Patients suggestive of prior aspiration—a diagnosis suggested 306
252 often have high fevers, night sweats, cough with foul- by the finding of centrilobular, tree-in-bud opacities in 307
253 smelling sputum, hemoptysis, fatigue, and weight loss. a similar anatomic distribution on prior chest imaging 308
254 These symptoms can go on for weeks—longer than studies.16,17 Pleural effusion and empyema have been 309
255 what is typical for community-acquired pneumonia. associated with lung abscesses 25% and 8% of the time, 310
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Laboratory test abnormalities include leukocytosis with respectively.18
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a left shift and elevated values of C-reactive protein
258 Necrotizing pneumonia is a rare but severe complication 313
259 of a bacterial infection.19,20 Acute necrotizing 314
260 pneumonia often is caused by S aureus, Streptococcus 315
261 pneumoniae, K pneumoniae, H influenzae, and P 316
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aeruginosa.21 Of special interest is community-acquired
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methicillin-resistant S aureus containing the gene for
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Panton-Valentine leukocidin, a toxin known to cause
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necrotizing pneumonia with rapid development of
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respiratory failure and shock.19 Clinical factors 322
268 contributing to the development of acute necrotizing 323
269 pneumonia are similar to those in lung abscesses and 324
270 include diabetes mellitus, alcohol abuse, and 325
271 corticosteroid therapy. Patients with acute necrotizing 326
272 pneumonia typically appear severely ill with cough, 327
273 fever, hypoxia, tachycardia, and tachypnea and rapidly 328
274 progress to respiratory failure and septic shock. 329
Figure 3 – Axial high-resolution CT scan demonstrates a solid central
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nodule surrounded by ground-glass opacity—the halo sign. Laboratory test abnormalities are similar to those found
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343 Figure 4 – A-B, Axial CT scan (A) obtained in a 47-year-old woman with acute myelogenous leukemia and pulmonary mucormycosis. There is central 398
ground-glass attenuation with a rim of more dense consolidation— the reversed halo sign. There is small adjacent ground-glass opacity. Axial CT scan
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(B) obtained in a 57-year-old man with aortic valve endocarditis and septic emboli. The left lower lobe has subpleural air-space opacity, comprising
345 central ground-glass attenuation and a rim of more dense peripheral consolidation, consistent with the reversed halo sign. Also, there are several 400
346 nodules at the right base, including a cavitary nodule medially. 401
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in lung abscesses, as previously mentioned.15,16 compared with abscesses.19,24 Surgical intervention has
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Characteristic radiographic findings include areas of been recommended early on if lung necrosis and
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consolidation containing multiple foci of poorly defined gangrene have set in because antibiotic penetration to
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low attenuation areas suggestive of necrosis. These the affected areas is compromised by diminished or 407
353 changes are identified best on chest CT scans following absent blood supply.25,26 Pleural effusions are 408
354 IV administration of contrast material. These areas associated with necrotizing pneumonia approximately 409
355 subsequently may coalesce to form larger cavities and, if 23% of the time,24 some of which can be empyema. 410
356 this process continues, can lead to frank lobar gangrene The incidence of this complication is difficult to assess 411
357 (Fig 8). because conclusions are drawn from small studies and 412
358 case reports. One study reports empyema in 6 of 413
359 Features on the CT scan that point toward lung 414
100,000.27
360 gangrene include obscuration of the pulmonary arterial 415
361 supply to the involved segment or lobe and paucity of Septic pulmonary emboli result from hematogenous 416
362 contrast material uptake in the lung parenchyma with seeding from an infected extrapulmonary site.28 Risk 417
363 central necrosis affecting > 50% of the involved lobe factors include IV drug use and infected invasive devices 418
364 (Fig 9).22,23 Necrotizing pneumonia tends to occur in such as central venous catheters and pacemakers and 419
365 Q13 regions of the lung that are less gravity dependent other such as prosthetic valves. Septic thrombophlebitis, 420
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383 Figure 5 – A-B, Coronal CT scan (A) obtained in a 66-year-old man demonstrating a thick-walled cavitary mass with an irregular internal wall in the 438
384 superior segment of the left lower lobe. Pathologic test results helped confirm primary squamous cell carcinoma of the lung. Axial CT scan (B) obtained 439
in a 66-year-old man demonstrating a thick-walled cavitary mass with an irregular internal wall in the superior segment of the left lower lobe.
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Pathologic test results helped confirm primary squamous cell carcinoma of the lung.

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Focal hyperluciencies-Suspect pulmonary cavitary disease
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443 498
444 Confirm cavities
Step 1
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(Exclude mimics)
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446 Mimics 501
Cysts
447 Emphysema
Review old imaging studies (if available) +
Step 2
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Obtain history to determine duration of disease
448 Infected Bullae 503
Cystic Bullae
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450 505
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452 Acute/subacute Chronic 507
Step 3 Step 4
(<12 weeks) (>12 weeks)
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454 509
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457 Step 5 Step 6 Step 7 512
458 Acute infections Chronic Infections Malignancy Autoimmunity 513
459 514
460 515
Clinical History & Investigations: Clinical History & Investigations:
461 Fever, chills, productive cough,
Clinical History &
Older, Weight loss, chronic
Clinical History & Investigations: 516
Investigations: History of connective tissue
462 aspiration risk, elevated WBC,
Fevers, weight loss, chronic
cough, hemoptysis, fatigue,
disease, arthralgia, myalgias, 517
elevated Pro-calcitonin smoking history,
cough, hemoptysis, fatigue rash, fever, positive serology.
463 (bacterial infections) history of malignancy 518
464 519
465 520
CT features CT features CT features CT features
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468 Lung abscess TB
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Primary lung
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print & web 4C=FPO
Necrotizing pneumonia NTB

cancer RA
Septic emboli Fungal
470 Fungol infection Parasitic
Metastatic to GPA 525
lung
Nocardia Viral
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472 See Table 2 See Table 3 See Table 4 See Table 5 527
473 Figure 6 – Algorithmic approach to cavitary lung disease. GPA ¼ granulomatosis with polyangiitis. Q39 528
474 529
475 530
476 pelvic thrombophlebitis, and Lemierre syndrome also Pulmonary nocardiosis most commonly is caused by 531
477 may be implicated.1,29 Fever, dyspnea, chest pain, cough, Nocardia asteroides, which is found primarily in soil; the 532
478 fatigue, and hemoptysis are frequently present. respiratory tract, skin, and GI tract are the primary 533
479 Progression to respiratory failure, septic shock, portals of infection. Patients with defects in cell- 534
480 empyema, or renal failure can occur. Positive blood mediated immunity are predisposed to infection, 535
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cultures are common, and the most commonly isolated including patients who have undergone solid organ or
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organisms are staphylococcal species, Fusobacterium stem cell transplant who are receiving
483 538
necrophorum, K pneumoniae, and Streptococcus immunosuppressive therapy and those with AIDS,
484 539
485
viridans.29,30 Radiographically, septic emboli appear as lymphoma, and leukemia. Low-grade fevers, weight loss, 540
486 well-defined, peripheral or subpleural nodules of various cough, fatigue, and chest pain are often present, and 541
487 size (0.5-3.5 cm) with evidence of cavitation in up to acute respiratory failure can occur.10 The CNS is the 542
488 85% of patients. A characteristic feature is the finding of most common extrapulmonary site of infection with 543
489 nodules simultaneously appearing in various stages of Nocardia. Patients may have one or more brain 544
490 cavitation because of repeated seeding of the lungs, most abscesses and can have symptoms of headache, nausea, 545
491 often from endocarditis. As further evidence of a vomiting, seizures, or altered mental status.31 546
492 hematologic origin, nodules may be associated with Radiographically, pulmonary nodules and consolidation 547
493 548
feeding vessels, variously reported in 67% to 100% of are common, and cavitation can occur in both (Fig 11).
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cases (Fig 10).24,29,31-33 Pulmonary nodules range in size from 0.6 to 2.9 cm.
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551 TABLE 1 ] Cavity Mimics Q20 606
552 607
Cavity Mimic Definition or Radiographic Appearance CT Scan
553 608
Cyst Round parenchymal lucency with a
554 609
well-defined thin wall (< 2 mm
555 thick)5
610
556 611
557 612
558 613
559 614
560 615
561 616
562 617
563 618
564 619
565 620
566 621
567 622
568 Emphysema Focal areas or regions of low 623
attenuation, usually without
569 624
visible walls6
570 625
571 626
572 627
573 628
574 629
575 630
576 631
577 632
578 633
579 634
580 635
581 636
Infected bullae Radiographic evidence of previous
582 bullous disease and the 637
583 development of an air-fluid level7 638
584 639
585 640
586 641
587 642
588 643
589 644
590 645
591 646
592 647
593 648
594 Cystic bronchiectasis Lack of bronchial tapering and an 649
595 increased bronchoarterial ratio8 650
596 651
597 652
598 653
599 654
600 655
601 656
602 657
603 658
604 659
605 660

