SOLITARY NODULE 2019

1. Clinical Approach to
Solitary Pulmonary Nodule
Dr. SHIVAOM CHAURASIA
Internal Medicine
Resident

2. Definition:
• A solitary pulmonary nodule is defined as an x-ray density completely
surrounded by normal aerated lung with circumscribed margins, of
any shape, usually 1–6 cm in greatest diameter.
• Morphologically, nodules are classified as
• solid or
• Subsolid - subdivided into
• pure ground-glass nodules (ie, no solid component) &
• part-solid nodules (ie, both ground-glass and solid components) .
• Lesions that measure >30 mm - considered masses, (much higher
likelihood of being malignant).

3. GENERAL PRINCIPLES:
• The goal of a evaluation of the solitary pulmonary nodule (SPN) is to
determine if the lesion is more likely malignant or benign.
• A lesion greater than 3 cm - high likelihood of malignancy.
• Benign nodules with low-risk characteristics should be closely followed.
• There is a >60% survival rate of patients who have a malignant SPN
removed (Chest 1997;111:1710).

4. • At present, only two radiographic criteria are thought to predict the benign
nature of a solitary pulmonary nodule:
• lack of growth over a period >2 years and certain characteristic patterns of
calcification.
• a dense central nidus, multiple punctuate foci, and “bulls eye” (granuloma) and
“popcorn ball” (hamartoma) calcifications are highly suggestive of a benign lesion.
• Large lesion, asymmetric calcification, chest symptoms, associated
atelectasis, pneumonitis, or growth of the lesion revealed by comparison
with an old x-ray or CT scan or a positive PET scan - suggestive of a
malignant process and warrants a histologic diagnosis.

5. • Small “ground-glass” opacities GGOs, when biopsied, are found to be
atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), or
minimally invasive adenocarcinoma (MIA).
• AAH is usually a nodule of <5 mm and is minimally hazy, also called nonsolid
or ground glass
• (i.e., hazy slightly increased attenuation, no solid component, and preservation of
bronchial and vascular margins).
• Patient age – probability of malignancy rises with increasing age.

6. Epidemiology:
• Approximately 150,000 SPNs are identified each year in the United
States.
• It has been estimated that such a nodule is noted on 0.09% to 0.20%
of all chest radiographs.

7. Etiology:
• Malignancy accounts for approximately 40% of SPNs.
• Granulomas (both infectious and noninfectious) account for 50% of
undiagnosed SPNs.
• The remaining 10% are composed of benign neoplasms, such as
hamartomas (5%) and other causes.

9. Risk Factors:
• Smoking is the most important associated risk factor for almost all
malignant SPNs.
• For infectious etiologies - an immunocompromised state promotes an
increased risk.

10. Lung Cancer Screening:
• Screening high-risk patients using low-dose chest CT resulted in a
20% relative reduction in mortality from lung cancer compared to
screening with chest X-ray (N Engl J Med 2011;365:395).
• DIAGNOSIS:
• Diagnosis of the SPN is made radiographically, usually via chest X-ray or CT
scan.
• Most frequently, the nodule is noted incidentally.

11. Clinical Presentation:
• Most patient remain asymptomatic.
• Sometimes the nodule may precipitate
• cough, chest pain, hemoptysis, or sputum production depending on the
etiology .

12. History:
• Typical screening questions for malignancy including weight loss and night
sweats.
• Hemoptysis - indicate malignancy but may also prompt investigations for
antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis,
tuberculosis (TB), and hereditary hemorrhagic telangiectasia (HHT).
• Arthritis and arthralgias should be ruled out - for possible undiagnosed
rheumatoid arthritis or sarcoidosis.
• Exposure history including recent travel history related to endemic
mycoses (histoplasmosis, coccidioidomycosis, etc.) , TB exposures.

13. • A history of previous malignancies increases the risk of metastatic
disease of the lung.
• Immunosuppressed state (HIV, organ transplant, or chronic steroids) -
increased risk of infectious causes.
• Smoking is linked to 85% of lung cancers.
• Occupational history - possible asbestosis , silica, beryllium, radon,
ionizing radiation, among others.

