Pet-Negative Lung Mass

Author: Alejandro Bribriesco
Institution: Cleveland VA Medical Center
Date Reviewed: December 2024
Original Case: Daniel Raymond, MD; Cleveland Clinic Foundation
Learning Domain: General Thoracic
Learning Objective: Work up of Lung Mass, Surveillance
PowerPoint File: File Pet_Negative_Lung_Mass.pptx

 

Presentation

  • 69 yo male presents with 6 months of persistent cough
    • PMH: 110 pk-yr smoker; nephrolithiasis
    • PSH: Inguinal hernia repair; cystoscopy with stent; lithotripsy
    • Denied hemoptysis, weight loss, neuro symptoms, bone pain
  • CXR reveals:

 

Referred to Local Oncologist

CT scan obtained:  2.7 x 1.5 cm Left Upper Lobe Mass

 

PET Scan Obtained

Report: “No FDG-uptake in lung lesion”

 

Core Needle Biopsy Obtained

Path report: “Small fragment of epithelial-lined inflamed fibroconnective tissue-admixed with skeletal muscle, cartilage and mucoid material . . . May represent inflammatory process, hamartoma or other unusual lesion”

 

Repeat CT Scan Obtained in 3 Months

Report: “Interval growth now measuring 3.7 X 1.8 cm lesion ”

 

Repeat in Additional 6 Months

Report: “Continues to enlarge . . . 5.6 x 4.5 cm”

 

Multidisciplinary Thoracic Tumor Board

  • Growing lung mass in heavy smoker high concerning for malignancy 
    • Based on CT scan: cT3 N0 Mx / cStage IIB
  • Repeat non-surgical biopsy vs minimally invasive surgical excisional biopsy/wedge resection?
    • Given high pre-test probability/suspicion: recommended proceeding with surgical resection if lymph nodes deemed negative by invasive sampling
    • If occult malignancy detected: PD-L1, molecular sequencing, consideration of induction/neo-adjuvant therapy
  • Staging complete
    • Bronch/EBUS revealed no evidence of malignancy
    • Brain MRI negative

 

Patient Referred to Thoracic Surgery

  • Stable respiratory status, no hemoptysis, neuro symptoms or bone pain.
  • Denied Chest wall pain
  • Very good exercise tolerance concordant with PFTs
  • FEV1 = 2.97 L (126%)
  • DLCO = 20.37 (88%)
  • Plan to proceed with minimally invasive exploration, left upper lobe wedge resection with intraoperative pathologic assessment
    • Possible completion upper lobectomy
    • Possible chest wall resection

 

Taken to the OR for Surgical Biopsy

  • Intra-operative findings:  No pleural disease, lesion not adherent to chest wall.  Large wedge resection performed:
  • Frozen section: Non-small cell lung cancer-adenocarcinoma
  • Left minimally invasive completion upper lobectomy performed
    • Final surgical path:  pT2bN0M0 / pIIA mucinous adenocarcinoma
      • PD-L1: 50%
      • EGFR, ALK, ROS-1 negative
    • Uncomplicated post-op course
    • Discharged home POD#2
  • Subsequently referred for adjuvant systemic therapy (chemotherapy and immunotherapy)

 

PET (-) Malignancies

  • Size, location and histologic subtype are determinants of PET avidity in lung cancer
    • Low avidity histology:  Bronchoalveolar cell carcinoma, well differentiated adenocarcinoma (W/D AC), mucinous adenocarcinoma and carcinoid tumors 
    • Size < 1 cm
    • Peri-diaphragmatic location
      • Due to movement
  • PET NPV ~85-95%

S. Iwano et al  Lung Cancer 2013; 79(2): 132-6. J Wang et al Clin Lung Cancer 2012; 13(2):81-9.

 

False Negative Biopsy of the Lung Nodule

  • Choice and accuracy of Bx modality depends on:
    • Size
    • Location 
  • Transthoracic (CT-guided) Core Needle Biopsy:
    • Sensitivity: ~90% / Specificity: >95%
    • Negative Predictive Value  ~80%
    • False negative rate: 7.48%
  • Transbronchial Biopsy*:
    • Sensitivity ~75% / Specificity ~60%
    • Negative Predictive Value ~50%*
    • False negative rate: ~20%
    • *New technology (robot-assisted bronchoscopy) likely to increase accuracy

L Quint et al Cancer Imaging 2006 6(1):163-7. Schreiber et al Chest 2003 123:115S-28S. AT Ho et al Lung 2023 201(1): 85-93.

 

Conclusion

  • A negative PET scan does not rule out malignancy
    • Multidisciplinary Tumor Board is key
    • Pre-text probability based on clinical context (i.e. smoking history) and tumor behavior (growth)
    • Surgical biopsy may be warranted vs needle biopsy
  • Mucinous adenocarcinoma of the lung
    • Infrequent subtype of NSCLC-adenocarcinoma (2-10%)
    • Frequently PET (-) even at large sizes given mucin deposits
    • Difficult to diagnose on needle/non-surgical biopsy
  • PD-L1 and molecular testing important to guide treatment strategies