661 TABLE 2 ] Acute and Subacute Cavities 716
662 717
Cavity Patient Background Radiographic Findings Laboratory Findings
663 718
Lung abscess Alcoholism, diabetes mellitus, Typically unilateral and Positive sputum cultures
664 719
convulsive disorders, drug solitary cavities with thick, Leukocytosis with left shift,
665 abuse, elderly, and dental irregular walls, often with elevated procalcitonin C
720
666 infections an air-fluid level level 721
667 High fevers, night sweats, Predominantly in the 722
668 cough with foul-smelling posterior segments of the 723
sputum, fatigue, and weight upper lobes and superior
669 724
loss segments of the lower
670 lobes
725
671 726
Necrotizing Diabetes mellitus, alcohol Usually unilateral and Positive sputum cultures
672 pneumonia abuse, and corticosteroid solitary pulmonary Leukocytosis, elevated 727
673 therapy consolidation with multiple procalcitonin C level, 728
674 Usually severely ill, may have foci of poorly defined low- elevated ESR and CRP 729
675 respiratory failure and shock density areas suggestive level 730
of necrosis
676 731
Tends to be more common in
677 regions of the lung that are 732
678 not gravity dependent 733
679 Septic emboli Central venous catheters, Multiple, bilateral, Positive blood cultures 734
680 pacemakers, right-sided peripherally located Leukocytosis, elevated ESR 735
681 prosthetic valves, IV drug nodules that cavitate; and CRP level 736
682 abuse, and Lemierre usually seen in different 737
syndrome stages of cavitation
683 738
Fevers, dyspnea, chest pain, May see a feeding vessel sign
684 cough may progress to Nodules may be 0.5-3.5 cm. 739
685 respiratory failure and septic 740
686 shock 741
687 Nocardia Patients who have undergone Pulmonary nodules and Positive PCR results with 742
688 solid organ or stem cell consolidation, most respiratory sample 743
689 transplant who are receiving commonly bilateral Microscopy of respiratory 744
immunosuppressive therapy Cavitation can occur in sample (gram positive
690 745
and patients with AIDS, both nodules and and modified acid fast)
691 lymphoma, and leukemia consolidation. No zonal 746
692 Low-grade fevers, weight loss, predominance 747
693 and cough 75% of cases may have 748
694 Respiratory failure may occur. crazy-paving appearance 749
around nodules, cavities,
695 750
masses, or consolidations
696 Nodules may be 0.6-2.9 cm. 751
697 752
Cryptococcus Exposure to aged pigeon Multiple bilateral, peripheral Positive sputum culture
698 droppings More common in nodules and masses that Positive serum latex 753
699 patients who are cavitate agglutination results 754
700 immunocompromised Nodules may be 0.7-2.8 cm. Positive for b-D-glucan 755
Fever, cough, dyspnea,
701 756
headache May be
702 757
asymptomatic
703 758
Coccidioidomycosis Severe disease is common in Focal or multifocal Peripheral eosinophilia
704 hosts who are consolidation is the most May have positive BAL,
759
705 immunocompromised and common finding. Cavities sputum, or lung biopsy 760
706 travel to endemic regions are seen in 2%-8% of cultures 761
707 (Southwest United States, cases. Positive complement 762
Mexico, Central and South Phantom infiltrates may be fixation, immunodiffusion,
708 763
America). seen. and urine antigen
709 Profound fatigue, erythema Nodules may be 0.5-3.0 cm.
764
710 nodosum or erythema 765
711 multiforme, arthralgias, 766
712 cough, fever, subacute time 767
course
713 768
714 (Continued) 769
715 770
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771 TABLE 2 ] (Continued) 826
772 827
Cavity Patient Background Radiographic Findings Laboratory Findings
773 828
Invasive pulmonary Prolonged neutropenia, T-cell Solitary or multiple nodules Positive for serum
774 829
aspergillosis deficiency, organ transplant with a halo sign, and galactomannan and b-D-
775 Fevers, cough, dyspnea, 1-2 weeks after the halo glucan 830
776 hemoptysis unresponsive to sign appears the nodule Positive for BAL 831
777 antibiotics can cavitate leading to an galactomannan 832
778 air crescent sign 833
Also may see pleural-based
779 834
wedge-shaped areas of
780 consolidation 835
781 Usually > 1 cm 836
782 Mucormycosis Poorly controlled diabetes and Radiographically similar to Organisms in tissue at 837
783 immunocompromise IPA histopathologic 838
784 Patients are often severely ill, Also may see reversed halo examination 839
785 with fevers, cough dyspnea, sign more commonly than Negative for b-D-glucan 840
and hemoptysis. in IPA
786 841
787 CRP ¼ C-reactive protein; ESR ¼ erythrocyte sedimentation rate; IPA ¼ invasive pulmonary aspergillosis; PCR ¼ polymerase chain reaction. 842
788 843
789 Seventy-five percent of cases may have a crazy-paving Coccidioidomycosis is caused by the fungus 844
790 appearance around nodules, cavities, masses, or Coccidioides. This organism is endemic in the soil of the 845
791 846
consolidation.32 Crazy-paving is defined as an area of southwestern United States, parts of Mexico, and
792 847
ground-glass attenuation, frequently well defined, within Central and South America. Infection results from the
793 848
which a pattern of interlobular septal thickening can be
794 849
795
identified, restricted to the area of ground-glass 850
796 attenuation.33 Pleural effusion has been reported in 851
797 10% to 36% of cases. There also may be associated 852
798 bronchiectasis (40%).34-37 The diagnosis can be made 853
799 from microscopic examination of bronchial washings 854
800 and BAL with modified acid-fast stain and Gram stain 855
801 or positive polymerase chain reaction of the respiratory 856
802 sample.38,39 857
803 858
804 Fungal Pathogens: Cryptococcus neoformans is the most 859
805 common Cryptococcus species encountered in the 860
806 United States and other temperate climates in the world. 861
807 It is considered one of the principal pathogens in 862
808 863
humans and is found in soil and aged pigeon
809 864
droppings.40 Pulmonary involvement occurs after
810 865
inhalation of spores and more commonly affects
811 866
individuals who are immunocompromised.41 Patients
812 867
813
typically present with fever, cough, shortness of breath, 868
814 chest pain, and headache; however, some patients may 869
815 be asymptomatic.42,43 Radiographically, the common 870
816 manifestation is multiple bilateral, peripheral nodules 871
817 and masses, although a random distribution also has 872
818 been described. Pulmonary nodules range in size from 873
819 0.7 to 2.8 cm.44 Cavitation, when present, occurs within 874
820 nodules or masses and less commonly in foci of 875
821 876
air-space consolidation, especially in hosts who are Figure 7 – Axial CT scan obtained in 42-year-old man demonstrating
822 877
immunocompromised.42,45 Sputum culture, b-D-glucan an irregular thick-walled cavity with dependent air-fluid level and
823 peripheral ground-glass halo involving the apical segment of the right 878
and serum latex agglutination test results may be upper lobe and superior segment of the right lower lobe. Biopsy results
824 879
positive.46 helped confirm abscess, but a specific pathogen was not isolated.
825 880

