Evaluation of solitary pulmonary nodule

Imaging findings classic enough to be considered diagnostic. Hamartomas do not undergo malignant transformation. No further evaluation required.

[Figure caption and citation for the preceding image starts]: Computed tomography (CT) section with soft tissue configuration, showing a right lung hamartoma, as incidental finding in an asymptomatic patient. Note the central calcification and several small spots of fat within the nodule. This nodule was stable over a 12 year period and no intervention requiredFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Angioinvasive fungi (e.g., Aspergillus, Pseudallescheria boydii, Fusarium, and Zygomycetes) can be seen as nodules with halo sign or ground-glass opacity surrounding a nodule.

Occasional calcifications can be seen in the spleen or liver. Unfortunately there is overlap in the clinical and radiologic presentation of different infectious etiologies.

May be falsely positive in active infectious processes due to tuberculosis or fungal infections.

The specific role of fungal serologies in solitary pulmonary nodule is unclear. These tests are valuable for detection of exposure to histoplasmosis, cryptococcosis, aspergillosis, coccidioidomycosis, and mucormycosis.

Does not help differentiate latent tuberculosis infection (LTBI) from tuberculosis disease.

Identifies the size, location, edge characteristics, and pattern of calcification. Growth can be evaluated when old films are available for comparison.

Usually calcifications are absent or eccentric. Increased enhancement of the nodule (>15 Hounsfield units) with the use of intravenous contrast indicates increased vascularity, which suggests possible malignancy.​​[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a right upper lobe apical solid nodule with a surrounding ‘ground glass’ halo, in a patient with seropositive rheumatoid arthritis on methotrexate. Other similar nodules were seen throughout both lungs, and remain stable for >2 years, consistent with inflammatory benign rheumatoid nodulesFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Can help distinguish benign from malignant disease, as it indicates metabolically active disease with positive uptake of FDG.

More than 90% of malignant nodules will have positive uptake. More than 70% of benign nodules do not show up as a hot spot.

This test is most useful for intermediate-probability nodules and for staging purposes. False-positive tests may occur with infectious or inflammatory granulomas. False negatives may occur with bronchoalveolar carcinoma and carcinoids.​[Figure caption and citation for the preceding image starts]: Computed tomography (CT) sections from two cases with benign perifissural nodules. Note the smooth margins and the normal undisturbed adjacent fissureFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: PET CT scan with 18-fluorodeoxyglucose (18-FDG) showing a low uptake in a semi-solid right upper lobe posterior lesion. Surgical resection confirmed adenocarcinoma with primarily lepidic patternFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Flexible bronchoscopy allows small cytologic or pathologic samples to be obtained.

Yield depends on the size and location of the nodule, and presence or absence of bronchus sign (i.e., a bronchus leading directly to a peripheral pulmonary lesion, visible on CT).[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a posterior left upper lobe spiculated nodule, with ‘bronchus sign’ in a female non-smoker. Bronchoscopic forceps biopsy and brushing assisted by radial EBUS miniprobe localisation, confirmed a non-Hodgkin’s lymphomaFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Risk of pneumothorax or bleeding, as well as local expertise, determine the feasibility of this technique. Transthoracic needle aspiration (TTNA) has a higher yield than flexible bronchoscopy with large peripheral lesions.[Figure caption and citation for the preceding image starts]: Computed tomography (CT) section capturing the transthoracic core biopsy needle targeting a left lower lobe lobulated nodule. Histopathology confirmed a well-differentiated squamous cell lung cancerFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Extrapulmonary cancers that metastasize to the lung include melanoma, sarcomas, and adenocarcinomas of the colon, breast, kidney, and testicle. Tests aimed at identifying previously unrecognized primary malignancies might include abdominal and pelvic CT scans accompanied by imaging of the brain with CT scan or magnetic resonance imaging.​[47]National Institute for Health and Care Excellence. Metastatic malignant disease of unknown primary origin in adults: diagnosis and management. Apr 2023 [internet publication]. https://www.nice.org.uk/guidance/CG104 [48]Krämer A, Bochtler T, Pauli C, et al. Cancer of unknown primary: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Mar;34(3):228-46. https://www.annalsofoncology.org/article/S0923-7534(22)04769-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36563965?tool=bestpractice.com

In metastatic disease, PET scan aids in the identification of the primary site and allows for appropriate staging whenever malignancy is confirmed. Certain metastatic lesions have a lower probability of 18-fluorodeoxyglucose (FDG) uptake, such as renal cell carcinoma.