14. Physical Examination:
• No specific physical exam findings.
• Signs of weight loss or cachexia - malignancy.
• Lymph node examination.
• Breast exam in women and testicular exam in young men.
• Skin examination - telangiectasias, erythema nodosum, rheumatoid
nodules .

15. Diagnostic Criteria:
• It is completely surrounded by lung parenchyma, unaccompanied by
atelectasis, intrathoracic adenopathy, or pleural effusion.
• The first step in managing an SPN is to stratify the patient in terms of
malignancy risk:
• low-, intermediate-, or high-risk categories.

17. Differential Diagnosis:

18. Diagnostic Testing:
Laboratories:
• Routine laboratory testing - rarely helpful unless the history and
physical exam strongly suggest an etiology.
• Hyponatremia - suggest syndrome of inappropriate antidiuretic
hormone (SIADH) associated with primary lung cancer.
• Hypercalcemia - lung cancer as well as sarcoidosis.

19. • Anemia - chronic pulmonary hemorrhage (e.g., HHT) or a chronic
inflammatory disease.
• Sputum culture - diagnosis of an infectious SPN.
• Sputum cytology (limited use) - peripherally located, small lesions.

20. Chest X-ray:
• A previous chest radiograph is an important tool in the initial
evaluation of an SPN.
• If an SPN has been present and unchanged on chest radiograph for
more than 2 years - further evaluation may not be warranted.
• Optimum technique for chest radiography - posteroanterior (PA) and
lateral views.
• Ground glass lesions may be followed for longer periods of time
(volume-doubling time may be extended in certain types of non–small
cell lung cancer).

21. • If an SPN appears on a new radiograph in less than 30 days - most likely
infectious or inflammatory.
• More likely that a lesion is
• benign: calcifications, a laminated appearance,
• malignant: spiculated, irregular border.
• Advantages-
• easy to obtain and delivers a low dose of radiation
• Disadvantages –
• Limited role in the initial characterization
• Most nodules will require chest CT for further evaluation.
• Insensitive for detection of small nodules less than 1 cm

23. Chest CT:
• The most important for SPN evaluation.
• Accurate volumetric measurement of lesion size –
• precise comparison to determine stability or growth.
• Features of an incidental pulmonary nodule to be assessed on CT are:
Size —
• an independent predictor for malignancy.
• Size is measured as the average of the long and short axes, rounded to the nearest
millimeter.

24. Attenuation —
• Solid lesions are more common, but part-solid lesions have a higher likelihood of
being malignant .
• Solid nodules – typically dense and homogeneous on imaging.
• Subsolid nodules – less than soft tissue attenuation (ie, density) on imaging ; normal
parenchymal structures, including airways and vessels, can be visualized through them.
Growth or stable size —
• For solid nodules, growth is defined as an increase in size of >2 mm .
• For subsolid nodules, growth - identified as an increased attenuation or an increase in the
size of or development of a solid component.

25. • Calcification and fat — Four benign patterns of calcification
• central, diffuse, lamellated - prior infection, particularly histoplasmosis or tuberculosis
• "popcorn" - hemartomas, sometimes carcinoid tumors.;; presence of fat within a smooth
bordered nodule is a reliable indicator of a pulmonary hamartoma.
• Border and lobar location —
• Benign nodules - a well-defined, smooth border,
• Malignant lesions - a spiculated (corona radiata sign) or lobular border.
• Enhancement —
• Malignant nodules - enhance more than 20 Hounsfield units,
• Benign Nodules - enhance less than 15 Hounsfield units
(sensitivity, 98 percent; specificity, 58 percent; negative predictive value, 96 percent).