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904 Figure 8 – A-D, Necrotizing pneumonia. Axial CT scans (A, B) of the right lung with lung and soft-tissue windows. There is a large area of 959
905 consolidation with surrounding ground-glass opacity and septal thickening in the right lower lobe. Areas of lucency within the consolidation are 960
906 consistent with cavitation. No pathogen was identified. Acute necrotizing pneumonia (STAIN, 0 magnification). Low-power image (C) shows Q25
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cavitation at the bottom of the image surrounded by marked acute inflammation. Acute necrotizing pneumonia (STAIN, 0 magnification). A
907 neutrophilic abscess at the bottom center of the image (D) is surrounded by marked acute and chronic inflammation with a few giant cells. 962
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910 inhalation of aerosolized spores and occurs in patients Others will develop symptoms similar to an acute 965
911 living in endemic regions or traveling to these areas.47 bacterial pneumonia such as cough, fever, and chest 966
912 Risk factors include AIDS, hematologic malignancies, pain. In highly endemic areas, up to 29% of patients with 967
913 pregnancy, diabetes, cardiopulmonary disease, smoking, community-acquired pneumonia have 968
914 and male sex. In primary coccidioidal infection (acute), coccidioidomycosis.48 Some distinguishing features are 969
915 the majority of patients (60%-80%) are either profound fatigue, erythema nodosum or erythema 970
916 asymptomatic or have mild influenza-like symptoms. multiforme, arthralgias, and subacute time course.10,49-51 971
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931 Figure 9 – A-B, Necrotizing pneumonia. Axial contrast-material-enhanced CT scan (A) obtained in the mediastinal window in a 74-year-old woman 986
who presented with shortness of breath, lethargy, and septic shock. Stenotrophomonas and methicillin-sensitive Staphylococcus aureus were in sputum.
932 987
There is dense consolidation in both lower lobes, with cavitation and nonenhancing lung (arrow) in the right lower lobe. Necrotic lung mass. Axial
933 contrast-material-enhanced CT scan (B) obtained in the mediastinal window in a 62-year-old woman with lung, skin, liver, and joint involvement 988
934 from granulomatosis with polyangiitis. A lung mass with a central area of nonenhancing lung (red arrow) is surrounded by a rim of enhancement 989
(yellow arrow), suggesting necrosis. A nodule with a similar appearance is posterior to the lung mass with a central area of nonenhancing lung
935 990
surrounded by a rim of enhancement.
chestjournal.org 9

991 1046
992 1047
993 1048
994 1049
995 1050
996 1051
997 1052
998 1053
999 1054
1000 1055
1001 1056
1002 1057
1003 1058
print & web 4C=FPO
1004 1059
1005 1060
1006 1061
1007 1062
Figure 10 – A-B, Septic emboli. Coronal (A) and axial (B) scans obtained with lung windows demonstrate multiple nodules in different stages of
1008 1063
cavitation in both lungs. Ground-glass opacity surrounds the cavity in the left apex. A feeding vessel sign (arrow) is visible adjacent to that cavity as
1009 well. Note the right-sided central line. 1064
1010 1065
1011 1066
1012 The most common radiologic manifestation of the acute Aspergillus is a commonly found environmental mold 1067
1013 form is focal or multifocal consolidation. Pulmonary that can cause a variety of pulmonary diseases, including 1068
1014 1069
nodules are another common feature and are similar in aspergilloma, chronic necrotizing aspergillosis (CNA),
1015 1070
size to the nodules seen with Cryptococcus. Cavities are and invasive pulmonary aspergillosis (IPA). In the host
1016 1071
seen in 2% to 8% of acute primary infections. These tend who is immunocompromised, inhaled Aspergillus can
1017 1072
1018
to resolve spontaneously but can persist to become invade the vasculature, with subsequent infarction and 1073
1019 chronic cavities. Another feature is phantom infiltrates tissue necrosis. IPA is seen primarily in patients with 1074
1020 in which parenchymal consolidation appears at one site, prolonged neutropenia, solid organ transplants, or T-cell 1075
1021 resolves, and then reappears in a new location.52 A deficiencies. Other risk factors include COPD, long-term 1076
1022 peripherally located cavity can rupture into the pleural steroid therapy, diabetes, and liver cirrhosis.55 1077
1023 space causing a pneumothorax (Fig 12).52 Diagnostic Symptoms of pneumonia, including productive cough, 1078
1024 tests include complement fixation, immunodiffusion, dyspnea, chest pain, hemoptysis, and fevers 1079
1025 and urine examination for fungal antigen.53,54 unresponsive to antibiotics, are typical. Laboratory test 1080
1026 result abnormalities may include a finding positive for 1081
1027 1082
galactomannan and b-D-glucan.56 A number of imaging
1028 1083
findings have been reported to occur due to infection
1029 1084
with Aspergillus. Of these, acute cavitation is most likely
1030 1085
1031
to be identified in its invasive form. IPA 1086
1032 characteristically manifests with multiple pulmonary 1087
1033 nodules, often > 1 cm,57 associated with a halo sign 1088
1034 (Fig 13A), which is defined as ground-glass attenuation 1089
1035 surrounding a solid central core; the ground-glass 1090
1036 component represents pulmonary hemorrhage due to 1091
1037 the angioinvasive nature of Aspergillus. One to 2 weeks 1092
1038 after the halo sign appears, especially following 1093
1039 successful treatment, nodules cavitate in up to 63% of 1094
1040 1095
patients, leading to an air crescent sign, as a result of
1041 Figure 11 – Pulmonary Nocardia. Axial CT scan obtained with lung 1096
windows in a 62-year-old man receiving long-term steroid therapy for tissue necrosis (Fig 13B).56,58,59 Another radiologic
1042 1097
polymyalgia rheumatica hospitalized for recurrent cough, fevers, and appearance of IPA includes pleura-based wedge-shaped
1043 night sweats demonstrates an area of consolidation with central cavi- 1098
1044 tation in the right upper lobe. There is a small adjacent ground-glass
areas of consolidation whose findings correspond to 1099
1045 opacity. hemorrhagic infarcts.57 1100

