Differential Diagnosis Based on Imaging Findings

Air Space Disease

Acute Consolidation

Air space consolidation results when alveoli are filled with material that attenuates the x-ray beam more than the surrounding lung parenchyma. When encountered in the acute setting, air space consolidation on imaging has a differential diagnosis ( Table 14.1 ).

TABLE 14.1

Differential Diagnosis of Acute Consolidation

DIAGNOSIS	COMMENTS
Infectious pneumonia	Alveoli are filled with pus or inflammatory fluid; fever and leukocytosis are often present
Aspiration of gastric contents	There is a predilection for gravity-dependent lung segments; Mendelson syndrome refers to chemical pneumonitis from aspiration during obstetric anesthesia
Alveolar pulmonary edema	Cardiomegaly and pleural effusions may be present; acute respiratory distress syndrome may be considered in severe cases
Pulmonary hemorrhage	Consider pulmonary contusion in the setting of trauma; there may be a history of anticoagulation or bleeding diathesis
Pulmonary infarction	Risk factors for pulmonary embolism are present; consolidation is peripheral and is more likely in the lower lobes

Chronic Consolidation

When air space consolidation persists on imaging studies over several weeks to months, the differential diagnosis shifts away from pneumonia, which typically has a more acute presentation, with subsequent resolution. Infectious, inflammatory, and neoplastic causes should be considered when chronic air space consolidation is encountered ( Fig. 14.1 ), and the most common entities are outlined in Table 14.2 .

Figure 14.1, Frontal chest radiograph of a 33-year-old woman with chronic eosinophilic pneumonia demonstrates focal peripheral air space consolidation in the left upper lung zone, which persisted on multiple studies.

TABLE 14.2

Differential Diagnosis of Chronic Consolidation

DIAGNOSIS	COMMENTS
Organizing pneumonia	Reverse halo sign seen in up to 20%; consolidation typically responds to steroid therapy
Chronic eosinophilic pneumonia	Often elevated eosinophils in bronchoalveolar lavage fluid and peripheral blood; upper lobe predominant consolidation; typically responds to steroid therapy
Poorly treated infection	May be due to suboptimal antibiotic choice or resistance; also consider fungal and mycobacterial infection
Adenocarcinoma	Air bronchograms may be seen
Sarcoidosis	Confluent granulomatous nodules may mimic consolidation
Lymphoma	Usually derived from bronchus-associated lymphoid tissue; air bronchograms may be seen
Lipoid pneumonia	Demonstrates areas of fat attenuation; generally indolent course
Churg-Strauss syndrome	Nearly all patients have asthma and eosinophilia

Pulmonary Nodules

Solitary Pulmonary Nodule

The differential diagnosis of a solitary pulmonary nodule on chest radiography or CT is broad, but more than 95% of the time the nodule is an infectious granuloma ( Fig. 14.2 ), malignant neoplasm (primary or metastatic), or benign tumor (e.g., a hamartoma). Nodule size, shape, density, calcification pattern, degree of contrast enhancement, fluorodeoxyglucose (FDG) avidity, and rate of growth are key imaging characteristics that when combined with clinical factors (e.g., patient age, immune status, clinical history) help narrow the differential diagnosis. Ultimately, this combination of factors may indicate a nodule's likelihood of benignity versus malignancy or even provide a specific diagnosis. There are many possible causes of a solitary pulmonary nodule ( Table 14.3 ).

Figure 14.2, Coned down frontal chest radiograph of a 70-year-old man with malaise and fatigue reveals a solitary, well-circumscribed pulmonary nodule overlying the lateral left middle lung zone. Surgical resection and pathologic analysis demonstrated the nodule to be a histoplasmoma.

