ICL 3.1: Lung Nodules

Question 1

what is the definition of a lung nodule?

Answer 1

a well-defined lesion < 30 mm (1.4 inches) in diameter observed on lung imaging (e.g., CXR or chest CT)

Question 2

what is the prevalence of lung nodules?

Answer 2

general population: 1/100 CT scans

endemic fungal regions (Histplasma, Blastomycosis: 20%)

heavy smokers aged >50 years account for >50% of lung nodules

Question 3

which active infections should be in your differential diagnosis when you see a lung nodule?

Answer 3

1. “walking pneumonia”

mycoplasma/chlamydia most commonly; ground glass appearance, not nodules really

2. tuberculosis (rare in US, common in other regions of world)
3. endemic fungal in endemic regions
   ex. histoplasmosis > blastomycosis in mid-west; coccidiomycosis in southwest
4. typical mycobacteria or opportunistic fungal (e.g. aspergillus) in immune compromised

Question 4

which non-infectious active inflammation causes should be in your differential diagnosis when you see a lung nodule?

Answer 4

1. organizing pneumonia (post-infection or secondary to drug)
2. local atelectasis secondary to mucous plug (e.g., in chronic bronchitis)
3. rheumatoid nodule (usually, only after >10 years of Rheumatoid Arthritis)
4. granulomatosis with polyangiitis (aka Wegener’s granulomatosis) –> will present with characteristic systemic signs and symptoms
5. enlarged benign lymph node usually near pleural or inter-lobar region
6. old inflammatory scar (granuloma)
   e. g. from histoplasmosis in mid-west US, or TB in some world regions
7. benign tumor like a hamartoma: typical radiological characteristics
8. metastasis from cancer elsewhere (more likely if multiple nodules)
9. early primary lung cancer

Question 5

what is the outcome of lung cancer diagnosed in late stage?

Answer 5

lung cancer symptoms occur late, when it is too advanced for cure in >85%

diagnosed in advanced stage means when the nodule is >3 cm and/or metastatic –> this happens in >85% if not in screening program…if a patient is diagnosed based on symptoms or signs, it is nearly always too late for cure.

advanced stage 5-year survival <5%.

Question 6

why do we screen for lung cancer?

Answer 6

this is because the cancer typically can grow for a long time without causing symptoms due to the large space in chest

once it’s late stage, 85% of the time you can’t cure it

this is why we need screening!!

failure to properly manage nodules that represent early lung cancer is a cause of mal-practice suits

Question 7

what are the characteristics of lung nodules associated with high risk for lung cancer?

Answer 7

1. spiculated = non-smooth margins; spiky; associated with growth of the cancer along the membranous septal of the lymphatics
2. larger
3. upper lobe nodule
4. non-calcified

Question 8

what are the characteristics of lung nodules associated with low risk for lung cancer?

Answer 8

1. smooth edge
2. smaller
3. calcified
4. on-upper lobe nodule

Question 9

what are the different calcification pattern of nodules?

Answer 9

malignant more likely to be non-calcified

if present, certain calcification patterns are reliably benign including:

1. central: Bulls-eye
2. laminated
3. homogeneous
4. popcorn (hamartoma)

however eccentric calcification does not exclude cancer

Question 10

which calcification patterns in a newly discovered 3 cm nodules will require follow up surveillance in CT imaging?

Answer 10

eccentric calcification

this is because scars can become malignant over time!

Question 11

what are ground glass opacities?

Answer 11

so you can see what’s behind it but it’s just hazy; they grow slowly

a lot of times they appear because of infection but other times they’re neoplastic and need to be followed but the good news is they grow slowly

GGO’s should be followed with repeat CT scans less frequently but for longer periods of time

so if you see a pure nodular ground-glass opacity in the right upper lobe and you do a follow-up CT scan after seven months that shows no interval change noted and biopsy confirmed benign lesion then according to current guidelines, this lesion would be followed at intervals over years, rather than biopsied or surgically removed

Question 12

what are the patient characteristics that are high risk for lung cancer?