1101 1156
1102 1157
1103 1158
1104 1159
1105 1160
1106 1161
1107 1162
1108 1163
1109 1164
1110 1165
1111 1166
1112 1167
1113 1168
1114 1169
1115 1170
1116 1171
1117 1172
1118 1173
1119 1174
1120 1175
1121 1176
1122 1177
1123 1178
1124 1179
1125 1180
1126 Figure 12 – A-B, Chest radiograph (A) and axial CT scan (B) obtained in 22-year-old man initially thought to have a spontaneous pneumothorax. 1181
1127 Radiographs and CT scans demonstrated a hydropneumothorax in the right lung and a solitary thick-walled cavity at the right apex. Wedge resection 1182
1128 demonstrated granulomatous inflammation, and Coccidioides immitis and C posadasii were identified with sputum culture and polymerase chain 1183
reaction.
1129 1184
1130 1185
1131 1186
1132 1187
1133 1188
1134 1189
1135 1190
1136 1191
1137 1192
1138 1193
1139 1194
1140 1195
1141 1196
1142 1197
1143 1198
1144 1199
1145 1200
1146 1201
1147 1202
1148 1203
1149 1204
1150 1205
1151 1206
1152 1207
1153 1208
1154 Figure 13 – A-B, Axial CT scan (A) demonstrates multiple solid nodules surrounded by ground-glass opacities or ill-defined fuzzy margins—the halo 1209
sign. Coronal high-resolution CT scan (B) demonstrates a crescentic lucency surrounding the nodule—the air crescent sign. This image is from a
1155 1210
different patient from the patient in Figure 13A.
chestjournal.org 11

1211 Mucormycosis is an infection caused by molds Step 5: Chronic Infections 1266
1212 belonging to the order Mucorales. Rhizopus and Mucor 1267
Mycobacterial Disease: TB is caused by M tuberculosis.
1213 1268
are the two genera most commonly noted to cause In more than 90% cases, it is a reactivation of a latent
1214 1269
infection. These molds are ubiquitous and are found in infection. The risk of conversion to active disease is
1215 1270
soil and decaying plant material. They gain access to the estimated to be up to 10% through a patient’s entire
1216 1271
host via inhalation, skin penetration, and less frequently lifetime and is higher in patients who are
1217 1272
1218
ingestion. The most frequently affected are those with immunocompromised.66,67 Patients with pulmonary TB 1273
1219 poorly controlled diabetes and those who are can present with chronic cough, sputum production, 1274
1220 immunocompromised.60 Patients are often severely ill weight loss, fevers, night sweats, loss of appetite, and 1275
1221 and present with fevers, cough, dyspnea, pleuritic chest hemoptysis. These patients may have HIV coinfection or 1276
1222 pain, and hemoptysis. At laboratory analysis, a positive come from an endemic region.68 Patients with 1277
1223 b-D-glucan result is not found because Mucor and tuberculosis may have a positive interferon gamma 1278
1224 Rhizopus do not produce this polysaccharide. A 1279
release assay, tuberculin skin test, or sputum microscopy
1225 diagnosis is usually made by means of histopathologic 1280
or culture.65,68 Radiographically, fibrocavitary disease
1226 1281
testing.10,61 Radiographically, the manifestation overlaps occurs in approximately 50% of patients with
1227 1282
with that of IPA. More commonly than in IPA, a reactivation TB and is seen more often in the apical and
1228 1283
reversed halo sign may be seen, which is defined as posterior segments of the upper lobes or the superior
1229 1284
curvilinear solid density surrounding a core of ground- segments of the lower lobes. Fibrocavitary disease is
1230 1285
1231
glass attenuation (Fig 4).62 As with IPA masses, nodules, defined radiographically as pulmonary infiltrates 1286
1232 a halo sign, consolidation, and cavitation are all characterized by nodular densities, linear fibrous scars, 1287
1233 seen.61,63,64 Cavity formation can occur after the volume loss due to scarring, and cavitation.68 Multiple 1288
1234 reversed halo sign or halo sign is noted.64,65 Although cavities usually are present and appear thick walled with 1289
1235 neither the halo nor the reversed halo sign is irregular inner margins, which can become thin and 1290
1236 pathognomonic of IPA or mucormycosis, their presence 1291
smooth with treatment (Fig 2).69-71
1237 is sufficiently suggestive, especially in the setting of a 1292
1238 host who is immunocompromised, to warrant initial Nontuberculous mycobacteria (NTM) are ubiquitous in 1293
1239 the environment, but concentrations are highest in water 1294
empiric therapy.
1240 and soil. The most common organism associated with 1295
1241 pulmonary disease is Mycobacterium avium complex 1296
Step 4: Chronic Cavities (> 12 Weeks in Duration)
1242 1297
(MAC), a term that encompasses many subspecies. To
1243 The differential diagnosis includes chronic infections, 1298
date, two distinct populations of patients have been
1244 malignancy, and autoimmune disorders. On the 1299
identified as frequently infected. The first group is
1245 basis of the clinical context, we can direct our 1300
1246
defined by underlying risk factors that include profound 1301
differential diagnosis into one of these three disease
1247 immunosuppression such as HIV; transplant; or 1302
categories.
1248 structural lung disease with architectural distortion such 1303
1249 Chronic infections and malignancy are suggested by as COPD, silicosis, prior TB infection, or cystic 1304
1250 fevers, weight loss, chronic cough, hemoptysis, and fibrosis.72-74 Patients in this setting can present with 1305
1251 fatigue. However, malignancy is more likely in a patient chronic productive cough, hemoptysis, malaise, fatigue, 1306
1252 with a smoking history, older age, and a personal or and weight loss. Patients with NTM may have positive 1307
1253 family history of cancer. If the clinical context suggests a sputum microscopy or culture results. Radiographically, 1308
1254 chronic infection, see step 5. If the clinical context MAC appears similar to reactivation TB, with upper 1309
1255 1310
suggests malignancy, see step 6. Chronic infections are lobe fibrocavitary disease (Figs 14A-D); however,
1256 1311
summarized in Table 3; malignancy is summarized cavities due to MAC may be smaller or thin walled, and
1257 1312
in Table 4. disease may progress more slowly. Common associated
1258 1313
1259
imaging findings include tree-in-bud opacities and 1314
Autoimmune disorders are suggested by a history of
1260 bronchiectasis.75-77 1315
connective tissue disease, arthralgias, myalgias, and
1261 1316
positive serologic test results. If the clinical context A second group of individuals at risk for NTM infection
1262 1317
suggests autoimmune disorders, see step 7. Autoimmune are elderly women who present with chronic
1263 1318
disorders are summarized in Table 5. nonproductive cough and weight loss. This group tends
1264 1319
1265 1320

