Pulmonary Nodule

Solitary Pulmonary Nodule

Solitary Pulmonary NoduleUp to 150,000 discovered each yearUsually detected incidentallyDefined as:

Single Surrounded by and within normal pulmonary

parenchyma <3cm=nodule >3cm=mass

Major question: Is the nodule benign or malignant?

Differential – Benign (70%)Infectious Granuloma (80%)

Histoplasmosis, Coccidioidomycosis, mycobacteria

Hamartoma (10%) Slow growing, “popcorn” calcification,

heterogeneous (fat, muscle, calcification)Inflammatory

Wegener’s, Rheumatoid noduleVascular

Differential – Malignant (30%) Primary lung malignancy

*Adenocarcinoma peripheralLarge Cell peripheralSquamous Cell central

Carcinoid tumorsCentral > peripheral

Lung metastasisMelanoma, sarcoma, colon, breast, kidney,

testicleOften present as multiple nodulesIn a person with h/o cancer, a SPN on CXR has a

25% probability of being a metastasis

Pulmonary Nodules51% of smokers 50 years and older have

pulmonary nodules on CT.Since only a small number of these are

malignant, how do we manage them?In the past, we use to closely monitor all

nodules for at least 2 years to confirm stability.Unnecessary surgery and biopsies have

potential morbidity and mortality.Unnecessary imaging increases healthcare

costs

Fleischner Society Guidelines


The Fleischner Society is an international, multidisciplinary medical society.

Experts in adult and pediatric radiology, pathology, pulmonary medicine and thoracic surgery.

2005 Consensus Statement MacMahon et al. Radiology

2005;237:395-400

Pulmonary Nodules

Definition Spherical, well circumscribed pulmonary opacity that

measures <3cm in size >3cm is a lung mass

Guidelines are primarily based on the size of nodule and risk factors for malignancy

Size Fewer than 1% of nodules <5mm are malignant. 18% of nodules 8-20mm are malignant. 50% of nodules larger than 20mm are

malignant.

Pulmonary Nodules

Risk Factors Smoking

Lung cancer is 10 times more common in smokers compared to non-smokers

History of lung cancer in a first degree relative

Exposure to asbestos, uranium and radon.

Rare in under 35 years of age


Management Considerations

Appearance Spiculated nodules have a higher risk Ground glass nodules can be low

grade cancers and grow slower Calcifications favor benignity Clustered nodules favor an infectious

process

Patients with Known Primary Malignancy

Management is typically based on the specific clinical situation and the relevant treatment protocol.

Makes patient management difficultCan’t assume that a nodule is malignant.No general guidelines established, but

frequent close follow up is usually indicated.Larger nodules may require PET or biopsy

Approach to SPN Goal is to remove all malignant nodules

while avoiding resection of benign nodules5yr survival is 70-80% in patients with Stage

1a NSCLCa that is resected Determine the probability of malignancy

Clinical factorsCharacteristics of the nodule on imaging

Chose management based on probability of malignancy

Clinical FeaturesSmoking historyAgeExposure to asbestosFamily HistoryPreviously diagnosed cancer

Age Probability the SPN is Malignant

35-39 3%40-49 15%50-59 43%>60 50%

Radiographic Features Size

Larger size associated with higher likelihood of malignancy 3mm associated with 0.2% risk VS 20mm associated with

50% risk of malignancy Border

Malignant: spiculated (corona radiata sign), scallopedBenign: smooth

DensityIncreased density argues against malignancyIn one study, SPNs <147 Hounsfield units were malignant

whereas SPNs >164 Hounsfield units were benignNo clear number to say what is benign and malignantRarely used a part of routine evaluation

Radiographic Features - Growth Malignant lesion doubling time is b/t 20-400 days Benign lesions either grow very quickly (infectious) or

remain stable for a prolonged period of time (hamartoma)

Traditionally there has been a “2yr rule” where if there is no growth at 2 yrs, it is considered benignRecent studies have challenged this rule○ 156 SPNs and masses from 1-14cm in size○ 74 of these cases had previous films for comparison

In 26 cases, there was documentation of no growth, yet 9 of these nodules/masses were found to be malignant

○ Advise to interpret 2 yr stability with caution Bronchoalveolar Cell Ca and carcinoid often grow

slowly Monitor growth with CT, not x-rays

Radiographic Features Ground Glass Appearance

Associated with malignancyOften associated with slow growing

bronchioloalveolar carcinoma Calcification

Suggests benign lesion○ Granuloma: laminated or central pattern○ Hamartoma: “popcorn” pattern, focal areas of fat and

calcification (“areas of very high and very low attenuation”)

Malignant calcification: stippled, eccentric (asymmetric)