Accurate sampling of a nodule depends on the location and size of the nodule, presence of bronchus sign (i.e., a bronchus leading directly to a peripheral pulmonary lesion, visible on CT), as well as local expertise and availability of fluoroscopy. The sensitivity is widely variable but has been reported to be 40% to 70% for 20 to 30 mm nodules. Endobronchial lesions occur as metastasis of a wide variety of cancers including renal cell carcinoma, thyroid carcinoma, esophageal cancer, ovarian cancer, melanoma, breast cancer, colorectal cancer, and sarcomas. Bronchoscopy has a 100% yield for endobronchial lesions.

Transthoracic needle aspiration is used under the guidance of CT. Pneumothorax complicates 20% to 30% of procedures. The choice between bronchoscopy and TTNA is based on lesion size and location, risks, and local expertise.

This is not routinely done and should not be the first diagnostic investigation. Yield is higher in large endobronchial lesions or large masses. However, in the current era of necessary molecular subtyping and testing for immune-checkpoint blockade therapy, sputum cytology does not provide enough cells to complete all necessary molecular subtyping and testing for immune-checkpoint blockade therapy, tests, so a tissue sample remains the ‘gold standard'

Rarely seen due to small size.

[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a small peripheral triangular nodule in the right lower lobe, consistent with an intrapulmonary lymph nodeFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Detailed history, physical exam, and laboratory findings allow the clinician to distinguish between the presence of sarcoidosis, rheumatoid arthritis, or granulomatosis with polyangiitis (formerly known as Wegener granulomatosis).

Granulomas may be caused by mycobacteria, fungal infection, extrinsic allergic alveolitis, pneumoconiosis, drugs, foreign bodies, sarcoidosis, granulomatosis with polyangiitis, and rheumatoid arthritis. Granulomas on tissue obtained by bronchoscopy or TTNA should be identified by a pathologist and stained for infectious agents before a noninfectious cause is assumed.

When lung nodules are found, other subcutaneous nodules are frequently present. An entity known as Caplan syndrome can occur when patients with rheumatoid arthritis are exposed to inorganic dust. These nodules are confined to the upper lobes, occur rapidly in crops, and may undergo cavitation.

[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a right upper lobe apical solid nodule with a surrounding ‘ground glass’ halo, in a patient with seropositive rheumatoid arthritis on methotrexate. Other similar nodules were seen throughout both lungs, and remain stable for >2 years, consistent with inflammatory benign rheumatoid nodulesFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Granulomas on tissue obtained by bronchoscopy or TTNA should be identified by a pathologist and stained for infectious agents before a noninfectious cause is assumed.

Necrobiotic nodules present as a central zone of eosinophilic fibrinoid necrosis surrounded by palisading fibroblasts, the nodule often being centered on necrotic inflamed blood vessels.

Patients with lung nodules due to rheumatoid arthritis frequently have high levels of rheumatoid factor, although seronegative cases have been reported.

Detailed history, physical exam, and laboratory findings allow the clinician to distinguish between the presence of sarcoidosis, rheumatoid arthritis, or granulomatosis with polyangiitis.​​[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a right upper lobe posterior cavitating nodule, with biopsy confirming granulomatosis with polyangiitisFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a left upper lobe peripheral elongated nodule, with contrast enhancement and a clear feeding and draining side, consistent with a small arteriovenous malformationFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a right lower lobe large nodule, with contrast enhancement and a clear feeding and draining side, consistent with an arteriovenous malformationFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

Granulomas may be caused by mycobacteria, fungal infection, extrinsic allergic alveolitis, pneumoconiosis, drugs, foreign bodies, sarcoidosis, granulomatosis with polyangiitis, and rheumatoid arthritis. Granulomas on tissue obtained by bronchoscopy or TTNA should be identified by a pathologist and stained for infectious agents before a noninfectious cause is assumed.

ANCA testing results depend on the extent and severity of the disease. Generalized granulomatosis with polyangiitis has >90% cytoplasmic ANCA or PR-3 positive. Limited granulomatosis with polyangiitis has 60% ANCA positive.

Usually present as endobronchial tumors with smooth borders, rounded and highly vascularized. Approximately 20% present as solitary pulmonary nodules. May cause postobstructive pneumonia. This type of tumor is usually slow-growing on serial imaging.