1321 TABLE 3 ] Chronic Infection 1376
1322 1377
Chronic Infection Patient Background Radiographic Findings Laboratory Findings
1323 1378
Mycobacterium HIV, from endemic region, Cavitation often occurs in the Positive TST or IGRA results
1324 1379
tuberculosis exposure history apical and posterior Positive sputum microscopy
1325 Chronic cough, weight loss, segments of the upper and culture results
1380
1326 fevers, night sweats, lobes and superior 1381
1327 hemoptysis segments of lower lobes. 1382
1328 Solitary or multiple cavities 1383
with thick, irregular walls
1329 1384
usually are present.
1330 1385
Nontuberculous Structural lung disease, Solitary or multiple Sputum microscopy and
1331 1386
mycobacteria immunosuppressed fibrocavitary changes and culture results Q21
1332 Chronic cough, hemoptysis, nodules primarily in the 1387
1333 fatigue, weight loss upper lobes 1388
1334 Middle-aged to elderly women Typically involves the right Sputum microscopy and 1389
1335 without structural lung middle lobe and lingula culture results 1390
1336 disease with nodules and 1391
1337 Chronic nonproductive cough bronchiectasis 1392
Also may see atelectasis,
1338 1393
consolidation with tree-in-
1339 bud and ground-glass 1394
1340 opacities 1395
1341 Frank cavitation can occur 1396
1342 Chronic necrotizing Structural lung disease, inactive Unilateral or bilateral Positive for Aspergillus IgG 1397
1343 aspergillosis or previously treated MTB, cavitary lesions in upper Positive sputum Aspergillus 1398
1344 prior lung resection, radiation lobes with adjacent pleural PCR results 1399
therapy, cystic fibrosis, or thickening, which may
1345 1400
lung infarction progress to form a
1346 Fevers, cough, dyspnea, bronchopleural fistula 1401
1347 malaise, hemoptysis One-half of these cavities 1402
1348 can develop an 1403
1349 aspergilloma. 1404
1350 Histoplasmosis Ohio and Mississippi River Cavities can be solitary or Positive complement fixation 1405
valleys, exposure to soil that multiple, typically located titers
1351 1406
contains large amounts of bird in the upper lobes and Sputum fungal stain and
1352 1407
or bat droppings, chicken associated with fibrosis. culture results Q22
1353 coops, more common in those Also may see punctate Histoplasma antigen in 1408
1354 with structural lung disease calcifications in the spleen, urine, blood, and BAL 1409
1355 Productive cough, fever, night liver, and mesenteric 1410
sweats, weight loss, erythema lymph nodes
1356 1411
nodosum, erythema
1357 1412
multiforme
1358 1413
Blastomycosis United States and Canada Cavities are uncommon but Potassium hydroxide smear
1359 surrounding the Ohio and can be solitary or multiple, of fresh sputum frequently
1414
1360 Mississippi River valleys and typically located on the will indicate the organism. 1415
1361 the Great Lakes upper lobes, and have thin Positive urine, serum, or BAL 1416
1362 More commonly affect the host or thick walls. antigens are helpful 1417
Q23 who is immunocompetent
1363 1418
Cough, fever, night sweats,
1364 malaise, skin and bone
1419
1365 involvement 1420
1366 Paragonimus Ingestion of raw freshwater crab Nodules with cavitation Characteristic eggs at 1421
1367 or crayfish Nodule size is most sputum or BAL testing 1422
1368 Endemic to Japan, China, Korea, commonly 2.0 cm. Peripheral eosinophilia may 1423
1369 and the Philippines be seen. 1424
Productive cough, chest pain,
1370 1425
back pain, fevers
1371 1426
1372 (Continued) 1427
1373 1428
1374 1429
1375 1430
chestjournal.org 13

1431 TABLE 3 ] (Continued) 1486
1432 1487
Chronic Infection Patient Background Radiographic Findings Laboratory Findings
1433 1488
Echinococcus South America, countries Majority of lesions are liver Serologic testing
1434 1489
surrounding the cysts, but lung is involved Peripheral eosinophilia may
1435 Mediterranean, the Middle 20%-30% of the time. be seen. 1490
1436 East, some sub-Saharan Pulmonary cavities may 1491
1437 African countries form. Cavity wall may 1492
1438 Often asymptomatic for years, calcify over time. 1493
may develop fevers, cough, Collapsed laminated
1439 1494
hemoptysis, wheezing, membrane may float in the
1440 anaphylaxis, or cavity, producing the 1495
1441 pneumothorax water lily sign. 1496
1442 Tracheobronchial Human papillomavirus, multiple Mucus plugging with finger- Bronchial tree tissue biopsy 1497
1443 papillomatosis papillomas in the in-glove appearance, 1498
1444 nasopharynx, larynx, and atelectasis, sold and 1499
1445 bronchial tree cavitary nodules 1500
Nodules are 0.5-5 cm.
1446 1501
1447 IGRA ¼ interferon gamma release assay; MTB ¼ Mycobacterium tuberculosis; TST ¼ tuberculin skin test. See Table 2 for expansion of other abbreviation. 1502
1448 1503
1449 1504
1450 1505
to present primarily with signs of chronic airway culture.80 Radiographically, Aspergillus manifests as
1451 1506
inflammation, including bronchiectasis and small unilateral or bilateral cavitary lesions in the upper lobes
1452 1507
airway disease manifesting as branching centrilobular or associated with adjacent pleural thickening, which may
1453 1508
tree-in-bud opacities. Although these findings may progress to a bronchopleural fistula. Approximately
1454 1509
1455
occur anywhere throughout the lung, a particularly one-half of these cavities can develop an aspergilloma 1510
1456 distinct pattern is the predominant involvement of the (Fig 15).56,60,62,81,82 1511
1457 lingula and middle lobe (Figs 14E-G). In more extensive 1512
Histoplasmosis is caused by the dimorphic fungus
1458 cases, frank cavitation may occur.78 1513
Histoplasma capsulatum. The fungus typically lives in
1459 1514
Fungal Disease: CNA is an indolent, destructive process soil that contains large amounts of bird or bat
1460 1515
1461
due to Aspergillus species in the lung, which can be droppings. In the United States, Histoplasma is endemic 1516
1462 differentiated from IPA because of its chronicity around the Ohio, Missouri, and Mississippi River valleys 1517
1463 (months to years).60 These patients will present with and St. Lawrence River area.82 Patients with structural 1518
1464 fever, cough, sputum production, dyspnea, hemoptysis, lung disease such as COPD are at risk and typically will 1519
1465 anorexia, weight loss, and malaise. Almost all patients have had symptoms of productive cough, malaise, fevers, 1520
1466 with CNA have underlying structural lung disease such night sweats, and weight loss. Less common symptoms 1521
1467 as COPD, inactive or previously treated TB, prior lung include chest pain due to mediastinal lymph node 1522
1468 resection, radiation therapy, cystic fibrosis, or lung enlargement, arthralgias, arthritis, erythema nodosum, 1523
1469 infarction.60,79 The most sensitive laboratory test is an and erythema multiforme.83 Positive complement 1524
1470 1525
Aspergillus IgG antibody. With sputum, Aspergillus fixation titer and sputum fungal stain and culture results
1471 1526
polymerase chain reaction testing is more sensitive than and positive Histoplasma antigen in urine, blood, and
1472 1527
1473 1528
1474 1529
1475 TABLE 4 ] Malignancy 1530
1476 1531
Malignancy Patient Background Radiographic Findings Laboratory Findings
1477 1532
Primary Smoking history, family history of lung Irregular internal wall and notch Tissue at histopathologic
1478 1533
cancer, and asbestos exposure sign examination
1479 Cough, weight loss, malaise, Usually solitary with an upper lobe 1534
1480 hemoptysis predominance 1535
1481 Metastatic Extrathoracic malignancy (commonly Multiple bilateral pulmonary Tissue at histopathologic 1536
1482 squamous cell) and smoking history nodules, which can cavitate and examination 1537
1483 Cough, weight loss, malaise, vary from irregular and thick to 1538
1484 hemoptysis regular and thin 1539
May see Cheerio sign
1485 1540

