Occult Pulmonary Adenosquamous Carcinoma Presenting With Synchronous Colonic Metastases

BackgroundGastrointestinal metastases from primary lung malignancies occur in 0.2-11.9% of autopsy series; symptomatic colonic involvement is exceedingly rare (0.1%), portending a dismal prognosis with a reported median survival of approximately 2 months.Case PresentationA 60-year-old woman with a 40 pack-year smoking history, chronic obstructive pulmonary disease, and prior cervical malignancy presented with a refractory acute exacerbation. In the absence of a discrete pulmonary parenchymal lesion, computed tomography pulmonary angiography incidentally identified mass-like left upper lobe bronchial wall thickening. Bronchoscopic evaluation revealed high-grade endobronchial stenosis. Mediastinal fine-needle aspiration confirmed non-small cell lung carcinoma; colonic metastases identified on staging PET-CT demonstrated TTF-1/Napsin-A positivity with a CK7+/CK20-/CDX2- immunophenotype, consistent with pulmonary adenocarcinoma. Sequential adrenal resection revealed divergent squamous differentiation (p40+/CK5/6+; TTF-1-/Napsin-A-) with KRAS/MYC and NF-1 amplification, supporting a final diagnosis of pulmonary adenosquamous carcinoma-an aggressive NSCLC variant comprising 0.4-4% of lung malignancies.Management and OutcomeTreatment followed evidence-based, histology-guided sequencing: concurrent carboplatin-pemetrexed chemoradiation, nivolumab upon platinum resistance, and cytotoxic salvage with docetaxel followed by vinorelbine. Palliative adrenalectomy addressed refractory pain. The patient survived 42 months from diagnosis, the clinical course was shaped by adequate tissue sampling, diagnostic challenges, and multidisciplinary histology-guided treatment acquisition.ConclusionThis case underscores the diagnostic and therapeutic complexity of lung adenocarcinoma presenting with synchronous colonic metastases without a discrete parenchymal mass, compounded by intratumoral heterogeneity and phenotypic divergence across metastases. Comprehensive tissue sampling enabling serial immunohistochemical and molecular characterization, coupled with coordinated multidisciplinary management, is essential to optimize diagnostic accuracy and therapeutic sequencing in this rare and clinically challenging disease entity.