Pulmonary Nodule (Case 11)

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Pulmonary Nodule (Case 11)

Smitha Gopinath Nair DO and Jennifer LaRosa MD

Case: The patient is a 68-year-old woman with a history of hypertension and diabetes mellitus who recently moved to New York from Ohio and presents for her annual physical examination. She is noted to have a 35 pack-year history of cigarette smoking and briefly worked with her husband installing home insulation. She complains of productive cough upon awakening every morning and dyspnea with moderate activity. On physical examination she is noted to be well dressed and overweight. Her lung exam reveals mild wheezing, and she has some clubbing of her fingers. A routine chest radiograph reveals a 1-cm nodule in the right mid-lung field.

Differential Diagnosis

Primary lung cancer

Coccidioidal pulmonary nodule



Histoplasma pulmonary nodule


Speaking Intelligently

A solitary pulmonary nodule (SPN) is a common clinical problem. It is typically an incidental finding on chest roentgenogram or CT scan of the chest, and in one study was seen in 25% of healthy, asymptomatic individuals. The majority of nodules will have a benign etiology. However, since lung cancer is both asymptomatic and curable in its early stages, it is imperative that all nodules be considered malignant until proven otherwise. The recommendations for further testing to evaluate the pulmonary nodule vary according to the pretest probability. If the pretest probability is less than 5%, the nodule should be followed with serial CT scans at 3, 6, 12, and 24 months. If it is between 5% and 60%, options include CT scan, positron emission tomography (PET) scan, biopsy, or resection. A pulmonologist may be consulted for guidance. If the pretest probability is greater than 60%, biopsy and resection should be strongly considered. See Figure 17-1.


Figure 17-1 Algorithm for solitary pulmonary nodule. (Reproduced with permission from Weinberger SE. Diagnostic evaluation and initial management of the solitary pulmonary nodule. In: UptoDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2011. Copyright © 2011 UptoDate, Inc. For more information visit www.uptodate.com.)


Clinical Thinking

• An SPN is defined as a lesion greater than 8 mm and less than 3 cm in diameter; it is within normal lung parenchyma and causes no distortion of other structures.

• Nodules can be broadly categorized as benign or malignant, which can be determined only by a tissue biopsy.

• There are patient characteristics that can suggest one etiology as being more likely than another.

• The lesion should be inspected for shape, size, the presence and pattern of calcification, growth rate, location, and density.

• The patient should be assessed for malignancy risk factors, including advanced age, smoking, and occupational and environmental exposures, and PFTs should be performed.


• The presence of occupational and environmental risk factors, especially cigarette smoking, should be diligently sought. Tobacco smoking increases a patient’s relative risk of lung cancer 10- to 30-fold over that of nonsmokers; this risk decreases after 5 years of smoking cessation but never falls to the level of a patient with no smoking history.

• Age is another leading risk factor. The older a person is, the greater the likelihood of malignancy. In one study, a solitary pulmonary nodule had a 65% chance of being malignant in patients over 50 years of age versus 33% in patients under 50 years of age.

• A past medical history of malignancy raises the suspicion of metastatic lung disease. Extrapulmonary malignancies that are most likely to lead to pulmonary metastases include sarcoma, malignant melanoma, and carcinomas of breast, colon, kidney, and testicle.

• SPNs, by definition, do not affect surrounding tissue and, as such, are almost invariably asymptomatic.

• Cough is a nonspecific symptom and may accompany any potential cause of SPN.

• Weight loss can accompany malignant (primary and metastatic) causes of SPN, as well as infectious etiologies such as Mycobacterium tuberculosis infection.

Physical Examination

As stated earlier, an SPN is defined by its size (<3 cm) and the fact that it does not distort or affect surrounding tissues. Therefore, the SPN rarely, if ever, causes abnormal findings on physical exam.

Tests for Consideration

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Chest radiographs are generally the initial method by which SPNs are identified.


• Nodular characteristics on CT scan, such as size, border, calcification, density, and growth, can help to predict if a nodule is benign or malignant.


Size: Larger nodules have a higher likelihood of being malignant than smaller ones. The odds of malignancy are estimated at 0.2% for nodules smaller than 3 mm, 0.9% for nodules 4 to 7 mm, 18% for nodules 8 to 20 mm, and 50% for nodules larger than 20 mm.

Border: Smooth borders generally indicate a benign etiology, while irregular and spiculated borders suggest malignancy; these findings are not highly specific, however.

Calcification: Benign lesions can have “popcorn” calcifications (as with hamartomas), concentric calcifications, or central calcifications (may indicate infection-related granulomas). Eccentric, laminated, and stippled calcifications suggest a more ominous etiology.

Density: Hounsfield units (HU) are a means by which the density of a structure can be determined radiographically. Though this modality is no longer used in the routine evaluation of SPNs, higher density lesions (>164 HU) are typically benign, and lower density lesions (<147 HU) are often malignant.

Growth: Malignant lesions have a volume doubling time between 20 and 400 days. A doubling time of 100 days correlates with a 30% increase in the diameter of a SPN. Lesions that are stable in size on CT scans over a 2-year period are believed to have doubling times consistent with benign etiologies.

FDG-PET: 18-fluorodeoxyglucose PET can help determine the likelihood of an SPN being malignant. It is most accurate when an SPN is greater than 1 cm. It has a high negative predictive value and a poor positive predictive value. A total of 78% of benign lung nodules will result in a normal FDG-PET, and 95% of malignant nodules will have an abnormal FDG-PET. Tumors with relatively low metabolic activity can produce false negative results; such examples include bronchoalveolar carcinoma and carcinoid.


Nodule Sampling: Biopsy of the SPN is imperative when malignancy is considered to be possible or likely. Biopsy techniques include transthoracic needle aspiration (TTNA), bronchoscopy with transbronchial biopsy (TBBX), and surgical resection.

TTNA is performed through the chest wall using either fluoroscopy or CT scanning to guide the biopsy needle. The overall diagnostic yield for suspected lung cancer is approximately 90%, a higher rate than that achieved with TBBX. TTNA biopsy success is increased with greater SPN size, increased number of needle passes, and the presence of an on-site histopathologist.


Bronchoscopy allows collection of airway cells using lavage, brushings, or direct biopsy methods such as needle or forceps. Though bronchoscopy has a high yield for central endobronchial lesions, most SPNs cannot be described as such. Therefore, bronchoscopy is the least likely maneuver to yield a positive biopsy result for the SPN. Fluoroscopy or EBUS helps localize the lesion and increase the diagnostic yield. Rates of success for nodules smaller than 2 cm vary from 10% to 50%.