1541 TABLE 5 ] Autoimmune Disorders 1596
1542 1597
Autoimmune Disorder Patient Background Radiographic Findings Laboratory Findings
1543 1598
Rheumatoid arthritis History or symptoms of Well-defined nodules of a Elevated rheumatoid
1544 1599
rheumatoid arthritis, few millimeters to a few factor level
1545 including joint pains and centimeters with central Elevated anti-CCP
1600
1546 fevers cavitation and sometimes antibody level 1601
1547 seen with the underlying Elevated ESR or CRP level 1602
1548 background of interstitial 1603
lung disease
1549 1604
1550 Granulomatosis with History of granulomatosis Multiple and bilateral Elevated serum 1605
polyangiitis with polyangiitis pulmonary nodules cytoplasmic anti-
1551 1606
May have symptoms Cavitation can occur in 25%- neutrophil antibodies
1552 including rhinosinusitis, 50% of nodules that are against protease 3 in 1607
1553 epistaxis, fever, malaise, usually thick walled. cytoplasmic granule 1608
1554 hemoptysis titers 1609
1555 1610
Anti-CCP ¼ Anti-cyclic citrullinated peptide. See Table 2 legend for expansion of other abbreviations.
1556 1611
1557 1612
1558 BAL all support the diagnosis.84,85 Radiographically, nodes are particularly suggestive signs of previous 1613
1559 cavities typically are found in the upper lobes, and histoplasmosis (Figs 16B and 16C).89 In 1614
1560 associated fibrosis can be seen in up to 30% of patients contradistinction, although TB also may result in splenic 1615
1561 (Fig 16A).86-88 Findings of numerous punctate and hepatic calcifications, these are characteristically far 1616
1562 1617
calcifications in the spleen, liver, and mesenteric lymph less numerous.
1563 1618
1564 1619
1565 1620
1566 1621
1567 1622
1568 1623
1569 1624
1570 1625
1571 1626
1572 1627
1573 1628
1574 1629
1575 1630
1576 1631
1577 1632
1578 1633
1579 1634
1580 1635
1581 1636
1582 1637
1583 1638
1584 1639
1585 1640
1586 1641
1587 1642
1588 1643
print & web 4C=FPO
1589 1644
1590 1645
1591 1646
1592 1647
1593 Figure 14 – A-G, Nontuberculous mycobacteria. Axial (A, B) and coronal (C) CT scans obtained in a 68-year-old woman with sputum culture-positive 1648
1594 nontuberculous mycobacteria demonstrating thick-walled cavities, bronchiectasis, bronchial wall thickening, and several tree-in-bud opacities in the 1649
right lower lobe. Coronal CT scan (D) demonstrates fibrocavitary disease in the lung apexes bilaterally, with traction of the hila and fissures (arrows) Q26
1595 1650
superiorly. Axial CT scans (E, F, G) demonstrate multiple thick-walled cavities confined to the right lung with tree-in-bud opacities bilaterally.
chestjournal.org 15

1651 1706
1652 1707
1653 1708
1654 1709
1655 1710
1656 1711
1657 1712
1658 1713
1659 1714
1660 1715
1661 1716
1662 1717
1663 1718
1664 1719
1665 1720
1666 1721
1667 1722
1668 1723
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1669 1724
1670 1725
1671 1726
1672 1727
1673 Figure 15 – A-C, Aspergilloma. Axial CT scan (A) demonstrates solid masses in dependent positions within biapical cavities, consistent with fungus 1728
balls. Bronchiectasis with aspergilloma (hematoxylin-eosin, 2 magnification). Image (B) shows a markedly dilated cavitary airway surrounded
1674 by acute and chronic inflammation and a thick rim of fibrosis. This pathology slide is from a different patient from the radiographic image of 1729
1675 Figure 15A. Bronchiectasis with aspergilloma (Gomori methenamine silver, 20 magnification). Image (C) shows that within the airway lumen is a 1730
1676 fungus ball with the morphology of the Aspergillus species. The fungal organisms are highlighted by the Gomori methenamine silver stain. This 1731
pathology slide is from a different patient from the radiographic image of Figure 15A.
1677 1732
1678 1733
1679 1734
1680 1735
1681 1736
1682 1737
1683 1738
1684 1739
1685 1740
1686 1741
1687 1742
1688 1743
1689 1744
1690 1745
1691 1746
1692 1747
1693 1748
1694 1749
1695 1750
1696 1751
1697 1752
1698 1753
print & web 4C=FPO
1699 1754
1700 1755
1701 1756
1702 1757
1703 Figure 16 – A-C, Histoplasmosis. Axial high-resolution CT scan (A) demonstrates a thick-walled, cavitary nodule with eccentric calcification in the 1758
1704 right upper lobe. Coronal CT scan (B) obtained with a mediastinal window demonstrates large calcified lymph nodes in the right hilum and a thick- 1759
walled, cavitary nodule (arrow) with eccentric calcification in the right upper lobe. Coronal CT scan (C) obtained with a mediastinal window Q27
1705 1760
demonstrates multiple punctate calcifications in the spleen.

1761 Blastomycosis is caused by Blastomyces dermatitidis and, nodules are common, with cavitation noted in 15% to 1816
1762 similar to Histoplasma and Coccidioides, lives in the soil, 59% of cases.1 In one series, the most common nodule 1817
1763 1818
particularly in moist soil. It typically is found only in the size was 2 cm.99
1764 1819
United States and Canada surrounding the Ohio and
1765 Echinococcosis results from infection with Echinococcus 1820
Mississippi River valleys and the Great Lakes.
1766 1821
Pulmonary blastomycosis occurs when the fungus from granulosus, a tiny tapeworm found in dogs (the
1767 1822
the soil is inhaled.90 More commonly seen in a host who definitive hosts.) Echinococcosis is found in Africa;
1768 1823
is immunocompetent, these patients are often Europe; Asia; the Middle East; Central and South
1769 1824
asymptomatic. In those who develop symptoms, the America; and, in rare cases, North America.97 Patients
1770 1825
1771 illness begins about 30 to 45 days after exposure, with are often asymptomatic for years; however, if signs or 1826
1772 cough, fevers, night sweats, weight loss, and malaise symptoms develop, chest pain, cough, hemoptysis, or 1827
1773 being common. Skin is the most common pneumothorax are seen. Patients also may develop 1828
1774 extrapulmonary site of infection. It often begins with a wheezing, fever, urticaria, and anaphylaxis if antigenic 1829
1775 papulopustular lesion that progresses to ulcerative, material is released from a cyst.99 Laboratory analysis 1830
1776 may reveal peripheral blood eosinophilia and positive 1831
verrucous, or crusted lesions (Figs 17A and 17B). The
1777 serologic test results.98,100 Radiographically, liver cysts 1832
bone is the second most common extrapulmonary site of
1778 are the most common finding; however, 20% to 30% of 1833
infection, and most patients with osteomyelitis have
1779 1834
concomitant pulmonary blastomycosis.91 Patients may cases develop lung cysts. If air enters the ruptured cyst, it
1780 1835
Q14 have positive sputum smears; cultures; or urine, serum, can appear as a crescent-shaped lucency or have a
1781 1836
or BAL blastomycosis antigen.92,93 Radiographically, cavitary appearance. There also may be evidence of a
1782 1837
cavitation occurs less frequently in blastomycosis than in collapsed laminated membrane that may float in the
1783 1838
1784 histoplasmosis and TB. Cavities can have thin or thick cavity, producing the water lily sign (Fig 18).36 1839
1785 walls, be single or multiple, are more commonly located Eventually, the cavity wall calcifies.1,100 Q16
1840
1786 in the upper lobes (Fig 17C), and can result in 1841
Viral Infections: Human papillomavirus can cause
1787 posttreatment scarring.94 1842
1788
tracheobronchial papillomatosis. Chronic infection 1843
1789 Parasitic Diseases: Paragonimiasis is a food-borne with H papillomavirus may result in multiple 1844
1790 illness caused by the lung fluke Paragonimus papillomas within the nasopharynx, larynx, or 1845
1791 westermani and is associated with the ingestion of raw tracheobronchial tree. Respiratory papillomas may 1846
1792 freshwater crab or crayfish. The majority of cases occur undergo malignant transformation to squamous cell 1847
1793 in Asia, although some cases have been acquired in the carcinoma in 3% to 5% of patients.101 Radiologic 1848
1794 United States.5,95 Productive cough, chest pain, back features include mucous plugging with finger-in-glove 1849
1795 pain, fever, and dyspnea are common; however, some appearance, atelectasis, and solid cavitary nodules 1850
1796 1851
patients can be asymptomatic.96 At laboratory testing, (Fig 19). Diagnosis is made by means of transbronchial
1797 1852
Q15 an elevated blood eosinophil count and visualization of biopsy.100,102 Pulmonary nodules range from 0.5 to
1798 1853
eggs on BAL can be seen.97,98 Radiographically, 5 cm in size.103
1799 1854
1800 1855
1801 1856
1802 1857
1803 1858
1804 1859
1805 1860
1806 1861
1807 1862
1808 1863
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1809 1864
1810 1865
1811 1866
1812 1867
1813 Figure 17 – A-C, Photograph (A) shows two hyperkeratotic verrucous papules (arrow) in a patient with cutaneous blastomycosis. Photograph (B) shows Q28 1868
1814 discrete hyperkeratotic ovoid pink plaque (arrow) in a patient with cutaneous blastomycosis. Axial CT scan (C) obtained in a 53-year-old man, a Q29
1869
current smoker with a history of diabetes with cavitary blastomycosis, demonstrates multiple cavitary lesions bilaterally, along with additional
1815 1870
scattered, ill-defined, small air-space opacities throughout the lung, most prominent in the upper lobes.
chestjournal.org 17

