T HE L UNG N ODULE Rohit Kumar, MD Assistant Professor of Medicine Thomas Jefferson University

O UTLINE Definition Risks of malignancy Approach to diagnosis Current guidelines for follow up Cases

D EFINITION A radiographic opacity ( approximately round) that is < 3 cm in diameter, completely surrounded by pulmonary parenchyma. ( no associated adenopathy, atelectesis or pleural abnormalities).

W HY SHOULD WE FIND NODULES ? Smoking continues to be a highly prevalent Most lung cancer presents at a later stage Survival for late stage lung cancer is still poor Malignant nodules represent a potentially curable form of lung cancer Recent trials indicate screening might be beneficial

CXR S TUDIES 4 Randomized Clinical Trials in 1970s Mayo Clinic Study Czech Study Sloan Kettering study Johns Hopkins study CXR + Sputum cytology CXR + Sputum cytologyvs. Usual Care Usual Care CXR + Sputum cytology vs. vs. CXR alone

PLCO Smoker + Non-smoker Age CXR Randomize 150,000 No Screen Year ………… 20

N ATIONAL L UNG S CREENING T RIAL 30 pack years Age CT Randomize 52,000 CXR Year

NLST – S TUDY POPULATION Inclusion criteria 55 to 74 years At least 30 pack-year smoking history If former smokers, had quit within previous 15 years Exclusion criteria Previous lung cancer CT chest within 18 months before enrollment Hemoptysis Unexplained weight loss of more than 15 lbs in last year 60%Males 90%Whites 50%former smokers 75%less than 64 years old

NLST- R ESULTS 20% reduction in lung cancer specific mortality 247 deaths/ 100,000 person-years compared to 309 deaths/ 100,000 person-years 6.7% reduction in overall mortality Number Needed to Screen – 320

E PIDEMIOLOGY 1 in 500 CXR’s demonstrates a lung nodule >150,000 nodules are identified each year Incidence of cancer in nodules ranges between 10% to 70% ( 35%) Most nodules are benign- infection / hamartoma ELCAP – 23% subjects had nodules, 2.7% malignant Mayo Clinic – 1500 pts: 70% had nodules, 1.4% malignant

DD X “B ENIGN ” L ESIONS Vascular AV malformations Pulmonary artery aneurysm Infectious Tuberculosis MAI Aspergilloma Histoplasmosis Echinococcus Blastomycosis Cryptococcus Coccidiomycosis Ascariasis Difofilaria Inflammatory Rheumatoid nodule Sarcoidosis Wegener’s granuloma Congenital Bronchogenic cyst Other Rounded atelectasis Pulmonary Amyloidosis Tumors Hamartoma Lipoma Fibroma

DD X M ALIGNANT N ODULES Primary Lung Cancer Non-small cell Squamous cell Adenocarcinoma Large cell Bronchoalveolar carcinoma Small cell Carcinoid Lymphoma Metastatic Cancers Colon Testicular Breast Melanoma Sarcoma Renal Cell Carcinoma

D ECISION TO PERFORM FOLLOW UP STUDIES SHOULD DEPEND ON …. Nodule Size Nodule characteristics ( morphology) Growth rate ( doubling time) Patient risk profile

N ODULE S IZE > 3 cm – Mass ► should be biopsied/ removed Size Likelihood of malignancy < 3 mm 0.2% 4-7 mm 0.9% 8-20 mm 18% > 20 mm 50% Midthun et al. Lung cancer 2003

N ODULE G ROWTH R ATE A 30% increase in diameter represents doubling of volume ( assuming lesions are spherical) Depends on nodule morphology: Solid nodules – 149 days Sub solid nodules – 457 days Pure Ground Glass – 813 days Doubling time of malignant tumors is rerely less than a month or more than a year Stability of a solid nodule over 2 years is considered a sign of benignity

N ODULE M ORPHOLOGY Opacification of underlying parenchyma Solid Ground Glass Borders Calcification Fat - benign Cavitation Air bronchograms Location in the Upper Lobes malignant

B ORDERS Spiculated Scalloped Smooth Corona radiata sign 80-90% of spiculated nodules are malignant !

C ALCIFICATION Malignant Benign Eccentric/ Stippled Popcorn Central/ Laminated

T HE S UB S OLID N ODULE Atypical Adenomatous Hyperplasia BACAdenocarcinoma

P ATIENT F ACTORS Age Smoking Various prediction models: Family history of lung cancer Pneumonia Occupational exposure

Risks of Malignancy ___________________________________

SPN- CHANCE OF MALIGNANCY Cummings, ARRD 1986;134:453 & Toomes, Cancer 1983;51:534

Factors Affecting Malignant Probability of SPN Spiculated Margins5.54 Age > 70 years old4.16 Size cm3.67 Doubling time < 465 days3.40 Smoker2.27 Age years old1.90 Size 1.1 to 2.0 cm0.74 < 1 cm0.52 Smooth Margins0.30 Never Smoked0.19 Doubling Time > 465 days0.01 Gurney JW. Radiology, Likelihood Ratio

R ISK F ACTORS Ost et al, NEJM: June 2003

Management ___________________________________

K EY N OTES Compare OLD films Assess patient risk Assess operability

SPN MANAGEMENT STRATEGY Excision High risk lesion, low risk pt Biopsy Intermediate risk Observation Low risk lesion, high risk pt Requires serial CT scans Bx if change When in doubt, take it out.

M ANAGEMENT OF N ODULES < 8 MM

F LEISCHNER S OCIETY G UIDELINES

T HIS DOES NOT APPLY TO ….. Patients with known or suspected malignant/ metastatic disease. Patients < 35 yrs – unless other cancer. Patients with unknown fever.

M ANAGEMENT OF N ODULES > 8 MM

F OLLOWING S UBSOLID N ODULES 2 year rule does not apply Change in the solid component TBNA indicated for non surgical pts, multifocal disease, and where proof of malignancy needed before surgery.

F OLLOWING S UBSOLID N ODULES Pure GGO: < 5 mm : No follow up 5-10 mm : 3-6 month, then annually for 3-5 year > 10 mm : 3-6 month, then surgery GGO with Solid component: > 10 mm: Consider PET scan, then Surgery

32 YEAR OLD, NON - SMOKER, WITH RECURRENT SINUS INFECTIONS Differential Diagnosis? Work-up?

A NSWER Differential Diagnosis Wegener’s Granulomatosis Cavitary Pneumonia TB Squamous Cell Carcinoma Other lung cancer Approach Lab tests (ANCA) Sputum culture & cytology FOB Trial of antibiotics PET less likely to help in diagnosis PET good for disease outside the chest

65 YEAR - OLD SMOKER ; 2 CM NODULE Peripheral or central? Approach?

A NSWERS Peripheral lesion Best approach: Assess for surgical candidacy PFTs PET scan +/- Head CT/MRI If good candidate  VATS If not good  CT-guided biopsy

42 YEAR - OLD SMOKER FROM O HIO Differential Diagnosis? What next?

PET SCAN – DOES IT HELP YOU ? SUV 2.0

A NSWER : Blastomycosis

42 YEAR OLD SMOKER WITH WEIGHT LOSS Differential Diagnosis? Next Step?

CT SCAN  What next?

A NSWER PET scan Surgical Candidate? VATS vs. TTNA Diagnosis: Lymphoma

C ASES 66 yr male smoker with FEV1 0.7L

C ASES 57 yr asthmatic female from Puerto Rico with cough

ELCAP PET sensitivity CT sensitivity Yield of bronchoscopy vs needle vs navigation/ ebus