28. PET scan:
• 18-Flourodeoxyglucose positron emission tomography (FDG-PET) can help distinguish
malignant and benign lesions (cancers are metabolically active and take up FDG avidly).
• Sensitivity - 80% to 100% ;; Specificity - 79% to 100% of detecting malignancy.
• False negatives - bronchoalveolar carcinoma, carcinoid, and mucinous neoplasms
• False positives - common in “inflammatory” conditions (infectious and autoimmune
processes).
(Higher incidence in nodules <10 mm (Lung Cancer 2004;45:19).
• Most commonly - in the evaluation of low-to-moderate risk indeterminate nodules for
further risk stratification

29. Diagnostic Procedures:
• If a nodule is considered high risk - best approach is to undergo biopsy and
pursue resection.
• Any change of an SPN on serial imaging warrants resection or invasive
biopsy.
• If a lesion has low-risk characteristics - no indication to pursue biopsy .
• Biopsy - when there is discordance between clinical risk stratification and
imaging tests.

30. Transthoracic needle aspiration:
• Usually performed under the guidance of fluoroscopy, ultrasound, or CT (more
common).
• Most commonly for nodules with a peripheral location.
• For diagnosis of malignancy, sensitivity, specificity, and yield of TTNB are usually
>90, >99, and >90 percent, respectively, even for nodules measuring <1 cm.
• A nondiagnostic biopsy does not rule out malignancy.
• The main complication of TTNA
• pneumothorax - 25% incidence of minor pneumothorax and 5% major requiring chest tube
drainage.

31. Bronchoscopy:
• Conventional bronchoscopy -limited role in the evaluation of an SPN.
• R-EBUS (Radial Endobronchial Ultrasonography) and navigational
bronchoscopy are superior to conventional bronchoscopy for the diagnosis of
lung malignancies .
(providing diagnostic yields over 80% regardless of lesion size )(Am J Respir Crit
Care Med 2007;176:36).
• Other interventional techniques - electromagnetic navigation and CT
virtual bronchoscopy.

32. Surgical biopsy
• Gold standard for diagnosis of a pulmonary nodule and can be curative for some
malignancies.
• For patients who are surgical candidates,
• a diagnostic wedge resection by video-assisted thoracic surgery (VATS) is the preferred
procedure or
• intermediate risk of malignancy when nonsurgical biopsy is nondiagnostic or suspicious
for malignancy .
• Additional indications - a benign diagnosis is suspected that requires therapy
(eg, mycobacterial disease), in whom nonsurgical biopsy was nondiagnostic.
• VATS is safe in experienced hands and can be performed as a day or short stay
(three to five days) procedure at many centers.

35. TREATMENT:
• Overall treatment strategy is to identify lesions with significant malignancy
risk and pursue surgical resection when possible.
• If a nodule has low-risk characteristics and stable over a period of 2 years,
- no further treatment is warranted.
• Further follow-up of ground glass lesions may be necessary, as the volume-
doubling times of these lesions may be prolonged.
• If a specific etiology for the SPN is diagnosed (e.g., a connective tissue
disease or infection), then treatment is targeted toward the underlying
process

36. Other Nonpharmacologic Therapies:
• Although surgical resection is preferable in patients with either a high-risk
lesion or biopsy proven malignancy,
• If surgical resection is not an option, there are other less effective
therapies.
• Stereotactic radiation is currently the most widely utilized therapy in this
clinical situation.
• This mode of external beam therapy aims to decrease collateral radiation-induced
damage to adjacent lung tissue.
• Experimental approaches, including brachytherapy and radiofrequency
ablation.

37. Surgical Management:
• Surgical resection of an indeterminate SPN is indicated in the
following situations:
• The clinical probability of malignancy is moderate to high (>60%).
• The nodule is hypermetabolic by PET imaging.
• The nodule has been proven malignant by biopsy.
• A combination of surgical techniques, including VATS,
mediastinoscopy, and thoracotomy, can lead to diagnosis (via
intraoperative frozen section), staging, and potential cure.

38. References:
• Harrison’s_Principles_of_Internal_Medicine,_Twentieth_Edition_(Vol.
1_&_Vol.2
• The_Washington_Manual_of_Medical_Therapeutics,_34th_Edition_(
cnvtd_pdf)
• Uptodate

39. THANK YOU!!!