1871 (Fig 20).108 There is an upper lobe predominance.109 1926
1872 Diagnosis is made by means of histopathologic testing. 1927
1873 1928
The most common type of primary cavitary lung cancer
1874 1929
is non-small cell lung cancer, especially squamous cell
1875 1930
carcinoma (69%-81%).107,108 Adenocarcinomas, large
1876 1931
cell carcinomas, and small cell carcinomas are unlikely
1877 1932
1878
to cavitate.72 Primary or secondary pulmonary 1933
1879 lymphoma has a broad spectrum of appearances, 1934
1880 including consolidation, masses, and cavitating 1935
1881 nodules.110 1936
1882 1937
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Pulmonary metastases, most often from squamous

1883 1938
1884
primaries such as head and neck, cervical, skin, or 1939
1885
sarcomas, also may cavitate. The radiographic 1940
1886 morphology of these cavities varies from thick and 1941
Figure 18 – Axial high-resolution CT scan obtained in a 37-year-old
1887 woman admitted for treatment of Echinococcus pneumonia demon- irregular to very smooth and thin, simulating a cyst.72,111 1942
1888 strates a thick-walled cavity with collapsed laminated membrane—the Rarely, metastatic disease leads to the Cheerio sign, 1943
water-lily sign (arrow). There is dense consolidation anterior to the
1889 cavity. defined as multiple tiny cavitary nodules typically only a 1944
1890 few millimeters in size, most often associated with GI 1945
1891 malignancies (Fig 21).36 1946
1892 Step 6: Malignancy 1947
1893 Step 7: Autoimmunity 1948
1894
Cavities are found relatively frequently in primary lung 1949
cancer, with an incidence of up to 11% on plain chest Rheumatoid arthritis (RA) is a systemic autoimmune
1895 1950
radiographs104 and up to 22% on CT scans.105 disorder characterized by synovial inflammation,
1896 1951
1897 Woodring et al106,107 suggested that the maximum wall auto-antibody production, cartilage and bony 1952
1898 thickness of the cavity can help differentiate between destruction, and common pulmonary complications.112 1953
1899 malignant and nonmalignant causes, with a maximum Fifty percent to 80% of patients with RA will have a 1954
1900 wall thickness > 15 mm indicating malignancy in more positive rheumatoid factor, anti-cyclic citrullinated 1955
1901 than 90% cases. However, these studies looked at plain peptide antibody, or both.113 Common pulmonary 1956
1902 chest radiographs rather than CT scans. A more recent findings include interstitial lung disease (ILD), pleural 1957
1903 disease, and rheumatoid nodules. Rheumatoid nodules 1958
study evaluating cavity maximum wall thickness on
1904 1959
chest CT scans did not find a difference between are found in 20% of patients and radiologically appear
1905 as multiple well-defined nodules, a few millimeters to a 1960
malignant and nonmalignant causes; however, it
1906 1961
appeared that malignant cavities were more likely to few centimeters in size. These nodules occasionally
1907 1962
have an irregular internal wall (49% vs 26%) and have develop central necrosis (Fig 22). A background of
1908 1963
an indentation of the outer wall of the cavity underlying ILD may help with the diagnosis.114,115 A
1909 1964
1910 (54% vs 29%) as compared with a benign cavity variety of ILD patterns is seen on high-resolution CT 1965
1911 scans in RA; however, the usual interstitial pneumonia 1966
1912 pattern is seen most frequently (40%-62% of cases). In 1967
1913 usual interstitial pneumonia, high-resolution CT scans 1968
1914 show subpleural, basilar-predominant reticular 1969
1915 abnormalities with honeycombing and traction 1970
1916 bronchiectasis.6 Pleural effusions are noted in up to 1971
1917 70% of patients at autopsy; however, only 3% to 5% of Q17 1972
1918 patients have symptoms.116 Because both RA and lung 1973
1919 1974
cancer are associated with cigarette smoking, a cavitary
1920 1975
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lung cancer always should be in the differential

1921 1976
diagnosis.
1922 1977
1923 Granulomatosis with polyangiitis (GPA) is a systemic 1978
1924 autoimmune disease characterized by necrotizing 1979
Figure 19 – Axial CT scan demonstrates a thick-walled cavity with an
1925 1980
irregular nodular margin due to tracheobronchial papillomatosis. granulomatous inflammation and vasculitis of the upper

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1998 Figure 20 – A-B, Squamous cell carcinoma of the lung. Axial (A) and coronal (B) CT scans demonstrate a thick-walled cavitary mass (arrows) in the Q30
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left upper lobe. The internal walls of the cavity are irregular.
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2033 Figure 21 – A-C, Axial (A) and sagittal (B) high-resolution CT scans obtained in a 36-year-old man with a history of autoimmune pancreatitis with a 2088
2034 diagnosis of metastatic adenocarcinoma of the pancreas demonstrate innumerable randomly distributed cavitary nodules with basilar predominance. 2089
Axial PET/CT scan (C) through the lung bases. There is diffuse abnormal activity throughout both lungs, greatest in the lung bases. Biopsy results
2035 2090
helped confirm pulmonary metastatic disease from pancreatic cancer.
chestjournal.org 19