TABLE 14.3

Differential Diagnosis of Solitary Pulmonary Nodule

DIAGNOSIS	COMMENTS
Granuloma	May be other calcified granulomas or calcified lymph nodes; likelihood dependent on where patient has lived (far more common in Midwestern United States)
Lung cancer	Calcification seen in 6%–7%; most lung cancers double in volume every 1–18 months
Metastasis	Patients with melanoma, testicular cancer, or sarcoma more likely to have a solitary metastasis than primary lung cancer
Intrapulmonary lymph node	Often found along fissures or in a subpleural location; morphology may be triangular, oval, round, or trapezoidal
Pulmonary nodule mimic	Consider clothing artifact (button), nipple shadow, skin or chest wall lesion, healing rib fracture, and enostosis in a rib
Hamartoma	Fat within a nodule nearly pathognomonic; popcorn calcification sometimes present
Pulmonary carcinoid	Location generally more central; can enhance avidly; high false-negative rate on FDG PET imaging
Infection (nongranulomatous)	Round pneumonia, septic embolus, or abscess
Mesenchymal or neural tumor	Consider fibroma, chondroma, lipoma, or neurofibroma
Arteriovenous malformation	Feeding artery and draining vein; multiple in hereditary hemorrhagic telangiectasia
Inflammatory nodule	Rheumatoid nodule or granulomatosis with polyangiitis

FDG, Fluorodeoxyglucose; PET, positron emission tomography.

Multiple Pulmonary Nodules

Centrilobular Distribution

Diseases that involve the centrilobular bronchioles, pulmonary arterioles, or lymphatics may produce multiple centrilobular nodules. These nodules characteristically are evenly spaced from one another and spare the interlobular septa and pleural surfaces ( Fig. 14.3 ). Nodules in this distribution may be solid or of ground-glass attenuation, and the most common entities producing this pattern are outlined in Table 14.4 . If the nodules are branching, with a V or Y shape, it is termed a tree-in-bud pattern .

Figure 14.3, Axial CT scan of a 35-year-old woman with subacute hypersensitivity pneumonitis demonstrates diffuse ground-glass centrilobular nodules, with scattered areas of hypoattenuation due to air trapping.

TABLE 14.4

Differential Diagnosis of Multiple Nodules With Centrilobular Distribution

DIAGNOSIS	COMMENTS
Hypersensitivity pneumonitis	Ground-glass nodules; exposure to organic antigen identified in 50%; air trapping usually present
Respiratory bronchiolitis	Upper lobe predominant ground-glass nodules; history of cigarette smoking
Pulmonary arterial hypertension; pulmonary capillary hemangiomatosis; pulmonary veno-occlusive disease	Ground-glass nodules; due to pulmonary edema and/or hemorrhage; dilated main pulmonary trunk
Metastatic calcification	Upper lobe ground-glass nodules ± calcification; hypercalcemia
Endobronchial infection, bronchopneumonia	Solid or ground-glass ± tree-in-bud opacities; bacterial, viral, or fungal causes
Follicular bronchiolitis	Solid or ground-glass nodules ± tree-in-bud opacities; immunosuppression or connective tissue disease
Pneumoconioses	Solid centrilobular nodules; especially siderosis and coal workers' pneumoconiosis
Langerhans cell histiocytosis	Upper lobe predominant solid or ground-glass nodules; early in disease course; history of cigarette smoking

Perilymphatic Distribution

On CT imaging, diseases that involve the perilymphatic channels are typically subpleural and are along bronchovascular bundles, interlobular septae, and fissures. Unlike centrilobular nodules, nodules with a perilymphatic distribution are generally unevenly spaced from one another. There are several diagnostic considerations for nodules with a perilymphatic distribution ( Table 14.5 ).

TABLE 14.5

Differential Diagnosis of Multiple Nodules With Perilymphatic Distribution

DIAGNOSIS	COMMENTS
Pulmonary sarcoidosis	Concomitant symmetric hilar and mediastinal lymph nodes; patients commonly between 20 and 40 years of age
Silicosis and coal workers' pneumoconiosis	Nodules range from 1–10 mm in diameter; nodules have an upper lobe and posterior distribution
Lymphangitic carcinomatosis	Adenocarcinoma (lung and breast) most common cause; associated pleural effusions are common
Nodular pulmonary amyloidosis	Patients usually in sixth decade of life and often asymptomatic; lower lobe and peripheral distribution often appreciated
Lymphocytic interstitial pneumonia	Associated with HIV (in children) and Sjögren syndrome; scattered thin-walled perivascular cysts often present

Random Distribution

Multiple pulmonary nodules that are diffusely distributed and without architectural predominance—that is, lack a centrilobular or peribronchovascular distribution—are likely random. These nodules may be variable in number and density, and often the underlying pathophysiologic mechanism is hematogenous dissemination. There are several diagnoses to consider when pulmonary nodules are found to have a random distribution ( Table 14.6 ).

