The Solitary Pulmonary Nodule

1. The Solitary Pulmonary Nodule Author: Andrew Hope, MD Editor: Amy Shaheen, MD, Assistant Professor of Clinical Medicine Duke University Medical Center

2. Pulmonary Nodule: Definition & Incidence • Definition: • Approximately round lesion that is less than 3 cm in diameter, completely surrounded by aerated lung. • >3cm is a mass, highly likely to be malignant • Incidence of malignancy among SPN is widely variable in case series (10-70%) • Incidence: • 0.09-0.20% of routine CXRs have a solitary pulmonary nodule (SPN)

3. Benign (70% of time in non-known CA pts) Infectious granuloma (i.e. histo, cocci, TB, atypical mycobacteria, crypto, blasto) Benign neoplasm, i.e. hamartoma, lipoma Other infection, i.e. abscess, echinococcal cyst, aspergillus, etc Causes of benign lesions: Infectious granulomas, 80%. Hamartomas, 10%. Malignant Bronchogenic carcinoma Metastases, i.e. breast, head/neck, melanoma, colon, renal cell Carcinoid Pulmonary Nodule: Differential Diagnosis

4. Pulmonary Nodule: Diagnostic Modalities • Diagnostic modalities: • High resolution (remember this when ordering!) chest CT scans—initial test of choice. • CT scan with contrast—dependent on institution • MRI (only for patients who cannot get IV contrast; no better than CT!) • PET scan. Used for patients with intermediate probability of malignancy— good choice for excluding malignancy in many patients without obvious treatment plan. Useful only for lesions >1cm, where it has a 97% sensitivity. Expensive; Medicare recently reimbursed $1912 for PET vs $276 for CT.

5. Pulmonary Nodule: Radiographic characteristics to evaluate • Radiographic characteristics to evaluate for malignancy: • Associated with benign process • Stability in size over 2 years—highly associated with benign disease • Calcification in the correct pattern more likely benign (i.e., diffuse, laminar/”popcorn”, or central)  • Assoc. with malignancy • Spiculation or “corona radiata sign”, 4-5 mm linear strands radiating from lesion • Change in size: doubling time for cancer usually >1 month and <1 year • Larger size (>2.3cm) • Upper lobe location

6. Pulmonary Nodule: Patient characteristics to predict malignancy • Patient characteristics to predict malignancy: • See table from Ost D et al, NEJM 2003. Age and smoking status, as well as previous cancer history are important patient characteristics. Click here for .pdf file of this table

7. Pulmonary Nodule: Decision for Surgery • Decision for surgery: • In general, the decision for surgery takes into account the risk of malignancy compared to the risk for surgery. If the risk/benefit ratio is acceptable taking into account patient comorbidities, cancer risk profile, and available radiographic data including PET scan, the patient should be referred for VATS. The initial surgical approach is usually excisional biopsy with wedge resection and removal of the nodule. If frozen sections indicate malignancy, the surgeon will proceed to lobectomy with mediastinal lymph node dissection at the same time. • Use of decision analysis to identify surgical candidates • Sophisticated mathematical models using likelihood ratios and baseline patient risk have been developed to predict the percentage likelihood of cancer in a given patient with a SPN. The details of three models are available on UTDOL. However, given the models’ complexity and the fact that patient preference should guide therapy, institutional protocols still vary in approach.

8. Pulmonary Nodule: Patients with High Surgical Risk • Patients with high surgical risk. • Patients with high surgical risk present more difficulty, and unfortunately surgical risk tends to cluster with the patients who are more likely to have malignancy (i.e. smokers, the elderly). For these patients, a biopsy can help guide whether surgical risk is worth taking: • TTNA. Best for patients who are not surgical candidates, to make tissue diagnosis. Variable sensitivity—does not rule out malignancy. • Bronchoscopy. Best for central/endobronchial lesions or mediastinal LAD. Again, able to rule in malignancy, but not rule it out. • Follow up for patients not referred for surgery: • Serial high resolution CT scans should be performed at 3, 6, 9, 12, 18, and 24 months to rule out enlargement of the nodule or development of new nodules.

9. Pulmonary Nodule: Proposed algorithm for approach to SPN Click here for .pdf file of this algorithm

10. Pulmonary Nodule: Question (1) A 62 y/o woman is evaluated because of abnormal results on chest radiograph. She smokes 1 pack of cigarettes per day, with a 50-pack-year history. She has a morning cough productive of small amounts of yellow sputum. She has hypertension, for which she takes metoprolol, and type 2 diabetes mellitus, which is managed with diet and metformin therapy. Her BMI is 30. Her BP is 145/90 mmHg. Chest radiograph shows a 1.5cm nodule in the left upper lobe; no previous radiographs are available for comparison.

11. Question 1

12. Pulmonary Nodule: Correct Answer rationale 1 D) PET scanning uses 2-fluoro-2-deoxy-D-glucose (FDG) as the positron emitter and measures the relative concentration of the agent in the nodule. Because FDG competes with glucose for uptake into the nodule, elevated serum glucose can lead to a false-negative test. It is, therefore, important that patients with diabetes mellitus have good serum glucose control before PET scanning. The cell type of the tumor is not important in the imaging, and lesions larger than 1 cm can be assessed by PET scanning. Blood pressure control, has no influence on PET imaging, and the study is not potentially nephrotoxic because it does not use radiocontrast agents. (MKSAP-13)

13. Pulmonary Nodule: Question (2) A 38 y/o woman who has never smoked is evaluated because of a well-circumscribed nodule in the right lower lobe, which was discovered on a chest radiograph during a routine physical examination. There is no family history of cancer, the patient has never had cancer herself, and the lesion is completely calcified. A CT scan of the chest done 2 years ago showed a 0.8cm nodule in the right lower lobe. Another CT scan is ordered, and it shows the nodule is eccentrically calcified and has grown.

14. Question 2

15. Pulmonary Nodule: Correct Answer rationale 2 D) This patient likely has a benign granuloma, which is growing. The characteristics of the nodule, well-circumscribed, lower lobe location make it less likely to be a malignancy. In addition, the patient’s young age, the fact that she has never had cancer, and the fact that she is a nonsmoker also make cancer unlikely. The nodule should be removed. TTNA is unhelpful because a negative aspirate would not rule out the clinical suspicion of cancer. A PET scan would be a reasonable option if the lesion were larger; PET scanning cannot discriminate well is the lesion is less than 1cm. Lobectomy is too extensive if the lesion is not malignant. Removal of the nodule allows for minimal resection; if the frozen section at the time shows cancer, then a formal lobectomy can be accomplished during the same surgery. (MKSAP-13)

16. Pulmonary Nodule: Sources • Ost D, Fein AL, and Feinsilver SH, “The Solitary Pulmonary Nodule”, NEJM 2003;348(25): 2535-2542.  • Tan BM, Flaherty KR, et al., “The Solitary Pulmonary Nodule”, Chest 2003;123(1 supp):89S-96S. • UTDOL, 2005