2091 and lower respiratory tract and kidneys.117,118 Patients 2146
2092 with GPA can present with fever, malaise, night sweats, 2147
2093 2148
anorexia, dyspnea, cough, purulent nasal discharge,
2094 2149
epistaxis, and hemoptysis.119 Anti-neutrophil
2095 2150
cytoplasmic antibody positivity occurs in up to 90% of
2096 2151
patients with severe systemic disease and in up to
2097 2152
2098
78% with limited disease. Elevation of serum 2153
2099 cytoplasmic anti-neutrophil cytoplasmic antibody 2154
2100 against proteinase 3 titers frequently occurs in patients 2155
2101 with GPA and may be associated with disease 2156
2102 activity.7,120 Radiographically, multiple and bilateral 2157
2103 lung nodules are most common and occur in 40% to 2158
2104 70% of patients. Cavitation occurs in 25% to 50% of 2159
2105 these nodules and is more common in nodules > 2 cm 2160
2106 2161
Figure 22 – Axial CT scan obtained in a 45-year-old woman, a former (Fig 23).120 Common associated findings include
2107 2162
smoker with a 30-year history of rheumatoid arthritis and incidental evidence of chronic airway inflammation, manifesting as
2108 pulmonary nodules, demonstrates an irregular, lobulated, and spicu- 2163
lated cavitary nodule in the left upper lobe. Surgical biopsy results helped focal or diffuse bronchial wall thickening and narrowing
2109 2164
confirm a rheumatoid nodule. or obstruction and bronchiectasis. Nonspecific foci of
2110 2165
2111
parenchymal consolidation also are commonly seen. 2166
2112 Other diseases such as ankylosing spondylitis, primary 2167
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2139 2194
2140 Figure 23 – A-C, High-resolution CT scan (A) obtained in a 73-year-old man with a history of pyoderma gangrenosum and with granulomatosis with 2195
2141 polyangiitis proved by means of pathologic testing demonstrates multiple bilateral cavitary masses and nodules. The larger, more anterior lesion in the 2196
right upper lobe has a dependent air-fluid level. Granulomatosis with polyangiitis (STAIN, 0 magnification). Image (B) shows a cavitary granu- Q31
2142 2197
lomatous lesion in a patient with clinical granulomatosis with polyangiitis. This cavitary lesion is surrounded by granulomatous inflammation and
2143 vasculitis. This pathology slide is from a different patient from the radiographic image in Figure 23A. Granulomatosis with polyangiitis (STAIN, 0 2198
2144 magnification). Image (C) shows a cavitary granulomatous lesion in a patient with clinical granulomatosis with polyangiitis. This area shows Q32
2199
geographic necrosis surrounded by granulomatous inflammation. This pathology slide is from a different patient from the radiographic image in
2145 2200
Figure 23A.

2201 pulmonary amyloidosis, eosinophilic GPA, sarcoidosis, 12. Bartlett JG. Treatment of anaerobic pleuropulmonary infection. 2256
2202 Ann Intern Med. 1975;83:376. 2257
and systemic lupus erythematosus rarely cause
2203 13. Takayanagi N, Kagiyama N, Ishiguro T, Tokunaga D, Sugita Y. 2258
pulmonary cavities and are beyond the scope of this Etiology and outcome of community-acquired lung abscess.
2204 Respiration. 2010;80(2):98-105. 2259
review.
2205 14. Wang JL, Chen KY, Fang CT, Hsueh PR, Yang PC, Chang SC. 2260
2206 Changing bacteriology of adult community-acquired lung abscess 2261
in Taiwan: Klebsiella pneumoniae versus anaerobes. Clin Infect Dis.
2207 Conclusions 2262
2005;40(7):915-922.
2208 2263
Diagnosing the cause of cavitary lung disease is a 15. Kuhajda I, Zarogoulidis K, Tsirgogianni K, et al. Lung abscess:
2209 etiology, diagnostic and treatment options. Ann Transl Med. 2264
challenge given the broad differential diagnosis and 2015;3(13):183.
2210 2265
2211
varying manifestations. Significant advances have been 16. Stark DD, Federle MP, Goodman PC, Podrasky AE, Webb WR. 2266
Q18 made in chest imaging with CT scanning, especially Differentiating lung abscess and empyema: radiography and
2212 computed tomography. AJR Am J Roentgenol. 1983;141(1):163-167. 2267
2213 increasing awareness of the wide variety of associated 2268
17. Moreira JS, Camargo JJ, Felicetti JC, et al. Lung abscess: analysis of
2214 findings identified in association with lung cavities. 252 consecutive cases diagnosed between 1968 and 2004. J Bras 2269
2215 Although imaging findings such as the halo sign, Pneumol. 2006;32:136-143. 2270
2216 reversed halo sign, peripheral nodules in varying stages 18. Huang HC, Chen HC, Fang HY, Lin YC, Wu CY, Cheng CY. Lung 2271
abscess predicts the surgical outcome in patients with pleural
2217 of cavitation, or an irregular internal wall constitute an empyema. J Cardiothorac Surg. 2010;5:88. 2272
2218 important component of our algorithm, radiographic 19. Chatha N, Fortin D, Bosma KJ. Management of necrotizing 2273
2219 findings alone are usually insufficient for definitive pneumonia and pulmonary gangrene: a case series and review of 2274
the literature. Can Respir J. 2014;21(4):239-245.
2220 2275
diagnosis. As a consequence, clinical context provides 20. Tsai YF, Ku YH. Necrotizing pneumonia: a rare complication of
2221 2276
critical clues and must be combined with the imaging pneumonia requiring special consideration. Curr Opin Pulm Med.
2222 2012;18:246-252. 2277
findings to narrow the differential diagnosis. We
2223 21. El-Baz A, El-Damati A, Aljehani Y, et al. Management of acute 2278
2224
propose this algorithm as a systematic approach to the necrotizing lung infections: the role of surgery. Ibnosina J Med 2279
evaluation of cavities in the hope that it will provide an Biomed Sci. 2014;6:9-13.
2225 2280
efficient scheme for diagnosis and, ultimately, 22. Hammond JM, Lyddell C, Potgieter PD, Odell J. Severe
2226 pneumococcal pneumonia complicated by massive pulmonary 2281
2227 appropriate therapy. gangrene. Chest. 1993;104:1610-1612. 2282
2228 23. Curry CA, Fish EK, Buckley JA. Pulmonary gangrene: 2283
2229 Acknowledgments radiological and pathologic correlation. South Med J. 1998;91. 2284
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2230 Q19 Financial/nonfinancial disclosures: None declared. 2285
24. Hyewon S, et al. Focal necrotizing pneumonia is a distinct entity
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2018 - Cavitary Lung Disease

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REV 5.5.0 DTD CHEST1599_proof 13 April 2018 10:44 am EO: CHEST-17-2419

2 Special Features [ -#- CHEST - 2018 ]

REV 5.5.0 DTD CHEST1599_proof 13 April 2018 10:44 am EO: CHEST-17-2419

4 Special Features [ -#- CHEST - 2018 ]

Necrotizing pneumonia NTB

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6 Special Features [ -#- CHEST - 2018 ]

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8 Special Features [ -#- CHEST - 2018 ]

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10 Special Features [ -#- CHEST - 2018 ]

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12 Special Features [ -#- CHEST - 2018 ]

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14 Special Features [ -#- CHEST - 2018 ]

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16 Special Features [ -#- CHEST - 2018 ]

REV 5.5.0 DTD CHEST1599_proof 13 April 2018 10:44 am EO: CHEST-17-2419

Pulmonary metastases, most often from squamous

lung cancer always should be in the differential

18 Special Features [ -#- CHEST - 2018 ]

REV 5.5.0 DTD CHEST1599_proof 13 April 2018 10:44 am EO: CHEST-17-2419

20 Special Features [ -#- CHEST - 2018 ]

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22 Special Features [ -#- CHEST - 2018 ]

REV 5.5.0 DTD CHEST1599_proof 13 April 2018 10:44 am EO: CHEST-17-2419

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