1. Corona radiata (spiculated)2. Scalloped border3. Air bronchus sign4. Smooth, well-marginated nodule, dense central calcification typical

of histoplasmosis5. Central calcification and laminated fibrous tissue 6. Calcification and fat, typical of a hamartoma

**Images from UTD and NEJM

Initial ManagementDetermine the probability of

malignancy based on: Clinic factors Radiographic features

Ost D et al. N Engl J Med 2003;348:2535-2542

Assessment of the Risk of Cancer in Patients with Solitary Pulmonary Nodules

Management Low Probability

Follow with serial CT scans [Fleischner society criteria]

Traditionally q3 months X 4 q6 months X 2 Intermediate Probability

< 1cm serial CT scans> 1cm PET○ If negative serial CT scans○ If positive excision

High ProbabilityExcision

CT-ScansIn general, if a SPN has been stable

for 2 yrs, it is likely benign Certain types of malignancy are

notorious for slow growthCarcinoid, bronchioloalveolar

Interval f/u with CT scan depends on size and risk for cancer

Size Risk of Malignancy

Interval Follow up

<4mm LowHigh

None12 months

4-6mm LowHigh

12 months6-12 then 18-24 months

6-8mm LowHigh

6-12 then 18-24 months3-6 then 6-12 then 24 months

>8mm Low or High 3, 6, 9, and 24 months

Metabolic Imaging FDG-PET scan (18-

flourodeoxyglucose)Metabolically active cells take up the

FDG more readilyUsed for patients with nodule >1 cm

who have an intermediate probabilityAdditional advantage: staging

PET-Scan95% sensitivity, 78% specificityFalse Positives:

Infectious or inflammatory processesFalse Negatives:

Nodules with low metabolic activity:Bronchioloalveolar tumors, carcinoid tumors Small lesions (<1cm)

Nodule SamplingThrough the airway:

BronchoscopyThrough the chest wall:

Percutaneous needle aspiration Percutaneous needle biopsy

Decision depends on: size, location, local expertise

Bronchscopy Good for central nodules

Air bronchus sign Poor for small, peripheral SPNs At its best, sensitivity is only 70%

CT showing bronchus leading to lesions ; “air bronchus sign”

Specimens collected by washings, lavage or direct sampling

Several techniques being studied for futureEndobronchial U/S with fluoroscopyCombining FISH with cytology

Percutaneous needle aspiration or biopsy Diagnostic yield is about 90%

Up to 97% when biopsy is performed Better for evaluating small SPNs

Verses bronchoscopy Aspiration obtains material for cytology Biopsy obtains core tissue

Evaluates architectureBetter for diagnosing benign nodules

Complications: pneumothorax, bleeding

Surgical ResectionIndicated if:

Likelihood of malignancy is high Positive PET Scan Percutaneous sampling proved malignancy

Done via VATS or thoracotomyVATS has replaced thoracotomy in

many cases, especially for nodules close to the pleura

-Low probability: -Serial CT scans-Intermediate probability: -Serial CT scans (<1cm) vs PET (>1cm)-High probability: -Excision

Low Intermediate HighDiameter of Nodule (cm)

<1.5 1.5-2.2 >2.2

Age <45 45-60 >60

Smoking status Quit >7yrs ago

Quit < 7yrs ago Never quit

Nodule margins Smooth Scalloped Spiculated

Key Points SPN: a single lesion both within and

surrounded by pulmonary parenchyma Malignant (30%) or Benign (70%)

Malignant: bronchogenic carcinoma, carcinoid tumor, metastasis

Benign: infectious, inflammatory, hamartoma Determine likelihood of malignancy

Clinical factors, radiographic features Once likelihood of malignancy is

determined, you can determine initial management

Key Points Low probability: serial CT scans Intermediate probability: serial CT scans

(<1cm) vs PET (>1cm) High probability: Excision CT scans preferred to X-rays for serial imaging Nodule sampling done through: bronchoscopy,

percutaneous aspiration or biopsy Definitive intervention is excision by VATS or

thoracotomy

Solitary Pulmonary NoduleBasic strategy is to identify

malignant versus benignDefinition: Opacity with diameter <

3cmLarger lesions are called massesIt occurs in 1 every 500 CXR

Nodules prove to be malignant in 40% of cases

Most often Bronchogenic carcinomaMost common benign is hamartomaBenign lesions: rheumatoid

granuloma, healed infarct, pulmonary anurysm, Wagner’s granulomatosis

Solitary Pulmonary Nodule

Early ResectionStudies have proven that early resection

results in 5-year survival rate of 50%If nodule is 1cm or less rate is about

80%Survival rate after discovery of

bronchogenic carcinoma is 15% and hence the importance of early discovery in terms of cure

