Differential Diagnosis for a 65-year-old Man with a Lung Mass

Single Most Likely Diagnosis

• Adenocarcinoma of the lung: Given the patient's 45 pack-year history of smoking and the presence of a large lung mass with bulky mediastinal adenopathy, adenocarcinoma is the most likely diagnosis. The biopsy result suggesting adenocarcinoma further supports this. The expected staining pattern for lung adenocarcinoma is CK7+ CK20- TTF1+, and the EGFR mutation status can vary. Therefore, options A (CK7+ CK20- TTF1+ EGFR-wildtype) or B (CK7+ CK20- TTF1+ EGFR-mutated) could be expected, with B being more common in non-smokers but possible in smokers as well.

Other Likely Diagnoses

• Squamous Cell Carcinoma: Although less likely given the biopsy result, squamous cell carcinoma could still be considered, especially with a significant smoking history. However, the staining pattern would typically be CK5/6+ p63+, which does not match the provided options closely.
• Small Cell Carcinoma: This aggressive form of lung cancer is strongly associated with smoking. The staining pattern might include TTF1+, synaptophysin+, and Chromogranin+, with a high Ki67 index, but the morphology and initial biopsy result point more towards adenocarcinoma.

Do Not Miss Diagnoses

• Metastatic Adenocarcinoma: It's crucial not to miss the possibility of a metastatic lesion to the lung, especially from a gastrointestinal primary, which could present with CK7- CK20+ CDX2+ staining. However, the clinical context and biopsy results provided lean more towards a primary lung malignancy.

Rare Diagnoses

• Neuroendocrine Tumors: While less common, neuroendocrine tumors (like typical or atypical carcinoids) could present with synaptophysin+ and Chromogranin+ staining. However, the clinical presentation and biopsy results provided do not strongly suggest this diagnosis.
• Large Cell Neuroendocrine Carcinoma (LCNEC): This is a rare and aggressive form of lung cancer that could show TTF1+, synaptophysin+, and Chromogranin+ with a high Ki67 index, similar to small cell carcinoma but with a different morphology. The provided staining pattern D (CK7+ TTF1+ synaptophysin+ Chromogranin+ Ki67 95%) might suggest this, but it's less likely given the initial diagnosis of adenocarcinoma.