Answer 12

1. rare in age <35
2. tobacco; 10-35x increased risk
3. radon, asbestos, uranium exposure
4. race, family history; black and hawaiian men have increased risk
5. emphysema; 3x increase
6. idiopathic pulmonary fibrosis; 4x increase
7. prior history of cancer

Question 13

what are the nodule characteristics that are high risk for lung cancer?

Answer 13

1. nodule size: arger nodule size, increased risk
2. nodule morphology

spiculated more likely cancer

round; more likely non-cancer or metastatic

non-calcified more likely cancer
Benign calcification pattern

3. nodule location:
   upper lobe more likely cancer
4. nodule multiplicity

single nodule more likely primary lung cancer

5. nodule growth rate (volume doubling time)

malignant solid nodules typically 100-400 days

malignant non-solid nodules typically 3-4 years

Question 14

what are the Fleischner guidelines?

Answer 14

guidelines to use when deciding management of incidental nodules

these are the people who don’t have the criteria for lung cancer screening but you find a nodule incidentally aka everybody!

Question 15

what are the Lung-RADS guidelines?

Answer 15

guidelines to use when deciding management of nodules found during screening

Question 16

what are the Fleischner guidelines for solid nodules <6 mm in diameter?

Answer 16

1. low risk patients = low age, smoking, low risk nodule characteristics

generally needno further follow-up – the average risk of cancer in solid nodules ≤6 mm has been estimated at less than 0.15%, or <1 in 6,600.

2. high risk patients = greater age, heavy smoking, suspicious morphology, upper lobe location

cancer risk into the 1%–5% range; therefore, follow-up at 12 months under most circumstances

Question 17

what are the Fleischner guidelines for solid nodules 6-8 mm in diameter?

Answer 17

1. low risk patients

only a single follow-up chest CT at 6-12 months is advised, with a third CT scan at 18-24 months to be “considered“, depending on characteristics

2. high-risk patients

CT at 6-12 month interval

if very high risk (e.g, qualifies for annual LCDT screening), 6 months interval.

Question 18

what is the key to increased survival of lung cancer?

Answer 18

early stage diagnosis!! and the key to early diagnosis is screening!!

the stage Ia 5-year survival is >60-80%

if stage 1a is discovered by screening even better: >80%

screening is associated with >20% reduction in mortality from lung cancer

low dose CT (LDCT) of chest annually for those eligible.

Question 19

who is eligible for lung cancer screening?

Answer 19

ANNUAL screen for high risk subjects:

1. age 50-77
2. > 30 pack-years smoking history
3. quit <15 years prior
4. able and willing to undergo surgical resection

USPSTF decreased age to start from 55 to 50 in 2020

Question 20

how many people actually get screened for lung cancer?

Answer 20

an estimated 6.8 million people in the US meet eligibility criteria for lung cancer screening yet only 4% of those eligible are currently in screening…..

this may be partly because of:
1. the concentration of current smokers within groups of lower socioeconomic status

2. direct relationship between socioeconomic standing and participation in medical screening programs; it’s important to address this health care disparity
3. partly lack of physician acceptance based on 2011 NLST study but this should change following 2020 NELSON study report that confirms benefits reported in NLST study!!!

Question 21

one of your long time patients asks you at a routine office visit whether they should enter an annual low dose CT screening program for lung cancer. which of the following would qualify her to do it?

A. age 50

B. smoked 29 pack year history

C. quite smoking 20 years prior

D. Gold stage D COPD on 4 liters of O2

Answer 21

age 50

Question 22

what is the NELSON study?

Answer 22

13,195 men and 2594 women enrolled in Europe with a minimum follow-up of 10 years

the cumulative rate ratio for death from lung cancer in screening group compared with control group at 10 years was:

0.76 (95% confidence interval [CI], 0.61 to 0.94; P=0.01).

CONCLUSION:
this 2020 study strongly corroborates 2011 NLST study and is likely to increase physician acceptance

Question 23

how has specificity and positive predictive value of nodule screening improved?

Answer 23

there’s a lack of specificity because the LDCT screening will identify a million tiny little nodules

but now, evidence supports increase in threshold for positive nodule to > 6 mm because nearly 1/2 of the false positives in NLST were <6 mm

so not acting on <6 mm nodules improves specificity and increases positive predictive value (true positives/all positives) from 3.8% to 7.2%

also sidenote: there’s a low cancer prevalent in baseline nodules <6 mm

Question 24

what is the management algorithm for screen detected lung-nodules?