TABLE 14.6

Differential Diagnosis of Multiple Nodules With Random Distribution

DIAGNOSIS	COMMENTS
Hematogenous metastases	Lower lobe predominance; metastases may be small in size, as from thyroid cancer, or may be large (cannonball), as from seminoma
Fungal infection	Can be miliary or larger; histoplasmosis, blastomycosis, and coccidioidomycosis; aspergillosis or zygomycosis in the immunocompromised
Miliary tuberculosis	May be seen in primary or postprimary infection; miliary nodules imply active infection and poor prognosis
Septic emboli	Peripheral and lower lobe predominance ± cavitation
Adenocarcinoma of lung	Rarely presents as multiple nodules in a random distribution
Rheumatoid necrobiotic nodules	Nodules wax and wane with rheumatoid arthritis activity; miliary nodularity occurs early, prior to pulmonary fibrosis
Amyloidosis	Nodules may cavitate and/or show calcification
Granulomatosis with polyangiitis	Nodules ± cavitation
Benign metastasizing leiomyoma	Often a history of hysterectomy for uterine leiomyomas; nodules enhance with contrast and may cavitate

Calcified Pulmonary Nodules

A variety of disease entities can present with multiple calcified pulmonary nodules, with causes that include neoplastic, infectious, metabolic, and inhalational factors ( Fig. 14.4 ). Clinical history and the size, appearance, and distribution of the nodules can add specificity. The most common entities producing multiple calcified pulmonary nodules are outlined in Table 14.7 .

TABLE 14.7

Differential Diagnosis of Multiple Calcified Pulmonary Nodules

DIAGNOSIS	COMMENTS
Chronic granulomatous disease	Tuberculosis and histoplasmosis most common; may be associated findings such as calcified lymph nodes
Metastatic disease	History of sarcoma or medullary thyroid cancer; mucinous adenocarcinoma metastases may calcify; treated choriocarcinoma metastases may calcify
Pneumoconioses	Particularly silicosis and coal workers' pneumoconiosis
Healed varicella pneumonia	Generally 2–3 mm in size; diffuse distribution
Pulmonary alveolar microlithiasis	Sandlike calcifications, often ≈1 mm in size; lower lobe predominant
Metastatic calcification	Upper lobe predominant; centrilobular ground-glass nodules; hypercalcemia
Pulmonary amyloidosis	May be associated with tracheobronchial amyloidosis
Multiple chondromas	One component of the Carney triad—paragangliomas, gastrointestinal stromal tumors, pulmonary chondromas

Cavitary Pulmonary Nodules

A cavitary lung nodule usually contains air, but may also contain blood, pus, or debris. A cavitary nodule has a definite wall with thickness of at least 4 mm and should not be confused with a cyst, which is a thin-walled, air-containing lesion. Chest radiography may identify cavitary nodules, although CT offers increased sensitivity and provides improved lesion localization and characterization. There are several entities to consider when cavity pulmonary nodules are encountered ( Table 14.8 ).

TABLE 14.8

Differential Diagnosis of Cavitary Pulmonary Nodules

DIAGNOSIS	COMMENTS
Pneumonia and lung abscess	Typically from Staphylococcus aureus, Pseudomonas aeruginosa , or Klebsiella pneumoniae; tuberculosis and fungal pneumonia also cavitate
Metastases	Usually a primary squamous or transitional cell carcinoma; nodules often have round, well-demarcated borders
Primary lung cancer	Squamous cell carcinoma most likely to cavitate; cavitation most likely when mass is >3 cm
Pulmonary emboli	Lower lobe and peripheral distribution; septic emboli cavitate more commonly than bland emboli
Granulomatosis with polyangiitis	Cavitation occurs in nearly 50% of patients with nodules; nodule size variable; may be associated with consolidation
Rheumatoid lung nodules	Occur in <1% of rheumatoid arthritis patients; more common in men and in upper and middle lung zones
Congenital lesions	Congenital pulmonary airway malformation; pulmonary sequestration

Pulmonary Masses

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