PULMONARY BOARD REVIEW:
PULMONARY NODULES
1. Multiple Pulmonary Nodules: some etiologies according to immune status
a. Immunocompetent
1) Neoplasm - The unexpected discovery of multiple pulmonary nodules in the absence of
explanatory elements in the history or on physical examination should raise concern for
metastatic malignancy. The most common malignancies to present in this fashion include
primary neoplasms of the testes, ovaries, kidneys, breast, and anal canal, as well as
melanomas and sarcomas
2) Infection: Bacterial (septic emboli), Viral, Fungal, MTB, MAI, Parasite (hydatid cyst)
3) CVD: Wegeners, RA, Churgg Strauss
4) AVMs
5) Inflammatory Disorder: COP, IIP (RBILD, DIP, LIP)
6) Granulomas: Sarcoidosis
7) Pneumoconiosis: Beryllium, Silicosis, Talc
b. HIV:
1) Bacterial PNA
2) MTB
3) KS
4) Lymphoma
5) MAI
6) Lung Cancer
7) Aspergillus
c. Lung Transplant:
1) PTLD
2) Aspergillus
3) CMV
4) B.O.
5) Carcinoma
2. Solitary Pulmonary Nodule: single, radiologically visible lesion that is within and surrounded on
all sides by pulmonary parenchyma. It is not associated with other, potentially related pulmonary
pathology, such as hilar or mediastinal enlargement or a pleural effusion. The upper limit in size of a
"nodule" is arbitrary and is generally considered to be either 3 or 4 cm. Lesions larger than 3 to 4 cm
are classified as "masses" and are more likely to be malignant.
a. Etiologies: Malignant = ~50%, Benign = ~50% (80% infectious granuloma, 10% hamartoma)
1) Malignant: Primary vs. Metastatic (breast, head/neck, melanoma, renal, sarcoma, colon),
Carcinoid
2) Infectious Granuloma (MTB, MAI, Fungus)
3) Benign Neoplasm: Hamartoma, Lipoma, Fibroma
4) AVM
5) Bronchogenic cyst
6) Inflammatory – Wegeners, RA
7) Other – pseudotumor, rounded atelectasis, amyloidoma, hematoma, infarct, intrapulmonary
lymph nodes
b. Factors influencing probability of Cancer:
1) Size:
(a) Lung cancer appears to be rare in nodules < 5 mm in size, and it is safe to repeat the CT at
1 year in these patients
(b) ~80-90 percent of solitary nodules larger than 3 cm in diameter are malignant
2) Change in size: nodule that grows at a rate consistent with cancer (doubling time of 30 to 360
days)
3) Number:
(a) more than six nodules are thought to indicate inflammatory lung disease
(b) Synchronous lung cancers are increasingly recognized as CT screening has become more
prevalent, and multifocal bronchoalveolar cell or adenocarcinoma is often the histology,
particularly in women who never smoked or quit cigarette smoking many years earlier
4) Density:
(a) Nonsolid nodule (previously termed ground-glass opacity) is a density through which
aerated lung parenchyma is visible - possess a relatively low risk of cancer (approx.
15%); as their size rises > 1.5 cm, the risk of malignancy, particularly BAC rises
(b) Solid nodules are the most common, a lower proportion are cancer. Inflammatory
diseases of the lung, particularly tuberculosis (typical and atypical) and mycoses,
generally produce solid nodules that can be expected to eventually calcify, permitting
their designation as benign. Only approximately 15% of solid nodules < 1 in diameter
contain cancer, but as solid nodule size increases, the proportion that is cancer increases.