Endobronchial biopsy is usually required to differentiate from small cell carcinoma. Bronchial brushings, sputum specimens, and lavage fluid rarely provide enough tissue for a conclusive diagnosis.

Despite risk of bleeding, endobronchial biopsies are indicated, and hemorrhage is easily controlled with cold saline or epinephrine.

Identifies the size, location, edge, and characteristics of the nodule. Typically multiple or solitary nodules or masses, with air bronchograms, airway dilation, positive angiogram sign, and surrounding haloes sign.

Nodal disease is more common than extranodal disease, so specifically check for regional lymphadenopathy.

Can help distinguish benign from malignant disease, as it indicates metabolically active disease with positive uptake of FDG. Typically positive in lymphoma.

Use of flexible bronchoscopy for diagnosis of malignancy allows obtaining small cytologic or pathologic samples with variable yield depending on the size and location of the nodule, and presence or absence of bronchus sign (i.e., a bronchus leading directly to a peripheral pulmonary lesion, visible on CT). Washings, brushing, and transbronchial needle aspiration may increase the yield. It may be difficult to obtain enough tissue to establish a lymphoma diagnosis. Ancillary investigations such as immunohistochemistry, flow cytometry, and molecular analysis are frequently required when lymphoma is suspected.

Pneumothorax complicates 20% to 30% of transthoracic needle aspiration procedures. The choice between bronchoscopy and TTNA is based on size and location of the lesion, local expertise, and risks.

It may be difficult to obtain enough tissue to establish a lymphoma diagnosis. Ancillary investigations such as immunohistochemistry, flow cytometry, and molecular analysis are frequently required when lymphoma is suspected.

Most common in lower lobes. Multiple lesions in 30% of cases. Usually round or oval, ranging in size from 1 to several centimeters in diameter. Also known as arteriovenous fistula. Patients with multiple arteriovenous malformations (AVMs) in the lung usually have arteriovenous communications in the skin, mucosa, and other organs. Osler-Weber-Rendu syndrome may be considered.

[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a left upper lobe peripheral elongated nodule, with contrast enhancement and a clear feeding and draining side, consistent with a small arteriovenous malformationFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing a right lower lobe large nodule, with contrast enhancement and a clear feeding and draining side, consistent with an arteriovenous malformationFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

In cases of significant hemoptysis, pulmonary angiogram is combined with bronchial artery embolization.

In cases of severe systemic AVMs, the chronic hypoxemia may cause polycythemia. However, more commonly, epistaxis may result in anemia.

In generalized amyloidosis, the lung is frequently spared. When involved, it is usually in the form of diffuse interstitial infiltrates involving the septal and perivascular areas of the lobule, and is associated with poor outcome.

Localized nodular amyloidosis or amyloidomas are very rare, with solitary or multiple nodules, variable in size and shape, subpleural, with benign course, and calcified in 30% of cases.

The diagnosis of amyloidosis frequently requires transthoracic needle aspiration or thoracotomy.

The choice is based on the size and location of the lesion, local expertise, and risk assessment.

The nodules are usually waxy, paucicellular, eosinophilic deposits of amyloid material that demonstrates apple-green birefringence on Congo Red stain. Immunohistochemistry, special stains, and electron microscopy are useful additional pathology tests.

Can help distinguish benign from malignant disease, as it indicates metabolically active disease with positive uptake of 18-fluorodeoxyglucose (FDG). False-positive tests may occur with infectious or inflammatory granulomas. False-negatives may occur with bronchoalveolar carcinoma and carcinoids.

In patients with asthma and/or bronchiectasis and serum eosinophilia, ongoing mucoid impaction should trigger investigations for a probable allergic bronchopulmonary aspergillosis (ABPA)[49]Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis-state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64. https://academic.oup.com/cid/article/37/Supplement_3/S225/353708?login=false http://www.ncbi.nlm.nih.gov/pubmed/12975753?tool=bestpractice.com

[Figure caption and citation for the preceding image starts]: Computed tomography (CT) showing two areas (red circles) of mucoid impaction of the left upper lobe subsegmental bronchi, resulting in appearance that mimics a noduleFrom the collection of Dr George Tsaknis, MD, PhD, FRCP(London), MRQA, MAcadMEd, PGCert; used with permission [Citation ends].

On occasion (e.g., when there is diagnostic uncertainty or when the patient is unable to cough adequately), flexible bronchoscopy is necessary for diagnosis and treatment.