Answer 24

Lung-RADS criteria says:

90% of screen-detected nodules require no intervention prior to next yearly LDCT

higher category associated with shorter interval imaging and/or tissue sampling

PET CT restricted to nodules > 8 mm solid component

Question 25

patient evaluated for lung cancer screening who is 61 y/o, >30 pack-years smoking, quit 2 years ago, able and willing to undergo surgery if necessary.

first CT scan: 8/16/17 shows RUL, spiculated nodule 12 mm in diameter

since it was high risk, they got PET/CT: 09/27/17
SUV: 3.7 (cut-off 2.5)

what would you do next?

Answer 25

so he meets the next step options:

1. evaluate for surgical resection
2. give antibiotic, test for fungal infection, and do 3 month f/u CT

you should give antibiotic, test for fungal infection, and do 3 month f/u CT because antibiotic followed by 1-3 month follow-up is an option when chance of non-malignant causation is high –> it could be a mucous plug in patient with chronic bronchitis and/or active smoker, atypical pneumonia or ndemic fungal infection (Histoplasmosis or blastomycosis)

1-3 months follow-up for a 1-2 cm nodule identified on screening will not adversely affect outcomes

but do not lose track, be sure to follow-up!

however, the CT on 11/15/2016 (3 months): Did not decrease in size, fungal tests negative (serum galactomannan for aspergillus, urine histoplasmosis antigen) and he was positive for adenocarcinoma of the lung

he’s at high risk for second lung cancer so continue annual LDCT screening

Question 26

Nodule discovered at hospitalization for COPD exacerbation

Nodule characteristics:
round, central calcification, 2 cm LUL.

Patient characteristics
60 y/o, >40 pack years, active smoker, able and willing to undergo surgical resection

next steps?

Answer 26

no need to follow-up this nodule because it’s 2 cm round, central calcification >99% so high probability it’s benign

patient should be entered into annual LDCT screening due to high risk = age, 30+ pack year history, active smoker

should be counseled on smoking cessation

however, criteria wasn’t followed and they did a PET CT to assess for malignancy
SUV <1.0 and it was read as negative for malignancy so this just confirmed the need not to follow up, keep in screening and counsel on smoking cessation

then, 3 month follow-up CT showed a ew spiculated nodule RUL but cancer doubling time doesn’t show up in 3 months so give antibiotics!!!! probably was a mucous plug or atypical pneumonia in a patient with chronic bronchitis

Question 27

what is a risk with transthoracic FNA?

Answer 27

pneumothorax

Question 28

Heavy smoker, with severe COPD; High Risk

Nodules identified on CT scan, LUL nodule PET positive

LUL nodule grew on 3 month follow-up CT

Biopsy positive for fungus and treated with itraconazole but then 3 months later the nodule is ginormous.

what do you do?

Answer 28

teaching points:
1. some nodules that are PET positive and grow are infection, not malignancy

2. need to test for galactomannan, histo antigen.
3. consider course of empiric antibiotics
4. counsel smoking cessation

Question 29

how should you modify Important to lung nodule management protocol in histoplasmosis endemic regions?

Answer 29

we do all these PET CTs on people and we get all these false positives, there’s large interregional variation in specificity of positive results

for people in endemic regions of histomycocis or blastomycosis, the specificity is even worse!!

Question 30

what is the summary of LDCT lung cancer screening?

Answer 30

1. NELSON study (2020) supports mortality reduction reported in NLST study >20% mortality reduction
2. based on NELSON study, USPSTF in 2020 recommended to decrease age for start of screening from 55 to 50.
3. based on standard of care screening data since 2014, evidence supports increase in threshold for positive nodule to > 6 mm –> this markedly reduces number of false positive nodules, follow-up CT scans, and associated costs
4. currently, only 4% of 6.8 million eligible have pursued screening thus, most lung nodules are discovered incidentally at time of imaging done for another purpose
5. lung nodules detected through screening are somewhat different from those detected incidentally