Pulmonary nodule differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Overview

Pulmonary nodule may be differentiated according to imaging (size, border characteristics, and attenuation), histological, and clinical features, from other diseases that demonstrate similar imaging findings. Common differential diagnosis of pulmonary nodule, include: hamartoma, granulomas, rheumatoid nodule, and single metastasis.

Common Differential Diagnosis

• The table below summarizes the findings that differentiate pulmonary nodule from other conditions that cause similar radiological findings on conventional radiograph.

Differential Diagnosis for Solitary Pulmonary Adapted from Erasmus et al.
Differential Diagnosis	Causes
Malignant neoplasms	Bronchogenic carcinoma Carcinoid tumor Pulmonary lymphoma Pulmonary sarcoma Solitary metastases
Benign neoplasms	Hamartoma Adenoma Lipoma
Infectious inflammatory	Granuloma (tuberculous/fungal) Nocardia infection Round pneumonia Abscess
Non-infectious inflammatory	Rheumatoid arthritis Wegener's granulomatosis Sarcoidosis
Vascular	Arteriovenous malformation Infarction Hematoma
Congenital	Bronchial atresia
Miscellaneous	External object Pseudotumor Pleural thickening

Differential Diagnosis

Diseases	Clinical manifestations							Para-clinical findings					Gold standard	Additional findings
	Symptoms						Physical exam
								Lab Findings	Radiology			Histopathology
	Productive cough	Hemoptysis	Weight loss	SOB	Fever	Other	Auscultation	Sputum analysis	Nodule	Nodule content	Other findings
Pulmonary Nodule(benign)	-	-	-	-	-	Asymptomatic	Normal pleural friction rub egophony Crackling or bubbling Whispered pectoriloquy Absent breath sounds	Normal	Single Round, oval <5 mm nodule Ground glass	Fat Calcification Types: Central dense nidus Diffuse solid Laminated Popcorn	well-defined smooth border Growth rate > 18 months Cavity wall thickness of 1 mm	N/A	N/A	↓ O2 Sat
Pulmonary Nodule (malignant)	++	++	++	+	-	Non resolving pneumonia Wheezing Chest pain Cachexia Fatigue Loss of appetite Dysphonia Dysphagia	Normal pleural friction rub egophony Crackling or bubbling Whispered pectoriloquy Absent breath sounds	Tumor cells	Single or multiple Small or > 2 cm of size	Calcification Amorphous Punctate Reticular Stippled or eccentric Cavity Ulceration	Spiculated border Rapid growth rate (Doubling time 1-18 months) Cavity wall thickness over 15 mm	Central necrosis Cavity lined by viable cancer cells without necrosis	Biopsy and histopathology	↓ O2 Sat
Diseases	Productive cough	Hemoptysis	Weight loss	SOB	Fever	Other	Auscultation	Sputum analysis	Nodule	Content	Other findings	Histopathology	Gold standard	Additional findings
Abscess	++	-	-	+	++	Pleuritic chest pain Foul smelling sputum Night sweats Fatigue	Decreased breath sound Bronchial breath sound Inspiratory crackles Localised crepitations	Causative agents	Vary in size Round in shape	Fluid/gas-fluid level Consolidation Cavity persists longer than consolidation	. The wall of the abscess is typically thick and the luminal surface irregular Bronchial vessels and bronchi are truncated	Centrally, necrotic tissue mixed with necrotic granulocytes and bacteria Neutrophilic granulocytes with dilated blood vessels Inflammatory oedema	Histopathology	Clubbing of finger
Septic pulmonary emboli	-	-	-	++	++	Chest pain Focus of primary infection (Most common, right heart endocarditis)	Prominent P2 component of second heart sound Decreased breath sound Rales Crackles Pleural friction rub	N/A	Multiple peripheral nodules Size 0.5– 3.5 cm Variable shapes	Central low attenuation Feeding vessels Pleura based wedge-shaped lesions	Air bronchogram Abscess or infection related changes at the primary focus	N/A	Culture and sensitivity	N/A
Fungal infection	+/-	+	-	+	+	Chest pain Hypersensitivity or allergic reactions History of travel	Decreased breath sound Rales Crackles Pleural friction rub	KOH stain: Fungi	Multiple nodules Size 0.5– 3 cm nodules surrounded by ground-glass opacity/halo	Cavity	Halo sign in aspergillosis Patchy infiltrate Consolidation Mediastinal adenopathy	Specific causative agent	Culture and sensitivity	N/A
Parasites	+/-	+/-	+/-	_	+	Asymptomatic Chest pain Pneumothorax Wheeze Urticaria Rarely, anaphylaxis	Decreased breath sound Rales Crackles	N/A	Cysts: Single or multiple well-defined homogenous Coin lesion: 1–3 cm	Cyst: Fluid or gas Worm Coin lesion: Central necrotic Granulomatous reaction and fibrous wall	Calcified cyst wall Consolidation Pleural effusion Worm	Presence of larvae or eggs	Visualization of parasite, egg or larvae	N/A
Diseases	Productive cough	Hemoptysis	Weight loss	SOB	Fever	Other	Auscultation	Sputum analysis	Nodule	Content	Other findings	Histopathology	Gold standard	Additional findings
Mycobacterial infections	+	+	+	++	+/-	Chronic cough Night sweats Dyspnea Wheezing Cachexia Fatigue Loss of appetite	Decreased breath sounds Rales Rhonchi Bronchial breath sounds	AFB+	Micronodules in the subpleural region and peribronchovascular interstitium Fluffy upper zone shadowing Cavity	Superinfected cavities shows air-fluid level	Fluffy upper zone shadowing Interlobular septal thickening Homogeneous and dense consolidation	Granulomas: necrotizing or non-necrotizing Langhans giant cells Caseous necrosis	Culture and sensitivity	N/A
Chronic inflammatory conditions (Granulomatosis with polyangiitis)	+/-	+	-	+	-	Hoarseness Chest pain Stridor	Pleural friction rub Absent breath sound Crackles	N/A	Multiple round lesions Size 0.5 to 10 cm	Patchy or diffuse ground-glass opacities, or both	Cavity Thick wall Irregular inner contour Atelectasis	Pathologic triad of granulomatous inflammation, vasculitis, and necrosis	Biopsy	c-ANCA p-ANCA
Diseases	Productive cough	Hemoptysis	Weight loss	SOB	Fever	Other	Auscultation	Sputum analysis	Nodule	Content	Other findings	Histopathology	Gold standard	Additional findings
Pulmonary AVMs	-	+/-	-	+	-	Epistaxis Palpitation Chest pain GI bleeding Mucocutaneous telangiectasia	Bruit	RBCs	Solitary or multiple nodules Round, oval, or polycyclic Size 1 to 5 cm	Feeding pulmonary arteries and draining pulmonary veins	Well-defined borders Lower and middle third of the lung	Not recommended	Pulmonary angiography	N/A
Pneumoconiosis	+	-	+	+	-	Chest pain	Fine crackles Rhonchi Bronchial breath sounds Expiratory wheezing Egophony Bronchophony	Inorganic particle	Solitary or multiple nodules Size 1 - 10 cm In the upper lobes	N/A	Massive fibrosis or conglomerate masses Small nodular opacities lymphadenopathy eggshell calcification	Calcification Central necrosis Dense collagen Malignant cells	CT scan	N/A

ABBREVIATIONS:

N/A: Not available , SOB: Shortness of breath