5) Characteristics:
(a) Calcification - Pattern: diffuse homogenous (old granuloma), central, concentric
(histoplasmosis), popcorn (hamartoma)  benign
(b) Edge and contour – speculated  malignant
6) Age: Lung cancer is rare before the age of 40 years, but its incidence increases steadily from
40 to 80 years
(a) 3 percent in patients between ages 35 and 39
(b) 15 percent between ages 40 and 49
(c) 43 percent between ages 50 and 59
(d) 50 percent or higher at age 60 or above
7) Gender: As cigarette smoking has increased in women, the incidence of lung cancer has risen
8) Tobacco: The incidence of lung cancer directly correlates with the pack-yrs of cigarettes
smoked. It appears that the incidence of lung cancer stops increasing after smoking cessation,
but it does not drop to the levels of individuals who never smoked. Consequently, it is
common to encounter patients with newly diagnosed lung cancer who stopped smoking many
yrs or decades earlier
9) Spirometry: There is a statistically significant association between a spirometrically
demonstrated obstructive ventilatory impairment and lung cancer
10) Occupational history: Asbestos exposure, after a latency period of 20 to 40 years, predisposes
to lung cancer acting synergistically with the risk posed by cigarette smoking. Workers
exposed to respirable radioactive gas in the production and disposal of fissionable materials
have an increased risk of lung cancer. Uranium miners and individuals working with heavy
metals such as cadmium and nickel are known to have an increased lung cancer risk.
Individuals with idiopathic pulmonary fibrosis and pneumoconioses probably have an
increased risk of acquiring adenocarcinoma or bronchoalveolar cell carcinoma
11) Endemic granulomatous disease: As the nationwide incidence of tuberculosis has declined,
except notably in immigrants from endemic areas and in HIV-positive individuals, M
tuberculosis has become a less common etiology of pulmonary nodules. When CT screening
for lung cancer was performed in the Midwest United States, an area endemic with
histoplasmosis, a high false-positive rate was observed
c. Diagnostic Technique:
1) Evaluate according to risk factors and CT assessment of growth
2) Algorithm #1: CT assessment of nodule growth by Libby, Henschke Chest 2004 et al. –
assess size, density, and risk factors
(a) Low Risk Nodules: nodules < 5mm, nonsolid nodules 5-10mm  repeat CT in one year
(b) Intermediate Risk Nodules:
(1) part solid and solid 5-9mm and some > 10mm  repeat CT in 6 weeks (consider
ABx)
(2) consider PET
(c) High Risk Nodules by risk factors: Biopsy  FNA or VATS
(d) Repeat CT in 3 months if benign FNA or if does not change or resolves on 6 week CT
(e) If does not change in volume in 6 months  small risk malignancy < 10%
(f) Fails to change over 2 years  benign
(g) Summary: non-calcified solid nodule > 5mm  repeat CT in 6 weeks (consider ABx) or
PET
(1) If partial resolution or no growth or negative PET  repeat CT 3 months
(2) If growth or positive PET  biopsy
3) Algorithm #2: see attached Ost et al NEJM 2004 approach - in general, unless the likelihood
of lung cancer is low/intermediate or the risk of a surgical procedure is high  favor
removing by VATS such nodules without a biopsy (FNA).
4) Algorithm #3: for <1 cm nodule – see Guidelines for Management of Small Pulmonary
Nodules Detected on CT Scans: A Statement from the Fleischner Society
5) FNA: may give three results –
(a) Malignant
(b) Specific benign – carcinoid, hamartoma, MTB…
(c) Nonspecific benign (inflammation, atypia, hyperplasia, blood, bronchial cells,
granuloma) - requires careful following for further growth
6) PET: better if > 1cm, SUV > 3 c/w malignancy
7) Bronchoscopy – limited usefulness if peripheral and <2cm
8) VATS – diagnostic
Guidelines for Management of Small Pulmonary Nodules Detected on CT Scans: A Statement from the Fleischner Society. Radiology 2005; 237: 395-400.
Patients known to have or suspected of having malignant disease.—Patients with a cancer that may be a cause of lung metastases should be cared for
according to the relevant protocol or specific clinical situation. Pertinent factors will include the site, cell type, and stage of the primary tumor and whether
early detection of lung metastases will affect care. In this setting, frequent follow-up CT may be indicated.
Young patients.—Primary lung cancer is rare in persons under 35 years of age (<1% of all cases), and the risks from radiation exposure are greater than in
the older population. Therefore, unless there is a known primary cancer, multiple follow-up CT studies for small incidentally detected nodules should be
avoided in young patients. In such cases, a single low-dose follow-up CT scan in 6–12 months should be considered.
Patients with unexplained fever.—In certain clinical settings, such as a patient presenting with neutropenic fever, the presence of a nodule may indicate
active infection, and short-term imaging follow-up or intervention may be appropriate.