What is the diagnosis and AJCC stage for a 3‑cm right lower‑lobe non‑small‑cell lung carcinoma that is TTF‑1 positive, with malignant involvement of mediastinal nodes stations 4R and 7 (N2) and hilar node 11R (N1), MET immunostain 50% positive, and PD‑L1 0%?

Diagnosis and Staging of Right Lower Lobe Non-Small Cell Lung Carcinoma

This is a TTF-1 positive primary lung adenocarcinoma, staged as AJCC Stage IIIA (T2a N2 M0), based on the 3 cm tumor size and ipsilateral mediastinal lymph node involvement at stations 4R and 7. 1, 2

Diagnosis: Primary Lung Adenocarcinoma

The diagnosis is primary lung adenocarcinoma based on the following immunohistochemical profile:

• TTF-1 positivity is the key diagnostic marker, as TTF-1 is characteristically positive in primary lung adenocarcinomas and helps distinguish them from metastatic disease and squamous cell carcinoma 1, 3
• The positive TTF-1 staining confirms this is a primary pulmonary origin rather than a metastasis from another site 1, 3
• TTF-1 negativity would have suggested either squamous cell carcinoma or metastatic disease from a non-pulmonary primary 1, 4

AJCC TNM Stage Classification

T Stage: T2a

• The 3 cm tumor size classifies this as T2a (tumors >3 cm to 5 cm) according to the 7th edition TNM classification 1, 2

N Stage: N2

• Involvement of mediastinal lymph node stations 4R and 7 defines this as N2 disease (ipsilateral mediastinal and subcarinal lymph nodes) 1, 2, 5
• Station 11R (hilar node) involvement represents N1 disease, but the presence of N2 disease supersedes this in staging 1, 2
• The combination of both N1 (station 11R) and N2 (stations 4R, 7) nodes indicates multi-station nodal involvement 5

M Stage: M0

• No mention of distant metastases, therefore M0 (no distant metastasis) 1, 2

Final Stage: IIIA

• T2a N2 M0 = Stage IIIA according to AJCC 7th and 8th edition staging systems 1, 2

Prognostic and Predictive Biomarkers

MET Expression (50% positive by SP44)

• MET overexpression at 50% may have therapeutic implications for targeted therapy consideration, though this is not standard first-line treatment 1

PD-L1 Expression (0%)

• PD-L1 proportion score of 0% indicates this tumor would not be a candidate for single-agent immunotherapy as first-line treatment 6
• PD-L1 negativity suggests the tumor may have a better prognosis compared to PD-L1 positive tumors, particularly in adenocarcinoma 6, 7

TTF-1 Positivity

• Beyond its diagnostic utility, TTF-1 positivity is associated with improved overall survival in advanced lung adenocarcinomas (18 months vs 9 months for TTF-1 negative tumors) 8
• TTF-1 positive tumors have higher rates of EGFR mutations (24% vs 6%), making molecular testing particularly important in this case 8

Critical Staging Considerations

Pathologic confirmation of N2 disease was appropriately obtained through transbronchial needle aspiration of mediastinal nodes, which is the recommended approach over proceeding directly to surgery 1, 5

Common Pitfall to Avoid

• Do not proceed with surgical resection as the primary treatment without considering multimodality therapy, as N2 disease (Stage IIIA) requires neoadjuvant therapy or definitive chemoradiation rather than upfront surgery 5
• The presence of multiple positive mediastinal stations (4R and 7) suggests this may represent more extensive N2 disease requiring definitive chemoradiation rather than surgical resection 5

Treatment Implications

This Stage IIIA (N2) disease requires multimodality treatment:

• Platinum-based concurrent chemoradiation is the standard approach for N2 disease with multiple station involvement 5
• Neoadjuvant chemotherapy followed by surgery may be considered only in highly selected cases with discrete (non-bulky) N2 involvement 5
• Given the PD-L1 0% status, single-agent immunotherapy is not indicated as first-line treatment 6
• Comprehensive molecular testing (EGFR, ALK, ROS1, BRAF, KRAS) should be performed given the TTF-1 positive adenocarcinoma histology 1, 8