Condition	Differentiating characteristics and diagnostic tests
Bacterial
Actinomycosis	Anaerobic culture from deep-needle or biopsy sample (which may require four weeks for growth); elevated CRP level and ESR; sulfur granules on tissue histology
Lung abscess	Blood, pleural fluid, or sputum culture; bronchoscopy with tissue histology; characteristic computed tomography or ultrasound findings
Mycoplasma pneumoniae infection	Cold agglutinin titer > 1:16; enzyme immunoassay; mildly elevated hepatic transaminase levels or ESR; multiplex PCR respiratory panel; normal or mildly elevated white blood cell count; point-of-care serologic testing
Tuberculosis	Chest imaging; exudative pleural fluid showing normal or low glucose level, lymphocytic predominance, and elevated adenosine deaminase level; sputum analyses and culture; tuberculin skin testing or interferon-gamma release assay
Typical community-acquired pneumonia	Blood or sputum culture; chest imaging; multiplex PCR respiratory panel; travel history; urine antigen testing
Fungal
Aspergillosis	Characteristic histology on tissue biopsy; chest imaging; elevated galactomannan level in bronchoalveolar lavage; elevated serum immunoglobulin E level; serology; sputum fungal culture
Blastomycosis	Blood or urine antigen testing; histology; sputum or bronchoscopy culture on specialized media (which may require four weeks for growth); travel history
Cryptococcosis	Association with HIV-infected or other immunocompromised hosts; blood, bronchoscopy, cerebrospinal, sputum, or urine fungal cultures; serologic and antigen testing
Histoplasmosis	Characteristic histopathologic findings on lung tissue or mediastinal lymph node biopsies; enzyme immunoassay on urine, blood, or bronchoalveolar lavage samples; fungal cultures; serologic testing; travel history
Paracoccidioidomycosis	Histology; serology; travel history
Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia	Association with HIV-infected or other immunocompromised hosts; PCR; respiratory histology; serum beta-D glucan assay
Sporotrichosis	Histopathologic findings of pyogenic granuloma; radiographic findings (may mimic tuberculosis); sputum culture
Neoplastic
Lung cancer	Histology on any clinical sample
Lymphoma	Chest imaging; lymph node and/or bone marrow biopsy; peripheral blood analysis
Parasitic
Loeffler syndrome	Larvae in respiratory secretions or gastric aspirate; peripheral eosinophilia
Paragonimiasis	Enzyme-linked immunosorbent assay on serum sample; history of exposure to undercooked seafood; leukocytosis with eosinophilia; trematode ova in bronchoalveolar lavage, 24-hour sputum, stool, fine-needle aspiration, thoracoscopy, or transbronchial biopsy
Viral
Influenza pneumonia	Antigen testing; chest imaging; multiplex PCR respiratory panel; reverse transcriptase–PCR; serology
Other
Collagen-vascular lung disease	Assays for various autoantibodies
Eosinophilic pneumonia	Bronchoalveolar lavage cell count showing > 25% eosinophils; exposure and travel histories; lung biopsy
Granulomatosis with polyangiitis (Wegener granulomatosis)	Abnormal findings on antineutrophil cytoplasmic autoantibody testing, complete blood count, histology, or peripheral blood smear; elevated CRP level and ESR; hematuria
Sarcoidosis	Characteristic findings on pulmonary imaging; histopathology showing noncaseating granulomas Confirmatory tissue diagnosis should be obtained before administering glucocorticoids, which may trigger dissemination of an undiagnosed endemic mycosis