Growth of a NoduleMalignant nodules grow at a

constant rate expressed as doubling time

This usually falls between 25 and 450 days with a median of 120 days

An increase of 28% in nodule diameter indicates doubling

Benign lesions grow slowly with doubling time exceeding 500 days

It is almost conclusively a benign lesion if size is stable for 2 years ( doubling time exceeding 720 days )

A doubling time of less than 20 days signifies inflammatory process

Growth of a Nodule

CalcificationRadiographic pattern of calcium

deposition is helpful Benign lesions tend to have central,

laminated (bull’s eye), diffuse or popcorn pattern

Malignant lesions have speckled or eccentric pattern

High Resolution CTHRCT is the most sensitive and

specific for assessing the size, shape, calcification and edge of a nodule

Type 1 Type 2 Type 3 Type 4

PET ScanHighly valuable noninvasive toolIt is 95% sensitive for identifying

malignancy and 85% specific False positive results may occur in

lesions that contain active inflammatory tissue (histoplasmomas)

BiopsyBx has a high yeild in establishing DxBronchoscopy can not access a

nodule if it is peripheral and smallIf CT shows a bronchus entering a

nodule its yeild is much higherTransthorathic needle aspiration

(NAB) has a sensitivity of 80% to 90%

SurgeryThoracotomy to resect a malignant

nodule carries significant death of 3% to 4% but for a benign lesion it is 0.3%

Thoracoscopy carries less significant morbidity and lessens hospital stay

It is not known if the 5-years survival is different between the two approaches

Benign vs MalignantAge <48nodule diameter<1.5never smokednodule edge type1doubling time >500 dcalcification in benignNeedle Bx: benign dis

Needle Bx: Nonspecific

>48>1.5ever smokedtype330 to 400 daysindeterminate

patternmalignant diseasesuspicious cells

Review all prior CXRGet CT scansIf probability of cancer is <10% wait

and watchIf it is high thoracotomy should

interveneBronch & NAB reserved for pt who are

reluctant to go for surgery before Dx

Decision Making

If results are intermediate: Thoracotomy, NAB and PET are equal in terms of 5-years survival

PET is slightly more effective,noninvasive

If PET is +ve but other criteria are low for malignancy, then ANB is needed to R/O infectious granulomas

Decision Making

CASE1 -

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CASE1 -asbestosis

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Case-2 nodule Lung

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Case-2- Cacified nodule -breast

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Case-3

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Case-3- Pulmonary HAMARTOMA-fairly well-defined PN in the right mid zone associated with a central nidus and a laminated calcification in a pulmonary hamartoma

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Case-4

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Popcorn calcification in Hamartoma

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Case-5 ct scan Low attenuation in nodule

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Case-5-Hamartoma-ct scan Low attenuation in nodule

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Case- 6

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Case- 6-multiple small calcific PNs due to old healed histoplasmosis

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Case 7 [ 5 YEARS APART CXR]

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Case 7 [ 5 YEARS APART CXR]

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wo chest radiographs 5-years apart showing a high-density solitary pulmonary nodule remaining unchanged over a 5-year period. One of the most reliable imaging features of a benign lesion is as a benign pattern of calcification and periodic follow-up with CT showing no growth for 2 years. The high density of the well-defined nodule suggest that this is calcified granuloma and no further follow-up is indicated except in patients with calcium producing tumors such as a primary osteosarcoma , medullar ca thyroid mets

Case 10

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Case 10 --old healed TB. Note the loss of lung volume/fibrosis in the right upper zone and the associated pleural calcification due to a previous tuberculous empyema. Calcific granulomas are also noted in the left apical region

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Case 8

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Case 8-calcification at both the lung apices associated with a right lower paratracheal calcified lymph node due to healed tuberculosis

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Case 11

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Case 11 -dense nidus of central calcification in an adenocarcinoma of the lung

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Case 15 -

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Case 15 -shows a central pulmonary carcinoid associated with dense amorphous calcification (arrow)

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case 22

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case 22 -a large PN at the right lung base with central high density due to calcification in a metastatic deposit from a leiomyosarcoma of the uterus

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case 24

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case 24 - multiple high-density lung masses in a patient with a nonmucinous adenocarcinoma of the sigmoid colon

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Differential Diagnosis Of Multiple Pulmonary Nodules Metastatic Rumors Infectious Granulomas Rheumatoid Nodules Sarcoidosis Metastatic Pulmonary calcification Amyloidosis Chronic hypersensitivity pneumonitis Bronchiolitis –associated interstitial lung disease Lymphoid Interstitial Pneumonia Infections[ e.g., viral, granuloma] Pulmonary Hyalinizing granuloma Malignancy[e.g. Multifocal adenocarcinoma

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Pulmonary Nodule